National Institute on Drug Abuse

RESEARCH

MONOGRAPH SERIES

Methodological Issues

in Epidemiological,

Prevention, and

Treatment Research

on Drug-Exposed

Women and Their

Children

U.S. Department of Health and Human Services • Public Health Service • National Institutes of Health

117
Methodological Issues

in Epidemiological,

Prevention, and Treatment

Research on Drug-Exposed

Women and Their Children

Editors:

M. Marlyne Kilbey, Ph.D.

Khursheed Asghar, Ph.D.

Research Monograph 117

1992

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES

Public Health Service

Alcohol, Drug Abuse, and Mental Health Administration

National Institute on Drug Abuse

5600 Fishers Lane

Rockville, MD 20857

For sale by the U S Government Pinting Office

Superintendent of Documents. Mail Stop SSOP. Washington, DC 20402-9328
Associate Editors, NIDA

CORYL L. JONES, Ph.D.

Division of Epidemiology and

Prevention Research

JAG H. KHALSA, Ph.D.

Division of Epidemiology and

Prevention Research

ELIZABETH R. RAHDERT, Ph.D,

Division of Clinical Research

BEATRICE A. ROUSE, Ph.D.

Division of Applied Research

VINCENT SMERIGLIO, Ph.D.

Division of Clinical Research

ACKNOWLEDGMENT

This monograph is based on the papers and discussions from a technical

review on “Methodological Issues in Epidemiological, Prevention, and

Treatment Research on Drug-Exposed Women and Their Children” held on

July 25-26, 1990, in Baltimore, MD. The review meeting was sponsored by

the National Institute on Drug Abuse.

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The National Institute on Drug Abuse has obtained permission from the

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the text. Further reproduction of this copyrighted material is permitted only as

part of a reprinting of the entire publication or chapter. For any other use, the

copyright holder’s permission is required. All other material in this volume

except quoted passages from copyrighted sources is in the public domain and

may be used or reproduced without permission from the Institute or the authors.

Citation of the source is appreciated.

Opinions expressed in this volume are those of the authors and do not

necessarily reflect the opinions or official policy of the National Institute on Drug

Abuse or any other part of the U.S. Department of Health and Human Services.

The U.S. Government does not endorse or favor any specific commercial

product or company. Trade, proprietary, or company names appearing in this

publication are used only because they are considered essential in the context

of the studies reported herein.

NIDA Research Monographs are indexed in the Index Medicus. They are

selectively included in the coverage of American Statistics Index, BioSciences

Information Service, Chemical Abstracts, Current Contents, Psychological

Abstracts, and Psychopharmacology Abstracts.

DHHS publication number (ADM)92-1881

Printed 1992

ii
Preface

Prenatal exposure to drugs of abuse has become a major public health concern

of national importance. It has adversely affected the lives of hundreds of

thousands of babies born each year in the United States to drug-dependent

mothers, The cost of providing intensive care to drug-exposed infants can be

enormous. The care and treatment of one infant could run to more than

$100,000 depending on the severity of sickness, Many of the infants born to

drug-abusing mothers do not remain with the parents, which produces an

excessive burden on the resources of foster care provider agencies, The

National Institute on Drug Abuse (NIDA) has assumed a lead role in supporting

research on identifying prenatal effects of drugs of abuse on the behavioral,

intellectual, and physical development of these infants and on determining their

effects on reproductive outcomes in the addicted mother. Moreover, NIDA is

placing an increased emphasis on research related to the prevention and

treatment of developmental anomalies induced by drugs of abuse. This

research will be helpful in reducing suffering in the lives of babies, families, and

society at large.

Methodological difficulties and confounding variables have been impeding

progress toward the research goals identified above. It is clear that, in dealing

with the special problems of drug dependence, interaction and collaboration

among different disciplines should be encouraged-interaction between those

who have studied human development for many years and those who are

experienced in dealing with the problems associated with drug dependence.

Therefore, NIDA sponsored two research technical reviews that focused on the

experimental design issues inherent in research into the effects of prenatal

exposure to drugs of abuse. The purpose of these technical reviews was to

bring together panels of eminent researchers to consider how meaningful data

can best be obtained and to identify the kinds of research questions that can be

addressed given current technological limitations.

The proceedings of the first technical review, published in another NIDA

monograph, were related to the conduct of controlled studies on the effects

of prenatal exposure to drugs of abuse.

iii
This monograph represents the proceedings of the second technical review on

epidemiological, prevention, and treatment research on the effects of prenatal

drug exposure on women and children. The following NIDA staff members

participated in its planning and served as associate editors of this monograph:

M. Marlyne Kilbey, Ph.D., cochair (Dr. Kilbey also served as science adviser to

the Director of NIDA during 1989); Khursheed Asghar, Ph.D., cochair; Coryl L.

Jones, Ph.D.; Jag H. Khalsa, Ph.D.; Elizabeth Ft. Rahdert, Ph.D.; Beatrice A.

Rouse, Ph.D.; and Vincent Smeriglio, Ph.D.

M. Marlyne Kilbey, Ph.D.

Chair

Department of Psychology

Wayne State University

Detroit, Ml 48202

Khursheed Asghar, Ph.D.

Chief

Basic Sciences Research Review Branch

Office of Extramural Program Review

National Institute on Drug Abuse

Parklawn Building, Room 10-42

5600 Fishers Lane

Rockville, MD 20857

iv
Contents

Page

Preface iii

Session: ldentifying Research Questions,

Designs, and Analyses

Methodological Issues in Prevention Research on Drug

Use and Pregnancy 1

Lewayne D. Gilchrist and Mary Rogers Gillmore

Measurement Issues in the Evaluation of Experimental

Treatment Interventions 18

A. Thomas McLellan

Discussion: Statistical Analysis in Treatment and

Prevention Program Evaluation 31

Joel W. Ager

Session: Quantificatlon of Extent and Duration of Drug Use

Role of Biologic Markers in Epidemiologic Studies of Prenatal

Drug Exposure: Issues in Study Design 41

Michael B. Bracken, Brian Leaderer, and Kathleen Belanger

Detection of Prenatal Drug Exposure in the Pregnant Woman

and Her Newborn Infant 61

Enrique M. Ostrea, Jr.

V
Methodological Issues in Obtaining and Managing Substance

Abuse Information From Prenatal Patients 80

Robert J. Sokol, Joel W. Ager, and Susan S. Martier

Discussion: Caveats in Testing for Drugs of Abuse 98

David A. Kidwell

Session: Subject Selection, Recruitment, and Retention Issues

Who Is It Going To Be? Subject Selection Issues in Prenatal

Drug Exposure Research 121

Peter A. Fried

Subject Recruitment and Retention for Longitudinal Research:

Practical Considerations for a Nonintervention Model 137

Ann Pytkowicz Streissguth and Carol T. Giunta

Subject Recruitment and Retention Issues in Longitudinal

Research Involving Substance-Abusing Families: A Clinical

Services Context 155

Judy Howard

Perinatal Substance Abuse and AIDS: Subject Selection,

Recruitment, and Retention 166

Kenneth C. Rich

Discussion: Subject Selection, Recruitment, and Retention

in Longitudinal Studies Involving Perinatal Substance

Abuse and Human lmmunodeficiency Virus Infection 183

Emmalee S. Bandstra

Session: Measurement Issues

Measures of Pregnant, Drug-Abusing Women for Treatment

Research 194

Anne M. Seiden

Assessing Acute and Long-Term Physical Effects of In Utero

Drug Exposure on the Perinate, Infant, and Child 212

Emmalee S. Bandstra

vi
Methodological Issues in the Assessment of the Mother-Child

Interactions of Substance-Abusing Women and Their Children 228

Dan R. Griffith and Catherin Freier

Discussion: Measurement Issues in the Study of Effects of

Substance Abuse in Pregnancy 248

Claire D. Coles

Session: Research Envlronment Issues

Studies of Prenatal Drug Exposure and Environmental

Research Issues: The Benefits of Integrating Research

Within a Treatment Program 259

Karol A. Kaltenbach and Loretta P. Finnegan

How the Environment Affects Research on Prenatal Drug

Exposure: The Laboratory and the Community 271

Claire D. Coles

Discussion: Research Environment and Use of Multicenter

Studies in Perinatal Substance Abuse Research 293

Kenneth C. Rich

Session: Intervention Issues

Program and Staff Characteristics in Successful Treatment 305

Elizabeth R. Brown

Process Measures in Interventions for Drug-Abusing Women:

From Coping to Competence 314

Elaine A. Blechman, Thomas A. Wills, and Vera Adler

Discussion: Dilemmas in Research in Perinatal Addiction—

Intervention Issues 344

Loretta P. Finnegan

vii
Session: Legal Issues In Research With Pregnant Women

and Children

Alcohol- and Drug-Dependent Pregnant Women: Laws and

Public Policies That Promote and Inhibit Research and the

Delivery of Services 349

Ellen Marie Weber

Mandatory Reporting of Child Abuse and Research on the

Effects of Prenatal Drug Exposure 366

Douglas J. Besharov

Discussion: Effect of Legal Stipulations on the Conduct of

Treatment and Prevention Research 385

Judy Howard

List of NIDA Research Monographs 394

viii
Methodological Issues in Prevention

Research on Drug Use and Pregnancy

Lewayne D. Gilchrlst and Mary Rogers Gillmore

INTRODUCTION

This chapter examines conceptual and methodological issues relevant for future

approaches to planning and conducting research to prevent drug-related

problems in women and children. It begins with a brief historic overview of

prevention strategies and then identifies critical issues in conceptualizing

research on prevention of drug-related problems in women and children and the

methodological challenges that accompany these conceptual issues.

CURRENT THEORIES AND MODELS OF PREVENTION

A review of drug prevention efforts in this century suggests that the field is

following (albeit slowly) developments in heart disease and cancer prevention

by moving toward approaches that recognize the complexity of human behavior

and the limitations of unidimensional or single-focus strategies for achieving

lasting behavior change. During the past 40 years, several different models of

prevention have been in use. Virtually all these models emphasize one aspect

of human functioning, but none can be said to be based on a realistically holistic

view of human behavior (Jones 1990). Prior to 1960, prevention programers

assumed that lack of information was the fundamental reason why individuals

engaged in health-compromising or -damaging behavior. However, it became

clear that providing clear information about consequences was not sufficiently

powerful as an intervention to achieve marked or widespread changes in

behavior. The next model, called the individual deficiencies model, assumed

that some personality deficit (e.g., lack of self-esteem or positive self-image,

lack of good values, or the inability to make good decisions) led individuals to

engage in behavior harmful to themselves, Empirical tests of preventive

interventions focused solely on building self-esteem, and values clarification

also suggested that this intervention is not powerful enough to achieve

widespread changes in behavior.

1
The next paradigm to emerge, the social influences model, has wide currency at

the present time. Tests of this model dominated prevention research in the

1980s. This model assumes that individuals act in accordance with social

pressures and that they can be taught to recognize these pressures and can

learn skills to resist these influences. Tests of this model applied to smoking

prevention and cardiovascular disease prevention have shown some positive

results (Pentz et al. 1989a). Resistance to the social influences model has

broadened in recent years to a more inclusive life skills training approach that

recognizes that many individuals have not had enough experience to handle

complex social or interpersonal situations well. Thus, skills training focuses on

a host of issues beyond substance use and abuse. Studies of these skillsbuilding programs show some positive results. However, most tests of these

models have occurred in schools and, thus, do not capture the most at-risk

individuals, It also appears true that the initially positive effects from skillsbuilding interventions decay rapidly for many individuals once the formal

intervention program is over.

A more realistically complex prevention paradigm is emerging in

comprehensive, multilevel community development approaches aimed at

simultaneously modifying-in mutually reinforcing ways-both individuals and

the environments in which they are embedded through coordination of multiple

program elements, including mass media; teacher, parent, and student training;

and involvement of a spectrum of community leaders in social planning, social

action, and advocacy activities (Blackburn et al. 1984; Bracht 1990; Farquhar et

al. 1984; Flay 1986; Hawkins et al. 1991; Lasater et al. 1984; Pentz 1986). A

variety of principles from communication and social marketing theory, social

learning theory, diffusion of innovations theory, and community organization

theory are employed in these drug abuse prevention efforts. Current research

suggests that there is a generalizable set of procedures for initiating and

sustaining effective prevention activities in communities (Bracht 1990). This set

of procedures appears applicable across a range of communities, including

minority communities. To date, the most complete tests of the community

development approach to drug abuse prevention are still in progress. In the

past 5 years, the work of Pentz and associates (Pentz et al. 1989a, 1989b,

1989c) and of Hawkins and colleagues (1991) has shown positive results from

multiple-element, community-based efforts targeting adolescents and focused

specifically on drug abuse prevention.

What the nascent science of prevention still lacks is an integrated theory of

change that will encompass individuals and their environmental contexts,

Review of the progression of prevention strategies in this century reveals a

tension between two philosophies and, indeed, two lines of prevention-relevant

investigation: (1) the public health philosophy directed at increasing population2
wide knowledge through mass communication aimed at the largest possible

target audience and (2) the clinical-developmental philosophy directed at

assessing “where the client is” and then starting an intervention based on that

and on understanding the sometimes unique psychological and situational

factors that shape individual behavior (Bibace and Walsh 1990). With the public

health approach, entire population subgroups are the target audience (e.g.,

adolescents, women, minorities). Planners rely on broad demographic

categorizations to determine program content, and there is an implicit

assumption that motivations to use drugs are similar for all members of a

targeted demographic group. The clinical-developmental approach, in contrast,

assumes that motivation for initial and continued drug use varies substantially

“as a function of interindividual and intraindividual differences” (Jones 1990, p.

259). This philosophy assumes the possibility of large differences in motivation

and receptivity to intervention even among demographically similar individuals.

Researchers and planners with this philosophy place great emphasis on

sensitivity to social, psychological, environmental, cultural, and developmental

factors that influence individuals’ behavior (Baumrind and Moselle 1985).

Because the clinical-developmental philosophy seems to call for individualized,

time-consuming, and, thus, expensive interventions, this philosophy has not

been well employed in drug prevention program development, even though the

limited effectiveness of generic public health philosophy strategies is widely

recognized.

It is no longer feasible to think in single-cause/single-remedy terms about

prevention of drug abuse. With regard to preventive interventions to reduce

drug-related problems during and after pregnancy, it seems highly desirable to

develop programs that integrate the sensitivity and specificity of clinicaldevelopmental approaches with the efficiency and generalizability of public

health approaches. The next section examines potential new directions for

integrating these approaches to increase the scope and efficacy of preventive

interventions to reduce drug-related damage to women and children.

CONCEPTUAL ISSUES IN PREVENTION RESEARCH

The evolution of specific interventions to prevent drug-produced damage to a

developing fetus has barely begun. To better address the goal of reducing drug

use before, during, and after pregnancy in women of childbearing age,

prevention researchers will need to expand their conceptual horizons in at least

three areas. First, there is a need to develop a deeper common understanding

of the concept of prevention. Second, clinical-developmental models and

theories are needed to better ground prevention program messages and

methods in empirically based understanding of the belief and value structures of

individuals (women and men) in various population subgroups. Third, if

3
preventive interventions are to have any lasting effects, better account has to

be taken of the broader environments in which target audiences live, and

environmental factors in preventive efforts must be enlisted and accounted for

rather than ignored.

Defining Prevention In the Context of Pregnancy

One of the thorniest issues related to documenting the impact of preventive

interventions relates to establishing common agreement about what constitutes

“success.” In planning the best approach to prevention, what is the optimal

outcome for which one should strive? Should one strive to prevent the onset of

drug use among women of childbearing age or focus on the more circumscribed

goal of complete abstinence of all drugs during pregnancy? Is merely reducing

drug use (as opposed to attaining complete abstinence) during pregnancy a

sufficient gain to conclude that a prevention program should be continued or is

worth the cost? Is a prevention program a success if, following childbirth,

women relapse rapidly to drug use? Program goals are unclear in many current

prevention demonstration programs. Goals are stated in general terms-often

as general as “some intervention is better than none,” and improvement on any

of dozens of variables is counted as success. Intervention methods are

proposed but not linked to desired outcomes or specific goals. Finally, certain

outcome variables are measured, but their relationship to the originally

articulated program goal is not identified.

Case management should not be the only preventive intervention relevant to

reducing drug-related damage to women and children. If the bottom line is to

reduce the number of drug-damaged children born each year, numerous

strategies can be used. Efforts can be made to decrease drug use before,

during, and after pregnancy in women of childbearing age; to reduce the

incidence of pregnancy in drug-using or potentially drug-using sexually active

groups; and to reduce drug use during and after pregnancy to minimize (but not

eliminate) drug exposure. Therapy programs can be developed to normalize

the development (that is, prevent the onset of problems) in drug-exposed

children. These various prevention foci or goals reflect the classic nosology of

primary, secondary, and tertiary prevention activities.

Prevention program planners could benefit from clearer and more flexible

understanding of these different levels and types of prevention. Primary

prevention is preventing initial occurrence of any problem; in the present case,

this means preventing onset of drug use in women of childbearing age or at

least preventing drug use before conception and pregnancy. This primary

prevention goal is not addressed in much current programing for women and

children. The vast majority of extant studies related to drug use and women

4
and children take place in health care settings that require that a woman be

pregnant to be eligible for study enrollment. At this point, it is too late for

primary prevention.

Secondary prevention is the minimization of problems given the existence of the

risk factor-use of substances by a woman who is pregnant. Programs

designed to reduce or eliminate drug use after conception fall into the

secondary prevention category. This category contains the bulk of the studies

to date.

Tertiary prevention in classic terminology covers efforts to reduce the impact or

disabling consequences of drug exposure on infants. Few empirical studies to

date relate to this tertiary prevention goal. In current conceptualizations of

preventive interventions, these distinctions among the levels of prevention seem

blurred, and this blurriness reduces researchers’ effectiveness-first, in isolating

important issues for empirical study and, second, in reporting the results from

prevention studies in ways that are maximally useful to policymakers and to

community-based clinicians and practitioners. Without clarity at this

fundamental conceptual level, research on preventive interventions will continue

to be seen as fragmented and equivocal, and results from multiple studies will

not be meaningfully aggregated. In short, prevention will not advance as a

coherent science.

Understanding the Audiences’ Beliefs and Values

A second area that needs broader understanding and conceptual clarity is the

integration of clinical/developmental knowledge into the planning of preventive

interventions. Successful prevention programing rests on accurate

understanding of the lives and concerns of targeted program recipients.

Numerous studies demonstrate that information alone-that is, providing

individuals and communities with facts-has only a small impact on problem

behavior. As the advertising industry has shown, understanding the

psychological processes involved in individuals’ perceptions of events and

behavior is central to selecting persuasion techniques that will influence

motivation and actual behavior. Without understanding audience beliefs and

values, messages and methods intended to persuade individuals to engage in

more healthy behavior can be dismissed easily by the intended audience as

irrelevant or, worse, as offensive. Three factors appear to strongly influence

beliefs and values and, thus, the receipt of potential preventive interventions:

gender and gender role socialization, culture and ethnicity, and developmental

maturity.

5
Gender and Gender Role Socialization. Emerging research on the

psychology of women and on gender role socialization so far has not been well

used to develop new perspectives on tailoring preventive interventions for

preventing drug-related harm to women and children. Gilligan and colleagues

(Gilligan 1982; Gilligan et al. 1988) present evidence for gender-specific

differences in ethics, psychological and interpersonal priorities, and sense of

morality. Blechman (1980, 1984), Gilchrist and colleagues (1989), Miller

(1986), Beschner and colleagues (1984), and many others present evidence

that the method and the content of interventions intended to affect women’s

behavior should be tailored specifically for women. Prevention program

planners need deeper understanding of the beliefs, values, attitudes, feelings,

fears, and intentions that shape women’s behavior in the realms of sexual

activity and drug use. Luker’s classic work (Luker 1975) on women’s costbenefit thinking regarding becoming pregnant and carrying a pregnancy to term

illustrates the utility of examining decisions and behavior that initially appear

irrational or self-destructive from the perspective of individual women’s personal

values and belief structures.

Culture and Ethnicity. With regard to the importance for prevention

programing of understanding culture- and ethnic-specific beliefs and values,

Marin’s work in analyzing aspects of Hispanic culture that have relevance for

acquired immunodeficiency syndrome prevention programing serves as a

model (Marin 1990; Marin, in press; Marin and Marin 1990). Marin analyzes

central aspects of Hispanic culture and how this culture differs from the

individualistic-oriented culture of mainstream American society. Examining

such cultural values as allocentrism (i.e., other-oriented or collectivistic

orientation) and familialism (i.e., the tendency for family members to seek help

from each other rather than from outsiders), she concludes that the most

effective strategies for preventing drug initiation and reducing current drug use

among Hispanics would be those directed toward and involving whole families

and communities rather than those focused solely on individuals. Similar

cultural analyses have begun with regard to black women’s beliefs and values

(Flaskerud and Rush 1989; Mays and Cochran 1988). Mays and Cochran

recommend health messages for black communities that appeal to a sense of

responsibility to others in the community and to ensuring a good future for the

other blacks. In most racial subgroups there exists pride in being a member of

the group. Can this pride be used to foster healthy babies? There are norms in

many minority subcultures that highly prize fertility and childbearing. Can these

norms be harnessed in some way to create social censure for parents when

infants are born damaged by drugs and to foster community and especially

masculine pride in producing drug-free, healthy babies?

6
Developmental Maturity. With regard to developmental maturity, the work of

Bibace and Walsh (1990), Baumrind (1985, 1987), Jordan and O’Grady (1982),

and others provides interesting information about the ways in which children

and adults fail to understand or fail to make use of widely available educational

efforts aimed at improving their own health and well-being. Appreciating

the concept of prevention requires a fairly high level of cognitive maturity.

Pursuing a developmental approach to prevention program development is

not limited to programing aimed at children (Bibace and Walsh 1990). As

health psychologists frequently show, many adults commonly rely on immature

thinking with respect to the probable harmful consequences of their own

cigarette smoking, alcohol consumption, and lifestyle (Stoeckle and Barsky

1980). How do women justify to themselves and to others continued drug use

and unprotected intercourse in the face of health promotive information? What

techniques can practitioners use to break down these false justifications?

Sensitive understanding of the kinds of personal differences sketched above

seems central to improving the acceptability and efficacy of current and

potential preventive interventions, There is so little solid information available in

these areas that is directly applicable to designing preventive interventions that

it is hard to know what questions are relevant,

Understanding Environmental Contexts

The third area requiring conceptual broadening and clarity relates to

understanding environmental contexts in which behavior occurs. Environments

are important to prevention programers for two reasons. First, interventions,

both preventive and remedial, are delivered in the context of environmental

institutions and organizational systems, and these systems can become units

of interventions. Thus far, the health care system has had most of the

responsibility for preventive interventions related to drug use during (but not

before or after) pregnancy. There is a need to examine other institutional and

organizational opportunities for achieving drug prevention goals (Gilchrist 1990).

Second, environments in the form of systems and social networks exert

exceedingly powerful direct and indirect influences on the recipients of a

prevention program. There is abundant evidence that individuals have a strong

tendency to behave in ways that fit the norms of their social networks (Fisher

1988). When an individual attempts to behave in ways that appear inconsistent

with social network values, the networks resist such change and often exert

strong antichange influences (Schachter 1951). As prevention programers

become more adept at analyzing environments and environmental/situational

supports, it may be possible to conclude that it is more effective to address

preventive intervention efforts toward people in the target individuals’

7
environment rather than to address target individuals (in this case, women)

directly. Prevention program developers need to ask such questions as: How

might parents, peers, and sexual partners of women at risk for drug involvement

before, during, and after pregnancy be enlisted as assistants for ensuring

infants’ health by creating expectations that will keep young women drug free?

RESEARCH METHODOLOGY AND DESIGN ISSUES

The above outline of conceptual issues suggests that there are four types of

methodological challenges for prevention researchers: (1) those relevant for

carefully defining prevention program goals and outcomes, (2) those relevant

for developing valid and feasible assessment tools for collecting critical clinicaldevelopmental information for more productively focusing preventive

interventions, (3) those relevant for documenting environmental contexts

affecting individual behavior and prevention program implementation, and (4)

those relevant for shoring up criticisms that undermine the persuasiveness of

current prevention study designs.

Defining Prevention Program Goals and Outcomes

Understanding of the various levels of prevention-primary, secondary, or

tertiary-should undergird selection and reporting of specific outcomes.

Reporting that a prevention program worked or did not work is less important

than carefully documenting how it worked and for whom. In the past, prevention

researchers have assumed that the ultimate good to come from their research

was a treatment manual filled with empirically validated treatment procedures.

These manuals-often as specific as scripts-are widely disseminated (or are

intended to be so). However, the assumption that a treatment manual is the

most valuable result from prevention research needs to be reexamined. Given

the gender, cultural, maturational, and community influences that shape human

behavior in different ways, what may be most useful to disseminate is an

empirically identified process for developing a preventive intervention that when

undertaken will produce the most sensitively tailored and most powerful

program possible. Such a blueprint for action must contain valid tools or

models for assessing key elements at the individual and the community levels.

More importantly, this blueprint would outline what to do with each type and

level of information to plan the most effective preventive approach.

This view of the best ultimate product for prevention research suggests that

much more emphasis than is now the case be placed on analyzing the process

of prevention program development and on identifying positive and negative

influences on prevention program implementation. Such analyses necessarily

will have to deal in detail with political and “climate” issues and sensitive

8
identification of factors that affect optimal program delivery. Finding solutions

to important process problems (such as systematic investigation of methods

for keeping clients enrolled in a specific intervention effort) may need to become

the legitimate central focus for some prevention research studies.

If researchers take seriously the need to address environmental issues that

influence women’s behavior, they will have to grapple with how to enroll

members of women’s social networks in intervention studies. Many women

have steady sexual partners, although they may not be legally married to them.

Sampling and enrolling couples, families, and possibly extended family

networks in prevention-related studies, rather than continually focusing only on

individual women, will require creativity, perseverance, and focused study but

should be amply rewarding in terms of yielding new knowledge.

Prevention researchers should be encouraged to collect and report processrelated data so that eventually meta-analyses might be conducted across

studies on process factors similar to the analyses now done on treatment

outcomes (Tobler 1986). Methodological challenges involved in documenting

program processes also should include dealing with the cost of launching and

sustaining programs in given communities. Typically, a cost-benefit analysis is

not undertaken when testing an intervention, although such information is

central for informing policy decisions. Prevention researchers need to think

through how much of a reduction in drug exposure or other targeted outcomes

warrants continuation and replication of a given program.

Collecting Relevant Clinical-Developmental Information

Prevention researchers need to develop the conceptual frameworks and,

above all, the assessment procedures capable of capturing gender, cultural,

maturational, and community organization issues that have high relevance for

selecting the most powerful persuasion and intervention strategies. Existing

cross-sectional survey techniques may have limited utility for this task.

Coordinated ethnographic studies involving multiple investigators, locales,

and common goals may be useful in developing an empirically validated

understanding of belief and value structures relevant for building persuasive

prevention techniques for specifically targeted audiences.

The Theory of Reasoned Action (Fishbein and Ajzen 1975; Ajzen and

Fishbein 1980) and the related Theory of Planned Behavior (Ajzen 1985) can

be employed as frameworks for analyzing beliefs and values and the patterns

in the relationship of these behavioral influences on decisions and behavior

(Baker 1988; Davidson and Morrison 1983). The Theory of Reasoned Action

considers the affective response to performing a behavior and the perceived

social norms about the behavior. This theory has proven useful in

9
understanding decisions related to sexual behavior but has not been applied

often to understanding drug use, particularly among women. The integration

of recent advances in social learning theory (e.g., Bandura’s concept of selfefficacy) into the Theory of Reasoned Action appears promising. Relevant

questions to pursue include the following: What are the values underlying

reported voluntary decreases in many women’s drug use during pregnancy?

How can practitioners capitalize on these values to sustain low drug use rates

after pregnancy? Does a woman’s sexual partner(s) exert a disproportionally

large influence on her use of drugs before and after pregnancy? If so, what is

the basis for this influence? How can this influence be manipulated? What

protective factors reduce the influence of drug-using sexual partners and peers?

How can these factors be strengthened?

The goal of tailoring preventive interventions to fit women’s lives and needs

will require some creative attention to asking researchable questions that will

illuminate important aspects of women’s lives. The task also will require better

assessment tools than are now available. Using theory to construct and then to

test assessment procedures for practitioners to use in identifying important foci

for intervention is a viable and useful goal for future prevention research. The

goal also suggests that researchers expend more energy not only in tailoring

qualitative methods to women’s unique needs but also in more fruitfully

combining them with traditional quantitative methods (Glanz et al. 1990).

Documenting Environmental Contexts

Prevention research to date has been so focused on treatment techniques for

individuals that the field hardly has the terminology available to discuss

environmental contexts that include service system characteristics. There is

some evidence that the way whole service systems are constructed greatly

affects and can limit the possible effects of an intervention. Mental health

researchers have gone farther than drug researchers in defining and studying

organizational environments and how such environments affect program

delivery and patient outcome (Morrissey et al. 1982). Currently, there Is great

need for drug prevention practitioners and researchers to develop common and

explicit definitions of such terms as “case management” and “outreach” so that

these intervention processes can be studied in valid and reliable ways. Here

again, mental health/mental illness research may be of assistance (Harris and

Bachrach 1988).

Research Methodology Issues

Design Issues. Methodological challenges in the more conventional sense for

future prevention research involve finding feasible designs for documenting the

10
impact of prevention programs. The most convincing evidence of any

intervention’s effectiveness comes from a true experimental design where

subjects are randomly assigned to conditions. However, true experimental

designs often are not practical and sometimes are ethically questionable. The

wait-list control group strategy can be problematic because treatment must be

offered to wait-listed individuals within a reasonable period following their

recruitment into a study. This “reasonable period” often does not allow for a

long enough followup period for drawing valid conclusions about the preventive

effects of an intervention, A more viable design strategy is to compare the

relative efficacy of two or more prevention strategies, randomly assigning study

participants to different (carefully defined) intervention conditions. In this way,

all patients/clients/study participants receive treatment, yet random assignment

allows more confidence in drawing conclusions about the relative effectiveness

of different treatment approaches.

Where random assignment to conditions is clearly not possible, researchers

might be more creative in combining features of more than one type of quasiexperimental design to offset some of the threats to internal validity that occur

with a single design. Finding a comparable “nonequivalent” control group is

the most challenging aspect of quasi-experimental designs. Researchers

often match experimental and control groups on the basis of demographic

characteristics without any thought as to why those particular characteristics,

as opposed to some others, should be the basis for matching. If differences in

these demographic characteristics cannot plausibly account for any differences

observed between groups on the key dependent variables, then it makes no

sense to match on them. Good matching and good choice of a control group

requires considerable knowledge about the phenomenon of interest. Recently,

some investigators have embedded evaluation experiments on specific

interventions within longitudinal survey designs (e.g., Hawkins et al. 1991).

This strategy has strong appeal in that the longitudinal data can be used to

test hypotheses about factors that predict drug use before, during, and after

pregnancy, while at the same time, the evaluation experiment, if carefully

conducted, can provide information about intervention effectiveness. The

longitudinal data then can be used to assess the long-term effects and the

conditions related to success of the intervention.

Data Analysis Issues. If more complex prevention theories and research

designs are developed, more complex analysis strategies will be needed to

evaluate them. Clearly, multivariate analyses are warranted in which the effects

of several variables are taken into account simultaneously. Structural equation

modeling appears particularly promising, although it is not a panacea and

should be judiciously employed with careful attention to sample size and

underlying assumptions. There are three areas in which structural equation

11
modeling appears particularly useful. First, structural equation modeling is a

useful alternative to the traditional analysis of covariance for evaluating the

effectiveness of an intervention in a quasi-experimental design. Threats to

internal validity can be incorporated explicitly in the model, and the unreliability

of measures-which can result in bias when applying the analysis of

covariance-is taken into account. With longitudinal data, or designs with

pretest and posttest measures, the possibility of correlated error can be

examined and, if found, can be explicitly incorporated into the model, thus

eliminating a potential source of bias.

Second, structural equation modeling is useful for evaluating “causal” models in

which the indirect and direct effects of variables specified by theory are taken

into account. It is superior to path analysis in that the unreliability of measures

recognized in estimating the model and correlated error that normally

represents a threat to validity can be explicitly incorporated in the model. And

third, structural equation modeling provides a statistical means to test whether

the same model explains drug use equally well for subpopulations such as

persons from different ethnic and racial backgrounds. Although infrequently

done, structural equation modeling is also useful in evaluating the outcomes of

true experiments, especially with regard to detecting flaws in the experiment

(Costner 1985; Hawkins et al. 1991).

Finally, even in the best designed studies, some subjects will be lost to attrition.

Recent methodological advances have yielded analysis strategies in addition to

structural equation modeling to deal with sample selection bias that can be

applied to correct for biases due to attrition. Since attrition poses a serious

threat to internal validity, such procedures should be considered when

analyzing data from studies of intervention effectiveness. The key ideas can be

found in the econometrics literature (Heckman 1976; Goldberger 1981); for a

less technical explanation and example of an application, Berk’s (1983) article is

useful. In sum, directions for sophisticated and complex analyses to improve

evaluations of prevention programs currently exist. The challenge is to equip

individuals who are committed to drug prevention with these skills. This speaks

to the need for research training programs and to fostering what the National

Institute of Mental Health calls “public-academic liaisons,” where community

systems experts and community-based practitioners closely collaborate with

university-based statisticians and research specialists.

CONCLUSION

The most expeditious direction for growth in research on prevention of drugrelated harm to infants might be accomplished by research in which communitybased practitioners conduct clinical-developmental assessments-incorporating

12
attention to gender, culture, ethnicity, and developmental maturity-of carefully

defined target communities or social networks of related individuals within

carefully defined communities and organizations. This empirical assessment of

salient beliefs and values would be incorporated into carefully planned,

individually tailored, multifaceted, multisystem, “locally owned,” public healthstyle community or network development campaigns. The goal would be for

interventive efforts at the individual and at the community or network level to

trigger, support, and reinforce each other to reduce drug-related damage at

least to children, if not to all network members. The responsibility for initiating

this assessment, planning, and intervention process need not fall solely on

health care workers. The following are critical questions to be addressed with

this effort: Can valid and workable assessment protocols be developed so that

professionals in any community system can use them to begin local, antidrug

community development efforts? Can community development strategies that

have proven successful in heart and cancer prevention research be used to

mobilize and shape values and behavior change in apparently diffuse and

disorganized high-risk communities and social networks? What modifications

will need to be made in existing community development strategies to maximize

the participation of high-risk communities and networks?

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16
AUTHORS

Lewayne D. Gilchrist, Ph.D.

Associate Dean

Mary Rogers Gillmore, Ph.D.

Research Assistant Professor

University of Washington School of Social Work, JH-30

4101 15th Avenue, N.E.

Seattle, WA 98195

17
Measurement Issues in the Evaluation

of Experimental Treatment

Interventions

A. Thomas McLellan

INTRODUCTION

Drug abuse among expectant mothers is perhaps the most expensive,

complex, and pernicious health care problem of this era. The multiple

questions associated with prevention and treatment of drug abuse by the

mother, as well as the even more complex questions of drug effects on

the development of the child, require years of methodologically sound research.

The purpose of this chapter is to outline some of the methodological questions

and possible solutions in performing this type of research. The author

discusses methodological issues developed through work in the field of

treatment evaluation that may be useful to those performing similar types of

studies within the perinatal addiction field.

This chapter focuses on issues of patient and treatment measurement that

would be encountered in an evaluation of an experimental treatment or a

novel therapeutic program. The first part of the chapter deals with the

rationale and methods associated with collecting patient information at the

start of a treatment intervention; the middle part deals with the measurement

of the intervention; and the last part deals with the rationale for and the

methodological issues in measuring patient outcome following an intervention.

MEASUREMENT AT BASELINE

Purposes of Patient Evaluation at Baseline

There are clinical and research reasons for measuring patients at the start of a

treatment intervention. First, it is important to be able to describe the current

and past status of the patient along a variety of dimensions that will be relevant

for clinical and research decisions. For example, it will be necessary to get

some sense of chronicity of the presenting problems, indications of the severity

18
of comorbid problems, and characteristics associated with suitability for the

research studies for which the patient may be qualified. Second, it is important

to collect information that will be useful in the establishment of a treatment plan

and the setting of reasonable treatment goals, Finally, these initial measures

that are taken at the start of an intervention also will serve as the baseline

against which future comparisons can be made. This will be the basis for

evaluations of improvement and outcome in the patients and, thereby, the

evaluation of the efficacy of the intervention.

An important conceptual point that should be considered at this time (and will

be reemphasized in all parts of the chapter) is that it is essential to form a

reasonable expectation of what the proposed treatment intervention should be

able to achieve in the target patient population in realistic, measurable terms.

Perhaps the most common problem in the design and conduct of treatment

evaluations occurs at the start of the process where an investigator fails to

develop realistic, measurable objectives for the treatment. This, in turn,

produces a failure to select patients who have appropriate constellations of

problems that realistically can be affected by the intervention, a failure to

measure the selected patients on those aspects of the target problem that are

expected to change, and a failure to allocate adequate time and resources to

fully implement the treatment in sufficient quantity and intensity to produce the

desired changes.

Methods of Patient Measurement at Baseline

With regard to the methods that can be used for measuring patients at the time

of treatment admission, there are three types and all should be considered in a

thorough evaluation. Each type of measure has its strengths and limitations.

Interview. This is a time-consuming and relatively expensive method of

collecting information from a patient. Also, there is a possibility of interviewer

bias and interviewer error in the collection of information. At the same time,

the interview is a personal and clinically engaging method of beginning an

interaction with a patient and can be an important consideration in treatment

studies where patient retention and patient compliance issues will be significant

determinants of the overall efficacy of the intervention. Furthermore, given

adequate training and practice, an interview can be an excellent method for

ensuring that a patient understands the intent of the questions that are asked,

thus maximizing the validity of the reported data.

Questionnaire. This is a rapid, easily administered, inexpensive method for

collecting information, However, it is impersonal and can produce questionable

results in situations where the specific questions are not easily understood by

19
the patients or where the reading level of the patients is in question. At the

same time, computerized questionnaires can offer a rapid, engaging, and

private environment for patients to answer questions that can be understood

easily and that lead to clear, unambiguous answers.

Objective Measures. Laboratory-based objective measures include breath

and urine samples for drug and alcohol use as well as physical examinations

and laboratory test data for other health care problems. These measures have

the obvious advantage that they cannot usually be distorted by the patient, but it

is important to point out that even these measures are sensitive to methods of

collection and methods of analysis. Supervised observation of urine and breath

samples is really the only way to ensure that these measures will be valid. In

addition, there are many methods of analysis for these tests, and they may vary

substantially in sensitivity and cost,

Tlme Intervals to Measure

In the collection of the initial baseline data, it is important to remember the

subsequent purposes of the information. As indicated, the first purpose of the

data often will be to develop an overall assessment of the nature and severity

of the patient’s condition for treatment purposes. This, in turn, means that

problematic behaviors or conditions should be assessed over the entire life of

the patient, since the onset and chronicity of problems likely will be an important

factor in treatment decisions and possibly in predicting outcome. At the same

time, the investigator will want to be able to assess progress and outcome at

the subsequent followup points, and this will not be possible if only lifetime

measures are taken at baseline. For this reason, the investigator should select

a “time window” that will serve as a measure of the recent status of the patient

and will serve as a comparison point for future followup measures.

Again, there is no single time interval that is ideal. The factors that go into the

selection include the memory limits of the patient (Can she remember the past

year, 6 months, or 30 days accurately?) and the needs of the evaluation study.

For example, if the time window of measurement is the past 6 months and the

investigator wishes to measure improvement, then it will not be possible to do a

1- or a 3-month followup since the intervals will not be comparable. The first

followup point will have to be at the 6-month point. Again, while there is no

single preferred interval, many investigators have chosen to measure the

patient’s behaviors during the previous 30 days since it represents a period that

is usually (but not always) representative of their lives during the time before

treatment admission. Most patients can remember the past 30 days with

acceptable accuracy, and this interval enables multiple followup measures (e.g.,

1-, 3-, 6-, 12-month followup).

20
Validity of Measurement

Regardless of the method(s) used, two important issues are reliability and

validity of the information that is collected. It is important to note in this regard

that absolute validity does not exist. Rather, there are conditions under which

validity is going to be maximized, and conversely, conditions that will minimize

accuracy of reporting and the ability of the patient to understand or to give

accurate information. For example, timing is an extremely important issue with

regard to validity. Often, the initial contact with a patient, usually at the time of

admission, is not a good time to collect information. First, the patient may be

reluctant to provide information without having some assurance that her needs

will be met. Second, there may be issues of instability, perhaps due to drug

detoxification, withdrawal, or even intoxication effects,

A second important issue with regard to validity is the confidentiality of

information. This is of particular concern and, often, especially difficult with

regard to the pregnant drug abuser. It is important to be able to know the limits

under which the confidentiality of the information collected can be maintained.

These limitations are often subject to State and local agreements with

prosecutors and human services personnel, and these agreements are

important to negotiate before the initiation of the research. For example, it is

often (but not always) the case that mothers with drug problems may enter

treatment programs and provide complete, candid information that will not be

subpoenaed. Furthermore, it is sometimes (but not always) the case that

potential charges (e.g., child neglect and abuse) are suspended or not carried

forward pending satisfactory participation in treatment. These issues of

confidentiality will be important to discuss candidly with the prospective subject

at the same time she consents to participate in the study.

It is also possible to maximize the validity of information collected if the subject

can clearly understand the purpose of the information. When the information

collected can serve the mutual purposes of the patient and the research and

clinical staff, the patient can see it is in her interest to provide accurate, valid

information. Another major factor in the collection of valid information concerns

the interpersonal conditions under which the information is collected. An

interviewer should convey a legitimate interest and concern for the patient and

her child. It is critical to develop an interpersonal rapport during the course of

patient interviews, The interview and all other data collection should be done in

a quiet, private setting that will promote concentration and reflection. To the

maximal extent possible, it should be stressed to the woman that complete and

candid answers will not negatively affect the services or treatments she could

receive from the program. This is best done under conditions where a

prospective client has voluntarily come to a treatment organization seeking

21
services. Less than optimal are criminal or judicial situations where judgments

are likely to be rendered based on the data collected in the interview. Under

these conditions, collecting information as part of intake into a criminal justice

intervention is particularly difficult. It is often difficult to have faith in information

given by individuals who know their answers will determine their sentence and/

or fine. There is no satisfactory method of ensuring validity under these

conditions. It is much more likely that valid information can be obtained in a

treatment situation where the interests of the patients in obtaining services are

consistent with the interests of the researchers and clinicians in getting accurate

data.

Continuous vs. Categorical Data

Regardless of the methods used for collecting data, it is important to utilize

measures of patient status and behavior that can indicate change from

baseline, through treatment, to the posttreatment followup period. For example,

rather than ask “if’ a patient has used alcohol in the week before admission

(i.e., a yes-no categorical measure), it is much better to ask how many days the

patient has used alcohol in that week and/or how many absolute ounces of

alcohol have been drunk on a typical drinking occasion (i.e., measures that vary

on a continuum from 0 upwards). These measures can always be reduced later

into discrete categories, but the availability of continuous measures provides the

investigator much greater sensitivity of measurement and the opportunity to use

more powerful statistical techniques in the analysis of the data. For example, in

the question of drinking during the prior week, it is possible that a subject would

report, “Yes, I drank every day,” at the start of treatment, but, “Yes, I drank only

1 day,” by the end of treatment. The categorical measure of this variable (i.e.,

Did you drink during the past week-yes/no?) would fail to capture the change

that occurred following treatment.

Summary

At the time of admission, several factors are important in the collection of

information from patients. First, it is important to use multiple types of

measures, including interview, questionnaire, and objective laboratory test

information. Each of these types of measures not only has clear strengths but

also has some limitations. Second, it is important to maximize the likelihood of

obtaining valid information by making sure that the patient is able to understand

the nature of the questions asked and by developing conditions under which the

patient can feel safe and assured that the information provided can be handled

in a professional way with the greatest protection of confidentiality. Third, it is

equally important to measure the behaviors and qualities of the patient that will

be the focus of the interventions to be provided. In this regard, it is crucial to be

22
clear from the very beginning exactly what aspects of the patient you feel the

intervention can realistically change (e.g., attitudes about drug use, alcohol use,

substance abuse-related behaviors, health service utilization, etc.).

MEASUREMENT OF TREATMENT INTERVENTION

Purpose of Treatment Measurement

It is no longer adequate in a research design to state only that a particular type

of intervention will be provided and that this intervention will be compared

against “standard treatment” or “a placebo condition.” It is essential to use the

same care and effort in measuring the treatment provided as that used in

measuring the patient. This is particularly important in the case where the

intervention is found to be successful. Accurate measures of the nature and

extent to which the treatment is provided will enable subsequent workers in the

field to accurately reproduce the intervention and, with it, the positive results.

Treatment measurement is also important for determining whether the results

that are seen at followup are due to the effects of the intervention or to some

external factor. It often has been the case in treatment evaluation studies

that a certain type of treatment has been delivered to patients followed by

assessments of drug use or other outcomes 6 months after the end of

the intervention. When favorable outcomes have been seen, these good

results have been attributed to the behavioral intervention. Without knowing

whether the patients have achieved (or even made progress on) the goals of

the treatment during the treatment process or whether those who received the

“full amount” of treatment did better than those who received little care, it is not

possible to conclude that the results are due to that treatment.

Methods of Treatment Measurement

There are quantitative and qualitative measures of treatment. Quantitative

measures of treatment provide a record of how much of each type of service or

intervention has been received by the patient. This is important in ensuring that

an “intensive, experimental treatment” provides more treatment services and/or

sessions than the “control condition” or “treatment as usual.”

Qualitative measures of treatment provide indications of whether the

treatment was implemented in the intended manner and whether it achieved

its intended goals. Given two-stage treatments such as detoxification

followed by rehabilitation, or education followed by skill training, it is essential to

be sure that the objectives of the first stage (e.g., complete detoxification,

full understanding of educational material) have been achieved before initiation

of the second stage.

23
It is often necessary to combine these types of measures, as in the case of

multicomponent treatment interventions such as those involving social services,

medical care, pharmacological therapies, and, perhaps, with behavioral or skill

training techniques. Quantitative evaluation of the components through

measurement of the number and types of sessions on a weekly basis can be

combined with equally important qualitative measures of the patient’s opinions

regarding the treatments and staff ratings of the patient’s progress through

treatment. Combined quantitative and qualitative measures, such as whether

the patient has received the amount and duration of the intended treatment

and whether that was what she expected, can be important for addressing

issues of dropout and treatment retention.

It is important to evaluate the patient with interim measures throughout the

course of the treatment intervention, again taking care to target those aspects

of the patient that can reasonably be expected to change. For example,

regular urinalysis and breathalyzer results can be recorded on a weekly or

even daily basis. This is an objective record of patient change and an important

dimension throughout the course of treatment. This can be combined with

regular assessments of patient knowledge in interventions where the effort is

designed to teach the patient about drug use or some other aspect of health

care.

These quantitative and qualitative measures applied throughout the course of

treatment also can help in the assessment of whether patients have achieved

the target goals of treatment. If a treatment is a pharmacologic intervention

designed to achieve a target blood level of a medication, it is important to

determine exactly how many patients achieved that blood level. If the treatment

under study is a behavioral intervention and it is expected that the intervention

will be able to teach a patient a new strategy dealing with the problem, it will

be critical to determine how many patients learned how to perform the skill

by the end of the intervention, prior to assessing outcome. Finally, even in

standard drug abuse treatment programs where one of the critical goals is the

confrontation of denial, it is important to determine how many patients reduced

or eliminated their denial by the end of the treatment.

Techniques of Intervention Measurement

As in the measurement of the patient, it is important to measure multiple

dimensions of the treatment intervention using multiple methods of assessment.

For example, a simple chart review should provide a quantitative measure of

the number of sessions attended. It is possible to ask the patient and/or the

treatment provider directly, on a regular basis, how many sessions or services

have been received. It is also possible to get qualitative judgments by

24
independent raters regarding the progress of patients along critical dimensions

(e.g., understanding what drugs can do to health, acceptance of addiction,

participation in group therapy) during the course of treatment. In addition, it is

essential to get measures of alcohol and drug use through objective laboratory

tests throughout the course of treatment.

Summary

It is as important to measure the nature and quantity of treatments provided

as it is to measure the patients. As in the case of patient measurement,

multiple methods are available and suggested: quantitative assessment of the

number, intensity, and duration of treatment services provided to patients; and

qualitative measures of the extent to which the goals of treatment have been

met, the patient’s satisfaction with the intervention, and the extent to which

the intervention was delivered as intended. These measures will ensure that

the interventions studied are delivered in the manner, amount, and intensity

necessary to effect the desired changes, Again, it is essential to develop a

clear idea of what the treatment realistically ought to be able to accomplish by

the end of the intervention. This will be helpful in constructing treatments of

appropriate duration, intensity, and focus, It is often the case that interventions

are designed to achieve detoxification, patient education, reduction of denial,

and the learning of relapse prevention skills. However, the patient population

often has multiple problems (drug use, health care issues, psychiatric problems,

pregnancy), and the treatment is designed for delivery within a 28-day period.

Complicating this immediate problem of overexpectation on the part of the

investigator can be the additional problems that the intervention is improperly

applied for only a fraction of the time intended and without measures of the

progress of the patient during the course of the treatment. This inadequately

applied and evaluated intervention often is followed by a 12-month followup with

the expectation on the part of the investigator that there will be significant and

broad behavioral changes among participating patients. This is truly unrealistic

and unfair to a treatment intervention. It is far better to determine realistically

what an intervention can do, develop a realistic expectation of the duration and

intensity of treatment required to produce the desired change, and then

construct measures of the specific behavioral attitudinal factors that are

expected to be changed.

POSTTREATMENT FOLLOWUP

Purpose of Followup

The ultimate measure of the efficacy of a treatment intervention is the outcome

of the patients receiving the intervention, following its completion. Two types of

25

318-164 0 - 92 - 2 : QL 3
measures are possible at followup. First, improvement from the baseline can

be measured through a simple comparison of the experimental group from the

baseline to the followup point. Obviously, to achieve this, it will be important

to ask the same questions at followup as were asked at the time of treatment

admission. This is why so much preparation and thought should go into the

initial assessment.

A second measure available at followup is an assessment of the overall

status of the patient following treatment (i.e., her outcome) relative to either an

absolute goal set before treatment (e.g., abstinence, employment, not being in

jail) or against the outcome of a matched control group (i.e., a group of similar

patients who have not had the same intervention).

It is important to note that these two kinds of measures are different.

Improvement is not the same as outcome. A patient may show a 50-percent

“improvement” in drug use from admission to followup but still not have

achieved the desired “outcome” of total abstinence. Therefore, it is important

to be able to assess both measures for a comprehensive evaluation. Again,

in this regard, the use of continuous variables as measures will be extremely

helpful for both purposes.

Measurement Issues In Followup

The first issue is that the evaluator at the followup point must be independent of

the treatment process. A followup evaluation where the person collecting the

information was part of the treatment process will not be taken seriously. It is

not possible for that person to be completely objective, nor is it possible in most

cases for the patients to provide truly accurate answers to a person they have

been in treatment with for many months. Thus, it will be important to have

independent staff to track and interview these patients.

Another important issue is the length of followup. There is no standard

followup assessment point. The point following the completion of treatment

at which a patient should be assessed is almost entirely a function of the

expectations about the effects of the intervention under study. It is pointless

to do a 1 P-month followup on a brief, limited intervention such as a

detoxification procedure when it is expected that the detoxification will not

by itself have long-term consequences and likely will be followed by other

interventions. Here, the “real” expectations of the detoxification are that:

l The procedure will safely reduce the drug levels in the patient. (Thus, drug

levels and detoxification side effects should be measured daily.)

26
l The patient will be engaged in treatment. (Thus, dropout levels will be

important.)

The patient will accept referral to ongoing rehabilitation. (Thus, the

proportion of patients who accept and remain in rehabilitation for 2 weeks

or more would be an example of one appropriate followup measure.)

Obviously, longer and more involved treatments will require longer term

followup contacts. However, even here, a majority of relapses to drug and

alcohol dependence occur within the first 3 months following completion of

care. Therefore, even in long-term followup studies, it is wise to include

intermediate followup measurement points at 3 and/or 6 months following

treatment.

Locating and Contacting Patients at Followup

Perhaps the most important aspect of followup is the tracking and locating of

patients. The success of a posttreatment followup is almost entirely a function

of the preparation and effort employed during treatment. It is critical to state

that followup efforts cannot be initiated after the patient has left treatment;

they must be started at the time of admission and must involve the patient

throughout the treatment.

Steps In Preparlng the Patient for Followup. There are several systematic

steps that must be undertaken to prepare for a followup evaluation. First, the

patient should be told at admission and throughout treatment that a followup

assessment will be performed. The patient should sign a consent to permit

followup at that time. At the time of admission, the patient should be asked to

provide the names and addresses of at least three separate persons who will

know her location at the time of the followup. It should be stressed to the

patient that these sources will be used only to help locate the patient and that

no information will be provided to the three contact persons or to any other

individual or agency without her consent. In the author’s experience, female

sources are more reliable and stable sources of patient contact than male

sources. Thus, at least one of these names and addresses should be a mother,

sister, aunt, or close woman friend. Once these names and numbers are

provided, it is important for followup technicians to verify the telephone numbers

and addresses while the patient is in treatment. Often, false information is

provided at that time, and this can be brought back to the patient and corrected

with a reaffirmation of the confidentiality.

It also will be important at the same time to collect any information about

sources of money or other benefits or services that the patient may be

expecting to receive following treatment. For example, addresses where

27
welfare, Social Security, veterans’ benefits, payroll, and/or unemployment

checks will be mailed will be important to record. Similarly, it is important to

record the full name and address of the patient’s social worker or caseworker at

the welfare office, as well as names and addresses of people in the Social

Security or the parole or probation office with whom the patient has had contact.

These are the kinds of contacts that are likely to know the whereabouts of

the patient at followup. The patient should be asked to sign a “release of

information” form to those people and those agencies early in the course of

the treatment, and again, these sources should be called and verified and the

followup worker should inform (where possible) the individuals at these

agencies that they will be recontacted at followup for help in locating the

patient. This followup information should be checked again at the time of

treatment discharge to detect any changes and as a reminder of the followup

contact that will occur subsequently.

A final issue regarding the preparation of the patient is the use of financial

incentives. Please remember that followup can be a lengthy and intrusive

process and unless there is something “in it” for the patient, the investigator

cannot always be assured of cooperation. Therefore, the author and

colleagues always have found it is essential to provide a minimum of $20 and

sometimes as much as $50 to patients to defray their transportation costs and

to compensate them for their time associated with coming in and providing with

information. This is an excellent investment in that, without the followup

information, virtually all the baseline and during-treatment measures will be of

little value. The patient should be reminded of the followup financial incentive

at the time of treatment discharge and at the beginning of each followup contact

effort.

Staff Preparatlon. A second area of preparation involves the institution of

standard procedures among research or project staff members. For example,

the staff must prepare a log sheet on which the date, day, time of day, and a

space for comments are listed for each patient to be contacted. Each contact

attempt (telephone call, visit, letter) to anyone associated with the patient must

be recorded with ample notation documenting exactly who was contacted, the

result of the contact, and the plan for the next contact. This will prevent calls to

only one number or repeated contacts at times when it is clear that no one is at

home.

It will be important for the research project to have a separate telephone that

can accept collect telephone calls from patients. In addition, it will be important

to hire staff people who can work flexible hours. It is not possible to do patient

followup from “nine to five.” It is necessary to have staff members who can

work evening and/or late night hours and on weekends. In addition, it will be

28
important to develop a telephone manner that will ensure confidentiality.

That is, the followup telephone must be answered by all personnel in a manner

that will convey professionalism and at the same time will not convey any

association with alcohol or drug abuse (e.g., “Hello, may I help you?” rather

than “Perinatal Drug Research, can I help you?“). Furthermore, the staff must

be trained to request information from agencies and relatives of the patient but

nor to provide information about the patient.

Agency Preparation. It is important to have the backing of the funding

agency or agencies, local government agencies, and the sponsoring institution

(e.g., a university or hospital). It also will be important to have letters from

each of these organizations officially underwriting the followup effort (without

identifying it as a drug or alcohol abuse effort), thereby legitimizing the activity.

Remember that many people are trying to contact these patients. For this

reason, concerned relatives and the other social service agencies will not

provide information unless they know that it is a legitimate inquiry (as indicated

by these letters) and that it is permitted by the patient (the release of information

signed by the patient will help in this regard).

Collateral Informatlon. There have been suggestions regarding the use of

collateral information, which is information about the patient provided by an

employer, spouse, or some other member of the family or social network.

Some investigators in the field do not accept patient reports and seek to confirm

the reported data with the reports from “more trusted” collateral sources such

as a spouse. This can produce many problems. First, it is rare that a spouse

knows detailed information about the patient. Patients often report (under

conditions of confidentiality) more alcohol, drug use, and crime than the spouse

knows about. Second, the use of collateral information risks the confidentiality

of the patient, and this is important in securing the patient’s cooperation. It is

most important to assure patients that no agency or individual will learn

any information about them from the followup effort. Finally, even though

consistently reliable information has been provided at followup by using

technicians who are not part of the treatment process and by ensuring patient

confidentiality, it is wise to obtain breath and urine samples on subjects to

confirm these reports.

Summary

The final discussion of followup measurement highlights earlier discussions of

patient and treatment measurement. Followup is the best assessment of the

efficacy of a treatment intervention. Therefore, it is critical to have a clear set of

baseline measures on the patient in those areas that are expected to be able to

improve with the intervention and to repeat these measures at followup to

assess improvement and outcome.

29
The measures that are collected at followup are essentially identical to the

measures that were collected at the time of treatment admission but in

abbreviated form. However, the same methodological issues, techniques, and

considerations apply. As at the time of the initial assessment, the patient

should be measured in all those areas that are expected to be changed, the

patient should be assessed with multiple methods (interview questionnaire and

objective laboratory data), and all care should be taken to assure the patient

that the information will be treated in a professional manner and that her privacy

and confidentiality will be protected.

An effective posttreatment evaluation requires effective tracking, locating, and

reinterviewing each patient following treatment. The ability to recontact these

patients after treatment is almost entirely dependent on the level of information,

patient preparation, and interagency cooperation established during the time

the patient was in treatment. Followup is an important but difficult job that must

be coordinated from the very start of treatment and must involve the patient,

followup staff, clinical program, and sponsoring agency or agencies.

AUTHOR

A. Thomas McLellan, Ph.D.

Scientific Director

Penn-VA Center for Studies of Addiction

Philadelphia Veterans Administration Medical Center

Building 7

University Avenue

Philadelphia, PA 19104

30
Discussion: Statistical Analysis in

Treatment and Prevention Program

Evaluation

Joel W. Ager

INTRODUCTION

This chapter focuses on problems of statistical analysis in the context of

evaluations of substance abuse treatment and prevention programs. In another

chapter (this volume), Sokol and colleagues address additional statistical issues

in the context of research that studies the antecedents and/or consequences of

substance abuse (particularly of alcohol) during pregnancy. Of course,

appropriate statistical analysis depends heavily on other aspects of the

research, including the specific questions asked; the theories, if any, generating

these questions; the sampling schemes for inclusion of subjects, situations, and

variables: the psychometric properties of the variables: and the designs used.

This chapter also comments on implications for analyses of issues discussed in

the chapters by Gilchrist and Gillmore and by McLellan.

The statistical and design issues to be discussed fall under four major headings:

1. Types of designs and their associated statistical analyses

2. Covariance and other adjustment techniques in analyses of quasiexperimental design data

3. Modeling change

4. Meta-analysis

STATISTICAL AND DESIGN ISSUES

Types of Designs and Associated Statistical Analyses

Completely Randomized and Randomized Blocks Designs Usually Wlth

Repeated Measures. In most treatment and prevention program evaluations,

31
pretest, posttest, and followup data will be obtained. The major differences

among designs will be in how subjects are selected and then assigned to

treatment and control conditions. The ideal, of course, would be to assign

subjects to conditions randomly. The great advantages of completely

randomized or randomized blocks designs are well known and need not be

elaborated here. For ethical, logistic, or other reasons such random assignment

often is not deemed possible. However, the investigator should not overlook

the possibilities of random assignment of intact groups (e.g., clinic sites or civic

subgroups) to treatments when such subgroups are sufficiently numerous.

Most problems in the statistical analysis and interpretation of results occur

because randomization was not possible.

When randomization of subjects to treatments is possible, it is almost always

desirable also to stratify on factors (e.g., age, gender, race) that might be

expected to be related to the outcome(s). There are two major reasons for

stratifying. One is the increase in statistical power as a result of smaller withincell variances. The other, perhaps more important, reason is the ability to

assess block by treatment interaction effects. Significant interactions,

particularly those of a higher order, may be inconvenient to interpret, but at

least they provide a warning about the generalizability of the main and lower

order interaction effects. Grant reviewers and others often object that such

stratification makes the design too complex or that the resulting cell sizes

become too small. On the contrary, power for main effects tends to be highernot lower-with more refined stratification because the smaller mean square

error more than offsets loss of degrees of freedom (df) for error. As noted

above, stratification also makes possible better assessment of the degree of

generality of the treatment effects.

Corresponding to stratification of subjects is the breakdown of treatments into

components. If facets of the treatments are identified, they usually can be

arranged in a factorial or in fractional replications layout so that the effects of

these facets and their combinations can be assessed. In this context, theories

of treatments can make specific contributions (Lipsey 1990). Analyses of data

from such designs can be extremely useful in answering questions concerning

why and how treatments work or fail to work. When costs can be attached to

facet levels, a good basis for cost-benefit analysis should be available from data

generated by such designs.

The Regression-Discontinuity Design. When randomization of subjects or

units to treatments is not possible, what are the alternatives? A little-used

treatment that seems to hold much promise is the regression-discontinuity

design (Cook and Campbell 1979; Trochim 1984, 1990). In this design,

selection of the subjects for the treatments is made on the basis of a pretest;

32
only subjects scoring above (or below) the cutoff are selected into the

treatment. The pretest need not be the same variable as the outcome but

presumably is related to it. The treatment effect then is represented as the

difference between groups on the regression surface evaluated at the cutting

point on the pretest. Variations of the design are possible; for example, the

pretest could be a composite of several selection variables (Trochim 1990).

Also, in theory at least, it should be possible to assign the selected subjects

randomly to several treatments or treatment combinations.

Analysis of this design can be quite complex. The most difficult task is

determining the appropriate regression surface. One suggestion is to use

polynomial fitting (including polynomial term by group interactions) using a

backward elimination procedure. Visual inspection of scatter-plots of the

pretest/posttest relationship also is advocated. Problems can occur when the

cutting point on the pretest is not reliably or consistently used in the selection

procedure. Also, compared with the sample-randomized design, the statistical

power of this design is considerably less; at least 2.75 times as many subjects

are needed to give comparable power.

Despite its complexity of analysis and relative lack of power, the regressiondiscontinuity design has inherent advantages over the nonequivalent groups

design even when the latter is analyzed with covariate adjustments. The main

advantage is that the internal validity of this design approaches that of the

randomized design because the subject selection process is fully known. This

design probably should be used more often than it is in situations in which

treatment is assigned on the basis of pretest scores.

Adjusting for Selectlon Bias in Nonequivalent Group Designs

Methods of Adjustment. Of all the variations in quasi-experimental designs

discussed by Cook and Campbell (1979), the one that probably is used most

frequently in evaluations of treatment programs is that involving pretest/posttest

measures on nonequivalent treatment and control groups. There is an

extensive literature (e.g., Cook and Campbell 1979) on selection and other

biases inherent with this design and the consequent problems of interpretation.

In practice, these biases may lead to either overestimates or underestimates of

treatment effects. Several statistical and/or design methods can be used to

minimize such biases: analysis of covariance (ANCOVA), block and matching

design, and gain-score analysis. However, none of these is completely

satisfactory in eliminating bias.

A major problem with the use of ANCOVA to adjust for initial group differences

is that of unreliability of the covariate, even when pretest scores are available to

33
serve as the covariate. Such unreliability will result in underadjustment of the

posttest scores, which in turn leads to bias in estimating the treatment effects.

Depending on initial group differences, the bias may be in either direction (i.e.,

overstating or understating of treatment effects).

As Gilchrist and Gillmore (this volume) point out, use of structural models (e.g.,

LISREL) (Jöreskog and Sörborn 1979, 1984) has been suggested as a way of

eliminating effects of covariate unreliability on estimation of treatment effects.

In these nodels, pretest and posttest variables are represented by latent

constructs. Each construct is measured by several manifest (observed)

variables. Because the measurement model part of the LISREL analysis

accounts for unreliability, the constructs can be assumed to be perfectly

reliable. LISREL and other structural models (e.g., Bentler 1985) have had

fairly extensive use in recent years, particularly in the social sciences. Few

studies, however, have applied these models to the problem of evaluating

treatment effects in quasi-experimental designs. As Gilchrist and Gillmore point

out, this approach appears promising and may be more widely used as

investigators become more acquainted with these structural models and trained

in their use.

Sensitivity Analysis. Model specificaiton is another problem with the use of

covariance adjustments in dealing with selection or attrition biases. If all

relevant covariates are not included in the model, then underadjustment will

result. Moreover, inconsistencies across studies or even within analyses of the

same study may occur if different covariate sets are used. Wainer (1989) gives

several examples of such inconsistent analyses in his recent paper, “Eelworms,

Bullet Holes and Geraldine Ferraro: Some Problems With Statistical

Adjustment and Some Solutions.”

As Gilchrist and Gillmore suggest in their chapter, several sophisticated modelbased procedures-some of which are discussed by Wainer (1989)—have

been proposed recently that are designed to address the problems of

nonresponse and self-selection. Among these are Rubin’s Mixture Model

(Rubin 1987) and Heckman’s Selection Model (Heckman and Robb 1986). The

purpose of these techniques is to evaluate the robustness of the findings (e.g.,

treatment effects) over a set of plausible assumptions about distributions of the

relevant variables in the nonobserved sample. These “sensitivity” analysis

procedures do not guarantee definitive answers to the adjustment problem but

allow uncertainties to be more accurately characterized. A good introduction to

these methods is found in a set of discussion papers based on the Wainer

article that constitute the summer 1989 issue of the Journal of Educational

Statistics. (These methods are difficult to use, particularly for those unfamiliar

with Baysian statistics.)

34
The Modeling and Evaluation of Change

The Two Groups Pre-Post Score Design. As with covariance adjustment,

use of gain scores to adjust for selection factors on the evaluation of treatment

effects in quasi-experimental design has been strongly criticized, beginning with

the work of Lord (1958) in the late 1950s. In their widely cited paper on this

issue, Cronbach and Furby (1970) conclude that use of difference scores is

rarely if ever justified with correlational data.

The main criticisms of use of gain scores have focused on two main points.

The first problem is similar to one associated with the use of pretest scores as

covariates; namely, to the extent that the pretest scores contain measurement

error they necessarily will be correlated negatively with the pre-post difference

scores. According to the critics, this correlation, in turn, will lead to biased

estimates of change. A second criticism of difference scores is that they are

alleged to be inherently unreliable. Using the traditional formula for difference

score reliability, which assumes equal prescore and postscore population

variances, it has been noted that, as the pre-post correlation approached the

equivalence reliabilities of the pre and post measures, the reliability of the

difference scores tended to zero. Some authors (e.g., Overall and Woodward

1975) even claimed to find a paradox in the mixed design analysis of variance

(ANOVA) in that higher pre-post correlations produce greater statistical power

for the tests of within-subject effects yet result in a lowered reliability of the

difference scores. It should be noted that the mixed design evaluation of the

group by pre-post interaction is statistically equivalent to comparing the two

groups on their difference scores via an independent groups t-test. Despite

these criticisms by Cronbach and others of the use of difference scores in the

evaluation of treatments and the seeming paradox involving reliability and

power, the mixed design analysis continued to be used widely, although

perhaps with some guilt. After all, what were the alternatives? At least in

describing the mixed design analysis, one did not have to use the term

“difference scores” explicitly.

More recently, several methodologists, among them Rogosa and colleagues

(1982), have mounted a defense of the use of difference scores. Rogosa

showed that imposition of the equal pretest, posttest population variance

assumption forces the negative pretest-difference score correlation. In

situations in which there are reliable individual (or group) differences in true

gain, the posttest population variance could be expected to be larger. As one

example, suppose those with higher initial scores tended to show the greatest

gains. Under these circumstances the plot of pretest and posttest scores would

tend to show a fan-shape pattern and the postscore variance would be larger.

In this case, as Rogosa points out, the reliability of the difference scores could

35
be quite respectable even when the pre-post correlation was high. When the

treatment and experimental groups have different mean gains, a similar fanshape plot results, and again, the reliability of the difference scores calculated

on the combined groups (and not within groups) would not be as low as

suggested by the paradox discussed above. Rogosa does point out that

although difference scores are unbiased and perfectly appropriate estimates of

true change, they contain little information about the nature of change. To

model change more adequately, one would need to measure the dependent

variable at several time points.

Evaluation of Treatment Effects Over Time. When one or more followup

scores are obtained on the dependent variable(s), the effects of most interest

are the group x time interactions. Because there is usually interest in the nature

of change over time, trend components or other planned contrasts can be used

for this purpose. Again, evaluating the group by contrast interactions is

advisable. Tests of contrast have considerably more power to detect specific

patterns of change than the omnibus tests usually performed. Note also that

df=1 tests do not assume compound symmetry (or sphericity) as do the df>l

omnibus tests. Even when several outcome measures are considered in a

multivariate analysis of variance (MANOVA) or multivariate analysis of

covariance (MANCOVA) design, such trend contrasts should be considered.

Using Tlme Series Analysis To Evaluate Effects of “Natural” Interventlons.

Another type of statistical analysis may be appropriate when assessing

changes in outcome or other behavior as a function of what might be termed

“natural” interventions is of interest. Such interventions might be changes in

law, societal attitudes, or more specific institutional changes (e.g., in policies,

treatment procedures, or eligibility requirements). For this analysis,

observations on the dependent variable(s) of interest, either longitudinal or

cross-sectional, for many time points (at least 50) are required. Also needed is

specification of the time source of the intervention. The main purpose of the

time series analysis (TSA) in this situation is to model and evaluate treatment

effects that are presumed to result from the intervention.

An example of this use of TSA is the ongoing evaluation by the author and

colleagues of the effects (if any) of the recent liquor-labeling law on maternal

drinking. For the baseline data, drinking histories and the MAST questionnaire

collected over the past 3 years from all maternity clinic patients at Hutzel

Hospital in Detroit are being used. The postintervention series will continue for

another 3 years. Other medical background and substance use data are also

available on these patients. For the patients seen in any given week, several

drinking indices are calculated (e.g., average amount of alcohol per day, the

proportion of drinking days). To assess the trend in use among the at-risk

36
maternal drinkers, the 90th percentile of these measures for the weekly

samples also is determined.

The modeling of the time series consists of two stages (Cook and Campbell

1979). In the first, the structure of the correlated error is determined and

included in the model. Overall linear trends and possible seasonality effects

also are evaluated and included if necessary. The second and most difficult

part of the analysis is the modeling of the intervention. Should the effect be

represented as gradual or abrupt? If there is a decrease in drinking, will it

increase over time to baseline? Because a number of possible patterns of

intervention effects will need to be modeled, a cross-validation design will be

employed.

Although TSA has not been used much in the health sciences to evaluate

natural interventions, it is routinely used in economics. With the wider

availability of computerized health records, more use of this approach in the

health sciences seems likely.

Meta-Analysis: Aggregatlng lnformation About Intervention Effects Over

Studles

No single study will provide complete information on the effectiveness of a given

treatment or prevention approach. It is not surprising that for investigators and

policymakers questions about the generality and robustness of results on

treatment effects have become more urgent, One method for aggregating

results over studies that has found increasing favor is meta-analysis (Glass et

al. 1981; Hunter et al. 1982; Hedges and Olkin 1985). One reason for the

increasing popularity of this approach has been the development of

sophisticated statistical methods for not only aggregating effect sizes but also

for evaluating sampling error in the primary studies, determining the

homogeneity of results among studies, and developing models of the

differences in results among studies.

The results of a meta-analysis, however, are limited by the quality of the primary

studies forming the databases. A second and equally serious problem is that

reports of the primary study often lack the detailed information needed by the

“meta-analyst” to assess the quality of the various facets of the study or even to

compute the needed effect sizes.

Another difficulty encountered in aggregating results of treatment and

prevention studies is that the studies may use quite different outcome

measures. If investigators within a certain research area could agree on a set

of core outcomes to be obtained by all studies, this problem could be alleviated.

37
Looking ahead to the future prospects for this approach, it is ironic to note that

as analyses of the primary studies become more sophisticated, the metaanalysis of them will tend to become more difficult. For example, combining

results from studies using structural equation modeling as the main statistical

analytic method becomes a difficult challenge.

Despite the difficulties, I believe that meta-analysis will become increasingly

important as an approach in the health and social sciences. Not only does it

contribute to what is known, but it is also a useful basis for assessing what is

not. Perhaps its greatest contribution is to the efficient planning of future

primary studies.

DISCUSSION

I endorse McLellan’s plea for investigators to measure as many different

outcome variables as possible and to do so with continuous measures if

possible (McLellan, this volume). As he points out, abstinence may not be the

only worthwhile goal for a treatment or prevention program. For example, if

heavy maternal drinkers can be persuaded to cut down, the effects on improved

infant outcomes may be greater than inducing light or even moderate maternal

drinkers to abstain. Of course, more detailed dose-response information

concerning the relation between maternal substance abuse and infant and child

outcomes would be useful in refining goals for programs and outcomes to be

assessed.

Gilchrist and Gillmore (this volume) suggest greater emphasis should be placed

on evaluating program effect on improving infant outcomes. Although the wellbeing of the offspring is an ultimate criterion, I suspect that direct program

effects on the infant and child variables will be relatively small and probably

mediated by maternal substance abuse behavior as well as other maternal

variables. Perhaps the best way to evaluate ultimate program effects is through

analysis of structural models within which possible mediating variables can be

accommodated, as they suggest. Poland and colleagues (1990) have used this

general approach in looking at the effects of quality of prenatal care on birth

weight.

SOME CONCLUSIONS

No statistical techniques, however sophisticated, can compensate completely

for a poorly selected sample, lack of randomization, unreliably measured

variables, and lack of theoretical base (or at least specific questions to be

addressed). Many of the statistical models and methods designed to overcome

the above problems are mathematically complex, difficult to implement, and

38
difficult to interpret. Despite these factors, such methods are potentially useful,

particularly to the extent that they help evaluate the degree of uncertainty

inherent in results and conclusions.

REFERENCES

Bentler, P.M. Theory and Implementation of EQS, a Structural Equations

Program. Los Angeles: BMOP Statistical Software, 1985.

Cook, T.D., and Campbell, D.T. Quasi-Experimentation: Design and Analysis

Issues for Field Settings. Chicago: Rand McNally, 1979.

Cronbach, L.J., and Furby, L. How should we measure “change”—or should

we? Psychol Bull 74:68-80, 1970.

Glass, G.V.; McGraw, B.; and Smith, M.L. Meta-Analysis in Social Research.

Beverly Hills, CA: Sage, 1981.

Heckman, J.J., and Robb, R. Alternative methods for solving the problem of

selection bias in evaluating the impact of treatments on outcomes. In:

Wainer, H., ed. Drawing Inferences From Self-Selected Samples. New

York: Springer-Verlag, 1986. pp. 63-107.

Hedges, L.V., and Olkin, I. Statistical Methods for Meta-Analysis. New York:

Academic Press, 1985.

Hunter, J.E.; Schmidt, F.L.; and Jackson, G.B. Meta-Analysis: Cumulating

Research Findings Across Studies. Beverly Hills, CA: Sage, 1982.

Jöeskog, K.G., and Sörborn, D. Advances in Factor Analysis and Structural

Equation Models. Cambridge, MA: Abt Books, 1979.

Jareskog, K.G., and Sörborn, D. LlSREL VI User’s Guide. Mooresville, IN:

Scientific Software, 1984.

Lipsey, M.W. Theory as method: Small theories of treatments. In: Sechrest,

L.; Perrin, E.; and Bunker, J., eds. Research Methodology: Strengthening

Causal Interpretations of Non-Experimental Data. Agency for Health Care

Policy and Research. DHHS Pub. No. (PHS)90-3454. Washington, DC:

Supt. of Docs., U.S. Govt. Print. Off., 1990. pp, 33-56.

Lord, F.M. Further problems in the measurement of growth. Educ Psychol

Meas 18:437-454, 1958.

Overall, J.E., and Woodward, J.A. Unreliability of difference scores: A paradox

for measurement of change. Psychol Bull 82:85-86, 1975.

Poland, M.L.; Ager, J.W.; Olsen, K.L.; and Sokol, R.J. Quality of prenatal care;

selected social, behavioral, and biomedical factors: and birth weight. Obstet

Gynecol 75(4):607-612, 1990.

Rogosa, D.; Brandt, D.; and Zimowski, M. A growth curve approach to the

measurement of change. Psychol Bull 92:726-748, 1982.

Rubin, D.B. Multiple Imputation for Nonresponse. New York: Wiley, 1987.

Trochim, W.M.K. Research Design for Program Evaluation: The RegressionDiscontinuity Approach. Beverly Hills, CA: Sage, 1984.

39
Trochim, W.M.K. The regression-discontinuity design. In: Sechrest, L.; Perrin,

E.; and Bunker, J., eds. Research Methodology: Strengthening Causal

Interpretations of Non-Experimental Data. Agency for Health Care Policy

and Research. DHHS Pub. No. (PHS)90-3454. Washington, DC: Supt. of

Docs., U.S. Govt. Print. Off., 1990. pp. 119-140.

Wainer, H. Eelworms, bullet holes and Geraldine Ferraro: Some problems with

statistical adjustment and some solutions. J Educ Stat 14(2):121-140, 1989.

ACKNOWLEDGMENT

The work described in this chapter was supported in part by National Institute

on Alcohol Abuse and Alcoholism grants P50 AA-07606, R01 AA-06966, R01

AA-06571, and R01 AA-8906.

AUTHOR

Joel W. Ager, Ph.D.

Professor

Departments of Psychology and Obstetrics and Gynecology

Wayne State University

71 West Warren

Detroit, Ml 48202

40
Role of Biologic Markers in

Epidemiologic Studies of Prenatal

Drug Exposure: Issues in Study

Design

Michael B. Bracken, Brian Leaderer, and Kathleen Belanger

INTRODUCTION

Exposure assessment plays a central role in epidemiologic studies. It is crucial

for minimizing the effects of misclassification and the influence of confounding

variables and for improving the probability of revealing the true associations

between exposure and health effects.

Exposures to risk factors can be assessed by direct or indirect methods.

Indirect techniques are used extensively in epidemiologic studies. They

focus on using questionnaires and statistical modeling to estimate exposures.

In contrast, direct-method techniques employ personal monitoring and biologic

markers (biomarkers) to provide an integrated measure of exposure. Personal

monitoring refers to objective measurement of an individual exposure to a

risk factor of interest (urinalysis of consumed drugs; use of personal

monitoring to assess human contact with air, water, or food contaminants;

etc.). Theoretically, biomarkers are indicators of dose and can serve as

correlates or surrogates of exposure. However, in practice it is difficult to

relate biomarkers to specific levels of exposure or to a specific source of

exposure because of limitations in the understanding of such factors as drug

uptake, distribution, metabolism, and site and mode of action of the agents of

interest. Biomarkers by themselves may not identify the mode or magnitude

of the exposure and, thus, need to be supplemented by other direct or indirect

assessment measures.

Biomarkers are increasingly being used in a variety of epidemiologic studies

(Perera 1987; Harris et al. 1987). This chapter argues that the utility of

biomarkers will not be fully realized unless they are used within the context of

well-designed and properly conducted epidemiologic studies. Indeed, in the

41
absence of a rigorous methodologic framework, biomarkers could be

misleading. The chapter presents an example of a study design, which the

authors call a nested prospective study, as an example of how biologic

monitoring can be incorporated into epidemiologic studies of prenatal drug

exposure.

DEFINITIONS OF BIOMARKERS

In this chapter, biomarkers are considered to measure both exposure and

disease outcomes. Our definitions are the same as those of the Committee on

Biologic Markers of the National Research Council.

A biologic marker of exposure is an exogenous substance or its

metabolite(s) or the product of an interaction between a xenobiotic agent

and some target molecule or cell that is measured in a compartment within

an organism.

A biologic marker of effect is a measurable biochemical, physiologic, or other

alteration within an organism that, depending on magnitude, can be

recognized as an established or potential health impairment or disease

(Committee on Biologic Markers, Subcommittee on Reproductive and

Neurodevelopmental Toxicology 1989, p. 2).

A biomarker of exposure is an indicator that an exposure (concentration of the

agent multiplied by the time in contact with it) has taken place. It is

quantitatively related to exposure through pharmacokinetics, which describe

rate of uptake, distribution, metabolism, and elimination of the agent in the

body. Biomarkers of exposure are measures of internal dose (amount of the

agent or its metabolites retained in the body over a given period) or of

biologically effective or administered dose (amount of the agent or its

metabolites at the cell or target site where the health or comfort effect occurs).

Biomarkers of health or comfort effects can be indicators of early biological

effects, altered function or structure, and clinical disease.

Biomarkers can be unchanged exogenous agents (e.g., nicotine or heavy

metals), metabolized exogenous agents (e.g., cotinine), endogenously

produced molecules (e.g., alpha-1-antitrypsin), molecular changes (e.g., DNA

adducts), and cellular or tissue changes (e.g., cell histology).

Within an epidemiologic context, the use of biomarkers has the potential to

further specify relationships that may exist between an exposure and a disease

outcome. Biomarkers may permit exposure to be modeled more precisely; they

may indicate biologic mechanisms by which an exposure may cause disease;

42
and they may be used to identify the precursors of disease. All the above may

bring increased specificity, statistical power, and validity to epidemiologic

studies.

Factors lnfluenclng the Choice of Biomarkers

The factors that influence the effectiveness of or determine the suitability for the

use of a particular biomarker in an epidemiologic study include the following:

1. Potential for Use—Is there a sensible biologic interpretation of the marker

compound? Is there potential for obtaining samples? What is the extent of

variability of the marker from individual to individual?

2. State of Development-Has the marker been evaluated in animal, human

clinical, or large population studies?

3. Properties of the Marker—Is it specific to the exposure of interest (e.g.,

cotinine is specific to tobacco smoke exposure, whereas DNA adducts can

result from a range of sources)? Is there sufficient sensitivity? (Can it be

measured at levels relevant to the exposures of interest or is the lower

detectible limit well above levels consistent with normal exposure ranges?)

What is the level of understanding of the metabolic characteristics of the

compound? What is the invasiveness of sample collection? For example,

does blood need to be drawn or can a urine or breath sample be used?

4. Laboratory Issues

l Sample collection and handling: Do samples have to be frozen? What

is the stability of the marker in time? Are there losses to surfaces of

storage containers? Is there cross-reactivity?

l Analytical methods available: What is the accuracy and sensitivity of

the analytical method?

l Cost: Are the samples easily handled and stored? Can inexpensive

calorimetric analysis be done, or is gas chromatography (GC)/mass

spectrometry analysis required? Is extensive extraction of sample

required?

5. Methodological Issues-What is the sample size (e.g., is the collection

analysis such that it can be done on a large population, or is the cost and

complexity such that only a few samples can be collected and analyzed?),

and what is the potential for confounders?

43
6. Overall Relevance of the Biomarker-What is its relevance to the exposure

and etiology of the health effect of concern?

ADVANTAGES OF MONITORING PRENATAL DRUG EXPOSURE WITH

BIOMARKERS

First, it is evident that some mothers may not remember, may not wish to

remember, or may not wish to report the use of drugs during pregnancy.

Although this comment is particularly pertinent to the use of illicit drugs, even

the use of pharmacologic agents or social drugs (cigarettes and alcohol) may

not be recalled accurately, if at all. Recall of episodic drug use is also often a

problem. Respondents may report that they used an over-the-counter or

prescription drug for a few days for relief of, for example, a headache, hay

fever, asthma, or insomnia. However, they are often uncertain about which

specific weeks during pregnancy they used the drug or how many times they

used it. Several studies have reported inaccurate recall of drugs in pregnancy

(MacKenzie and Lippman 1989; Harlow and Linet 1989).

Of even greater concern than poor recall of drug use is the reporting of

exposures that may be biased with respect to the disease of interest. Although

this is more of a problem in case-control studies (Werler et al. 1989), even

prospective studies may be affected. For example, a woman who is

experiencing vaginal bleeding during pregnancy may alter her reports of

cocaine use, both of which may increase her risk of precipitous preterm labor.

Second, some exposure may be difficult to measure (e.g., environmental

tobacco smoke) or impossible to measure (e.g., radon, electromagnetic fields)

in any way other than by monitoring. An investigator might construct an

interview to ask about the respondents’ perception of how smoky the air is or

how many cigarettes their spouse smokes, but even by developing

sophisticated questions, this clearly falls short of measuring contaminants in the

subjects’ breathing zone. Similarly, questions about electric blanket and other

electric appliance use, or even the development of complicated house wiring

codes (Barnes et al. 1989), are of uncertain validity with respect to a

respondent’s exposure to electromagnetic fields.

Third, individuals show considerable variation in how well they metabolize

drugs. This is due to inherent interindividual differences in the genotype and

also to the concurrent use of other drugs. For example, genetic variability in the

ability to induce placental enzymes necessary for metabolizing xenobiotic

substances has been reported (Nebert and Jensen 1979; Gottlieb and

Manchester 1986). Increased induction may prevent teratogens from crossing

the placenta and reaching the fetus.

44
Individuals who smoke show dramatic differences in their ability to metabolize

other drugs because cigarette smoke induces enzyme activity for other drugs

(Okey et al. 1986), including caffeine. Figure 1 shows lower caffeine levels in

urine among active smokers compared to nonsmokers, with daily caffeine

intake held constant. To fully understand the role of either maternal smoking

(Martin and Bracken 1986) or caffeine (Martin and Bracken 1987) on fetal

growth retardation, for example, the interactive effects of the two exposures

must be evaluated, preferably through the use of biomarkers of exposure. In

many circumstances, exposure to the fetus of a particular drug may be

estimated more precisely from a biomarker in the mother’s urine than from

reports of her own consumption of or exposure to a particular product.

FIGURE 1. Relationship of urinary caffeine to daily caffeine intake by smoking

status

SOURCE: Yale Perinatal Epidemiology Unit, unpublished data 1990

45
Fourth, women metabolize drugs differently during pregnancy. Thus, exposure

to the same amount of a drug leads to different levels in the circulating system

in early pregnancy than exposure to the same amount of drug later in

pregnancy. Figure 2 shows the rate of urinary caffeine at four points in

pregnancy for three daily levels of caffeine based on coffee, tea, and soda use

only. The interactive effects of smoking are avoided by using nonsmokers only.

Women who reported not using coffee, tea, or soda still consumed caffeine from

other sources. Among women using 50 mg or less caffeine daily, there is a

marked increase in urinary caffeine levels as pregnancy progresses, reflecting a

decreased ability to metabolize caffeine. This effect appears to be less marked

in the highest consumption group in these data. This finding supports

theoretical models developed earlier by Mattison (1966). The effects of caffeine

FIGURE 2

SOURCE: Yale Perinatal Epidemiology Unit, unpublished data 1990

Relationship of urinary caffeine to stage of pregnancy by daily

46

caffeine intake
on the fetus are further enhanced by the inability of the fetus or newborn to

metabolize caffeine (Lambert et al. 1986). Thus, fetal exposure to a drug differs

at various stages of pregnancy. This can be modeled with precision only by

using biomarkers.

Fifth, for many drugs of interest, the metabolic product may be of greater

teratogenic potential than the drug. For example, ethanol metabolizes to the

more toxic acetaldehyde, although lower levels are found in maternal blood

(Adickes 1989). For reasons cited above, the metabolic products circulating in

the individual cannot be predicted with any accuracy, and their direct

measurement is preferred.

Finally, hypotheses concerning the relationship of an exposure to a health

outcome may require that a distinction be made between total exposure and

peak exposure or between frequency and recency of exposure-all of which

may be more accurately characterized with biomarkers. Recency of exposure

will relate to the half-life of a drug’s metabolism, and this is most accurately

assessed by actual measurement since it may be confounded by other

exposures. Similarly, while peak intake exposures may be assessed by a

questionnaire, peak blood levels of a drug may more accurately predict a health

outcome.

THE NECESSITY FOR REQUIRING QUESTIONNAIRE DATA TO

COMPLEMENT BIOMARKERS

The advantages offered by biomarkers should not be viewed as precluding the

use of more traditional questionnaire data. These two types of data collection

complement each other rather than one being a substitute for the other. Some

reasons for this follow.

1. Many drugs (e.g., cocaine and marijuana) have short half-lives, and use will

be missed unless extremely frequent urine analyses are taken (Little et al.

1986).

2. Sporadic and infrequent exposures that may have great etiologic relevance

(e.g., drinking and drug binges) are likely to be missed in a large proportion

of the exposed population. Some of these exposures may be measured

more accurately by well-constructed questionnaires.

3. For case-control studies, monitoring does not necessarily reflect exposure

at the time of the etiologic event. For example, a study that measures

electromagnetic fields in the homes of mothers who delivered a child with a

birth defect may be inaccurate because of seasonal changes in electric

47
use, remodeling of the house that changes the wiring configuration, or

changes in the inhabitants’ patterns of electric use.

Monitors placed in the home will measure only part of the individual’s total

exposure. For example, a woman’s exposure to environmental tobacco

smoke may occur primarily at her workplace or while commuting, situations

in which monitoring may not be feasible.

Some exposures may be expected to change during pregnancy-for

example, occupational exposures, since a woman may change jobs,

change job responsibilities, or stop working at some time during her

pregnancy. Although a biomarker might be the best measure of a specific

occupational exposure, a brief telephone interview is probably the most

cost-efficient way to determine whether the woman still is working at the

same job.

Questionnaires provide the data from which exposures for large

populations can be estimated or modeled. Validating questionnaire

measurement with a biomarker helps develop questionnaires that can be

used in large population studies to estimate exposure or dose.

INTERRELATIONSHIP OF BIOMARKERS WITH MORE TRADITIONAL

METHODS OF DATA COLLECTION

Based on the above arguments, we see no circumstances where biomarkers

would be collected in the absence of questionnaire data to evaluate exposure to

the same substances. Moreover, biomarkers must be related to time

“windows,” which are related to the questionnaire data whenever possible. For

example, an investigator may measure dietary nutrients from a blood sample at

the end of a period for which the respondent is asked to provide a 24-hour or 7-

day food frequency questionnaire.

The rationale for the foregoing recommendation is twofold. First, respondents

may not accurately recall data being obtained by interview. In this case, the

biomarker can be considered a measure of “compliance,” not unlike the use of

markers in a randomized trial, to check that a drug regimen is being followed.

Second, the validity and reproducibility of many of the biomarkers being

proposed for epidemiologic research need to be established. Collection of

concurrent interview data may facilitate this work. Conversely, the validity of

questionnaire data also needs to be studied, and the biomarkers may assist

with this. Important methodological contributions may arise from research that

has used both types of data collection.

48
THE NESTED PROSPECTIVE STUDY

In a large prospective study, it is generally not feasible to monitor the entire

cohort for biomarkers. Not only would this entail great expense, from laboratory

costs and from the cost of collecting the data, but also it is likely to be inefficient.

If subgroups of the population under study can be monitored in more detail,

then conclusions drawn from them may be generalizable to the entire

population. For this process to be reliable, however, it is necessary that the

monitored subgroups be representative of the population from which they are

drawn, and the only guaranteed method of ensuring this is by picking them at

random.

A second feature of the nested prospective study is the need to calculate a

more complex set of power calculations. In most prospective studies, an

estimate of exposure in the population is made together with a statement of

what difference in clinical outcome the study wants to be able to detect. In the

nested study, additional calculations must be made to estimate the exposure

levels anticipated by the biomarkers and to take into account the randomization

in the study design. The number of subjects randomly chosen for the monitored

group may be determined by the ability of the marker to identify an exposed

group and by the degree to which significant clinical outcomes in the exposed

subgroup can be observed. Moreover, although appropriate randomization

should allow a reconstruction of the entire cohort, the process incurs some loss

of statistical power that should be adjusted for in the overall analyses.

AN EXAMPLE: THE YALE STUDY OF ENVIRONMENTAL TOBACCO

SMOKE AND INTRAUTERINE GROWTH RETARDATION

Overall Design of the Yale Study

Figure 3 displays the principal elements in the Yale nested prospective study.

Overall, it is anticipated that 3,193 respondents will enter the study. From a

previous study, we estimate that 400 women will have their first antenatal visit

before 12 weeks of pregnancy and, therefore, will be eligible to enter an

intensively monitored group who will be monitored four times in their pregnancy:

The first time will be soon after their first interview, at approximately 12 weeks

gestation, and then at 20, 28, and 36 weeks. The intensive group is studied for

interindividual changes in exposure and in response to exposure as pregnancy

progresses. Their monitoring protocol is described in more detail later.

Some of the analyses of differential exposure across pregnancy require a larger

sample size than will be derived from the intensively monitored group. Thus, a

further 873 women are randomly selected from all women admitted to the study

49
*Randomly pick one

T=telephone interview: Q=questionnave; U=urine sample; PHW=personal. home, work nicotine monitor

FIGURE 3. Nested prospective study of effects of environmental tobacco

smoke on fetal growth retardation; randomization and data

collection in monitoring window

SOURCE: Yale Perinatal Epidemiology Unit, unpublished data 1990

after 12 weeks gestation, and they form a biochemically monitored group. It is

not necessary that every woman in this group be monitored at each period;

consequently, they are randomly selected for monitoring at 20, 28, or 36 weeks

gestational age. At times, when a subject is not being biochemically monitored,

exposure is assessed by a telephone interview.

To obtain sufficient statistical power to address the study’s main etiologic

hypotheses, a further 1,920 women have their exposure during pregnancy

monitored by telephone interview alone. Again, a third of this group is

randomized for telephone interviews at 20, 28, or 36 weeks.

50
Because each subject was randomized to her particular monitoring group, each

of the entire cohort of 2,793 subjects can have her overall exposure assessed

by generalizing from other groups in the randomized cohort. The intensively

monitored group cannot be compared directly with the rest of the cohort

because they are selected on the basis of very early first antenatal care visits.

However, they can be contrasted statistically with the rest of the cohort to see

how they compare on exposure. Moreover, change in biologic exposure during

pregnancy, as assessed by biomarkers, is unlikely to be differentially biased in

the intensively monitored group.

Every woman in the entire cohort of 3,193 subjects is given a standardized

interview before monitoring starts and a postpartum interview within 2 days of

delivery, and her child is examined by a trained perinatal nurse. These

sessions provide data that describe the characteristics of the entire study

cohort, elicit data about potential confounders, and form the basis for the

variables describing study outcomes.

Monitoring Protocols

Intensively Monitored Subjects. In each of the four 1 -week monitoring

periods, the subject wears a passive smoke monitor and, on the morning of the

last monitoring day, provides a urine specimen for cotinine analysis. Therefore,

the cotinine measure overlaps with some of the monitoring period evaluated by

the passive smoke monitor. At the end of each monitoring period, the

respondent is given a brief interview that elicits her responses to questions

about exposure during that period. The same questions are used in the

telephone interview for the rest of the cohort.

One of the four monitoring periods is picked at random for home and work

monitoring. During the same 7-day period that the respondent wears a passive

nicotine monitor, she places one in her home for 7 days and, if she works, one

in her workplace for the days she works. Standard protocols are used.

After delivery, a maternal urine is collected so that nicotine exposure can be

assessed for the latter part of pregnancy. The neonate’s urine also is collected

so that a more direct measure of fetal exposure to nicotine can be obtained by

assessing cotinine. Placentas of the women in the intensively monitored group

also are collected and examined according to protocols described in a following

section.

Biochemically Monitored Subjects. During 1 week picked at random from

weeks 20, 28, or 36, the subjects in the biochemically monitored group follow

the same protocol as that of intensively monitored subjects for using the

personal nicotine monitor and for providing a urine sample.

51
Importance of Monitoring Windows

The Yale study uses 7-day exposure windows during which time biomarkers are

obtained. The use of precise monitoring windows also serves to focus the

period over which questionnaire data can be collected and permits a direct

comparison of data collected by both methods, Since the 7-day monitoring

windows are based on specific weeks of gestation (using each subject’s first

day of last menstrual period), data from one subject also can be compared with

other subjects in the study cohort. In addition, using gestational age-based

monitoring windows permits precise replication of the study by other

investigators.

The use of monitoring windows during pregnancy also permits more precise

analysis of the effect of time of exposure on a reproductive outcome. It is well

known that exposures to some teratogens late in pregnancy have no effect on

embryologic development, whereas earlier exposure during a “critical” period

can have devastating effects (Bracken 1984). For intrauterine growth

retardation (IUGR), differential exposure at various points in pregnancy may

have a variety of effects on the developing fetus, leading to IUGR, no IUGR, or

particular patterns of growth retardation (Keirse 1984).

Three primary measures of exposure are used in this study. First, we ask very

detailed questions about exposure to environmental tobacco smoke (ETS);

second, we use a passive smoke monitor that measures the air in the subjects’

breathing zone for nicotine; third, we collect maternal urines to measure

cotinine. The three exposure measures, the passive smoke monitor, and the

urinary and placenta analyses are described more fully below.

ENVIRONMENTAL MONITORING

Passive Smoke Monitor

ETS is a complex mixture of more than 4,000 chemicals found in the vapor and

particle phases. Given this complex mix, it is necessary to identify any air

contaminants or class of air contaminants for monitoring that would be

indicative of the presence and amount of ETS in an indoor environment. Some

of the ETS contaminants are associated solely with the combustion of tobacco

(e.g., nicotine or tobacco-specific nitrosamines), whereas others are emitted by

several other sources in the indoor and outdoor air (e.g., carbon monoxide or

nitrogen dioxide). In addition, individual or classes of ETS air contaminants

have not been singled out as being principally associated with the health and

comfort effects of concern. Therefore, it is neither practical nor feasible to

measure all contaminants associated with ETS. Assessing exposure to ETS is

52
best accomplished by monitoring concentrations of a proxy or marker

compound. A proxy or marker compound for a complex source, such as ETS,

is one that is easy and inexpensive to monitor and whose concentration is

directly related to the source and concentrations of important contaminants

emitted from the source. A proxy compound need not be directly related to the

effects under study.

Over the past few years, several compounds have been proposed as possible

markers for ETS (National Research Council on Environmental Tobacco Smoke

1988; Surgeon General 1987). Although no single compound has been

identified as an “ideal” marker, vapor phase nicotine in ETS has been shown to

be a suitable marker (Leaderer and Hammond 1991). Nicotine is unique to

tobacco, is emitted in similar quantities from different brands of cigarettes,

exists indoors at concentrations that are easily measured, and is related to

other ETS contaminants. In addition, nicotine and cotinine—a metabolic

byproduct of nicotine measured in blood, urine, and saliva-have been used

extensively for many years as biomarkers of exposure to ETS and active

smoking. Hammond and Leaderer (1987) described an inexpensive and

accurate passive monitor for vapor phase nicotine that makes it possible to

measure personal nicotine exposures and concentrations in indoor

environments over periods from 1 day to several weeks. This passive monitor

allows for the measurement of personal exposures to ETS in many individuals

and in a variety of indoor spaces.

The passive monitor, shown in figure 4, is small, lightweight, and unobtrusive

(Hammond and Leaderer 1987). Its principle of operation is based on passive

diffusion of nicotine to a chemically treated filter. The monitor consists of a

modified 37mm diameter and 16mm high polystyrene air sampling cassette

containing a support pad and a filter treated with an aqueous solution of 4-

percent sodium bisulfate and 5-percent ethanol. The monitor samples at a rate

of 24 mL/min. After exposure, the collected nicotine and bisulfate are desorbed

in water, the pH is adjusted with 10 N sodium hydroxide, and the neutral

nicotine molecule is concentrated into 250 mL of heptane by liquid/liquid

extraction. An aliquot of the heptane solution is injected into a gas

chromatograph with nitrogen-selective detection for quantitation of the nicotine.

The passive nicotine monitor is used to assess the personal exposures to

ETS and the levels in various indoor environments in which the respondents

spend their time. As a personal monitor, it is worn by respondents on the

outermost garment, as near as possible to their breathing zone, during the

waking hours for a 1-week period. During sleep hours, the monitor is placed on

the respondent’s nightstand. To monitor indoor spaces, respondents place a

monitor for a 1-week period in the main living space of their home and near their

53
FIGURE 4. Passive monitor for nicotine in the air

SOURCE: Hammond and Leaderer 1987, copyright 1987, American Chemical

Society

work station. Personal and indoor space monitoring is conducted over a 1-

week period corresponding to the respondents’ reported exposure via a short

questionnaire and the collection of the respondents’ urine samples on the last

day of the monitoring period. For quality control, a 5-percent duplicate sample

and field blanks are collected. Laboratory technicians are blind to the exposure

status of the respondents’ home and workplace samples.

BIOMARKERS

Urinary Cotinine Analysis

The principal biochemical markers that have been used as a measure of ETS

exposure include carboxyhemoglobin, nicotine, cotinine, and thiocyanate

(National Research Council on Environmental Tobacco Smoke 1986; Surgeon

General 1987). Carboxyhemoglobin is not considered a reliable measure since

it is affected by sources of carbon monoxide other than tobacco smoke (Jarvis

and Russell 1984). Thiocyanate may be a good indication of chronic exposure

since it has a relatively long half-life (14 days) (Lynch 1984); however, assays

are not sensitive at low levels and, therefore, are inappropriate to measure ETS.

Nicotine and cotinine, a metabolite of nicotine, are the most specific indicators

of tobacco smoke (Lynch 1984); and of these, cotinine has a longer half-life (2

days vs. 30 minutes for nicotine) and can be measured at low levels in serum,

saliva, and urine. Cotinine urine levels are highly correlated with cotinine blood

levels (Jarvis 1984). For these reasons, we have chosen to use cotinine as a

54
measure of ETS in our study, and we obtain urine for the analysis since this is

less invasive and more acceptable to study respondents than using blood.

Urine specimens are collected by the respondents in a sterile plastic container

during the first morning void. The samples are kept under constant refrigeration

until they are transported to the laboratory, usually within 48 to 72 hours of

collection. Each sample is measured and aliquoted into three 5 mL containers,

which are frozen at -80°C . One aliquot is used for GC analysis.

There are two methods of cotinine analysis in use, radioimmunoassay and GC.

A correlation of 0.93 (Peyton et al. 1981) has been reported for measuring

cotinine in urine by these two methods. We have chosen to use GC because

this method allows us to measure cotinine, nicotine, and caffeine In the same

analysis. Since a 24-hour urine sample is not collected, creatinine also is

measured, and the cotinine/creatinine ratio is used to eliminate differences due

to variability in urine volume. Maternal and infant urine samples are analyzed in

exactly the same way.

Amniocentesis

During the initial interview, respondents are asked if they anticipate having an

amniocentesis during their pregnancy. Approximately 15 percent of women in

this study have indicated they plan to have an amniocentesis and have agreed

to have a portion of the amniotic fluid reserved for cotinine analysis. When the

amniocentesis is performed, no additional fluid is removed since, after the

amniotic fluid is centrifuged to obtain fetal cells for genetic analysis, the

supernatant is reserved. This fluid, essentially fetal urine, is analyzed using the

same procedures as described for the maternal and infant urine.

Newborn Urine

The first urine from each newborn in the study is collected by taping a small

plastic bag over the infants’ genitals and waiting for them to void within the next

2 hours. Approximately 5 mL can be obtained by this method, which is

sufficient for analysis. The newborn urines are analyzed by GC using the same

procedures as those for maternal urines.

Placenta Analysis

We are investigating the use of biomarkers in the placenta to study the

mechanisms whereby exposure to environmental tobacco smoke during

pregnancy may result in IUGR. Two specific types of marker are being used:

(1) placental enzymes, which are usually considered to modify exposure; and

55
(2) DNA chemical addition products (adducts), which are considered to

represent measures of effect.

Placental Enzymes. Since enzymes may be induced in response to the

presence of specific substrates in human tissue, enzymes may be induced in

the placenta to metabolize chemical exposures of the mother. A substrate of

particular interest is benzo[a]pyrene, a toxic component of cigarette smoke.

Using the aryl hydrocarbon hydroxylase (AHH) enzyme assay (as modified by

DePierre et al. 1975), we can measure the overall ability of the placenta to

metabolize benzo[a]pyrene. Preliminary data (M. Sanyai, personal

communication) indicate that women who report smoking during their

pregnancy have higher levels of the enzyme than do women who do not smoke

during pregnancy. However, higher levels of enzyme activity alone may not be

indicative of a negative effect since the same enzyme system has the potential

to metabolize benzo[a]pyrene to more toxic or less toxic intermediates. A more

specific indication of toxicity is the potential of metabolites to bind covalently

with DNA. The covalent binding of some metaboiites (e.g., anti-BD-diol epoxide

[BPDE]) is sufficiently strong to alter the fidelity of DNA replication or

transcription processes in cells. It is likely that similar metabolites also may be

produced in the placenta from benzo[a]pyrene substrates. To estimate the DNA

binding potential of these metabolites in the placenta, human placenta

homogenate is incubated with radiolabeled benzo[a]pyrene and salmon sperm

DNA. After DNA extraction, a liquid scintillation counter is used to measure the

radioactivity. In the preliminary data, the ratio of total benzo[a]pyrene

metabolites produced (measured by AHH activity) to reactive DNA binding

molecules has shown a dose-response relationship to the number of cigarettes

smoked during pregnancy.

DNA Adducts. Although DNA damage may play an important role in the

etiology of many important diseases, direct investigation has been limited by a

lack of well-established methods that are sensitive enough to provide direct

measurements of chemical damage occurring in human DNA. Preliminary

studies (M. Sanyal, personal communication) indicate that the recently

developed 32P-postlabeling assay (Randerath et al. 1981, 1985) is capable of

measuring chemical alterations in DNA at levels of sensitivity low enough to

detect DNA damage resulting from environmental exposures. 32P-postlabeling

is performed by isolating DNA, digesting it to mononucleotides, and postlabeling

the mononucleotides with radioactive phospate using an enzymatic process that

is highly specific for DNA nucleotides, including adducts. Nucleotides

containing aromatic adducts then are separated from normal nucleotides by

thin-layer chromatography, and autoradiograms are made showing maps of

DNA adducts. Levels of the adducts then can be estimated by the density of

the autoradiograms or, more accurately, by scraping the thin-layer

56
chromatograms and quantifying the radioactivity present. The procedure can

detect many different chemical addition products of either known or unknown

structure, although present methods typically are most sensitive at detecting

relatively large aromatic adducts.

The measurement of DNA adducts may provide an important means to quantify

the biologically effective dose of environmental exposures because the quantity

of adducts present in the placenta may integrate exposure over time and take

into account individual differences in the pharmacokinetics and metabolic

activation of agents capable of interacting with DNA. These refined estimates

of dose have great potential for improving our ability to demonstrate doseresponse associations in epidemiologic studies. In addition, the assay to be

used in these studies is not specific for a single adduct, but detects adducts

from many aromatic hydrocarbons. Thus, human DNA can be treated to detect

a range of alterations, and the sources of exposure causing those changes can

be identified.

CONCLUSION

The use of biomarkers in epidemiologic studies of prenatal drug exposure is

becoming increasingly more common. A range of markers is already available

and, if carefully chosen, they may offer some advantage over more traditional

methods of assessing exposure to teratogens and provide new measures of

disease outcome. However, there are also significant disadvantages to using

many biomarkers, and the precise role of biomarkers in epidemiologic studies

remains unclear. To elucidate the problems and benefits of specific biomarkers,

epidemiologic studies that use them should be carefully constructed so that

methodological studies of the validity and reproducibility of the biomarkers can

be carried out alongside the primary etiologic question that is being addressed.

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AUTHORS

Michael B. Bracken, Ph.D.

Professor and Vice Chairman

Department of Epidemiology and Public Health

59
Kathleen Belanger, Ph.D.

Associate Research Scientist

Departments of Epidemiology and Public Health and Obstetrics and

Gynecology

Brian Leaderer, Ph.D.

Fellow

John B. Pierce Foundation Laboratory

Professor of Epidemiology and Public Health

Department of Epidemiology and Public Health

Perinatal Epidemiology Unit

Yale University Medical School

60 College Street

New Haven, CT 06510

60
Detection of Prenatal Drug Exposure

in the Pregnant Woman and Her

Newborn Infant

Enrique M. Ostrea, Jr.

INTRODUCTION

In 1985 a survey by the National Institute on Drug Abuse showed that about 23

million people in the United States used illicit drugs (Abelson and Miller 1985).

A sizeable portion of these drug users are women of childbearing age or are

pregnant. In a recent survey of 36 major hospitals, the prevalence of drug

abuse among pregnant women ranged between 0.4 and 27 percent (Chasnoff

1989), and these figures probably are underestimated (Ostrea et al. 1990a).

Drug abuse during pregnancy is a major health problem since the associated

perinatal complications are high. These include a high incidence of stillbirths,

meconium-stained fluid, premature rupture of the membranes, maternal

hemorrhage (abruptio placentae or placenta praevia), and fetal distress (Ostrea

and Chavez 1979; Chasnoff et al. 1985; Oro and Dixon 1987; MacGregor et al.

1987). For the newborn infant, the mortality as well as the morbidity rates are

high (Zuckerman et al. 1989; Zelson et al. 1971; Ryan et al. 1987; Fulroth et al.

1989; Chasnoff et al. 1986, 1989; Ostrea et al. 1976, 1987; Oleske et al. 1983).

For instance, there is a high incidence of asphyxia, prematurity, low birth

weight, infections, pneumonia, congenital malformations, cerebral infarction,

and drug withdrawal and an increased risk of acquired immunodeficiency

syndrome. Long-term sequelae in the infants are also not uncommon and

include delays in physical growth and mental development, sudden infant death

syndrome, and learning disabilities (Wilson et al. 1979; Chavez et al. 1979a,

1979b; Chasnoff et al. 1982; Wilson 1989). Because of these immediate and

long-term problems, infants born to women who have abused drugs during

pregnancy should be identified soon after birth so that appropriate intervention

and followup can be done. For other reasons, an accurate identification of the

neonates who are exposed to drugs in utero is important. The data are vital for

epidemiologic surveys for identification of women who will need postnatal

support or for assessment of the effectiveness of programs designed to reduce

the incidence of drug abuse among pregnant women.

61
Unfortunately, the identification of the drug-exposed mother or her neonate is

not easy. Maternal admission to the use of drugs is not frequent and is often

inaccurate because of fear of the consequences stemming from such

admission. Even with maternal cooperation, such information regarding the

type and extent of drug usage is often inaccurate (Ostrea and Chavez 1979).

Similarly, many of the drugs to which the fetus is exposed in utero do not

produce immediate or recognizable effects in the neonates (Kandall and

Gartner 1974). Currently, there are several methods used to detect prenatal

drug exposure in the pregnant woman or her infant. Each method has its

advantages and shortcomings. An update and critical assessment of these

various methods is the subject of this chapter.

Methods to detect substance abuse in a pregnant woman or intrauterine drug

exposure in a neonate ideally should address not only the type(s) of drug

abused but also the amount, frequency, and duration of drug exposure.

Although the acquisition of all this information is not usually possible, two

general methods are employed to achieve this: maternal interview (maternal

self-report), laboratory tests, or both.

MATERNAL INTERVIEW

Maternal interview, if accurately used, has the greatest potential for obtaining

comprehensive information on the type, amount, frequency, and duration of

drug use in the mother. The two systems of maternal interview generally

used-routine and structured-are described below.

Routine Interview

Routine interview forms an integral part of the obstetric history, which is

obtained either prenatally or when a woman in labor is admitted to a medical

facility. The accuracy of the data obtained by this method depends on the

attention devoted to the interview (Chasnoff 1989). Cursory interviews often

result in underreporting of drug use, whereas the incidence increases by

threefold to fivefold if a more organized protocol to monitor drug use is

employed. Still, there are many elements inherent in the routine history-taking

that affect its accuracy: maternal fear of the consequences of admittal;

underestimation of drug use, even by those who admit to the use of drugs; and

physical discomfort experienced by the woman, particularly if she is in labor

(Ostrea et al. 1990b; Ostrea and Chavez 1979). Under these circumstances,

the reporting of drug abuse by the mother can be as low as one-fourth of the

true incidence (Ostrea et al. 1990a).

62
Structured lnterview

Structured interview follows a more organized approach to the maternal

interview, frequently employing a standard questionnaire. Examples of this are

the Khavari Alcohol Test (Khavari and Farber 1978) or its modification (Khavari

and Douglass 1981) and the Cahalan Volume Variability Scale (Cahalan et al.

1969). The structured interview is more accurate since more time is spent in

the interview, which is frequently conducted in a more favorable environment.

Commonly, the interview is obtained on several occasions over the pregnancy.

As such, structured interviews frequently are used as research tools. On the

other hand, structured interviews are expensive to conduct and time-consuming

and, therefore, may not be practical for routine clinical use.

There are some methodological problems inherent in structured interviews as a

measure of substance use during pregnancies (Day et al. 1985). First, in the

assessment of frequency and quantity of drug use, the recall phenomenon by

the patient may not be accurate, particularly if interviews are spaced far apart.

For instance, an interview obtained at the end of each trimester frequently will

reflect only recent drug use. Second, the frequency of drug use often is

reported as a constant and seldom reflects variability in use. Therefore, the

major effects of episodic excesses that may be relevant to a teratogenic

problem may be masked. Similarly, quantity of drug use may reflect only the

“usual” amount used and miss episodes that are greater or less than usual.

Potency of drugs abused also varies and may not be assessed by the usual

counts employed. Third, there is also the problem of patients deliberately

misrepresenting their drug use. To some extent, this problem is addressed

by the use of a bogus pipeline technique (Jones and Sigall 1971).

LABORATORY TESTS

The following questions should be addressed in any laboratory test that is used

to detect prenatal drug exposure in the pregnant woman or neonate: (1) How

broad should the screen be? (2) What is the sensitivity of the test? (3) What is

its specificity? The broadness of the screen determines how many drugs can

be identified in a single test panel. The spectrum can be limited or broad.

A limited or narrow spectrum is usually less expensive; however, its use is

limited to situations where only specific drugs are of interest. The sensitivity

of a test determines the ability of the test to detect a drug when present at

concentrations greater than or equal to its predetermined analytical cutoff point.

Tests that are used for screening purposes usually have high sensitivity (99

percent) even at the expense of a low specificity (high false-positive rate), since

once a test result is negative, further testing usually stops. The specificity of a

test expresses the measure of certainty in the identity of a substance that is

63
detected by the test. Tests with high specificity are used to confirm the results

of initial screening tests. Cross-reactivity is low in tests that have high

specificity; consequently, false-positive results are few.

Most of the laboratory tests for drug detection are used for screening.

Confirmation with the use of another, nonrelated procedure usually is needed

if results are to withstand further scrutiny. As mentioned, the confirmatory

test should be highly specific. For medicolegal purposes, further forensic

confirmation may be needed to establish the unequivocal identity of the drugs

initially identified. It is apparent that, as more confirmatory tests are done, the

testing process becomes more expensive. Thus, the extent to which tests

beyond the initial screen are carried out is determined by the reasons that

initiated the test.

Analytical Procedures

The various analytical procedures that currently are used for drug detection

are shown in table 1 (Schonberg 1988). These are color or spot tests, thinlayer chromatography (TLC), immunoassays, high-performance liquid

chromatography (HPLC), gas chromatography (GC), and gas chromatography/

mass spectrometry (GC/MS).

Color or Spot Test. The color or spot test is the simplest and the earliest of

the drug tests. The test is based on a color reaction that develops when a small

amount of urine is added to a reagent that reacts with the drug present in the

urine. The procedure is easy to perform, quick, and inexpensive. Neither

special equipment nor experienced technical skill are required to perform the

test. However, the color or spot test has a high rate of false-positive and falsenegative results. Furthermore, high concentrations of the drug must be present

in the biologic fluid to form the color reaction. Examples of color or spot test are

the tests for salicylate (Trinder 1954), ethchlorvynol (Frings and Cohen 1970),

and ethyl alcohol (Kozelka and Hine 1941).

Thin-Layer Chromatography. TLC is the ideal analytical method for the

broad spectrum screening of a drug. Development of the technique over the

years has increased its sensitivity and ease of operation. However, there are

several drawbacks to the use of TLC. The procedure requires extraction and

concentration of the drug metabolites, which have to be separated from other

endogenous compounds so that interference with the drug’s migration and

identification are minimized. The color development of the migration spots may

differ, depending on the freshness of the reagents. Further staining also is

needed to develop reactions by other types of drugs. A permanent copy of the

results is also difficult because the color reproduction of the spots may not be

64
TABLE 1. Comparison of commonly used analytical techniques
TABLE 1. Comparison of commonly used analytical techniques (continued)

SOURCE: Schonberg 1988. copyright 1988. American Academy of Pediatrics
accurate. Last, since TLC has a broad spectrum in the detection of drugs, its

specificity is low and usually will need confirmation with other techniques

(Sunshine 1963; Sunshine et al. 1966; Davidow et al. 1968; Heaton and

Blumburg 1969; Kaistha and Jaffe 1972).

Immunoassay. The advent of immunoassays and the ability to produce

antibodies to various drugs (haptens) have added a powerful, sensitive, and

rapid analytical method for drug detection. The two most commonly used

methods are RIA and enzyme immunoassay (Baselt 1984).

RIA is based on the principle that a radioactive-labeled drug will compete with

the unlabeled drug for binding sites in a specific antibody, and the amount of

binding of the radiolabeled drug to the antibody is related to the concentration

of the unlabeled drug in the sample. Since the level of radioactivity can be

measured, RIA is semiquantitative It is a highly sensitive test that can detect

drugs and their metabolites at very low concentrations in the sample.

There are some disadvantages to the use of RIA. The procedure requires

expensive equipment (gamma scintillation counter) and special training of

personnel to conduct the test. The test can detect only one drug at a time, so

that testing for a panel of drugs can be time-consuming. Cross-reaction with

other compounds also can occur. Compared with TLC, the test is more

expensive due to the cost of reagents, equipment, and personnel time.

Enzyme immunoassay is a more commonly used procedure compared with

RIA since it is semiquantitative, more rapid, and less expensive. The reagents

used in enzyme immunoassay are also stable and have longer shelf life. The

principle of the test is similar to that of RIA except that it uses an antigen or

hapten labeled to an enzyme instead of to a radioactive element. The test is

based on the competition between the enzyme-labeled and unlabeled antigen

(hapten) for the antibody. The hapten enzyme compound is enzymatically

active unless bound to an antibody. The enzymatic reaction can be quantitated

spectrophotometrically or flourimetrically.

In general, there are two types of enzyme immunoassay that are commonly

used in drug detection: EMIT and fluorescence immunoassay. EMIT consists

first of incubating the serum with a buffered mixture that contains a limited

amount of antibody, a small amount of enzyme-labeled drug, substrate, and

cofactors for the enzyme. Enzyme activity is measured kinetically (e.g.,

generation of NADPH) by a spectrophometer. The drug concentration is

obtained from a standard curve in which enzyme activity is plotted against

drug concentration. Fluorescence immunoassay, on the other hand, utilizes

antibodies that react with the antigen (drugs) and produce fluorescence that can

67
be quantitated. The various types of fluorescence immunoassay differ in

the kind of fluorophors they use. One added modification to fluorescence

immunoassay has been the use of light in a polarized plane (fluoresence

polarization immunoassay) to excite the fluorophore and detect its flourescence

in the polarized plane. Other systems of immunoassay, such as the enzymelinked immunoabsorbent assay (ELISA), recently have been introduced for drug

analysis. However, the principal use of ELISA has been in the identification of

microbiological agents.

Enzyme immunoassays have their disadvantages. The test is expensive,

principally due to the cost of reagents. Cross-reaction with other substances

also occurs, so confirmatory tests are required.

High-Performance Liquid Chromatography. HPLC is another highly

sensitive and specific method for drug detection. The method consists of the

extraction of the drug from the biologic sample, the derivation of the drug,

its injection and elution from the column using specific solvents, and the

identification of the substance in the eluate from its elution time. Commonly,

flame ionization or electron capture detectors are used. Recently, the use of

diode array/ultraviolet (UV) visible spectral detectors has further enhanced the

specificity of the method. Like the mass spectrometer, the UV spectrum of the

specific eluate can be matched by computers against the spectrum of known

standards to achieve a high degree of accuracy in specific identification, Again,

like the mass spectrometer, HPLC is expensive and requires experience and

skill to operate. Likewise, the technique is time-consuming and, therefore, has

been used principally for confirmatory purposes (Mule 1971).

Gas Chromatography. GC has been one of the most sensitive and specific

techniques in drug detection. However, the analysis is time-consuming

since the procedure involves the extraction of the drug into a solvent, its

concentration and conversion into a volatile derivative, injection into a gas

chromatograph, elution from the column, and detection and quantitation

by comparing its retention time with a known standard. Furthermore, the

equipment is expensive and requires considerable technical skill to operate.

Therefore, GC has not been used for mass screening but as a confirmatory

test for other more sensitive and broad screening procedures,

Gas Chromatography/Mass Spectrometry. The most specific tool for the

identification of drugs has been a combination of GC with MS. GC separates

the biologic extract into its various peaks, and MS is used to establish the

identity of each peak. The latter is achieved by the conversion of the compound

in each peak into its electrically charged ion fragments. Different compounds

break down into different fragment patterns, and like fingerprints, no two

68
fragment patterns are alike, These fragment patterns then are matched by

a computer with the known fragmentation patterns of analytic standards.

Because of its high specificity, GC/MS is commonly used for the ultimate

identification of drugs and their metabolites in biologic samples. Thus, it is an

indispensable tool in forensic work (Costello et al. 1974).

The drawbacks to GC/MS are (1) the enormous expense of the equipment;

(2) the time involved with the preparation, separation, and identification of drugs

in the samples; and (3) the highly technical skill that is needed to operate the

system.

SPECIMENS USED IN DRUG TESTING

Urine

The testing of drugs in biologic fluids is by far the most common method used

to detect drug abuse in a pregnant woman or intrauterine drug exposure in a

neonate. However, there are several limitations to this method. Identification of

drugs in biologic fluids will differentiate only those who have been exposed to

drugs vs. those who have not. The test cannot provide information on the

amount, frequency, duration, or time of last drug use.

Among the biologic fluids, urine has been most often tested owing to several

advantages (Schonberg 1988): (1) Urine collection is easy and noninvasive;

(2) drug metabolites in urine usually are found in higher concentrations than in

serum due to the concentrating ability of the kidneys; (3) large volumes of urine

can be collected; (4) urine is easier to analyze than blood since it is usually

devoid of protein and other cellular constituents; (5) the metabolites in urine

usually are stable, especially if frozen; and (6) urine is amenable to all the drug

testing methods described above.

However, there are several drawbacks to the use of urine for testing. Foremost

is the high rate of false-negative results (Ostrea and Chavez 1979; Ostrea et al.

1990b). Urine collection, unless closely watched, easily can be substituted with

a clean specimen. Urine samples can be tampered with by dilution or by the

addition of ions, such as salt, that may interfere with the testing methods. Drug

metabolites in urine also only reflect very recent use of the drug; therefore,

negative results may occur if the woman abstains from use of the drug a few

days before testing (Schonberg 1988). In the infant, the incidence of falsenegative urine tests is also high, ranging from 32 to 63 percent (Halstead et al.

1988; Ostrea et al. 1989; Osterloh and Lee 1989). Urine specimens must be

obtained as close to birth as possible to reflect the intrauterine exposure of the

infant to drugs. The longer after birth that urine is collected and tested, the

69
greater the likelihood of a false-negative test. Likewise, as in the mother, drug

metabolites in the infant’s urine only reflect recent use of drugs by the mother.

Recent abstention by the mother from the use of drugs may result in a negative

urine test in the infant. The detection rate for drugs in the urine can improve if a

battery of tests, rather than a single test, is used (Osterloh and Lee 1989).

Meconium

In the past 2 years, the author and colleagues at Wayne State University have

developed a new method for identifying the intrauterine exposure of infants to

drugs by testing their meconium for drugs (Ostrea et al. 1988, 1989). The

concept behind this method was based on our initial research in pregnant,

morphine-addicted monkeys (table 2), which showed that a high concentration

of morphine metabolites was present in the gastrointestinal tract of their pups

(Ostrea et al. 1980). This was interpreted to be a consequence of morphine

being deposited in the gastrointestine through the bile or in swallowed fetal

urine through the amniotic fluid. This hypothesis was further tested in rats that

were given cocaine, morphine, or cannabinoids during pregnancy (table 3). The

presence of corresponding drug metabolites was substantiated in the intestine

of their pups (Ostrea et al. 1989).

TABLE 2. Distribution of morphine in the tissues of addicted newborn

monkeys

Monkey Number

A13 A84 A83 A24 A23 A87

Gestational age, days 118 125 135 147 155 161

Fetal weight, g 240 368 340 365 372 510

Age of addiction, days 71 89 80 104 113 100

Total maternal morphine, g 11.9 14.8 13.6 17.9 19.4 15.7

Tissue Concentration of Morphine, mg/g Tissue

Gastrointestines

Liver

Cerebellum

Heart

Spleen

Thymus

Lungs

Kidneys

Cerebrum

Brain stem

SOURCE: Ostrea et al.

15.8 128.9 108.4

0 0 0

15.7 37.9

16.2 72.5

0 0 69.7

0 0 35.5

0 0 0

0 0 15.4

1980, copyright 1980, S Karger

53.7

47.6

17.2

73.9

66.4

169.5

46.2

9.8

0

31.9

13.2

24.5

0

42.1

0

6.8

53.3

16.2

0

3.0

0

70
TABLE 3. Recovery of drug metabolites in intestines of rat pups whose dams

received drugs during pregnancy

Drug (route) Dose per Day

Rat Weight

(g)

Number of

Pups

Drugs In Pups’

Intestines*

(mg/g)

Pup 1: control animal†0 212 15 0.00

Pup 2: cocaine HCI (SC) 50 mg/kgx10 days 198 11 0.47

Pup 3: morphlne SO4 (SC) 50 mg/kgx12 days 216 13 1.38

Pup 4: cannablnold (oral) 25 mg/kgx12 days 223 12 2.50

*Represents drug concentration in pooled intestines

†Dam received no drugs durlng pregnancy.

KEY: HCI-hydrochloric acid; sc=subcutaneous

SOURCE: Ostrea et al. 1999, copyright 1989, Mosby-Year Book, Inc.

In subsequent clinical studies, we tested the urine and meconium of 20 infants

of drug-dependent mothers for the metabolites of cocaine, morphine, or

cannabinoids (table 4). High concentrations of drug metabolites were found in

meconium during the first 2 days, and some stools still tested positively on the

third postnatal day. In contrast, only 37 percent of the drug-dependent infants

had positive urine screens, and for each positive result only one drug was

identified, usually corresponding to the drug that had the highest concentration

in the stool samples (Ostrea et al. 1989).

The sensitivity of meconium analysis is high when compared to other methods

of drug detection, such as maternal hair analysis (see below) and structured

interview (see above) of the mother (Ostrea et al. 1990b). In a study of 26

subjects (table 5), the abuse of at least one drug (besides alcohol) during

pregnancy was identified in 73 percent of the subjects by structured interview,

using a modified Khavari questionnaire (Khavari and Douglass 1981), in 69.2

percent by meconium analysis, and in 75 percent by maternal hair analysis.

Abuse of two or more drugs was identified in 23 percent of the subjects by

history and in 35 and 50 percent of the subjects by meconium and hair

analyses, respectively. There was a 96-percent concordance in cocaine

detection by meconium and hair analysis and a 73-percent concordance for

heroin and cannabinoid (table 6). This study showed that meconium analysis

has a high sensitivity in detecting maternal drug abuse. Compared with

maternal hair analysis, it has the advantage of being noninvasive. The

sensitivity and specificity of meconium analysis also have been confirmed

recently by other investigators (Maynard et al. 1991). Compared with maternal

and neonatal urine testing, meconium analysis was found to be 96 percent

sensitive and 77 percent specific.

71
TABLE 4. Recovery of drug metabolites in meconium of drug-dependent

infants (n=20)

Cocaine

(mg/g stool)

Day 1 Day 2 Day 3 Day 1 Day 2 Day 3

6.35 3 23 (-) 3.26

2.34 2.17 1.17 1.19

1.77 9.68 3.67 (-)

10.86 11.29 (-) (-)

(-) (-) (-) 536

4.54 17.78 103 (-)

(-) (-) (-) 0 69

2.39 2.16 107 3.75

5.40 6.41 0. 41 (-)

(-) (-) NS 11 74

(-) (-) (-) (-)

11.48 041 (-) (-)

7 40 6 70 NS 5 36

11.42 0 29 NS 6.95

3.29 1991 6.10 (-)

0.26 (-) NS 226

1 76 3.52 242 124

NS 16.23 13.15 NS

0.95 0 14 (-) (-)

0.06 0.03 (-) (-)

*Urine drug screen by the TDx imnunoassay system (Abbott)

1.72

1.17

(-)

(-)

12.11

(-)

0.97

2 43

(-)

14.97

(-)

(-)

5 73

0 73

(-)

077

1 21

0 41

(-)

(-)

0.56

(-)

(-)

(-)

(-)

(-)

0.54

2.31

(-)

NS

(-)

(-)

NS

NS

(-)

NS

124

(-)

(-)

(-)

KEY: (-)=negatwe for drug tested. NS=no sample

Morphine

(mg/g stool)

Day 1

(-)

(-)

(-)

0.13

0.05

0 34

(-)

(-)

(-)

(-)

0 06

013

0 .48

0 67

(-)

0 14

(-)

NS

0.07

0.19

Cannabinold

(mg/g stool)

Day 2

(-)

(-)

(-)

0.29

(-)

0 66

(-)

(-)

0.09

(-)

0 09

(-)

037

(-)

(-)

(-)

(-)

0.22

(-)

0.17

Day 3

(-)

(-)

(-)

(-)

(-)

(-)

(-)

(-)

(-)

NS

(-)

(-)

NS

NS

(-)

NS

0.12

0.09

(-)

0.05

Urine

Screen*

(-)

(-)

(-)

(-)

Opiates

Cocaine

(-)

(-)

Cocaine

Opiates

(-)

Cocaine

Cocaine

(-)

NS

(-)

(-)

Cocaine

(-)

(-)

SOURCE Ostrea et al. 1989, copyrlght 1989, Mosby-Year Book, Inc.

Ostrea and colleagues (1990a) recently have used meconium analysis to

determine the prevalence of illicit drug abuse in a large population of women

delivering at a tertiary perinatal center. By self-report, the incidence of drug

abuse in the mothers was 10.5 percent. In contrast, 42 percent of the infants

tested showed cocaine, heroin, or cannabinoid metabolites in meconium; 38.9

percent were positive for cocaine or heroin alone (table 7) (Ostrea et al. 1990a).

These results indicate an extent of the drug abuse problem in pregnancy in the

population studied and a magnitude that was unrecognized.

72
TABLE 5. Antenatal drug exposure in 26 pregnant women as determined by

analysis of infant stool and maternal hair and by maternal history

Infant

Stool

Maternal Maternal

Hair History

Number of subjects

with samples

Detection of 1 drug

Detection of drug

Exposure to:

Cocaine

Heroin

Marijuana

26/26 16/26 26/26

(100%) (61.5%) (100%)

69.2% 75.0% 73.0%

34.6% 50.0% 23.0%

61.5% 66.8% 76.9%

34.6% 25.0% 7.7%

26.9% 31.3% 19.2%

SOURCE: Ostrea et al. 1990b

TABLE 6. Concordance of drug detection by meconium and hair analysis

Drug Detected Meconium vs. Hair Analysis

Cocaine

Hair

Morphine

Hair

Cannabinoid

Hair

Sensitivity=(11/12) 92%

Specificity=(4/4) 100%

Sensitivity=(3/4) 75%

Specificity=(8/12) 67%

Sensitivity=(3/5) 60%

Specificity=(8/9) 89%

73
TABLE 7. Prevalence of intrauterine exposure to cocaine, opiates, or

cannabinoids in 1,000 infants delivered in a tertiary perinatal center

Means of Detection Percent Positive

Meconium analysis

For cocaine, morphine, or THC

For cocaine or morphine

Maternal self-report

42

38

10.5

SOURCE: Ostrea et al. 1990a

Recent developments in meconium testing have included tests for

methamphetamine in addition to tests for cocaine, opiates, and cannabinoids

(Silvestre and Ostrea 1991). Similarly, meconium testing, formerly analyzed

only by RIA, also can be analyzed by enzyme immunoassay (Ostrea et al.

1991a), latex agglutination inhibition test (Gervasio and Ostrea 1991), GC/MS

(Ostrea et al. 1991 b), and solid-phase RIA (Lucena and Ostrea 1991).

Meconium analysis is a new, sensitive, and noninvasive method for detecting

intrauterine exposure of infants to drugs. The procedure is quantitative, rapid,

and easily performed. The test is useful for diagnostic purposes and is also

an important, sensitive, and noninvasive research tool for clinical and

epidemiologic studies.

Hair

Analysis of hair for drugs has been developed recently (Baumgartner et al.

1989). The test is based on the principle that illicit substances and their

metabolic products in the patient’s blood become incorporated in the hair follicle

and grow into the cuticle and hair shaft. The drug, once deposited in the hair

shaft, remains for an indefinite period. As the hair grows, at the rate of one or

one-half centimeter a month, the deposited drug follows the growth of the hair

shaft. Thus, hair analysis not only will allow the detection of drug use in a

person but also (through sectional analysis) will provide information on the

duration and time of drug use. The information, particularly on the chronicity

of drug use, makes hair analysis advantageous over urine or other body fluid

testing. Furthermore, quantitative detection of drugs in hair has been correlated

to the amount of drug use in the past.

Hair has been successfully analyzed to detect use of opiates (Baumgartner et

al. 1979), cocaine (Baumgartner et al. 1982) phencyclidine (Baumgartner et al.

74
1981), and methamphetamine, antidepressants, and nicotine (Ishiyama 1983).

The analytical procedures that have been employed include RIA (Baumgartner

et al. 1989), GC/MS (Balabanova and Homoki 1987), HPLC (Marigo et al.

1986), and collisional spectroscopy (Pelli et al. 1987).

The validity of hair analysis for drug detection also has been demonstrated in

the neonate (Graham et al. 1989) and in pregnant women (Welch et al. 1990).

In these situations, the technique has been found to be highly sensitive (Welch

et al. 1990).

There are some drawbacks to the use of hair for testing (Bailey 1989). The test

is expensive and time-consuming since extraction and concentration of minute

amounts of drugs in the hair are necessary. The amount of hair available for

a sample may be a problem, particularly in the newborn infant or in patients

with cropped hair. Patients can refuse to give hair samples if fearful of selfincrimination (Ostrea et al. 1990b). Last, since hair grows slowly, very recent

or acute use of drugs may not be detected by hair analysis.

Other Specimens

Other types of specimens have been tested for drugs. These include

perspiration, nail clippings, menstrual blood, semen, and saliva (Smith 1981;

Smith and Liu 1986). However, the use of these specimens for drug detection

has been uncommon.

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AUTHOR

Enrique M. Ostrea, Jr., M.D.

Professor of Pediatrics

Wayne State University School of Medicine

Chief of Pediatrics

Hutzel Hospital

4707 St. Antoine Boulevard

Detroit, MI 48201

79
Methodological Issues in Obtaining

and Managing Substance Abuse

Information From Prenatal Patients

Robert J. Sokol, Joel W. Ager, and Susan S. Martier

INTRODUCTION

Heavy prenatal alcohol exposure has been increasingly recognized as a major

perinatal risk particularly in the last two decades (Jones and Smith 1973).

Illicit drug abuse, especially of cocaine, in reproductive-age women and in

association with pregnancy also has been associated with worsened perinatal

outcomes (Dombrowski and Sokol 1990). Cocaine abuse is now epidemic.

Clearly, there is increased need for ongoing clinical studies, both animal and

human, on the antecedents and consequences of polysubstance abuse for

pregnancy and antenatal outcomes.

This chapter deals with key methodological issues involved in obtaining and

managing substance abuse information. There is a vast refereed literature that

is, for the most part, readily available to investigators and clinicians dealing with

these issues, Since the authors have been involved with prenatal screening

of patients for substance abuse for over 18 years and, using various

methodologies, have screened more than 40,000 consecutive prenatal clinic

patients in two inner-city environments, the experiences of this research group

will be shared as “tricks of the trade.”

To present these “tricks” the chapter is presented in two parts: (1) key

problems and issues in data collection and (2) key issues in quantification, data

management, and statistical analysis of substance abuse variables in relation to

outcomes of the offspring.

DATA COLLECTION

How to obtain reliable and valid information reflecting the prenatal exposure of

the fetus to alcohol has been described previously (Sokol et al. 1985a). This

section presents a potpourri of issues evolving from experiences in this area

80
because of its particular value to other researchers studying substance abuse in

pregnancy.

Avoid Denial

Denial is a recognized component of alcohol dependence. In addition to

alcohol, the most widely abused drugs in pregnancy are illicit, including

marijuana, cocaine, and opiates (i.e., heroin). Thus, denial also complicates

obtaining reliable estimates of prenatal exposure for these substances.

Although the phenomenon of denial of heavy alcohol use has been studied in

detail (Nadler et al. 1987), how this phenomenon applies to other substances

is much more “impressionistic” and has not yet been studied. Biochemical

detection of drugs in meconium is substantially more accurate than interview

in documenting exposure history (Welch et al. 1990), and this method can be

used as a basis for studying denial of drug use. Thus, the issue is overcoming

patient denial to obtain data that will reflect perinatal drug exposure with

adequate precision, accuracy, and reliability for research use.

Heavy maternal drinking is a major fetal risk that must be detected to be

prevented. Currently, obtaining an alcohol history is the only practical way to

identify heavy exposure. Anecdotal evidence suggests that acknowledging

problem drinking is complicated not only by psychologic denial but also by

warnings not to drink. A “natural experiment” in a prenatal clinic permitted

testing of this hypothesis. In a pilot for a large prospective study of 314

pregnant women, 269 patients were assessed for alcohol abuse using the

Michigan Alcoholism Screening Test (MAST) and the “cut down-annoyed-guilteye opener” (CAGE) questionnaires, measures of chronic alcohol problems and

dependence, and prenatal and current drinking histories. The rate of problem

drinking among these 269 women was markedly lower than that found in more

than 8,000 previous histories in this and another large antenatal clinic. These

269 patients had been seen by a nurse who interviewed the patients before any

other health care provider warned them of damage to the fetus by drinking and

drug use. The interview order was changed so patients were seen by the

alcohol/drug screener first. Trimmed t-tests showed no significant demographic

differences or differences in rates of abstinence in groups interviewed Nurse

First (n=150) and Nurse After (n=164) the change in order. For those who

drank, MAST and CAGE scores were significantly higher in the Nurse After

group (MAST p<.006, CAGE p<.009); reported embryonic (periconceptional)

absolute alcohol/day increased significantly (p<.01); and reported current

absolute alcohol/day was statistically unchanged. These results document

quantitatively an increase in reported drinking related to nonjudgmental patient/

health care provider interactions and are consistent with the interpretation that

guilt-inducing warnings increase denial and are counterproductive. Thus, the

81
first step in minimizing denial is to maintain a nonjudgmental, focused approach

in obtaining an alcohol history. Patients should be reassured that if they abstain

from or limit drinking in pregnancy they can have a healthier baby (Nadler et al.

1987).

A second step to avoid denial is not to ask quantity and frequency initially

but rather to focus initially on the consequences of substance abuse on the

patient’s life (Sokol et al. 1989a). For example, a four-question battery with high

sensitivity and adequate positive predictive value (i.e., the T-ACE questions in

table 1) was developed. The T-ACE sidesteps denial and has the advantage

of brevity, making it particularly useful in the prenatal clinic. Other short

questionnaires have been evaluated (Mar-tier et al. 1990; Bottoms et al. 1989).

TABLE 1. The T-ACE questions. A score of 2 is considered positive,

suggesting that the patient may be a risk drinker (i.e., an individual

drinking enough potentially to damage her baby).

T Tolerance. How many drinks does it take to make you feel high?

(Score 2 if drinks.)

A Annoyed. Have people annoyed you by criticizing your drinking?

(Score 1 if positive.)

C Cut down. Have you felt you ought to cut down on your drinking?

(Score 1 if positive.)

E Eye opener. Have you ever had a drink first thing in the morning to

steady your nerves or get rid of a hangover? (Score 1 if positive.)

SOURCE: Sokol et al. 1989a, copyright 1989, Mosby-Year Book, Inc.

A similar approach is used for other drugs. Questions about illicit substances

are avoided until the end of the first interview. As the patient leaves, she is

asked, “By the way, do you use cocaine.?” Cocaine is asked about because of

current patterns of use. If the patient says, “Yes,” she is asked about quantity,

frequency of use, and drug use by her significant other.

At the second prenatal visit, a more structured approach to eliciting drug history

is taken. In settings where prevalence of illicit drug use is very high, the

interview should begin with questions about licit (prescription) drugs and then

move to illicit drugs (i.e., the “oblique approach”). This represents a third step to

minimize denial.

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Although necessary, helping the pregnant woman avoid denial of illicit drug use

is not sufficient for a valid history. Manuals are available that list drugs and their

street names, but terms vary from community to community. Listening to the

patient and keeping abreast of popular drug names is a must. This also applies

to quantification of drugs (e.g., knowing what a “dime” is for drugs and a “jumbo”

is for beer). Knowing the amount of money spent on drugs might be a useful

indicator, but because costs change, further refinement is needed. Routine

urine drug screens are well known to most clinic populations, and the steps

clients take to avoid detection may account for the low sensitivity of these

screens. Nonetheless, a positive initial urinary drug screen should initiate a

probe for use of other drugs (Sokol et al. 1985a). The same is true of drug

abuse by a patient’s partner.

In summary, a nonjudgmental but aggressive approach to eliciting substance

use/abuse information is valuable in avoiding denial and, thus, in obtaining a

valid history of use.

Assume She Uses a Lot

Over the years many individuals have been involved with screening for prenatal

drug use, on both a clinical and a research basis. In our present study, more

than 20 people have been trained for screening over the past 3 years.

Evaluating the experience of these screenings is enlightening. Even though

rates of abstention and drinking levels have remained consistent throughout the

study, there has been a wide variation in rates by screeners. Abstention rates

by screeners have ranged from 4.9 percent to 26.0 percent, whereas the

frequencies of problem drinkers have ranged from 2.2 percent to 7.9 percent.

To deal with this variability and the implied underascertainment, it is important

to maintain a clinic staff with a fresh outlook-screeners who continue to probe,

who do not become bored with following the same script in the same way, and

who are persistent. Role playing between screeners, duplicating interviews,

should be done weekly to help screeners deal creatively with problems that

arise within a structured format.

The most successful screeners assume that any given patient has a reasonable

probability of using one or more substances. Therefore, the attitude has to be,

“Don’t take no for an answer.” This is not a particularly risky strategy as there is

little if any evidence of “overreporting” (Morrow-Tlucak et al. 1989; Jacobson et

al. 1989).

This approach is extended by “overestimating” substance use. For example, if

the patient admits to drinking one bottle of beer, the interviewer responds with

the supposition that the patient is drinking jumbos (a 40-ounce bottle). The

83
message to the patient is that it is okay to admit to drinking jumbos. Also,

when asking a patient how much wine it takes to make her feel “high,” quantity

is suggested in bottles rather than glasses. Experience indicates that patients

are much less likely to report amounts above that initially suggested by the

screener. As applied to other substance use, if the patient admits to smoking,

the term “regular cigarettes” is used, implicitly suggesting to the patient no

surprise at her smoking marijuana or other substances,

A final component of these tactics involves a “meta-approach” of monitoring

the detection rates of screeners. This is a very valuable method from two

perspectives. First, many study designs utilize weighted samples, often in a

block design, which requires modification of proportions of patients admitted to

the study at various use levels. Thus, monitoring the frequency of reported

substance use is a natural part of the study design. Second, monitoring the

frequency of abstinence/use can document any deterioration in performance,

detected by comparing one interviewer with others and/or with previous

detection rates.

Where, How, and With Whom?

Patients do not think in ounces of absolute alcohol or in milligrams of

tetrahydrocannabinol; thus, one can expect substantially better detection if

substance use is placed within social context, For example, it is useful to

associate drug use with special events (holidays and birthdays), the site of

use (bars or the home of a friend), or sexual behavior. Further, the use of an

occasion-by-occasion (day-by-day) approach requires much less “mental agility”

than asking an individual to apply the concept of “on the average” to a week or

a month-which may be well beyond the patient’s capacity, especially if he or

she is poorly educated.

QUANTIFICATION, DATA MANAGEMENT, AND STATISTICAL ANALYSIS

Data Input and Preliminary Analysis

Data Preparation. Problems inherent in the preliminary stages of data input,

construction of appropriate database systems, data cleaning, and evaluation of

data integrity and reliability usually are underestimated. In this section, some

techniques and procedures are outlined that we have found helpful in dealing

with these data preparation problems.

Computerized data entry screens can be set up, naming each variable and its

makeup in character fields, integers, or floating points. Upper and lower limits

are stated for each variable so that entry is stopped if a value falls outside the

84
range. The data entry person reviews the screen for each case entered before

signaling the computer to continue. The authors’ experience indicates that the

efficiency and reliability of direct entry using such screens fully justifies the initial

additional effort required to construct them.

Coding and Data Cleaning. An aspect of data preparation that requires

careful thought is coding. This is particularly a problem when there are various

types of missing data, including “no response” and “not applicable.” For

example, in screening women for alcohol history, one should differentiate

among women abstinent all their lives, those with no problems associated with

drinking, and those to whom a screening device was not administered for other

reasons. For example, if using the MAST, it is useful to specify a separate code

for each of these categories. Generalizing from this, it is best to code as many

categories of response as may be determined reliably. These may be collapsed

for various statistical analyses. Thus, distinctions that may be useful later are

not lost.

One problem in statistical analyses is ensuring that missing data and other

special codes are not included in the statistical calculations, These are

assigned values very different from actual scores (e.g., -99 or -88) which

makes their inadvertent inclusion in analysis easy to spot. Furthermore, the

descriptive statistics in most statistical packages include output of the maximum

and minimum scores used in the analysis. Again, this makes inadvertent

inclusion of codes representing missing data easy to flag.

Problems in Longitudinal Evaluation of Fetal Exposure: Relational

Databases

The fact that maternal data are collected throughout pregnancy represents a

rich source of longitudinal information and, at the same time, a set of most

difficult design and analysis problems. The main difficulties stem from the fact

that the women will have varying numbers of visits at different gestational

ages. An additional difficulty is that often the gestational age itself cannot be

ascertained as accurately as one would wish. Consequently, the record for

each patient must be individualized. Because of the problems of differential

record size, the use of relational databases is recommended rather than the

traditional rectangular type. For example, the use of INGRES (Epstein 1977)

running under UNIX (McGilton and Morgan 1983) allows up to 49 variables to

be represented in each relation; relations then can be joined as necessary

using a maternal identification number for the purpose of conducting a particular

set of statistical analyses.

85
Despite the problems in representing complex longitudinal data sets, there are

questions that can be addressed with this type of data that are difficult, if not

impossible, to answer with cross-sectional data. For example, the pattern of

abuse behavior within individual patients over the course of pregnancy can be

tracked and then related to outcome. The timing of the substance abuse or

change in abuse over trimesters may be important and may have differential

effects on specific outcomes (Ernhart et al. 1987). All such questions

essentially require longitudinal data and analyses.

Missing Data Problems and Estimating Missing Values

The problem of missing data is endemic in field research, especially in studies

with a longitudinal component. As a first step in preparing the data for

multivariate analysis, it is useful to screen the data array for both individuals

and variables having excessive amounts of missing data. Typically, dropping

relatively few subjects and/or variables will eliminate the bulk of the missing

values. For estimating the remaining missing values, several procedures are

available, ranging from the simple, but crude, to the more complex, but precise.

An example of the former is replacing the missing value by the group mean for

that variable. More elaborate methods use multiple regression procedures to

estimate the missing values from the data that are available for the given

subject. In some cases, iterative procedures are used for this purpose.

List-wise deletion is the most common technique for handling missing data

available in the widely used statistical packages (e.g., SPSS, SAS, BMDP)

(SPSS 1986; SPSS, Inc. 1988; SAS Institute, Inc. 1985; Dixon 1985). In this

method, those subjects missing a score on any variable in the analysis are

eliminated. Unfortunately, this procedure often results in a large drop in sample

size with the consequences of both lower statistical power and bias in the

remaining sample. The most widely used statistical packages, for the most

part, have not included as options the more sophisticated multiple regressiontype methods for estimating values; an exception is BMDP (Tabachnik and

Fidell 1983). There is reason to believe, however, that such routines will

become available in future versions.

Skewed Distributions and Outliers. Many of the variables, both independent

and dependent, used in substance abuse research tend to have highly skewed

distributions. Certainly this is true for the abuse variables themselves (e.g.,

smoking, alcohol and other drug use), as well as for some extraneous variables

(e.g., medical risks). Infant outcome variables (e.g., number of birth anomalies)

are also often positively skewed. Even birth weight, which in its continuous

form may be only slightly skewed, becomes highly skewed when trichotomized

into very low, low, and normal.

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There are two major consequences of skewed distributions for statistical.

analysis. The first is that most inferential techniques used with the usual

multivariate techniques (e.g., multiple regression, linear discriminant function

analysis, analysis of variance) assume a multivariate normal distribution of the

variables. Although the statistical tests (e.g., F) are relatively robust to

moderate violations of normality assumptions, such tests become problematic

when skewness is extreme. (It also should be noted that kurtosis [e.g., a

relatively heavy frequency of cases in the tails of the distribution] also tends to

have a biasing effect on sampling distributions of the usual test statistics.)

There are several techniques that can be used to minimize the degree of

skewness and its effects on the analysis, One common method is use of the

log or square root transformations. Other nonlinear transformations also can be

used, but transformed values often have little psychological “reality” (i.e., they

are harder to interpret and understand than the raw values). Another approach

is to recategorize the variable, in effect collapsing the extreme categories.

Robust and nonparametric analyses that involve less restrictive distributional

assumptions also might be used when available for the particular analysis of

interest.

Another problem concerns variables with different marginal distributions, In this

case, the maximum magnitude of the Pearson correlation coefficient is less than

unity (Carroll 1961). This can be a problem with dichotomous or trichotomous

variables with a relatively small proportion of cases in the extreme category.

For example, the maximum point biserial R between a normally distributed

variable and a dichotomous variable with 5 percent of cases in the less frequent

category is only .47. As Carroll has shown, it is always possible to calculate R

2

max for any two marginal distributions, The R

2

 max then represents the

predictable variance in y. The same interpretation can be made for multiple

R

2

 max.

An example of the effects of extreme splits on R arose in the Cleveland study

(Sokol et al. 1985a) on the antecedents of fetal alcohol syndrome (FAS). Of

the 8,331 patients in this study, 25 (.3 percent) had a diagnosis of FAS. A

multiple regression model, including as predictors MAST, proportion drinking

days, parity, and race (all significant), yielded a multiple point biserial R

2

 of

.061. Although the 6.1 percent of variance accounted for seems almost

inconsequential, this interpretation changes radically when one considers that

the max R2

 with this split on the outcome is only .118; that is, over one-half of

the predictable variance is accounted for by these predictors.

A final problem that can be considered an extreme form of skewness is that of

outliers. Such scores are so extreme that they are considered not to be from

87
the same distribution as the rest of the scores. Outliers are a particularly

serious problem because such scores can have a very large, and possibly

biasing, effect on the analysis. Recategorizing such scores (e.g., by

“Windsorizing”) or eliminating them (e.g., “trimming”) is usually recommended.

Interrater Reliability

Problems with the various types of biases that may affect measurements of the

various independent and dependent variables (e.g., attrition and ascertainment)

are well known and will not be discussed here. Issues of reliability and validity

are also generally recognized. One type of reliability, however, that is of critical

importance but is often overlooked is that of interrater reliability. Raters viewing

the same behavior in a number of patients can differ both in ranking individuals

on the scale and also in the absolute scale value assigned. A reliability index

that takes both types of error into account is the intraclass correlation (ICC).

Use of the ICC for different interrater study designs has been discussed by

Shrout and Fleiss (1979). For categorical variables, coefficient kappa can be

used (Cohen 1960).

Interrater reliability was an issue in the Detroit (Jacobson et al. 1988) study in

the assessment of infant dysmorphology. Training was continued until the

interrater agreement on the dysmorphology counts was viewed as adequate-in

this case, the ICCs improved from .69 to .92.

Statistical Analysis

Drug Research-Inherently Multivariate. Research on the antecedents and

consequences of alcohol and other drug abuse in human populations is usually

correlational in design and almost always multivariate in analysis. To ensure

validity and interpretability of such analyses, it is necessary that the study

design include a sampling of the relevant variables that is as complete as

possible. In generating such a list of variables, it is useful to organize them into

domains. On the predictor (independent variable) side, such domains typically

include (1) background/demographic information, (2) medical risks, (3) other

substances of abuse, and (4) the target abuse variable set. On the outcome

(dependent variable) side, domains might include neonatal outcomes and later

cognitive development.

The first three domains represent extraneous variables and are used primarily

to make appropriate statistical adjustments of the target variable. They also

may be evaluated as possible moderator variables as discussed below. In

studies of the effects of maternal drinking on infant outcomes, a relatively

small set of background variables has been found to be consistently related to

88
target variables and to outcomes. This background set usually includes the

mother’s age, parity, and race.

Under medical/obstetric risks (excluding other substance abuse), such

conditions as hypertension, diabetes mellitus, and other major medical

complications are usually included. One usually excludes from medical risks

those medical conditions or previous pregnancy outcomes that may, in large

part, be due to abuse of either the target drugs or other substances. A case in

point might be previous spontaneous abortions. Although certainly a risk factor

for adverse outcome in the present pregnancy, inclusion of this variable in the

predictor set might well inappropriately reduce the outcome variance

attributable to abuse of the target drug or other substances.

Designation of certain of the substance abuse variables as target variables and

others as “extraneous” variables is to some extent arbitrary. Polydrug use and

abuse is the rule, and the challenge is to root out their individual and joint

(interactive) effects on the specific outcomes. The way in which the treatment

of the target set differs from that of the other abuse variables is that the target

set tends to be measured more extensively and in depth. Investigators need to

be aware that the effects of target variables may be overstated because they, in

aggregate, are likely to be more reliably measured.

In most investigations, several outcome domains are apt to be of interest.

Effects of the abuse variables and their combinations may be specific to certain

outcomes. In addition, certain immediate outcomes in turn may be mediators or

moderators of later adverse effects. For example, using the Cleveland data set,

Greene and colleagues (1991) found that occurrence of alcohol-related birth

defects (ARBDs) apparently mediated the relationship between maternal

drinking and later cognitive development, in that those infants who had a higher

anomaly count tended to have the lower IQs.

Adjusting for Extraneous Variables. The term “extraneous” does not mean

that the variables so labeled are unimportant; on the contrary, they are

absolutely critical in the multivariate analysis. As briefly outlined below, there

are several types of extraneous variables, including confounders, covariates,

mediators and partial mediators, moderators, and suppressors. Appropriate

specification of type of extraneous variable implies a path-type causal model,

whether or not the model is made explicit. Agreement between a particular

model and data does not prove that the model with its causal pathways is

correct, as many models may be in reasonable concordance with the data.

Nevertheless, one may be able to conclude that the model is a viable one at

least. Furthermore, and perhaps more importantly, construction of such models

requires investigators to make their causal assumptions about the variables

explicit.

89

318-164 0 - 92 - 4 : QL 3
Confounders, as defined by Schlesselman (1982), meet the following criteria.

First, a confounder is related to, but not caused by, the exposure variable.

Second, it has a relationship, not necessarily causal, to the outcome. Finally, a

confounder is expected to relate to outcome even in the absence of the

exposure variable. Thus, in studies of effects of maternal drinking on birth

weight, smoking would qualify as a confounder, whereas, as mentioned above,

previous spontaneous abortions probably would not because previous abortions

might be due in part to the exposure variable of maternal drinking. When

variables of this latter type are treated as confounders, they tend to adjust out

valid variance in the exposure variable leading to an underestimate of the

exposure effect. In multiple regression, linear discriminant function (LDF) and

logistic regression analyses confounders are included in the predictor set.

Although analysis of covariance (ANCOVA) has been criticized as a method of

adjusting for extraneous variables in correlational designs, the problems of

possible overadjustments or underadjustments also arise in the other

multivariate procedures, for example, multiple regression (MR) and LDF

analyses. In ANCOVA, the dependent variable is residualized for the covariates

based on the (pooled) within-group regressions, ANCOVA has been used in

the determination of thresholds for ARBDs using race, parity, smoking, and

“examiner” (dummy-coded) as the covariates; this last covariate represented

an adjustment for an aberrant examiner who consistently underreported the

number of ARBDs (Sokol et al. 1989b). A variation of ANCOVA developed for

use in the Cleveland studies also should be noted (Sokol et al. 1985b). In this

approach, only the control group (e.g., combined light drinkers and abstainers)

is used to determine the regression coefficients. Use of this approach avoids

possible problems with heterogeneity of regression. Little precision in

estimating the regression coefficients is lost since the low abuse groups are

typically much larger than the heavy abuse groups.

The concern with mediation and partial mediation is the issue of direct vs.

indirect effects of the abuse variable on the outcomes. For example, quality of

home environment might act as a mediator of the effects of maternal alcohol

abuse on cognitive development. In this path model, maternal alcohol abuse

would lead to a deficient home environment, which in turn would result in poorer

cognitive performance of the offspring. If, in addition, there were direct effects

of maternal drinking on cognitive development, this would be an example of

partial mediation. Again, we emphasize that such mediators and partial

mediators are only identified as such within hypothesized path models.

Suppressor relationships between variables occur when the part correlations

are (reliably) larger than the corresponding zero-order correlations (Smith et al.,

in press). Addition of a suppressor variable to a multiple regression equation

90
results in improved prediction, primarily because nonvalid variance is partialled

out of the target predictor(s). When two variables both have positive

correlations with the criterion variable but are negatively correlated with each

other, suppression is said to occur. A pattern in which two highly correlated

variables have greatly different validities also can give rise to the suppression

phenomenon. Suppression is probably often overlooked. Unfortunately, no

satisfactory significance tests are yet available to establish reliability of the

patterns of suppression.

If the relationship between two given variables (e.g., a predictor xand an

outcome y) changes as a function of third variable z, then z is termed a

moderator. Moderators usually are identified in correlational designs by

including crossproduct terms in LDF or MR analyses. Thus, moderator effects

are closely akin to interaction effects in ANCOVA. The identification and

interpretation of moderator effects is based on significance of the regression

coefficients for the crossproduct terms. In interpretation, the sign of the

regression coefficient needs to be carefully noted. Assuming both predictors

are positively related to the criterion, a positive crossproduct term denotes a

synergistic moderator effect (i.e., the joint effect of the predictor and moderator

is greater than would be expected from their individual effects). An antagonistic

effect occurs when the regression coefficient is negative, indicating that the joint

effect is less than predicted from the individual effects. Antagonistic effects can

occur, for example, when each of two substances acting alone produces a

negative infant outcome but the addition of the second abuse variable produces

a relatively small incremental effect.

Interactive effects may be of considerable importance given the typical pattern

of polydrug abuse. A study of the impact of substance use on perinatal loss

demonstrates this. Although alcohol and cocaine abuse have been reported to

be associated with late spontaneous abortion and preterm delivery, critical

appraisal of polydrug use and risk for pregnancy loss is lacking. Based on a

Detroit sample of 3,943 consecutive black gravidas registered for care in a core

city prenatal clinic and screened for substance abuse, 133 (3.4 percent)

experienced fully documented pregnancy loss (Sokol et al. 1986). Using

discriminate analyses, 77 pregnancies resulting in spontaneous abortion, 40 in

stillbirth, and 16 in neonatal death were contrasted for substance abuse and

control variables with those resulting in survival. First trimester registration was

uncommon. The median gestational age of the mothers’ first antenatal clinic

visit was 23 weeks, Abortion was related to alcohol abuse and to narcotic use.

Stillbirth was related only to alcohol abuse, but neonatal death, at a mean of 26

weeks, was associated with cocaine in conjunction with cannabis or narcotic

use (Sokol et al. 1990). Though substance abuse occurred in 14.5 percent of

pregnancy losses, the effect sizes were small, ranging up to 2 percent. The

91
odds of pregnancy loss for substance (alcohol and other drug) abusers was

increased 1.8±.5-fold (p<.002). These results confirm a relationship of alcohol

abuse to late abortion and stillbirth. They also demonstrate the difficulty

of differentiating drug effects given underreporting of polydrug use, the

infrequency of pregnancy loss, and selection bias against pregnancy losses in

perinatal databases, Thus, it is likely that the strength of these associations is

considerably underestimated. Further studies of the potential synergistic effects

on perinatal outcomes of substances of abuse are needed (Sokol et al. 1990).

Race is another example of a strong moderator effect on the effects of maternal

drinking and occurrence of ARBDs as discussed below.

Modeling the Nature of Relationships. There are three major questions for

the statistical analysis of relationships between predictors and outcomes. The

first is that of the existence of a reliable relationship as determined from tests

of the null hypothesis of no relationship. A second question is that of the

magnitude of relationships (e.g., as assessed by a multiple correlation). The

third and probably most important set of questions concerns the nature of these

relationships.

In the initial stages of analysis, emphasis tends to be on the problems of

identification of those target independent variables and extraneous variables to

be retained in a reduced model. The focus is on identification of reliable linear

relationships. Once a reduced set of variables has been identified, attention

turns to the determination of the nature of the relationships between target

variables and outcomes.

For studies of the effects of substance abuse on infant outcomes, two critical

issues are threshold and susceptibility. For the first, one must establish, if

possible, a point on the abuse scale below which there are no discernible

negative effects on outcome (“no-effect zone”) and above which such negative

effects can be reliably detected. The presence of a threshold indicates

nonlinearity of the relationship. For this purpose, we have used an ANCOVA

approach in our studies of the effects of maternal drinking on ARBDs. Women

were categorized into five groups based on an estimate of absolute alcohol per

day; the dependent variable was number of ARBDs adjusted for age (or parity),

race, smoking, and possibly examiner bias. Pair-wise differences between

adjacent group means were evaluated using one-sided t-tests. Although this

approach inflates Type I error, the concern in this case was Type II error (not

finding a true difference), which is minimized in this analysis (Ernhart et al.

1987).

92
In the above analysis, there was an interaction with race. That is, for the groups

at a lower level of drinking (the first three groups), there was no difference

between blacks and whites on ARBDs. For the two heaviest drinking groups

(above threshold), there was a significantly greater number of ARBDs for the

black infants. Analyses for each group separately revealed a higher threshold

for whites (above 4.0 ounces of absolute alcohol per day) than for blacks (3.0

ounces). These results were interpreted to represent a susceptibility effect for

blacks with regard to the effect of maternal drinking on ARBDs (Sokol et al.

1989b).

A similar methodology was used to study threshold exposures, by race, for full

FAS. Alcohol-attributable adverse perinatal outcomes ranged from subtle

neurobehavioral abnormality to anatomic ARBDs, FAS, stillbirth, and abortion,

thus suggesting a “continuum of reproductive causality” for this fetotoxic/

teratogenic agent. A no-effect zone below and a dose-response relationship

above a threshold of more than four drinks a day during the embryonic period

for ARBD in a sample of 1,290 pregnancies is noted above. A threshold for

a more severe adverse outcome with greater fetal exposure has not been

documented in humans. To test the hypothesis that higher doses lead to worse

outcomes, the dose-response relationship for FAS (25 cases) in the same

sample was evaluated by logistic regression analysis. The model (shown in

table 2) was highly significant (x2=28.004). There was no significant increment

in risk with increased exposure until Group 5, indicating a higher threshold for

FAS than for isolated ARBD. These results provided a step in defining an

overall dose-response relationship for prenatal alcohol exposure and adverse

pregnancy outcomes in the “continuum of reproductive causality.” Results are

encouraging for prevention since the high-risk population appears well defined

and delimited (Sokol et al. 1988).

COMMENTS AND CONCLUSIONS

Research in this area is not easy. Ideally, one should be able to explicitly

formulate and test models based on animal work, known biologic mechanisms,

previous human studies, and clinical studies. Indeed, measurement and

analysis strategies, particularly adjustments for extraneous variables, imply

such models whether or not they are stated explicitly. Nevertheless, much of

the work with humans must be considered largely exploratory. Consequently,

one needs to measure and evaluate large numbers of variables with (if

possible) large samples. Because of multiple comparison problems inherent in

such exploratory research, cross-validation designs are often useful.

As indicated at the outset, this chapter does not attempt to be comprehensive in

the discussion of data collection preparation and analysis problems and

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TABLE 2. Logistic regression model relating increasing prenatal alcohol

exposure to risk for FAS

Exposure Number

Groups Drinks/Day N

0 bserved

% FAS

Expected

% FAS

1 0 374 0.3 0.4

2 507 1.4 1.0

3 265 1.9 2.4

4 79 5.1 5.4

5 >6 65 12.3 11.7

SOURCE: Sokol et al. 1988, copyright 1988, Research Society on Alcoholism

solutions but rather to focus on those problems we have found to be most

troublesome (and challenging).

In summary, our major points are outlined below:

1. For data collection, one must (1) minimize denial (underreporting) of

substance abuse; (2) improve accuracy of reporting history of substance

use by placing such use by the patient in her own chronological and

geographic setting; and (3) train, retrain, and monitor data collection

personnel to maintain reliability and motivation.

2. With regard to data preparation, areas to be considered are (1) the use

of coding schemes that distinguish among different types of responses,

(2) strategies to eliminate the bulk of the missing data and to estimate

the remaining missing values, (3) problems in analysis due to extreme

skewness and transformational techniques for these, (4) problem of

“outliers” and methods designed to minimize their effects, and (5)

assessment interrater agreement whenever observer judgments are

required in obtaining the measurements.

3. In comments on data analysis, noted are (1) the inherently multivariate and

correlational nature of research in substance abuse and pregnancy; (2) the

usefulness of considering domains (or sets) of independent, extraneous,

and dependent variables; (3) the problem of attributable risk and the related

problems of appropriate adjustments for extraneous variables; (4) the

various types of extraneous variables—confounders, covariates, mediators,

and suppressors—with some examples; (5) the important problem of the

nature of relationships among the independent, extraneous, and dependent

94
variables; and (6) the specific question of existence of thresholds for effects

of the various substances on various outcomes, an increasingly important

problem for human studies.

As important as it is to document the existence, nature, and magnitude of

relations between substance abuse variables and maternal and infant

outcomes, an equally important question is the delineation of reasons for

abusive behavior in pregnancy. Once these reasons are better understood,

more appropriate interventions can be developed, evaluated, and implemented.

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of Engineering, University of California. Berkeley, CA: University of

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A. Alcohol teratogenicity in the human: A detailed assessment of specificity,

critical period, and threshold. Am J Obstet Gynecol 156:33-39, 1987.

Greene, T.; Ernhart, C.; Sokol, R.; Mar-tier, S.; and Boyd, T. Prenatal alcohol

exposure and cognitive development in the preschool years. Neurotoxicol

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Jacobson, S.; Sokol, R.; Jacobson, J.; Martier, S.; Kaplan, M.; Ager, J.; Billings,

R.; and Bihun, J. How much underreporting of pregnancy drinking can be

detected by one year postpartum? Alcohol Clin Exp Res 13:344, 1989.

Jacobson, S.; Sokol, R.; Jacobson, J.; Shankaran, S.; Mattier, S.; Ager, S.;

Moran, G.; and Weinshenker, L. Measurement of the face for alcohol-related

birth defects: Reliable? Alcohol Clin Exp Res 12:339, 1988.

Jones, K.L., and Smith, D.W. Recognition of the fetal alcohol syndrome in early

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Martier, S.; Bottoms, S.; Sokol, R.; and Ager, J. Pregnancy risk drinking:

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Underreporting of alcohol use in pregnancy: Relationship to alcohol problem

history. Alcohol Clin Exp Res 13:399-401, 1989.

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obtaining an alcohol history. Alcohol Clin Exp Res 11:212, 1987.

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reliability. Psychol Bull 86:420-428, 1979.

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defining an overall fetal alcohol dose-response relationship in human

pregnancy. Alcohol Clin Exp Res 12:339, 1988.

Sokol, R.; Debanne, S.; Ager, J.; Martier, S.; Ernhart, C.; and Chik, L.

Maximizing the efficiency of a study on alcohol-related birth effects by means

of data collection and analytic strategy dissociation. Am J Perinatol 2:245-

249, 1985b.

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detection of risk-drinking. Am J Obstet Gynecol 160:863-870, 1989a.

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pregnancy loss. Alcohol Clin Exp Res 14:341, 1990.

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exposure and spontaneous abortion (SAB), stillbirth and neonatal death.

In: Society for Gynecologic Investigation Scientific Program and Abstracts,

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maternal risk-drinking. Recherche Genecologie 1:425-430, 1989b.

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prenatal clinic. In: Chang, N., and Chao, H., eds. Early Identification of

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96
Welch, R.; Martier, S.; Ager, J.; Ostrea, E.; and Sokol, R. Radioimmunoassay

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ACKNOWLEDGMENT

The research reported in this chapter was supported all or in part by National

Institute on Alcohol Abuse and Alcoholism grants P50 AA-07606, R01 AA06966, R01 AA-06571, and R01 AA-8906.

AUTHORS

Robert J. Sokol, M.D.

Dean

Wayne State University School of Medicine

Scott Hall

540 East Canfield Street

Detroit, Ml 48201

Joel W. Ager, Ph.D.

Professor

Department of Psychology

Wayne State University

Professor

Department of Obstetrics/Gynecology

Hutzel Hospital

Susan S. Martier, M.S.S.A., C.S.W.

Research Assistant

Department of Obstetrics/Gynecology

Wayne State University

Hutzel Hospital

4707 St. Antoine

Detroit, Ml 48201

97
Discussion: Caveats in Testing for

Drugs of Abuse

David A. Kidwell

INTRODUCTION

In an effort to combat drug abuse and provide for a safe workplace, widespread

testing of urine for drugs of abuse has become a reality. Drug screening

laboratories have emerged in a variety of environments, including government

and industrial facilities, emergency rooms, psychiatric centers, and substance

abuse centers. To stay within budgetary constraints, the tests must be

inexpensive. Yet, through the courts, society has demanded that urine tests

meet accepted scientific criteria for validity.

A good testing program must employ two independent assays, and these must

be in agreement before a sample is considered positive. The first test is a

screening test, which serves to filter out the many negative samples and to

identify the drug to be confirmed. To meet cost criteria, the first test inevitably

is based on thin-layer chromatography (TLC) or an immunoassay. Since the

second test is performed on fewer than 5 percent of the samples, it can be more

expensive. Gas chromatography/mass spectrometry (GC/MS) generally is used

as the confirmation test.

Drug testing also has played a role in epidemiological studies evaluating the

effects of drugs. Since many drugs of abuse do not show obvious permanent

effects, a long-term measure of drug exposure is desirable. For most studies,

urinalysis is employed partly because of familiarity with the technology, although

other matrices could be used. This chapter reviews some of the techniques

used in screening and confirmation of drugs of abuse in various matrices and

discusses the principles, advantages, and disadvantages of each, with special

emphasis on application of these results in a research program.

METABOLISM OF DRUGS

Before discussing the issues involved with testing drugs, a basic understanding

of how the body deals with drugs is necessary. Figure 1 depicts the urine levels

98
Time After Ingestion (hours)

FIGURE 1. Excretion curve for LSD

SOURCE: R.L. Folte, personal communication, 1964 (also, see Francom et al.

1986)

of LSD in two individuals who ingested identical doses of LSD (Francom et al.

1986), Figure 1 illustrates two points: (1) The excretion of a drug is timedependent. Usually after the initial dose, the concentration of a drug increases

rapidly in the urine, reaches a maximum, and then declines in an exponential

manner (Chiang and Hawks 1986). (2) Individuals show variation in the rate of

excretion and total amount excreted in various body fluids for a given dose of a

drug. Therefore, amounts found in urine cannot be readily correlated to amount

used or degree of intoxication (Chiang and Hawks 1986).

CUTOFF LEVELS

To state that a sample is positive for drugs, at least two criteria must be met:

(1) The sample must be positive by the screening test above a set cutoff level;

and (2) the sample must be positive by a confirmation test above a set cutoff

level.

99
Cutoff levels are used to ensure that the screening and confirmation tests are

sensitive enough to reliably detect the presence of a drug. A low cutoff level

may give so many positives in the screening test as to overwhelm the slower

and more costly confirmation test. However, cutoff levels often are set with

consideration of the workload of the laboratory and the possibility of passive

ingestion of drugs rather than the sensitivities and specificities obtained by a

given test. For these reasons, comparison of two matrices, such as blood/urine,

saliva/urine, or meconium/urine, is difficult since the cutoff levels may not be

comparable. Thus, if a single cutoff level were employed, one matrix may be

favored over another. Cutoff levels employed in most testing laboratories for

urine can be found in the Federal Register (DoD Civilian Drug Testing Program

1987). Any research employing an independent laboratory for testing of a

sample is likely to have that sample tested at these cutoff levels unless prior

agreement is reached.

SCREENING TECHNOLOGY

The screening test does not need to be infallible (Warner 1987). It may call

some samples positive for a drug when none was present (i.e., a false-positive),

but it should detect all those samples that have drugs present (i.e., no falsenegatives). Therefore, only two requirements must be met by the screening

test: (1) It must be specific enough to avoid an excessive number of falsepositives; and (2) it must have a sensitivity equal to or less than the cutoff levels

determined by the researcher to avoid false-negatives.

The following sections discuss the two types of screening tests that are

commonly employed: (1) TLC and (2) immunoassays-radioimmunoassay

(RIA), enzyme-multiplied immunoassay technique (EMIT) (Syva Corporation,

Palo Alto, CA), and fluorescent polarization immunoassay (FPI). The principles,

advantages, and disadvantages of each test are examined.

Thin-Layer Chromatography

TLC requires extraction of the urine sample before the analysis. This is more

labor-intensive than an immunoassay, which can be run on the sample directly.

Nevertheless, TLC can be as cost-effective as immunoassay since it can detect

many drugs simultaneously, whereas immunoassay can detect only one drug or

drug class per test (Kaistha and Tadrus 1975).

The detection levels for TLC are in the 0.5-1.0 μg/mL range for most

substances (Kaistha et al. 1975; Kaistha and Tadrus 1976). These

sensitivities are much higher than the cutoff most frequently used and,

therefore, are not adequate for most testing. Nevertheless, TLC often is

100
employed for testing drugs where immunoassays are unavailable or a broad

screen is desirable, such as in a hospital emergency room to identify a

substance causing an overdose.

One of the most widely used commercial systems is Toxi-Lab. This system is

supplied with an extensive compendium of drugs and their TLC characteristics,

Cullen and Kidwell (1987) evaluated Toxi-Lab for the analysis of more than 400

randomly selected, drug-free urine samples. These samples were being tested

to determine if other drugs may be present that were not detected by

immunoassay. Since samples are mailed by surface mail from distant places,

they may be weeks old before testing. The age of the sample has not been

shown to be a problem for immunoassay. However, Cullen and Kidwell (1987)

have observed that with TLC urine degradation can lead to more than a 30-

percent false-positive rate for the barbiturates. Often, a spot would appear that

was identical in all respects to phenobarbital, but no phenobarbital could be

detected by GC/MS. Also, due to the simple extractions employed in Toxi-Lab,

many neutral compounds are coextracted. These have led to large brown

streaks that obscured any compound present and reduced the sensitivity

tenfold from that achievable with fresh samples. For these reasons, TLC is not

recommended for older samples that have not been refrigerated.

lmmunoassays

The alternative method for drug screening Is an immunoassay. All

immunoassays employ antibodies, Antibodies are proteins made in mammals

that recognize, bind to, and elicit defenses against foreign substances. The

compound that an antibody binds is termed the antigen. Two general types

of antibodies are employed in immunoassays: polyclonal and monoclonal.

Poiyclonai antibodies are isolated from animal serum and are often mixtures

of antibodies with different specificities. In contrast, monocionai antibodies are

frequently single protein molecules grown in cell culture and have a single

specificity. In a mixture of polyclonal antibodies, there are generally antibodies

that will recognize and bind different parts of an antigen. In contrast,

monoclonal antibodies, being a single compound, will recognize and bind only

one type or part of an antigen. Therefore, monoclonal antibodies may not

recognize related compounds such as metabolites.

As employed in immunoassays, antibodies may be considered to function

as a lock and key. The antibodies are the lock and the drug is the key. The

specificity of the lock will determine the number of keys that will fit. The more

specific the antibody, the less interference from other materials of similar

structure will occur. However, with a specific assay, there is little chance of

observing related compounds such as metabolites or designer drugs.

Therefore, researchers should select the immunoassay depending on their

101
goals. If detection of only a single compound, such as cocaine, is desired, a

monoclonal-based immunoassay should be used. If detection of cocaine and

its metabolites—such as ecgonine, benzoylecgonine, methylecgonine, and

norcocaine—is desired, then a polyclonal immunoassay should be used.

If a new matrix is being explored where concentrations of the potential

metabolites are unknown, then the choice of immunoassay is critical. For

example, meconium testing has been proposed to measure long-term drug

exposure by the newborn in the mother’s womb (Ostrea et al. 1988). Since a

fetus does not have the mature enzyme system of an adult, the application of

an assay that detects only benzoylecgonine as the principal metabolite of

cocaine (out of five) may miss many positives if benzoylecgonine is not

produced by the fetus and secreted into meconium. Also, cutoff levels for

meconium may be entirely different than those for urine. Thus, several

specimens of a new matrix should be analyzed either by a nonspecific method,

such as GC/MS, or by several immunoassays to determine the most prevalent

metabolite profile and appropriate cutoff levels.

The binding of an antibody, be it monoclonal or polyclonal, is the fundamental

part of any immunoassay. The distinction between all immunoassays is the

manner in which this binding is measured. Described in the following sections

are three different immunoassays that employ different techniques to measure

binding of the antibody to its antigen.

Radiolmmunoassay. RIA was first described in 1959 by Rosalyn Yalow as a

method to detect insulin (Yalow and Berson 1960). For her work in this area,

she received the 1977 Nobel prize in Medicine or Physiology. To perform the

test (figure 2), a known amount of radioactively labeled drug (antigen) is mixed

with a small quantity of urine (a few hundred microliters). Then, an antibody

to the drug is added. The antibody is not able to distinguish between the

radioactively labeled drug and the drug that may be present in the urine. The

antibody and drug-antibody complex are separated from the urine, and the

radioactivity is measured. The more radioactivity bound to the antibody, the

less drug present in the test sample.

The separation of bound drug from unbound drug is the labor-intensive part of

RIA and may be performed in many ways (Skelley et al. 1973). Two methods

are most popular. One method relies on the addition of a second antibody that

is directed against the first antibody. Because the second antibody crosslinks

the first antibodies, a large insoluble molecule is formed. This precipitate is

pelleted by centrifugation, and the supernatant containing the unbound antigen

is discarded. Then the radioactivity in the pellet is counted directly in the tube.

102
FIGURE 2. Steps used in RIA

103
The other popular method relies on binding the antibody to the walls of the

reaction vessel. After the initial drug-antibody reaction, the unbound materials

are poured out. The radioactivity bound to the antibodies, which are coated on

the walls of the tube, then is determined.

A typical plot of radioactivity observed vs. concentration of antigen is shown

in figure 3a. This curve is similar in shape and principle to an acid-base titration

curve. This curve also may be made linear, as shown in figure 3b (Henson et

al. 1985). One should note that the linear curve generated mathematically

in figure 3b from the normal binding curve is somewhat misleading. The

precision near either end of this curve can be poor. Therefore, in measuring

either small drug concentrations or high ones, severe errors may occur. High

concentrations must be measured by diluting them into the working range of

the RIA. In contrast, low concentrations are problematical since the binding of

the antibody may be affected depending on the matrix being analyzed. Often,

an extraction and concentration step is used to reduce the matrix effect and

increase the concentration of the analyte to a more precise part of the working

curve.

The advantage of RlA lies in its sensitivity; 10-12 to 10-15 moles of antigen can

be determined routinely. This sensitivity is the result of the low radioactive

background of most materials and the high sensitivity of radioactive

measurements. Also, RIA is rugged; as long as the antibody-antigen reaction

is specific, few false-negatives will occur. The major disadvantages of RIA

are the risk of exposure to radiation and the restrictive laws regulating the

distribution, use, and disposal of the low-level radioactive waste generated.

Enzyme-Multiplied Immunoassay Technique. In 1972 Rubenstein and

colleagues (1972) developed the homogeneous assay on which EMIT is based.

EMIT employs enzymes rather than radioactivity as the determinant of antibody

binding. A common enzyme system used for EMIT is glucose-6-phosphate

dehydrogenase, which uses nicotine adenine dinucleotide phosphate (NADP)

as a cofactor to oxidize glucose and reduce the NADP. The reduced NADP

absorbs ultraviolet light at a longer wavelength than does the oxidized

form. The activity of the enzyme can be measured as a rate of increase in

absorbance due to the production of reduced NADP. The binding of the

antibody to an enzyme-labeled drug decreases the activity of that enzyme.

Only a few enzymes with the active site close to the surface show this effect

(Rubenstein 1978).

The principle behind EMIT can be seen in figure 4. To perform the assay, the

rate of turnover of the enzyme must be measured. The decrease in activity is

measured as a decrease in absorbance after a set period compared with a

104
Concentration of

Drug in Sample

Log10 of Concentration

of Drug in Sample

FIGURE 3. Typical data generated by RIA. Figure 3a shows a raw calibration

curve, and 3b shows a calibration curve after mathematical

processing.

standard. If no drugs are present in the test sample, then all the enzymelabeled drug is bound and the activity of the enzyme is reduced. The bound

enzyme-labeled drug produces little reduced NADP, and the absorbance at 340

nm is correspondingly low. If a detectable quantity of drug is present in the test

sample, then the drug competes with the drug-enzyme conjugate for the

antibody binding sites (recall the discussion of RIA above). This releases some

105
FIGURE 4. Steps used in an EMIT immunoassay

of the enzyme-labeled drug, restores its activity, and produces more reduced

NADP. Therefore, the absorbance at 340 nm increases.

The advantage of EMIT over RIA is that no radioactivity is involved, which

makes disposal of waste products relatively easy. Also, the shelf life of the

106
reagents is increased since no radioactive decay is present, and therefore, the

signal can be started and stopped and labor can be saved since the assay is

performed without a separation step. A disadvantage of EMIT is that it cannot

be used if the test sample is cloudy or has interfering substances that absorb at

340 nm. Since binding of antibodies is necessary, all the discussion about the

cautions in measuring of very high or low concentrations of analyte that apply to

RIA also apply to EMIT.

Possible Problems With EMIT. EMIT is the test that has had the most publicity

about its susceptibility to adulteration. Like RIA, an adulterant that prevents

binding of the antibody to the drug-labeled enzyme would generate a falsepositive. Unlike RIA, EMIT is vulnerable to generating a false-negative by

reducing the activity of the enzyme or changing the NADP cofactor.

One system that could be used to test for adulteration in urine tests that employ

EMIT technology is to monitor the initial rate of the enzyme reaction before the

antibody is added. If this rate was too low, then that sample would be flagged

as not testable. Few laboratories use this method as it increases the complexity

of the analysis slightly and, more importantly, few customers ask for these data.

Fluorescent Polarizatlon Immunoassay. The principles of FPI were first

developed by Perrin in the 1920s (Perrin 1926), and its application to the

detection of antigens bound to antibodies was first described by Dandliker and

Feigen (1961). The principles and practice of FPI and its application to

biological systems have been the subject of several review articles (Soini and

Hemmila 1979; Dandliker and de Saussure 1970; O’Donnell and Suffin 1979).

FPI is related to light scattering, and its basis can be seen in figure 5. If a

polarized light beam excites a stationary, fluorescent molecule, the molecule will

emit light that is polarized. If the molecule rotates before the light is emitted,

then the polarization of the emitted light is lost. Small molecules, such as

drugs, rotate faster than larger molecules, such as antibodies. An antibody

binding to the smaller, fluorescent molecule would make a large complex with a

slower rotational period. This large complex would not rotate significantly

before fluorescence of the molecule had occurred; therefore, the polarization of

the initial exciting light would be retained. If the antibody is prevented from

binding the fluorescently labeled drug (because other molecules fill the site),

then the polarization is lost. The steps used in FPI are similar to those used in

EMIT, with the only difference being how the signal is interpreted.

The shelf life of the reagents in FPI is increased over both EMIT and RIA since

no radioactivity or enzymes are involved with this analysis. Like EMIT, labor

can be saved since the assay is performed without a separation step. The

107
Polarized Excitation Polarized Emission

Fixed Rotation

(polarization retained)

Free Rotation

(polarization lost)

Polarized Excitation Unpolarized Emission

FluorescentLabeled Drug

Antibody Complex

FIGURE 5. Principle of FPI

sensitivity of FPI is somewhat less than can be achieved by RIA and EMIT, but

it is sufficient for most drug assays (Caplan and Levine 1989). The sensitivity is

limited by the theoretical maximum of polarization being 0.4 (due to the random

distribution of molecules) and by the inherent fluorescence of the sample.

Interference by fluorescence is especially severe if proteins, as in blood plasma,

or certain vitamins are present.

Like EMIT, FPI also is sensitive to several adulterants (Dandliker and de

Saussure 1970). The TDx

 system (Abbot Laboratories, Irvine, TX) reduces or

eliminates all known interferences by a 250-fold dilution of the urine in buffer

before an assay is performed and a careful background subtraction routine.

However, such fluorescent materials as endogenous riboflavin metabolites or

surreptitiously added fluorescence dyes still pose a problem. Abnormally high

levels of such species are indicated to the operator as an untestable sample by

the TDx instrument (Wilkerson et al. 1989). In these cases, a policy decision

must be made as to whether such a sample should be tested by alternative

technology to avoid discarding a potential positive.

108
CONFIRMATION TESTS

Some people in the forensic and parole community rely exclusively on

immunoassays or TLC to detect drug abuse and forgo the confirmation test.

This is a mistake. Hoyt and colleagues (1986) surveyed legal professionals,

forensic experts, and arbitrators about the legal defensibility of various test

methods and found that, without a confirmation test, little confidence was

placed in the result. For research purposes, where no punitive action possibly

could be taken against the individual, a confirmation test may be unnecessary

as long as the 5- to 10-percent potential false-positive rate is considered in the

analysis. However, for new matrices with little history of usage, such as

meconium, or for drugs where false-positive rates are unknown, the falsepositive or false-negative rates may be quite high and severely bias the data.

In these cases, GC/MS confirmation would be desirable. Where the results

may be used in a punitive action, the National Institute on Drug Abuse

guidelines require confirmation by GC/MS. Since this chapter deals mainly with

research studies, no further discussion of confirmation by GC/MS will be done.

ALTERNATIVES TO URINALYSIS FOR DRUG TESTING

Saliva Analysis

Saliva analysis would be an ideal alternative to urinalysis since saliva can

be obtained under direct observation without the privacy issues involved in

urinalysis. Previous research has indicated that many drugs are present in

saliva in concentrations that parallel those found in blood (Thompson et al.

1987; Cone et al. 1988; Danhof and Breimer 1978; Sharp et al. 1883). Thus,

there may be a better relationship to the concentrations of drugs in saliva and

the degree of intoxication of an individual. However, drugs do not remain in

saliva or the blood for as long as in urine. Also, since the kidneys concentrate

many species approximately 100 times, the concentrations of drugs in saliva

are lower than in urine.

Few studies of cocaine in saliva have been completed, with most relying on

detection by immunoassays (Thompson et al. 1987; Cone et al. 1988). The

first report of the detection of cocaine in saliva came from a study of the

metabolism of radiolabeled cocaine (Inaba et al. 1878). Later, cocaine was

found in the saliva of impaired drivers (Peel et al. 1984). Most studies show

similar pharmacokinetics of plasma and saliva levels for cocaine. However,

in a recent controlled study, cocaine was found in saliva of chronic addicts 5 to

10 days after abstinence (Cone and Weddington 1989). This long detection

window was attributed to accumulation of cocaine in deep body compartments.

109
Only two studies on the saliva levels of morphine have been reported (Leute et

al. 1882; Gorodetzky and Kullberg 1874). The latter was a controlled study

examining the metabolism of heroin in plasma and saliva. This study followed

the metabolism of heroin by several immunoassays. Heroin was detected for

only 2 to 4 hours in each medium, but this short detection window may have

been due to the insensitivity of the immunoassays employed.

A study on saliva (Kidwell 1990) was initiated that had four objectives: (1)

develop sensitive mass spectrometric-based techniques to analyze drugs in

saliva, which would allow for a confirmation test; (2) determine what metabolites

may be present in saliva and their approximate concentrations, which would

assist with development of screening tests; (3) evaluate the SalivaSac

(BioQuant, Ann Arbor, MI) as a collection device for saliva; and (4) compare

saliva to urine for ease of detection and generation of false-negatives. This

initial study concentrated on the drugs cocaine and heroin.

An analytical technique for cocaine and heroin and their metabolites based on

liquid chromatography (LC)/MS was developed for saliva analysis. LC/MS has

an advantage over GC/MS in allowing the analysis of larger volumes of samples

(50 to 500 μL) and the direct analysis of aqueous solutions, LC analysis has

been employed before for the analysis of cocaine and its metabolites in urine

(Jatlow et al. 1978).

Selected ion traces for an individual with a high level of drugs in the saliva is

shown in figure 6. The chromatography for cocaine and methylecgonine is poor

because the conditions available for analysis in LC/MS are limited since the

buffers used must be volatile and in high concentration and only acetonitrile/

water or methanol/water eluents are practical. Still, with deuterated internal

standards, the analysis is acceptable.

In contrast to GC/MS spectra, LC/MS spectra typically only show protonated

molecular ions with little or no fragmentation. Thus, only the relative retention

time and the intensity of a single ion are available for determination of the

presence of a substance. If more information is necessary, such as a

fragmentation pattern, tandem mass spectrometric techniques must be used.

Saliva Collectlon—The SalivaSac. The SalivaSac is a “pill” consisting of a

bag made of dialysis material and containing an osmotically active material.

The dialysis membrane serves two purposes: (1) It filters the aqueous portion

of the saliva from the mucopolysaccharides, which gives saliva its slimy feel.

The SalivaSac produces a solution much like water. (2) It controls the rate of

absorption of water to prevent a dry-mouth feel. The osmotically active material

(sucrose in the devices employed in this study) facilitates the flow of water. The

110
FIGURE 6. LC/MS ion trace of saliva from a cocaine user

NOTE: The retention time and peak shape of the benzoylecgonine and the d3-

benzoylecgonine internal standard are identical.

SalivaSacs used in this study were of the stimulatory type containing citric acid,

which increases the production of saliva (Kidwell 1990).

One problem occurs with the SalivaSac: The large amount of sucrose used as

the osmatic material produces a saturated solution when dissolved by the

saliva. This changes the concentration of the saliva and any materials

contained inside by diluting it with sugar. This dilution effect was found to be

about a factor of two in this study (Kidwell 1990). The manufacturer

recommends measuring the density of the saliva solution and adjusting the

concentrations of drugs accordingly. No adjustment was made to the data in

this study because this factor should be constant and inconsequential if the

saliva is always obtained in the same manner. An adjustment to the drug

concentrations should be made if they are compared with other collection

devices or for correlation to blood plasma levels.

Concentration of Drugs In Saliva and Urine of Drug Users. Table 1 lists

the total amount of drug or its metabolites in urine of the individuals tested

compared with saliva. The concentrations of the drugs in table 1 for urine

111
TABLE 1. Total concentration of cocaine species and opiates in urine and

saliva (ng/mL)

Sample

1

28

45

52

91

Cocaine

(urine)

(627)

4,470

1,970

Cocaine

(saliva)

14

315

183

Opiates

(urine) Opiates

115

130

138

140

149

151

159

171

175

184

185

194

195

212

218

222

223

233

272

“DF”

1,400 42

150

3,700

9,200

14,600

5,900

4,100

(571)

7,900

2,381

(600)

181

11,000

238

17

78

34

478

58

81

17

6

22

17

857

87

84

3,000 3

1,288 ?

1,600 25

639

325 ?

194

1,627 69

NOTE: ?=possible low level by LC/MS; values in parentheses derived from LC/

MS data after negative results by immunoassay

were measured mostly by immunoassay. In a few cases (not shown), the

concentrations of drugs were confirmed by LC/MS. The concentrations in saliva

were the total of all the various metabolites as measured by LC/MS. In only a

few cases were immunoassays run since the sensitivity would have been

inadequate. Because of the cross-reactivities, EMIT is most sensitive to

benzoylecgonine and morphine, with the other metabolites being only sightly

cross-reactive.

112
Comparison of Saliva and Urine Results-The Pitfalls. The cocaine results

in table 1 illustrate the problem in comparing different matrices by a specific test

such as an immunoassay. If EMIT was the only method used to test the urine

and saliva, then 14 to 25 urine-positives and only 2 to 25 saliva-positives would

have been found. Therefore, saliva would have appeared to be a much poorer

matrix than urine, partially due to the high cutoff level of the EMIT tests. If EMIT

was used to test the urine and LC/MS to test the saliva, then 14 of 25 positives

for urine would have been found and 17 of 25 positives for saliva. In this case,

saliva would have appeared a better matrix since LC/MS is more sensitive than

EMIT and has a broader screen. When the saliva/urine samples that showed

a discrepancy were tested by LC/MS, the missed urine positives were due

primarily to the incorrect metabolite present. This is indicated by parentheses in

table 1.

Further research may show that saliva is likely to be a poorer matrix than is

urine due to the lower concentrations of drugs present. However, saliva’s ease

of collection and less opportunity for dilution, substitution, or adulteration still

may make it a worthy test medium.

Hair Analysis

The short half-life of many drugs of abuse in urine makes detection of infrequent

drug use difficult. On the other hand, hair sequesters many drugs of abuse and

retains them for long periods (Baumgartner et al. 1981, 1982; Marigo et al.

1986). Since hair grows at a rate of approximately 1 cm per month (Meyers and

Hamilton 1951), a time line of drug use could be established. However, before

hair analysis could be employed in any research program, several important

questions need to be answered. For example, what is the sensitivity of hair

analysis? Could a single use be detected? What if the results of urinalysis and

hair analysis disagree? What confirmation technology is appropriate? What

are the mechanisms of incorporation, retention, and loss of drugs of abuse in

hair? Only the last question will be addressed in this chapter (for a more

complete description, see Kidwell and Blank 1990).

Mechanisms for the Incorporation of Drugs. One hypothesis for the

incorporation and retention of drugs in hair may be that of a dynamic

equilibrium. Two opposing forces are interacting between incorporation and

retention of the drug in the hair and loss of the drug to the environment. Drugs

may be incorporated into the hair shaft as one of three possibilities. They may

be incorporated from the blood as the hair grows, from sweat, or from another

external source. Sweat could be a potential rich source of drugs of abuse since

drugs are known to be excreted in sweat (Smith and Liu 1986; lshiyama et al.

1983; Smith and Pomposini 1981), and the concentrations of materials in it

113
would increase as water evaporates. The retention in the hair may be by

ionic forces; in this case, differences in the charge on the drug would affect

profoundly the amount retained. For example, negatively charged species

such as aspirin are not well retained in hair (Harrison et al. 1974), whereas

cationic species such as hair dyes are well retained. The loss from the hair

could result from such things as normal washing, dyeing, perming, and

bleaching or by degradation of the drug in the hair shaft.

One model of a dynamic equilibrium is the dying of hair. If you apply red hair

dye to blond hair, the hair will turn red. The incorporation of the dye into the

hair is rapid and the binding of the dye quite tenacious. Yet, exposure to the

sun for several weeks or repeated washing will decrease the red color intensity.

The color would fade either through leaching of the dye from the hair or through

gradual degradation of the dye into colorless compounds. If the hair was

redyed several weeks later, the original red color would be restored. In this

example, a rapid uptake of dye is followed by a slow decrease in dye

concentration. Interestingly, most hair dyes are cationic compounds and so

are most drugs of abuse that are found in halr in high concentrations.

If this dynamic equilibrium mechanism is reasonable for drugs of abuse,

several concerns arise. Dynamic equilibrium implies that drugs endogenously

deposited into hair can be removed and also that drugs exogenously present

could be incorporated into hair. Therefore, the amount of drug ingested may

not be correlated with the amount found in the hair. For example, as hair ages,

drugs endogenously deposited would have had time to leach out and their

concentrations fall below the detection limit of the assay. On the other hand,

drugs deposited in recently grown hair would not have had time to leach out

and may be detected in hair at high concentrations even though usage was

constant.

Passive Exposure. To determine if external contamination and passive

exposure can mimic drug use, hair from a cocaine user was soaked in an

aqueous solution of p-bromococaine, a derivative of cocaine, at 1 μg/mL for 1

hour. It then was rinsed and air-dried and extracted according to literature

procedures for cocaine (Baumgartner et al. 1982). The hair was washed once

with ethanol, three times with phosphate buffer (pH 7), rinsed three times with

water, and then the cocaine remaining in the hair was extracted two times with

0.6N HCI. Cocaine and p-bromococaine were quantitated in all solutions by

GC/MS; the results are shown in figure 7.

The washout kinetics for the cocaine and the externally introduced

p-bromococaine are similar, again implying that external contamination can

mimic drug use even at as low a concentration as 1 μg/mL. Significant amounts

114
FIGURE 7. Extraction profile of a cocaine user’s hair

NOTE: The p-bromococaine axis is 10 times the cocaine axis. Hair 1 and hair

2 are final extraction steps with acid.

of cocaine and p-bromococaine were found in the final hair extracts. Note that

even though the hair in both cases was not dissolved in the drug extraction step

the quantity of p-bromococaine was 67 times greater in the extract than in the

last wash. This ratio between the quantity extracted from hair and that in the

last wash has been suggested by some to distinguish between active and

passive exposure (Baumgartner et al. 1989). Although the criteria are arbitrary,

those researchers used a factor of 10 between the extract and the wash. In this

case, the cocaine user would have been considered a user of p-bromococaine.

Little added discrimination would be gained by increasing this ratio since, at that

point, most users of drugs would be considered negative.

Metabolite Screening as a Possible Solutlon to Passive Exposure. One

method to distinguish between active ingestion of a drug and passive exposure

is to measure the metabolites of the drug rather than the parent compound.

Cocaine is one of the few drugs that is excreted primarily as its metabolites.

115
Many of the other drugs of abuse are excreted as the parent drug; in this

case, passive exposure could be of concern. Presumably, if the metabolites

of cocaine were found in the hair, then it would be assumed that the individual

ingested the drug. This is only partially true. Cocaine is metabolized via

the esterases present in the human body to three primary metabolites:

benzoylecgonine, methyl ecgonine, and ecgonine. However, these

“metabolites” also may be formed in vitro by hydrolysis with base. For example,

if negative urine is spiked with cocaine and then made basic with sodium

carbonate to pH 10, the cocaine will completely degrade to ecgonine within 12

hours at room temperature. In vitro basic conditions will produce exactly the

same metabolites from the parent drug as will human metabolic processes,

depending on time, pH, and temperature.

As is well known, hair typically is washed with detergents in normal personal

hygiene. These detergents are basic, typically a pH of 10. In fact, even tap

water is pH 8 and buffered at this pH to prevent lead from leaching from the

water pipes. With normal hygiene, hair is constantly being exposed to basic

conditions under which cocaine, if present, may degrade into “metabolites.”

Whether this occurs is unknown.

Differences Between Hair Types. Hair is an extremely heterogeneous media,

which is treated differently among probably every individual on earth. Are there

differences between hair types on the uptake and retention of drugs? One

answer to this question is to compare the self-reported drug use history

between users with two types of hair: black and brown, The use histories were

matched as closely as possible. As shown in table 2, the results indicate a

dramatic difference between hair types. For example, one individual with black

hair indicated use of 250 mg of cocaine on only one occasion, and 6.4 ng/l 0

mg of cocaine was found. Compare that to an individual with brown hair who

also indicated use of 250 mg of cocaine on five separate occasions. In this

case, the cocaine level in the hair was below the detection limit of about 1 ng/10

mg (Kidwell and Blank, unpublished data).

Similarly, data for a heavier user—100 mg/week—with black hair showed a

small amount of cocaine in the hair. Compare this to an individual with brown

hair who uses 2 1/2 times as much cocaine per week. In this individual, the

amount was below the detection limit. Incidentally, differences in uptake and

retention of drugs with hair coloration also were shown in some controlled

animal studies (Harrison et al. 1974; Forrest et al. 1972).

116
TABLE 2. Comparison of cocaine present in different hair types

Use

Black

Amount Detected

ng/10 mg Use

Brown

Amount Detected

ng/10 mg

250 m g once

4-5 g total

100 mg/wk

500 mg/wk

6.4 250 mg once 0

3.5 250 mg 5 times 0

2.2 2-4 g total 2.2

18 5 g total 0

250 mg/wk 0

250-500 mg/day 20

SOURCE: Kidwell and Blank, unpublished data

SUMMARY

Four mass screening techniques for drugs of abuse (TLC, RIA, EMIT, and

FPI) have been described. For small-scale screening, TLC is the most

cost-effective. Although it cannot achieve the sensitivity of the other three

immunologically based techniques, TLC is sufficient for many purposes. All

screening techniques are subject to interferences that can generate falsenegatives or false-positives. These results must be taken into account in

analysis of the research data.

In applying technology in new areas of research, one has to be aware of the

basis and limits of that technology. Testing of drugs of abuse in urine is a wellknown technology in which most of the problems have been discovered. This

technology is less proven for other media, such as hair, saliva, or meconium,

leaving potential pitfalls for the unwary researcher.

NOTE

1. The detection limits listed in the Toxi-Lab Drug Compendium are all within

this range. Other TLC procedures are sensitive down to 0.1 μg/mL for

certain drugs (see Kaistha and Tadrus 1976).

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AUTHOR

David A. Kidwell, Ph.D.

Research Scientist

Naval Research Laboratory

Department of the Navy

Code 6177

Washington, DC 20375-5000

120
Who Is It Going To Be? Subject

Selection Issues in Prenatal Drug

Exposure Research

Peter A. Fried

INTRODUCTION

In the area of research on the effects of prenatal drug exposure on infants and

children, the most powerful tool available is the longitudinal design. This

approach can come closest to answering the two fundamental questions that

underlie the at-risk research discussed in this monograph. The raison d’être of

prenatal developmental drug research is to discover whether the maternal drug

use affects the development of the exposed offspring and, if so, to identify at an

early age those children who will develop behavioral problems.

However, although the longitudinal approach may be the design of choice, it is

encumbered with a host of problems (not necessarily unique to the longitudinal

design), many of which focus around aspects of subject selection. To explicate

some of these issues, this chapter refers to several longitudinal studies reported

in the literature (and, in many cases, currently under way). However, the

primary focus is on the prospective study with which the author has been

involved since 1978, with emphasis on the relevant methodological procedures

rather than on the data collected.

This work-the Ottawa Prenatal Prospective Study (OPPS)—has focused on

the consequences of prenatal exposure to marijuana and cigarettes. During the

development and course of this research, a host of subject selection issues

have arisen. The resolution of the issues and the logic behind the resolution

serve as the focus for this chapter. The general testing procedures that have

been followed, are being followed, and are projected have been outlined

elsewhere (Fried 1989) and are not described or discussed here in detail.

Information describing the potential role that marijuana might play in the course

of human pregnancy and developmental outcome was, prior to the late 1970s

limited to two polydrug case reports. This virtual absence of objective

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318-164 0 - 92 - 5 : QL 3
information, the findings reported from animal studies (for a review, see Fried

1984), the relatively widespread use of marijuana by women of reproductive

age, and the cooperation of the major teaching hospitals in Ottawa were the

impetus for OPPS. These factors also contributed to the approach to subject

selection and subject maintenance.

RAMIFICATIONS OF RECRUITMENT STRATEGY

Between 1979 and 1985, approximately 700 women residing in the Ottawa

area were recruited into OPPS. The study was brought to the attention of the

mothers-to-be by their obstetricians and/or notices in waiting rooms of prenatal

clinics. Any information that was disseminated at this juncture in the work

did not mention marijuana but, rather, discussed in general terms how certain

lifestyle habits during pregnancy may affect the unborn child in infancy and in

the future. The pregnant woman could contact the research staff either by

mailing a prepaid postcard available at all locations where the study was

publicized or by telephoning the research facility. Upon contact, the prospective

subject was given further details about the lifestyle habits that were of particular

interest to the researchers, namely, the use of marijuana, cigarettes, and

alcohol. The initial conversation emphasized that, for purposes of comparison,

it was of considerable importance that the staff members recruit women who did

not use any drugs during the course of their pregnancy. If, at this point, the

woman was interested in participating in the study, a time was arranged for a

one-on-one meeting (almost always at the home of the mother-to-be) where an

informed consent form was signed and an interview took place. During this

visit, which lasted about 2 hours, the female interviewer attempted to establish

rapport with the subject while gathering information on parental health and

medical history, demographics, and maternal drug use (Fried et al. 1980).

At numerous points in this research, decisions must be made about subject

selection-as a result of problems common to most if not all longitudinal,

prospective (cohort) prenatal drug studies. Furthermore, as in OPPS, the

decision options often are restricted. All too frequently the option chosen,

while not optimal from a research point of view, is the only possible pragmatic

choice. If this is the case, it is essential for the researcher to be explicit about

the decision(s) and, as much as possible, to ensure that the consequence(s) is

borne in mind in the interpretation of the results.

An illustration of this dilemma revolves around the volunteer nature of the

subjects entering OPPS. Like all longitudinal prospective studies of maternal

drug use, random selection and random assignment to groups are not feasible,

and the researcher is left with, at best, a quasi-experimental design and all the

drawbacks that such a research approach entails, Dictated by ethical, financial,

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and other pragmatic limitations, participation in OPPS was of a more voluntary

nature (i.e., less implicit psychological coercion) than is usually the case in

similar, parallel types of work. With the procedures employed in OPPS, it

became readily apparent that the women who entered the research were, in

general, self-selected on the basis of being highly motivated. Although not

investigated systematically, it was noted that there was a variety of reasons

for volunteering, including the desire to know the consequences of their own

particular drug habit, the feeling that they were doing everything right and

wished to be reinforced (both drug users and non-drug users), and the wish to

prove that their particular habit was not harmful to their offspring. Furthermore,

the high degree of initiative required to participate, the inclination to read

notices or pay attention to statements made by obstetricians, and the

attendance in prenatal care situations all are factors that potentially can

contribute to bias. The potential bias of a sample recruited in this fashion

must be considered. The term “bias” is used in the sense of a difference

between the target population to which one plans to generalize the findings

and the population from which the sample is drawn,

The self-motivation of the women who initially volunteered to participate in

OPPS clearly restricts the degree of generalizability of much of the

epidemiological and maternal characteristic data collected. It should be

emphasized that this type of voluntary approach also has advantages,

among which are the reliability of self-report and the enhancement of a longterm commitment of the women to the study. These aspects have been

elaborated on elsewhere (Fried 1989).

Recognizing the limitation of subject entry procedures and the role they play in

the interpretation of the findings is only the first step. The researcher must, to

the extent possible, attempt to document qualitatively and quantitatively the

extent of bias within the sample used in the research. In OPPS, this was

undertaken using two sources of information. The most recent Canadian

government census with respect to such demographic variables as family

income, level of education, parity, and drug use prevalence was utilized. In

addition, by using obstetrical records of the hospitals involved with OPPS,

information was gathered on nonparticipating women who gave birth during

the same period as the study group sample.

As alluded to above, entry into OPPS was of a more voluntary (i.e., subjectinitiated) nature than is typically the case in prospective, longitudinal studies.

For example, in a study examining prenatal marijuana and alcohol exposure

(Scher et al. 1988; N. Day, personal communication, November 1989),

women were approached by researchers when the mothers-to-be came to

the university-affiliated hospital during their fourth prenatal month. The refusal

123
rate was approximately 15 percent. A similar initial recruiting procedure and

refusal rate was noted in Streissguth and colleagues’ longitudinal, prospective

study of social levels of drinking (Streissguth et al. 1981). A somewhat more

“aggressive” recruiting procedure is described by Chasnoff and colleagues

(1985) in their pioneering work examining cocaine use in pregnancy. In this

project, all cocaine-using women referred to a perinatal chemical dependence

program in a university-affiliated hospital were enrolled in a longitudinal study.

Eighteen percent of the women referred to the program refused to cooperate

with the project.

With recruitment procedures in which researchers actively contact all or most

subjects in a given center over a specific period, the risk for bias along certain

dimensions may be reduced, but it still exists. There is the limitation that the

subjects may not represent those eligible but not appearing at the particular

recruiting site. One way of at least partially overcoming such a shortcoming is

by using a multicenter research design. However, logistical and financial

burdens often prevent this approach from being undertaken. Therefore, once

again, it is essential that the representativeness of the study population be

detailed so that those who read the reports emanating from the work can

determine whether the findings are applicable to their subject pool.

Once the initial recruiting has taken place, it is often necessary to screen

subjects for relevancy to a study’s objectives. In other words, in a longitudinal,

prospective study, cases frequently have to be selected on a “risk” variable(s),

with not all subjects being “of interest.” Pragmatism dictates that only those

mothers-to-be for whom the variable(s) is relevant (and relevant comparison

subjects, as discussed below) will be chosen for followup. The choice typically

involves consideration of the following criteria.

What is the risk variable in question? Within OPPS the primary drug of interest

is marijuana. When the study was initiated in 1978, very little information

was published with respect to lifestyle habits of marijuana users, and no

information was available pertaining to such habits in a predominantly middleclass sample such as the population from which the expected participant in

the OPPS would be drawn. Obviously, the ideal situation would be to recruit

and follow up women who used only marijuana and no other potential

neurobehavioral teratogens during pregnancy. However, it was felt that it

would be unlikely to find sufficient numbers of such “pure” use. Subsequent

investigation substantiated this concern, For example, at least 85 percent of

middle-class women consume caffeine-containing beverages during pregnancy

(Jacobson et al. 1984; Watkinson and Fried 1985; Streissguth et al. 1989). The

pilot work that preceded OPPS also suggested that there would be a significant

correlation between marijuana use and cigarette smoking. A similar expectancy

124
was that a correlation (not as strong as cigarettes) would exist between

alcohol and marijuana use. Thus, the decision was made to include women

who used these substances either together with the risk factor of primary

interest or on their own without marijuana. On the other hand, the use of hard

drugs was known to be relatively low among the population from which the

OPPS sample was to be drawn. Given the reports in the literature of the time

of neurobehavioral teratogenic effects of such substances, subjects were

excluded from the study if they reported use of such substances as

amphetamines, LSD, or opiates more than twice either during the year

before pregnancy or during pregnancy.

Inclusion and exclusion criteria for sample selection are dependent on the

risk variable under investigation. For example, in the area of cocaine and

pregnancy, the high rate of marijuana use among crack users would result in

severe limitations to sample size and generalizability if cannabis users were

excluded.

Other, not so clear-cut factors also influence the decision to retain exposed

subjects for followup. An illustrative problem is in the domain of personality

traits and drug use. Depression is frequently reported among drug-using

women (Burns 1986). It is difficult to determine whether the depression

contributed to drug use or whether the depression is a consequence of the

drug habit. Should depression be considered as a criterion of exclusion?

Most researchers with this or analogous problems include all subjects and rely

on statistical procedures to disassociate such variables. Although not a subject

selection issue, it bears mentioning at this point that the statistical approach

appropriate for evaluation of these variables is not “cut and dried.” Entering into

the decision is the issue of whether the potentially confounding variables are

possible outcomes of drug use, are independent of drug use, or are mediating

variables.

The extent of usage of the risk variable being investigated is a factor in subject

selection. For example, does one include those who used the drug in question

on a very infrequent basis? The approach that many researchers have taken

is to stratify subjects for the drug(s) in question (e.g., heavy users, light users,

and nonusers), with the heavier category being oversampled (Streissguth et al.

1989; Fried and Makin 1987). A slightly different procedure has been described

by Day and colleagues (1989) in which the study cohort was selected from the

women who received an initial interview. Each woman who reported, in that

first screening, an average of at least three drinks a week during her first

trimester was included in the followup sample. In addition, the next woman

who reported drinking a lesser amount also was retained in the followup cohort.

This sampling approach permitted the recruitment of all of the heavier drinkers

and a proportional sample of other drinking patterns.

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SELECTION OF COMPARISON SUBJECTS

The selection of subjects for comparison is a vital component of longitudinal

work. Control subjects, whether nonusers of the drug in question or drug

users with differential (lesser) patterns of use than the principal group under

investigation, are required for all studies that go beyond pure description.

Although many studies match along particular dimensions, this procedure is

not essential and, in fact, can lead to practical and interpretative problems.

Matching cannot be assumed to solve the problem of the impact of the

confounding variable for which the procedure was implemented. Having

similar values on a particular measure between matched groups does not

guarantee that the matched variable has a similar effect, for there may well be

an interactive component coming into play. From a design point of view, there

are such issues as the following: (1) On how many variables should matching

be attempted (a conflict between the ideal design vs. the practicality of finding

sufficient subjects)? (2) How exact should the matching be (e.g., with age

within 8 months, 2 years, etc.)? (3) If one loses a subject, what does one do

with the match? (4) Matched variables cannot be analyzed as potentially

confounding (potential risk) factors because their distribution across risk and

control groups has been equalized artificially. Further pros and cons of

matching are discussed elsewhere (Anderson et al. 1980; Martin 1986;

Strauss and Allred 1988).

For control subjects to serve their assumed purpose, they must be derived from

a population similar to that of the cases of primary interest. They must be

followed to the same extent and be exposed to the same manipulations (e.g.,

testing, care, observation). Relying on established, historical norms as a basis

of comparison may be inappropriate because of such factors as the length of

time that has elapsed since the norms were established and the makeup of the

standardization sample. A preferable approach is to select controls randomly

or, in some otherwise nonbiased fashion, from a population similar to that of the

experimental subjects to reduce preexisting group differences on nuisance

variables. Two examples drawn from OPPS emphasize the importance of this,

Means of vocabulary scores obtained from the 4-year-old children of very light,

moderate, and regular users of marijuana are seen in figure 1. Pertinent to the

present discussion are the scores of the regular users, which are nine points

above the standard age score equivalents. Only by comparing those scores to

the other two user categories can one observe a drug effect. The overall high

scores in all three groups on this test of verbal comprehension are presumed to

reflect the effect of environmental factors common to all the subjects.

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Marijuana Categories

FIGURE 1. Peabody vocabulary scores of 4-year-old children of marijuana

users

In figure 2, a reverse situation is demonstrated in tests of academic

achievement for children born to active and passive smokers. Although the

children in the experimental groups performed below age-corrected standard

scores (norm=100), the impact is lessened by the fact that the control children

also scored lower than the norm on two of the three tests. In this case,

performance in all three drug conditions was affected by the fact that most

of the children were in a French immersion program in which virtually all

instruction was in French, while the tests administered were normed on

children attending English schools.

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FIGURE 2. Academic achievement scores of 6- to 9-year-old children of

active and passive smokers

OUTCOME AFFECTS DECISION OF RETENTION OF SUBJECTS

The selection issue continues beyond the choice of which mothers-to-be to

retain for followup. It extends after the birth of the infant and may be contingent

upon parameters associated with the offspring. There are some instances in

which circumstances make it obvious that, beyond basic birth data, outcome

variables at a later age would not be useful. One example would be the

untestable baby (e.g., an infant with cerebral palsy). However, many less

clear cases frequently come into play in the area of prenatal drug exposure.

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Confounding Data

Certainly, it is not possible to consider all such variables, but a discussion of a

few that have arisen in OPPS and other longitudinal prospective studies will

serve to indicate the problem. Many drugs, when used during pregnancy, are

associated with reduced birth weight and/or prematurity (Fried and O’Connell

1987). These birth parameters have effects on a host of outcome measures as

the child develops. Should a low-birth-weight child or a premature subject be

dropped from a longitudinal study? This would appear unwarranted as it is

possible that one essentially is eliminating a subject that has shown a drug

effect measured at one stage of development. If the subject is retained, then

the issue moves to a question of statistical treatment of a related variable-not

unlike that mentioned above with respect to potentially confounding variables.

For example, when a regression model is used, one approach is to examine the

unique contribution that the drug in question makes on the offspring’s behavior

once the possible confound of birth weight has been considered (Mau 1980).

An alternative approach involves a chronological, causal chain rationale in

determining what variables should be considered as potentially confounding

factors (e.g., Sampson et al. 1989). In this approach, it is concluded that if birth

weight, for example, is affected by use of a particular drug during pregnancy,

then that should not be controlled statistically in an examination of a relationship

between the drug in question and a later outcome measure. The statistical

arguments are beyond the scope of this chapter (for a discussion, see Fried and

Watkinson 1988), but the relevant point is that no matter how the data may be

treated statistically, the low-birth-weight and premature subjects should not be

eliminated from the followup phase of the work. Thus, in cases in which the

drug being investigated may have a particular effect at birth, that effect may

serve as a mediating variable for an outcome at a later age, and it would be

inappropriate to exclude those subjects in the prospective study.

The decision to retain subjects in the above example is fairly obvious,

However, in OPPS, somewhat more difficult decisions had to be made with

respect to offspring selection and retention. The use of multiple offspring of

the same mother is one such example. Because possible entry into OPPS

was over several years, several participating women had two or even three

children eligible for inclusion. Whether they should be included was not a

straightforward issue. On the one hand, using siblings appears to violate

the assumption of independence on which statistical tests are based.

However, considering the child as the unit of analysis, each has a unique

prenatal history. Although type of prenatal drug use is often consistent across

several pregnancies, it is rarely consistent in quantity or pattern. The potential

problem with independence includes such possible confounding variables as

the mother’s gene pool, her education, her medical conditions, the family

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income, the home environment, and her childrearing practices. A factor in the

decision to include multiple offspring is the need to have as large a sample as

possible (nearly always a problem in research dealing with illegal substances).

Finally, there is the important empirical opportunity to investigate the question

of the degree of similarity or dissimilarity among siblings, although because of

sample size, findings remain at almost anecdotal level. In OPPS, data are

collected from all eligible subjects, and the outcome measures are analyzed

with the random selection of one offspring’s data and with all the offsprings’

data. To date, both approaches have yielded similar results.

An extension of this issue is the question of dealing with multiple births. Here,

however, the issue of lack of independence is more problematic, with much less

variance between the siblings. That plus the few such cases have dictated that,

although the subjects are followed, for publication purposes, only singleton

births have been reported. Nevertheless, collection of parallel data on multiple

birth siblings is not an opportunity to be missed.

Missing Data

An inescapable problem with longitudinal, prospective work is the issue of

treatment of missing data. Any cases with missing data on the primary drugs

of interest clearly must be deleted from the analysis. Dealing with cases with

missing data on the outcome variables is dependent on several factors and

involves several steps. The initial question is whether the missing dependent

variables occur randomly or systematically across groups. If differential loss

across groups is noted, the underlying reasons for loss should be investigated

as they may be important in understanding differences among the groups.

For example, some children may be uncooperative for some tests. If this

behavior were to occur more often in one of the drug groups, this should not

be overlooked as a potential consequence of maternal drug use.

With random or minor loss of data, several options are available. The case

can be dropped if the sample is large. However, if the sample is small, mean

values for the variables affected may be substituted. Within OPPS, the strategy

is to use the overall means of the variables as substitutes, which is a more

conservative approach than substituting the means for the variables for each

group.

If missing data occur with the control variables, the first step would be to

examine the proportion of cases missing the relevant data. If the percentage

is less than some predetermined value (the OPPS figure is 15 percent), then

the group mean is substituted as a score. If the proportion of missing cases is

greater than the a priori cutoff figure, one of two approaches may be

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appropriate. The variable may be dropped if it is highly correlated with another

control variable that has few or no missing data. If this is not possible, the

mean value for the missing scores is substituted and the analysis is run with all

cases. The analysis then is repeated omitting those with missing data, and the

two analyses are compared. If the results are similar, the larger sample with the

substituted values may be retained. If they are dissimilar, a decision must be

made as to which result is more valid.

Outliers

A related problematic issue pertains to the distribution of variables and the

influence of outlying cases. For distributions that are skewed, appropriate

transformations have been described in the literature. For example, log (for

extreme positive skewness) or square root (for moderate positive skewness)

transformations will reduce the influence of outlying cases, but all interpretations

of the results then must be in terms of the transformed variables. If this

approach is employed with the major independent or dependent variables in

the study, problems may well arise with the interpretation. On the other hand,

transforming control variables in this manner is not as problematic.

An alternative strategy is to change the extreme scores to one unit larger than

the next score. Finally, deleting the outlying case may be considered, but if the

sample size is of concern, analyses can be run with and without the offending

case to ascertain the influence of the outlier.

LIMITING SUBJECT ATTRITION

Up to this point, the issues discussed pertain to the experimenter’s decision

as to whether to retain or reject subjects. However, how does the researcher

keep subject attrition to a minimum over a considerable length of time? There

is no one technique that is uniformly appropriate for all types of studies, but

a common element is that extensive outreach activities are essential. Two

approaches are described below. One is employed in OPPS, a highly

motivated predominantly middle-class sample, whereas the other has been

used by Day and coworkers (N. Day, personal communication, November

1989) with a sample of low-socioeconomic status (SES) women,

Low-Risk Sample

In OPPS, techniques to enhance the retention of subjects are initiated at the

point when women enter the study. The interview during each trimester of

pregnancy is conducted by a trained female interviewer at the place of choice

of the mother-to-be, usually the participant’s home. The same interviewer is

131
involved with each of the interviews (up to three) during pregnancy. The

interviewer is skilled in establishing rapport with a range of people—from

“straight” to drug-using subjects.

Once the baby is born, testing is carried out at the hospital, then up until 3 years

of age at the mother’s home, and later at university facilities. In all cases the

same staff, blind to the drug history, “followed” the infant/child during his or her

entire participation in OPPS. These staff members were competent in being

able to advise the women, if asked, on general parenting issues.

However, the key aspect contributing to a high retention rate among the

women participating in OPPS is the method of feedback. Two forms of

feedback are given. Within 2 weeks of testing, a telephone call from the

principal investigator to the family is made and a detailed description is given

with respect to strengths and weaknesses observed in the child. No attribution

to drug use is made in the feedback and, if necessary, an emphasis is placed

on the impossibility of assigning such a cause-and-effect role in a single

subject.

The second form of feedback has been altered over the years. Initially, a

general letter was sent each year describing the basic findings, again

presenting the results in terms of risk factors. Recently, because the test

battery has become so extensive once the child reaches 4 years of age

(Fried 1989), get-togethers have been undertaken to which the mother and

father are invited via a mailing. At this session, data are presented via slides,

and an extensive question-and-answer period is encouraged. Tokens of

appreciation are given to the attendees (e.g., buttons with the OPPS logo

imprinted are given to all, and some T-shirts with the logo are presented as

door prizes).

The comments received either during the telephone feedback or at the annual

get-together leave little doubt as to the importance of these approaches in

maintaining continued participation. Aside from individuals moving from the

Ottawa area, the retention rate of the study cohort over the past 8 years is more

than 95 percent.

High-Risk Sample

A somewhat different approach to maintain contact and foster continued

participation has been used by Day and coworkers (N. Day, personal

communication, November 1989) with a less motivated, low-SES sample.

At the initial interview that took place in an outpatient clinic during the mother’s

fourth month of pregnancy, names and telephone numbers of the mother-to-be

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and the people she designated as significant others were obtained. Contact

was maintained by telephone at least every 6 months. If that was not

successful, attempts were made to contact the subject by mail. A newsletter

(written in a chatty manner) was sent every 3 months informing the mothers of

the study results. This procedure fulfills a dual purpose of maintaining subject

contact and updating address files. If the post office returns the letter or if the

woman cannot be located by telephone, local contacts (including significant

others identified earlier), medical records, and a reverse telephone directory

(listing the address of a particular telephone number) are used. Finally, a

professional tracking system that identifies individuals through social security

and credit data can be employed.

If, after being contacted, subjects are reluctant to come for a scheduled

appointment, additional information is given to the participant with respect to

the content of the upcoming interview for which she had been scheduled. If

necessary, taxicab vouchers, pickup by the staff, reimbursement (above the

scheduled amount), and small gifts for the children are added inducements in

this work. In the study, the women were reimbursed financially with a nominal

amount ($15) for participating beyond the initial intake to defray various costs

and to serve as an incentive for continued participation. Together, these

procedures were successful in retaining these relatively difficult subjects for

the duration of the work.

It is appropriate to raise here the issue of payment of subjects. For some

samples, this is clearly not necessary; for others, payment must be deemed

appropriate and necessary. One cannot expect a low-SES individual to, in

essence, pay to participate in a longitudinal study in which expenses

are bound to be incurred. The issue of payment as incentive to continued

participation is more problematic. Should the payment be in cash or is it more

appropriate to give particular goods (e.g., food, toys, books)? The obvious

problem with cash is how it may be used subsequently. Giving goods, however,

is not an automatic solution as they can be bartered for whatever the cash

might have been used to purchase. There is no clear solution to this dilemma,

but the researcher must be aware of the appropriate amount within the subject’s

environmental circumstances to compensate the subject for the participation.

The more the payment can be connected to continued participation, the better

(e.g., giving a sum at each testing session and a bonus for complete

participation). The details of the remuneration should be outlined in the

informed consent that the subject signs before entry into the study.

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INFORMED CONSENT

The informed consent merits comment from an additional point of view with

respect to subject selection issues. The purpose of an informed consent is to

inform the subject about aspects of the study and rights of the participants

(i.e., process for withdrawal if she chooses; repercussions, if any, of both

participation and withdrawal; form of feedback; availability of counseling; degree

of confidentiality; remuneration, if any). These elements must be presented in

a form that can be understood by the participant. As obvious a point as this

may seem, the written consent is frequently couched in language that requires

an advanced degree to understand. It is not sufficient to have a sentence at the

end of the informed consent stating that “I have read the above and understand

the contents.” An additional aspect of the informed consent should be a series

of oral questions asked by the researcher that would ascertain whether the

participant really understands the content and the implications of the form.

For example, one might ask: “When are you allowed to withdraw?” or “What

happens if something is found to be wrong with the baby?”

The informed consent should include a clear statement of the researchers’ legal

obligations. For example, if abuse is noted by the research team, most (if not

all) State and Provincial governments require that it be reported to appropriate

authorities. A parallel obligation exists when continued maternal drug use is

noted. These aspects of the consequences of participating in the longitudinal

study must be part of the information dispensed to the individual.

CONCLUSION

This far-from-inclusive chapter has highlighted areas of subject selection

ranging from initial screening of potential subjects, choice of the followup cohort,

decisions pertaining to the retention of subjects within the followup cohort, and

factors that may enter into the retention of the cohort over an extended period.

It is rare that within any of these topics there is a simple, universal answer or

approach that can be applied in a “cookbook” fashion. However, by using the

experience of workers in the area of longitudinal consequences of maternal

drug use, research design (as it pertains to subject selection) has steadily

become a more sophisticated facilitating process in this fundamental phase of

prenatal drug exposure research. Continued and possibly accelerated progress

in this methodological area will occur if researchers are encouraged by

reviewers and editors to provide more detailed information about subject

selection procedures within their publications.

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REFERENCES

Anderson, S.; Aquier, A.; Hauck, W.W.; Oakes, D.; Vandaele, W.; and

Weisberg, H.I. Statistical Methods for Comparative Studies: Techniques for

Bias Reduction. New York: Wiley, 1980.

Burns, K.A. Developmental evaluation and intervention for drug-exposed

infants. In: Chasnoff, I.J., ed. Drug Use in Pregnancy: Mother and Child.

Lancaster, MA: MTP Press, 1986. pp. 94-105.

Chasnoff, I.J.; Burns, W.J.; Schnoll, S.H.; and Burns, K.A. Cocaine use in

pregnancy. N Engl J Med 313(11):666-669, 1985.

Day, N.; Jasperse, D.; Richardson, G.; Robles, N.; Sambamoorthi, U.; Taylor,

P.; Scher, M.; Stoffer, D.; and Bloom, M. The effect of prenatal exposure to

alcohol on infant growth and morphology. Pediatrics 84:536-541, 1989.

Fried, P.A. Prenatal and postnatal consequences of marijuana use during

pregnancy. In: Yanai, J., ed. Neurobehavioral Teratology. Amsterdam:

Elsevier, 1984. pp. 275-285.

Fried, P.A. Postnatal consequences of maternal marijuana use in humans. In:

Hutchings, D.E., ed. Prenatal Abuse of Licit and illicit Drugs. Ann N Y Acad

Sci 562:123-132, 1989.

Fried, P.A., and Makin, J.E. Neonatal behavioural correlates of prenatal

exposure to marihuana, cigarettes and alcohol in a low risk population.

Neurotoxicol Teratol 9(1):1-7, 1987.

Fried, P.A., and O’Connell, C.M. A comparison of the effects of prenatal

exposure to tobacco, alcohol, cannabis and caffeine on birth size and

subsequent growth. Neurotoxicol Teratol 9(2):79-85, 1987.

Fried, P.A., and Watkinson, B. 12- and 24-month neurobehavioral follow-up of

children prenatally exposed to marijuana, cigarettes and alcohol.

Neurotoxicol Teratol 10(4):305-313, 1988.

Fried, P.A.; Watkinson, B.; Grant, A.; and Knights, R.M. Changing patterns of

soft drug use prior to and during pregnancy: A prospective study. Drug

Alcohol Depend 6:323-343, 1980.

Jacobson, S.W.; Fein, G.G.; Jacobson, J.L.; Schwartz, P.M.; and Dowler, J.K.

Neonatal correlates of prenatal exposure to smoking, caffeine, and alcohol.

Infant Behav Dev 7:253-265, 1984.

Martin, A.O. Methodologic issues in investigations of drug abuse in pregnancy.

In: Chasnoff, I.J., ed. Drug Use in Pregnancy: Mother and Child.

Lancaster, MA: MTP Press, 1986. pp. 117-135.

Mau, G. Moderate alcohol consumption during pregnancy and child

development. Eur J Pediatr 133:233-237, 1980.

Sampson, P.D.; Streissguth, A.P.; Barr, H.M.; and Bookstein, F.L.

Neurobehavioral effects of prenatal alcohol: Part II. Partial least squares

analysis. Neurotoxicol Teratol 11(5):477-491, 1989.

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Scher, MS.; Richardson, G.A.; Cable, P.A.; Day, N.L.; and Stoffer, D.S. The

effects of prenatal alcohol and marijuana exposure: Disturbances in

neonatal sleep cycling and arousal. Pediatr Res 24(1):101-105, 1988.

Strauss, M.E., and Allred, L.J. Methodological issues in detecting specific longterm consequences of perinatal drug exposure. Neurobehav Toxicol Teratol

8(4):369-373, 1986.

Streissguth, A.P.; Barr, H.M.; Sampson, P.D.; Bookstein, F.L.; and Darby, B.L.

Neurobehavioral effects of prenatal alcohol: Part I. Research strategy.

Neurotoxicol Teratol 11(5):461-476, 1989.

Streissguth, A.P.; Martin, D.C.; Martin, J.C.; and Barr, H.M. The Seattle

Longitudinal Prospective Study on Alcohol and Pregnancy. Neurobehav

Toxicol Teratol 3(2):223-233, 1981.

Watkinson, B., and Fried, P.A. Maternal caffeine use before, during and after

pregnancy and effects upon offspring. Neurobehav Toxicol Teratol 7(1):9-17,

1985.

ACKNOWLEDGMENTS

OPPS has been supported in the past by grants from the National Research

Council of Canada and National Health and Welfare, Canada. The work

presently is supported by National Institute on Drug Abuse grant DA-04874.

B. Watkinson assisted with statistical analysis, C. O’Connell with research

assistance, R. Gray with data analysis, and H. Lintell with data collection.

AUTHOR

Peter A. Fried, Ph.D.

Professor of Psychology

Department of Psychology

Carleton University

Ottawa, Ontario K1S 5B6

CANADA

136
Subject Recruitment and Retention for

Longitudinal Research: Practical

Considerations for a Nonintervention

Model

Ann Pytkowicz Streissguth and Carol T. Giunta

INTRODUCTION

Recruitment and retention of subjects are the two most crucial aspects of

longitudinal research. The success of the entire project hinges on whether the

appropriate subjects can be convinced to participate at the outset and made

to feel it is worth their while to continue over the many years it often takes to

complete the study. In this chapter, the authors draw on personal experience

with five longitudinal prospective studies over a 30-year period.

Prospective longitudinal research is not new; in fact, it has been the backbone

of child development research since the late 1920s when the Berkeley Growth

Study (Bayley 1949) began. How else would one be expected to understand

normal child development without systematic observational studies that tracked

the child into maturity? In the early 1960s the prospective longitudinal method

was used on a grand scale to determine the causes of disease and impairment

in young children. The Collaborative Perinatal Project involved a national

sample of more than 53,000 pregnant women from 12 centers and a cohort of

more than 34,000 children followed through the age of 7 years (Broman et al.

1985; Niswander and Gordon 1972). These pioneering studies have served as

models for the authors’ approach to longitudinal prospective research on the

prenatal environment as it influences postnatal development of the child.

This methodologic chapter draws most heavily on three large-scale studies that

have been initiated over the past 16 years: (1) the Seattle Longitudinal

Prospective Study on Alcohol and Pregnancy (the alcohol study), which was

designed to examine the long-range effects on children of their mother’s social

drinking during pregnancy and the possibly exacerbating or ameliorating effects

of tobacco, caffeine, drugs, medications, diet, and/or the postnatal environment

137
(Streissguth et al. 1981, 1989a, 1989b); (2) the Seattle Longitudinal Prospective

Study on Maternal Iron Deficiency During Pregnancy (Streissguth et al. 1983);

and (3) the Seattle Cocaine and Pregnancy Study (the cocaine study)

(Streissguth et al. 1989c). Each study began with a cohort of approximately

500 subjects. These studies differed not only in their targeted agents and

populations but also in their year of onset—1974, 1980, and 1989, respectively.

We have learned that what works for one time in history may not work for

another. Times change, motivations change, populations change. Unless

longitudinal prospective studies can be flexible and creative in meeting these

changes, their success will be limited-not by lack of worthy hypotheses but by

the mechanics of subject recruitment and followup. In this chapter, the authors

urge investigators not only to learn from the past but also to be flexible in

planning for the future. Moreover, funding agencies and review committees are

urged to respect and encourage flexible approaches to this essential and

expensive aspect of successful longitudinal research.

Careful attention to recruitment and retention of subjects is important for several

reasons: (1) maintaining sample size and power to detect effects if they are

present; (2) avoiding bias in sample selection and data collection; and (3)

generalizing the findings to larger populations (Cox 1958; Harway 1984).

Although the focus of the studies described in this chapter is on pregnancy

followup, many of the techniques will be useful for longitudinal research in

general.

This chapter deals with the population-based study that uses a nonintervention

followup model. In the drug and alcohol field, the nonintervention model, which

historically has been used widely in the field of child development, is useful

for answering basic questions relative to human behavioral teratology: What

are the long-range effects of prenatal alcohol exposure (or cocaine exposure)

on the neurobehavioral development of the child. A companion chapter by

Howard (this volume) describes recruitment and retention issues in longitudinal

prospective studies using a referral model of recruitment and a clinical

intervention followup. The two types of designs require different approaches

to recruitment and followup because direct service to subjects is not an explicit

aspect of the nonintervention model study design. Whichever model one

chooses, careful attention to recruitment and retention sets the stage for

successful longitudinal prospective research.

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CONSIDERATIONS IN PLANNING THE STUDY

Prenatal vs. Postnatal Recruitment

For population-based pregnancy outcome studies, it is essential to estimate at

which point the population best can be approached in full and in a standardized

manner. How this question is answered depends on the goals of the study. In

the social drinking study, the authors hypothesized that timing of exposure was

critical, so enrollment was demanded at a standard time during pregnancy to

optimize self-report of alcohol consumption. The pilot studies had shown that

most of the women in the study population would be in prenatal care by the fifth

month of pregnancy. As we were not interested in alcohol-abusing problem

drinkers who might deliver without prenatal care, it was of no concern if they

escaped the study net. We opted for a more homogeneous, low-risk group of

mothers who were not engaging in other high-risk behaviors and who had

adequate prenatal care. In this study, the standard interview was conducted

during the fifth month of pregnancy, regardless of when the women entered

prenatal care, and all women who were not in prenatal care by midpregnancy

were purposely precluded from participation. This served the dual needs of a

standard interview time and a population that was generally low risk and had

adequate prenatal care.

In the cocaine study, it was recognized that many potential subjects would not

be receiving regular prenatal care; therefore, to standardize the self-report

period, the authors opted for an inhospital postpartum interview. From the

standpoint of study design, it is a less expensive, less complex design to recruit

at delivery. Possible disadvantages, such as a more retrospective recall of

drinking and drug use during pregnancy, can be dealt with by procedures that

maximize recall for the period before pregnancy as well as for the different

trimesters of pregnancy (e.g., see Giunta et al. 1987; Day et al. 1985;

Streissguth et al. 1989c). In the alcohol study, about 10 percent of the prenatal

sample failed to deliver at the hospitals at which they had been recruited

prenatally. This precludes neonatal assessments of the infants and makes

obtaining uniform medical records data difficult. Restricting the sample to those

planning to deliver at the study hospitals and to remain in the area for at least 1

year targets subjects most likely to be available for followup.

Short-Term vs. Long-Term Followup

It is wise to build in tracing procedures that will permit long-term followup even

though the immediate commitment and funding may allow for only short-term

followup. Although subsequent consents must be obtained for later phases, if

the subjects cannot be found they cannot be asked to participate. For example,

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in the alcohol study, 66 percent of the original followup cohort was examined

at 7-1/2 years of age using the tracing procedures described here. When the

investigators went back to the original screening sample and tried to locate

additional control subjects after 7 years, only 20 percent were found because

adequate tracing information on noncohort families had not been obtained.

Frequent vs. Occasional Followup

The decision to employ frequent vs. occasional followup hinges primarily on

the type of subjects being examined, the overall resources for the study, and

the outcomes to be obtained. Experience has shown that middle and upper

class mothers (particularly volunteers) are busy and are not eager to commit

themselves to a frequent followup schedule. On the other hand, in following

high-risk populations from lower socioeconomic backgrounds, it would be

virtually impossible to follow them without frequent contacts due to their

transiency, their lack of familial and employment stability, and their general

lifestyle.

Maintaining the “Blind” Examlner

Although it is clearly less expensive to send an examiner to the home to

examine the baby, it is preferable to examine children in the standardized

laboratory situation (with which all children are unfamiliar) and to employ an

outreach worker to locate the subjects, set up the appointments, and transport

the subjects as necessary. This maintains the examiners “blind” to many

aspects of the family environment that might bias their impressions of the child

and also permits a supportive relationship to develop between the mother and

the outreach worker, which facilitates further followup. In the authors’ study

design, the outreach workers are the key to successful subject retention.

Human Subjects Considerations

It is desirable to obtain the consent for the entire funded study at the outset.

This way the parents know from the start what is expected of them, and the

study does not waste precious resources on subjects who may decline to

participate in later components. The authors were surprised to discover that

some things that were presumed to be objectionable to mothers (like taking a

brief IQ test or allowing us to take a small sample of their infants’ hair for drug

screening) were not protested once the feeling of trust was established. On the

other hand, compliance decreased when the protocol called for infant blood

samples in the iron study.

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Special precautions are necessary in studies involving questions about the use

of illicit drugs. To protect the study records from subpoena, a Certificate of

Confidentiality should be obtained from the Secretary of the Department of

Health and Human Services, US Public Health Service. Recruitment also is

improved by disassociating the project staff from the usual hospital staff and

assuring the subjects that data are not entered into the medical records of

either the mother or her baby. Human subjects restrictions on recruiting

unemancipated teenage mothers (below age 18) without consent from their

parents makes it especially difficult to include young mothers without a special

protocol. (For these younger teenagers, it is also important to assure them that

the information will not be released to schools or parents without their

permission,)

Despite the focus on subject retention implicit in outreach activities, it is

important to note explicitly that subjects do have the right to withdraw from a

study, and this right must be respected.

Special Problems With Illicit Drug Use and Research in the 1990s

Fear of losing their babies is a paramount concern among women who use illicit

drugs during pregnancy. Fear of disclosure of information on illicit drug use is

a frequent reason for refusal to participate in followup studies, particularly as

voiced by a spouse or boyfriend. Media flurries about “crack babies” and

prosecuting mothers for child abuse often can have a direct and immediate

effect on the rate of enrollment at any point in time. The outreach worker

should be apprised of current State law so that proper reassurances can

be given to women at recruitment. For example, at this time in the State of

Washington, prenatal use of illicit substances is not considered child abuse;

knowing this provides additional reassurance to the mother who is considering

enrolling in the study and divulging information about illicit drug use. (Besharov

and Weber, this volume, discuss the legal aspects of this complex problem in

greater detail.)

Additional problems associated with studying mothers who take illicit drugs

during pregnancy involve their frequent lack of a stable social support system

and the overwhelming problems with day-to-day survival that many of these

women face. The authors found that these factors necessitated a much more

active role on the part of the cocaine study staff than had been assumed in the

social drinking study. These activities are described in greater detail in

succeeding sections.

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Screening To Optimize Subject Recruitment

In the two major drug outcome studies, a screening device was used to

optimize selection of the followup cohort, Screening produces a more

generalizable sample (as needed for behavioral teratology studies) compared

with recruiting directly from drug treatment populations or accepting only

referred patients, As the use of alcohol and illicit drugs is not reliably reported

in medical records, the authors prefer the screening method to the medical

records surveys for recruiting a more representative sample of users.

Recruitment from a screening instrument can greatly reduce the cost of the

study design. In the alcohol study, the investigators felt it was essential to

optimize the honest reporting of drinking during pregnancy. At that time,

drinking was common (81 percent of the pregnant women). Private interviews

were given in the home to 1,529 mothers who met the study criteria for being

in prenatal care by the fifth month of pregnancy, who were not planning to

immediately move out of the area, and who lived within a 20-mile radius of

Seattle. It took six full-time interviewers to accomplish this in 1 year. From this

screening cohort, a computerized priority score was developed based on 19

different drinking patterns and control features: it was used to select the

approximately 500 infants who were examined neonatally and for succeeding

postnatal exams (Streissguth et al. 1981). This was an effective strategy for

optimizing recruitment of the followup cohort when studying a relatively frequent

phenomenon.

For the cocaine study, in which pilot studies (Streissguth et al. 1989c) indicated

that only 15 percent of the inner-city mothers and only 3 to 5 percent of the

suburban mothers reported use during pregnancy, a more efficient screening

device was needed. To meet this need, a one-page Hospital Screening

Questionnaire (the HSQ, also called the “Purple Screening Form”) was

developed that is distributed to all mothers delivering babies each day at each

study hospital. (This form, which elicits recall of alcohol and other drug use

before pregnancy and during pregnancy, is available from the authors on

request.) The HSQ is self-administered, but any woman who has difficulty filling

it out can be helped by the recruiter, It is also confidential; subjects are asked

not to put their names on it and the mother puts it in a special envelope for

returning it. Reading the form at the time it is picked up permits the recruiter to

target for the followup study those mothers who have reported cocaine use

during pregnancy as well as appropriate controls, This reduced the number of

women getting 30-minute personal interviews on alcohol and other drug use

during pregnancy from 8,000 to 500. Only the 500 women who met the intake

criteria according to the HSQ were asked to be in the followup study and given

the personal interview on alcohol and other drug use during pregnancy. For this

study, two half-time recruiters could screen 4,000 mothers per year delivering at

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two hospitals and could enroll and interview 250 mother/baby pairs for the

followup study. (This includes weekdays only; additional staff would be

necessary to cover weekends.) Thus, the specialized screening procedures

appropriate to each study enable the staff to recruit a population-based cohort

that most precisely meets the needs of each study.

RECRUITING SUBJECTS

Settlng the Stage for Success

Naming the study appropriately is important for the subjects as well as for staff

members, The authors use a positive-sounding name originally borrowed from

Little (1977), the Pregnancy and Health Study, which reflects the broad goals of

the projects. As new studies evolve, they become P and H-2, etc. because it

would jeopardize children and mothers, both users and controls, to be identified

with a “cocaine study.” As the children in the alcohol study have grown up and

themselves become the primary focus for outreach, an additional name change

has become necessary because Pregnancy and Health Study is not an

attractive study name to teenagers. The new name, the “Seattle 500,” has a

sense of collegiality and solidarity that appeals to teenagers and does not

embarrass them.

The people who do the recruiting are the most important ingredient in

successful recruitment. In the alcohol study, six young women who were similar

to the study mothers in age, race, and social class served as recruiters.

Recruitment was solid at 86 percent. Each interviewer was carefully screened

in terms of openness of attitudes about drinking (none were in recovery or

thought to be judgmental about drinking), and the mothers seemed to relate

easily to them. In the cocaine study, similar criteria were used in selecting the

primary interviewers; however, without considerable additional inducement,

recruitment of cocaine-using mothers was originally steady at only 58 percent.

Obviously, what worked for a licit drug at one time did not work 16 years later

for an illicit drug at a time when considerable media hostility was being directed

toward mothers using drugs during pregnancy. When inducement was changed

(see “Positive Inducements” below), 84 percent of these same women were

recruited.

Constraining Recruitment To Enhance Followup

At the time of recruitment, with its pressure to enroll as many women as

possible within the specified period, it is often difficult to remember that

decisions will constrain the followup for years to come. Enrolling only mothers

who live within a narrow radius of the study site will minimize followup costs.

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This is possible when studying a substance that is widely used. On the other

hand, the rarer the behavior, the more widely afield one must go for subjects

and the higher the followup costs. Likewise, enrolling only mothers who had

telephones and cars would reduce the need for scheduling and transportation

but would bias generalization to only one type of mother. The investigators try

to constrain the subjects geographically at the outset and target only women

who plan to remain in the area for at least 1 year. On the other hand, they do

not constrain for telephones and automobiles but rather develop outreach

procedures to deal with each type of family enrolled, preferring to have a more

broadly representative cohort.

Positive Inducements

In the alcohol study, the sample was predominantly white, married, middle

class, and well educated. Mothers agreed to two followup exams of their babies

within the first 18 months after birth, without payment or material reward.

They were told that they would be reimbursed for transportation costs and,

occasionally, for sibling child-care costs. The staff and subjects believed that

by enrolling in this important study of prenatal influences on child development

they would help other mothers have healthier babies. No other positive

inducements were necessary.

Additional positive inducements were necessary, however, to enroll mothers in

the cocaine study. The pilot studies had shown that subject remuneration was

essential. During the first 3 months of the study, mothers were offered $10 for

each of the four visits. Enrollment was flat at 58 percent, a figure that was

considered inadequate for the type of generalizations the authors wanted to

make. A review of the literature revealed that other longitudinal investigators

(Capaldi and Patterson 1987) found $50 per visit to be a minimal amount to

ensure adequate compliance. In fact, this is a figure commonly cited for adults

who are asked to come in for various types of laboratory assessments, Why

should mothers get less for bringing in their babies? The recruitment rate rose

immediately upon raising the remuneration, and it has remained stable at 84

percent,

Types of positive inducements offered by some studies include well-baby

checkups, medical care, baby photographs, and baby presents. The authors’

studies used none of these, but in the alcohol study, the children were given

coloring books at age 4, fancy balloons at age 7, and $20 at age 14.

Project outreach workers also help the mothers solve whatever obstacles

stand in their way in terms of bringing their babies in for examinations, be it

transportation, child care, scheduling flexibility, etc. In the cocaine study,

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outreach workers have helped mothers solve many other types of problems

such as buying diapers, getting baby furniture, getting breakfast the morning

of the examination, obtaining referral for counseling, getting medical care for

themselves and their families, getting into alcohol and other drug treatment

programs, and getting help for their friends. These activities helped bond the

mothers to the study but are not interventions in the sense that they directly

interfere with the baby or the mother’s interactions with her baby.

TRACING SUBJECTS

General Philosophy

The authors agree with Showstack and colleagues (1978) that losing track of

subjects is a much more common cause of subject attrition than are refusals or

withdrawals. Therefore, successful tracing activities devoted to keeping track of

the cohort over time become essential.

Throughout all contacts with study mothers and their families, the project staff

maintains a nonjudgmental manner, communicating a willingness to act

as advocates for the women if needed. The staff is friendly and open in

relationships with the mothers and their families and is respectful of them as

individuals.

As a general philosophy, staff members also continue to correspond with and

trace every subject enrolled in the study, even though they may have moved

out of the area or missed an individual exam. Some subjects move back into

the area at a later date or contact the staff for an exam when they return to town

on vacation or to visit relatives. Even mothers who have refused one exam

often participate in the next. Thus, the denominator is kept constant across

exam ages, and compliance is often better when children are older and mothers

are less pressured.

In the alcohol study, after 14 years, contact still is maintained with almost all

the subjects, even those out of state and out of the country. By the time the

children were 7-1/2 years old, 20 percent had moved outside the original 20-

mile radius of Seattle. The number who can be brought back for followup

exams in the laboratory depends on available funding.

Specific Techniques

Over the past 16 years, the investigators have gradually improved the

tracing techniques to ensure even more successful followup. At the time of

enrollment, subjects are asked specifically about plans to move and for the

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names, addresses, and telephone numbers of three family members and/or

friends to whom the project staff may turn for help in the event that the mother

cannot be located. The staff also asks each mother for the name under which

her telephone is listed, for her authorization to contact the telephone company

for an unlisted number, for her social security number, for permission to obtain

her address changes from social welfare agencies, and if applicable, for the

name of her social worker. For mothers with frequent home changes, current

addresses also can be obtained (for a small fee) through national credit check

agencies. The mother’s birthdate also is obtained for tracing addresses through

government agencies. This information has proven useful in overcoming most

barriers that were previously encountered in tracing women who remained in

the community but moved so many times that the staff could not find them.

Some women are designated “special-care mothers” for whom the outreach

worker needs to establish immediate contact after recruitment, without

waiting for the next scheduled appointment. Special-care mothers are

defined as women who are so socially isolated that they have no one to list

as “references,” who have no stable housing, and who have immediate needs

that the staff can help with (e.g., bassinets, diapers, housing, legal aid).

Periodic written communications also are mailed to the families, with the

envelopes marked: “Address correction requested.” This allows the staff

to immediately begin tracing mothers who have moved, even though it may

be months or years before their next appointment. Annual custom-designed

birthday cards are sent to the children in the alcohol study. Custom-designed

Mother’s Day cards are sent to the cocaine study mothers as well as

newsletters every 3 months. The newsletters have a chatty, upbeat tone; they

include pictures of the outreach workers and examiners, news about how the

study is progressing, tips on baby care, recipes, and notes about community

resources and activities. They encourage mothers to give out our telephone

number to any friends who have concerns about alcohol and other drugs and

pregnancy. The newsletter also reminds mothers to notify us if they change

their address or telephone number. These communications are sent even to

mothers who have moved out of town so that contact with them can be

maintained. (For additional information, see Giunta et al. 1987.)

Other useful techniques involve using the reverse telephone directory and

driving out to a mother’s last known address (in a State car, in pairs) and talking

with neighbors. A pleasant, positive approach and conveying the idea that

this a health-related issue (the baby’s clinic appointment) often can lead to

success. In talking with a mother’s references, it is often necessary to take

time to establish a feeling of trust before the forwarding address can be

obtained. Occasionally, after a negative contact with one outreach worker, it

146
is useful for another worker to be the main contact with the family for awhile.

Certain public records, such as death certificates and local court records for

both civil and criminal offenses, also can be useful for tracing mothers who are

lost to followup.

Staffing Needs

In the alcohol study, one full-time outreach position is needed just for

maintaining the sample, scheduling appointments, transporting subjects,

and doing mailings for 500 subjects per year. During the 1983 wave of data

collection, this outreach worker scheduled and brought in 40 to 45 children

per month (Giunta et al. 1987). The study averaged a 4-percent “failure” rate

for appointments and a 15-percent cancellation rate. A few subjects needed

repeatedly rescheduled appointments but finally were brought in. For this

7-1/2-year followup examination, staff members saw 95 percent of the subjects

who had been seen at age 4, and over the 7-1/2-year period, study subjects

demonstrated an 85-percent followup rate without any differential loss of more

highly exposed subjects.

In the cocaine study of very high-risk mothers and babies, a different half-time

outreach worker is responsible for bringing subjects in for each of the closely

spaced infant examinations. Each one sets the stage for the next, The study

has a 93-percent rate of followup at 4 months and a 94-percent rate at 6-1/2

months; the 12-month exams are in progress. However, inclusion of a

suburban hospital has escalated transportation costs and outreach worker time.

Each outreach worker brings in 20 to 23 mother/baby pairs per month over a 2-

year period for each exam phase.

RETAINING SUBJECTS

Bondlng to the Study

The authors believe that this is the single most important feature of subject

retention. Even in the cocaine study, where a larger monetary remuneration

was necessary to recruit mothers, what keeps the subjects returning for

repeated exams is the positive feeling of support that they get from

participation. Mothers express this to the outreach workers in a variety of

ways.

Each Encounter a Positive Experience

It is the authors’ philosophy that each encounter with the study should be a

positive experience. The staff communicates feelings of respect and support

147
and the willingness to help. Participation in the study enhances feelings of

self-worth, and this becomes particularly important among women whose

experiences with institutions are primarily as recipients and are often negative.

The mothers seem happy to know that the staff believes they are contributing

something very important to the project and to other mothers by participating in

these studies.

Personalized Communications From the Study

Each communication from the study is thought of as not only a manifestation

of the staff’s interest in the mothers but also a manifestation of the importance

of the study. A special color stationery is used for each study. Each study

has its own logo, which appears on the envelope and letterhead. Stamped

self-addressed envelopes of the same color are enclosed for easy returns.

Important communications are addressed by hand rather than on the computer;

attractive postage stamps rather than postage metering machines are used.

These small tokens appear to be most meaningful in the cocaine study, in which

a larger proportion of the mothers are single and have little social support.

Those who are estranged from their own families seem particularly needy and

responsive to personal touches, which they say they view as a measure of the

staff’s concern.

Although the examiners remain “blind” throughout the study in terms of

prenatal exposures and home environments, the outreach workers have

access to this information. In dealing with mothers who have used illicit drugs

during pregnancy, it is useful to have the new outreach workers acknowledge

to the mothers that they have this information when they interview mothers at

followup visits regarding postnatal drug use. Mothers thus are spared from

having to use denial in dealing with new outreach workers to “save face.”

Mothers were less willing to admit to illicit drug use postnatally when the

outreach worker did not indicate that she knew about their prenatal use.

Remuneration and Feedback

In addition to the $50 remuneration for each visit (see “Positive Inducements”

above), the mothers are either driven to and from their appointments or

reimbursed for transportation costs. About 40 percent of the cocaine study

mothers need to be transported. Mothers are not given specific reports on their

babies’ exams but are given the measurements, if they wish to have them, to

chart their babies’ growth over time. Examiners answer the mother’s questions

in general terms, focus on positive aspects of the child’s performance, and

suggest that a mother discuss special concerns with her baby’s doctor or nurse.

Families without a source of well-baby care are given referrals for such care.

148
Mothers are not given advice about how to parent or interact with their children

nor are they treated differently according to exposure history. Specific referrals

are made for any serious medical problems observed in the course of the

examination. After a study has been ongoing for many years, some mothers

want to know what has been learned. Mothers requesting this information are

sent occasional letters describing the findings in general terms.

STAFF RECRUITMENT, TRAINING, AND INSPlRATlON

Project outreach workers from many different backgrounds have proven to be

equally effective. What the authors look for is not a particular academic degree

but a type of person who communicates concern without being condescending

and who cares without being judgmental. The outreach workers are open,

straightforward, efficient, and, above all, good problemsolvers. They are flexible

in meeting the needs of individual mothers but determined in their efforts to

locate each baby for examination and to leave each mother feeling good about

her participation in the study. Outreach workers often give mothers their home

telephone numbers and strive continually to reduce barriers to communication.

They are trained in-house by previous outreach workers through the use of our

outreach manual (Giunta et al. 1987) and by what they learn from the mothers,

Some outreach workers feel that a social work background helps them listen

with an “educated ear” and that a feminist perspective is a useful orientation.

Others are able to use their own life skills as a basis for concern and

understanding.

Although no special degrees are required for outreach workers, they should not

be poorly paid. Writing job descriptions with adequate outreach salaries is

important for staff stability, which, in turn, enhances subject retention. The

outreach worker often must work irregular hours to accommodate the needs of

mothers; compensating for such services can be difficult on restrictive budgets.

Planning for sick leave and vacations also is complicated when outreach

workers are employed over long periods.

Outreach work is so demanding and intense that it is essential to provide

support for staff members in this position. Brainstorming sessions in which

they share experiences and ideas are particularly useful to get a new slant on

hard-to-trace mothers. Various types of in-service opportunities, such as child

abuse conferences and programs about female drug and alcohol abuse, are

also helpful for outreach workers. Budgeting for these costs in advance is

important.

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MAINTAINING CONTINUITY THROUGH TIME

No matter how dedicated the outreach staff, changes in personnel are

inevitable. Thus, successful longitudinal prospective studies will need to

devise ongoing systems for maintaining continuity through time despite

personnel changes.

The availability of computer systems has improved the project outreach service

greatly compared with what was available 16 years ago. The outreach files

utilize a database management package with a mail manager and a word

processor that produces personalized confirmation letters and facilitates

labeling newsletters. This system permits the outreach worker not only to

update name and address information for each subject as it is available but

also to schedule each baby’s appointment according to his or her adjusted age

as necessary for many infant examinations conducted during the first few years

after birth. Thus, by entering the birth date and the gestational age at delivery,

the outreach worker can schedule the followup exam at the correct time even

before all information is available in the main database from the medical records

or maternal interviews.

Outreach workers also keep systematic notes on their attempts to contact each

mother. A “Subject Contact Sheet” is filled out for each contact and filed in

the locked tracing files, arranged alphabetically by mother’s last name. The

sheet is accessible only to the outreach staff. Thus, all old contact sheets are

available to each new outreach worker at each new examination phase.

Individualized outreach notes on each subject provide invaluable information

to the outreach worker who finds the trail cold on a particular mother.

BUDGETING FOR SUCCESS

Outreach costs are not cheap. They often are undervalued in peer review

compared with the unquestioned costs of instrumentation for data collection.

Yet, without adequate outreach, the most precise outcomes will not yield

results. Review committees and agencies accustomed to dealing with shortterm projects usually have no idea about the skill involved with successful

outreach and the attendant costs.

The direct relationship between the budget and the followup rate becomes

accentuated as the children get older and more dispersed from the target area.

The older the subjects and the longer the interval between exams, the higher

the outreach costs. The task is not impossible, but it is expensive. Capaldi and

Patterson (1987) described a longitudinal study in which families were paid up

to $300 per year plus bonuses for three 1-hour home visits and a half day of

150
office tests. They concluded that high pay for subjects, highly trained home

visitors, and written materials targeted to the subjects were the key to doubling

recruitment and a followup rate of 100 percent,

Finally, the authors note again the importance of budgeting appropriately

for each study at the outset. Agencies are urged to be responsive to the

unanticipated outreach needs of longitudinal prospective studies (due to

changing times and populations) and the tremendous resource represented

in studies that have been ongoing for many years. Experience with long-term

studies has led the investigators to believe that some of the most important

outcomes are measurable only later in the child’s life (Streissguth et al. 1989b).

Yet, to track the child and his or her family over those years, some contact is

necessary, which costs money even when it does not involve major datacollection phases. When dealing with issues of such major significance to the

population as the impact of prenatal alcohol and drug exposure on the health

and functioning of the next generation, it seems imperative to take a long-term

rather than a short-term view. High recruitment and retention rates are

essential for successful longitudinal prospective research.

IS THERE A CONSENSUS?

In preparation for this chapter, a brief questionnaire was sent to colleagues

experienced with longitudinal prospective studies of children whose mothers

used alcohol and/or other drugs during pregnancy. Responses were received

from eight investigators, representing a total of 12 such studies. The factors

most frequently noted or associated with successful followup were the quality of

the subjects’ personal relationship with the staff, adequate remuneration, and

the services provided by the study. The biggest problems the investigators

encountered in such studies were obtaining sufficient money for recruitment and

retention, finding suitable subjects, motivating subjects from low socioeconomic

backgrounds, and dealing with lifestyle factors of drug-abusing mothers (such

as transiency and dangerous neighborhoods). When asked what longitudinal

researchers might like to communicate to government agencies, the responses

focused on three topics: (1) the amount of money it requires to recruit and

follow up mothers in these projects and how labor-intensive this process is, (2)

the amount of time necessary to run these studies and to analyze the data, and

(3) the difficulty in maintaining an operational study and retaining key staff

during periods in which the project is not refunded or when negative results are

obtained during certain periods.

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CONCLUSIONS

For longitudinal prospective studies, successful recruitment and retention of

subjects over long periods is essential and expensive. It is essential because

without successful recruitment and followup of subjects no outcome could be

evaluated, and it is expensive because the creative task of motivating, tracing,

and transporting subjects for repeated examinations over long periods is

extremely labor-intensive. Outreach activities represent a far greater part of

the successful research budget than most nonlongitudinal researchers realize.

The essential ingredient for successful recruitment and retention of subjects in

longitudinal research is the personal commitment of each subject to the project.

The expense of obtaining this goal covers both the imaginative resources of

the research team in determining how to inspire and maintain this commitment

and their continual evaluation and upgrading of their outreach efforts. Although

costs will vary greatly depending on the goals of the project and the type of

subjects needed, recruitment and retention costs (including subject

remuneration for some types of studies) are a valid and important component

of the budget for longitudinal research. Without successful followup there is no

study.

REFERENCES

Bayley, N. Consistency and variability in growth of intelligence: Birth to 18

years. J Genet Psychol 75:165-196, 1949.

Broman, S.; Beir, E.; and Shaughnessy, P. Low Achieving Children: The First

Seven Years. Hillsdale, NJ: Erlbaum, 1985.

Capaldi, D., and Patterson, G.R. An approach to the problem of recruitment

and retention rates for longitudinal research. Behav Assess 9:169-177,

1967.

Cox, D.R. Planning Experiments. New York: Wiley, 1958.

Day, N.L.; Wagener, D.K.; and Taylor, P.M. Measurement of substance use

during pregnancy: Methodologic issues. In: Pinkert, T.M., ed. Current

Research on the Consequences of Maternal Drug Abuse. National Institute

on Drug Abuse Research Monograph 59. DHHS Pub. No. (ADM)85-1400.

Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1985. pp. 36-47.

Giunta, C.T.; Barr, H.M.; Gillespie, J.M.; and Streissguth, A.P. Techniques for

Minimizing Subject Attrition in Longitudinal Research. Pregnancy and Health

Study Technical Report No. 87-01. Seattle: University of Washington, 1987.

Harway, M. Some practical suggestions for minimizing subject attrition, In:

Mednick, S.A.; Harway, M.; and Finello, K.M., eds. Handbook of Longitudinal

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pp. 133-137.

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Little, R.E. Moderate alcohol use during pregnancy and decreased infant birth

weight. A!m J Public Health 67(12):1154-1156, 1977.

Niswander, C.A., and Gordon, M., eds. The Women and Their Pregnancies.

Philadelphia: W.B. Saunders, 1972.

Showstack, J.A.; Hargreaves, W.A.; Glick, I.D.; and O’Brien, R.S. Psychiatric

follow-up studies: Practical procedures and ethical considerations. J Nerv

Ment Dis 166:34-43, 1978.

Streissguth, A.P.; Barr, H.M.; Grant, T.; Martin, J.C.; Brown, Z.; Mayock, D.; and

Ramey, S.L. Cocaine and the Use of Other Drugs During Pregnancy.

Pregnancy and Health Study Technical Report No. 89-03. Seattle:

University of Washington, 1989c.

Streissguth A.P.; Barr, H.M.; Labbe, R.F.; Smith, J.R.; Darby, B.L.; Smith, N.J.;

Martin, D.C.; and Doan, R.N. Alcohol use and iron status in pregnant

women. Alcohol Clin Exp Res 7(2):227-230, 1983.

Streissguth, A.P.; Barr, H.M.; Sampson, P.D.; Bookstein, F.L.; and Darby, B.L.

Neurobehavioral effects of prenatal alcohol. Part 1: Literature review and

research strategy. Neurotoxicol Teratol 11(5):461-476, 1989a.

Streissguth, A.P.; Bookstein, P.L.; Sampson, P.D.; and Barr, H.M.

Neurobehavioral effects of prenatal alcohol. Part III: PLS analyses of

neuropsychologic tests. Neurotoxicol Teratol 11(5):493-507, 1989b.

Streissguth, A.P.; Martin, D.C.; Martin, J.C.; and Barr, H.M. The Seattle

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Toxicol Teratol 3:223-233, 1981.

ACKNOWLEDGMENTS

The work described in this chapter was funded by grants from NIDA (DA05365), the National Institute on Alcohol Abuse and Alcoholism (AA-01455),

and the National Institute of Child Health and Human Development (2789-5).

Janet Gillespie, Abigail Halperin, Margaret Edgar, Therese Grant, Pam Phipps,

Sally Lang-Stoddard, Natasha Grossman, Sandy McAuliff, Pamela Swanborn,

and Linda Peters recruited and/or performed followup components with the

subjects of these studies. Biostatisticians Helen Barr and Donald C. Martin

assisted with the analysis of data. Coinvestigators for these studies were Joan

C. Martin, Sharon Landesman Ramey, and Heather Carmichael Olson, Senior

Fellow. Professional consultation over the past 16 years has been provided by

Ruth E. Little and Loretta P. Finnegan.

AUTHORS

Ann Pytkowicz Streissguth, Ph.D

Professor

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318-164 0 - 92 - 6 : QL 3
Department of Psychiatry and Behavioral Sciences

2707 Northeast Blakely

GG-20

University of Washington School of Medicine

Seattle, WA 98195

Carol T. Giunta, M.S.

Psychology Intern

Psychology Service (1166)

San Francisco VA Medical Center

4150 Clement Street

San Francisco, CA 94121

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Subject Recruitment and Retention

Issues in Longitudinal Research

Involving Substance-Abusing Families:

A Clinical Services Context

Judy Howard

INTRODUCTION

The professional literature contains little information describing successful and

unsuccessful methods for recruiting and retaining subjects in research projects

dealing with chemically dependent women and their children. Although the

Handbook of Longitudinal Research (Mednick et al. 1984) addresses methods

for conducting longitudinal studies of birth and childhood cohorts in general, it

does not include information specific to this population. This chapter reports

some strategies that have proven effective during two 3-year longitudinal

studies of substance-abusing families.

Recruiting and retaining chemically dependent families in research projects

requires familiarity with the lifestyle of this client population and knowledge of

their complex needs. Unlike families who have participated in prior studies of

preterm infants (Parmelee 1977; Siegel 1984) or children from disadvantaged

backgrounds (Lazar and Darlington 1982; Weikart 1989), chemically dependent

families have unique characteristics that profoundly affect the recruitment and

retention plan. These characteristics include (1) intermittent altered mental

status secondary to the acute effects of alcohol and/or other drugs, (2) the

effects of chronic alcohol and/or other drug use upon cognition, (3) the often

untreated health care problems inherent in this population (e.g., sexually

transmitted diseases, hepatitis, acquired immunodeficiency syndrome [AIDS]),

(4) the violence associated with the drug lifestyle, (5) the “high-roller” economics

of the drug culture, and (6) the disease of addiction and its implications (e.g.,

chronicity, recidivism). Ongoing professional interaction with these families

demands that members of the research team be aware of these factors to help

them maintain the professional objectivity necessary for conducting longitudinal

research with this difficult population.

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RECRUITMENT OF STUDY POPULATION

It is imperative that any recruitment strategy be designed with the specific

study population in mind (Capaldi and Patterson 1987; Howard et al. 1986;

McCorkle et al. 1984; Young and Dombrowski 1989). Furthermore, the

recruitment process requires a bidirectional focus-on the referral sources

and on the subjects. If the research design entails a population with specific

attributes (e.g., subjects who are both pregnant and substance abusing),

referral sources where such individuals may be identified have to be located,

and their cooperation with research staff must be solicited. Following this, the

subjects have to be recruited in such a manner that they will be motivated to

participate in the project.

Referral Sources

In initiating the recruitment process for the 3-year study at the University of

California, Los Angeles (UCLA) School of Medicine, Department of Pediatrics,

my colleagues and I first established collaborative relationships with a variety

of referral sources. A common referral source for chemically dependent

subjects, for instance, would be a health or treatment center that identifies and

provides services to substance-abusing individuals. In States where infants

exposed prenatally to drugs are reported as being at high risk for child abuse

and neglect, an additional referral source would be the local child protective

services agency and/or the family court system.

Following identification of potential referral sources in reasonably close

proximity to the research center, the research team must devise the appropriate

“invitation” for use in recruiting subjects into the study. Such an “invitation”

should include a clear description of the research project as well as of the

participants’ role. Also, it should convey an attitude of sensitivity to the subjects’

life situations and needs.

Subject Recruitment

With chemically dependent families, a recruitment approach must allow more

flexibility than would be necessary with families who are not involved with illegal

activities. This flexibility enables project staff members to meet with subjects

“on their own turf.” The illicit nature of substance-abusing families’ activities

and their frequent changes of address necessitate a personal, one-on-one

approach; furthermore, the project staff must be available to conduct intake

interviews on weekends and during the evenings.

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Although financial incentives have proven effective in recruiting and retaining

subjects in some studies, particularly in the case of lower income families

(Capaldi and Patterson 1987) our experience with incentives has focused on

the provision of individualized services rather than payment to clients. Both

approaches are costly but seem to be effective.

INHERENT VALUE OF CLINICAL SERVICES IN RESEARCH

My colleagues and I believe that provision of services in conjunction with

conducting research is critical for subject retention and for ethical reasons.

Thus, we maintain two separate staffs: The clinical staff provides ongoing

services to project families, and the research staff is responsible for conducting

the evaluations in the home and in the laboratory. These two staffs work

separately to guarantee that research staff members remain “blind” to the

experimental and control groups.

As data collection progresses and findings are analyzed, the work of the

research staff may appear to be increasingly important-sometimes seeming to

tip the balance between the two staff components. Exacerbating this, in certain

academic settings, research in general may seem to be valued over provision of

clinical services to families. Therefore, the clinical staffs role in client

retention-and, thus, in ensuring that research data can be collected-may

need to be accentuated as a critical project element. Just as research staff

members may feel a sense of accomplishment when they are able to report

their findings, the clinical staff also can experience such professional

satisfaction when given opportunities for conference presentations and

development of products such as informational brochures, manuals, and

educational audiovisual materials.

RETENTION OF SUBJECTS

Strategies Used With Non-Substance-Abusing Clients

One longitudinal study conducted at UCLA that began in 1972, and focused on

the developmental outcome of preterm infants, initially recruited 135 subjects,

retaining 100 through the 12th project year (Cohen et al., in press). The first 2

years of the project emphasized individualized health care provided by a clinicbased pediatrician and a public health nurse who made home visits. During the

remaining 10 years, project intervention was far less intensive but remained

consistent. During this period, a psychologist and a pediatrician conducted

periodic testing of the children and were available for consultation with families

as needed.

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Subjects were tracked over this 12-year period through four different means:

(1) parents’ employers, (2) parents’ driver’s licenses, (3) names of three family

members or friends, and (4) records of ongoing health care at UCLA Medical

Center. Maintaining contact with the subjects involved a tremendous amount of

effort on the part of research staff members. However, it is the staffs

impression that the intensive early intervention provided the foundation for the

ongoing willingness of subject families to continue with a 10-year schedule of

testing procedures (S. Cohen, personal communication, 1990).

Strategies Used With Chemically Dependent Subjects

Unlike the families served in the preceding longitudinal project, chemically

dependent families present even more problems in tracking subject

whereabouts. Furthermore, the chaotic lifestyle associated with alcohol

and other drug abuse puts these families at particularly high risk for attrition.

Many of them do not have driver’s licenses, for instance. They tend to be

unemployed; relatives and friends may not be willing to tell researchers where a

family is located; and their health care is often sporadic. Thus, subject retention

has become a primary focus for our staff. We have used a strategy that

focuses on the family as a whole, which we feel has contributed to subject

retention.

Based on the experience with families of preterm infants described above, as

well as on our experience in working with chemically dependent families, we

have combined two approaches in our research projects. In providing intensive,

individualized services that include both clinic-based and in-home assessment

and intervention, an interdisciplinary team is used to ensure that health and

psychosocial issues as well as concrete concerns, such as finances, housing,

food, legal problems, respite, and child care, are addressed. Along with

conveying an attitude of concern for the participants’ well-being and respect for

their worth as human beings, the staff has approached each subject with

consistency, reliability, flexibility, and honesty, while maintaining a professional

role.

The research staff also needs to develop relationships with extended family

members and any other individuals who may be providing care for the

research subjects. Thus, it is helpful if project staff members can help facilitate

appropriate services and referrals for other family members when indicated.

For instance, if a newborn is the identified subject and the project staff observes

that an older sibling has a health or developmental problem, it demonstrates

concern for the family if the staff is able to assist this child in obtaining needed

services.

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Retention of Subjects and Collaboration With Community Agencies

Continued relationships with community agencies are essential in retaining

research subjects. As a project progresses, community agencies not only can

help secure services for families (such as financial assistance, help with food

and housing, and legal consultation) but also can assist the research staff in

tracking family movements. Because a chemically dependent parent may

engage in illegal activities, family members, friends, and neighbors may

withhold information about a family’s whereabouts from the research staff if

they suspect that the family is in trouble with the legal system. Thus, without

the assistance of those community agencies with sufficient “clout” to maintain

contact with these families, research staff members may not have access to

records that identify changing addresses and telephone numbers. Furthermore,

the coordinated advocacy on behalf of these families that results from ongoing

collaborative intervention among research staff members and community

agency personnel can greatly enhance services to this population.

Erratic Caregiving

Complicating this type of family focus in working with chemically dependent

clients is the fact that children with substance-abusing parents frequently have

multiple caregivers, including biological parents, extended family members, and

foster caregivers. If a child is in temporary out-of-home placement, for example,

the project staff needs to sustain relationships with the biological parents while

continuing to provide services to the other caregivers.

The situation can be compounded further by the special issues surrounding

each group of caregivers. For instance, biological parents who are chemically

dependent require an intensive focus to address their own personal needs.

Although extended family members may be reluctant to request help for

themselves, they may require assistance in dealing with their own feelings of

anger and grief and with their concerns regarding the addicted parent (who

may be a son or daughter) as well as the child’s health and development.

Likewise, foster parents have issues that are different from those of biological

parents and extended family members. These usually are less focused on

personal feelings about chemical dependency and more directed toward

organizing daily schedules for the children who may be under their care,

including coordinating home visits by involved professionals and biological

parents, keeping the children’s health care appointments, and participating in

evaluations that are part of the research project. Thus, maintaining a family

focus in work with chemically dependent clients involves far more than

assessing the child’s development and health status.

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Age and Subject Retention

The age of a subject at the time of his or her enrollment in a research study

also may be a factor in determining attrition rates. For instance, Capaldi and

Patterson (1987) and Ellickson and coworkers (1988) report that older children

enrolled in a study that spans several years may be harder to retain once they

become adolescents. This may be due to a lack of intensive family intervention

early on in the study to ensure parental commitment to the project and/or the

increasing independent behavior of the older child as he or she becomes an

adolescent.

RETENTION OF PROJECT STAFF

It is our impression that staff continuity relates directly to subject retention.

Thus, measures for preventing staff burnout are an important aspect of the

research plan in work with chemically dependent families; examples of these

are described below.

Staff Training and Support

The tone for program operation is established by the director of the research

project. Identification of staff members who have the range of necessary

professional backgrounds and experience, as well as interest in the research

area, is critical to the success of any project. However, once the staff has been

hired, the project director is responsible for arranging inset-vice training, staff

support, and opportunities for innovation within the framework of the project

design to ensure effective services and reliable findings and to promote

retention of project staff members.

A Common Knowledge Base

As a basis for providing informed services, interdisciplinary research and clinical

staffs need to establish a common knowledge base in a variety of areas related

to the research focus. In serving chemically dependent families, we have found

it critical to update the staff regarding the latest findings on the backgrounds,

lifestyles, and health problems of substance-abusing parents; the disease of

addiction; cultural issues; and community resources. It is also important for the

staff to be familiar with child health care issues (including symptoms of pediatric

AIDS, hepatitis, congenital syphilis, and other health problems that have been

noted in children who were prenatally exposed to alcohol and/or other drugs)

and with areas of developmental assessment and their implications for future

functioning.

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Knowledge About CommunIty Agencies. Furthermore, because chemically

dependent families may have frequent interactions with child protective

services, family court systems, criminal court systems, and law enforcement

agencies, it is necessary for staff members to learn about the specialized roles

of these various organizations and the relationships among them. It is also

important that the project staff be familiar with the expertise, responsibilities,

and limitations of the multiple professional disciplines of the team that is

involved with these families.

Knowledge of Family Systems. In addition, we have found that the clinical

staffs knowledge of family systems and family functioning is essential as

research data regarding caregivers and the effects of the environment on child

development are collected and interpreted. An infant may be placed in the care

of a maternal grandmother, for example, but the biological mother also may

reside within the home. Although child protective services may identify the

maternal grandmother as the primary caregiver, in reality the biological mother

may be spending the most time caring for this infant. Thus, in assessing

attachment behaviors, it is the biological mother, not the maternal grandmother,

who should be involved with the laboratory evaluation. Accordingly, one feature

of staff development programs must be to alert the clinical and research staffs

to the importance of clearly identifying the roles of various family members so

that a consistent interpretation of collected research data is possible.

Nature of Addiction. Another focus for staff development programs relates to

the nature of addiction, which can impair an individual’s ability to behave in a

controlled fashion and to make sound decisions. It is not uncommon for

chemically dependent parents to be neglectful and/or abusive toward their

children and each other. In two of our longitudinal projects, for instance, in spite

of less than 5-percent subject attrition and provision of intensive, home-based

intervention, suspected child abuse and/or neglect was reported in several

cases. These reports included failure to thrive on the part of the infant; child

neglect due to a mother’s absenteeism while on a “binge”; cigarette burns,

sexual abuse, and school truancy in connection with older siblings; and

domestic violence. Thus, the clinical and research staffs need to be aware of

their mandated responsibilities with respect to reporting cases of suspected

child abuse and neglect.

Assessment of Danger. Finally, just as intrafamily and community conflicts

arise around alcohol and other drug abuse, project staff members must learn

how to assess situations that potentially may be dangerous for them during

home visits and while transporting clients to and from appointments. Staff

safety is an additional issue that needs to be highlighted when dealing with

chemically dependent subjects.

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Staff Attitudes

In conjunction with this common knowledge base, project staff members need

time to focus on their own attitudes, emotions, and biases in working with this

complex population. In our experience, some professionals who choose to

work in this field come from backgrounds in which there was alcoholism,

substance abuse, physical abuse, or neglect, whereas others who may not

have experienced this type of family dysfunction also may require time to come

to terms with their views about substance abuse. Therefore, opportunities

should be available for staff support, venting of feelings, and exploration of how

a professional’s attitudes can affect his or her intervention with these families.

Staff Differences and Cooperation

To further promote a supportive and productive working environment in dealing

with these complex families, there must be respect among team members for

individual skills and different styles of approaching clients and a provision within

the program design for a certain degree of staff autonomy. Over time, this can

be facilitated through regularly scheduled meetings that incorporate case

presentations and group case discussions. In addition, it is helpful when project

directors can set aside time for individual case consultations with project staff

members. Finally, both research and clinical staffs can benefit from access to

interdisciplinary supports such as drug treatment counselors, pediatricians, and

hospital Suspected Child Abuse and Neglect Team coordinators.

Fostering a work environment that provides opportunities for individual staff

members to develop and implement creative approaches to intervention and

research not only encourages staff “ownership” of the project but also can

enhance significantly individualized services provided to clients. For instance,

in connection with one of our projects, research staff members were responsible

for interviewing chemically dependent parents regarding their childhoods and

experiences with family members, Clinical staff members were apprised that

sensitive issues (e.g., a history of physical or sexual abuse) might be uncovered

during these interviews and, in response to staff members’ suggestions, made

themselves available to clients following these sessions to assist as needed. In

another case, a staff member was able to arrange, through local churches,

delivery of Thanksgiving food baskets to needy program participants. Sending

birthday and holiday cards or taking clients to lunch are additional efforts staff

members have made to enhance both project services and their own positive

feelings about working with these families.

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Caseloads

It is particularly significant in the area of staff support to ensure that caseload

sizes are manageable, since this benefits clients and helps prevent staff

burnout. It has been our experience that a chemically dependent family

generally includes more than three individuals, all of whom require attention

from the project staff. On average, four community agencies are involved per

family-representing at least two individual staff members each. Thus, a

caseload of 20 to 25 families can entail more than 75 family members, with an

additional 8 community agency representatives for each family. When a project

has a home-based component, which is critical for effective intervention with

chemically dependent families, caseloads not exceeding 25 to 30 families are

sufficiently manageable to permit effective tracking, home visitation, and

coordination of center-based appointments and activities.

Administrative Support

Finally, the role of an administrative and support staff in ensuring that project

activities can be conducted with minimal complications is also significant.

Procedures that promote effective communication among staff members as well

as practical systems for recordkeeping, appointment scheduling, and notating

completed or failed laboratory and in-home evaluations can greatly enhance

project operation. Thus, “front-line” staff persons who answer telephones and

interface with clients, community agency representatives, and even grant

agency staff must be incorporated as part of the research team.

CONCLUSION

Research in general is essential to increase knowledge. Informed research is

based on a rudimentary understanding of the subject to be examined. To study

the development of children who have been exposed prenatally to drugs, we

need to be able to conduct longitudinal research. This chapter attempts to

highlight the types of activities and programs that have proven successful in

retaining substance-abusing parents and their children in research projects.

The study of chemically dependent families is obviously complex, not only

because of the seriousness of the problem of addiction but also because of

lack of information about these clients’ chaotic lifestyles and the effects of

polysubstance abuse. Because of the nature of illicit substance abuse, some

professionals may conclude that retention of these subjects in a longitudinal

study is not feasible. However, such a study is possible given the provision of

informed, individualized services and an interagency approach that often

includes the legal and child welfare systems.

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REFERENCES

Capaldi, D., !and Patterson, G.R. An approach to the problem of recruitment

and retention rates for longitudinal research. Behav Assess 9:169-177,

1987.

Cohen, S.; Parmelee, A.H.; Beckwith, L.; and Sigman, M. Biological and social

precursors of 12 year competence in children born preterm. In: Greenbaum,

C., and Auerbach, J., eds. Cross National Perspectives in Children Born at

Risk. Norwood, NJ: Ablex, in press.

Ellickson, P.L.; Bianca, D.; and Schoeff, D.C. Containing attrition in schoolbased research: An innovative approach. Eval Rev 12(4):331-351, 1988.

Howard, K.I.; Krause, M.S.; and Orlinsky, D.E. The attrition dilemma: Toward a

new strategy for psychotherapy research. J Consult Clin Psychol 54(1):106-

110, 1986.

Lazar, I., and Darlington, R. Lasting Effects of Early Education: A Report from

the Consortium for Longitudinal Studies. Monographs of the Society for

Research in Child Development. Vol. 47, Nos. 2-3. Chicago: University of

Chicago Press, 1982.

McCorkle, R.; Packard, N.; and Landenburger, K. Subject accrual and attrition:

Problems and solutions. J Psychosoc Oncol 2(3/4):1 37-146, 1984.

Mednick, S.A.; Harway, M.; and Finello, K.M., eds. Handbook of Longitudinal

Research. Vol. 1. Birth and Childhood Cohorts. New York: Praeger, 1984.

Parmelee, A.H. Planning intervention for infants at high risk identified by

developmental evaluation. In: Mittler, P., ed. Research to Practice in Mental

Retardation. Vol. I. Baltimore, MD: University Park Press, 1977. pp. 171-

177.

Siegel, L.S. Home environmental influences on cognitive development in

preterm and full-term children during the first five years, In: Gottfried, A.W.,

ed. Home Environment and Early Cognitive Development. New York:

Academic Press, 1984.

Weikart, D.P. Hard choices in early childhood care and education: A view to

the future. Young Child 44(3):25-30, 1989.

Young, C.L., and Dombrowski, M. Psychosocial influences on research subject

recruitment, enrollment and retention. Soc Work Health Care 14(2):43-57,

1989.

ACKNOWLEDGMENTS

Leila Beckwith, Ph.D., served as co-principal investigator for the study

described; Sarah Simpson, M.A., provided information about the specific

intervention techniques that contributed to subject retention; and Vickie

Kropenske, M.S.N., Susan B. Edelstein, M.S.W., and Mary Beth Sorensen,

M.S.W., supplied clinical consultation about subject recruitment and retention

throughout the research project.

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The projects discussed in this chapter were funded by National Institute on Drug

Abuse grant R0-1-DA4139 and by the U.S. Department of Education,

Handicapped Children’s Early Education Program, grant G008530060.

AUTHOR

Judy Howard, M.D.

Professor of Clinical Pediatrics

Intervention Program

Department of Pediatrics

University of California, Los Angeles School of Medicine

Rehabilitation Center, 23-10

1000 Veteran Avenue

Los Angeles, CA 90024-1797

165
Perinatal Substance Abuse and AIDS:

Subject Selection, Recruitment, and

Retention

Kenneth C. Rich

INTRODUCTION

Perinatal acquired immunodeficiency syndrome (AIDS) is now a major focus of

attention in the field of chemical dependence research. Illicit drugs are being

used in a high proportion of pregnancies (Chasnoff et al. 1990), and the

occurrence of human immunodeficiency virus-l (HIV-l) infection has a close

association with substance abuse (Guinan and Hardy 1987). As many as 4

percent of deliveries have been reported to be from HIV-infected women

delivering at hospitals serving high-risk populations (Nicholas et al. 1989).

However, despite the importance of this problem, knowledge of the

consequences of perinatal substance abuse and HIV infection is inadequate

due, in part to the difficulty in performing studies in a population with major

psychosocial and medical needs. The execution of studies on perinatal AIDS

requires a careful integration of the medical and psychosocial needs of the

study subjects with the scientific design. This chapter discusses some of the

problems of scientific design, particularly subject selection, in association with

issues of recruitment and retention.

PERINATAL HIV INFECTION

The increasing prevalence of HIV infection in chemically dependent women and

the widespread consequences of HIV infection in their infants is forcing the

reassessment of study design in the field of perinatal chemical dependence.

Therefore, it is important to determine the magnitude of the problem of HIV

infection at any potential study site and to understand the impact of HIV

infection on chemically dependent women and their offspring. Although

excluding HIV-infected subjects from perinatal substance abuse studies may be

appropriate now, as the epidemic spreads, the omission of a substantial

minority of potential subjects may result in unacceptable bias of the outcome in

future studies.

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Seroprevalence

Quality information on the background seroprevalence of HIV in infants is

difficult to find. The incidence of AIDS among pediatric patients that is reported

by the Centers for Disease Control (CDC) is biased by an inefficient reporting

system and stringent diagnostic criteria that may underestimate the incidence

by as much as fiftyfold (Nicholas et al. 1989). Some of the best data that are

available are those from the anonymous HIV screening of newborns that is

being conducted by State health departments through funding from CDC. In

this surveillance study, samples are collected from all newborns at the time of

phenylketonuria (PKU) screening and tested by techniques described by Hoff

and colleagues (1988). The data have the advantage of having a useful

denominator that has minimal ascertainment bias. The data are usually

available from State health departments, but whether the hospital providing the

sample can be identified depends on the policies of the individual State health

department.

The seroprevalence of HIV infection among pregnant women has been found to

vary considerably throughout the country. It ranges from 4 percent in highprevalence areas, such as parts of New York City (Nicholas et al. 1989), to 0.8

percent in moderate areas, such as inner-city hospitals in Massachusetts (Hoff

et al. 1988). A majority of cases are associated either directly or indirectly with

substance abuse. There is some suggestion that the overall occurrence of

symptomatic AIDS in high-prevalence areas is now leveling off (Thomas et al.

1990). In other areas where the epidemic is less mature, a continuing increase

in prevalence is being observed. In Chicago, repeated studies of a cohort of

female intravenous drug users from March 1988 through June 1990 showed a

surprisingly high seroconversion rate of 7.67 percent per person-year (Wiebel et

al. 1990). In view of these data, careful consideration must be given on

whether to screen all women and infants who enroll as subjects in studies of

chemical dependence since HIV infection can have direct or indirect effects on

many of the commonly used outcome indicators. Whether screening needs to

be performed in all parts of the country is debatable, but not doing so will

potentially leave a study open to retrospective criticism if the local

seroprevalence increases during the life of the study.

Transmission Rate

Of the infants born to HIV-infected women, approximately 18 to 30 percent

eventually will be found to be infected (Mok et al. 1987; Blanche et al. 1989). It

remains unclear whether infection occurs at the time of delivery or at some point

earlier in the pregnancy. There is evidence that infection can occur as early as

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8 weeks of gestation (Lewis et al. 1990). It is likely that some cases also

become infected intrapartum, although definitive proof is lacking.

The role of the placenta in transmission is poorly understood. It may become

infected or simply may serve as a conduit for transmission of infected

leukocytes (Lewis et al. 1990). Substance abuse also may affect the integrity of

the placenta. Cocaine use is associated with abruptio placentae (Chasnoff et

al. 1985), but it is not known whether this disruption of the placental barrier

increases the risk of transmission.

Other factors also may play a role in determining which infants become

infected. Candidates include intercurrent cytomegalovirus infection or sexually

transmitted diseases or the immune-depressing effect of some substances of

abuse. However, despite considerable interest in a theoretical manner, there

have been remarkably few published data to document the true role of

cofactors, which suggests that the studies are negative or that unexpected

difficulties have been encountered.

Diagnosis of HIV Infection In Infants

The difficulty in identifying HIV infection early in life is based on the fact that

infected infants often have negative HIV cultures and p24-antigen assays

(Nicholas et al. 1989), and the antibodies present in the infant may be of either

maternal or fetal origin. Transplacentally acquired maternal IgG anti-HIV

antibody decays slowly and becomes undetectable in 75 percent of infants by 1

year of age, although infants can lose antibody and still be infected (Mok et al.

1987). Other techniques, such as polymerase chain reaction assay, show

promise in the early identification of infection in infants (Rogers et al. 1989), but

they are not routinely available or have significant technical problems.

Clinical Consequence of HIV lnfection

The overall clinical course of pediatric HIV infection has been reviewed (Falloon

et al. 1989). The median age of presentation of symptoms is 8 months and

median survival is 77 months (Scott et al. 1989). There appear to be two

groups of infected infants: those who become ill and succumb within the first

year of life and those who remain only mildly affected for years. In the longterm survival group, one sees such clinical symptoms as lymphoid interstitial

pneumonitis and, in the short-term group, encephalitis and Pneumocystis carinii

pneumonia (Scott et al. 1989). Severe neurologic disease occurs in 16 percent

of patients and can become the dominant feature of the chronic course.

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It should be remembered that the immunologic and infectious consequences of

pregnancy and substance abuse, irrespective of HIV infection, are essentially

unknown. It has been reported that immunologic abnormalities occur in infants

of HIV-negative mothers (Culver et al. 1987). Rich and colleagues (1989) have

found that there is a correlation between maternal and offspring immune

function in HIV-negative subjects that suggests an influence of the prenatal

maternal environment on the infant immune function, irrespective of HIV

infection. Thus, one might expect an increased number of infections due to a

variety of social and environmental reasons, although definitive proof is lacking.

Another clinical factor that enters into the design of studies is treatment of HIV

infection. Zidovudine now is approved for children, and some of its most

apparent effects are on the neurologic disease. As time goes on, the ethical

demands of patient care will require more patients to be on Food and Drug

Administration-approved drugs or treatment research protocols. It is apparent

that these treatments will have profound effects on subject selection and study

design.

Additional Factors

The actual or intended identification of HIV infection status in subjects of

research studies brings into play a watershed of new problems that are not

seen in many other types of perinatal studies. Some of these are social,

whereas others are realities of the disease process that is occurring

simultaneously in the mother and infant.

HIV Fear and Bias. Fear and bias against HIV-infected patients is extensive. It

is common for HIV-infected women to refuse to tell family members or others,

such as babysitters, of their HIV status or that of their infant. This is based on a

bias perceived by infected women against HIV-infected individuals that might

result in the loss of lodging, social support, or employment. The maintenance of

secrets isolates the patient, interferes with the psychological processing of the

disease, and hampers attempts at improving social supports.

The bias continues through other parts of daily life. For example, enrolling an

HIV-infected child in an enrichment program at a public school, such as a 0-3

program, requires special procedures. It requires special permission and

education of the staff and the parents of other children and may be

accompanied by media coverage. The medical establishment also is not

immune to the fear and bias. In addition to the few well-publicized cases of

physicians refusing to care for infected patients, patients report numerous

instances of small perceived slights that they interpret as the result of the bias.

The author and colleagues at the University of Illinois at Chicago have found

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that patients understand the need for universal precautions and, indeed, are

uncomfortable if a phlebotomist does not wear gloves. However, they also

know that mask, gown, and gloves are not necessary for routine care. As the

staff on a given unit experiences more patients with HIV infection and becomes

better educated, the bias diminishes. However, it is likely that any study that

identifies HIV-infected mothers and infants for the first time will find a previously

unexpected wellspring of staff concern and bias. The amount of time and effort

necessary for the study leadership to deal with the HIV fear and bias should not

be underestimated.

Effect of Medical Status on Study Participation. The mother’s clinical

status helps determine the degree to which she can have her infant participate

in studies. The course of HIV infection tends to be shorter among substanceabusing minority women than in other groups, most likely because of such

factors as diminished access to medical care, poor nutrition, chaotic lifestyle,

and the immunologic consequences of intravenous substance abuse

(Rothenberg et al. 1987). As the mother becomes more ill, medical care

and study participation become more problematic and practical issues of daily

living assume greater importance and become a limiting factor in study

participation. Some of the issues include difficulty in using public transportation,

the need for frequent, intense medical visits and hospitalizations, and the need

for sophisticated in-home medical care. If the mother experiences central

nervous system (CNS) disease, the unique problems of studies in HIV-infected

populations become even more acute. The mother may not be able to

participate in the care of her child due to memory lapse, decreased cognitive

function, or decreased motor ability. The study team also may experience the

tragedy of helping plan for the death of both participants or for the continuing

care of one after the death of the other.

The infant’s clinical state also complicates study participation. As the infant

becomes more ill, frequent medical visits and hospitalizations become

necessary. In studies requiring frequent blood drawing or large amounts of

blood, there is competition between clinically indicated studies and those

indicated for research due to the real limitations of the blood volume of infants.

Furthermore, neurologic and developmental studies may be invalid due to

intercurrent illness. Therefore, the study must have the flexibility to deal with

intercurrent illnesses.

Consequences to Chemical Dependence Programs. HIV infection in the

mother also has implications for chemical dependence programs. Chemical

dependence treatment is complicated by a diagnosis of HIV infection, especially

when newly established. It can be viewed as an intruding factor by staff

170
members who already have a full agenda in handling the dependency needs

As a consequence, the staff may resist performing HIV screening.

SUBJECT SELECTION

The selection of experimental subjects for perinatal AIDS and substance abuse

studies depends not only on the object of the study but also on the limitations

imposed by the biology of HIV infection, the limits of the state of the art of the

diagnosis of infants, and the treatment of HIV infection, For studies intended to

be more than descriptive studies, the selection of controls is critical and must

take into account several factors. However, despite the complexities, the

biology of the infection provides opportunities along with the potential pitfalls.

Staging of HIV Illness

A problem in study design is appropriate controls for the huge spectrum of the

effects of the HIV illness per se. Because of this spectrum, if the focus of the

study is not on HIV infection, the presence of this infection could be considered

a confounding variable and the subjects excluded. If HIV-infected infants are to

be included, it will be necessary to classify the HIV infection on the basis of the

stage of disease since the clinical state may range from virtually asymptomatic

to overwhelming illness.

The stages of HIV infection can be categorized by widely used standardized

classification schemes. For infants, the most commonly used scheme is the

CDC classification of pediatric HIV infection in which patients are classified as

being in the indeterminant (P-O) category-during the first few months of life

when it is unclear whether infection has occurred because of the presence of

passively acquired maternal antibody-or in the infected but asymptomatic

(P-l) or the symptomatic (P-2) category. Within the latter two categories are

subgroups that describe the immunologic function (P-1A or -1B) and clinical

categories (P-2A through E) (Centers for Disease Control 1987a). For women,

the most widely used classification scheme is the CDC system in which

class II patients are asymptomatic, class III have persistent generalized

lymphadenopathy, and class IV have symptomatic disease (Centers for Disease

Control 1987b). For patients who have progressed beyond the asymptomatic

stage, the effects are likely to be so profound that the HIV infection will need to

be handled as an independent variable. The classifications are likely to be

revised and updated in the near future.

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Use of lndeterminant Illness Infants as Controls

Since fewer than one in three infants born of HIV-infected mothers are infected,

the uninfected infants can be used as the controls for the infected. Their use as

controls has an advantage in that the infected infants usually are identified

retrospectively as they become older and, therefore, there is less bias in their

care and management compared to an identified control group. The theoretical

disadvantage of using this control group is the possibility that there may be

some as yet unidentified difference in those who ultimately become infected

compared to those who do not.

HIV-Induced CNS Disease

HIV-induced CNS disease deserves special mention. Many studies of perinatal

substance abuse examine development and cognitive function in the infant as

an endpoint. Studies using the Bayley Scales showed that definitely infected

infants had significantly worse function, particularly in the motor area, than

those who only had passively acquired maternal HIV antibody or than

unexposed controls (Hittleman et al. 1990). A progressive encephalopathy may

develop, with tragic consequences of developmental delays and loss of

previously acquired skills (Belman et al. 1988). The neurologic process can

become a dominant part of the clinical syndrome. The symptoms can be subtle

or progress rapidly to a full-blown state over a period of a few months,

The mother can develop a host of neurologic abnormalities as well. These

range from AIDS dementia complex-with its early loss of memory, apathy, and

changes in motor function and later major intellectual and motor dysfunction-to

peripheral neuropathy and myelopathy and chronic meningitis (reviewed by

Michaels et al. 1988). The mother’s CNS disease may secondarily affect her

ability to care for and nurture the infant, which further compromises the

development of the infant and underscores the need for appropriate controls.

Effect of HIV Treatment

Another confounding factor in HIV infection is the effect of HIV treatment.

Zidovudine, a purine analog with antiretroviral activity, has been remarkably

successful in temporarily slowing the progression of adult HIV infection from

asymptomatic to symptomatic AIDS (Volberding et al. 1990). The effects of

zidovudine are to reduce symptoms of HIV infection, such as fever and weight

loss, to improve T-cell counts, and to reduce the occurrence of secondary

infections. However, the effect is temporary and disease progression eventually

continues.

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Few pediatric patients have been examined in depth. It has been reported that

a major effect of zidovudine is increased verbal and performance IQ in patients

with encephalopathy as well as in some with no overt evidence of

encephalopathy (Piuo et al. 1988). Other effects of antiretroviral treatment

only now are being reported in pediatric patients. In the future, combination

drug regimes are likely to be used. Each of these schemes will have varying

consequences as treatment schemes move toward the ideal. The

consequence to studies of perinatal HIV and substance abuse is to make

treatment effects a major independent variable. Since each drug or

combination is expected to have varying degrees of success, it will not be

legitimate to lump the effect of treatment into a single variable.

Additional Biases In Subject Selection

Obtaining appropriate subjects and controls for studies can be biased by

several factors. Of these, some of the most important are that (1) subjects

frequently give inaccurate information about risk factors for HIV infection; (2) the

referral patterns of HIV-infected patients may be different than those of

noninfected patients; and (3) the intervention of State child protection agencies

may result in an inadvertent bias.

Patients frequently give inaccurate information about risk factors during the

initial encounter with the investigative team. As a result, if patients are

screened for HIV serostatus only on the basis of admitted risk factors alone,

many will be missed. The experience of the author and colleagues is that even

with trained, sensitive female interviewers, many potential subjects deny the

presence of any risk factors on first contact, even if they are not being asked to

specify which risk factors they have. However, after the patients have become

more comfortable with the study personnel, all readily participate in long,

detailed interviews about risk factors, which frequently contradict the results of

the original screening. Therefore, laboratory screening of only those patients

who admit to having a risk factor is inadequate.

Another source of bias comes from two factors: There are many more

chemically dependent women than HIV-infected women, and the source of HIVinfected and uninfected women may be different. A prescreening mechanism

that keeps the number in balance and reduces the potential bias may be

needed. One possible mechanism would be to base the entry of uninfected

women on the recruitment of an infected one. All women at risk in a population

would be listed consecutively as they come to the attention of the study. After

identification of an infected woman, only the next predetermined number of

uninfected controls on the list would be asked to participate in the study. This

mechanism helps keep the time of enrollment of the infected women and their

173
controls similar so that unintended “creep” in the diagnosis or management of

the groups does not occur.

SUBJECT RECRUITMENT

Since the potential subjects for these studies are a disenfranchised group who

often are hidden from the medical system, the study design must recruit from

the points at which patients are likely to surface. At these locations, special

efforts will be needed to identify appropriate subjects rapidly and efficiently. In

addition, the recruitment strategy will need to be tailored to the type of subject

and the frequency of the occurrence of the condition that is the object of the

study. For example, a study interested in young infants of HIV-infected women

will need to cast a wide, shallow net due to the low number of women who are

both infected and pregnant or newly delivered. A study interested in HIVinfected nonpregnant women and their offspring of any age can afford to work

more intensely with a few sources.

Possible Sources of Subjects

One of the most fruitful sources of subjects for perinatal AIDS studies is

obstetric prenatal clinics and delivery rooms. Although many women in the

target population elect not to receive prenatal care, strong consideration should

be given to establishing a routine voluntary screening system for those

pregnant women who want to receive prenatal care. A program could be

justified in medium- to high-seroprevalence areas on the basis of good clinical

care alone because of the high risk to the infant of the disease. Prenatal

screening is routine for such disorders as PKU that have a miniscule prevalence

in comparison with HIV infection. For those women who do not receive prenatal

care, a system for rapid screening for HIV antibodies could be established. As

in any diagnostic procedure for HIV infection, informed consent needs to be

obtained with pretest and posttest counseling. Since locating patients for giving

results and conducting posttest counseling is labor-intensive and inefficient,

immediate feedback of the results is useful.

Another potential source of patients is drug treatment programs. Again, in

medium- to high-seroprevalence areas, the prevalence in a chemical

dependence program may be sufficiently high to warrant screening on the basis

of sound medical practice as well as research potential. Resistance may be

encountered among staff and patients if screening is not currently a routine part

of care. However, identification of HIV disease has treatment potential,

particularly at the conclusion of the pregnancy, and the pregnancy may be the

only “handle” that is effective in bringing the women into the medical system.

174
Another potential source of referrals is the State child protection agency.

Although several ethical dilemmas can be encountered in this source of

patients, our experience has been that the agency is eager to develop a

working relationship with potential sources of quality medical and psychosocial

care for HIV-infected infants.

At the University of Illinois, investigators also have found a fruitful network of

recruitment possibilities among those who work in the numerous small social

agencies that abound in large metropolitan areas. Networking at the level of

the social worker or nurse may be more successful than at the physician level.

Some of the practical concerns of recruitment and retention of a similar program

have been described (Young and Dombrowski 1989).

Problems and Pitfalls In Subject Recruitment

In addition to the problems of identifying a source of subjects, a number of other

problems are likely to be encountered in enrolling subjects. One of these is the

lack of efficacy in identifying women on the basis of admitted risk factors. An

anonymous seroprevalence survey at the University of Illinois found, that 1.1

percent of women delivering were HIV-infected. When simultaneous

confidential (nonanonymous) screening was done using the same sample, the

seroprevalence among those who agreed to testing was only 0.6 percent.

Fewer than half admitted to having risk factors usually associated with HIV

infection (Wenstrom and Zuidema 1989). This suggests an active refusal

process among those who knew or suspected they were infected. We have

since found that, as expected, the refusal rate depends greatly on the technique

of the person seeking permission, At the University of Illinois, approximately

one-third of women accept screening if asked as part of the routine prenatal

clinical process. However, if a member of the study team seeks approval, the

acceptance rate increases to approximately three-quarters. Obviously, care

must be taken to ensure that the consent is without coercion and that options

are presented.

Ethical Dilemmas In Subject Recruitment

Several ethical dilemmas come up in the recruitment of women and their infants

into studies of HIV infection and substance abuse. Some are universal to all

perinatal substance abuse programs, whereas others are unique to HIV

seropositive women and infants.

One of the dilemmas is the concern for confidentiality. In view of the adverse

social and economic consequences of unauthorized knowledge of HIV status,

the dissemination of information on patient HIV status is held to a higher

175
standard of confidentiality than most other medical information and,

consequently, should not be released without legal authorization. On the other

hand, knowledge of HIV status is a key piece of medical information and does

need to be known by caregivers. Furthermore, notification of sexual partners

is required by some States and some intramural Federal programs, and

notification of the local health department usually is required. These

requirements can complicate the sense of trust between the investigative team

and the patient. In our experience, these conflicting needs are accepted if

patients are notified at the time that informed consent is obtained for the study.

Another ethical dilemma is the payment of subjects in money or in services,

Participation can become a financial burden. Payment of large sums may be a

form of coercion of the infant under the theory that the mother may not be an

advocate for the welfare of her infant. However, some reimbursement for costs

encountered seem reasonable. The question also has been raised about the

ethics of providing higher quality services to patients in return for study

participation than is customary for the community. This also could be

considered a form of coercion although the solution of making the services of

similar high quality for all patients in the population is generally not under the

control of the study team.

Ethical conflicts also arise because of the need for involvement of State child

protection agencies. As in any perinatal chemical dependence study, subjects

must be monitored for abuse and neglect. This can confuse the role of the

scientific observer with the role of the caretaker and must be discussed with a

potential study subject in a forthright manner. Paradoxically, in Chicago more

services are available for HIV-seropositive infants under the protection of the

State than the “routine” cases that are not infected. A close working

relationship with the agency may allow careful monitoring of borderline cases of

child neglect and abuse and the building in of services that may keep the family

intact.

Finally, there is a dilemma in the decision to approach a patient for enrollment in

one of several competing studies. There is no dilemma if study objectives do

not overlap and one does not affect the outcome of the other and does not

require excess testing. However, in the study of HIV infection, treatment

protocols do provide a dilemma. For example, should an experimental HIV

treatment protocol in which some amelioration of symptoms can be expected

take precedence over an epidemiologic study in which treatment is a major

confounding variable? At this time, we submit that the opportunity for “pure”

epidemiologic studies untrammeled by the effects of treatment is past.

Therefore, an epidemiologic study will require careful crafting and attention to

sample size and statistical power to take into account the effects of treatment.

176
In addition to the design problems, the study also must take into account the

need for laboratory samples that may exceed the safe amount of blood that can

be drawn.

RETENTION OF HIV-INFECTED SUBJECTS

Special efforts often need to be made to retain appropriate subjects for studies.

The target population is distinguished in being a hidden, disenfranchised group

with few of the usual social supports and access to medical care. They tend to

come to the attention of the medical system for crises and then disappear until

the next crisis. They are highly mobile, and locating them for continued care

may be a challenge. Therefore, retaining subjects for longitudinal studies must

take into account the labor-intensive challenge and problems of continuing

followup and appropriately plan and budget for it.

As in any program targeted to this group, the definition of retention must be

flexible. Patients may not keep appointments but will nearly always maintain

contact with the study team and will return, even if not at the time originally

expected. Given this flexibility, we have found that more than 85 percent of

patients can be retained over a 1-year period for epidemiologic studies and an

even higher proportion can be retained for other types of studies such as

treatment protocols.

A key to retention is the provision of services to the subject that gives them

something in return for the effort that it takes to participate in the study. The

system of care can be thought of as a “seamless” system that provides medical

and social care while collecting the data necessary for the study.

Provision of Services: Medical

Many mothers fail to obtain care for themselves, but with encouragement they

will do so for their infants. Therefore, providing well-rounded pediatric care

(acute as well as preventive) has value. The care can be provided by qualified

nursing personnel or by physicians. It further has the advantage that the study

protocols can be incorporated into an integrated system of care and service.

This allows the objective collection of longitudinal data from reliable sources,

Furthermore, it cuts down on the burden of multiple visits and increases

efficiency of patient tracking. Disadvantages of this system are that it is

expensive and may complicate the blinding of observers if blinding is necessary

to achieve the study objectives.

Care for the mother also can be provided as part of the system. The mother’s

care is often sporadic and triggered by acute illness. If objective longitudinal

177
data are needed on the mother’s health, consolidating care to one location is

essential due to the unreliability of retrospective data collection from a variety of

nonstandardized sources. A particularly well-accepted format is the provision of

care for the mother and infant by a physician qualified in internal medicine and

pediatrics. It is efficient and reduces the number of visits necessary.

Specialized HIV-related care also can be included in the program. In the past,

much of the care of HIV-infected pediatric patients has been provided by

specialists. The expected clinical course now is becoming sufficiently well

understood that, throughout much of the course, day-to-day direct care by a

specialist is not necessary. HIV treatment, especially with zidovudine, is

becoming generally accepted and can be managed by an internist or

pediatrician. As the mother or infant becomes more ill, greater input will be

needed on the part of specialists, and it will become more complex to dovetail

study and patient needs. It is also important to provide access to treatment

research protocols should the patient desire them. In our system, the care by

specialists and the access to treatment protocols are included in the package.

Provision of Services: Psychosocial

The provision of psychosocial services is another incentive for continuing

participation. Several services can be provided that demonstrate the value of

the study to the patient in a manner useful to the patient. These services are

expensive but have high value in patient retention, ranging from concrete

services to coordination with drug treatment programs to provision of counseling

and group therapy.

Concrete services include intercession by the study personnel to obtain

services that patients are eligible to receive but are having difficulty in obtaining.

For example, transportation assistance is often necessary but is difficult to

obtain. This was found to be a major problem in Chicago because of the wide

catchment area from which patients are drawn and because many subjects do

not own cars. Transportation can be provided by the study in the form of

taxicab vouchers or subway/bus tokens. Another useful aid to the patient is

acting as a spokesperson with the public aid system, a bureaucracy that is often

overwhelmingly complex for the unsophisticated patient. Another essential

service is coordination of complex medical and psychosocial care. This

coordination of services may require multiagency team meetings, coordination

of skilled in-home medical services, child protection agency services, and so on.

Individual and group therapy also assists in retaining patients. Since HIV

infection has multifaceted consequences, numerous preexistent psychological

problems become exaggerated and new ones appear. It has been observed

178
that substance abuse may increase transiently after the diagnosis. There is

also a high risk of attempted suicide around the time the infection is diagnosed;

therefore, access to treatment services within the context of the study is a key

retention technique.

Access to chemical dependence programs is also important. Access may be

limited, particularly for pregnant women. Once enrolled in a program,

considerable effort must be expended to ensure that the goals of the study and

the chemical dependence program are complementary.

SUMMARY

Studies that involve subjects who are HIV infected as well as chemically

dependent present special challenges to the study team. HIV infection is now

so common in many parts of the country and infection can potentially influence

so many commonly used endpoints for perinatal chemical dependence studies

that HIV must be considered in these studies. Some of the factors that need to

be taken into account in the design of studies include the staging of HIV illness,

the consequences of HIV-induced CNS disease, the effects of HIV treatment,

and the biases in subject selection that arise due to inaccurate information

about risk factors and imbalance in sources of subjects and controls. In

addition, the study team needs to remember the community and staff fear and

bias that are often encountered in the care of HIV-infected patients. Fruitful

sources of subjects for perinatal studies include prenatal clinics and delivery

rooms, chemical dependence programs, and the network of community social

agencies. Retention of this challenging group is strongly aided by the

establishment of a seamless system of services that includes all aspects of

general medical care, HIV specialty care, access to treatment protocols, and

psychosocial care.

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ACKNOWLEDGMENTS

The work described in this chapter is supported in part by National Institute on

Drug Abuse grant DA-03651 and by National Institute of Allergy and Infectious

Diseases and National Institute of Child Health and Human Development grant

Al-82505.

AUTHOR

Kenneth C. Rich, M.D.

Associate Professor

Department of Pediatrics, Mail Code 856

University of Illinois at Chicago

Clinical Sciences Building, Room 1240

840 South Wood Street

Chicago, IL 60612

182
Discussion: Subject Selection,

Recruitment, and Retention in

Longitudinal Studies Involving

Perinatal Substance Abuse and Human

lmmunodeficiency Virus Infection

Emmalee S. Bandstra

The acute and long-term effects of in utero alcohol and other drug exposure

have been a subject of intense investigative interest for at least three decades.

However, the epidemics of so-called “cocaine babies” and “AIDS babies” have

necessarily turned the eyes of the country (government officials, health care

professionals, educators, and the lay public) on perinatal drug research. They

want to know the number of affected infants and answers to probing questions

regarding projected outcome. Scientific scrutiny and appreciation of the

complexity of the issues are lacking. Cocaine may be the current target in the

“war on drugs,” but the underlying issues relevant to conducting longitudinal

followup studies are similar to those faced in past studies involving other

substances such as alcohol and marijuana. However, difficulties in selecting,

recruiting, and retaining subjects for current studies of perinatal substance

abuse are exacerbated by the illegal nature of cocaine use and its related

lifestyle of criminal activity, violence, and sexual abuse and by health care

issues concerning human immunodeficiency virus (HIV) infection and other

sexually transmitted diseases. Furthermore, efforts at constructing careful

study designs and maintaining control of identified cohorts of study participants

can be thwarted or enhanced by the evolving community “support” systems

(Bandstra 1990). This monograph wrestles with the intricacies of prospectively

planning quality longitudinal research that will yield meaningful data. Much is to

be learned from the distinguished investigators who share their formulae for

successful subject selection, recruitment, and retention in four other chapters of

this monograph (Streissguth and Giunta; Fried; Rich; Howard).

Embarking on longitudinal research into perinatal substance abuse requires

gathering the resources to select, recruit, and retain subjects. The studies

usually involve interfacing numerous collaborators within an interdisciplinary

183
team who must learn to overcome barriers to recruitment, guarantee

confidentiality, secure informed consent, obtain objective and blinded

observations, provide necessary services to drug-exposed and control infants

and their families, and retain cohorts over considerable time.

The issue of subject selection is more complex than it may at first appear.

Which subjects to select depends on the scientific question to be addressed.

Selection also is limited by the practical matter of whether appropriate subjects

using the drug or drugs in question are available in the investigative team’s

community. One of the first questions posed by reviewers of research

proposals is the feasibility of recruiting a sufficient number of subjects over the

specified enrollment period to address the research hypotheses adequately.

It behooves each investigative team to explore thoroughly the patterns of

substance abuse within the proposed recruitment catchment area before

initiating costly and cumbersome prospective longitudinal followup studies.

Shifts in drugs of choice within a community can wreak havoc on a tightly

designed study attempting to recruit subjects over time. With careful

monitoring, astute investigators can anticipate shifts and launch pilot studies to

assess the impact of newly introduced substances. In South Florida, the Dade

County Medical Examiner’s Office, the Metro-Dade Police Department, the

Jackson Memorial Hospital Emergency and Trauma Units, and private and

public drug rehabilitation centers have assisted University of Miami investigators

in tracking community trends in drug usage.

Decisions regarding subject selection necessarily involve criteria for subject

exclusion. The other chapters in this monograph acknowledge that

polysubstance abuse confounds nearly every study. For example, the use

of caffeine, tobacco, alcohol, and marijuana is nearly impossible to eradicate

from a cocaine-using study population. However, it may be possible in a

single-site study of perinatal drug abuse to exclude exposure to opiates,

methadone, amphetamines, phencyclidine (PCP), and sedatives/hypnotics

without significantly jeopardizing the number of eligible subjects. In other

words, the investigation probably can successfully recruit adequate numbers

of subjects who have used cocaine in combination with the so-called “gateway”

drugs. However, the permutations on the varying combinations of drug type,

dose. and duration are still numerous.

Time of recruitment significantly affects study design. Prenatal studies as

previously conducted in Seattle and Ottawa are more difficult to implement with

cocaine-abusing women (Streissguth and Giunta, this volume; Fried, this

volume). Prenatal care may introduce bias since drug-using women who do

seek and comply with prenatal care demands may have better outcomes than

those who fail to do so. Recruitment at delivery is fraught with obvious

184
difficulties, including maternal fear of legal retribution, mistrust of confidentiality

pledges by the investigative team, and physical and psychologic discomfort

associated with labor and delivery. These difficulties notwithstanding, the

delivery hospitalization may be the only window of opportunity for recruitment

and evaluation of adverse perinatal outcome of in utero drug exposure.

Correct identification of race/ethnicity is essential to defining the population

under investigation. Cosmopolitan centers must cope with considerable cultural

diversity, which may complicate the scientific aspects of the study as well as the

efforts to recruit and retain subjects. It may be necessary to provide ethnically

sensitive professional staff fluent in English, Spanish, and French (or Creole),

unless the investigation specifically excludes certain groups or mandates that

the study participants be fluent in English. Assigning race/ethnicity is not

always an easy task. A classification scheme limited to “black,” “white,”

“Hispanic,” “Oriental,” and “other” is inadequate to describe the racial/ethnic

diversity (e.g., Caribbean-born black individuals) in certain study populations.

Infants resulting from biracial unions generally are assigned the same race/

ethnicity as the mother. Specifically questioning the mother regarding selfidentified race/ethnicity, country of birth, and primary and secondary languages

(of both parents) significantly enhances the ability to recruit the desired target

population and to determine the generalizability of the outcomes noted.

Fried (this volume) notes analytical difficulties associated with inclusion of

multiple births and subsequent births from the same mother. He appropriately

suggests that only singleton births be reported or that only one randomly

selected member of a twinship be included in the analysis, Multiple births

exceeding twins are so rare that they probably should be excluded at the

outset. Investigators choosing to include only one twin in the analysis should

nonetheless perform all studies on both twins to allow random selection of one

twin for data analysis, to foster maternal-infant bonding to the twinship, and to

enhance compliance with the appointment schedule. Subsequent pregnancies

are also problematic. Even if subsequent drug-exposed siblings are not

enrolled, the research team often must cope with the additional needs of older

and younger siblings to retain successfully the original cohort. The number of

siblings may be quite large over the course of a longitudinal study. At the

University of Miami/Jackson Memorial Hospital, a preliminary tracking survey

was conducted of 240 cocaine-using women who delivered during the 6-month

period January through June 1989. The mean maternal age was 26 years, and

the mean parity was 4. By June 1990, 44 of the 240 women had a repeat

pregnancy. Twenty-nine of the women had delivered live-born infants, of whom

14 were documented at delivery to be cocaine exposed.

Fried also cautions against excluding infants with adverse outcomes such as

intrauterine growth retardation or prematurity from longitudinal perinatal drug

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studies. In large study populations, controlling statistically for the independent

contributions of birth weight and gestational age is feasible. However, in

smaller study populations a disproportionately high number in the drug-exposed

group of small for gestational age or preterm infants, some of whom may have

suffered severe neurodevelopmental handicaps due to central nervous system

hemorrhage or ischemia, may produce uninterpretable results. An alternative or

complementary approach might be to focus separately on the outcome of in

utero drug exposure within specified birth weight and gestational age categories

while matching or controlling statistically for confounding variables contributing

to intrauterine growth retardation or prematurity.

Preterm infants, especially very-low-birth-weight infants, deserve special

attention in future research programs. Few institutions have sufficient numbers

of very-low-birth-weight, preterm, cocaine-exposed infants to conduct

meaningful large-scale longitudinal followup. The University of Miami and the

other participating centers of the National Institute of Child Health and Human

Development Collaborative Neonatal Research Network are planning a

multicenter study to assess the outcome of very-low-birth-weight, preterm,

cocaine-exposed infants. A multicenter study would allow enrollment of larger

numbers of subjects in a shorter time span than a single-site investigation. The

individual sites would benefit from a well-planned cohesive study protocol

drawing on the expertise of internationally known consultants; a centralized

database; a consulting biostatistical center to facilitate quality control, data

entry, and analyses; and referral laboratories for performing assays unavailable

onsite at the participating centers. The funding institute(s) would benefit from

the enhanced generalizability of the results due to the ability to examine

intersite variations in outcome.

The chapters by Streissguth and Giunta, Fried, Rich, and Howard proffer vastly

different philosophies regarding subject selection, recruitment, and retention.

Each style has worked well in its own setting and in its own era.

The Seattle studies over the past 17 years (Streissguth and Giunta, this

volume) have emphasized volunteer recruitment utilizing a screening

questionnaire followed by an intensive interview. Positive-sounding project

titles have fostered a nonjudgmental approach. By study design, no specific

developmental feedback or interventions have been given. Streissguth and

Giunta emphasize the need for monetary inducement in the current population

of cocaine-using women in contrast to previous study populations. Participants

in the ongoing cocaine study are paid well ($50 per visit) for their involvement

and are given transportation and extensive social service support. Although

this model might be termed a “nonintervention” model, participation probably

has some therapeutic value for study and control families. It should be

186
remembered that subjects soon discover the local rates for research

participation in various studies and within a study. Even-handed distribution of

inducements and services is vital to retaining subjects and especially controls,

In the oral presentation of her chapter, Streissguth also mentioned “E” for

evangelism. An investigative team without at least an altruistic atmosphere

probably is doomed to failure. Substance-abusing women are unlikely to

comply unless study demands are complemented with convincing, heartfelt

sensitivity.

The Ottawa Perinatal Prospective Study (Fried, this volume) also used a selfinitiated volunteer recruitment, but significant feedback was given as an

incentive for remaining in the study. Disclosure regarding the findings on the

individual child was coupled with explanations of the findings of the overall

study at group parties and in an annual letter. Fried indicates that incentive

monies, small gifts, and a bonus for complete participation also were given.

The Los Angeles-based studies (Howard, this volume), recruited from a referral

base of social service agencies and the Child Protection Team, hava

extensively used the support of the community agencies to facilitate compliance

and have exhaustively provided concrete resources, but not money, to the

participating families of substance-exposed infants. Howard asserts that the

program relies heavily on the “clout” of legal authorities to maintain contact with

the families. She notes the increased complexity of studying substanceexposed infants within their extended families. Multiple caregivers, shifts in

family dynamics, and psychiatric problems of the substance-abusing parents

and other family members pose considerable study design difficulties.

Furthermore, foster families add a new dimension to perinatal substance abuse

research. Family case management is successful when caseloads are small

and manageable and when well-trained staff know how to access community

resources. Separate clinical and research staffs are maintained to guarantee

“blinded” observations by the research staff.

In today’s era of cocaine-using women, it is evident that social service providers

are so overwhelmed that scientific investigators routinely confront numerous

unmet needs in terms of food, shelter, transportation, clothing, health care, daycare for the infant and siblings, drug rehabilitation, vocational rehabilitation, and

legal aid-all of which interfere with a family’s ability to comply with research

expectations.

Networking with other professionals within the institution, community, State, and

Nation is essential to successful research and service endeavors in the field of

perinatal substance abuse. The most formidable barriers to longitudinal

research are imposed by philosophical differences and “turf protection” among

187
professionals and agencies. Even the nomenclature symbolizes the problem.

Drug-using pregnant and postpartum women are referred to as “patients” by

health care professionals, “clients” by social service providers and drug

rehabilitation specialists, and “subjects” by scientific investigators.

Unfortunately, health care professionals often fail to acknowledge social and

substance abuse problems of their patients, whereas drug rehabilitation

specialists often avoid health care issues in their clients. Investigators

conducting longitudinal research on perinatal substance abuse and HIV

infection must address the “patient” and “client” needs of their “subjects” if the

scientific objectives are to be met.

How to interface with State and local agencies without breaching confidentiality

regarding substance abuse issues is extremely problematic. Obtaining a

Department of Health and Human Services Certificate of Confidentiality may

alleviate some, but not all, of the legal concerns surrounding these issues.

When a scientific study also identifies HIV-infected women and children, the

confidentiality issues escalate further. The Chicago experience (Rich, this

volume) with recruiting and following HIV-infected mothers and their offspring

emphasizes how intricately interwoven are the issues relevant to perinatal

substance abuse and HIV infection.

In planning any prospective study of perinatal substance abuse, HIV screening

is an essential element. The relationship of substance abuse, especially

nonintravenous cocaine abuse, to HIV infection in women of childbearing age is

an important consideration in its own right. However, even if epidemiology is

not a specific objective, conclusions regarding neonatal and infant outcomes of

perinatal drug exposure cannot be interpreted fully without assessing HIV status

concomitantly. Difficulties exist with ascertaining the ultimate HIV status of the

neonate due to interference from transplacentally acquired maternal antibodies.

The need for prospective assignment of infants to study and control groups in

controlled studies of in utero exposure often necessitates excluding infants of

HIV-infected mothers from participating.

HIV seropositivity and HIV infection in drug-abusing mothers significantly

complicates the assessment of pregnancy outcome and long-term followup of

the mother/infant dyad. The long-term neurologic sequelae of HIV infection in

infants is under intense scrutiny in numerous institutions. A research question

not yet explored is whether in utero drug exposure exacerbates the adverse

neurologic consequences of HIV infection in young children. Children with HIV

infection generally develop normally in the first months of life but either fail to

progress or experience developmental regression thereafter (Epstein et al.

1985, 1986). Problems with perceptual motor function, expressive speech,

hyperreflexia, increased tone, spasticity, bilateral pyramidal tract signs,

paraparesis, spastic-ataxic gait, seizures, acquired microcephaly, and

188
neuropathologic findings, including diffuse calcification of the cerebrum,

cerebellum, and pons; reduced brain volume; ventriculomegaly; and vacuolar

degeneration of the spinal cord have been described in the literature. Newer

antiviral agents, used either prophylactically or when symptoms of HIVassociated encephalopathy are apparent, may offer hope but introduce an

unavoidable bias in followup studies.

One of the more successful mechanisms to retain subjects for longitudinal

research in perinatal substance abuse and/or perinatal HIV exposure is to

provide opportunities for combined maternal and infant health care visits. Rich

(this volume) points out the advantages to HIV-infected mothers and their

infants of such a concrete service by a family medicine specialist or general

practitioner trained in obstetrical and pediatric care.

At the University of Miami/Jackson Memorial Medical Center, Drs. Gwendolyn

Scott, Celia Hutto, and Mary Jo O’Sullivan are conducting longitudinal studies

on perinatal HIV infection using a combined Special Immunology Clinic

attended by pediatricians and obstetricians. The mother’s routine postpartum

and interconceptional gynecologic examinations and study-mandated clinic

visits are scheduled to coincide with the infant’s comprehensive pediatric health

care and developmental assessments. Dr. Gene Burkett and I also have found

the format of a combined mother and infant clinic attended by an obstetrician

and a pediatrician extremely beneficial in fostering compliance with scheduled

visits within a followup program dealing with postpartum substance-abusing

women and their offspring.

Successful teams are usually multidisciplinary and include physicians,

psychologists, nurses, social workers, case managers, and related

professionals to render diagnostic and interventional services as dictated by the

study protocol. There is no substitute for personal contact by the scientific

investigators in the patient process.

The most stressful component in any longitudinal research program is subject

retention. The value of case managers who are known by the mother and/or

alternate caregiver and who maintain regular and intensive telephone and home

visitation contacts with the family cannot be overemphasized. The brunt of the

responsibility for subject retention is felt by the case managers, who often are

undercompensated due to lesser educational achievements, although they may

have “life experience” credentials far superior to other professional team

members. The University of Miami has relied heavily on an intense medical

center-based case management system for tracking and coordinating social

and health care services, but the investigators have found it optimal tc limit

caseloads to approximately 35 per case manager. Attention to the morale and

189
esteem of individual team members, especially those who operate

independently during outreach visits, is vital. Adequate salary increases,

appropriately timed promotions, incentive pay, comfortable workspace,

congenial team interactions, and frequent investigator-led organizational

meetings facilitate retention of staff members and study participants.

One approach to improvement of staff morale is seeking assistance from

experts on stress management and group dynamics. At the University of

Miami, the number of investigators and support staff dealing with various

aspects of perinatal addiction is growing exponentially. Researchers studying

perinatal HIV infection at the university are undergoing a similar growth

phenomenon and have begun to take advantage of stress management

techniques offered by seminars and individual counseling when appropriate.

The resources for the acquired immunodeficiency syndrome programs have

been provided through a National Institute of Mental Health grant to the

Department of Psychiatry. Similar programs dedicated to professionals in

perinatal substance abuse research would significantly enhance an institution’s

ability to conduct productive longitudinal investigations without costly personnel

turnover or unproductive phases of depression or burnout among key

personnel.

Prospective longitudinal studies as described in this volume necessitate

gathering extensive tracking information at the outset. Streissguth and Giunta

suggest planning to track for 10 years or more even if funding is not available

currently. Successful tracking may include frequent family contacts, newsletters

and holiday greeting cards with “address correction requested,” and such

personal touches as handwritten envelopes and attractive postage stamps.

Prospective and ongoing efforts are absolutely critical to successful subject

retention.

This section of the monograph deals with subject selection, recruitment, and

retention in labor-intensive prospective longitudinal studies. Today’s computerdriven society offers innovative opportunities for tracking research subjects.

One method of tracking long-term outcome of birth cohorts is to link hospital

records with later school records using identifiers common to both sets of

records (e.g., child’s name, gender, and birth date and mother’s name and birth

date). The methodology, known as database linkage, has been used in health

and consumer research (Scott et al., in press). There are two main classes of

database linkage research designs, historical prospective and historical

retrospective. In a historical prospective study conducted at the University of

Miami, infants within three birth weight groups 1,500, 1,501-2,500, and

>2,500 grams) were identified from Jackson Memorial Hospital birth records for

1975-76 (Carran et al. 1989). Using a relational database, the birth records

190
were linked to computerized school records during 1986. Successful tracking of

70 percent was obtained in this inner-city research population. In a historical

retrospective study, Shaw (1989) has studied all children receiving special

education services during 1988 in 52 Dade County inner-city schools and has

compared them to two groups of normal-achieving classmates born during the

same month In 1978.

Prospective studies also can be facilitated by sophisticated database

networking such as the Dade County Birth Registry (figure 1). The registry is a

computer-based case management system for all high-risk and handicapped

children up to 5 years of age who receive services from any agency in Dade

County. The registry data also can be linked to hospital and school records,

Similar registries will be mandated in 1992 by Public Law 99-457. The

implications for tracking many identified drug-exposed infants through school

age are obvious. Of course, careful strategies for maintaining confidentiality

must be implemented.

Funding agencies can facilitate prospective longitudinal research studies by

allowing simultaneous enrollment of subjects in service demonstration projects.

Such a mutually supportive endeavor would enhance subject retention in

research investigations while improving the objective assessment of service

delivery.

CONCLUSION

Subject selection and retention are two of the most challenging aspects in

longitudinal studies involving perinatal substance abuse and HIV infection.

Today’s researcher in perinatal substance abuse must be well versed in basic

sciences, medicine (including pediatrics, obstetrics and gynecology, and

psychiatry), psychology, social services, public health policy, and legal issues.

The topics of perinatal substance abuse and HIV infection have given new

dimensions to the concept of “networking,” which no longer means simply

establishing a “referral” system for “patients,” ”clients,” or “subjects” (depending

on one’s perspective), but now means attempting to break down the turfprotection barriers that cause agency gridlock and impede successful study

implementation and service delivery. Networking also means implementing

“user-friendly,” but “access-limited” database linkages to ensure confidentiality.

With careful prospective study designs, nonjudgmental approaches to subjects

and their families, adequate monetary and social service incentives, and the

use of sophisticated computerized databases for tracking subjects, clinical

studies in perinatal substance abuse and HIV infection should yield meaningful

long-term followup data well into the 21 st century.

191
FIGURE 1. The Florida Handicapped and At Risk Demonstration Project links

all providers with a distributed computer network that supports (1)

case management with an agency or between agencies, (2) a

registry of all children who are screened or referred for special

preschool services, and (3) tracking of all services received from

birth through high school. Personal computers (PCs) are used at

individual sites using the disk operating system (DOS). DOS will

operate under UNIX, which is functional at multiuser sites.

192
REFERENCES

Bandstra, E.S. Medical issues for mothers and infants arising from perinatal

use of cocaine. In: Drug Exposed Infants and Their Families: Coordinating

Responses of the Legal, Medical and Child Protection System. American

Bar Association Center on Children and the Law Monograph. ISBN

No. 0-89707-550-1. Washington, DC: American Bar Association, 1990.

Carran, D.T.; Scott, K.G.; Shaw, K.; and Beydoun, S. The relative risk of

educational handicaps in two birth cohorts of normal and low birthweight

disadvantaged children. Top Early Childhood Special Educ 9(1):14-31,

1989.

Epstein, L.G.; Sharer, L.R.; Joshi, V.V.; Fojas, M.M.; Koenigsberger, M.R.; and

Oleske, J.M. Progressive encephalopathy in children with acquired immune

deficiency syndrome. Ann Neural 17:488-496, 1985.

Epstein, L.G.; Sharer, L.R.; Oleske, J.M.; Connor, E.M.; Goudsmit, J.; Bagdon,

L.; Robert-Guroff, M.; and Koenigsberger, M.R. Neurologic manifestations of

human immunodeficiency virus infection in children. Pediatrics 78:678-687,

1986.

Scott, K.G.; Shaw, K.H.; and Urbano, J.C. Developmental epidemiology. in:

Friedman, S.L., and Haywood, H.C., eds. Developmental Follow-Up,

Concepts, Genres, Domains and Methods. New York: Academic Press, in

press.

Shaw, K. “The Contribution of Low Birth Weight and Other Medical

Complications to Educational Handicaps.” Unpublished doctoral dissertation,

University of Miami, 1989.

ACKNOWLEDGMENTS

The work described in this chapter was supported in part by National Institute

on Drug Abuse grant DA-06556-01 and project BRH-P01010-02, Bureau of

Maternal and Child Health and Resources Development (Section 301, Public

Health Service Act), Health Resources and Services Administration,

Department of Health and Human Services.

AUTHOR

Emmalee S. Bandstra, M.D.

Associate Professor of Pediatrics and Obstetrics and Gynecology

Department of Pediatrics (R-131)

Division of Neonatology

University of Miami School of Medicine

P.O. Box 016960

Miami, FL 33202

193
Measures of Pregnant, Drug-Abusing

Women for Treatment Research

Anne M. Selden

INTRODUCTION: MAGNITUDE OF THE PROBLEM AND SOME CAUTIONS

Increasing numbers of pregnant, drug-abusing women are reported today, a

problem some people call an epidemic. To compound the problem, there are

severe shortages of treatment programs for pregnant, drug-abusing women,

with the general shortage of treatment slots exacerbated by the fact that some

drug abuse treatment programs specifically exclude pregnant clients (Cole

1990). Wisely or not, program directors may fear that they lack the expertise

or resources to address the special obstetric and psychological needs of this

population, or they may fear liability for the child if treatment fails with the

mother or fails to avert damage to the child.

There are no accurate epidemiologic data to indicate if the numbers of

pregnant, drug-abusing women are increasing or if the apparent upswing is

caused by increased reporting and awareness of the problem; obtaining such

data is a clear research need.

Several known trends indicate that at least part of the increase is real:

High school surveys show that although the casual or experimental use of

some drugs may be dropping, the frequent use associated with or predictive

of addiction appears to be increasing (Adams et al. 1989).

Licit and illicit drugs of abuse are used in all social classes, and women

who as a group were previously thought to use less are increasing their use

of several substances to the levels previously seen only in men. For at least

some substances, such as tobacco, women are showing greater difficulty

in quitting than men, even when they want to (Office of the Surgeon General

1988). These trends may be related to the observation that depression is

associated with use of substances and with difficulties in quitting (Covey et

al. 1990) and that diagnosable depression is more prevalent in women than

men (Weissman and Myers 1978).

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As smaller families and planned pregnancies become the norm among those

who have their lives well organized, it is entirely possible that unplanned

pregnancies will be increasingly concentrated in the drug-using segments of

the population. Therefore, the incidence of drug-exposed pregnancies could

continue to rise even if some parameters of drug use decline.

There are four major public health rationales for emphasizing treatment of

substance abuse or dependence during pregnancy even more than at other

times: (1) the hope of decreasing damage to the developing fetus by arresting

or diminishing drug use during the remainder of a pregnancy; (2) the hope of

enhancing childrearing by providing the newborn with at least one drug-free

parent; (3) the opportunity for case finding based on the fact that many

pregnant, drug-abusing women seek prenatal care and, thus, come to the

attention of health care providers; and (4) the possibility that pregnancy

represents a time of heightened motivation for decreasing drug abuse for at

least some women. Unless the fourth rationale is supported by research, the

mounting evidence for fetal damage early in pregnancy could suggest that

scarce resources for treatment should be devoted to women before they

become pregnant. An obvious approach to this problem is to obtain the

best possible data on women’s spontaneous changes in drug use after

pregnancy occurs and after women become aware of pregnancy. This

would help target which patterns of drug use, if any, spontaneously improve

with pregnancy (suggesting the use of supportive treatments that enhance the

spontaneous effect). Such research also could identify drug-use patterns that

are predictably resistant to spontaneous change with pregnancy and, therefore,

require vigorous intervention if any intervention is to be of help. In addition,

intervention in any pregnancy, if effective, not only serves as secondary or

tertiary prevention of damage to the index pregnancy but also could serve as

primary prevention of potential damage to future pregnancies,

Prospective studies of cohorts of drug-abusing women who are not yet

pregnant might yield useful information, but ethical issues and observation

effects are likely to limit the information that can be obtained. Given that it

already is known that use of at least some drugs can be damaging to the

fetus and that others appear to pose risks, it is difficult to continue to observe

drug-using women who are at risk of pregnancy without intervening to

discourage drug use, encourage prevention of pregnancy, or both. Also,

because information about drug hazards during pregnancy is broadly available

and increasingly disseminated, it is difficult to imagine that even asking the

necessary questions to conduct prospective research would not affect either

drug use, contraception, or both. The populations of women who would be

least susceptible to such deterrent effects probably are the same women who

are most difficult to capture for longitudinal research.

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EFFECTS OF PREGNANCY ON DRUG USE

Pregnancy is often a time in which women report heightened motivation to

cease drug use. At the simplest level, the physiology of pregnancy occasionally

makes some drugs less attractive: Nausea or fatigue in early pregnancy may

make sedative drugs less appealing or make abstaining from them a little

easier.

More poignantly, many women state quite strongly that, however willing they

were to abuse their bodies with drugs, they fear damaging the baby and cannot

bring themselves to do to the baby what they were doing to themselves-not

only a telling comment on the depths of their self-esteem but also a useful

motivator for entering treatment. Many women identify with the baby, want to

provide a better life for the baby than they had themselves, or recognize that a

drug-using lifestyle that they had accepted for themselves is not the context in

which they wish to parent. (Anecdotally, one also hears of some expectant

fathers who share this maturational motivation: wanting to revise their lifestyles

to be a better parent. Although the frequency of this motivation may be less in

men than women, when present it would be of obvious potential benefit both to

the individual men concerned and to their partners and children).

Of course, this heightened motivation is not present in all drug-abusing women,

and when it is present, it is not always strong enough to bring about abstinence

in the absence of treatment and/or other supportive factors.

It also is known that the physiology, discomforts, and circumstances of

pregnancy can engender influences or motivations that are associated with

increased drug use-influences such as anxiety, fear, depression, and/or guilt;

situations of partner or family conflict; or frank desires to end the pregnancy by

attempting to induce abortion or premature labor with, for example, cocaine.

WHAT HAPPENS TO DRUG ABUSE WHEN WOMEN BECOME

PREGNANT?

Some women stop drug use as soon as they become pregnant or even in

preparation for pregnancy. Some would like to stop but do not or cannot;

they presumably would seek and welcome treatment if effective and userattractive treatment is available. Some would not seek treatment on their own

but can be persuaded to seek it by pressure from family, friends, and health

professionals. Some would not accept treatment on their own but may accept

it if the alternative were criminal sanctions and/or loss of custody of children.

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Loosely, the first category above may more often correspond to the Diagnostic

and Statistical Manual Ill, Revised, category of psychoactive substance abuse

and the other three to that of psychoactive substance dependence (American

Psychiatric Association 1987). At present, there are few data on the proportions

of pregnant women falling into these four groups, even though such data would

be important in health care planning and resource allocation and even for

planning rational, fair, and effective use of legal and child protective service

strategies.

Treatment planning is further complicated by lack of information about the

incidence of dual diagnosis (substance abuse complicated by coexisting

psychiatric and/or medical diagnoses) and the incidence of complicating life

circumstances (such as homelessness, isolation from extended families, and

adverse family situations, including partners who physically or sexually abuse

the women as well as partners or children who abuse and/or deal in drugs).

Although drug abuse occurs in all social classes, the family chaos frequently

engendered by parental drug abuse is likely to be compounded where other

resources are lacking and women must obtain drugs through criminal activities

or by remaining dependent on a partner who supplies the drugs. All the above

factors can (1) complicate treatment, (2) require more extensive treatment for

those least able to afford it, and (3) contribute to treatment dropout, failure, or

relapse. As discussed more fully below, information about the incidence of

these complicating factors in a treatment sample is essential if the extent to

which outcome data can be validly compared across treatment settings is to be

known.

GENERAL LOGIC AND MEASUREMENT STRATEGIES: WHAT WE WANT

TO MEASURE AND WHY

For this chapter, it is assumed that, in general, treatment of pregnant drug

abusers is a good thing if the treatment is sufficiently effective, if it does not

backfire and make things worse, and if effective treatment is not too costly to

be feasible. The problem of potential negative effects of treatment so far has

received more attention in the general psychotherapy literature than in the

chemical dependency treatment literature (e.g., Strupp 1977). Thus, measures

in several domains need to be considered.

Sample Selection and Eligibility Criteria

Is the woman pregnant? Are there any characteristics of the pregnancy or her

plans for it that should exclude her from a given study? Is she too far along in

pregnancy or not planning to maintain the pregnancy or retain custody of the

child-factors that might create a poor match between a woman and a program

that heavily emphasizes preparation for motherhood?

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Does the woman use drugs? If so, does her use meet the study’s criteria for

substance abuse and/or dependency? Are there any characteristics of her

drug use pattern or of her goals for modifying it that should exclude her from a

given study? Are there concomitant medical or psychiatric diagnoses whose

treatment is so imperative as to take priority over drug abuse treatment (or

render meaningful participation impossible)? Can she give informed consent

and be an active participant in her own care? Should a given study accept

a patient whose housing arrangements, transportation needs, or other life

circumstances make regular and meaningful participation in care and treatment

unlikely?

Ethically, excluding a woman from a treatment program, even a research one

that requires such exclusion, imposes an obligation to make every effort to refer

the patient for more suitable treatment elsewhere, since these exclusionary

criteria are disturbingly reminiscent of some of the reasons cited by other

programs for excluding all pregnant women.

Measures of Maternal Motivation for Treatment and Predictors of

Sustained Motivation

What characterizes women who (1) seek treatment on their own; (2) can be

persuaded to accept treatment by pressure from family members, referring

health professionals, or other community resources; or (3) accept treatment

only if compelled by legal sanctions? How do these groups of women differ in

what they want out of treatment and what they fear from it? How does their

motivation change over time?

What evidence can be found of the intensity of a woman’s motivation for

treatment and of the strength of the ambivalence that is almost universally

present? What goals does she have from treatment, and how realistic are

they? Is she there only to please others, to avoid criticism or sanctions, or to

protect her baby (and perhaps even that only during the pregnancy); or can

she see a drug-free lifestyle as a more satisfying choice for herself? Does she

seek a drug-free lifestyle or only a reduction in dose or in use of certain drugs?

How committed is she to a process of setting her own goals or complying with

program goals? What other potentially useful and/or competing goals does she

have for her life besides a drug-free lifestyle? In what other ways (besides

modifying drug use) might she want to use treatment to enhance her lifestyle?

Other Maternal Characteristics

What is the woman’s history of drug use? What is her family and personal

history, including past or present sexual and physical abuse and neglect? Is

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there a history of prior drug abuse treatment? Is there a dual diagnosis or

complicating physical illness and life circumstances?

Characteristics of the Treatment Program

Which ingredients are provided in the treatment package? Are they standard

or individualized? For a given patient, what was the quantity and quality

of her utilization of each ingredient? Levels of training, experience, and

personal characteristics of treatment personnel may be highly pertinent to a

full description of the ingredients they provide.

Outcome Measures

In-treatment outcomes may include mastery of specific treatment elements

offered. (Not all programs will offer all elements nor will all generally successful

participants necessarily succeed in every single element.) Examples include

participation and progress in treatment elements for which she has contracted,

cognitive mastery of cognitive components, emotionally meaningful participation

in therapy sessions, verifiable progress toward attaining any coping skills for

which training is offered, participation and progress in 12-step groups, and

maintaining clean urines during treatment.

Posttreatment outcomes may include maintaining clean urines; maintaining

aftercare as contracted; maintaining active participation in 12-step programs

(which appear to be an economically feasible way to provide needed aftercare

for prolonged periods, perhaps for a lifetime); learning from any lapses or

relapses, with maintenance of or quick return to aftercare and/or 12-step

programs; and improving one’s quality of life. In the case of women treated

during pregnancy, improved obstetric outcomes and infant health are additional

positive outcomes, as is quality of parenting, especially where parenting

education is a specific program component.

Long-term outcomes need to include general quality-of-life measures, with

particular emphasis on psychological constructs such as self-esteem, selfconfidence, and self-efficacy, and realistic optimism for the future as well as

effective coping with the inevitable negatives, since sustained recovery is

less likely without ongoing progress in these areas. Educational-vocational

habilitation or rehabilitation, normally a major long-term outcome, is a salient

need for women who start with educational and job skill disadvantages; yet

its timing for women who are already responsible for the care of several small

children may be difficult. Taking on too many responsibilities at once can be a

source of stress and, therefore, a trigger to relapse. Program and outcome

measures in this area need to fit the realities of women’s lives.

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Since chemical dependency is by nature a chronic and relapsing disease,

realistically, treatment programs should look for more than complete sustained

abstinence as a positive outcome. Successful treatment outcomes can include

lapses and even relapses if the patient is able to be candid about them, take

them seriously, look for triggers and learn something from them, and follow

them with intensified participation in aftercare and/or 12-step work.

Combined, Interactive, and Second-Level Measures

Comparison of specific entry characteristics of the women, specific in-program

outcomes, and specific long-term outcomes permit the formation and ultimately

the validation of several hypotheses important to treatment improvement. For

example, what patient and treatment characteristics, alone and in interaction,

predict risk of a patient’s losing her motivation, or conversely, predict the

likelihood of developing her own motivation after entering treatment under

duress? Can these predictor variables be validated by using them to modify

programs or individual treatment plans to enhance retention? Can they be

used to rationally assign patients to different programs (e.g., inpatient vs.

outpatient, women-only vs. mixed-gender programs, and different types of

programs)?

What baseline variables characterize women who benefit from treatment, and

what are the kinds or elements of treatment? Are there different predictors for

early dropout, for late dropout, and for achieving and maintaining abstinence

during the pregnancy vs. avoiding relapse later? Are dropouts always treatment

failures? An important and often neglected question is: Do characteristics

of women or programs that avoid one kind of adverse outcome increase the

risk of others? For example, could excessive emphasis on abstinence during

pregnancy encourage postpartum relapse? Could facilitating entry into the

program and preventing dropout sometimes result in a less strongly motivated

cohort for whom a lower percentage of long-term success might be predictable?

And if so, is this always bad or unmodifiable?

Could there be different intake predictors of what kinds of outcomes constitute

success? For example, does the diagnostic distinction between substance

abuse vs. dependence (or any other cluster of characteristics) differentiate

between a group of women who must permanently avoid any addictive

psychoactive substance to prevent full relapse and a group who could use

alcohol socially and moderately? What predictive power, if any, does the

abuse vs. dependence diagnostic distinction confer? How must success

criteria be modified for the dual-diagnosis patient?

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Under what circumstances are elements of treatment helpful vs. harmful? For

example, could the confrontation that helpfully challenges one woman to break

through her denial cause another woman lasting damage to self-esteem with

increased depression and drug use, perhaps even suicide? Can a program that

insulates a woman too much from the environment to which she will return after

initial treatment result in enhanced risk of relapse when she does return to it?

Could a program that is too intensive be as harmful as one that is not intensive

enough (Miller and Hester 1980)? When Is it beneficial for a woman to defer

her other responsibilities (such as work or child care) in favor of a focus on

treatment goals, and when does that cause harm by disrupting what may be

the healthiest areas of function in her life? When is it helpful for a marginally

motivated patient to be in a group with more motivated ones, and when does

such a patient suffer alienation, lose self-esteem, drag down the other group

members, and perhaps incur their wrath?

Treatment Cost-Beneflt Conslderatlons

Can it be demonstrated that treatment programs, perhaps even costly ones,

pay for themselves in terms of reducing high costs associated with premature

births or otherwise damaged babies? If they pay for themselves with some

patients, but not with others, how well can it be predicted which patients? Can

costlier treatments, such as inpatient treatment, be justified if the indications can

be refined so as to use these costly treatments sparingly, when they are most

needed?

Research Cost-Benefit Considerations

In searching for the above predictor variables, it is easy to get lost in a costly

and unproductive “fishing expedition.” All possible maternal variables cannot

be measured against all possible outcome measures to produce interpretable

data. Guidance from theory is needed. In complex treatment strategies, a

careful search must be made for active ingredients, specific indications, and

measurable intervening variables.

A simple-minded example suggests a general strategy: If, for example, it is

believed that assertiveness training might help in relapse prevention, either

alone or as part of a social skills training package, it probably would be

predicted that it helps some patients more than others, Those who already

display adequate assertiveness might not need it, and those who are the least

assertive may be unable to learn it in the time available. It might be predicted

to be an active ingredient only for those who, at baseline, have a moderate

assertiveness deficiency: of those, it may be effective only for the ones

who demonstrate that they can acquire the skill, maintain it, and generalize it

appropriately to real life.

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If studies are to be as comparable as possible, similar inclusionary and

exclusionary criteria should be used across studies. However, depending on

the specific research questions asked, there is a potential conflict between the

goals of isolating variables and producing generalizable results.

Studies whose aim is to verify effects of a particular drug on the developing

human fetus ideally would hold other factors constant. For example, if

researchers want to determine what lasting fetal consequences result from

first-trimester cocaine use, they would seek a sample of women who can be

proved to have used cocaine during the first trimester, and not later, and they

would want to eliminate such potential confounds as use of other drugs,

exposure to other toxins, and potentially complicating maternal medical

problems and life circumstances. Such a sample, if located, would be ideal

for isolating effects of first-trimester cocaine use on the fetus.

However, any findings about treatment approaches that help stabilize cocaine

abstinence for the balance of pregnancy in such a sample would have limited

generalizability to the bulk of drug-abusing pregnant women because the

majority use more than one drug, seek prenatal care after the first trimester,

have at least some complicating medical and/or psychosocial conditions, and

have at least some lapses or relapses before achieving abstinence, if indeed

they achieve it at all.

Therefore, a sample that is most generalizable to the drug-abusing pregnant

population will not be ideal from the standpoint of isolating specific effects of

specific drugs in specific doses or at specific times in pregnancy. Nor will it be

likely to be ideal from the standpoint of partitioning out which adverse fetal

effects occur as a result of the pharmacologic or toxic effects of the drugs in

question vs. which occur as a result of other circumstances of a drug-using

lifestyle, such as poor maternal nutrition and weight gain, delayed and/or

sporadic use of prenatal care, increased incidence and delayed treatment of

infections and other medical complications of pregnancy, and increased

incidence and severity of maternal psychosocial and biological stress. It would

be more ideal if these problems could be reduced by providing excellent

prenatal care even in the face of continued drug use-a formidable challenge.

DISCUSSION OF SPECIFIC MEASURES

Meaning/Context of Pregnancy to the Women

If a drug-abusing woman is pregnant, what does she intend to do about the

pregnancy? Answers include a continuum ranging from “end it,” to “do just

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about nothing” in terms of health care or lifestyle modification, to “make an allout effort” in terms of seeking every possible enhancement to the pleasure

and health of mother and developing fetus as well as every possible

enhancement of the lifestyle in which the pregnancy is occurring. Answers

may affect eligibility for the study and may serve to describe the subjects

further. Almost certainly both the place on the continuum from “end it” to

“enhance it” and the content of what forms of ending or enhancing were

contemplated would vary among groups of newly pregnant women and for

women with different pregnancies. “Ending it” could mean suicide for one

woman, abortion for another, giving a child up for adoption for another, and for

yet another, chemical forms of Russian roulette. Thus, paradoxically,

knowledge that certain drugs are risky to the baby can increase their use, and—

for a woman who wants to let fate decide whether she carries a baby to term—

knowledge that prenatal care can save babies’ lives can decrease the chances

of seeking that care.

Similarly, “enhancing” a pregnancy for one woman may mean entering or

strengthening a marriage or partnership, but for another woman it may mean

finally deciding to throw out an abusive partner. For one woman it may mean

furthering her career; for another it may mean dropping out of school or a job.

For one woman it may mean continuing in dietary or drug indulgences (which

are her current version of “the good life”); for another it may mean ritualistic

and even superstitious abstention from many usual pleasures. For one

woman it may mean assiduous compliance with whatever her chosen advisers

recommend during pregnancy; for another it may mean adopting a perceived

“adult” status that includes a declaration of independence from (or opposition to)

any form of compliance.

Simple tallies of engagement in healthy prenatal behaviors may fail to capture

important dimensions of the meaning of a particular pregnancy to a particular

woman; conversely, simple measures of the degree to which the baby is

planned or wanted, while important, should not be expected to predict the

content of the mother’s conscious or unconscious pregnancy-ending or

pregnancy-enhancing behaviors, either in the realm of drug use or of other

behaviors that may affect pregnancy outcomes and either alone or in

conjunction with drug use.

Similarly, simple measures of the extent of attachment to the developing baby

probably are not going to be linearly related to healthy relationships once the

babies are born. There is undoubtedly such a thing as too much attachment

as well as too little. Furthermore, attachment may be based on realistic or

unrealistic hopes for what the baby will do for the mother’s life and well-being.

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An obstetric history scale for pregnant drug abusers ideally should include not

just the number and obstetric outcome of previous pregnancies but also a

scaling of past emotional responses to past pregnancies and their outcomes

(Raskin, in press), consideration of life events at the time, and coping methods

used, including drug use.

Measures Confirming Pregnancy

Standard obstetric examination is sufficient and is confirmed by standard

pregnancy tests (which in general measure hormones of pregnancy and only

indirectly indicate the presence of a viable fetus).

Gestational age and the absence of major anatomical abnormalities can be

assessed through ultrasonography. Estimating gestational age through

menstrual cycle history is frequently inaccurate in drug-abusing populations for

a host of reasons: Drug use, malnutrition, and gross stress all are associated

with a higher incidence of menstrual irregularity, and maternal recall may be

less accurate under chaotic life conditions. Ultrasonography around 16 to 17

weeks is considered most accurate for determining gestational age and still is

pertinent for detection of major abnormalities in time for abortion if that is being

considered. However, early ultrasound can be done only in the subsample of

women who present early for prenatal care. Self-report data on date of last

menstrual period should be gathered in the usual way because they are

available to some extent from all women and are therefore more generalizable

to future clinical samples. Such self-report data should be supplemented with

whatever other cautionary data the woman can give, such as prior menstrual

irregularity, and with more objective data available during pregnancy

(ultrasound) and from neonatal examination after birth.

Measures Confirming Drug Abuse

Biological Measures, Retrospective and Concurrent. The advantages and

disadvantages of particular methods will not be discussed here, since other

chapters in this monograph address these issues.

Biological measures of past drug use have potential prospective psychological

consequences. If an accurate record of what a woman has ingested in the

past can be established through, for example, a highly accurate hair analysis—

and if the drug use can be pinpointed in relationship to onset of pregnancy by

measuring, for example, a progesterone surge in the same hair sample—and

if this were done routinely, it could result in more accurate information on the

timing of drug effects in specific developmental stages and determination of

whether pregnancy was followed by increased, decreased, or unchanged drug

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use. However, some women might be deterred from entering treatment by fear

of such a record of past behavior that could be used against them or, at least,

that could enhance guilt. The woman entering treatment hopes to modify her

current and future behavior; there is nothing she can be offered with regard to

past behavior other than help in dealing with guilt or the hope that future

technology will permit reversal of consequences of past behavior.

Biological measures of current drug use have psychological consequences.

Ongoing monitoring of current drug use permits validation of ongoing self-report

measures, Therefore, it encourages honesty in self-report by removing any

motivation to give a misleading optimistic report. Ongoing monitoring permits

early detection of relapse and allows modification of treatment. Since few if

any patients will be monitored for the rest of their lives, the goal of relapse

prevention includes engaging the patient in ongoing self-monitoring. Therefore,

in treatment it seems best to use biological monitors as a backup and validity

check on self-report measures rather than as a substitute for the latter.

This may be particularly feasible during pregnancy, because urine samples are

obtained regularly at prenatal visits for medical checks, With the patient’s

advance permission, toxicology screens could be done on these urines at any

time. The focus in the drug treatment program then could be on the ongoing

self-report. Urines could be used as backup to the veracity of self-report, at

reduced cost, by running only a random sample of them for toxicology (the

so-called Bogus Pipeline technique); however, if this technique is used during

pregnancy it means that the routine samples used obstetrically must be

specimens obtained under observation. Otherwise, the patient who is tempted

to use someone else’s urine to escape drug detection also could avert detection

of obstetrically important evidence of bacteria, protein, or sugar in the urine.

Where there is a choice, the use of a method that gives immediate feedback

offers significant clinical advantages. A delay of even several days in detecting

a discrepancy between self-report and urine results makes it easier for the

patient to forget what she was experiencing psychologically at the time of use

and makes it easier for her to elaborate defensive mechanisms.

Self-Report Measures of Drug Abuse History. The Addiction Severity Index

(ASI) provides comparability of data with that obtained from other drug abuse

treatment programs (McLellan et al. 1985). However, the ASI references selfreport of past use to standard time intervals, which are not keyed to the duration

of a pregnancy. Therefore, when used to measure self-reported drug use in

relationship to a pregnancy, the ASI drug use items should be cast in time

intervals related to landmarks of pregnancy: the time when conception most

probably occurred, the time when the woman first suspected pregnancy, and

205
the time when she was first certain she was pregnant. Differences in drug use

around these three landmarks reflect not only the potential impact of the drugs

on the fetus but also the impact of the pregnancy on the woman’s drug use.

It is also useful to know the extent to which common symptoms of pregnancy

(e.g,, fatigue, nausea) and psychological responses to awareness of the

pregnancy (e.g., pleasure, displeasure, anxiety, depression) were associated

with either spontaneous decrease of drug use or increased use as an attempt

to cope. Concurrent life events (emotional and/or physical abuse, moves,

increased or decreased closeness with sexual partner and significant others,

and illness in self, children, and other family members) should be recorded

along with drug and nondrug coping attempts and their success,

Informant Histories of Patients’ Drug-Using Behavior. Self-report measures

are limited by patients’ ability or willingness to give an accurate history. Reports

from close friends and/or family members have their own inaccuracies but do

provide another source of information. Using an ASI-Informant version would

help eliminate differences related to format.

Measures of Psychiatric Status

Individual differences in patients in the somewhat overlapping areas of

psychiatric diagnoses and personality characteristics are important to measure

for at least three reasons.

First, there is no point in providing a standard drug abuse treatment protocol if

the patient is too disabled by a concomitant psychosis or too immobilized by a

concomitant depression to participate meaningfully in the treatment.

Second, a coexistent and possibly preexistent psychiatric diagnosis is common

and has been associated repeatedly with poorer response to drug abuse

treatment and greater risk of relapse (e.g., Kosten and Kleber 1988). These

conditions deserve treatment in their own right. Furthermore, the success of

drug abuse treatment applied to a sample with a higher prevalence of these

poor prognostic indicators cannot be compared readily with the outcomes of a

different treatment applied to a sample in which these conditions are less

prevalent.

Third, the triggers associated with relapse for different patients are highly

individual but appear to be associated with personality characteristics. Thus,

information about personality characteristics as well as lifestyle vulnerabilities

and support system strengths and weaknesses could be incorporated

meaningfully into individual and group treatment for relapse prevention.

Plausible examples include the following:

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Individuals with shyness or social phobia often use drugs in an attempt to

cope with social situations, and they may have difficulties in refusing social

encouragements to use drugs.

Individuals with high degrees of depression or generalized anxiety often give

a history of short-term relief of these affects by drug use, and they may fail to

notice that long-term use generally increases the frequency and intensity of

these affects. The reinforcing effect of the drug in short-term relief of painful

affect is far more strongly learned and therefore more enduring than is the

potentially punishing effect of the drug in long-term exacerbation of affect—

immediate effects are almost always more strongly learned than remote

ones (Wikler 1971).

Self-esteem, which is frequently impaired in drug abusers, typically rises

with effective treatment and falls with relapse. The fall may antedate the

chemical relapse, but there are not enough careful prospective studies of

relapse to establish this point firmly. Most experienced clinicians believe

that a state of falling self-esteem in an abstinent recovering patient indicates

risk of relapse. “State vs. trait” self-esteem has not been as clearly

differentiated. There is a general clinical belief that high usual levels of

self-esteem are protective against momentary blows to self-esteem, but this

has not been effectively disentangled from the fact that high self-esteem

usually is associated with more effective social interactions, lessening the

occurrence of damage to self-esteem.

Closely related to self-esteem but distinguishable from it is self-efficacy

or locus of control. Successful rehabilitation from several disabling medical

conditions and successful achievement of educational and vocational

advancement, all have been associated strongly and persistently with

individuals’ beliefs that their actions rather than uncontrollable fate determine

their lives (Strecher et al. 1966). On the other hand, there have been some

indications that individuals who expect to control their life circumstances may

be particularly vulnerable to events that shatter that expectation. Locus of

control appears to be related to self-esteem in that individuals with external

locus of control attempt to regulate self-esteem by attaching themselves

to powerful others and esteeming themselves insofar as they succeed in

pleasing the significant other, whereas individuals with internal locus of

control are vulnerable when their expectations of control are thwarted such

that they can blame only themselves. Women as a group are more likely

than men to have external locus of control, as are persons of lower

socioeconomic status.

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Stressful life events are of obvious importance as contributors to

exacerbation of ongoing psychiatric illness and as potential triggers for

drug abuse relapse.

Support systems, when adequate, are major buffers in dealing with stressful

life events (Lin et al. 1966).

These variables, if measured at intake, may need to be repeated after a

period of active treatment and again in aftercare. Depression, anxiety, and

other symptoms observed at intake may reflect drug use and/or immediate

withdrawal states, and in such cases, the symptoms may diminish or dissipate

with a period of abstinence. Measures taken between 1 and 2 months after

beginning drug abuse treatment are usually more predictive of continuing

problems.

A major unresolved problem in the diagnosis of psychiatric comorbidity is that

current diagnostic instruments do not converge as much as would be desired,

particularly in the area of personality disorders (Gaulier et al. 1990). Some

reasons variance occurs are that self-report, informant report, and clinician

data tap partially independent domains; different items and different cutoff

points in different instruments may obscure real convergence; traits that

conceptually make up different syndromes overlap to a considerable extent

and may be measured more reliably as traits than as syndromes; and

personality tests normed on non-drug-abusing samples may apply differently

to drug-abusing populations. In addition, in the case of pregnant women, items

that refer to somatic experience and identity may be affected by pregnancy in

ways that are not yet fully studied. In the meantime, it is important to remember

that psychiatric diagnoses arrived at with the use of different respectable

instruments will not capture exactly the same patients, especially for Axis II

diagnoses.

Obstetric Measures Related to Course and Progress of Pregnancy

Important areas to be measured include the following:

Nutritional status: estimated by diet history at intake and at 28 weeks,

compared with weight gain and other dietary outcome measures such as

hemoglobin and folate levels at intake and 26 weeks

Complications: incidence, severity, and timing of any complications (such as

infections, increased blood pressure, diabetes, preterm labor, or anything

else requiring hospitalization)

206
Adequacy of prenatal care: gestational week of first visit, number and

percent of scheduled visits kept by trimester, and extent of outreach required

to achieve acceptable level of care

Group Measures of Treatment Efficacy

Progress of chemical dependency treatment for a group rather than an

individual usually involves simpler measures recorded as percentages, such

as percent of eligible patients who enter a program, drop out (defined as

permanent cessation before achievement of objectives), “fade out”

(absenteeism from scheduled sessions), or achieve such goals as 12-step

group participation (e.g., percent attending a specified number of meetings

per week during active treatment; percent selecting a home group and a

sponsor, and percent completing specified steps). Progress also may be

measured in percent of patients whose partners and/or other family members

participate in the primary treatment program and/or outside support groups and

percent achieving treatment outcome goals initially and maintaining them over

followup.

CONCLUDING NOTE

Research demonstration projects are noted for designing programs that appear

to work in the pilot or research phase but never get broadly implemented for a

variety of reasons. Although there are many barriers to service implementation

for noncost reasons that lie outside the scope of this chapter, it should be clear

that any program recommended for large populations at mostly public expense

must justify not only efficacy but also cost. In the case of chemical dependency

treatment for pregnant women, even persons who do not give high priority to

the well-being of the women may be persuaded to support treatment for them

if costs of treatment can be favorably balanced against the costs to the public

of not providing treatment. This again brings up the paradox with which this

chapter started: Greater concern for the baby (and costs of the baby’s care)

than for the mother may motivate the public to fund treatment, just as it may

motivate the pregnant woman to enter treatment. However, sustained

abstinence will occur only as part of a lifestyle that is demonstrably preferable

from the perspective of the woman.

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pp. 11-141.

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(CDC)88-8046. Rockville, MD: U.S. Public Health Service, 1988.

Raskin, V.D. Maternal bereavement in the perinatal substance abuser. J Subst

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Strupp, H. Psychotherapy for Better or Worse: The Problem of Negative

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Weissman, M.W., and Myers, J.K. Affective disorders in a US. urban

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ACKNOWLEDGMENTS

This work was supported by National Institute on Drug Abuse grant SRCD (27),

5 R18 DA-06378.

Ellen Mason, M.D., Mary Driscoll, R.N., M.P.H., Valerie Raskin, M.D., Karen

Sobieraj, M.S.W., Brian Flay, D. Phil., Bruce Bonecutter, Ph.D., and Martin

Harrow, Ph.D., participated in the delineation of issues.

AUTHOR

Anne M. Seiden, M.D.

Chairperson

Department of Psychiatry

Cook County Hospital

Associate Professor

Department of Psychiatry

University of Illinois at Chicago

1825 West Harrison Street

Chicago, IL 60612

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Assessing Acute and Long-Term

Physical Effects of In Utero Drug

Exposure on the Perinate, Infant,

and Child

Emmalee S. Bandstra

INTRODUCTION

Perinatal centers nationwide estimate that in excess of 10 percent of all

deliveries are affected by in utero exposure to illicit drugs as documented by

maternal history and/or urine toxicology (Chasnoff 1989; Bandstra et al. 1989).

Furthermore, a recent study by Ostrea and colleagues (1990) showed that 40

percent of the infants delivered at Detroit’s Hutzel Hospital had meconium

stools positive by radioimmunoassay for cocaine, heroin/morphine, or

cannabinoids. Therefore, accurate identification of infants who have been

drug-exposed in utero is essential to clarify perinatal mortality and morbidity

trends. Although the longitudinal study design clearly is the most powerful tool

in perinatal drug research, assessment of acute outcomes also may be

valuable.

Collaborative relationships forged between clinical investigators of perinatal

substance abuse and those skilled at assessing the pharmacology and

physiology of various organ systems may be mutually advantageous. Clinical

research into the prevention and management of numerous neonatal

complications (e.g., perinatal asphyxia, intrauterine growth retardation [IUGR],

prematurity, central nervous system [CNS] hemorrhage and ischemia, and

cardiorespiratory disorders) may be seriously confounded by in utero exposure.

Published studies on neonatal populations uncharacterized regarding in utero

drug exposure therefore may be subject to significant retrospective criticism by

reviewers within all disciplines.

This chapter focuses primarily on methodological issues related to in utero

cocaine exposure, but the spectrum of polydrug exposure is always present

in clinical studies. Special emphasis is given to the following adverse

consequences: spontaneous abortions, stillbirths, congenital structural defects,

212
IUGR, and prematurity. Key points in establishing measurable endpoints with

respect to the CNS also will be illustrated.

SPONTANEOUS ABORTION AND FETAL DEMISE

One of cocaine’s devastating effects appears to be early labor and uncontrolled

delivery. Pregnant, cocaine-abusing women may suffer spontaneous abortions

or stillbirths. Furthermore, many drug-using women pay little attention to

contraception and, thus, seek therapeutic or self-induced abortion, sometimes

with cocaine as an abortifacient, as a remedy for an unwanted pregnancy.

Abruptio placentae was first mentioned as a cocaine-related complication

by Acker and colleagues (1983). Bingol and colleagues (1987) showed a

tenfold increase in the number of stillbirths, all of which were related to

abruptio placentae, in pregnant cocaine-abusing women compared with a

drug-free control group. No other series has yet confirmed fetal demise as a

statistically significant complication among cocaine users. However, Critchley

and colleagues (1988) reported a fetal death secondary to maternal cocaine

abuse. At the University of Miami/Jackson Memorial Hospital, Burkett and

coworkers (1990) also have reported a cocaine-induced fetal and maternal

death.

The true impact of drug exposure on perinatal mortality may be related more

to early pregnancy losses and third trimester stillbirths than to neonatal demise

per se. Past pregnancy histories should be carefully analyzed for frequent or

unexplained fetal losses. Screening for substance abuse should be an integral

part of the obstetrical evaluation of spontaneous abortions or stillbirths. Gross

and histopathologic examinations of postmortem tissues and organs in drugrelated maternal, fetal, or neonatal deaths and in placentae from stillborn or

live-born drug-exposed infants should be incorporated into clinical practice

and pertinent research study protocols. Cocaine’s propensity for causing

spontaneous abortion and stillbirth may confound clinical studies of congenital

malformations unless the fetal remains are examined carefully and subjected

to toxicologic, morphologic, and chromosomal examinations.

CONGENITAL MALFORMATIONS

Investigations in mice show conflicting results regarding the effects of cocaine

on the development of congenital malformations. “Nontoxic” doses of cocaine

administered to gravid mice have been shown to be teratogenic (Mahalik et al.

1980). A subsequent paper in 1984 from the same investigators showed

significant increases in the fetal resorption ratio and the rate of fetal anomalies

compared to controls (Mahalik et al. 1984). The researchers reasoned that

213
cocaine-induced blockage of norepinephrine uptake is responsible for placental

vasoconstriction and fetal hypoxia, which produce the defects.

Other reports conflict with the above findings, however. In the study by

Church and coworkers (1988), subcutaneous cocaine injections in Long-Evans

rats were shown to have adverse effects on maternal weight gain, maternal

food and water consumption, fetal weight, maternal and fetal fatalities, fetal

edema, abruptio placentae, and cephalic hemorrhage, but few congenital

abnormalities were observed. Fantel and MacPhail (1982), using the Virgin

Sprague-Dawley rat model, showed no increase in congenital defects but

found fetal growth retardation induced by cocaine.

Chasnoff and colleagues (1988) compared 50 infants exposed to cocaine

during the first trimester of pregnancy with 30 noncocaine polydrug-exposed

infants and noted a significant increase in genitourinary tract malformations.

Physical examination and renal ultrasound were employed in the diagnosis.

Two cases of ileal atresia also were detected. Some of the cocaine-exposed

infants also had been exposed to heroin, marijuana, alcohol, and nicotine.

Chavez and coworkers (1989) also confirmed a relationship between cocaine

use in early pregnancy and urinary tract defects in the population-based Atlanta

Birth Defects Case-Control Study. Little and colleagues (1989) showed a

significant difference between 53 cocaine-exposed infants and 100 unexposed

infants with regard to congenital anomalies, specifically cardiomegaly, atrial

septal defect, and ventricular septal defect. The cocaine-exposed group

also had a higher rate of exposure to tobacco, marijuana, alcohol, and

methamphetamines. In contrast, other investigators have not observed

increased rates of congenital malformations in cocaine-exposed infants

(Cherukuri et al. 1988; Hadeed and Siegel 1989; MacGregor et al. 1987).

Polydrug exposure confounds clinical studies attempting to relate cocaine

exposure to congenital defects. Alcohol causes many of the same anomalies

noted in cocaine-exposed infants, including microcephaly, cardiac defects,

and genitourinary tract anomalies (Jones et al. 1973; Jones 1986). Mice

exposed in utero to alcohol develop genitourinary anomalies, principally

hydronephrosis (Boggan et al. 1972). Marijuana increases nearly fivefold the

risk of delivery of an infant with features of fetal alcohol syndrome (Hingson et

al. 1982).

Investigations also are hampered by the inability to ascertain the presence and

magnitude of first trimester exposure due to lack of suitable biologic markers

and inaccuracy of maternal self-report (Zuckerman et al. 1989). Maternal hair

samples (Graham et al. 1989) may provide some insight into time course and

quantification of in utero drug exposure and may permit better verification of

drug-free comparison groups.

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ABNORMALITIES IN INTRAUTERINE AND POSTNATAL GROWTH

PATTERNS

The most frequently described consequence of in utero cocaine exposure is

“low birth weight,” a term commonly used by the lay public as well as scientific

investigators. Many studies attempt to document an increased incidence of

low birth weight in cocaine-exposed infants as a harbinger of the potential

costs to society of dealing with their anticipated problems. However, confusion

surrounds the term low birth weight. Low birth weight refers to infants weighing

less than 2,500 g at birth; “very low birth weight” (VLBW) refers to infants

weighing less than 1,500 g at birth; and “extremely low birth weight” refers to

infants weighing less than 1,000 g at birth. Perinatal statistics rely heavily

on these categories, designated regardless of gestational age, because birth

weight (BW) is a more objective and measurable parameter than gestational

age. Unfortunately, the categories make little sense without knowing the

relationship to gestational age. Neonates should be classified by BW,

gestational age, and a standard for intrauterine growth. The most commonly

used standard of intrauterine growth is the University of Colorado Medical

Center classification (Battaglia and Lubchenco 1967) despite the problem of

applying high-altitude BW norms to sea-level populations.

Infants are classified as small for gestational age (SGA) if their growth

parameters fall below the 10th percentile for the gestational age. SGA infants

may be constitutionally small or “intrauterine growth retarded.” Symmetrical

growth retardation affects weight, length, and head circumference and suggests

longstanding aberration of fetal growth; asymmetrical growth retardation

involves sparing of head growth and denotes a late-onset compromise of the

feto-placental unit (Gruenwald 1963).

Complete physical examination, including neurologic assessment, should be

performed at birth and at each encounter during the longitudinal followup.

Measurements of weight, length, and head circumference should be performed

by a trained examiner. Dysmorphology examination formats with checklists

beyond a “yes” or “no” for “normal facies” and “physical anomalies” enhance

the physical examination. Photographs also provide a permanent record for

review.

Standard gestational age assessment, such as the Ballard modification of

the Dubowitz examination (Ballard et al. 1979), should be performed and

interpreted in light of obstetrical parameters of gestational age, if known, A

recent report (Constantine et al. 1987) from the Infant Health and Development

Program revealed that Ballard estimates of gestational age based on physical

criteria more closely correlated with dates estimates and yielded higher

215
proportions of correct classifications of prematurity and SGA than did estimates

based on neurologic criteria or combined neurologic and physical criteria.

The most consistent teratogenic consequence of in utero cocaine exposure is

IUGR (MacGregor et al. 1987; Cherukuri et al. 1988; Chouteau et al. 1988;

Hadeed and Siegel 1989; Fulroth et al. 1989; Zuckerman et al. 1989). The

last study involved a prospective survey of 1,126 mothers receiving prenatal

care in the Boston City Hospital clinic system. Maternal drug histories and

urine toxicology screening for cocaine and marijuana were performed during

the first prenatal visit and delivery hospitalization. The investigators found

independent contributions of cocaine and marijuana with regard to decreased

growth parameters of BW and length and an independent contribution of

cocaine with regard to decreased head circumference. Multiple regression

analysis, including prepregnancy weight and pregnancy weight gain, suggested

that cocaine may have an indirect negative effect on fetal growth mediated

by maternal undernutrition as well as an independent, direct negative effect.

The observed negative impact on intrauterine growth was not apparent when

infants were classified only by maternal self-report, thus underscoring the need

for urine toxicology screening.

In future studies, emphasis should be placed on IUGR to determine whether

in utero cocaine exposure further compromises neurodevelopmental outcome

measurements beyond the anticipated adverse effects of impaired intrauterine

growth (Smeriglio 1989). Such a study would require elucidation of other

potential etiologies for IUGR (Gross 1989; Evans 1989).

For example, congenital infections must be extensively explored with respect

to in utero drug exposure. Congenital syphilis and cytomegalovirus (CMV),

the two most common entities to cause CNS injury, have been reviewed

elsewhere (Prober and Arvin 1989). Congenital syphilis is on the increase

in major metropolitan areas (Ricci et al. 1989). This reflects the surge in the

incidence of sexually transmitted diseases in the general population and

specifically in the drug-using culture. The pattern is exacerbated by pregnant

substance abusers failing to seek prenatal health care. Fortunately, mandatory

serology screening for syphilis facilitates identification. The current rates of

seropositivity for syphilis, usually untreated, identified among cocaine-users

in the University of Miami/Jackson Memorial Hospital delivery population is

approximately 25 percent (unpublished data). The diagnosis of congenital

syphilis should be considered in any neonate born to a mother with a reactive

serology for syphilis. Congenital syphilis may be associated with the following

findings: growth retardation, prematurity, bullous skin lesions, maculopapular

rash, “snuffles,” skeletal lesions, jaundice, hepatosplenomegaly,

lymphadenopathy, and CNS involvement.

216
CMV occurs in 1 to 2 percent of all live births, The incidence of CMV among

cocaine-using pregnant women is not known. Congenital CMV infection can

be confirmed by isolation of the virus from urine or saliva, ideally within the first

postnatal week. Congenital CMV can result from either primary or recurrent

maternal infection, but the majority of infants symptomatic at birth have been

exposed to primary maternal infection. The clinical manifestations of CMV are

as follows: prematurity, growth retardation, microcephaly, CNS involvement,

chorioretinitis, hepatomegaly, splenomegaly, jaundice, and petechiae. Longterm sequelae include cognitive and developmental delays, learning and

behavioral disorders, seizures, neuromuscular disorders, and sensorineural

hearing loss. Approximately 10 percent of infants apparently asymptomatic at

birth develop long-term sequelae (i.e., progressive sensorineural hearing loss,

potentially impaired cognitive development, and behavioral problems) (Prober

and Arvin 1989).

In addition to IUGR, postnatal growth patterns of drug-exposed infants also

should be assessed. Attention should be paid to malnutrition and deficiencies

in vitamins and minerals (e.g., iron deficiency anemia) and exposure to

environmental toxins (e.g., lead). Landrigan and Graef (1987) termed childhood

lead poisoning the “silent epidemic.” Shukla and coworkers (1989) concluded

that high in utero lead exposure, reflected by maternal blood lead concentration,

followed by a relatively high postnatal lead exposure, detrimentally affects an

infant’s growth in terms of stature. Conversely, infants exposed to lead in utero,

but not postnatally, experienced “catchup” growth. Lead may be dispersed in

air, dust, and soil. Prevalence rates of elevated blood lead levels are highest in

densely populated urban areas, the very dwelling places of many of the study

participants in perinatal substance abuse programs. Childhood lead poisoning

is defined as a whole blood lead concentration of 25 mg/dL together with an

erythocyte protoporphyrin level of 35 mg/dL or above (American Academy of

Pediatrics 1987). Neuropsychologic dysfunction, including cognitive impairment

and behavioral disorders, may occur in asymptomatic children with elevated

blood lead levels. The Academy recommends that all children at risk for lead

exposure be screened at approximately 12 months postnatal age by means of

the erythrocyte protoporphyrin test, which provides a sensitive and inexpensive

screen for increased lead absorption and for iron deficiency.

PREMATURITY

The World Health Organization and many investigators set the dividing line

between preterm and term birth at 37 weeks gestation. Neonatologists

generally prefer to define preterm as less than 38 weeks and term as between

38 and 42 completed weeks of gestation (Lubchenco and Koops 1987).

217

318-164 0 - 92 - 8 : QL 3
Cocaine has been recognized as a contributing factor in premature delivery,

yet no studies thus far have focused on the specific consequences of in utero

cocaine exposure on outcome of premature infants already predisposed to

increased risk of death or long-term disability.

One of the most devastating complications of prematurity is periventricularintraventricular hemorrhage (PIVH), which occurs in approximately 40 percent

of VLBW premature infants (Volpe 1985; Shankaran et al. 1990). Hemorrhage

originates in the capillary bed of the fragile subependymal germinal matrix and,

in severe cases, fills and distends the ventricular system. Severe PIVH

also may cause hemorrhage into the parenchyma and/or progressive

hydrocephalus. Hambleton and Wigglesworth (1976) hypothesized that

increases in arterial blood pressure, under conditions of maximal dilatation

of the capillaries by hypoxia and hypercapnia, may be responsible for the

hemorrhage. The observation by Lou and coworkers (1979) that failure of

autoregulation occurs because of perinatal asphyxia in the premature infant

emphasizes that PIVH may be evoked by fluctuations of blood flow within a

pressure-passive cerebral circulation.

Cepeda and colleagues (1987) determined that VLBW infants delivered to

opiate-dependent mothers had a significantly lower incidence (23 percent) of

PIVH compared with infants of mothers who denied drug usage (52 percent),

p<0.05. Wurtzel and colleagues (1988) noted neither an increase nor a

decrease in PIVH in an uncontrolled study of 25 preterm cocaine-exposed

infants with a mean BW of 1,560 g and a mean gestational age of 32 weeks.

The PIVH rate was 16 percent, similar to the retrospective overall rate noted in

infants <=36 weeks. However, few VLBW preterm infants were assessed.

Another entity, periventricular leukomalacia (PVL), occurring as an isolated

finding or in combination with various grades of PIVH, is characterized by

echodense lesions evolving over several weeks into echolucent cysts within the

white matter adjacent to the ventricles. PVL, a predominantly ischemic lesion

that may have a hemorrhagic component, often is associated with severe

developmental delay, spastic diplegia, or quadriplegia. The lesion may result in

myelination delay. Van de Bor and coworkers (1989) have shown that magnetic

resonance imaging (MRI) is useful for detection of CNS myelination of preterm

infants with PVL. Their investigation of 33 preterm infants of less than 30

weeks gestational age studied at 44 weeks postconceptional age showed

significantly delayed myelination patterns in infants with PVL compared with

those with PIVH or without PVL or PIVH. The latter two groups had myelination

patterns similar to term infants at 44 weeks postconceptional age. DeVries and

colleagues (1988) also reported that transient periventricular echodensities,

even though unaccompanied by PIVH or periventricular cystic degeneration,

218
may herald neurologic abnormalities, especially dystonia, and may represent

mild PVL.

Determining whether in utero cocaine exposure affects the risk of PIVH, PVL,

or other lesions in VLBW infants is critical to understanding the pathogenesis

and prevention of these entities. It is not unreasonable to expect that in utero

cocaine exposure would have adverse CNS effects in VLBW infants due to its

profound effects on uterine blood flow. A case report of a term cocaineexposed infant alerted clinicians that cocaine could be responsible for neonatal

cerebral infarction, seizures, cortical atrophy, and neurodevelopmental delay

(Chasnoff et al. 1986). In utero stroke with resultant porencephaly in a term

infant also has been described in association with maternal polydrug abuse

(Tenorio et al. 1988).

Dixon and Bejar (1989) determined the incidence of CNS lesions detected

by echoencephalography in a group of 74 apparently healthy term infants

documented by urine toxicology to have been exposed in utero to drugs

(32 cocaine, 24 methamphetamine, and 18 stimulant/narcotic). Forty-one

percent of the 32 cocaine-exposed infants had abnormal echoencephalographic

lesions, which included white matter cavities, acute infarction, intraventricular

hemorrhage, subarachnoid hemorrhage, and ventricular enlargement. Similar

results were described for methamphetamine-exposed infants, except for a

significantly lower percentage of white matter cavities.

CNS ASSESSMENT

Most longitudinal neurodevelopmental studies have utilized physical and

neurologic assessments in conjunction with standardized neurodevelopmental

and neurobehavioral evaluations. Strict adherence to established norms,

verification of interobserver reliability among examiners, confirmation of

interpretations by reviewing videotaped assessments, and blinding of the

observers to medical and substance exposure histories are critical to

successful neurodevelopmental assessment.

Too little attention has been given to quantitation of neurologic examination

results. Many investigators simply resort to recording the neurologic exam

according to categorical representation of “normal,” “questionable,” “at risk,” or

“abnormal.”

Prechtl’s neurologic examinations, standardized on a large sample of full-term

infants, is a clinical and research instrument that is predicated on specifying the

optimal behavioral state or states in which most of the test items must be

administered and which of the infant’s responses are optimal. The examination

219
is lengthy and should be administered on a repetitive schedule (Prechtl and

Beintema 1964).

The Dubowitz neurologic assessment, useful for evaluating preterm and fullterm infants, also is recommended to be performed repetitively to determine

whether initially abnormal neurologic signs persist (Dubowitz and Dubowitz

1981).

The Brazelton Neonatal Behavioral Assessment Scale (NBAS) using Lester’s

cluster scores provides the most comprehensive assessment of the behavioral

repertoire of newborns (Brazelton 1976; Lester 1980) and is a useful tool in

comparative studies. Specific scales for preterm infants have been designed

(Brazelton 1984; Als et al. 1982; Korner and Tom 1990). Chasnoff and

colleagues (1989) showed significant impairment of orientation, motor, and

state regulation behaviors on the NBAS in infants who had been exposed in

utero to cocaine even when the exposure only occurred during the first

trimester. Eisen and coworkers (1991) documented abnormal habituation

patterns in cocaine-exposed vs. drug-free control infants during the first

postnatal week. Although early testing may be informative, performing the

NBAS serially over the first month may be more illuminating.

The Bayley Scales of Infant Development consists of mental and motor

scales as well as the Infant Behavior Record, which assesses the infant’s

characteristic behavior patterns during the assessment (Bayley 1969). Raw

scores are converted to the Mental Development Index (MDI) and Psychomotor

Development Index (PDI), respectively, which are standard scores based on a

larger sample representative of the US. population within the age range of 2 to

30 months. To date no other measure has been as widely used as the Bayley

Scales in this age range, and, thus, it may be the best tool for interstudy

comparisons. Many study designs incorporate examinations at 6, 12, 18, and

24 months. The advantage of such a schedule is the frequent early contact,

which fosters compliance for later evaluations. If attrition can be minimized

without such a repetitive schedule, focusing on an examination at 8 months and

at 18 to 24 months is logistically and financially advantageous. Preliminary data

on Bayley Scales performance in a relatively few cocaine-exposed vs. control

infants have not revealed significant differences in mean MDI or PDI scores

(Chasnoff and Griffith 1989). New investigative initiatives may need to include

more innovative measures of mental, psychomotor, behavioral, and special

sensory performance.

The Motor Assessment Inventory (MAI) appears to be an effective instrument in

evaluating muscle tone, primitive reflexes, automatic reactions, and volitional

movement in the first year of life (Chandler et al. 1990). Although the MAI is not

220
normed, interrater reliability has been reported as 0.72 (Harris et al. 1984). A

recent study found the MAI to be more than twice as sensitive as the Bayley

Motor Scale in detecting early signs of cerebral palsy (Harris 1987).

The Fagan Test of Infant Intelligence (visual information processing) is a unique

alternative to traditional assessments (Fagan and Shepard 1987). The test, a

visual preference paradigm that relies solely on face recognition, has been

applied to a variety of high-risk groups of infants. The equipment comprises a

viewing stage and an online computer for accurate administration and

automated scoring.

Long-term data on intelligence testing, special sensory assessments, and

behavioral and learning disorders in cocaine-exposed infants are as yet

unavailable. Controversy still exists regarding the use at age 3 years of the

revised version of Stanford-Binet; many investigators still administer the

previous version. One also could consider using the McCarthy Scales at

age 3 years to provide more objective evaluation of motor performance and

specific areas of strength and weakness than the Stanford-Binet, but the test is

more time-consuming. The McCarthy usually is preferred by the children due

to its more interesting performance tasks, Another approach is to assess IQ by

the Stanford-Binet at age 4 years, although this becomes a difficult timeframe

for 5-year grant cycles. All the tests should be interpreted in light of the

socioeconomic and family circumstances that strongly influence child

development.

Neurologic examinations and neurobehavioral assessments should be

coupled to state-of-the-art neuroimaging and neurophysiologic assessments.

Echoencephalography has become the mainstay of neonatal cranial imaging

due to its lack of ionizing radiation, portability, rapid performance time, and

reliability in detecting congenital structural anomalies, PIVH, periventricular

and subcortical leukomalacia, calcifications, cysts, and ventricular dilatation.

MRI now provides a safe, noninvasive, albeit expensive and time-consuming,

method of diagnosing these lesions as well as being uniquely capable of

delineating myelination patterns that could relate to neurologic function.

Repeat scanning is possible after fontanelle closure. No clinical studies thus

far have addressed the potential impact of cocaine on myelination patterns,

McArdle and coworkers (1987) reported MRI results of 51 neonatal brains (29 to

42 weeks postconception), which showed stages of progression of gray-white

matter differentiation and myelination. Cerebral gray-white matter differentiation

was graded on a five-point system (GW1 to GW5) and the distribution of myelin

stages on a four-point system (M1 to M4). Delayed myelination in the neonatal

period was defined as the absence of myelin in the corona radiata by 37 weeks

221
postconceptional age. Barkovich and coworkers (1988) described maturation

“milestones” as follows: The splenium of the corpus callosum should be of low

signal intensity by 8 months of age, the genu by 8 months of age, the anterior

limit of the internal capsule by 11 months of age, the deep frontal white matter

by 14 months of age, and the entire brain (except for some fine peripheral

arborization) by 18 months of age. Myelination delay strongly correlates with

abnormal motor tone and/or abnormal scores on the Bayley Scales in the first

postnatal year.

In addition to neuroimaging assessments, one might consider near infrared

oxygen sufficiency scope (NIROS-SCOPE) (Brazy et al. 1985), positron

emission tomography (Volpe et al. 1983), nuclear magnetic resonance

spectroscopy (Leonard et al. 1985), cerebral blood flow velocity measurements

(Bada et al. 1979; Altman and Volpe 1987), and acoustic cry analysis (Lester

1987). These modalities and others beyond the scope of this discussion may

expand research dimensions in the assessment of CNS structural anomalies

and/or functional derangements associated with in utero drug exposure.

CONCLUSION

The measurement of adverse fetal, neonatal, and infant outcome associated

with in utero drug exposure is fraught with difficulties, including misclassification

of the exposure(s), errors in determining timing and quantity of exposure(s),

numerous confounding variables, and inherent limitations of the measuring

instruments. However, careful attention to ensuring confidentiality of maternal

histories, utilizing state-of-the-art biologic markers, planning and executing

complete prospective data collection, standardizing examinations, maintaining

“blinded” observations, utilizing sophisticated technology appropriate for each

organ system, and emphasizing rather than excluding such subpopulations as

infants who are SGA or premature should yield valuable insights into the

outcome of the offspring of substance-abusing women,

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ACKNOWLEDGMENT

The research described in this chapter was supported in part by National

Institute on Drug Abuse grant R01-DA-06556-011 and Project BRH-P01010-02,

Bureau of Maternal and Child Health and Human Resources Development

(Section 301, Public Health Service Act), Human Resources and Services

Administration, Department of Health and Human Services.

AUTHOR

Emmalee S. Bandstra, M.D.

Associate Professor of Pediatrics and Obstetrics and Gynecology

Department of Pediatrics (R-131)

Division of Neonatology

University of Miami School of Medicine

P.O. Box 016960

Miami, FL 33101

227
Methodological Issues in the

Assessment of the Mother-Child

Interactions of Substance-Abusing

Women and Their Children

Dan R. Griffith and Catherin Freier

INTRODUCTION

One research question in evaluating the long-term development of infants

exposed to drugs in utero is the degree to which maternal behavior might

exacerbate or compensate for the neurobehavioral deficits commonly observed

in drug-exposed infants. To build an optimal maternal-infant relationship,

mother and infant must have the behavioral repertoire and the adaptability to

respond appropriately to the stimulation provided by the other. If the infant has

difficulties responding to environmental demands in an organized fashion, then

it becomes the responsibility of the mother to sustain the mother-infant

relationship by modulating her stimulation to fit the information-processing

needs of the infant (Horowitz 1984). When the mother is unable to fulfill this

function, the infant is likely to be exposed repeatedly to experiences that

overwhelm him or her and impede rather than facilitate development (Solnit

1984). When examining the relationship between substance-abusing women

and their prenatally drug-exposed children, one must evaluate the behavioral

characteristics of the infants (especially as these shape the mothers

behaviors), the personality and behavioral characteristics of the mother, and the

myriad of variables that affect both the infant’s and the mother’s behavioral

repertoires.

One of the major variables that affects maternal behavior is the child (Sameroff

and Chandler 1975). Many cocaine-exposed newborns, for example, have

been described as having fragile, disorganized, easily overloaded nervous

systems that leave them ill-equipped to organize and respond appropriately to

information from their internal or external environments (Chasnoff et al. 1985,

1989; Griffith 1989). The caretakers of these infants are required to limit their

interactions with the infants to those relatively few behaviors that do not exceed

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the cocaine-exposed infants’ low threshold for overstimulation. There is

variability from mother to mother as to how they respond to this requirement.

Some become increasingly frustrated with their failures to engage their

unresponsive infants until they reach the point of emotional detachment from

the infants and avoid any interactions with them. Other mothers continually

overstimulate their infants as if to compensate with their own excessive activity

for the infants’ lack of responsiveness.

Beyond the impact of the infant on the mother’s effectiveness as a parent,

many drug-using women share several characteristics that researchers have

found to interfere with the parenting abilities of drug-free women and may affect

the long-term outcome of their children. In the authors’ research population, for

example, 65 to 60 percent of the women at any point in time can be classified

as being of low socioeconomic status (SES). Researchers have indicated that

non-drug-using mothers from low-SES backgrounds tend to provide less

stimulation of an appropriate type to their infants. They vocalize to their infants

less often than mothers from middle-SES backgrounds (Field 1980) and, as a

group, decrease their interactions with their children as they grow into toddlers,

whereas mothers from middle-SES groups tend to increase their interactions

with their children (Farran and Ramey 1980).

Many of the drug-using women from the authors’ research population live

in high-stress environments. Many women are victims of sexual and/or

physical abuse, and about 70 percent are single parents with few sources of

social support. Crnic and colleagues (1983a) found that drug-free women

experiencing high stress with few social supports had greater relational

difficulties with their infants than mothers with either low levels of stress or

high levels of social support. Crnic and coworkers posited further that

relational difficulties experienced by mothers under stress may create greater

stress, thus compounding the relational difficulties.

A final common characteristic shared by the drug-using women participating in

the authors’ research is a high incidence of psychopathology. Of the women

on whom the authors have collected Minnesota Multiphasic Personality

Inventories (MMPls) during their pregnancies, 71 percent have had at least

one clinical scale score greater than or equal to 70. These elevated scores

have been shown to be predictive of poor interactive capabilities as measured

by the Brazelton Neonatal Behavioral Assessment Scale (NBAS) (Brazelton

1984) in the cocaine-exposed infants at 1 month of age (Griffith et al. 1989).

The authors found that 23 percent of the women completing the MMPI had

depression scale scores greater than or equal to 70. Several researchers have

linked maternal depression to poor-quality maternal-infant behaviors (Field et al.

1990; Cohn et al. 1990).

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Unfortunately, relatively few research projects have provided systematic

analysis of the relative contribution of maternal risk factors, child risk factors,

and interaction among factors to the continued socioemotional, behavioral, and

intellectual development of drug-exposed children. Studies that have looked at

some of these variables are reviewed in this chapter following a discussion of

the methods used and the methodological issues faced when assessing

mother-infant interactions with any population.

METHODS AND METHODOLOGICAL ISSUES IN THE ASSESSMENT OF

MOTHER-INFANT RELATIONS

A range of techniques has been used in the study of mother-child interactions.

Maternal questionnaires have been designed to assess maternal attitudes

toward the fetus (e.g., the Maternal-Fetal Attachment Scale [Cranley 1981]),

the neonate (e.g., the Neonatal Perception Inventory [Broussard and Hartner

1971]), the infant, the child, the demands of childrearing/child care, discipline,

and social support systems (e.g., the Maternal Social Support Index [Pascoe et

al. 1987). Several maternal questionnaires and behavioral checklists have

been developed to assess maternal perceptions of the child’s temperament and

characteristic behavior (e.g., the Infant Characteristics Questionnaire [Bates et

al. 1979] and the Infant Temperament Questionnaire [Carey and McDevitt

1978]).

However, the method with the greatest potential to give information on how

infant behaviors affect mothers and vice versa is the direct observation of

mothers and infants interacting with each other. Direct observations of

mothers and their infants have been made in the home and in the laboratory,

in structured and unstructured situations, focusing on a range of maternal and

child behaviors and using a variety of recording techniques. Regardless of the

specific observational methods chosen by a researcher, there are numerous

issues that affect the reliability and validity of the data collected.

Interrater Reliability During Mother-Infant Observations

The first research decision to be made when evaluating mother-infant

interaction is which behaviors to observe. The specific behavior chosen will

vary depending on the age of the infants or children being studied, which aspect

of mother-infant interaction is being studied, and the theoretical model of the

researcher. Regardless of the specific behaviors chosen, it is important to

provide explicit behaviors that can be defined in precise terms to achieve

acceptable levels of interobserver reliability (Ramey et al. 1978; Field 1977;

Bakeman and Brown 1980a). To provide an adequate representation of

behavioral differences among groups, one should select behaviors that are

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likely to occur in the populations being studied (Field 1977; Bakeman and

Brown 1980a). A final consideration is the degree to which observers can

reliably score the behavior without extensive training. This has the practical

advantage of saving time in the training of observers for the research team that

has designed the system and also increases the availability of the tool for use

by other researchers with other populations (Ramey et al. 1978).

The reliability of observational data can be affected by the method used to

establish interrater reliability. Lytton (1971) and Ramey and colleagues (1978)

cited research evidence that indicated that interobserver reliability dropped off

rapidly in observation episodes where the observers did not expect their

reliability to be checked. Ramey and colleagues (1978) suggested that perhaps

the most efficient way to maintain vigilance on the part of observers and,

consequently, high interobserver reliability would be to have observers score

their observations from videotape while informing them that random reliability

checks would be made of their scoring. Because of this potential loss in

reliability, Ramey and coworkers (1978) urged researchers to exercise extreme

caution when interpreting data that were scored during live observations. The

interobserver reliability for data collected live may be improved by having two

observers rate the behaviors simultaneously (Bakeman and Brown 1980a).

However, this technique, in additlon to requiring increased demands on the

observers’ time, would seem particularly obtrusive, especially for in-home

observations. An additional advantage of videotaping observational sessions is

that the events are preserved as they occurred. This allows for the analysis and

scoring of new behavioral dimensions as the researcher’s focus changes or

theoretical framework evolves.

A final issue regarding interrater reliability involves the statistical method used

to calculate the level of reliability. According to Ramey and colleagues

(1978), the two general methods for establishing interrater reliability are by

(1) correlating the total scores obtained by independent observers for particular

behaviors across observational sessions or (2) computing the percent of

agreement between independent observers on the occurrence of particular

behaviors. Ramey and colleagues (1978) stated that the preferred and most

rigorous method of estimating Interrater reliability is to compute percent

agreement by dividing the number of agreements between observers by the

number of agreements plus disagreements. This is particularly true if one

wishes to analyze the conditional probabilities of specific sequential

relationships among different behaviors (Ramey et al. 1978).

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Validity of Observations of Mother-Infant Interactions

One of the key validity issues for any observational study is the degree to

which the behaviors observed are an accurate reflection of the usual or typical

interaction between mother and infant. Perhaps the biggest threat to the

validity of observational data is the alterations that occur in maternal and infant

behavior because of the observer’s presence. The effect on maternal behavior

may be particularly significant if the mother knows or suspects which particular

behaviors the investigator is interested in observing. Researchers have tried to

deal with this issue by building a rapport with the mothers and visiting the

observation site frequently (Lytton 1971) or for a long enough period of time

(Thoman 1975) to habituate the subjects to the observers’ presence. Thoman

(1975), for example, began observing mother and infant separately and

together in the hospital nursery and then continued her observations in the

home where she spent 7-hour days with the family. She indicated that this

type of intensive observation combined with explanations to eliminate any

expectation on the part of the mother to interact with the observer seemed to

be effective in making the mother comfortable in the observer’s presence.

Thoman (1975) further noted, however, that this was only effective in reducing

the effects of observer presence up until the infant reached about 5 weeks of

age, at which time the infant began to watch the observer as well as the mother.

Beckwith and coworkers (1976) acknowledged and controlled for the presence

of the observer by including infant responses to the observer in their scoring

system.

Where the data are collected (either in the home or in the laboratory) and the

degree of control the researcher has over the situation (from highly structured

tasks to totally nonstructured situations) also affect the validity of observational

data. In spite of the previously noted observer effects, the home is probably the

best setting for deriving a sampling of maternal and infant behavior that most

closely resembles their usual mode of interaction. Observations in the home

allow the observer to gather firsthand information about the home environment

in terms of roles and activities of other family members, existence of appropriate

play materials, and the organizational level of the home, such as Caldwell’s

HOME (Home Observation for Measurement of the Environment) Scale (Elardo

et al. 1977). The home is the only place where truly unstructured observations

can take place. As soon as subjects enter the laboratory, they are exposed to

conditions that do not exist in their homes and that most likely alter their

behavior.

There are, however, several reasons why laboratory research is preferred.

The major advantage to laboratory research from a purely methodological

standpoint is the higher degree of control the researcher has over extraneous

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variables that might affect the subjects behavior. This type of control is

particularly important in studies where the researchers are attempting to

experimentally manipulate the behaviors of the mother-infant dyad to gain

information on cause-effect relationships between behaviors (Field 1977;

Gusella et al. 1988). Because the stimulus conditions affecting mothers and

infants vary from home to home, this type of control cannot be achieved even

with the addition of a structured task into the home environment (Lytton 1971).

One practical consideration in deciding where to observe the mother-infant

interaction is the lower costs of the laboratory study in terms of research hours

spent traveling from home to home as well as setting up and taking down such

technical equipment as video cameras. This is not an expense that can be

taken lightly when one considers the large numbers of subjects required to

unravel the relationships between mother-infant interactions and the myriad

of other variables that affect the outcome of the child. A second practical

consideration should be the safety of the observers. Many of the drug-using

women live in high-crime areas where a realistic assessment of the dangers to

observers must be made and precautions taken to ensure staff safety.

The decision to use structured vs. unstructured tasks depends in part on the

probability of occurrence of the behavior of interest. Structured tasks can serve

to prompt the subjects into performing specific behaviors that are unlikely to

occur otherwise. The structured tasks, however, do not allow one to draw

conclusions about the usual incidence rates for the behaviors observed.

Predictive Validity of Mother-Infant Interaction

Observations of mother-infant interactions have been used with varying

degrees of success to predict later mother-infant/child interactions

(Crockenberg and McCluskey 1988; Bakeman and Brown 1980a; Crnic et al.

1983b), the intellectual development of the child (Watt 1988; Watt and

Strongman 1985; Bakeman and Brown 1980b; Beckwith et al. 1976; Coates

and Lewis 1984; Pettit and Bates 1989), and the social/behavioral outcome of

the child (Jacobvitz and Sroufe 1987; Bakeman and Brown 1980b). Perhaps

the major difficulty faced by researchers trying to predict later behavior from

early mother-infant interactions is the ever-increasing and changing behavioral

repertoire of the infant, which in turn demands changes in the mother’s

behaviors. Furthermore, those behavioral aspects of mother-infant interaction

that may be important at one stage of development may have little importance

later on (Thoman 1975; Watt 1986). In fact, variability in infant behavior and

maternal behavior over time is probably the best sign of a healthy, fully

functioning dyad.

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Researchers have tried several solutions to the problem of predicting long-term

outcome from discontinuous development. Many researchers have attempted

to summarize the data collected on the incidence and/or duration of all discrete

behaviors observed into relatively global categories representing different types

of behavior. The decision as to which summary categories to create is often an

intuitive one based presumably on the authors’ hypotheses concerning motherinfant interactions. Coates and Lewis (1984), for example, in a study of full-term

infants at 3 months of age and their mothers, summarized maternal behaviors

observed into distal and proximal behaviors, vocal responsivity, responsivity to

distress, tactile responsivity, total amount of stimulation, and interaction level

(based on the total number of lo-second intervals where both maternal and

infant behaviors occurred). Using regression analysis, they found significant

relationships between maternal behaviors when the infant was 3 months old

and the child’s cognitive performance at 6 years. However, these results are

difficult to interpret, in part due to the lack of any maternal-infant interaction

assessment beyond the 3-month level and also due to their counterintuitive

nature. Coates and Lewis (1984) found, for example, that there was a negative

relationship between the amount of time mothers stimulated their infants vocally

at 3 months and reading achievement tests at age 6 years. Credibility of such a

finding would require much more information about what occurred between

mother and child during the intervening 5 years, 9 months between

assessments.

Jay and Farran (1981), in analyzing their observations of 3-year-olds and their

mothers, used four summative measures of behavior: total time spent in mutual

interaction, time spent in passive involvement, frequency of interactive behavior,

and frequency of controlling behavior. Using a stepwise multiple regression,

they found that each of the four summative behavior measures accounts for a

significant portion of the variance in the children’s 3-year Stanford-Binet IQ

scores and their 5-year Wechsler Preschool and Primary Scale of Intelligence

IQ scores. This study, however, only assessed children and their mothers at

one point in time. Consequently, nothing can be said about the predictive

validity of the mother-infant interaction.

The use of researchers’ intuition to select summative behavioral categories

makes it particularly difficult to interpret nonsignificant research findings. For

example, if a researcher finds no difference between mother-infant interactions

in preterm vs. full-term dyads, is it because there are no differences or because

the researchers chose the wrong summative categories? A number of

researchers have avoided this problem by allowing the behavioral data to select

the summative categories through factor analysis. Beckwith and colleagues

(1976), for example, observed and coded the behavior of premature infants and

full-term infants at 1, 3, and 8 months from the expected dates of birth for the

234
preterms and the actual dates of birth for the full-terms. Factor analyses of

behaviors at each observation period revealed five behavioral factors at 1

month of age (social interaction, responsive holding, verbal stimulation, mutual

gazing, and stressful holding), five behavioral factors at 3 months of age

(responsive social, mutual gazing, physical contact, control, and interference),

and four behavioral factors at 8 months of age (responsive social, intellectual

stimulation, control, and floor freedom).

It is important to note that the results of this study reflected the continuity and

discontinuity of mother-infant interactions over time. The social responsiveness

transcended all the observation periods, but the overall constellation of factors

changed with the children’s ages. Regression analyses revealed further

that different factors at each observation age were significantly related to

developmental outcome measures collected at age 9 months. Mutual gazing

at 1 month of age was predictive of success on a series of Piagetian tasks at 9

months but not of Gesell Developmental Quotient (DQ). Control at 3 months of

age was predictive of Gesell DQ at 9 months. For 8-month-olds the amount of

floor freedom they were allowed was predictive of Gesell DQ at 9 months.

In addition to creating summative behavioral categories, several researchers

have added global rating scales to their assessments of mother-infant

interactions in an effort to increase predictability. Jay and Farran (1981)

measured the overall impressions of observers about mothers interacting

with their 3-year-olds on three five-point rating scales assessing degrees of

maternal involvement with the child, maternal control of the child, and maternal

acceptance of the child. They found these global ratings to be better predictors

of the children’s IQ scores at ages 3 and 4 years than were the summative

measures of behavior that were generated during observation.

Crnic and coworkers (1983b) assessed the frequency, duration, and sequence

of infant and maternal behaviors in preterm and full-term dyads at 4, 8, and 12

months following hospital discharge. They found little consistency in specific

maternal behaviors or infant behaviors over the three assessments and were

not able to differentiate preterms from full-terms in terms of specific measures.

However, they were able to find significant results when using a summary

measure of maternal behavior (total amount of maternal activity) and global

ratings of maternal and infant affect collected at each assessment. These

measures indicated that mothers of preterm infants, compared with those of

full-term infants, were more active and displayed less positive affect when

interacting with their infants across the first year. Similar to their mothers, the

premature infants displayed less positive affect than the full-term infants across

the first year.

235
Finally, Jacobvitz and Sroufe (1987) in a prospective study, assessed behavior

of mothers toward their infants/children at 6 months, 24 months, and 42 months

of age using global rating scales at each age. At the 8-month assessment they

used a nine-point maternal interference rating scale estimating the mother’s

tendencies to disrupt the baby’s ongoing activity with her activities or intrusions.

At the 24-month assessment they used a scale rating maternal seductiveness.

At 42 months they assessed maternal overstimulation while the children were

engaged in a frustrating task. Mothers who provoked and teased their already

frustrated children rather than providing calm reassurance were scored as

overstimulating. At 6 years of age, 34 of the original 287 children who began

the study were diagnosed with attention deficit disorder with hyperactivity (ADDH) based on Diagnostic and Statistical Manual III criteria and were compared to

a matched control group of non-ADD-H children from the original research

population. Results indicated that the mothers of ADD-H 6-year-old children

were significantly more interfering at the 6-month assessment and significantly

more overstimulating during the 42-month assessment than were the mothers

of non-ADD-H children.

A final method through which researchers have tried to capture the stable

essence of mother-infant interaction and thereby improve long-range

predictability is by assessing what Tronick and Cohn (1989) refer to as the

coordination of mother-infant behavior. Watt (1986), for example, looked at the

relationship between mother-infant interaction in premature infants at 2 to 3

months corrected age and the infants’ Bayley Mental Development Indices

(MDI) at 6 months corrected age. When looking at mother behaviors or infant

behaviors in isolation, Watt found that, at 2 to 3 months, infant vocalizations

were negatively related, whereas maternal vocalizations were positively related

to 6-month Bayley MDI scores, This finding suggests a counterintuitive

negative relation between early infant vocalizations and later cognitive

development as well as a negative relation between rates of maternal and infant

vocalization at 2 to 3 months of age. By looking at infant behavior and its

synchrony to maternal behavior, however, Watt found infant vocalizations in the

absence of accompanying maternal behavior to be negatively related, whereas

infant vocalizations coordinated with maternal vocalizations were positively

related to 6-month Bayley MDI scores.

Bakeman and Brown (1980a) studied maternal-infant interactions in full-term

and preterm infants during feeding sessions at the time the infants were

released from the hospital and 1 month and 3 months postdischarge. When

analyzing the frequency and duration of discrete infant behaviors, they found a

number of differences between preterm and full-term infants at discharge that

had disappeared by the 1-month and 3-month followups. Persistent differences

238
were found, however, between preterm infants and full-term infants when

interaction patterns between infants and their mothers were examined. Preterm

infants were significantly more static in their patterns of interaction, more

frequently required maternal initiation of interaction, and were more likely to

be the ones to break off an interaction with their mothers. However, these

differences did not prove predictive of either cognitive or social abilities of the

infants when assessed at age 3 years (Bakeman and Brown 1980b). Bakeman

and Brown (1980b) attributed this lack of predictability at least in part to the

restriction of their observations to the feeding situation. They further posited

that the size of their sample was probably too small to pick up whatever weak

effects early interaction might have had on the child’s behavior years later.

As mentioned earlier in this chapter, there have been relatively few published

studies exploring mother-infant interactions within substance-abusing

populations. Lief (1985) and Chasnoff and Griffith (in press) have presented

descriptions of drug-using mothers based on clinical observations. A few

additional studies have directly assessed the parenting abilities of drug-using

women. Bauman and Dougherty (1983) assessed mother-child interaction in a

group of methadone-maintained women and their 2- to 6-year-olds compared

to a group of drug-free women and their similarly aged children. They found,

using summative measures of behavior, that methadone-maintained women

engaged in more aversive behaviors (i.e., provoke, threaten, and command)

than did drug-free mothers. They also found significantly more aversive

behaviors, especially complaining, emanating from the children of methadonemaintained women. Bauman and Dougherty further found the methadonemaintained mothers to be less adaptive as measured by their California

Psychological Inventory profiles.

Jeremy and Bernstein (1984) and Bernstein and coworkers (1984) also found

differences between methadone-maintained women and drug-free women

on interaction with their 4-month-old infants and psychological resources.

However, they carried their analyses a step further to examine the degree to

which drug use per se vs. poor psychological and psychosocial resources

were related to maternal interactive performance. Their findings indicated that it

was not drug use but the level of resources that was most predictive of

maternal interactive performance (Jeremy and Bernstein 1984). Bernstein and

colleagues (1984) made another important point that is too often overlooked

when substance-abusing mothers are discussed. They indicated that there

was a range of differences in maternal interactive performances among the

methadone-maintained women observed. About half the methadonemaintained women fell in the average range for interaction and about a third

of these did so in spite of having poor maternal resources.

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The data on the specific characteristics of mother-infant interactions among

drug-using populations are still rather sparse. A recent symposium presented

at the 1990 International Conference on Infant Studies, however, indicated that

several researchers are in the process of studying this population. Hans and

colleagues (1990) presented data indicating an interactive effect on maternal

behaviors between methadone use and psychopathology in mothers. Mothers

using methadone and diagnosed as having antisocial personality disorders

were significantly more dysfunctional in their interactions with their 24-montholds than were drug-free mothers. Mothers using methadone and having no

significant psychopathology or having affective disorders did not differ from the

drug-free mothers in their interactions with their children.

Rodning and colleagues (1990) presented data indicating that phencyclidineusing mothers and their extended family members demonstrated significant

deficits in their interactive performance with their 3- and 9-month-old infants

compared with drug-free mothers’ interactions with their children at the same

ages.

O’Connor and colleagues (1990) presented information indicating that maternal

alcohol consumption during pregnancy and the mother-infant interactions

between alcohol-using women and their 1-year-old infants both contributed

significantly to the variance in infant attachment behavior at 1 year.

INFANT TEMPERAMENT

Perhaps the most neglected area of mother-infant interaction research is the

contribution that the infants’ enduring characteristic temperaments have on the

relationship over time. Several approaches have influenced the manner in

which temperament is measured. Thomas and Chess’ (1977) approach to

temperament is the most widely cited and defines temperament as a behavioral

style or the “how” of behavior and rules out the content of behavior. It is seen

as a “goodness of fit” approach that emphasizes an interactive orientation of

the individual’s temperament characteristics and the environment. Buss and

Polmin (1975) divide temperament into four dimensions that are not specific

to content: emotionality, activity, sociability, and impulsivity. Rothbart and

Derryberry (1981) differ from this approach as they incorporate emotion-specific

content. Although these theorists approach temperament from different angles,

they all identify three major substantive issues for temperament research:

(1) biological contributions, (2) stability, and (3) influence on interpersonal

relationship.

238
Types of Instruments

Four methods have evolved for the measurement of temperament: parental

interviews, parental questionnaires, structured professional observations, and

home and laboratory observations.

Parent lnterviews and Parental Questionnaires. Most temperament

measures have been based on the nine temperament categories derived from

the New York longitudinal study (Thomas et al. 1968). The most widely used

infant-child temperament questionnaires are Baby Behavior Questionnaire

(Bohlin et al. 1981) Infant Behavior Questionnaire (Rothbart 1981) Infant

Characteristics Questionnaire (Bates et al. 1979), Infant Temperament

Questionnaire (Carey and McDevitt 1978), Toddler Behavior Questionnaire

(Hagekull and Bohlin 1981), Toddler Temperament Scale (Fullard et al. 1984),

Behavioral Style Questionnaire (Hegvik et al. 1982) and Parent Temperament

Questionnaire (Thomas and Chess 1977).

Structured Observatlons. Although sacrificing the depth of knowledge about

the child that the parental report provides, structured observations made by

trained examiners also provide measures of temperament. The most prominent

instruments used are the NBAS (Brazelton 1984) and the Bayley Infant

Behavior Rating Scale (Bayley 1969). These scales were not developed for

the intent of temperament assessment, and thus, both have weaknesses when

used for this purpose.

Home and Laboratory Observations. Laboratory and home observations

as measures of temperament have become more widely used. These

observations are typically done by observing certain specified interactions

(e.g., playing games, doing measurements, interactions with mother, and

interactions with strangers). These observations are videotaped frequently

and then are rated by observers using rating scales.

Advantages and Disadvantages of Types of Measurement

Parental interviews and questionnaires offer the possibility of obtaining

considerable data at low cost but have been criticized on several grounds.

The mother’s perception is seen to compromise objective determination of

the infant’s temperament. The mother’s responses are affected by prior

interactions between parent and infant. The psychometric properties of these

measurements have received little attention. These measures are criticized

most often as being colored by the personal involvement of the mother as the

observer. In contrast to this is the argument that the strongest asset of parental

reports is that they represent the distillation of innumerable observations

239
extended over time and events. As Carey (1983) points out, for the purposes of

some studies, the caregiver’s perception of the infant’s temperament may be

precisely the construct of importance.

Structured and observational laboratory and home assessments are relatively

free of subjective influence: These observations by trained observers may yield

more objective measures of temperament, but by necessity the periods of

observation are short and the range of naturalistic situations is constrained.

Consequently, the behaviors expressive of temperament may not be fully

displayed within this narrow observation, If these observations are not

structured so as to be common to all infants, the comparisons among infants

may be limited. Another criticism of these measures is that they need to be

modified to maximize individual differences.

Current Trend of Use In Research

Temperament research commonly focuses on certain mother-infant dyads that

may be of special clinical need, such as adolescent mothers, single-parent

mothers, twins, developmentally disabled infants, premature infants, small-forgestational-age infants, and infants with minimal brain dysfunction (MBD). The

authors are not aware of published studies of temperament with infants or

children who have had perinatal exposure to illicit drugs.

Studies that have focused on stability of temperament have had difficulty with

interpretation of results and predictability for several reasons: (1) The use of

different temperament measures at different ages may reflect the measurement

of different constructs; (2) in infants who have unique problems (e.g., motor

abnormalities/drug exposure), temperament may be more difficult to test as the

child gets older because such constructs as “activity” or “state regulation” may

not be appropriately tested by current measures; and (3) infants mature at

varying rates.

Recently, researchers have emphasized the need for multiple and even crossmethod assessment of temperament within the research or clinical setting. This

approach has been proposed to enhance predictability as correlations between

questionnaires and direct observations fall within the 0.20-0.50 range (Bates et

al. 1979; Rothbart and Derryberry 1981; Wilson and Matheny 1983).

Implications

Knowledge of the infant’s or child’s temperament enhances research in several

ways. Explaining temperament to the mother can help her to better understand

her child. It provides the clinician/researcher with an objective method of

240
interpreting the child’s contribution to the mother-infant interaction.

Temperament-environment interaction information may help clarify the

developmental outcomes of these children. Many studies have linked

temperamental patterns of the difficult child to behavior problems (Thomas

et al. 1968; Graham et al. 1973; Mclnerny and Chamberlain 1978). If certain

children can be identified at an early age as being at risk for behavior problems,

it may be possible to intervene and teach mothers healthier ways to interact

with their difficult children. It also may help to answer questions of future

socialization in these children, because an important feature of temperament

is its role in regulating social interaction.

Temperament research with perinatally drug-exposed infants and children may

involve several unique considerations. Due to drug exposure, these infants

tend to be more fussy and irritable at birth. It is difficult to know whether these

infants’ behaviors are a stable part of temperament or a result of drug exposure

that will change as these children develop. It is also important that drug

exposure is not diagnosed on the basis of temperament: Not all fussy/irritable

infants are drug-exposed infants. Furthermore, it is not likely that all drugexposed infants will have temperaments known as the “difficult child.” Carey

and coworkers (1979) examined MBD children and concluded that, although

many MBD children have “difficult” temperaments, some fell into the other

temperament types. Coll and colleagues (1982) emphasize that difficult

temperament in infants with state organization difficulties may be an interaction

between the infant’s unique organization of state behavior and the mother’s

response to the infant. This may change as the child develops, making it

difficult to demonstrate predictability and stability of temperament in these

infants. Perinatally exposed infants have a compromised central nervous

system that is reflected in their state organization. In the authors’ research,

these infants are less alert at 1-month observations. Crockenberg and Acredolo

(1983) have observed that infants who are more irritable at birth are less alert

at 1 month. Infants who have irritable temperaments and are less alert have

less involved contact with their mothers, and interaction is strained. Bell and

Ainsworth (1972) concluded that maternal behavior should be recognized as

a determinant of infant irritability over the first year of life. Drug-dependent

mothers have many expectations of the infant and have ineffectual coping

mechanisms that may contribute to infant irritability.

Despite these confounds, questions asked in the right way will provide

important data. However, researchers should use both parental reports and

professional observations in evaluating infant and child temperament. Studies

(Crockenberg and Smith 1982; Crockenberg and Acredolo 1983) also have

demonstrated the need to evaluate not only infant temperament but also the

mother’s characteristics and mother-infant interaction. Antecedent mother and

241
infant characteristics contribute significantly to the prediction of mother behavior

and mother-infant interaction.

CONCLUSIONS

Research into the factors that contribute to the optimal socioemotional,

behavioral, and intellectual development of drug-exposed children is just

beginning. The authors believe that this research must be multimethod and

collect, at the least, detailed information on the child, the mother, interactions

between the mother and child, interactions by mother and/or child with other

family members, and the home environment.

Information on the child should include repeated medical, developmental,

and behavioral evaluations from birth on to begin to differentiate those

behaviors/characteristics of the child that are enduring over time and those

that are affected by the environment. This information should be gathered

from standardized tests assessing a range of capabilities, parental interviews,

questionnaires assessing parental perceptions of the child’s behavior and

temperament, and observations by trained observers of the child’s behavior

over time in a variety of structured and unstructured situations.

Information about the mother and other significant adults in the child’s life

should include a detailed, lifelong drug-use history; information on the family

of origin; evaluation of personal resources (intelligence, education, support

systems, and psychological functioning before and after having the child, if

possible); questionnaires or interviews assessing attitudes toward self and

child; and direct observations of behavior by trained observers.

Assessments of mother-infant interactions (or interactions between the child

and/or mother and any other person) should include discrete maternal and

infant behaviors that are defined explicitly and occur regularly between mothers

and infants. Interrater reliability either should be checked continuously with

simultaneous observers or performed randomly on videotaped observation to

maximize reliability. Repeated assessments should be done in a variety of

situations to identify the continuous and discontinuous elements of interactions.

For maximum predictive validity of observational data from mother-infant

interactions, a combination of scoring systems is recommended, including

discrete infant and maternal behaviors, summative behavioral categories, and

global ratings by trained observers of the quality of the interactions. Predictive

validity will be enhanced further by analyzing the sequential patterns or

coordination of maternal and infant behaviors.

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Only by collecting information from many drug-using mothers and their infants

from various socioeconomic backgrounds can factors be analyzed that are most

likely to add to or detract from the optimal development of drug-exposed

children.

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AUTHORS

Dan R. Griffith, Ph.D.

Developmental Psychologist

National Association for Perinatal Addiction Research and Education

Suite 200

11 East Hubbard Street

Chicago, IL 60611

Catherin Freier, Ph.D.

Research Assistant Professor of Pediatrics

University of Miami School of Medicine

R 131, P.O. Box 016960

Miami, FL 33101

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Discussion: Measurement Issues in

the Study of Effects of Substance

Abuse in Pregnancy

Claire D. Coles

INTRODUCTION

It has been fairly clear for many years that abusing substances during

pregnancy leads to a higher risk for the mother, the pregnancy, and the

offspring (Coles and Finnegan, unpublished manuscript). Increased use of

cocaine by high-risk populations has strengthened concerns about its potential

teratogenic effects because of the data generated by decades of research on

heroin, methadone, alcohol, and other drugs. Consequently, greatly increased

interest in the effects of cocaine use in pregnancy has generated more funds

and research on the subject. There is considerable confusion about this issue

due to emotional reactions by care providers, the media, and others in response

to the genuine and perceived threats involved with substance abuse during

gestation.

In attempting to investigate the issues of maternal addiction or drug use, the

effects on pregnancy, and the short- and long-term outcomes for the child, both

opportunities and problems arise. The chapters by Seiden, Bandstra, and

Griffith and Freier (this volume) outline clearly the valuable knowledge to be

gained by appropriate measurement of the areas of interest as well as the

potential difficulties that must be circumvented. This chapter discusses sources

of some hazards to accurate measurement and suggests some partial

solutions.

ISSUES INVOLVING MEASUREMENT OF WOMEN USING DRUGS IN

PREGNANCY

What Is the Construct Under Study?

At the present time, there is a good deal of confusion about cocaine’s effects on

pregnancy and the developmental outcomes for offspring. Several different

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factors have become intermingled. In designing meaningful research,

investigators have to decide what it is they want to measure. The first issue is

whether they are going to measure only the teratogenic effects of cocaine or

whether they are looking at the outcome of polydrug use. Polydrug use must

be investigated since there is no population of any size to study that is using

only cocaine. Nevertheless, studies continue to be proposed and reported as

though the issue of exposure were simple and unambiguous. Unquestionably,

it would be of great interest to isolate the effects of cocaine in the absence of

confounding factors. However, this cannot be done adequately in human

samples except through the use of sophisticated statistical procedures (see

Ager, this volume).

A second issue is whether researchers are investigating the consequences

of cocaine and other drug exposure or of associated variables such as the

process of addiction or the effects of lifestyle. For example, would the same

consequences occur if the drug under study were not illegal and, therefore,

associated with a particularly deviant lifestyle? If cocaine could be purchased

legally at the local convenience store it surely would continue to cause physical,

emotional, and social damage as does its frequent associate, alcohol, but there

might not be as many infants suffering the effects of sexually transmitted

diseases, acquired immunodeficiency syndrome, and lack of prenatal care

occasioned to some degree by their mothers’ fear of being identified as

substance abusers.

In deciding on the construct to be investigated it is also important to discriminate

between “use” and “abuse.” This distinction appears to be recognized

conceptually in the investigation of alcohol. However, in dealing with illegal

substances, particularly with cocaine, often there is no attempt to define what

constitutes abuse, with the result that all use is assumed to be abuse, and

people are lumped together into categories like “cocaine addicts” or “crack

babies.” Some proposals for intervention and treatment programs do not even

attempt to measure impairment or addiction but assume that any baby with

a urine positive for cocaine has been born to an addict who will require a

protective service referral and drug treatment. Similar assumptions would not

be made if the drug in question were alcohol, nicotine, or caffeine. Aside from

the moral and ethical implications of this simplistic thinking, the problems in

methodology and data interpretation that ensue are potentially serious with

regard to social policy implications.

How Will Exposure Be Measured?

If researchers are not sure of the construct (e.g., the agent of exposure),

deciding how to measure it is difficult at best. Still, it might be decided that

249

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interest centers on the teratogenic effects of cocaine and associated drugs, with

lifestyle and addiction issues treated as confounders. But having made this

decision, researchers are faced with a new set of measurement issues because

there are certain rules about how to measure the effects of a teratogen

(Vorhees 1986). Level of exposure (dose), timing during pregnancy, and

duration are all important in determining how the offspring is affected. When

dealing with legal drugs, these factors are difficult to measure even though the

nature of the teratogen can be fairly well defined. That is, given that the

pregnant woman will report what she was drinking or smoking, how much, and

how frequently, the government can be relied on to have regulated the dose,

and the exposure can be calculated. The problems that arise do so because

self-report may not be reliable and because there are no biological tests that

can be used to confirm self-report (Barrison et al. 1982).

However, these are only minor issues compared with those that arise when

dealing with an unregulated commodity like cocaine. At the present time, there

is no way, including self-report, to establish amounts used. Terms used to

describe various quantities of cocaine in various forms (e.g., ball, rock, can,

line) do not have specific referents in the same way that the term “ounce” does.

Similarly, cocaine, like other illegal drugs, is cut to various degrees and with a

variety of other substances so that the amount and kind of exposure may vary

in this way also. These problems, added to the difficulties inherent in selfreport, make establishing any kind of classic dose/response curve from

nonlaboratory studies impossible.

Establishing Use: Some Other Problems in Measurement

There has been debate about how to identify women who are using cocaine

and how to monitor use (Zuckerman et al. 1989). Advocates of urine screens

and other biological measures point to the unreliability of self-report, and they

may select samples based on outcome of screens of infants or postpartum

women. These screens may be done on all women delivering in a particular

hospital, on women in treatment programs, or on women who are considered

“at risk” because they are minority women who did not receive prenatal care.

The biases inherent in such approaches should be obvious (this volume, see

Bracken et al.; Ostrea; Sokol et al.; Kidwell).

Advocates of self-report usually argue that the urine screen is inadequate as a

measure of use since it is confined to a particular point in time and tells nothing

about frequency or extent of use. They prefer to use repeated interviews of

women, a process that allows evaluation of duration and extent of use over

gestation (Day et al. 1985).

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In a recently concluded study of the effects of cocaine and other drug exposure

on neonates, Coles and colleagues (in press) used both methods of

establishing use-repeated interviews of mothers and urine screens of mothers

and infants. Although aware of the measurement problems discussed above,

they at least hoped to establish that the infant was under the influence of the

drug at the time of initial assessment and to relate that exposure to infant

behavior. As table 1 indicates, even this modest hope sometimes was

frustrated.

TABLE 1. Consistency of measures of cocaine use among admitted drug

users (n=79) and controls (n=39)*

Maternal

Self-Report

Postpartum:

Use <7 days

Mother/Infant

Urine Status

(EMIT)† Percent Possible Interpretation

Negative

Positive

Both negative

Both positive

Negative

Positive

Both positive

Both negative

Negative Mother and infant

inconsistent

Positive Mother and infant

inconsistent

56.76 • Correct

20.34 • Correct

12.71 • Maternal report incorrect?

5.1 • Maternal report incorrect?

• Sampling error?

2.5 • Maternal report incorrect?

• Timing of sample?

2.5 • Correct?

• Timing of sample?

*All control urines were negative. No false-positives noted in this group.

†EMIT=enzyme-multiplied immunoassy technique

Drug-using women and nonusing controls were interviewed postpartum and

agreed to be tested using the EMIT screening test. Shown are the percentage

of cases in which maternal report and outcome of urine screens were consistent

or inconsistent. When the results were inconsistent there were several types of

inconsistencies. In some cases both mother and infant urine outcomes were

251
the same, but these results did not agree with maternal report. This outcome

suggests that maternal report was inaccurate. However, in other instances,

maternal report agreed with one or the other of the urine outcome reports but

not with the second urine screen. This outcome is harder to interpret, and it is

easy to see how such an outcome might lead to inaccuracies when urine

screens are used to establish maternal use or infant exposure.

Examination of table 1 suggests that although maternal report is frequently

accurate, in some cases it is not. However, given the inconsistencies in

outcome seen, it Is impossible to establish what factors are causing falsenegative reports. In addition to inaccurate reporting, other problems may

interfere with accurate results. Samples may be collected in a way that

interferes with accurate analysis or may be collected at the wrong time. Finally,

laboratory analysis may not be correct. In a Centers for Disease Control study

conducted in a variety of laboratories, the accuracy of urine screen analyses

ranged from 0 to 100 percent (Hansen et al. 1985).

Given such data, it is difficult to be confident that infants always can be

classified correctly into the category “cocaine-positive,” particularly if only a

single screening measure is used.

ISSUES IN THE MEASUREMENT OF THE EFFECTS OF COCAINE AND

OTHER DRUG EXPOSURE ON INFANTS

In studying the effects of cocaine on infants, there are three layers of

measurement issues: (1) The usual infant measurement issues are still in

force, the most obvious of which is the discontinuity between neonatal

outcomes and later development (McCall et al. 1972), which leads to the

inability to measure constructs of interest in early infancy. This necessitates

longitudinal followup and the need to measure the “system” rather than the

individual. (2) Next are issues associated with measurement of teratogens and

drugs of abuse in general. These include the difficulty of discriminating among

the acute effects of prenatal exposures (and associated factors) and more

permanent deficits and the relatively small effects of substances of abuse on

infants when exposure is “moderate.” (3) Issues unique to the study of cocaine

include any specific effects of the drug that can be measured and the problem

of how to discriminate these effects from the “background” of other drugs and

lifestyle factors. For instance, if the use of cigarettes, alcohol, and marijuana

and the lack of prenatal care are all associated with low birth weight, how much

of the lower birth weight usually seen in “cocaine babies” is associated with

these other factors and how much with the drug under study? Will statistical

means be adequate to parcel out these effects? Is enough presently known

about the effects of these confounding factors to be able to establish the way in

which they affect the outcome measure that will be used?

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These are difficult issues and the most sensible approach at this early stage

may be to arrive at a good description of what is being investigated. Of course,

the ways this description will be carried out will be guided by previous

observations as well as by theory. For instance, whereas it is possible to

observe the cocaine-exposed infant in the neonatal period (always supposing

that he or she has been identified correctly), it may be impossible at this time to

discern the proportion of the child’s behavior that results from acute effects of

the drug vs. neurobehavioral alterations that will be associated with long-term

outcomes. However, to assume permanent brain damage in these

circumstances seems to be rash. Cocaine is a drug that has acute effects on

the autonomic and central nervous systems. At least as a beginning

hypothesis, therefore, should it not be assumed that behavioral alterations may

be related to these acute effects rather than assuming long-term damage?

Long-term effects only can be established by prospective followup, and such

studies usually have found that neonatal tests overidentify children at risk.

Another way to exercise restraint is to avoid being misled by analogies

(particularly verbal analogies). A common fallacy in this area results from the

current fascination with “attention disorders.” Most neonates show behavioral

alterations in the newborn period as a result of exposure to any drug. Such

alterations are usually apparent on the Neonatal Behavioral Assessment Scale

(Brazelton 1984) and often involve orientation and motor behavior. Orientation

often is described as the infant’s ability to pay attention to animate and

inanimate stimuli. From this observation, the assumption can be made that

attention will be affected at a later time and that drug exposure underlies deficits

in attention. However, there are at least two problems with this analogy. First,

the infant may be reflecting the acute effects of the drug rather than long-term

deficits; second, the neural systems that subsume orientation, a fairly primitive

response, and the ability to sustain attention in later childhood are probably

different. If the brain is sufficiently damaged, both systems may not work well,

but this may be a correlation rather than a direct relationship.

Correlations are particularly seductive when experimental control is impossible.

Correlation is not synonymous with causation. For instance, because a drugusing mother shows a particular response to a particular measure and the child

shows another deficit on a different test does not mean one caused the other.

In the absence of experimental control, there needs to be a good theoretical

reason, as well as several replications of the effect, before such a relationship is

interpreted as supporting evidence for causation. In addition, cross-validation is

necessary. Finding a pattern of relationships in a single sample does not

demonstrate that it is necessarily meaningful. The effect must be replicated in

other samples.

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Previous research on other substances of abuse (e.g., heroin and alcohol) has

much to say to those currently working on the effects of cocaine. At least one

finding has been identified consistently: Large environmental factors have

major effects on postnatal development. Small factors produce few effects,

which are often of short duration. Even factors like early intervention, which

have clear and beneficial effects, are not persistent when the environmental

changes are not maintained (Blumenthal 1989). Therefore, the investigator

should find ways to take into account not only the child’s status but also the

nature of the significant factors in his or her environment. These include

caretaking, social class, stability, social support, health, and family education,

which have been shown repeatedly to have a much greater effect on the child’s

outcome than prenatal drug exposure (in the absence of certain very damaging

circumstances) (Greene et al. 1991).

MOTHER/CHILD INTERACTION

Griffith and Freier’s chapter (this volume) presents clearly the issues involved

with the study of the interaction of substance-abusing mothers and their

children. They discuss the constraints and the advantages of various methods

of investigation of these phenomena. The authors also have identified an area

that is probably of great importance in understanding the outcome of

development in this group of children. Given the current status of research on

cocaine, which appears to suggest that the primary problems threatening

development in exposed children are preterm birth, polydrug exposure, and the

postnatal environment, understanding how the process of substance abuse (in

this culture and at this time) affects a woman’s ability to rear her children is of

great importance.

Because these issues have been so well outlined by Griffith and Freier, this

chapter comments instead on some potential issues in the study of such

relationships in a sample of addicted women and their children. First, it is

important to avoid overinterpreting the effects of neonatal behavior on maternal

response. Maternal feelings and behavior are influenced by several factors,

and the maternal/infant relationship may have different dynamics in the special

circumstances of addiction. Infant behavior has been shown to be a significant

factor in the relationship between preterms and their mothers in middle-class

samples and in disadvantaged samples. However, for the substance abuser,

the infant’s behavior, which may be temporary, may not be the most powerful

determinant of her perceptions and attitudes. These may be much more

influenced by her own feelings, her addiction process, her expectations (some

of them supplied to her by the media and by health care professionals), and

finally, by the nature and extent of her social support system. In research at the

Human Genetics Laboratory in Atlanta, the author and colleagues have found

254
these factors to be much more powerful in influencing maternal perception at 30

days postpartum than the child’s behavior, despite obviously aberrant infant

behaviors probably related to alcohol exposure (Coles et al., unpublished

manuscript).

Second, factors that influence children most are those that are consistent and

continuous. Maternal behavior and specific interactions will powerfully affect

the child only if the mother is the principal caretaker or an important presence

for her child. If her behavior is unpredictable; if she is inconsistently present; or

if she is emotionally unavailable due to her addiction process-these are all

factors that must be taken into account.

Finally, in this sample of children and mothers who are under great stress, it

may be necessary to adapt our thinking and the measures and methods that

have proved useful with middle-class samples. Different ways of measuring or

different ways of looking may have to be devised for the child growing up in a

housing project who has seen gun fights, killings, and police raids, who is often

unsure whether he or she will be fed, and who was born to a mother with a

substance abuse problem.

CONCLUSION

It appears that researchers are at a relatively early stage In understanding the

effects of cocaine on addiction; on the special treatment needs of women, in

particular, pregnant women and those with children: and on infant outcome.

Many questions remain to be asked, and there are several problems in forming

these questions. Given this situation, it may be appropriate to consider the

following:

1.

2.

Research should be directed at the appropriate level of investigation,

Should investigators look at the social system, family, mother, child, organ

system, or cell to find the effects of substance abuse? No single project

can answer all questions, but each should develop specific questions and

find measures to answer these. Researchers are still in the stage of

needing good epidemiological research and adequate descriptions of and

solutions to many methodological problems.

Given the great expense, effort, and potential risk involved with these

studies, the cost and benefit of various methods to be used should be

considered carefully. Should every cocaine-exposed child have a series of

expensive procedures in the absence of any evidence that these produce

meaningful effects? It could be argued that such procedures can wait until

more descriptive studies are done and the empirical and theoretical basis is

255
laid. However, a counterargument also could be made that, because the

cost to carry out such studies is so great, all available data should be

collected.

3. Although the study of some of these issues is just beginning, a body of

knowledge based on research findings already exists, and it seems

appropriate to consult it in generating hypotheses and in planning methods

for future work. This should be done with the rigor that is applied to any

other scientific effort so that preliminary results will not be overinterpreted.

For example, it was observed early in the process of clinical description that

several children exposed to cocaine also had intraventricular hemorrhage

(IVH). That these children were preterm and that such bleeds are common

in preterm children was not emphasized. Rather, an analogy was drawn

between infant bleeds and those of adults who had strokes as a result of

cocaine use. Further research now suggests that the incidence of IVH

does not appear to be higher in cocaine-exposed preterms than in

nonexposed preterms (Karmel et al. 1990), making inappropriate the

suggestion that all infants with cocaine exposure should have skull x-rays

or ultrasound studies. However, as Bandstra (this volume) points out, a

case can be made for investigation of some proportion of exposed infants

with these procedures.

4. “Falling in love with the test” is a problem mentioned by Campbell and

Stanley (1967). One also is reminded of the old saying, “To the man with a

hammer, everything looks like a nail,” when, in the rush to investigate the

horrible outcomes assumed to exist in children exposed to cocaine,

investigators have suggested a variety of measures. However, choice of

measures must depend on the problem to be studied. Just because a test

or a piece of machinery exists, does not mean that this procedure will be

important in the study of cocaine effects. Choice of measures should be

dictated by previous research, theory, and common sense.

5. Negative effects may indeed mean something. in reference to prenatal

cocaine effects on children it often is said that, “There must be something

there; we just haven’t found the test that will measure it.” This may be so.

However, it is important to continue to conduct investigations with the rigor

that would be applied to the study of any other phenomenon and not make

interpretations of outcome on faith but rather to use the methods of

scientific inquiry.

256
REFERENCES

Barrison, I.G.; Wright, J.T.; Sampson, B.; Morris, N.F.; and Murry-Lyon, I.M.

Screening for alcohol abuse in pregnancy. Br Med J 285:1318, 1982.

Blumenthal, J.B. “Parent/Child Development Centers in Birmingham, Houston,

and New Orleans: Program Description and Follow-Up Methods.” Paper

presented at the Symposium on Long-Term Effects of Early Intervention:

More Fuel for the Fire, at the biennial meeting of the Society for Research on

Child Development, Kansas City, MO, 1989.

Brazelton, T.B. Neonatal Behavioral Assessment Scale. 2d ed. Philadelphia:

Lippincott, 1984.

Campbell, D.T., and Stanley, J.C. Experimental and Quasi-Experimental

Designs for Research Chicago: Rand McNally, 1967.

Coles, C.D., and Finnegan, L.P. “Substance Abuse in Pregnancy:

Reproductive and Developmental Risk.” Unpublished manuscript.

Coles, CD.; Platzman, K.A.; Smith, I.E.; and Falek, A. “The Contribution of

Infant and Maternal Factors to the Perception of Behavior of AlcoholExposed Infants.” Unpublished manuscript.

Coles, C.D.; Platzman, K.A.; Smith, I.E.; James, M.E.; and Faiek, A. Effects of

cocaine and alcohol use in pregnancy on neonatal growth and

neurobehavioral status. Neurotoxicol Teratol, in press.

Day, N.L.; Wagener, D.K.; and Taylor, P.M. Measurement of substance use

during pregnancy: Methodologic issues. In: Pinkert, T.M., ed. Current

Research on the Consequences of Maternal Drug Abuse. National institute

on Drug Abuse Research Monograph 59. DHHS Pub. No. (ADM)87-1400.

Washington, DC: Supt. of Docs., U.S. Govt. Print. Off., 1985. pp. 36-47.

Greene, T.; Ernhart, C.B.; Ager, J.; Sokol, R.; Martier, S.; and Boyd, T. Prenatal

alcohol exposure and cognitive development in the preschool years.

Neurotoxicol Teratol 13:57-68, 1991.

Hansen, H.J.; Caudill, S.P.; and Boone, J. Crisis in drug testing: Results of

CDC blind study. JAMA 253:2382-2387, 1985.

Karmel, B.Z.; Gardner, J.M.; and Magnano, C.L. “Neurofunctional

Consequence of In Utero Cocaine Exposure.” Paper presented at the

Committee on Problems of Drug Dependence, Inc., Annual Meeting,

Richmond, VA, June 13, 1990.

McCall, R.B.; Hogarty, P.S.; and Hurlburt, N. Transitions in infant sensorimotor

development and the prediction of childhood IQ. Am Psychol 27:728-748,

1972.

Vorhees, C.V. Principles of behavioral teratology. In: Riley, E.P., and

Vorhees, C.V., eds. Handbook of Behavioral Teratology. New York:

Plenum Press, 1986. pp. 23-48.

257
Zuckerman, B.; Frank, D.A.; Hingson, R.; Amaro, H.; Levenson, SM.; Kayne,

H.; Parker, S.; Vinci, R.; Aboagye, K.; Fried, L.E.; Cabral, H.; Timperi, R.; and

Bauchner, H. Effects of maternal marijuana and cocaine use on fetal growth.

N Engl J Med 320(12):762-768, 1989.

AUTHOR

Claire D. Coles, Ph.D.

Director

Clinical and Developmental Research Project

Human Genetics Laboratory

Georgia Mental Health Institute

1256 Briarcliff Road, N.E.

Atlanta, GA 30306

Assistant Professor

Department of Psychiatry

Emory University School of Medicine

Atlanta, GA 30322

258
Studies of Prenatal Drug Exposure and

Environmental Research Issues: The

Benefits of Integrating Research

Within a Treatment Program

Karol A. Kaitenbach and Loretta P. Finnegan

INTRODUCTION

During the past 20 years, a literature on the effects of prenatal drug exposure

has developed. Concurrent with this growing database has been a recognition

that such research is embodied within a methodological enigma. The focus of

this chapter is on identifying environmental research issues that have an impact

on studies investigating the effect of prenatal drug exposure. Within this

context, two issues are discussed: (1) the need to ensure a scientific approach

in what is a most difficult field of applied research and (2) the need to employ a

model that addresses perinatal outcome within the framework of maternal

disease.

SCIENTIFIC METHOD

A basic tenet of research is the necessity for it to be systematic and controlled

if one is to have confidence in the data. That is to say, all variables that

produce an effect must be systematically separated from the variable or

variables under investigation. To separate confounding variables, an objective

set of rules for gathering and evaluating information should be defined clearly.

An objective set of rules demands that variables are operationalized,

representative samples are obtained, extraneous variables are controlled,

and the results can be replicated. Unfortunately, the most consistent feature

of outcome studies investigating the effects of prenatal drug exposure is an

absence of such control. The caveat that a number of confounding variables

could account for the findings of a study is offered repeatedly, either as a

qualification by investigators or as a criticism by reviewers. A list of potential

confounding variables present in this research can be constructed easily by

a review of the literature. Both between and within studies there may be

variations in amount and quality of prenatal care, assessment of withdrawal

259
symptomotology, use of pharmacotherapy, dose and duration of drug exposure,

and type of drug exposure. Often, this lack of systematic and controlled

research is excused on the basis of the degree of difficulty obtaining samples

within this population. Certainly, identifying and enrolling children born to drugdependent women in a research study presents both a practical and a scientific

challenge.

One of the most common approaches has been for investigators to identify

potential subjects at birth through the use of routine neonatal urine toxicology

screens, by urine toxicologies performed on “suspected infants,” or by

questioning “suspect mothers.” However, the last two approaches may lead

to biased samples. For example, if urine toxicologies are conducted only on

infants in whom there is some indication of prenatal drug exposure, the

sample may exclude infants who were exposed to drugs in utero but exhibited

no symptomatology. Similarly, reliance on the accuracy of maternal report,

especially when questions pertain to illicit drug use, may lead to a skewed

sample. However, whatever procedure is used to identify subjects in a

postpartum paradigm, documentation of prenatal drug use most often must

rely exclusively on maternal self-report, precluding any objective measure of

dose, duration, and type of drug use during pregnancy.

In the same manner, information pertaining to maternal health history obtained

either by maternal report or from medical charts may be limited. Again,

maternal self-report is often unreliable. And while one assumes that information

from medical charts is reliable, it may not be inclusive; and, as such, necessary

data may not be available. Another factor to be considered is that the amount

of maternal data collected is often a function of the length of hospital stay.

This constraint has several important implications. Minimum information may

be obtained because there is not enough time to conduct a lengthy maternal

interview; or, if extensive information is requested, maternal cooperation and

consent may be jeopardized because of an inability of the interviewer to

develop the necessary rapport. A lack of rapport also may affect the reliability

of the data in that it may be particularly difficult to establish positive rapport

among drug-dependent women within a short timeframe. A high incidence

of physical and sexual abuse both as children and as adults, psychiatric

comorbidity, involvement with child protective services, and involvement with

the judicial system have been found among drug-dependent women. Any of

these factors may impede the interviewer’s ability to establish the rapport

necessary for obtaining reliable information. Furthermore, if the woman has

been “identified” or “labeled” as an addict, her experiences with providers within

the health care system may have been negative. Pregnant drug-dependent

women often receive condescending and prejudicial treatment and, thus, tend

to have little trust in the system and less reason to cooperate with the system.

260
The punitive position reflected in the mandatory reporting regulations that

exist in numerous States does little to assuage this lack of trust. Clearly,

researchers who attempt to recruit a study population and obtain the wide

array of information necessary to define precisely the characteristics of their

sample, all within the timeframe of a 2- to 3-day postpartum hospital stay, have

a most difficult task.

A number of these issues can be addressed by conducting prospective studies

in which subjects are enrolled during pregnancy. Specifically, this approach

provides for the opportunity to obtain data on several maternal, medical, and

obstetrical variables that may be related to perinatal outcome and to obtain

qualitative and quantitative data on prenatal drug exposure. However, this

approach also can be limited and difficult. First, there is again the question of

obtaining a sample. In this model, two criteria define the study population:

pregnant and drug-dependent. If one uses the health care system and prenatal

care as the vehicle to obtain a sample, the method used to identify substance

abuse may affect the representativeness of the sample.

Second, if there is no integration of health care and substance abuse treatment,

project attrition is likely to be high, as the amount of prenatal care received by

drug-dependent women is often minimal. A lack of prenatal care is often a

function of the discriminating attitude and lack of understanding of the special

needs of this population present within the health care system. Furthermore, if

one is investigating perinatal outcome as a function of drug exposure, a lack of

prenatal care can be a significant confounding variable. An apparent solution

would be to obtain study samples from drug treatment programs. However,

although drug treatment programs would provide subjects that meet the drugdependent criteria, they often do not provide for women who are pregnant. The

availability of treatment programs for pregnant women is minimal. For example,

Chavkin (1990), at the Columbia University School of Public Health, found that

54 percent of New York City’s treatment programs excluded pregnant women.

The options available for pregnant drug-dependent women are limited because

treatment programs rarely have the medical expertise necessary to provide the

specialized care required by such high-risk pregnancies. Therefore, given the

present litigious climate, treatment programs often choose to exclude pregnant

women arbitrarily.

However, the high incidence of cocaine and crack use among pregnant women

recently has precipitated a crisis among multiple service systems and has led to

an increased recognition that it is essential to provide comprehensive services

that address the complex needs of pregnant drug-dependent women.

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Unfortunately, the increase of such comprehensive services is affected by

regional and philosophical and political climates, and it is challenged by

the exponential acceleration of criminal prosecution of women using illicit

drugs while pregnant. While these issues may be interpreted as an esoteric

discussion of a “catch-22” situation, the reality is that the research environment

in which prenatal drug exposure must be conducted is indeed compromised

and impeded by this circular dilemma.

THE DISEASE OF MATERNAL ADDICTION

Ambiguity also may exist in prenatal drug exposure research because outcome

measures center on the infant. Most research investigating the effects of

maternal substance abuse have been based on a linear teratogenic model.

Variations in the patterns and timing of drug use throughout pregnancy, poor

health and nutrition status, psychiatric comorbidity, high-risk behaviors,

dysfunctional relationships, and physical and sexual abuse-all conditions

common within the entity of maternal addiction-rarely are considered. One

could argue that if addiction is defined as a chronic relapsing disease, then

prenatal drug exposure research should be an attempt to determine the

prognosis of the infant within the overall context of the maternal disease. For

example, in a study designed to investigate the effect of maternal diabetes on

pregnancy outcome, it would not be acceptable to simply identify the mother as

a diabetic. All the factors pertaining to the disease, such as length of disease,

ability to be controlled by diet, oral medication or insulin, medication dose, and

compliance, would be just a few of the factors investigated in evaluating infant

outcome. Yet, although the terminology of perinatal addiction studies is widely

used, studies that evaluate the infant within the inclusive context of maternal

addiction are rare.

Admittedly, employing a maternal disease model is a very difficult and complex

task; and, as previously discussed, the existing research environment does not

easily support such a model. The classification of addiction as a disease does

not mean it has a singular biological etiology. Rather, the disease of addiction

has been defined as a complex, progressive behavioral pattern having

biological, psychological, medical, sociological, and behavioral components

(Donovan and Marlatt 1988). As such, the effects of maternal addiction must be

addressed within a multifactorial framework that takes into account all these

factors.

Interestingly, within the past several years, perinatal addiction studies have

been characterized by the acknowledgment (albeit usually as a disclaimer

qualifying the data, as previously mentioned) that socioenvironmental factors

related to maternal drug abuse may be significant factors affecting infant

outcome.

262
It would appear that what these studies are actually identifying is the need to

address perinatal outcome within the framework of the disease of maternal

addiction and its concomitant effects. Clearly, it is a challenge to conduct

research in this field. The issues addressed here have attempted to identify

how prenatal drug exposure research is hampered by environmental constraints

that only allow a narrow window through which to view the wide panorama of

maternal addiction.

One of the ways to widen the window is to provide specialized comprehensive

treatment programs for pregnant drug-dependent women in which research is

an integral component.

THE FAMILY CENTER TREATMENT MODEL

Although several models of maternal addiction programs have been

developed, differences among models usually reflect adaptations to local

needs, institutional philosophies, and resources. The models contain basic

components common across programs. As such, a model developed in

Philadelphia at Family Center (Finnegan et al. 1991), while historically unique,

includes denominators common to other programs and is presented here as

an example of how research can benefit by being integrated within such a

treatment program.

To promote effective addiction treatment and provide a framework for research

and evaluation, Family Center has developed a treatment model that reflects

a multivariable systems approach. Family Center is an outpatient voluntary

program designed to provide intensive medical and psychosocial services to

drug- and alcohol-dependent women who are pregnant. This multimodality

treatment program endeavors to facilitate the best possible physical,

psychological, and sociological outcomes for both mothers and infants.

Comprehensive medical services at Family Center include a prenatal clinic

staffed by obstetricians specifically trained in the field of addiction and high-risk

pregnancy. Infants exhibiting withdrawal are treated in the newborn nursery

by specialists in newborn medicine.

A wide range of psychosocial services is offered. Those services comprise two

components: education and treatment. The educational focus targets prenatal

and parenting courses, as well as acquired immunodeficiency syndrome (AIDS)

prevention counseling. Treatment aims are directed at developing personal

resources, improving family and interpersonal relationships, reducing and

eliminating socially destructive behavior, and facilitating the parent/child bond.

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In addition to their substance abuse, women are often weakened by

unemployment, illiteracy, homelessness, and legal issues. The Family

Center treatment model is designed to respond to each of the medical and

social variables that complicate addiction and recovery through the following

components.

Outreach

Outreach services should be an integral part of any treatment approach.

Utilizing workers who are indigenous to the neighborhoods and the culture of

the women facilitates an overall understanding of the impact of diversity in

treatment. Indigenous workers can serve as a conduit between addicted

women and a treatment facility. This can be particularly helpful in facilitating

appropriate medical care for pregnant substance abusers, who often do not

seek prenatal care.

Because the women are poorly nourished, they are frequently deficient in

vitamins, such as vitamin C (associated with nicotine smoking) and the B

vitamins (associated with cocaine use). In addition, iron deficiency anemia and

folic acid deficiency anemia occur during pregnancy. The frequent use of

needles contributes to increased medical complications such as abscesses,

ulcers, thrombophlebitis, bacterial endocarditis, hepatitis, and urinary tract

infection. Sexually transmitted diseases such as gonorrhea, syphilis, herpes,

and AIDS are common.

Due to the lack of prenatal care in women who are drug-dependent, fetal

wastage is common, either secondary to early spontaneous abortion or later

intrauterine death. The fetuses frequently are born prematurely and/or suffer

from intrauterine growth retardation. The reasons for poor fetal growth are

multifactorial and include intermittent intrauterine hypoxia, placental

insufficiency, and intermittent drug withdrawal of the mother and the fetus

leading to a need for more oxygen, The last problem is frequently complicated

by the concomitant use of other drugs, such as nicotine and cocaine, which

also decreases the oxygen supply.

The most common obstetrical complications in drug-dependent women who

have no prenatal care are preterm birth and low birth weight. Therefore, infants

may have all the complications of either intrauterine growth retardation or

premature birth, which include respiratory distress syndrome, hypoglycemia,

hypocalcemia, intracranial hemorrhage, hyperbilirubinemia, and infection. If the

infants are born at term, they may have pneumonia or meconium aspiration

syndrome.

264
If the maternal drug use includes opiates, neonatal withdrawal may occur.

Significant withdrawal symptoms are seen in about 60 percent of the infants.

These symptoms include central nervous system hyperirritability such as

hypertonia, increased Moro reflex, tremors, increased deep tendon reflexes,

and high-pitched cry. The infants have an exaggerated rooting reflex, yet their

sucking and swallowing reflexes are ineffectual and uncoordinated. In addition,

mottling, fever, rapid respiration, and sweating occur. Appropriate assessment

and rapid treatment are essential so that the infants may recover without

incident (Finnegan 1986).

Methadone maintenance has proven to be efficacious in the treatment of

pregnant opiate-dependent women, Aside from the previously mentioned

incidence of withdrawal symptoms in the neonate, other complications as a

result of the medication usually do not occur. Methadone, used appropriately

and coupled with comprehensive care, can decrease the complications of

pregnancy, childbirth, and infant development (Connaughton et al. 1977; Silver

et al. 1987).

Medical services for pregnant drug-dependent women must encompass the

perinatal, pharmacological, medical education, and referral components. The

perinatal services encompass care provided by a perinatalogist and a perinatal

nurse clinician. Antenatal testing is performed. Counseling and testing for

human immunodeficiency virus and nutritional counseling are provided. The

mother should deliver in a hospital where emergency services are readily

available in case complications occur in either the mother or the child. Since

the infants are frequently small, many of them may need intensive care.

If the pregnant woman has any specific medical complications, such as

hyperthyroidism or diabetes, appropriate medical consultation should be

obtained. Additionally, due to the impoverished conditions in which many of

the women live, many medical complications occur. By taking a good family

history, one can frequently ascertain the background of the patient, which may

lead to a clearer understanding of the addictive process in this woman.

Therefore, the team also must deal with providing an appropriate environment

so that the woman may stay in a healthy physical and psychological state.

Social/Demographic

Because of the many social problems associated with the women at Family

Center, it is usually necessary to attend to these needs over several months

before staff can focus on the psychological/behavioral/cognitive component. If

housing, clothing, and food issues are unattended, the women rarely respond to

drug treatment. When consistent provision for shelter, clothing, and food is

made, dramatic increases in initial recovery occur.

265
Over the years, the Family Center staff has developed a network of agencies

that assist in the area of housing. Even with existing liaisons, large amounts of

staff time are necessary to obtain appropriate shelter for the women.

Family Center maintains a clothing bank for women and children. A more

progressive plan is to have a small shop area and have members of the

recovery group oversee the operation, as well as generate donations and sort,

wash, and tag clothing.

The outpatient facility also has included a small food bank that consists of

cereal, soups, crackers, peanut butter, infant formula, and regular milk. It is

not unusual for pregnant addicts to appear at Family Center without having

eaten for several days. In addition to food, bus and subway tokens are

provided for transportation. The combination of a nourishing meal and a

way to return to Family Center encourages attendance.

Cultural/Gender Sensitivity. Treatment approaches have been modified

to account for gender-, race-, and culture-specific issues. In women-only

groups, Medical Assistance recipients may feel threatened if the group is

socioeconomically diverse. If the groups are sexually mixed, addicted women

will not communicate with and tend to defer to the men in the group; the high

incidence of sexual and physical abuse in drug-dependent women may

contribute to difficulties in relating to men.

Therefore, Family Center presently operates women-only groups. The

women express their fears and frustrations without fear of male retaliation.

The participants make the rules of the group, and the staff members serve as

facilitators only. These groups have been extremely successful in encouraging

the members to work out individual and interpersonal issues in a supportive

environment.

Treatment effectiveness is drastically reduced or impeded without a thorough

understanding of the interaction between social, cultural, and demographic

variables.

PsychoIogicaI/BehavioraI/Cognitive

Sobriety is only the initial step in the recovery, process. Behaviors related to

drug intake are altered, but to remain in recovery, other behaviors must be

modified.

Many times, the women remain developmentally at the age level of first drug

use. This can interfere with traditional expectations of educational, cognitive,

266
psychological, and vocational levels. The Family Center model assesses and

determines exactly at what level the woman is functioning. The woman is

assigned developmentally appropriate tasks to expedite cognitive development

delayed by long-term drug use.

Coping mechanisms are assessed and carefully monitored. Quite often, when

drug-seeking behaviors are modified, there are no other coping mechanisms

present. This requires intensive staff time to create and support tasks that

promote the necessary mechanisms.

Education often is used by the staff to assist in the promotion of self-esteem.

Classes for prenatal care, parenting, and child and adult development

contribute to an understanding of the process of physical and mental growth.

When the women have negotiated the developmental tasks described above,

they are ready for treatment regarding the issues of sexual abuse, physical

abuse, intimacy, and introspection, as well as feelings and associations that

trigger drug use. The Family Center model allows for differences in the

woman’s development and for variations in cognitive, psychological, and

behavioral abilities.

Mother-Infant lnteraction

Infants born to drug-dependent women often are subject to double jeopardy

(i.e., biological risk and a mother with few parenting skills). It is imperative,

therefore, that maternal addiction programs include strategies designed

to facilitate positive mother-infant interactions. At the birth of an infant, the

mother should be assisted in getting to know her infant and the infant’s unique

behavioral characteristics, Specific care-giving strategies for each dyad can

be developed by educating the mother about the competencies and needs of

her infant and by teaching comforting techniques and how to interact with her

infant in a positive, responsive manner. This type of intervention is essential

because infants exposed to drugs in utero tend to be difficult to feed; have a

poor sucking reflex, a high-pitched cry, and a rigid muscle response; and are

often irritable and difficult to console. They may have limited tolerance for

sensory stimulation. Without intervention, mothers who have limited caregiving

skills and resources are attempting to parent infants who are difficult to care for

and who provide little positive reinforcement (Kaltenbach and Finnegan 1988).

Newborn care and feeding techniques should be taught upon discharge. Home

visits also should be made to facilitate caregiving needs in relation to

environmental realities,

267
Early Childhood Development

The Parent/Child Center provides an early education intervention program for

both mothers and children. The primary focus of the center is on developing

and enhancing positive, responsive parenting skills to promote optimal

development of the children,

A children’s program, directed by an early childhood specialist, provides

a stimulating, responsive, and supportive environment for the children.

Mothers and infants are expected to attend the Parent/Child Center biweekly.

Videotaping is an important component in the development of responsive

parenting during the first 3 months of the infant’s life. The tapes can be used

as therapeutic intervention by discussing the meaning of the infant behaviors,

the maternal responsiveness to infant cues, and the effect of the mother’s

action on infant behaviors. After 3 months postpartum, the videotaping should

focus on mother and infant interacting in play and caretaking behaviors. The

meaning of certain infant behaviors, the mother’s perception of the situation,

and the effects of the mother’s actions on the infant should be discussed

(Fitzgerald et al. 1990).

Weekly parent education groups also should be conducted. These groups

focus on the basic developmental milestones of growth and development.

Drug-dependent women often have limited knowledge of the basic milestones

of behavior and, therefore, unrealistic behavioral expectations of their children.

This lack of knowledge, which may contribute to the incidence of child abuse

among drug-dependent women, is a risk factor that can be reduced significantly

with intervention.

Learning to set limits and practice appropriate discipline are also important

components of parent education. Addicted women tend to have very low

frustration tolerance; although this may foster abuse, conversely, it also may

result in an inconsistent pattern of responses to children’s behaviors in which

no appropriate limits are set. Since they have difficulty perceiving themselves

as capable of changing their own actions, the mothers often cannot see

themselves as agents of change in the lives of their children, except by physical

punishment. Thus, the behavioral problems often reported in preschool

and school-age children of drug-dependent women may be a reflection of

childrearing practices that are related to maternal addiction.

CONCLUSION

Environmental issues are key in accomplishing research in the perinatal patient

when drug exposure is a complication. The benefit of integrating research

268
within a treatment program clearly can be justified and, in most cases, will

enhance the quality of the research as well as satisfy ethical issues in this

population.

Integration of this research within a treatment program will (1) permit the

research to be more systematically accomplished and controlled; (2) permit

more accurate evaluation of ongoing drug exposure by way of urine toxicologies

and permit the establishment of rapport to obtain additional historical and, in

some instances, extremely sensitive information; (3) permit identification and

treatment of disease entities that may confound the outcome data; and (4)

permit counseling regarding social and legal variables that prohibit compliance

with research protocols.

Finally, the women and children in this study population are often

disadvantaged from a medical, psychological, and social standpoint. It is

the researchers’ responsibility while seeking answers to research questions

to provide the women with compassion, respect, and an environment that will

enhance their recovery from addiction to drugs, as well as to assist them in

ensuring the best possible intrauterine milieu for their unborn babies.

REFERENCES

Chavkin, W. Drug addiction and pregnancy: Policy crossroads. Am J Public

Health 4:483, 1990.

Connaughton, J.F.; Reeser, D.S.; Schut, J.; and Finnegan, L.P. Perinatal

addiction: Outcome and management. Am J Obstet Gynecol 129:679-686,

1977.

Donovan, D.M., and Marlatt, G.A., eds. Assessment of Addictive Behaviors.

New York: Guilford Press, 1988.

Finnegan, L.P. Neonatal abstinence syndrome: Assessment and

pharmacotherapy. In: Rubaltelli, F.F., and Granati, B., eds. Neonatal

Therapy: An Update. New York: Elsevier, 1986.

Finnegan, L.P.; Hagan, T.; and Kaltenbach, K. Scientific foundation of clinical

practice: Opiate use in pregnant women. Ann N Y Acad Sci 67(3):223-239,

1991.

Fitzgerald, E.; Kaltenbach, K.; and Finnegan, L.P. “Patterns of Interaction

Among Drug Dependent Women and Their Infants.” Paper presented at the

American Pediatric Society and the Society for Pediatric Research, Annual

Meeting and Exposition, Los Angeles, May 7-11, 1990.

Kaltenbach, K., and Finnegan, L.P. The influence of the neonatal abstinence

syndrome on mother-infant interaction. In: Anthony, E.J., and Chiland, C.

eds. The Child in His Family: Perilous Development: Child Raising and

Identity Formation Under Stress. Vol. 8. New York: Wiley, 1988. pp. 223-

241.

269
Silver, H.; Loriz-Vega, M.; Waper, R.; and Finnegan, L.P. Addiction in

pregnancy: High risk intra-partum management and outcome. J Perinatol

3(3):178-184, 1987.

AUTHORS

Karol A. Kaltenbach, Ph.D.

Acting Director, Director of Research

Family Center

Assistant Professor of Pediatrics, Psychiatry, and Human Behavior

Jefferson Medical College

Thomas Jefferson University

11th Floor

1201 Chestnut Street

Philadelphia, PA 19107

Loretta P. Finnegan, M.D.

Senior Adviser on Women’s Issues

National Institute on Drug Abuse

Associate Director for Medical and Clinical Affairs

Office for Substance Abuse Prevention

Alcohol, Drug Abuse, and Mental Health Administration

Department of Health and Human Services

Rockwall II, Suite 615

5600 Fishers Lane

Rockville. MD 20857

Professor of Pediatrics, Psychiatry, and Human Behavior

Jefferson Medical College

Thomas Jefferson University

Philadelphia, PA 19107

270
How the Environment Affects

Research on Prenatal Drug Exposure:

The Laboratory and the Community

Claire D. Coles

INTRODUCTION

Study of the effects of substance abuse on women of childbearing age,

pregnancy, pregnancy outcome, and child development must be carried out in

clinical settings and in the community-in treatment centers, prenatal clinics,

hospitals, well-baby clinics, social welfare agencies, child care and school

settings, and the homes of the research participants. Undertaking work in these

areas is enormously rewarding and provides ecologically valid data that cannot

be gathered in any other way. However, these environments influence the way

in which research must be carried out-the populations that can be studied, the

questions that can be asked, and the methods that must be used. This chapter

examines several aspects of these environments. In addition, some

suggestions are made for dealing with challenges raised by working in these

real world situations.

Although this chapter focuses on environments associated with collection of

data on outcomes of substance abuse during pregnancy, it would be one-sided

to suggest that only in the clinic, the housing project, or the crack house are

there environmental and sociocultural factors that affect the planning and

execution of research. The investigator’s environment and the relationships

between that environment and that of the substance abuser also affect the

research process. The current scientific or research milieu will direct the

investigator toward a particular question. Available resources will decide

whether a particular project can be carried out. The latest test or a favorite

methodology will direct the data to be collected. Experimenter preconceptions

or unintentional biases (Rosenthal 1967) as well as scientific theories (Kuhn

1970) will affect all aspects of the research process from the formation of the

problem to the interpretation and publication of the results (Koren et al. 1989).

271
Examination of the effects of substance use in pregnancy often is associated

with emotional reactivity because it involves attitudes about race, social class,

and women’s rights as well as current concerns about drug abuse. Therefore,

researchers have to be scrupulous in dealing with these issues to limit the

extent to which studies will be biased by reactions to them.

The investigator touches the substance abuser’s world at a few points only.

Since the investigator’s goal is to locate a population to study and/or to find

subjects for longitudinal followup, these points of contact are, typically, medical

settings, drug treatment agencies, and the homes of participants.

THE CLINICAL ENVIRONMENT: WORKING IN SOMEONE ELSE’S SYSTEM

The research protocol usually requires that many pregnant women be screened

for substance abuse and other factors and that their infants be examined in the

neonatal period to determine if they are affected by exposure. Therefore, the

investigator must have access to sites where pregnant women can be recruited

and where infants can be examined and medical records screened. The

population must be sufficiently large and of such a character that the sample

collected will be representative and will have a probability of exhibiting the

effects, if these exist, of the putative teratogen.

Although in theory such a population could be collected at many sites, in

practice such sites are limited and often related in systematic ways to social

class and access to resources. Pregnant middle-class women use private

physicians and health maintenance organizations. Although it would be

desirable to conduct research in such settings, physicians or clinics may not

have caseloads large enough or heterogenous enough to allow generalization,

and due to concerns about legal and financial issues, they may not be willing to

allow research to be conducted. They also may be concerned about the

disruption of routine or loss of confidentiality that even well-conducted research

may entail. It is probably not a coincidence that the majority of studies,

therefore, are carried out among poor women who are accessible through

teaching and charity hospitals and who are unlikely to object to research

protocols. These factors can result in a biasing of studies toward poor and

minority populations

Unless the investigators are part of the administrative hierarchy where research

will be carried out, they will arrive as “outsiders.” Hospitals, clinics, school

systems, and other places where suitable populations of women and children

can be found are often cooperative with research plans when they have had

positive experiences in the past with such projects or are unfamiliar with the

demands of research. They tend to be less cooperative when severely

272
stressed, when they have had negative experiences with past research, or

when they are interested in conducting similar research of their own.

Situations confronting researchers in such settings have been well documented

in the literature on program evaluation and community psychology (Anderson

and Ball 1978; Datta 1978; Trickett 1984). This literature provides many

suggestions for dealing with environmentally based problems that may arise.

Many of these problems have a common source; that is, the considerations and

constraints of the research process may come into conflict with, or be seen as

coming into conflict with, other institutional functions (Lorion et al. 1988).

Although most clinical staff members understand that research is important,

particularly in areas such as the effects of cocaine in pregnancy, they often

have difficulty dealing with the day-to-day activities associated with the process.

Some of the systemic obstacles common in research on substance abuse and

pregnancy are discussed below.

Systemic Obstacles

Stress Due to Clinical Considerations. Many settings where the effects of

substance abuse in pregnancy are investigated are already stressful. For

instance, a common setting is the neonatal intensive care unit of an inner-city

hospital that often is understaffed and oversupplied with patients. Staff in such

units deal with infants at high risk for mortality, multiple illness, and the

prognosis of poor, long-term outcome. The additional risks associated with or

perceived to be associated with maternal substance abuse may lead to

emotional reactions (Good et al. 1990) that can affect cooperation with a

research protocol.

Another common setting may be a publicly funded alcohol and other drug

treatment program that has 10 treatment slots for pregnant women and a

waiting list of several hundred. Staff may be struggling with reactions to legal

pressures, medical emergencies, acquired immunodeficiency syndrome (AIDS),

and child abuse as well as depressed and suicidal women. As a result, they

may view the researcher, checklist in hand, as an annoyance at best or, at

worst, as a frivolity that is draining away funds that could be used more

effectively in extended clinical services (D. Carson, personal communication,

1990).

Competition for Resources. Competition has many sources. Pressure to

publish and to attract funds is likely to produce competition even within a single

institution, Even in the absence of such pressures, competition for available

resources, including space, assistants, and computer time, may interfere with

carrying out a particular research effort. When a topic of research is of interest

273
to many departments within a hospital (e.g., cocaine abuse), there may be

competition for research subjects with particular characteristics (e.g., AIDS

cases) (J.V. Brown, personal communication, 1989).

Participation in Goals. If the clinic staff is in concert with the goals of the

research or see some benefit to themselves or their patients/clients,

cooperation is more likely (Lorion et al. 1987). Coulter and colleagues (1985)

reported gaining cooperation for a study of sexually abused children in the face

of considerable skepticism by adapting research procedures to the perceived

needs of the social agency and by providing services that the agency lacked.

These services included psychological evaluation of children and expert witness

testimony in custody proceedings even though both procedures added

considerably to the time demands on the research staff.

If such cooperation is not possible or is constrained by the design of the

experiment, protocols should be arranged, staff trained, and methods planned

that cause as little disruption as possible and that are unobtrusive. Because

people are more likely to be sympathetic to research they understand and

support, other methods for improving cooperation include providing inservice

and educational materials to staff, engaging staff in planning the goals of the

research, and providing feedback about outcomes on a periodic basis (Lorion et

al. 1987).

Increasing Staff Work Loads. In many settings, staff members already are

stressed and overburdened from dealing with a difficult client population,

making it unlikely that research procedures requiring extra work by the

treatment staff will be successful. Similarly, it is unwise to rely on hospital or

agency staff to carry out experimental procedures reliably or consistently unless

research staff can provide supervision. If extensive work is to be done at a

particular site, it is important to hire a staff person who works onsite and who

has experience working in such settings.

System Change. Any social system will resist change (Kuhn 1974). However,

systems that are under stress or in which personnel are dealing with

emotionally difficult issues may become more rigid and resistant to change.

Therefore, research procedures that are introduced should be as consistent as

possible with the existing system and should involve as little inconvenience as

can be arranged. Research personnel who are seen as outsiders and

procedures that make extensive demands on an ongoing system are unlikely to

be successful.

274
EFFECTS OF THE PHYSICAL ENVIRONMENT

Where you are affects what you can do. Many of the settings where lowincome, substance-abusing women and their children are seen are publicly

funded and are often old, inadequate, and overcrowded. As a result, the

investigator often has to “make do” by accommodating research ideals to

practical realities.

Although confidentiality considerations and common decency prevent

interviewing a prospective research subject in the hall or in front of other

patients, there may not be a room in a crowded prenatal clinic or postnatal ward

that can be dedicated to research, where materials can be left, and privacy can

be ensured. The ideal research protocol may have to be adjusted accordingly.

This might mean collecting data during obstetrical rounds when residents are

absent, leaving examination rooms available to conduct interviews, or

negotiating with colleagues to use their offices on a part-time basis. It also may

mean that lengthy interviews will have to be conducted during home or

laboratory visits to ensure privacy and reliability.

Similarly, although it is desirable that all neonates be evaluated the same

number of hours after birth, timing and hospital routine may interfere with

scientific rigor. The confusion and disruption of morning pediatric rounds may

prevent data collection, particularly if medical residents are not cooperative with

the research protocols. Therefore, it may be necessary for infants to be tested

only in the early afternoon when quiet spaces are available.

Even such seemingly irrelevant factors as the location of parking lots may affect

the research protocol. For practical as well as experimental reasons, evening

hours are most desirable for observation of sleep patterns in neonates.

However, in a recent study of cocaine-exposed infants (Coles et al. 1991),

research assistants, who were predominantly female, objected to evening hours

because it was not safe to walk to unguarded parking lots near the hospital.

Since morning hours were occupied with pediatric rounds and early afternoon

hours with physical and behavioral examinations, arrangements had to be made

to have hospital security guards accompany women to their cars. This problem

became more acute after several assaults and shootings occurred within the

hospital.

THE COMMUNITY: WORKING IN THE FIELD

Many factors related to the nature of development and the specific effects of

substance abuse (Coles et al. 1987) make longitudinal followup necessary and

an understanding of the social/cultural and physical environment important.

275
In the best of circumstances, longitudinal research is expensive and difficult. It

has special methodological problems, like attrition and historical changes, that

can threaten the validity of the data (Campbell and Stanley 1966), and it

requires a large staff who are persistent in their dedication to the project. The

socially disadvantaged women most often focused on in research on substance

abuse are probably least compliant with the goals of longitudinal research.

Also, such research has to be carried out in environments that are difficult for

the researcher to work in for a variety of reasons. When problems associated

with substance abuse are added, such research can be daunting to the wellinformed investigator. The effects of some of these obstacles in practical terms

are (1) the need to account for environmental effects on outcomes; (2)

limitations on the types of procedures that can be carried out in such settings:

(3) difficulty in locating and following subjects due to effects of social class,

poverty, and substance abuse; (4) misunderstanding between research

subjects and staff due to cultural and educational differences; and (5) personnel

problems, including staff safety and staff burnout due to social and

environmental conditions.

Effects of Special Physical and Social/Cultural Circumstances

The serious social problems associated with being poor, female, and of minority

status in the United States in the 1990s have received great attention and do

not need to be reexamined in detail here. However, it is in populations of this

kind that the majority of the studies of the effects of prenatal drug exposure are

being conducted. This situation has serious implications for the investigator. A

few statistics will be provided to suggest the extent to which environmental

effects must be taken into consideration.

In Atlanta, the population under investigation has many problems known to be

related to developmental outcome among children (table 1). There is only one

hospital that regularly provides prenatal and delivery services to the indigent.

Although there is a range of income levels among patients, the majority of

people served are black (89 percent), poor, and eligible for Medicaid

(unpublished data, Parents/Infants Resource Center, 1990). Many women live

in subsidized housing, which is the location of much of the drug-related activity

in the city.

In Georgia in 1988 (the most recent year for which statistics were available),

among black women, the infant mortality rate was 19.5 per 1,000, somewhat

higher than in many Third World countries (Hughes et al. 1989) and

approximately twice that of white women (L. Dismukes, personal

communication, 1990). Low birth weight and prematurity are more common

among the disadvantaged as well. Incidence of black infants weighing less

276
TABLE 1. Average characteristics of prenatal drug exposure study sample(s)

in Atlanta, 1980-1990*

Maternal Users of

Characteristics Alcohol/Other Drugs Controls

Average age (years)

Race

Black

White

Education (years)

Married

Parity (number of dependents)

Monthly income

Slosson IQ†

27

93%

7%

10.3-12.1

18%

2.5-3.6

$200-$600

72

24

89 and 91%

9 and 11%

11.5-12.5

40-50%

1.9-2.5

$250-$800

76

*These are averaged over several samples. Particular subsamples may vary.

†SOURCE: Coles et al. 1991

than 1,500 g (very low birth weight) was 2.7 percent for Georgia but was 5.5

percent for the city of Atlanta. This is in comparison with white infants for whom

the equivalent figures were 1.0 and 1.9 percent, respectively (L. Dismukes,

personal communication, 1990).

Table 1 indicates the average characteristics of prenatal drug study samples in

Atlanta over the past decade by drug use status. In the samples studied, the

mean educational level among alcohol and other drug users was reported to be

around 11th grade, but reading tests in this population indicated a mastery of

5th grade skills only (unpublished data, Parent/Infant Resource Center, 1990).

Intelligence testing of a subsample using standardized tests (which are probably

biased against this group of people) indicated a mean intelligence quotient (IQ)

of less than 80 (Coles et al. 1990).

In 1990, the Georgia Department of Family and Children’s services reported

that some kind of substance abuse was associated with 50 to 60 percent of all

reports of abuse and neglect made to protective services (Neims 1990). Social

services, including foster care, Project Head Start, medical and psychological

services, alcohol and other drug treatment, and programs for children with

developmental delays, are either overcrowded or unavailable (Hansen 1989).

In 1989, the Atlanta Police Department (Huguley 1989) reported that drugrelated crimes had increased significantly over the past 5 years (table 2) and

277
TABLE 2. Increase in illegal drug activity in Atlanta, 1982-1988

Drug-Related Crimes

Drug-related arrests

(% change)

1982 1985 1987 1988

N N N N

3,295 3,077 4,721 6,898

(-7) (+53) (+46)

Arrests for cocaine 276 395 1,268 3,450

possession (% change) (+43) (+221) (+172)

Value of drug seizures $518,243 $408,006 $1,117,426 $2,057,548

by narcotics unit (-21) (+17) (+84)

(% change)

SOURCE: Huguley 1969

that 12 percent of all homicides were drug-related, with most of them occurring

in low-income areas, frequently in the same housing projects where the women

in the study samples live. Given these factors, it is incumbent on the

investigators who work with such a population to take into account the

consequences of crime, poverty, and racism.

Several strategies can be attempted to deal with the experimental

consequences of these problems, including matching subjects or samples

as well as using statistical controls. However, it is unlikely that all such factors

can be “controlled” adequately or that the effect of all these negative elements

can be completely eliminated. Investigators should be constantly aware of

these issues and must remember that it will be difficult to overestimate the

effects on outcome. The safest procedure will be to document as fully as

possible the environmental factors that may be related to outcomes of interest

and to examine their interactions with the perceived effects of drug exposure.

Some Effects of Poverty and Limitations on Services. Limitations on

resources experienced by the population under study affect the research

outcome. Women may not have had adequate prenatal care and may have

been unable to find treatment for their substance abuse. These factors may

have affected the outcome of pregnancy through a higher incidence of preterm

birth, low birth weight, and other factors.

Postnatal services for children with special needs are limited and hard to

access. Even when investigators identify problems and make treatment

referrals, children may not be served (Neims 1990). In many cases,

278
researchers are in the position of observers who note problems, are aware of

potential solutions, but are unable to effect any changes in the situation even

though they may be mandated to report such things as child abuse. This

situation leads to secondary effects on the research staff who are often upset

and discouraged with their lack of ability to help people with whom they have

become involved. An argument could be made that the investigators, as

observers, should not attempt to intervene in this fashion. However, this

attitude is difficult to maintain in the face of extreme need.

Limitations on Procedures

Although the scrupulous researcher will want to assess environmental factors

carefully to ensure that there are no differences between contrast and

experimental groups and to provide information about the extent and power of

what differences do exist, the realities may limit the kinds of questions that may

be asked. Experimental procedures that are useful in middle-class samples

may lose their significance in samples that are overwhelmed by negative social

factors. In addition, the particular constraints resulting from environmental

factors may vary from location to location or among different ethnic and social

groups.

It is obvious that the limited reading and educational levels of many research

participants require that all questionnaires be read to participants and that

interview methods include ascertaining the women’s ability to understand the

questions asked. All research instruments and procedures have to be selected

and pretested with these limitations in mind. Questionnaires cannot be sent out

to be completed independently; they must be read to participants. Mothers

cannot be asked to keep logs of infant behavior or to use many currently

available materials on child development or parenting.

Another difficulty occurs due to mothers’ limited financial resources. Most study

participants do not have access to cars and must travel by bus. Therefore,

women cannot be asked to travel by themselves to the laboratory to keep

appointments. They either must be transported or the investigators must go to

them. Because child care is hard to arrange, siblings often must accompany

mother and infant anywhere they go. During data collection, some provision

must be made for these other children.

Even if a home visit is made, certain kinds of procedures are inappropriate or

impossible where space is limited or the area is dangerous. For instance,

although it is sometimes possible to conduct confidential interviews in the home,

in other cases no private place is available to the mother who may not want to

discuss her substance abuse history or current use in front of children or other

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family members. When children are being tested it may be impossible to do

tests in a standardized way if there is no place available that is not subject to

interruptions by siblings or television noise. The experimenters who are not

cognizant of these issues will find their data invalid or unreliable.

Another problem arises when the investigator would like to perform procedures

that involve equipment. For instance, if a higher incidence of sudden infant

death syndrome is suspected, it might be interesting to monitor infants’

physiological processes over the first few months of life. However, provision of

apnea monitors or similar expensive equipment in homes of substance abusers

where educational level is low and need for money high is likely to be

unsuccessful. Similarly, it is probably unwise, in the current climate, to take

expensive and easily resalable video equipment into drug abusers’ homes.

Therefore, although it would be interesting and probably informative to

videotape patterns of mother-child interaction (for example) in the home

environment, it would probably also be dangerous. More examples could be

given, but the basic point is obvious. The social and physical circumstances of

the research participants directly affect the choice of procedures and

instruments, and such decisions determine what data can be collected.

Finally, when research is undertaken in an area where there are strongly held

and perhaps unexamined beliefs, the potential for experimenter bias is

particularly great. Goldberg (1979) discusses how this tendency plays out in

longitudinal research on human development. Repeated assessment of infants

in a nonlaboratory environment where neither blindness nor strict protocols may

be maintained is an invitation to unconscious bias on the part of data collectors

as well as for research participants to be “helpful” in providing the most

desirable data (Orne 1962).

Subject Recruitment and Retention

Subject recruitment and retention is a matter of great concern in longitudinal

research. Unfortunately, motivation to enter into and participate in research

probably is limited among minority women of low socioeconomic status who are

abusing illegal substances. In addition to providing financial incentives (Capaldi

and Patterson 1967) and social and medical services (Thomas and Chess

1987) to the research participants, among the most effective ways of

maintaining the sample are frequent contacts by telephone, letter, and home

visits (Goldberg 1979). However, many poor women do not have telephones,

and others live primarily with relatives and may move frequently. This problem

is even more acute among women who are abusing illegal substances. Such

women may be involved with illegal activities or involved with men who are.

They may live in crack houses. Also, they may be homeless due to

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disagreements with family and friends about their behavior. In such

circumstances, interest in participating in a research study may be low, and

there may be considerable suspicion regarding the motives of the research

team who can be seen as agents of social service agencies, This last problem

has become acute lately due to the increased threat of arrest of women who are

identified as using cocaine in pregnancy (R. Moeti, personal communication,

1990).

Given these conditions, it is amazing that most women who are approached do

agree to participate and will sign an informed consent (Smith et al. 1987).

Among the populations studied in this research, however, recruitment does not

guarantee retention, and noncompliance with followup is common. Either

women cannot be located or do not respond to appeals to return for followup.

In addition, on some occasions when they can be found and do agree to be

retested, they will fail to comply, usually by not keeping the appointment or not

answering the door if a home visit is made. This behavior is frustrating to the

research staff who have a strong investment in maintaining the sample and

resent “wasting” their time. Sometimes staff have difficulty understanding why a

woman agreed to followup if she did not mean to cooperate. However, it is

common in Georgia, at least, for minority women to act in a compliant manner

when talking to people who seem to represent authority. They usually will not

say no to a direct request but often will indicate their lack of willingness to

participate by missing appointments, refusing to return calls, and so on (M.

Foster, personal communication, 1990).

This “misunderstanding” is a good example of the conflict in customs and

values that can occur between research staff and subjects. The majority of the

subjects in such research probably have a limited understanding of the

researchers’ purposes as well as many more urgent concerns of their own.

Therefore, since they do not place the same value on research as do the

investigators, they are most likely to continue in the project if they see some

value in this for themselves or for their children, Otherwise, they have little

reason to comply with the generally intrusive, boring, or annoying procedures.

There are several ways to handle these problems including treating research

participants with respect, providing monetary and other incentives, establishing

an ongoing relationship, and ensuring adequate funding to be able to carry out

these procedures, Finally, it is important for investigators and staff to be aware

of factors that interfere with followup.

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318-164 0 - 92 - 10 : QL 3
Cultural and Other Possible Sources of Misunderstanding

Characteristics of the Investigators. Unlike the populations described above,

the majority of people who conduct research are middle class, well educated,

and do very well on standardized tests. When they begin research on

substance abuse or child development among the poor, many researchers have

little experience with or understanding of the population they will be studying.

Although usually sympathetic, they often have life experiences and values

different from those of research participants. These factors make it important

that investigators are sensitive to the effects of these different cultural, social,

and physical environmental factors.

There are many potential sources of misunderstanding between these two

groups of people. Like most laypersons, the research participants may

misinterpret the meaning of the sometimes esoteric experimental procedures to

which they or their children are exposed. They may believe that test outcomes

are more significant than they actually are. For instance, if they are anxious

that the child has been harmed by their prenatal substance abuse, mothers may

interpret the examiner’s comforting or concerned remarks as more meaningful

or predictive than they actually are.

On the other hand, investigative staff may not understand some aspects of the

behavior of research participants or may find aspects of their lifestyles

upsetting. Local dialects or idioms may be hard to interpret or may prevent

subjects from understanding questions. Research staff members who are

asked to sit on a tattered couch in a room in which cockroaches are visible

scurrying up walls may exhibit distaste that will affect subsequent cooperation

by their hostess.

Personnel and Safety Considerations

It may be dangerous for research staff to go to the homes of drug abusers, and

many people feel concerned when asked to do so. However, the majority of

home visits will be carried out without any problems. In several longitudinal

research projects carried out in Atlanta in the past 10 years, participants,

including alcoholics, drug abusers, persons with schizophrenia, depressed

women, and contrast group members have been almost universally pleasant in

welcoming a variety of research staff, questionnaires, tape recorders, and other

paraphernalia into their homes.

Nevertheless, the circumstances place certain restraints on procedures that can

be conducted. For instance, as discussed later in this chapter, safety concerns

affect staffing patterns and training, which, in turn, affect research costs.

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Consideration of the potential dangers in the environment also affect the kinds

of procedures that will be possible. If followup is planned, home visits of some

kind are inevitable with this population. Researchers have devised a variety of

methods to deal with the potential problems of visiting drug users’ homes,

including sending a cab or university car with driver to the woman’s home to

pick her up, sending staff out in pairs in cars with State emblems on the side,

hiring off-duty policemen to accompany research workers to homes, and hiring

recovering drug users from the same neighborhoods to make contacts.

Although these are all reasonable solutions, each has particular potential

consequences for the data collection procedure and the possibility of future

contacts with the family, and these should be taken into consideration.

COPING WITH THE EFFECTS OF THE ENVIRONMENT ON RESEARCH

This brief overview of some of the effects of environment on the study of the

consequences of prenatal substance abuse may sound somewhat daunting.

However, despite these problems, there are many ways in which the

investigator can cope. Although there are real limitations on research methods,

collection of valid and reliable data and understanding of outcomes can be

facilitated by understanding the situation and planning ahead, selecting and

training staff, taking safety precautions, monitoring the research process, and

responding in a flexible way when necessary.

Understanding the Problems

The study of a new issue or area, particularly when it involves several real world

problems, must be undertaken with respect. Even for the person experienced

in the field, new situations arise. For instance, with the recent increase in

cocaine use, there were significant changes in the working environments with

which many investigators thought themselves familiar. Home visiting, which

had always been dangerous, became more dangerous. Followup over time,

which had been difficult, became impossible in some instances. Addicts

exhibited behavior changes consistent with alterations in drug use, and these

changes were potentially related to effects on infant development.

For these reasons, it is important for those undertaking work in this area to have

a thorough knowledge of the issues at both intellectual and practical levels.

Since the issues of substance abuse and child development encompass

several areas of specialization in medicine as well as the biological, behavioral,

and social sciences, the careful researcher will recruit appropriate colleagues to

contribute to the effort. For the obstetrician or developmental specialist, this

probably will involve working with professionals experienced in treating

substance abusers. For the alcohol or other drug treatment specialist, this will

283
involve finding an expert in high-risk infancy and/or a sociologist to avoid the

error of attributing all developmental problems to the teratogenic effects of the

drug.

Investigators also can avoid many errors in planning and execution by

examining the experience of previous workers in the same or similar areas.

Although this sounds simple (equivalent to researching the literature), it is

apparent that many people who are presently undertaking the study of the

effects of cocaine in pregnancy have omitted the obvious step of reading the

work of those who carried out very similar studies on infants of women who

abused other substances such as heroin and alcohol, thus putting themselves

in the position of “trying to reinvent the wheel.”

Staff Selection and Training and Safety Considerations

Staff should be selected and trained with consideration of the work that will

have to be done, the sites where it will be conducted, and the population

involved. It is probably not wise to plan to employ only white, middle-class

college students to interview low-income minority women because this

discrepancy could raise many cultural issues that might interfere with adequate

data collection. The extent to which the protocol requires rapport to be

established to gain confidential information should suggest the kinds of

experience needed by staff in a particular position. Similarly, if home visiting is

required, persons who will do this should be comfortable in this role not only for

their own sakes but also to put the research subject at ease.

However, although it is necessary to be attentive to cultural and ethnic issues, it

is important that this be done in a sensitive way. It is not appropriate, for

instance, to assume that because an individual is black that he or she will

necessarily be knowledgeable about the behavior and experience of Iowincome black women who are abusing drugs. Nor should it be assumed that an

educated white male will necessarily be insensitive, inept, or out of place in

such a role. More important than people’s social and ethnic backgrounds are

their attitudes, their social and professional skills, and their experience.

Staff should be trained thoroughly in the administration of all materials, in

methods for making research participants feel comfortable and respected, and

also in methods for maintaining their own physical and emotional safety. In

Atlanta, the author and colleagues at the Human Genetics Laboratory first

informally and then formally established several safety rules (appendix) that are

discussed with all staff persons before they are allowed to go into the field.

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For instance, the research directors do not allow anyone to make a home visit

alone; information about staff travel plans as well as information adequate for

tracing them is left with office personnel before each trip. Staff are required to

report back to the office before leaving for the day so that their whereabouts are

known, and the office is not closed until all staff have returned.

In the field, staff are instructed not to enter areas where they have reason to

believe that they may be in danger. They are encouraged to dress modestly

and not to carry large sums of money. Following a particularly unsettling

incident, it was decided that home visitors should never decide in the field to go

to another site where they could not be located.

Emotional well-being is also a concern because dealing with high-risk

populations, even when only collecting data, can be stressful. Not only can it

lead to emotional distress and burnout, but it can be associated with inaccurate

data collection. After some experience, the author and colleagues began

screening staff applicants carefully to ensure that they would be comfortable in

the sometimes difficult environments they would encounter. The difficulties and

potential dangers are carefully explained and applicants with some experience

in similar situations are preferred.

Despite these precautions, there have been some problems specifically related

to the issue of environment and the reaction of staff to environmental and social

factors. Staff may burn out and quit; if they stay, they may become less efficient

or less concerned with maintaining adequate data collection standards. In less

extreme situations, staff may allow their own feelings to bias their interactions

with research subjects. In one case, an interviewer systematically, although

unintentionally, biased a question about mothers’ feelings. Finding the idea that

mothers might have negative feelings about 30-day-old infants to be personally

unacceptable, the interviewer unconsciously worded the question in a way that

ensured that the mothers would answer positively. (That is, “You really like the

baby now, don’t you?“)

In another case, an interviewer did not reveal to the investigators that her

father’s alcoholism had influenced her to take the research position. As a

result, it was some time before her reluctance to talk with women about alcohol

abuse was uncovered, and valuable information about mothers’ drinking

behavior was not obtained.

Process Monitoring and Flexible Response

In the real world, things do not always work out as planned. The research

protocol is set up in advance based on theory and the best possible

285
assessment of methodological issues. Custom dictates that it should then be

carried out as planned. Unfortunately, this does not always work. Problems

arise as the project proceeds. Some might have been anticipated; others occur

as a result of environmental changes and could not have been foreseen.

Such a change occurred in a recent protocol that investigated neonatal effects

of cocaine in a hospital environment very familiar to the investigators. Infants

were to be tested on the third day of life because this would allow them to

recover from the birth process and because this period was consistent with

previous research. However, several months into the study, the hospital

implemented an early release policy (at 48 hours postpartum) for all full-term

infants. This change was due to financial constraints and was not subject to

negotiation to meet the needs of the research protocol nor to anticipate the

potential problems that might be associated with prenatal drug exposure.

Therefore, the assessment time had to be changed to the second day even

though new infants’ data could not be compared with that from previous studies.

In addition, infant testers had to adopt an “on-call” schedule since identification

and assessment of infants had to be done in such a short period.

A less obvious problem involved the collection of urines that were used to

confirm recency of cocaine and other drug exposure. Urines were ordered on

all consenting mothers and their infants. However, nurses who had to obtain

the samples sometimes let the urine, especially of female infants, be

contaminated and often did not obtain a second specimen. This bias tended to

be systematic rather than random in-two ways. First, this was a more significant

problem for female infants due to anatomical constraints. Second, nurses were

more reliable about collecting samples from babies known or suspected to be

drug exposed because they saw a purpose in the procedure in such cases but

not in the case of control infants. This problem was discovered through

monitoring of the outcome of data collection procedures on a monthly basis and

by sending the project nurse to question the neonatal nurses when the bias was

suspected. Following the discovery of this problem, changes were instituted to

correct it. Although it was difficult to deal with the female infant bias, it was

possible to have the research staff nurse collect samples from all infants at the

end of her routine examination.

Similarly, problems in questionnaire presentation can be found fairly quickly if

data are consistently examined and staff supervised on a routine basis. Such

rigor can be maintained only when there are adequate resources (i.e.,

supervisor time and money), and provision should be made for such processes

when research is planned and costs estimated.

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Other changes in protocol and errors in collection are more difficult to anticipate,

and one can only adjust to them. In some cases, changes in drug use habits or

characteristics of the population, which are annoying because they interfere

with established protocols, are data. An example of this process occurred

during 3 years of data collection on neonatal cocaine effects. From 1987 to

1990 the drug-using patterns of cocaine users in Atlanta underwent some

changes. For example, use of powdered cocaine (sniffing) and intravenous

cocaine use decreased, while crack use increased. Concurrent with this

change were several changes in vocabulary describing usage, drug type, and

amount that had to be incorporated into the research instruments.

Outside forces also affect clinical research protocol. As mentioned above,

economic constraints affect access to service as well as hospital policy. Legal

issues, particularly the prosecution of women using cocaine in pregnancy, have

affected the number of women willing to admit to cocaine use and to participate

in research. These factors cannot be anticipated or controlled. The only

possible response is to record what is going on and see how outcome is

affected.

SUMMARY

This has been a brief overview of some of the many ways in which the

environment in which prenatal drug research is carried out affects the process

of research and its outcome. In many ways, this chapter is a review of factors

that many people know about but rarely discuss in public. Most scholarly

articles present research in this area as though it is a smooth and orderly

process not much troubled by environmental constraints. The extent to which

research flaws are criticized, even those that are inevitable to the process,

discourages frank discussion of these problems that are familiar to most

investigators who attempt to conduct clinical research in difficult areas. The

purpose of this chapter is to make some of these issues more explicit so that

they can be planned for in future work and taken into account when current

work is reviewed.

REFERENCES

Anderson, S.B., and Ball, S. The Profession and Practice of Program

Evaluation. San Francisco: Jossey-Bass, 1978.

Campbell, D.T., and Stanley, J.C. Experimental and Quasiexperimental

Designs for Research. Chicago: Rand-McNally, 1966.

Capaldi, D., and Patterson, G.R. An approach to the problem of recruitment

and retention rates for longitudinal research. Behav Assess 9:169-177,

1987.

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Coles, CD.; Brown, R.T.; Smith, I.E.; Platzman, K.A.; Erickson, S.; and Falek,

A. Effects of prenatal alcohol exposure at 6 years. I. Physical and cognitive

development. Neurotoxicol Teratol 13:1-11, 1991.

Coles, CD.; Platzman, K.P.; Smith, I.E.; LaRossa, M.; and Falek, A. “Prenatal

Cocaine and Alcohol Exposure and Infant Outcome: Neonatal and 30-Day

Follow-Up.” Paper presented at the Annual Meeting of the Committee on

Problems of Drug Dependence, Inc., Richmond, VA, June 13, 1990.

Coles, C.D.; Smith, I.E.; and Falek, A. Prenatal alcohol exposure and infant

development: Immediate effects and implications for later development. Adv

Alcohol Subst Abuse 6(4):87-104, 1987.

Coulter, M.L.; Runyan, D.K.; Everson, M.D.; Edelsohn, G.A.; and King, N.M.P.

Conflicting needs and interests of researchers and service providers in child

sexual abuse cases. Child Abuse Neglect 9:535-542, 1985.

Datta, L.E. Front-end analysis: Pegasus or shank’s mare? New Dir Prog Anal

1(1):13-30, 1978.

Goldberg, S. The pragmatics and problems of longitudinal research with highrisk infants. In: Fields, T.; Sostek, A.; Goldberg, S.; and Shuman, H.H., eds.

Infants Born at Risk. New York: Spectrum, 1979. pp, 427-442.

Good, L.N.; Strickland, K.E.; and Coles, C.D. “Knowledge and Attitudes of

Public and Professionals About Substance Use in Pregnancy.” Paper

presented at the Annual Meeting of the Committee on Problems of Drug

Dependence, Inc., Richmond, VA, June 13, 1990.

Hansen, J.O. Suffer the children. Parts 1-7 and Followup. Atlanta JournalConstitution, June 4-10, 1989.

Hughes, D. Health of America’s Children. Washington, DC: Children’s

Defense Fund, National Commission to Prevent Infant Mortality, 1989.

Huguley, S.S. Illegal Drugs in Atlanta. The Problem-Oriented Approach to

Drug Enforcement Project. Atlanta, GA: Bureau of Justice Assistance,

Department of Justice, 1989.

Koren, G.; Graham, K.; Shear, H.; and Einarson, T. Bias against the null

hypothesis: The reproductive hazards of cocaine. Lancet 2:1440-1442,

1989.

Kuhn, A. The Logic of Social Systems. San Francisco: Jossey-Bass, 1974.

Kuhn, T. The Structure of Scientific Revolutions. Chicago: University of

Chicago Press, 1970.

Lorion, R.P.; Hightower, A.D.; Work, W.C.; and Shockley, P. The basic

academic skills enhancement program: Translating prevention theory into

action research. J Commun Psychol 15:63-77, 1987.

Lorion, R.P.; Work, W.C.; and Hightower, A.D. Community interventions: The

application of psychological skills in the “real world.” In: Sumprer, G., and

Walfish, S., eds. Clinical, Counseling, and Community Psychology: A

Student Guide to Graduate Training and Professional Practice. New York:

Irvington, 1988.

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Neims, S. “An Overview of Georgia’s Child Protective System.” Paper

prepared for Clinical and Developmental Research Program, Human

Genetics Laboratory, Georgia Mental Health Institute, Atlanta, GA, 1990.

Orne, M.T. On the social psychology of the psychological experiment, With

particular reference to demand characteristics and their implications. Am

Psychol 17(11):776-783, 1962.

Rosenthal, R. Covert communication in the psychological experiment. Psychol

Bull 67:356-367, 1967.

Smith, I.E.; Lancaster, J.S.; Moss-Wells, S.; Coles, C.D.; and Falek, A.

Identifying high-risk pregnant drinkers: Biological and behavioral correlates

of continuous heavy drinking during pregnancy. J Stud Alcohol 48(4):304-

309, 1987.

Thomas, A., and Chess. S. Origins and Evolution of Behavior Disorder: From

Infancy to Early Adult Life. Boston: Harvard University Press, 1987.

Trickett, E.D. Toward a distinctive community psychology: An ecological

metaphor for the conduct of community research and the nature of training.

Am J Commun Psychol 12(3):261-279, 1984.

AUTHOR

Claire D. Coles, Ph.D.

Director

Clinical and Developmental Research Project

Human Genetics Laboratory

Georgia Mental Health Institute

1256 Briarcliff Road, N.E.

Atlanta, GA 30306

Assistant Professor

Department of Psychiatry

Emory University School of Medicine

Atlanta, GA 30322

APPENDIX

Policy and Safety Guidelines for Field Workers

The following information is provided as a guideline for all individuals involved in

making home visits for the purpose of research or intervention. We would like

you to take every precaution to ensure your safety. Please follow these

guidelines carefully. Remember, your own intuition is often the most reliable

source of information. If you encounter a situation that “feels” dangerous, leave.

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General Safety

1.

2.

3.

4.

5.

6.

7.

8.

9.

10.

In the field, wear your State ID or hospital badge so that people will know

why you are there.

Always go out in pairs and never separate. No exceptions. Both workers

should go to the client’s home when making a home visit, and no one is

to stay in the car. If one partner does not feel comfortable

proceeding into any area, neither one should go.

Always leave name, study number, address, telephone number, and

approximate time of visit of each client home visit with secretary before

leaving. When returning, inform secretary that you are back safely.

Someone must stay in the office until you return.

Go only to designated home address (see above). If you have to go to

another location for any reason, call into office and give notice so that

someone will know your whereabouts at all times.

If you are doubtful about the safety of a given area, telephone or write

client and ask if she would meet you in a central location to conduct the

interview.

Do not carry valuables when going on home visits (e.g., jewelry, cash)

and do not leave personal items in the car.

Be alert to the people in the neighborhood, the position and location of

the building, exits and entrances, where public telephones are located,

and whether they are functioning. Do not enter a building whose

entrance is blocked by a group of people or objects.

Know where the entrances and exits in a client’s house are. Do not allow

client to lock an inside door and remove the key.

In case of an emergency, dial 911 immediately to get assistance and

then call project office.

Develop a code or signal with your partner that will alert him or her to a

dangerous situation and practice this beforehand. Have a word whose

use will indicate that it is time to discontinue the interview and leave.

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Automobile Rules

1.

2.

3.

4.

5.

6.

7.

In making home visits, use project or State cars that are clearly identified

with university and State logos. All drivers must be covered under State

or university insurance coverage.

Before deciding to use your personal car, be sure that your insurance

carrier provides adequate coverage.

If you receive a State car and it seems unreliable (e.g., does not start

well), do not drive it. Similarly, do not leave the office without adequate

gasoline. If something happens to a car in the field, call the office

immediately and someone will come to you.

Although you should always use seat belts and keep doors locked while

traveling, always keep vehicle doors unlocked when you are not inside so

that you will have an easy access if you have to leave quickly. Always

check inside car after completing home visit before entering the car.

Never transport clients in your own car under any circumstances.

Infants and children must be transported using approved safety

equipment and seats.

In the field, park only where there is easy access to the car or the street.

If this is not possible, use good judgment as to whether you should

proceed with the visit.

Relationship With Clients and Community

1. Make every possible attempt to get permission from client to schedule a

home visit rather than arriving unexpectedly. This is not only courteous

but will avoid unpleasant surprises.

2. Always treat clients with courtesy and respect. Respect their homes,

family, and property. Always act appropriately and with good manners.

3. Speak to residents in the neighborhood when passing, and if anyone

informs you not to proceed into a given area or apartment, do not

proceed.

4. Act like you know where you are going, as if you belong, and as if you

should be in the neighborhood.

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5. Do not run errands for clients. This is discouraged because it creates a

dual relationship.

6. To avoid violating confidentiality, do not leave any identifying patient

information in the car. Take only the information necessary for the

current visit(s) and keep it with you.

7. Do not discuss client’s history or business with family or neighbors Do

not identify yourselves as associated with substance abuse or with

mental health. If you have to give any information mention the university

or the hospital.

SOURCE: Adapted from safety guidelines developed by the staff of the

Georgia Addiction Pregnancy and Parenting Project and the

Clinical and Developmental Research Project, Human Genetics

Laboratory, Georgia Mental Health Institute, Atlanta, GA.

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Discussion: Research Environment

and Use of Multicenter Studies in

Perinatal Substance Abuse Research

Kenneth C. Rich

INTRODUCTION

In the field of perinatal substance abuse, the research environment is a major

factor in determining the type and content of studies that can be performed and

the likelihood of their success. The challenges presented by the research

environment are greater in perinatal substance abuse research than in many

other research fields because of the complex interrelationship between political,

social, environmental, and medical factors and the outcome that the study is

seeking to assess. As a consequence, the investigator is forced to contend

with a variety of factors that superficially appear to be peripheral to the research

agenda but require careful attention. These include the local clinical

environment in which the study is conducted and the broader philosophical and

political environment that determines the priorities for this type of research and,

consequently, the funding for it.

MACROENVIRONMENT AND PERINATAL SUBSTANCE ABUSE STUDIES

The macroenvironment in which studies are conducted influences whether a

study in a specific field of interest can be performed. Researchers prefer to

believe that good science will be recognized and supported regardless of

national or local political priorities and local institutional goals. The researcher

who is planning a study will find it useful to examine the different levels of the

macroenvironment to make the best fit to the national and local environment

under which the study will be conducted.

National Environment

The national environment is based on priorities developed through the political

and scientific policymaking process. The budgeted monies available for

research in a given discipline vary in response to both these forces as, for

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example, in the priority given to acquired immunodeficiency syndrome (AIDS) in

the recent past and to cancer research in the distant past. This translates into

changing funding availability and, consequently, changing the concentration of

research in a given field. There can be practical problems in the execution of

scientific initiatives that are stimulated by the political process resulting from the

different agendas and frames of reference of scientists and politicians (Bell

1990; Negrete 1990). However, the initiatives can provide good opportunities

for funding for investigators.

In areas that have not received intense pressure from the public and Congress,

fields of concentration are established on the basis of scientific and clinical

priorities identified by the agency or institute. The institute’s interest often is

specified by announcement of a specific initiative and the issuance of a

Request for Applications (RFA). An RFA may be backed with a specific budget

allocation, although the review process is generally a standard grant review

mechanism. RFAs from the Alcohol, Drug Abuse, and Mental Health

Administration or the National Institutes of Health (NIH) are published in the

weekly “NIH Guide for Grants and Contracts”’ and in the Federal Register.

Several agencies have an interest in perinatal drug abuse and publish RFAs in

the Federal Register.

Institutional Environment

In a time of decreasing public funding for health care for the indigent, many

institutions are becoming increasingly reluctant to participate in any initiative

that may increase their indigent population. Furthermore, some (particularly

private) institutions, may refuse to allow publicity for programs that seem to

cater to patients who might be perceived as undesirable by more affluent

patients. This may hamper recruitment efforts for a study and make obtaining

an institutional commitment more than a mere formality. However, the indirect

cost recovery of Federal grants and contracts may partially offset this problem.

MICROENVIRONMENT AND PERINATAL SUBSTANCE ABUSE STUDIES

Coles (this volume) and Kaltenbach and Finnegan (this volume) pointedly raise

many of the problems associated with designing a study to fit into and to make

use of study populations and resources. They also suggest several creative

solutions that may be useful to those embarking on similar studies.

Local Environment

The local environment consists of several components, including the clinical,

psychosocial, and cultural environments.

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Clinical. The clinical environment comprises the patient population and

facilities for their care. In some cases, the study population is a predetermined

group of patients who are participants in a multifaceted, multidisciplinary

program. Kaltenbach and Finnegan describe the Family Center “multivariable

system” approach in which comprehensive care is offered from prenatal care

through long-term postnatal care. The approach incorporates substance abuse

treatment, case management to deal with basic living needs, parenting

education, infant enrichment programs, and psychological care when a woman

is ready for it. Note that the basic needs, such as food, lodging, and medical

care, are handled first. Psychological care and helping the patient have insight

into her problems come considerably later and only after she has the

psychological resources to look at them. The approach is ideal for integrating

clinical care and research. It allows the ready incorporation of research studies

into the clinical milieu with a minimum of disruption of clinical procedures. It

also abrogates some of the methodological problems, such as bias of patient

selection, that are encountered in other studies that use convenience samples.

However, integration of the clinical and research programs in a single staff does

have the problem of the conflicting roles of the participant and the observer (see

below).

As Coles discusses, in many cases the investigator must use study subjects

who are not under the investigator’s direct control. Many groups will not

embrace the possibility of doing research, viewing it as a disruption of their

primary role of serving patients and as a potential cause of additional work.

These objections must be dealt with sensitively and the study procedures

altered as much as possible to take these problems into account. An approach

to similar problems has been discussed by Young and Dombrowski (1989).

Staff education and making the clinical staff feel a part of the process by

soliciting suggestions for improvement and listening to complaints are

important.

Psychosocial. The psychosocial environment in which one encounters the

study participants helps determine their willingness and ability to participate in

perinatal substance abuse studies. The participants have different views of

how the medical system can meet their needs and different priorities in their

lives than the investigators. The success of the study may hinge on its ability to

deal with these needs, including details of patient care. With a high scientific

agenda in mind, such problems as transportation or child care arrangements

may seem minor but may determine the study’s success. It is important to

incorporate adequate personnel into the study plan to deal with these problems,

It is also incumbent on review groups to recognize the importance of these

persons to the success of the study and to allow for them in considering

proposed budgets.

295
Cultural. Another part of the local environment is culture. Many of the potential

study subjects are from minority groups or from quite different social

backgrounds than the investigators. Coles gives an example of a potential

participant who cannot say no directly to an authority figure about participation

but indicates her lack of desire to participate by not showing up for

appointments, The author’s group has experienced similar behavior, usually

associated with very creative explanations about a busy schedule or what was

wrong with the car. This can have an adverse effect on staff morale unless staff

members are made aware of the different significance of the behavior in the

potential subjects’ culture and environment. It also follows that even staff

members who are from minority groups may have little firsthand knowledge and

understanding of those groups’ cultural issues if they have upper middle class

backgrounds and have no experience with the culture of the target population.

Thus, the investigators need to identify sources of information and guidance

about the culture of the study population.

Staff Stress

Staff stress may have many sources and take many forms. The identified

irritant often is markedly displaced from the source. The frustration expressed

about a noncompliant patient may be a reaction to the stress generated by a

dangerous environment, It is important to recognize the manifestations of

stress and deal with the root instead of the overt manifestation. Stress

management may include providing formal staff education and incorporating

staff members into selected parts of the decisionmaking process. Finally, a

means of generating psychological support from within the study staff should be

developed. In the author’s group, this is incorporated into the weekly team

meetings that plan and review clinical and study care of individual patients.

This helps reduce the tendency to burn out in the high-stress environment of

the study.

Role of Observer vs. Participant

Coles points out that the researcher has conflicting roles as both a scientific

observer and a participant in the life of the study participants for whom the

researcher is a care provider and an advocate. These roles easily can become

blurred, resulting in unsatisfactory research, difficult ethical dilemmas, and staff

burnout.

From the researcher’s viewpoint, the social supports developed by the team as

a part of patient care and participant retention efforts can influence the

outcome. For example, the outcome measure of many studies is infant

development. Efforts that are dictated by sound clinical care, such as

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enrichment of the social environment, improve the developmental outcome.

Treatment of chronic medical problems can lead to an apparent reduction in the

medical consequences of substance abuse. These results (desirable from a

patient viewpoint) bias the outcome measures by mitigating the adverse effects

of drug exposure and can cause these effects to be underestimated. Social

support efforts must be applied as uniformly as possible to the study and control

groups, and data must be collected to document that uniformity. One assumes

that both groups would experience enhanced infant development and that

differences between the groups could be attributed to drug effects.

From the social and ethical viewpoint, information may be collected by the study

that can affect the participants. For example, the observer may have

documented continuing drug use in the mother of a newborn. This information

might never have become available except as a part of a study in which a

sense of trust has developed between the mother and the study team. The

ethical dilemma is whether this information should be supplied to the State child

protection agency. An even more demanding situation occurs when an infant’s

urine tests positive for illicit drugs. In many States, one is required to report

this, The author’s group has attempted to deal with this by establishing ground

rules with the mother early in the interaction with the study. She is told that staff

members will report abuse and neglect but that they will take every step

possible to prevent the need for reporting. The group also has a Federal

Certificate of Confidentiality* that protects study data from subpoena but does

allow staff members to take action if there is evidence of abuse and neglect that

needs to be reported. Other chapters in this monograph (Weber; Besharov)

discuss these problems more fully.

Finally, a corollary to the social and ethical conflict for the researcher and

clinician is the conflict between the researcher collecting data for the study and

the researcher and others collecting data for clinical purposes. At the author’s

institution, the neonatologists care for the infant after delivery. They may order

tests and perform procedures that influence the outcome or, in the case of

prenatal substance abuse, determine whether the case is reported to the State.

The fine line between collection of data for study and for clinical purposes and

the difference in how the data may be handled with its long-term social

consequences is not readily comprehended by study participants. Thus,

researchers must be careful about promising confidentiality that cannot be

delivered because part of the care is under the direction of nonstudy personnel.

As both Coles and Kaltenbach and Finnegan point out, a study in the area of

perinatal substance abuse is dynamic, changing in response to the changing

environment and the needs of patients. It is not possible to set the process in

motion and then collect data. The challenge is in the ability of the study team to

meet many needs of participants while keeping the overall direction of the study

297
on course. No study in perinatal substance abuse can be as “clean” as one

might wish, but by keeping in mind the factors that influence the outcome

measures, quality research can be performed.

MULTICENTER COLLABORATIVE STUDIES

Some of the compelling questions of perinatal substance abuse cannot be

answered given the patient resources available at a single center. Enrollment

can be increased by a multicenter collaborative effort, which increases the

spectrum of questions that can be answered. However, the investigator must

consider carefully all the ramifications of developing a multicenter study.

Multicenter collaborative studies provide enormous advantages for some types

of studies but also are filled with potential pitfalls. These studies are often

complex, expensive, and cumbersome. The Federal medical and scientific

research program has several examples of multicenter collaborative studies that

have a well-developed scientific agenda but only a marginal managerial

structure for handling the added complexity of multicenter studies. For those

contemplating setting up a multicenter collaborative study, the following are

points to consider.

Reasons for Using Muiticenter Collaborative Studies

The most obvious reason for using multicenter studies is that they quickly allow

enrollment of many subjects with an uncommon trait. Many of the compelling

questions that face researchers in perinatal substance abuse are about traits

that are sufficiently uncommon that a single site cannot hope to enroll enough

subjects to draw reliable statistical inferences.

The essential first step in determining the need for multisite studies is making

power calculations to determine sample size needs. The basis for these

calculations can be a literature review, preliminary data, or an educated guess.

Unfortunately, many applications ignore these calculations and propose

examining questions that have no hope of being answered given the limits of

the accessible sample. The estimates of the number of subjects that can be

enrolled and retained and the frequency of the trait of interest often are made

based on ideal circumstances that do not occur in most clinical studies.

However, with realistic estimates, the investigators can make a decision about

the need for additional sites and can justify the additional complexity and cost to

the funding agency.

Multicenter studies have other advantages. Chief among these is the

development of a critical mass of expertise and creativity among the

298
investigators. Truly involved collaborators add immeasurably to the richness of

the fabric of the study. One of the most exciting aspects of multicenter studies

is the flow of creativity that can be generated from a diverse spectrum of

colleagues. However, the investigators should guard against the inclusion of a

“name” investigator whose only role may be to lend a patina of respectability to

the application. The review group usually will see through the ploy, and it is

demoralizing to the harder working members of the team.

Another potential strength is forcing a more organized and focused approach to

the study. In view of the need to ensure comparability between sites (see

below), multicenter studies often put additional efforts into formalizing the study

questions and methods. This has the added benefit of eventually producing a

better designed study that is more likely to answer the proposed questions.

Special Problems of Multicenter Studies

Multicenter studies bring a host of problems that are unique to these studies

and accentuate some of the routine problems encountered in any study of a

difficult patient population, such as determining a management style, ensuring

comparability between sites, ensuring that young investigators receive

adequate academic credit and a chance to show creativity, and imposing

special design considerations.

Management. Management of scientific endeavors has been described as

“organized anarchy.” Scientific activities do not fit easily into a strict reporting

system, and any system that attempts to force a good fit runs the risk of stifling

creativity and attracting investigators who lack imagination. However, a critical

need of multicenter studies is sufficient central direction to keep an eye on

strategic issues while allowing creativity. Physicians and nonphysician

scientists usually are untrained in management; therefore, some form of central

management is a critical need for multisite studies. The amount of time

management takes and the distraction from scientific issues it involves should

not be underestimated.

Different styles have been used for the management of multicenter studies.

The best one for a given study depends on the size of the study and the cast of

investigators. One style is a hierarchical management system. In this system,

the principal investigator (PI) assumes responsibility for many of the overall

management decisions and scientific direction of the study. This has the

advantage of providing a coherent, directed approach to the study. A

scientifically sound PI can “just say no” to side issues and data collection of

marginal importance and keep the focus on the central questions.

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Another management style is a matrix in which investigators use a networking

technique in which leadership is decentralized and based on working groups

with different areas of expertise. Numerous informal connections are made,

and decisions are reached by consensus. This takes advantage of creativity

and initiative but can result in an incoherent, unfocused study. Central

coordination and accountability become essential to take advantage of the

matrix style’s strengths and not be derailed by its problems. Examples of such

a management style are some of the large, federally financed experimental

treatment trials that took years of trial and error to create all the informal

connections and to meld them into an effective, efficient study. The ideal format

at any site depends on the resources and size of the project and on the

participants.

Coordination Between Sites. Coordination between sites is a necessity. This

requires the clear spelling out of specifications for all parameters of subject

characterization and procedures. It requires an agreement on procedures,

definitions, and techniques that is codified in a comprehensive procedure

manual. Formal training for the onsite personnel who collect data will be

necessary, and periodic reevaluation at each site will be necessary to ensure

that small changes in procedure are not inadvertently being incorporated, which

could cause a divergence of the long-term direction of the study at the different

sites.

Other more basic issues need to be resolved. If the referral patterns and

participant pool at different sites are dissimilar, results could be biased by the

number of subjects enrolled at each site. For example, long-term

neurodevelopmental outcome in drug-exposed infants may be altered by

environmental factors that are the result of socioeconomic status, To prevent

these biases, enrollment criteria need to be carefully spelled out and data

collected to define the sample population at each site.

Consideration also should be given to having a single site conduct nonroutine

laboratory studies to reduce site-to-site variability. If samples cannot be saved

or shipped, then an agreement will need to be made on the specific technique,

and some form of a quality assurance program will need to be developed. An

example of this need for comparability is urine testing for substances of abuse

that can be done by several techniques that vary by an order of magnitude in

sensitivity and also vary in specificity.

Data Management. Data management is more complex in multicenter studies

than in a single center study. The initial decision is whether a centralized or

distributed system or a hybrid of the two will best meet the needs of the study.

In a centralized system, the local data are collected and sent to the central data

300
manager for checking, computer entry, and analysis. In a distributed system,

data are collected, checked, and entered into the computer locally and

transmitted to the central system.

The advantages of the central system are the ease of ensuring the quality and

integrity of the database after the data entry stage, the need for fewer data

management personnel, and the comparability of procedures between sites.

However, the central system has some disadvantages. Among these is the

slow and cumbersome query process if problems are found with filling out

forms. For example, if an item is left blank on a form, it may be due to lack of

information, or it may be an inadvertent omission. Rapid feedback can allow

many of these queries to be resolved easily, whereas a long delay and a lack of

a sense of involvement in the data management process may lead to a greater

number of data points that cannot be resolved. Furthermore, in a centralized

system, data are not readily available for onsite quality assurance or

examination, and there may be delays in obtaining requested minianalyses due

to a backlog at the central data management center, especially at times when

abstract deadlines are approaching.

Academic and Scientific Credit. A major motivation for coinvestigators to join

a study is to obtain academic credit for promotion and tenure. In multicenter

studies, a degree of individual autonomy is lost, and considerable effort is

required on the part of all the participants. The opportunity for academic payoff

is delayed and, unless credit is fairly attributed to individuals, may be entirely

abrogated. Therefore, a system is required that preserves the ability of

coinvestigators to have their name as first author on some of the publications

and for them to have the opportunity to do important side studies.

At the same time, the integrity of the overall project must be preserved.

Possible conflicts between the individual study and the overall study include

competition for blood samples (especially in the newborn) and adding

procedures that make the study group subjects feel so overstudied that it

jeopardizes the central study. There is also the risk of individual investigators

using data from the central study that should be preserved for presentation as

part of the central study.

To keep coinvestigators vested in the study, a means of encouraging initiative

and creativity needs to be developed. A set of ground rules to which all

participants agree to adhere should address the issues of primacy of

authorship, restriction of certain topics to the main study, and quality of

publications. The latter issue is important to enhance the good name of the

study but needs to be done without appearing to promote censorship.

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Periodic Review and Advisory Group. In a complex organization, a periodic

review of the overall emphasis and progress of the study has considerable

merit. An outside review can either confirm the impression that the agenda is

correct or point out areas of needed change. Independent outside reviewers

who periodically evaluate the study also defuse future criticism about the

scientific merit and priorities of the studies.

An advisory group from the community that is being served also has value by

ensuring responsiveness to the community and constituency being studied.

Active members on the advisory group may help with recruitment and

fundraising. An advisory group also can help forestall criticism of exploitation of

study subjects by individuals or groups who have a political agenda.

Funding Mechanisms

Multicenter studies are expensive. They require duplication of some of the

costs at each site, such as the infrastructure for patient recruitment and

retention and for execution of the study. The issues of establishing

comparability between sites and developing a complex data management

system also add to the cost. However, many questions cannot be answered

without resorting to multicenter studies. Once a multicenter system is set up

and running efficiently, data and new knowledge stream from it.

Different funding mechanisms usually are used for multicenter studies rather

than for individual studies. Not all funding mechanisms are the same, and

some thought and discussion with a program officer should go into deciding the

type of application to make. The traditional and most flexible mechanism of

funding is the investigator-initiated grant (R01), which allows the investigator to

propose and execute a project with little input from the funding agency staff.

However, it should be remembered that the funds available usually are not

sufficient for a costly multicenter application unless an RFA has been published,

Another mechanism is the program project that covers a group of individual but

related studies and shares a core of facilities and expertise. Greater funding is

usually available for program projects than for individual grant applications. The

PI has flexibility in the execution of the project and can, within reason, alter the

direction of the project in response to changing knowledge. There is also more

flexibility in expenditure of funds.

A cooperative agreement is a mechanism in which the awarding agency

anticipates substantial programmatic involvement during the performance of the

award. It is used for some of the large, multicenter projects, such as the AIDS

Clinical Treatment Group sponsored by the National Institute of Allergy and

302
Infectious Diseases (NIAID). In the treatment trials, the PI at an individual site

has general discretion in determining participation in specific subprojects and in

expenditure of local funds. However, progress of the group goals is closely

monitored.

Another mechanism is the contract. It is extensively used by components of

NIH but not by the National Institute on Drug Abuse (NIDA). A specific area of

research need is identified, the work scope is defined by the agency, and a list

of “products” is drawn up. The awardee is expected to deliver the product that

has been defined by the agency, whether it is a specific set of data or a

laboratory technique. As a consequence, the program staff has major input into

the study, although they may elect to work in a collegial relationship with the

investigators in defining the specifics of the study. Contracts have the

advantage from a programmatic viewpoint of allowing a focused approach to a

well-defined question, and this mechanism might be especially valuable when

development of an important watershed of new knowledge is being hampered

by an identifiable missing piece of research infrastructure, information, or

technique or if there are few investigators working in the area. The major

disadvantage is the cumbersome process that must be observed to alter the

direction of the study in light of new knowledge and changing conditions.

Changes that are more than minor must be accompanied by an amendment of

the contract. From an investigator’s viewpoint, the contract mechanism reduces

investigator initiative and flexibility as the investigator must concentrate on the

products.

CONCLUSION

The environment influences the ability to perform studies of perinatal substance

abuse on many levels. At the macroenvironment level, national priorities and

national scientific agenda and priorities determine the funding availability. The

institutional environment determines the reception and support given to the

study. On the microenvironment level, the ability to conduct research depends

on the availability of a patient population. A multidisciplinary clinical

environment enhances the ability to retain and study patients but also poses

some scientific and ethical dilemmas as the investigators are often a part of the

clinical care team. Finally, since some scientific questions cannot be answered

unless many patients are available, multicenter studies should be considered as

a means of increasing the patient pool. However, they present several

challenges such as ensuring comparability between centers, more complex

data management, and the need to ensure academic and scientific credit to all

the investigators.

303
NOTES

1. A subscription to the Guide can be obtained free of charge from NIH Guide,

Printing and Reproduction Branch, National Institutes of Health, Building

31, Room B4BN08, Bethesda, MD 20892.

2. A Federal Certificate of Confidentiality can be obtained from NIDA.

REFERENCES

Bell, D.S. The irrelevance of research to government policies on drugs. Drug

Alcohol Depend 25:221-224, 1990.

Negrete, J.C. Political implications of scientific research in the field of drug

abuse: The case of cannabis. Drug Alcohol Depend 25:225-228, 1990.

Young, C.L., and Dombrowski, M. Psychosocial influences on research subject

recruitment, enrollment and retention. Soc Work Health Care 14(2):43-57,

1989.

ACKNOWLEDGMENTS

The work described in this chapter is supported in part by NIDA grant DA-03651

and by NIAID and National Institute of Child Health and Human Development

grant Al-82505.

AUTHOR

Kenneth C. Rich, M.D.

Associate Professor

Department of Pediatrics, Mail Code 856

University of Illinois at Chicago

Clinical Sciences Building, Room 1240

840 South Wood Street

Chicago, IL 60612

304
Program and Staff Characteristics in

Successful Treatment

Elizabeth R. Brown

INTRODUCTION

Women are a minority population in the majority of drug treatment programs.

Many outcome studies of addiction treatment omit women from their patient

populations. Therefore, a significant gap exists in understanding the

characteristics and successful strategies that will result in good treatment

outcomes for women. Moreover, the data gathered on male populations have

shaped the approaches to treatment used in most programs, and this maleoriented treatment model may not be appropriately applied to drug-dependent

women.

Until the 1970s few studies addressed the need for specialized drug treatment

programs for women. At that time new Federal legislation was enacted (Public

Law 94-371) that mandated the development of specialized drug treatment

programs for women. As a result, the National Institute on Alcohol Abuse and

Alcoholism and the National Institute on Drug Abuse (NIDA) funded research

efforts to define the characteristics of drug-using women and to develop

treatment programs designed to meet the special needs of female addicts.

One of the first studies contrasting male and female narcotics addicts was

reported by Eldred and Washington (1975), who interviewed 79 male and 79

female narcotics addicts as they presented for treatment in a methadone

maintenance program in Washington, DC. Both men and women presented at

a mean age of 25 years, had a mean of about 5 years of heroin use, began

using drugs at a mean age of 20, and had been admitted previously (63 percent

of 158 adults) to the program for treatment. However, there were significant

differences in the life situations and social contexts of drug use in the female vs.

the male addicts.

Male addicts most often were “turned on” to drug use by another man, whereas

female addicts were most often turned on by males. Female addicts were more

likely to report that their drug or money for drugs was given to them by someone

305
else, usually their spouse/partner. In addition, female addicts were more likely

to be separated, divorced, or widowed and living alone and also were more

likely to report that they had children. More women than men were

unemployed, and the majority of all patients were not receiving financial aid on

program entry.

Women are not a homogeneous group and differ in both patterns of drug use

and psychosocial dysfunction. Harrison and Belille (1987) analyzed 1,776

women entering inpatient chemical dependency treatment facilities affiliated

with the Chemical Abuse-Addiction Treatment Outcome Registry during 1982

and 1983. This was largely a white, Midwestern population base. There were

significant differences noted between women ages 30 and younger and women

older than 30 who entered treatment. Younger women were more likely to have

minority status, to be unemployed, to be single, to have dropped out of high

school, and to list their families or welfare benefits as their primary means of

support. Alcohol and tranquilizers were more commonly used by older women

compared with the use of marijuana, cocaine, other stimulants, and

hallucinogens by younger women. Polydrug abuse also was more common in

younger women. Younger women were more likely to report psychological

distress, such as depression, and were more likely to report legal offenses

during the previous year. A much higher proportion of the younger women

reported familial drug use and a higher prevalence of alcohol abuse and

violence in their family of origin and current family. Thus, approaches to

treatment not only need to be gender based but also need to recognize the

impact of the increased psychosocial adversity faced by younger women.

Although white women remain the largest group of female addicts, there have

been major shifts in the past decade toward increased drug use in minority

women, with Hispanic women showing the largest percentage increase. Tyler

and Thompson (1980) analyzed drug use patterns by race, age at first use, and

education for a group of 14,428 female patients who were admitted to 1,400

federally funded drug treatment centers during the third quarter of 1976 and for

whom data were compiled as part of the Client-Oriented Data Acquisition

Process. White women used heroin to a lesser degree than either AfricanAmerican or Hispanic women. Although marijuana was the second most

commonly used drug across all racial groups, it was used to a greater degree

by white women than by those of other races. Women who were 26 years of

age or older at first drug use were more likely to use sedatives, whereas women

who first used drugs at age 19 or 20 were more likely to be using heroin.

Another study of white vs. African-American women entering drug treatment in

either a therapeutic community or a methadone maintenance program was

reported by Moise and colleagues (1982). The subjects were 582 women who

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were participating in research studies carried out as part of the Women’s Drug

Treatment Collaborative Project. Women of both races were socially isolated,

lacked education and job experience, and were having difficulty with custody

disputes with respect to their children. White women more often had a history

of being married, and there was a greater tendency for the spouse or partner of

a white woman to be using drugs. Black women were more likely to have

ongoing responsibility for childrearing and to be living alone. White women as a

group used drugs earlier, had a greater incidence of drug use by their family

members, had more suicide attempts, and had more involvement in illegal

activities. More black women than white women grew up in broken homes and

economic disadvantage, but white women were more likely to access

professional services (private physicians, outpatient mental health facilities,

psychiatrists, and lawyers).

Although a majority of all women seek treatment primarily in outpatient settings,

white women are significantly more likely to enter residential treatment. This

may reflect the ability of white women to access more expensive residential

services as well as the increased number of black women with current

childrearing responsibility, because there are few programs that provide

accommodations for residential drug treatment of women with children. Often,

the only option available to a woman with children who is seeking residential

drug treatment is to place her children in foster care during the period of her

residential treatment. This is a major reason for failure to seek treatment for

many women, because they fear that once their children enter the foster care

system they will be unable to regain custody.

There has been concern in recent years that as the use of drugs by women,

particularly pregnant women, is increasingly criminalized, minority women will

be identified and prosecuted more often than white women. Chasnoff and

colleagues (1990) reported that the incidence of drug use in pregnant women in

Pinellas County, FL, as measured by anonymous urine toxicology studies done

at the first prenatal visit, was 16.3 percent in a public clinic vs. 13.1 percent in

patients receiving care in a private practice setting. The pattern of drug use

also was different. Respectively, public and private patients had 12.4-percent

vs. 11.3-percent positive urine toxicology for marijuana and 5.0-percent vs. 1.5-

percent positive samples for cocaine. White patients were more likely to use

marijuana, whereas black patients were more likely to use cocaine. Of the total

births (5,083) in Pinellas County during the time interval of this anonymous

sampling, 793 infants were black and 4,290 were white. Of infants reported to

the department of social services because their mother used drugs, 10.7

percent were black and 1.1 percent were white, despite a nonsignificant

difference in actual drug use rates.

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It is clear that women entering treatment programs in the 1990s present with

complex problems. Table 1 shows characteristics of a sample of women who

participated in a pilot project to assess the treatment needs of drug-dependent

pregnant women at Boston City Hospital in April-May 1990.

The impact of treatment for maternal drug use on the outcome of pregnancy will

be lessened considerably if the treatment is not comprehensive in nature

because many of the maternal health habits associated with drug use adversely

affect the pregnancy and, therefore, need to be addressed at the same time as

the drug habit. The confounding variables present in drug-using pregnant

women that contribute to low-birth-weight infants were described in an elegant

study of 1,226 women reported by Zuckerman and colleagues (1989). Of the

1,226 women, 216 (18 percent) used cocaine during their pregnancy. The

mean birth weight of infants of cocaine-using women was 2,847 g compared

with 3,254 g in drug-free women, and the mean head circumference of the

infants was 33.0 cm vs. 34.3 cm, respectively. This large difference was highly

significant but confounded by many other differences between the cocaineusing and drug-free groups. Multiple regression analysis showed that 93 g of

the 407 g difference in birth weight was due to cocaine use as measured

TABLE 1. Characteristics of drug-dependent pregnant women in a pilot

project

Characteristic Mean

Age

Gestational age

Gravida

Parity

Race=black 75

Medical problem 83

Current physical abuse 50

Felony conviction 38

High school dropout 50

No driver’s license 75

Lost custody of child 75

Not registered for WIC* 63

29 years

28 weeks

4.25

2.13

Percentage

*Special supplemental food program for Women, Infants, and Children

308
by positive urine toxicology during pregnancy. Women who reported cocaine

use but had negative urine toxicology with multiple urine samples (correlating

with infrequent use) did not show any significant decrease in infant birth weight

due to cocaine use. Women who used cocaine were more likely to smoke

cigarettes, to smoke marijuana, to use other drugs, to have a lower

prepregnancy weight, to have a lower weight gain during pregnancy, and to

have a greater number of sexually transmitted diseases than women who did

not use cocaine. Thus, any treatment program that aims to improve the

outcome of pregnancy in drug-using pregnant women will be unsuccessful if the

focus is on abstinence alone. Such programs need to be comprehensive and to

address the prenatal, medical, social (including food and housing), and

psychiatric (including issues of family violence) needs of women in treatment.

In Massachusetts, only 4 of 47 non-hospital-based treatment programs accept

pregnant women. Boston has only 15 residential beds for drug treatment of

pregnant women. Even if women are accepted, most treatment programs

operate on a male-oriented model, most patients and treatment providers are

men, and there is a lack of orientation to women’s help-seeking patterns, a lack

of provision for child care, and a lack of provision for attention to women’s

particular medical needs (general medical, prenatal, and postnatal care). Many

programs accentuate women’s social isolation and do not address economic

barriers for women by providing appropriate job counseling, vocational training,

or housing. As a result, women continue to underutilize substance abuse

treatment programs.

A comprehensive approach to drug treatment should include drug treatment

along with medical, social, and vocational services for women and child care,

preferably including medical and early intervention services for their children.

Studies of alcohol treatment facilities in California, reported by Beckman and

Amaro (1986), clearly showed that the availability of children’s services

attracted more women into treatment. Finnegan (1979) has demonstrated that

a family-oriented comprehensive treatment program for pregnant drug-using

women can result in pregnancy outcomes that approach those seen with

comparable non-drug-using pregnant women from the same socioeconomic

strata. Chasnoff and colleagues (1989) reported that if cocaine-using pregnant

women entered treatment in the first trimester and were able to stop their drug

use for the remainder of the pregnancy while remaining in prenatal care, then

the birth weight of the infants would closely approximate that of drug-free

women. Thus, a comprehensive approach to drug treatment in pregnant

women can substantially improve the outcome of pregnancy.

The multiple needs of drug-using women in Boston are further defined in a

recent presentation by Amaro (1990), who described the demographic profile of

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the first 157 women recruited into the National AIDS Demonstration Research

Project, funded by NIDA. The Boston project, called the MOM’s Project, is

designed to conduct human immunodeficiency virus (HIV) prevention with

pregnant women at high risk for this infection. Women receive a structured

interview on recruitment to the project, and a followup interview is done 6

months after entry. Services include counseling, HIV testing, group education

and discussion sessions, case management, and advocacy.

Women at high risk for HIV recruited into the MOM’s Project were mainly young

(ages 20 to 29, 66.7 percent), black (81.4 percent), and high school dropouts

(58 percent). One-fifth of the women were homeless and another fifth were

living with friends or relatives in an unstable living arrangement. One-third had

children living with them, but only half of these women were receiving public

assistance. Eighty-five percent of the women were actively using drugs when

recruited, and 30 percent were abusing two or more drugs; however, only 54

percent had ever been in any kind of treatment program. “Crack” was by far the

most commonly used drug of abuse (74 percent). Nearly half of the women

were engaging in sexual activity one or more times per day without using a

condom. The health history of these women was also significant: 57 percent

had a history of sexually transmitted diseases; 2.6 percent were diagnosed with

acquired immunodeficiency syndrome (AIDS) or AIDS-related complex; and 40

percent rated their own health status as fair or poor.

This description of a large group of pregnant drug-using women makes it clear

that the success of drug treatment will depend on the ability to provide

comprehensive services. Substance abuse treatment cannot occur

successfully unless other needs of women-social, medical, economic, and

emotional-are addressed at the same time. Currently, there are many barriers

within the drug treatment system that prevent such a comprehensive approach.

There are limited treatment slots available to pregnant and postpartum women

who wish to keep their children with them while in treatment. Few programs

provide treatment services that are culturally sensitive to the treatment

population. There is little prolonged aftercare provided after “graduation” from a

drug treatment program. Service agencies focus on separate pieces of a

problem (housing, battered women’s shelters, WIC, health services, mental

health services, child care, and job training) and are not able to coordinate

activities. Moreover, women must apply separately for each of these services

and are assigned a separate case worker in each agency. Often, women have

as many as 5 to 10 separate case managers coordinating services, none of

whom is aware of the work done by the others. Reimbursement mechanisms

do not recognize the need to provide “family care”; thus, residential treatment

programs cannot be reimbursed for child care activities.

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The Family Life Center at Harvard Street Neighborhood Health Center and

Boston City Hospital is moving to provide a “one-stop shopping” approach with

a focus on drug treatment in the context of improved parenting. One of the

greatest fears of drug-using women is that they will have their newborn infant

taken away from them. The Family Life Program, developed at the Boston City

Hospital and implemented in a neighborhood setting within a local health center

in the inner city, provides day treatment for substance abuse, prenatal care and

classes, postpartum obstetric care, pediatric primary care, parenting education

(including child development, nutrition, and parenting skills development), early

intervention programs for young children, onsite child care, and advocacy

services to help with the myriad social ills affecting women in treatment. The

services in this latter area range from a food bank and instructions for cooking

nutritious meals on a hotplate, to an onsite laundry with washers and dryers to

use while at the center, to a literacy training program leading to high school

equivalency certification.

An important aspect of advocacy is dealing with personal and sexual violence.

More than 50 percent of patients in treatment currently are abused; as

abstinence is achieved, women may become increasingly depressed, anxious,

and fearful of increased violence in their lives. The need for drug therapists to

be well versed in the treatment of abused women is discussed by Root (1989),

who suggests that drug treatment may be unsuccessful for many women unless

the issues of past and current physical and sexual abuse are concurrently

addressed. She suggests that many so-called treatment failures represent the

inability of some women to cope with ongoing abuse without the numbing effect

of drugs.

SUMMARY

Women come to drug treatment with lower self-esteem (Regan et al. 1984),

more social isolation, and more difficult life situations than men. Women are

more likely to present with mental health comorbidity such as depression

(Regan et al. 1982). Treatment programs modeled on outcome research on

male patients may not yield strategies that are successful with women. Only in

the past decade has research been undertaken into the specific population

characteristics of women in drug treatment. Programs must be designed with a

clear understanding of women’s psychological makeup and particular life stress,

including the need to care for their children and the reality of physical and

sexual abuse. Drug treatment often unmasks a variety of psychosocial

problems that, if not adequately addressed by the drug treatment program, may

result in relapse into drug use. Many women live in poverty and are

inadequately educated, two factors that can interfere with reintegration of the

recovered addict into the community. Thus, the drug treatment program, to

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provide successful long-term outcomes with respect to drug use, must provide

long-term aftercare that includes attention to the variety of social, medical, and

emotional problems faced by women who use drugs.

REFERENCES

Amaro, H. “HIV Prevention With Pregnant Women: Preliminary Findings From

the MOM’s Project.” Paper presented at the 98th Annual American

Psychological Association Convention, Boston, MA, August 12, 1990.

Beckman, L., and Amaro, H. Personal and social differences faced by females

and males entering alcoholism treatment. J Stud Alcohol 45:135-145, 1986.

Chasnoff, I.J.; Griffith, D.R.; MacGregor, S.; Dirkes, K.; and Burns, K.A.

Temporal patterns of cocaine use in pregnancy. JAMA 261:1741-1744,

1989.

Chasnoff, I.J.; Landress, H.J.; and Barrett, M.E. The prevalence of illicit drug or

alcohol use during pregnancy and discrepancies in mandatory reporting in

Pinellas County, Florida. N Engl J Med 322:1202-1206, 1990.

Eldred, C.A, and Washington, M.N. Female heroin addicts in a city treatment

program: The forgotten minority. Psychiatry 38:75-85, 1975.

Finnegan, L.P., ed. Drug Dependence in Pregnancy: Clinical Management of

Mother and Child. National Institute on Drug Abuse Services Research

Monograph Series. DHEW Pub. No. (ADM)79-648. Washington, DC: Supt.

of Docs., US. Govt. Print. Off., 1979.

Harrison, P.A., and Belille, C.A. Women in treatment: Beyond the stereotype.

J Stud Alcohol 48:574-578, 1987.

Moise, R.; Kovach, J.; Reed, B.G.; and Bellows, N. A comparison of black and

white women entering drug abuse treatment programs. Int J Addict 17:35-

39, 1982.

Regan, D.O.; Leifer, B.; and Finnegan, L.P. Depression, self-concept, and

violent experience in drug abusing women and their influence upon parenting

effectiveness. In: Harris, L.S., ed. Problems of Drug Dependence, 1983:

Proceedings of the 45th Annual Scientific Meeting, The Committee on

Problems of Drug Dependence, Inc. National Institute on Drug Abuse

Research Monograph 49. DHHS Pub. No. (ADM)84-1316. Washington, DC:

Supt. of Docs., US Govt. Print. Off., 1984. p. 332.

Regan, D.O.; Leifer, B.; Matteucci, T.; and Finnegan, L.P. Depression in

pregnant drug-dependent women. In: Harris, L.S., ed. Problems of Drug

Dependence, 1981: Proceedings of the 43rd Annual Scientific Meeting, The

Committee on Problems of Drug Dependence, Inc. National Institute on

Drug Abuse Research Monograph 41. NTIS Pub. No. 82-190760.

Springfield, VA: National Technical Information Service, 1982. pp. 466-472.

Root, M.P.P. Treatment failures: The role of sexual victimization in women’s

addictive behavior. Am J Orthopsychiatry 59:542-549, 1989.

312
Tyler, J., and Thompson, M. Patterns of drug abuse among women, lnt J

Addict 15:309-321, 1980.

Zuckerman, B.; Frank, D.A.; Hingson, R.; Amaro, H.; Levenson, S.M.; Kayne,

H.; Parker, S.; Vinci, R.; Aboagye, K.; Fried, L.E.; Cabral, H.; Timperi, R.; and

Bauchner, H. Effects of maternal marijuana and cocaine use on fetal growth.

N Engl J Med 320:762-766, 1989.

AUTHOR

Elizabeth R. Brown, M.D.

Associate Professor of Pediatrics

Boston University School of Medicine

Director of Neonatology

Maternity 2

Boston City Hospital

818 Harrison Avenue

Boston, MA 02118

313

318-164 0 - 92 - 11 : QL 3
Process Measures in Interventions for

Drug-Abusing Women: From Coping

to Competence

Elaine A. Blechman, Thomas A. Wills, and Vera Adler

INTRODUCTION

The purpose of this chapter is to recommend process measures to evaluate

interventions with drug-abusing women. The first part of the chapter answers

the question “What process?,” and the second part recommends process (and

related outcome) measures.

FUNDAMENTAL COPING PROCESSES

One kind of process that might be targeted is the psychological process

(or processes) crucial to a specific intervention. Taking this specific-process

approach, elements of a specific intervention, such as a residential treatment

program, would be described, and the crucial processes thought to be set

in motion by those program elements would be enumerated. Measure

then would be selected to assess whether program elements are faithfully

implemented and whether specific changes are reliably followed by

improvement on key outcome measures such as dirty urines. Thus, a

residential treatment program might encourage clients through daily encounter

groups to engage in higher levels of self-disclosure; in turn, increments in selfdisclosure might be expected to predict fewer dirty urines.

A second kind of process that might be targeted is a process (or processes)

involved with the abuse of drugs of all kinds that must be altered by any type of

treatment program to achieve a successful outcome. Taking this fundamentalprocess approach, psychological processes are specified that are presumed

to distinguish drug-abusing from non-drug-abusing women and that, when

changed, are presumed to predict significantly reduced drug abuse.

This chapter does not take the specific-process approach. A variety of specific

interventions now are being tested in the field. Each specific intervention

requires measures tied to its own elements. A compendium of measures tied to

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several specific interventions would be long and unlikely to advance knowledge

about shared processes of change resulting from diverse yet successful

methods of treating drug abuse in women.

Instead, this chapter takes the fundamental-process approach, focusing on

processes presumed fundamental to drug abuse and its successful treatment

(Bowers and Clum 1988; Garfield and Bergin 1986; Miller and Heather

1986; Wills 1982). More specifically, this chapter focuses on adaptive and

maladaptive coping processes reflected in reinforcer management, challenge

management, and affect management. This approach leads to a consideration

of how women faced with objective challenges (such as poverty and abuse)

shift from maladaptive to adaptive coping because of a specific intervention or

spontaneous, fortuitous life experiences.

A focus on fundamental coping processes offers two benefits to the field.

The first benefit is the development of a theoretical model specifying how

drug-abusing women cope maladaptively and how women who have ceased

to abuse drugs, or who never abused drugs, cope adaptively. This theoretical

model must be comprehensive enough to accommodate the mechanisms

underlying diverse specific interventions for women’s drug abuse. Such a

comprehensive theoretical model of the healing process would permit

interventions to be designed and evaluated on a rational basis. Researchers

could address questions about psychological and biological mechanisms

underlying all successful interventions, in addition to the usual questions about

whether a specific intervention works.

Proceeding from previous work on behavioral interventions with women

(Blechman 1984; Blechman and Brownell 1988), on substance abuse in general

(Blane and Leonard 1987; Kaplan 1980; Meyer 1986; Wills and Shiffman 1985),

and on opiate addiction in particular (Alexander and Hadaway 1982; Khantzian

1980, 1985; Tucker 1985), we develop a model that seems appropriate to

substance-abusing women and argue that:

1.

2.

3.

4.

5.

Maladaptive coping is a central feature of women’s drug abuse.

Adaptive coping is characteristic of fully recovered drug-abusing women.

Maladaptive coping characterizes poorly recovered drug-abusing women at

high risk for relapse.

Spontaneous recovery involves a shift toward adaptive coping.

Interventions for drug-abusing women are most likely to succeed when they

impart adaptive coping.

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This model pays particular attention to the plight of women in poverty since

they are faced with a disproportionate number of objective challenges, few

opportunities to learn adaptive coping, and many opportunities to learn

maladaptive coping.

The second benefit of studying fundamental coping processes is the potential

for development of measures that can chart the course of recovery. These

measures must be suitable for administration to drug-abusing women of all

socioeconomic classes and racial and ethnic backgrounds, including women

who are illiterate, physically ill, and psychologically distressed. They must be

suitable for administration in the settings where drug-abusing women are most

often found: Public hospitals that are crowded and noisy and in which space

and time for administration of research-focused measures are a luxury. At

the same time, measures must be chosen that are capable of capturing the

strengths of women who have ceased to abuse drugs or who, despite the

difficulties of their lives, have never abused drugs. These measures also must

be sensitive to methods of maladaptive coping (e.g., risky sexual behavior,

binge eating) other than drug use that are relied on by drug users and by

women who do not abuse drugs. Establishment of a theoretically informed set

of measures sensitive to the full range of coping strategies of adult women

would offer a great practical advantage to the evaluation of interventions and

to theory-driven basic research.

This chapter proposes measures to assess the fundamental coping processes

of reinforcer management, challenge management, and affect management.

Assessment of these processes is required for complete documentation and

understanding of the course of recovery. Since this chapter’s purpose is to

recommend process measures the scientific evidence for the proposed

theoretical model is only briefly noted. These questions now are being

addressed in our laboratories.

Coping via Reinforcer Management

The most basic coping process involves the continuous management of

reinforcers required for the individual’s physical, social, and psychological

survival. Individuals differ in the number and types of reinforcers they prefer

and in their capacity to delay pursuit and consumption of reinforcers. Despite

these individual differences, continuous management of reinforcers is a basic

requirement of human life.

In adaptive coping, the individual has a relatively large pool of preferred

reinforcers, which confer both short- and long-term gratification and benefits.

The individual knows how to obtain and consume these reinforcers and pursues

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and consumes them only when pressing life problems have been adequately

addressed. In maladaptive coping, the individual’s pool of reinforcers is

restricted to those with short-term gratification and long-term costs. The

individual is ignorant about how to obtain and consume some prized reinforcers

and often pursues short-term reinforcers instead of taking care of urgent

problems.

Sources of Survival and Gratification: Reinforcers. A commodity, activity,

or event can be said to have hedonic reinforcement value for an individual if

the individual makes a concerted effort to come in contact with the potential

reinforcer (the Premack principle). With the exception of extremely depressed

individuals, all people spend some time trying to contact reinforcers, particularly

reinforcers that have universal survival value (e.g., food, water, shelter)

(Blechman 1981).

Reinforcer Preference. People vary greatly in their attraction to reinforcers

(judged by their efforts to contact those reinforcers). In no particular order,

potential reinforcers include food, shelter, sleep, work, company of friends and

family, physical exercise, sexual gratification, money, status, love, shopping,

gambling, and of course, tobacco, alcohol, and other drugs of abuse. Origins of

reinforcer preference may be rooted in biology, learning history, and culture.

People vary greatly in the range of reinforcers to which they are attracted and in

the intensity of their pursuit of one or more reinforcers. Reinforcers are also

likely to be affected by multiple causes, including biology, learning history,

and culture (Leavitt 1982; Levison et al. 1983). Individuals whose lives are

organized around the pursuit of a limited range of reinforcers are popularly

considered addicts even when the reinforcer pursued has short- and longterm benefits (e.g., exercise). The behavioral evidence of addiction (even to

activities like shopping that do not directly induce changes in brain function) is

apparent when the individual spends a large amount of time trying to get in

contact with the reinforcer. What is interesting about the addictive pursuit of

reinforcers is that the behavior involved in chasing them is similar across

classes of reinforcers (e.g., shopping/using cocaine, going to the store/getting

cocaine, thinking and dreaming about shopping/cocaine, talking about

shopping/cocaine to others). Daily plans are made to have contact with the

reinforcer (e.g., finding ways to get money to shop/buy cocaine). The individual

looks forward with pleasure to the next contact with the reinforcer and is willing

to forego other pleasures and endure punishment (e.g., bankruptcy, family

arguments, sexual victimization, arrest) to hasten and increase opportunities for

contact with the reinforcer. The individual strongly believes that contact with the

reinforcer will induce a good mood and chase away a bad mood.

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Individuals who act as if they are addicted to a reinforcer generally report that

(and act as if) the reinforcer has mood-altering effects-abolishing bad moods,

promoting good moods, or both. A biological basis for these effects has been

established for drugs of abuse (Levenson et al. 1987; Pickens and Svikis 1988;

Schuckit 1987; Searles 1988) and for physical exercise. Some people report

(and display) mood-altering effects from activities (e.g., shopping) whose

biological basis is less clear.

Experimentation with reinforcers is inherent in human development from the

beginning of life. In adolescence, teens experiment with chemical substances,

sex, sports, school, and work. Some (with the help of learning history and

temperament) find healthy reinforcers with short-term mood-elevating an

mind-distracting benefits and long-term benefits as well. Some select

unhealthy reinforcers, such as drugs, that have short-term mood-elevating

and mind-distracting benefits and substantial long-term costs. Some find no

reinforcers. They become prone to depression and anxiety. Consistent with

this perspective, Shedler and Block (1990) have reported about a longitudinal

study of three groups of 18-year-olds. Those who experimented in moderation

with drugs and alcohol during adolescence were psychologically healthy; heavy

users and total abstainers were significantly less healthy.

Adaptive and Maladaptive Reinforcer Management. The list of reinforcers

provided above includes some with positive long-term consequences (e.g.,

exercise) and some with negative long-term consequences (e.g., drugs).

Coping is adaptive so long as preferred reinforcers have short- and long-term

benefits and do not replace management of life challenges. Coping is

maladaptive when there are evident short- and long-term risks and when

reinforcers are pursued instead of coping with challenges. Coping is also

maladaptive when nothing has hedonic value for the individual and when the

individual never veers from a focus on problems to pursue pleasure.

Coping via Challenge Management

The most obvious mode of coping involves the individual’s way of dealing with

life challenges. When coping is maladaptive, the individual employs a strategy

that is poorly matched to the nature of the challenge (e.g., denying the

existence of a real threat). When coping is adaptive, the individual employs a

strategy that is well matched to the nature of the challenge.

Objective Challenges. An objective challenge is evoked by any acute or

chronic event or condition with statistically probable negative consequences for

the individual (Lazarus and Folkman 1984). (Challenges also could be called

stressors or problems.) These may be challenges to affective, social, or

318
achievement competence or challenges to physical hardiness. Pregnancy,

poverty, minority ethnic/racial status, sexual victimization, human

immunodeficiency virus (HIV) infection, and diabetes all constitute such

challenges. Objective challenges include stressors operationally defined

as major life events (e.g., job loss), daily hassles (e.g., an argument with a

boyfriend), and problems created by the individual’s own actions (e.g., the

drug cravings of an addict in withdrawal). Thus, objective challenges are an

antecedent to and a result of coping. Maladaptive coping to objective

challenges threatens the individual’s survival by eroding physical hardiness

and affective, social, and achievement competence (Blechman 1981, 1984).

Subjective challenges are events without probable negative consequences but

are followed by increased distress and maladaptive coping on the part of an

individual. The discussion that follows focuses for the most part on coping with

objective challenges. It is presumed, however, that individuals who generally

cope adaptively (or maladaptively) with objective challenges do the same with

subjective challenges.

Objective challenges differ in respect to potential for avoidance, escape,

resolution, and accommodation. Some can be avoided (e.g., using condoms to

avoid pregnancy and HIV infection). Some can be escaped (e.g., getting an

education and a job to escape poverty). Some can be resolved (e.g., reaching

an agreement with a boyfriend to have sex as often as he wants but always with

condom protection). Those that cannot be avoided, escaped, or resolved are

at least amenable to accommodation (e.g., adopting a drug-free lifestyle and

getting prenatal care to ensure that a high-risk pregnancy results in a relatively

healthy mother and baby).

Many challenges in modern, urban society are chronic and recurring (e.g.,

possibility of rape) and require accommodation in which the individual exercises

self-control to make the best of a bad situation (e.g., marshalling resources to

recover from a brutal rape). Poor women are faced with a multitude of chronic,

recurring challenges yet are bereft of resources useful in coping with these

challenges (e.g., having no money to gain access to rehabilitative care after a

rape) (Blechman 1990a).

Challenge-Management Strategies. As noted above, some objective

challenges are amenable to avoidance or escape, others to resolution, and

others only to accommodation. Each of these approaches represents a

challenge-management strategy. (Since some of these strategies do not

resolve the problem at hand, they cannot be called problemsolving strategies.)

Each challenge-management strategy can be adaptive if it is wisely matched

to the challenge at hand. Imminently dangerous, uncontrollable challenges

319
require avoidance or escape. Challenges that will unleash a cascade of new

challenges if avoided or escaped require resolution or accommodation.

For an adaptive match between challenge and strategy, the individual must

sense threat or potential harm associated with the problem, acknowledge that

a problem exists, and recognize the nature of the problem. Thus, in adaptive

coping, the individual must be in affective and cognitive contact with an

objective challenge, experiencing short-term distress, “facing facts,” and

selecting and implementing a strategy that will minimize long-term risk and

maximize long-term benefit for self and others.

Maladaptive Challenge Management. Escape and avoidance are the most

readily available challenge-management strategies, perhaps genetically

programed, certainly available to all people from an early age, and sometimes

effective because they minimize short-term distress (Suls and Fletcher 1985).

Yet, escape and avoidance when mismatched to challenges are maladaptive.

Escape and avoidance when secured through the use of mind- and moodaltering substances (such as drugs and alcohol) are doubly maladaptive

because the substances incur a cascade of new objective challenges. Each

time the distress precedes a successful escape from a challenge, future

distress (and future escape attempts) are strengthened by negative

reinforcement. At the same time, mounting unresolved challenges promote

more real reasons for future distress (Alexander and Hadaway 1982).

Adaptive Challenge Management. In adaptive coping, the individual uses

resolution and accommodation when a challenge calls for these strategies

(Lazarus and Folkman 1984; Moos and Billings 1982). In turn, resolution and

accommodation require the use of subordinate skills of information exchange,

behavior management, and problemsolving with others and with self (Blechman

and Tryon, in press; Wills 1990a). Therefore, resolution and accommodation

are more arduous and less appealing than either escape or avoidance.

Whereas escape and avoidance minimize short-term distress, resolution and

accommodation require the individual to tolerate distress while grappling with a

challenge. The ability to successfully gain social support from significant others

has been shown to be effective for helping smokers (Mermelstein et al. 1986;

Wills and Vaughan 1989) and opiate users (Rhoads 1983; Tucker 1985) avoid

use of dangerous substances. Social integration also has been shown to be a

protective factor for drug abuse (McMahon and Kouzekanani 1991; Timmer et

al. 1985; Pakier and Wills 1990) and acquired immunodeficiency syndrome

(AIDS) risk behavior (Zielony and Wills 1990).

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Coping via Affect Management

The feelings tolerated while an individual grapples with a challenge, pursues a

reinforcer, or succeeds or fails at managing challenges and reinforcers require

coping via affect management (Blechman 1990b). Tronick has observed this

process in infants and calls it affect regulation. Lazarus studies this process

in adults and calls it emotion-focused coping. Wills studies this process in

adolescents and reports that adolescents with chronically high levels of

negative affect and low levels of positive affect, presumably resulting from

inadequate affect management, are at high risk for substance abuse (Wills

1990b; Vaccaro 1991).

We use the term “affect management” (rather than affect regulation or emotionfocused coping), recognizing that the process of dealing with affect is

continuous, often involves awareness and acceptance of affect rather than its

change, and is associated with reinforcer pursuit as well as with confrontation

of challenges. Affect management is defined here to subsume (1) monitoring

of feelings, (2) regulation of feelings, and (3) mood recovery.

Adaptive Affect Management. When coping is adaptive, the individual

manages feelings in ways that optimize the pursuit of reinforcers and the

confrontation of challenges. More specifically, when coping is adaptive, there

is:

1.

2.

3.

Continuous awareness and tolerance of the full range of feelings

associated with reinforcers and challenges. Continuous access to feelings

provides the individual with information that maximizes the management of

reinforcers and challenges.

Skillful regulation of feelings (e.g., from negative to neutral) and control of

impulses (e.g., delaying inappropriate action) so that neither feelings nor

impulsive behavior interferes with management of challenges and

reinforcers.

Rapid recovery of stable good mood, despite the outcome of struggles with

challenges and reinforcers. In adaptive coping the individual can bounce

back relatively quickly after failure confronting a challenge or loss of a

highly valued reinforcer.

Maladaptive Affect Management. When coping is maladaptive, the individual

manages feelings in ways that obstruct the pursuit of reinforcers and the

confrontation of challenges. More specifically, when coping is maladaptive,

there is:

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1. Continuous denial and avoidance of many of the feelings associated with

reinforcers and challenges. Limited access to feelings reduces information

about how to manage reinforcers and challenges.

2. Inept regulation of feelings (e.g., negative feelings cannot be moderated)

and control of impulses (e.g., action cannot be delayed) so that both

feelings and impulsive behavior interfere with management of challenges

and reinforcers. In addition, inept expression of feelings involves the

interpersonal domain of coping; responding to negative emotion through

inappropriate expression (e.g., blaming, yelling, or taking it out on others)

would have several negative consequences, including the erosion of social

support.

3. Difficulty returning to a good or neutral mood once struggles with

challenges and reinforcers are over. In maladaptive coping, the individual

does not bounce back after a failure in confronting a challenge or the loss

of a highly valued reinforcer.

Drug Abuse, Poverty, and Maladaptive Coping

When women abuse drugs, three maladaptive coping processes contribute to,

sustain, and are sustained by drug abuse. Maladaptive reinforcer management,

challenge management, and affect management trap women into drug use and

make escape from drug use and acquisition of adaptive coping increasingly

impossible (Billings and Moos 1983; Marlatt and Gordon 1985; Tucker 1985).

Most important, because of their short-term payoffs, these maladaptive coping

strategies become central features of drug-abusing women’s lives.

Processes of positive and negative reinforcement conspire to train women to

use drugs for reinforcer management (as the primary means of obtaining

pleasure), for challenge management (as the primary means of avoiding

or escaping from challenges), and for affect management (as a means of

regulating affect and impulses and recovering a good mood). Positive

reinforcement of drug use (presentation of a pleasurable event contingent on

the operant drug-using behavior) derives from the drug’s physiological impact

(when the user’s mood is elevated and sexual impulses are heightened), from

the drug user’s social milieu (when the user maintains social support and status

via drug use), and from the user’s economic plight (when the user turns a profit

by selling drugs). Negative reinforcement (removal or reduction of an aversive

event contingent on an operant behavior) of drug use derives from the drug’s

physiological impact on the drug user, particularly its capacity to distract

attention away from challenges, to diminish a bad mood, and to dull hard-tocontrol violent and sexual impulses.

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Poverty and Maladaptive Coping. Given these multiple opportunities for

learning maladaptive coping, it is understandable why drug use is so prevalent,

particularly among people facing numerous chronic and unmanageable

challenges (e.g., inner-city women) with few opportunities to learn adaptive

modes of coping and with many opportunities to observe maladaptive coping.

In addition to subcultural pressures for drug abuse, there are individual social

learning pressures from observing parents or friends use drugs (Biglan et al.

1985; Kandel et al. 1978) and biological pressure from an irritable temperament

that increases the hedonic value of drugs such as cocaine (Lerner and Vicary

1984).

Maladaptive Coping Among Poor Women. Among poor women, biology,

learning history, and the culture of poverty may conspire to promote a drugcentered way of life characterized by maladaptive coping. The culture of

poverty limits women’s access to reinforcers with long-term benefits (e.g.,

nutritious food, uninterrupted sleep) and overexposes them to reinforcers with

long-term costs (e.g., risky sex). Quite often, poor women’s survival seems to

require them to seek reinforcers with long-term costs. This is particularly the

case for risky sex, which many poor women barter for food, shelter, and drugs.

MEASUREMENT OF FUNDAMENTAL COPING PROCESSES

In the preceding section of this chapter, we argued in favor of measuring

fundamental coping processes central to drug abuse and to successful

treatments for drug abuse and specified three fundamental coping processes:

management of reinforcers, management of challenges, and management of

affect. Finally, we proposed that maladaptive coping reinforces and is

reinforced by drug abuse.

This section suggests methods for measuring these coping processes

and associated constructs (e.g., challenges). These same methods can

be used to measure outcomes likely to result when a woman shifts from

maladaptive to adaptive coping and begins to profit from drug abuse treatment.

Recommended process and outcome measures are listed below. Because the

methodology of coping assessment is still developing, several approaches to

coping assessment are suggested and the strengths of particular approaches

are noted. We make recommendations for specific measures when clear

evidence is available linking them to drug use and the measures are

appropriate for administration with a young, uneducated population.

323
Measures of Reinforcers

1. Addiction Severity Index (ASI) (as revised by Blechman and Adler)

(material reinforcers)

2. Perceived social support-Interpersonal Support Evaluation List (ISEL)

3. Social network structure-Social Network Index (SNI)

Measures of Reinforcer Management

4. ASI (as revised by Blechman and Adler)

5. Urine and breathalyzer tests

6. Expectancy for drug effects-Alcohol Expectancies Questionnaire

(AEQ)

7. Self-reinforcement-Frequency of Self-Reinforcement Questionnaire

(FSR)

Measures of Challenges

8. Major life events-Life Events Schedule (LES); weekly events-Recent

Events Scales (RES); subjective stress-Perceived Stress Scale (PSS)

9. Mincy-Sawhill-Wolf measure of residential environment stress

Measures of Challenge Management

10. Intention-Based Coping Inventory (IBCI) (adoptation of Wills’ RBCI)

11. Coping with temptation-Situational Competency Test (SCT)

12. Interpersonal communication (INTERACT/BLISS)

13. Substance-related assertion-Multidimensional Assertiveness Inventory

(MAI)

Measures of Affect Management

14. Bipolar mood adjectives (Zevon and Tellegen factors)

324
15. Depression-Beck Depression Inventory (BDI)

16. Vagal tone

17. Self-control-Self-Control Schedule (SCS)

18. Impulsiveness (Eysenck scales)

General Strategies for Selecting Process Measures

The following five principles guided the selection of the specific measures

enumerated above.

1.

2.

3.

4.

5.

Choose measures that tap fundamental, universal processes associated

with recovery from dysfunction. The decision to measure coping processes

was guided by this principle.

Sample key processes repeatedly over time. This approach allows for

documentation of the course of recovery.

Sample key processes under varying environmental circumstances.

Measure the environment as carefully as the person. Documentation of the

timing of daily hassles, major life events, and changes in the general quality

of the environment (e.g., associated with a move from one neighborhood to

another) allows for inferences about the way in which key processes shape

and are shaped by the environment.

Assume that every important outcome was once a process. Having chosen

measures of fundamental processes, transform these into outcome

measures. This is most easily done by administering the same measure

(of challenge management, for example) repeatedly during participation in

treatment (to reflect process) and repeatedly at the end of treatment and

during followup (to reflect outcome).

Measure key process and outcome variables with diverse methods,

including self-report, direct observation, and physiological measurement.

Expect discrepancies among these measures.

Measures of Reinforcers

Reinforcer management is a fundamental coping process. The following

sections describe methods of measuring reinforcer management. However, it is

a mistake to measure how the individual manages reinforcers while ignoring the

325
range of available reinforcers. When a limited range of reinforcers is available,

as is the case for indigent women, management of reinforcers is (for good

reason) likely to appear deficient.

Two classes of reinforcers deserve consideration and careful measurement:

material reinforcers (e.g., money, property) and social reinforcers (e.g., social

support).

Material Reinforcers (ASI). Availability of material reinforcers can be

assessed by gathering information about all sources of income available to the

respondent. The ASI, which has been revised by Blechman and Adler (1991)

for use with indigent substance abusers and described below as revised,

includes questions that can be used for this purpose.

Social Reinforcers (Assorted Measures). The perceived availability of social

reinforcers has an important impact on drug use initiation and relapse (Billings

and Moos 1983; Wills 1990c). Perceived social support depends on the size

and structure of the social network and the availability of particular supportive

functions (Cohen and Wills 1985; Wills 1991). The ISEL (Cohen and Hoberman

1983) is a psychometrically derived measure that taps dimensions of emotional

support, instrumental support, informational support, and social companionship.

The ISEL and related measures have been shown to predict drug use and

relapse (Billings and Moos 1983; Fondacaro and Heller 1983; Mermelstein

et al. 1986; Wills et al., submitted for publication; Wills and Vaughan 1989).

Standard measures of social network structure, such as the SNI (Cohen 1985),

independently predict drug abuse (McMahon and Kouzekanani 1991; Pakier

and Wills 1990; Tucker 1985) and AIDS risk behavior (Zielony and Wills 1990).

Recommended Measures of Reinforcers. We recommend the ASI (as

revised by Blechman and Adler 1991) to measure availability of material

reinforcers, the ISEL to measure perceived social support, and the SNI to

measure social network structure. These measures have demonstrated

correlations with drug use and have been administered successfully with

similar populations.

Measures of Reinforcer Management

Reinforcer management can be operationalized and measured in several ways

(for general discussions see Alanko 1984; Donovan and Marlatt 1988; Rouse et

al. 1985). This section lists a variety of approaches to measuring reinforcer

management, beginning with the most widely used self-report and biochemical

measures and ending with more experimental measures.

326
Self-Report Measure of Addictive Substance Use (ASI). The ASI (McLellan

et al. 1980a, 1980b) provides a self-report measure of the individual’s reliance

on drugs. The instrument includes scales for severity of drug abuse, psychiatric

symptomatology, and social relationships. The ASI scores for psychiatric

impairment and severity of addiction to alcohol and other drugs have been

shown to predict treatment outcome for drug abuse patients (McLellan et al.

1983; Rounsaville et al. 1986) and AIDS-related risk behavior (Zielony and

Wills 1990). The ASI has been used widely with drug-abusing populations

and, when resources are limited, is the best choice of a measure of reinforcer

management. Blechman and Adler (1991) have revised the ASI for use with

populations of indigent, pregnant substance abusers (Blechman and Adler

1991). They have simplified and adapted the language used in the ASI to

reflect the needs, abilities, and culture of this inner-city population of pregnant

substance abusers. In addition, they have included additional questions

dealing with pregnancy issues (e.g., the subject’s discovery of her pregnancy,

the degree and extent of the subject’s drug use before and after discovery of

pregnancy). Wills’ RBCI, described below, also includes scales to index use of

drugs as a coping mechanism.

Biochemical Measures of Addictive Substance Use (Assorted). Urine drug

screens and breathalyzer tests provide objective measures of the individual’s

reliance on drugs as a source of pleasure and relief from pain (Callahan and

Pecsok 1988). Although urinalysis aggregates drug use over considerable

periods, it has been shown to be sensitive for demonstrating the effect of life

challenges on drug abuse among methadone patients (Pakier and Wills 1990).

Measures of Expectancies About Addictive Substances (AEQ). Self-report

measures of expectancies about drug effects index the extent to which the

individual believes drugs will improve mood, reduce stress, and improve

performance. Generic measures tapping the expectancy that pleasure will be

enhanced and pain reduced by various drugs (alcohol, cocaine, marijuana)

have been shown to predict serious drug abuse in several populations (Annis

and Davis 1988; Kandel et al. 1978; McKirnan and Peterson 1988; Newcomb

et al. 1988). Measures of expectancies for alcohol consumption also have

shown predictive value for adolescent and adult drinking (Brown et al. 1985;

Christiansen et al. 1989; Cooper et al. 1988). The AEQ (Brown et al. 1980,

1985) has been used widely and seems well suited for use with drug-abuser

populations.

Cognitive Reinforcer Management (FSR)

It is important to assess cognitive mechanisms of reinforcement as well as

biological ones. The FSR (Heiby 1983) is a 30-item self-report scale that elicits

327
information about positive self-reinforcement. Items include thinking positive

thoughts about the self, praising oneself for good performance, maintaining

appropriate standards for performance, and not blaming oneself for failure.

Although this scale has not been extensively used in drug abuse research, it

taps a construct that is important for treatment outcome.

Recommended Measures of Reinforcer Management. The following

measures of reinforcer management are recommended: the revised ASI

for self-report of addictive substance use, urine and breathalyzer tests for

biochemical indices of substance use, the AEQ for expectancies about drug

effects, and the FSR questionnaire for cognitive reinforcer management,

Measures of Challenges

Challenges (problems or stressors) refer to aspects of the environment with

which a woman must cope to survive. All too often the woman’s style of

challenge management is assessed while the challenges facing her are

ignored. Challenges can be assessed subjectively via self-report or objectively

through checklists. In the assessment of interventions for drug-using women,

the substantial environmental challenges these women face cannot be ignored.

A successful intervention necessarily will affect the real and perceived

challenges that threaten women’s competence.

Subjectlve Challenges (Assorted Measures). Challenges usually are

measured via self-report checklists that index the occurrence of major life

events and/or everyday negative events (“hassles”). Although there are some

unresolved methodological issues (Baum et al. 1982; Cohen 1988), there is

general consensus for measuring challenges in this way. For measures of

major life events in general populations, the LES (Sarason et al. 1978) is a 57-

item checklist that indexes the occurrence and severity of major events during

the previous year. Adaptations of life events checklists also have been

developed for young adults (Newcomb et al. 1981; Johnson and McCutcheon

1980). Everyday negative events can be measured with the Hassles and Uplifts

Scales, which contain 117 and 135 items, respectively (DeLongis et al. 1982;

Lazarus and Folkman 1988). A shorter version is the RES (Wills 1985), a

24-item weekly events checklist based on the Unpleasant Events Schedule

(Lewinsohn and Amenson 1978) used with adolescents. In addition, measures

of subjective stress such as the PSS (Cohen et al. 1983) assess some

challenges not represented in stressful events checklists. The measures noted

above have been shown to predict substance use in samples of adolescents

and adults (Cohen and Williamson 1988; Newcomb and Harlow 1986; Wills

1986, 1990b). Because measures of major events, daily events, and subjective

stress may be differentially related to drug use, we recommend assessing

challenge at ail three levels whenever this is feasible.

328
Environmental Challenges. Challenges from the residential environment can

be measured by a residential index of underclassness (Mincy et al. 1990).

This index uses ZIP Codes of residence combined with census tract data to

determine the extensiveness of social marginality and behavioral deviance

(e.g., teen pregnancy, unemployment, homicide) in the immediately

surrounding neighborhood. The presumption is that neighborhoods in which

social marginality and behavioral deviance are high represent an extremely

stressful environment.

Recommended Measures of Challenges. For measures of psychological

challenges we recommend the LES for major life events, the RES for weekly

events, and the PSS for subjective stress, because these scales all have

demonstrated relationships with drug abuse. For a measure of environmental

challenge we recommend the Mincy and colleagues (1990) residential measure.

Measures of Challenge Management

Challenge management can be operationalized and measured in terms of

coping, communication, assertiveness, or self-esteem.

Coping (Assorted Measures). There are three fundamental coping processes

directed at reinforcer management, challenge management, and affect

management. However, in common usage, coping is equated with challenge

management. This section describes measures of coping with challenges

(problems or stressors).

The measurement of coping with challenges is the subject of active discussion

about methodology (Carver et al. 1989; Moos and Billings 1982; Stone et al.

1988, in press: Wills and Shiffman 1985). Investigators with a cognitive bent

favor the intention-based approach in which respondents set priorities for goals

in dealing with challenges (problems, stressors) (e.g., Stone and Neale 1984).

Investigators with a behavioral bent favor the response-based approach in

which respondents either report how they deal with a specific challenge

(problem, stressor) or demonstrate how they deal with challenges,

Self-report, response-based measures of coping include the Health and Daily

Living Form (Moos et al. 1984), the Ways of Coping Checklist (Folkman et al.

1986; Folkman and Lazarus 1988), and subsequent adaptations (Vitaliano

et al. 1985, 1990; Carver et al. 1989). An adaptation tested by Rohde and

colleagues (1990) with a sample of older adults produced a 17-item factor

termed Ineffective Escapism, which includes items on drug use. Items

contributing to this factor can be used as a measure of escapist, avoidant

coping.

329
The RBCI, a 54-item self-report, response-based inventory used with

adolescents (Wills 1985), measures 11 coping dimensions, including behavioral

coping, cognitive coping, social support, drug use, avoidance, aggression, and

entertainment. Wills (1985, 1986) has administered his response-based

coping measure and an eight-dimensional, intention-based inventory based

on work by Stone and Neale (1984) (in research with adolescents). He found

that response- and intention-based measures yielded equivalent, significant

relationships between coping and adolescent substance use. In Wills’

adaptation the intention-based measure is relatively brief and can be used to

assess coping with different types of problems and/or over different occasions.

There is some suggestion that the repeated measures approach produces

more reliable assessment (Wills 1986).

Role-play tests provide an opportunity to observe how respondents cope with

simulated temptations to substance use (Abrams et al. 1987; Chaney and

Roszell 1985; Shiffman 1985). Although more expensive than self-report

measures of coping, role-play tests are more suitable for young and poorly

educated adult populations because they present clients with specific situations

in which behavior can be elicited. Measures such as the SCT have been

shown to predict relapse to drug use (Chaney et al. 1978; Chaney and Roszell

1985).

Communication (INTERACT/BLISS)

During real-life, face-to-face communication (with peers, family members,

therapists) respondents demonstrate how they manage interpersonal

challenges (how they exchange information, influence behavior, solve

problems) (Blechman 1990a). The INTERACT/BLISS (Dumas and Blechman

1990) provides a direct observational measure of these three dimensions of

communication. The INTERACT/BLISS can be applied to live or videotaped

interactions with significant others or strangers in unstructured or structured

situations. Moreover, the INTERACT/BLISS can be applied to a verbal

administration of the ASI as revised by Blechman and Adler. The INTERACT/

BLISS is an interactive computer coding system that yields scores believed

indicative of the effectiveness of small-group communication (Blechman and

Tryon, in press).

Assertlveness (MAI). Measures of assertiveness presumably index success at

the behavior management dimension of communication. Assertiveness can be

measured via observation of response to specific temptations (as in the Chaney

and Roszell measure described above) or via self-report to a range of assertion

situations (Botvin and Wills 1985). Wills and coworkers have adapted a selfreport assertiveness inventory originally developed by Gambrill and Richey

330
(1975). Several applications with the MAI (Wills 1985; Wills et al. 1989) have

shown that nonassertive responses predict drug use among adolescents (Wills

et al. 1989) and AIDS risk behavior among adult drug addicts (Zielony and Wills

1990).

Self-Esteem and Self-Efficacy (Assorted Measures). Measures of selfesteem or self-efficacy index the individual’s subjective appraisal of success

at challenge management. Increased self-efficacy and self-esteem are

demonstrated outcomes of successful psychotherapy (Wills 1982) and a

predictable ingredient in effective social support systems (Thoits 1986; Wills

1987; Wills, In press). The use of multidimensional measures of esteem and

efficacy seems advisable because different dimensions correlate in opposite

directions with drug use. For example, feelings of generalized efficacy and selfregard are associated with low drug use, while social esteem and efficacy are

associated with high drug use (Wills and Vaughan, submitted for publication).

Psychometric studies with the Multidimensional Esteem Scales (MES) (Fleming

and Watts 1980) and the Spheres of Control (SOC) measures (Paulhus 1983)

have provided excellent subscales of self-esteem and self-efficacy that may be

adapted for specific populations.

Recommended Measures of Challenge Management

For measurement of challenge management, we favor the Wills IBCI with

scales to measure both productive coping and avoidant coping. When use

in a repeated-measures version, this inventory can be used to determine how

clients cope with different types of problems, and aggregate scores for coping

over different problems can be constructed. For assessing how clients cope

with specific temptations for drug use or other risky behavior, we favor the

Situational Competency Test. For measuring interpersonal behavior, we

recommend the INTERACT/BLISS for communication patterns and the MA

for assertiveness.

Measures of Affect Management

Affect management can be viewed and measured from four vantage points: the

communication of affect (Buck 1984), the subjective experience of affect, the

physiological expression of affect, and the self-control of affect-related behavior.

The INTERACT/BLISS, recommended above as a measure of interpersonal

challenge management, provides a measure of the communication of affect.

This section describes measures corresponding to the other three vantage

points on affect management.

331
Subjective Experience of Positive and Negative Affect (Assorted

Measures). Mood adjective checklists administered daily (e.g., Stone and

Neale 1984) or weekly (e.g., Wills 1986) yield information about respondents’

specific mood states and general sense of well-being (Diener 1984). Wills and

coworkers have found that adolescents prone to drug use report frequent

negative and infrequent positive mood states (Wills 1986; Wills and Vaccaro

1991). Tellegen and colleagues (Watson and Tellegen 1985; Zevon and

Tellegen 1982) have conducted factor-analytic research to determine mood

adjectives that are pure markers of independent dimensions of positive and

negative affects. Other measures of mood states have been derived from this

work (e.g., Diener and Emmons 1984; Watson et al. 1986).

The measures just described assess positive and negative affects. Other

measures focus specifically on negative affect (Watson and Clark 1984) and

on the occurrence and severity of depressive symptomatology. The BDI (Beck

1967) is used extensively to assess clinical levels of depression. For assessing

milder levels of depressive symptomatology in groups that are more like the

general population, the Center for Epidemiologic Studies Depression Scale

(CES-D) (Radloff 1977) has been used and validated with a variety of adult

and adolescent populations. Depression has been linked with drug abuse in

retrospective and prospective studies of adults (Christie et al. 1988) and

adolescents (Deykin et al. 1987; Kandel et al. 1978).

Physiological Expression of Affect (Vagal Tone). A measure of vagal tone

(more precisely, the respiratory component of heart rate variability) gathered

before, during, and after a challenge (e.g., a distressing conversation with

a boyfriend) provides an interesting, albeit experimental, measure of the

individual’s capacity to manage affect and remain calmly attentive in the face

of a challenge. What is known about vagal tone comes mostly from children,

who exhibit curious, sociable behavior and high vagal tone and have many

chances for learning during exposure to challenges (Kagan et al. 1984). Vagal

tone was chosen by Fox (1989) as a measure of reactivity based “on a welldocumented association between it and reaction to sensory stimulation,” Fox

(1989) collected longitudinal data from 88 healthy infants with high and low

vagal tone. Infants with high vagal tone were more reactive to positive and

negative events at 5 months and more sociable at 14 months. Thus, vagal tone

seems a promising physiological index of affect management and of

preparedness for learning and performance.

Self-Control of Affect-Related Behavior (Assorted Measures). In the midst

of reinforcer or challenge management, affect management is always an issue.

Effective reinforcer and challenge management requires self-control over affect

and affect-related behavior so that impulsiveness is limited and thoughtfulness

332
predominates. Several self-control inventories are available to measure this

process,

Eysenck and Eysenck (1977) developed three 134-item scales as independent

measures of impulsiveness, risk-taking, and nonplanning. These three

behavioral tendencies predict drug use in young adult populations (Labouvie

and McGee 1986; Newcomb et al. 1986; Wills et al. 1991).

The Rosenbaum SCS (Rosenbaum 1980) is a 36-item scale tapping a range of

problemsolving and emotion-control strategies, It has been used successfully

with a variety of clinical populations but not with addicts (Rosenbaum 1990), as

has a similar measure developed by Heppner (1989). Kendall and Wilcox’s

scale for children and adolescents (Kendall and Wilcox 1979; Kendall and

Williams 1980) contains simple items appropriate for school or institutional

administration with self-report or staff ratings, The Kendall-Wilcox scale has

been used in several clinical settings (Kendall and Williams 1980). A 22-item

adaptation of this scale is a strong predictor of drug use in adolescent samples

(Wills et al. 1991).

Recommended Measures of Affective Management. For measurement of

recent affective experience we recommend the mood adjectives developed by

Zevon and Tellegen (1982). For assessing depression we recommend the BDI

for clinical populations. Measures for vagal tone are described above. For

measuring self-control we recommend the Kendall and Wilcox scale and the

Eysenck scales for impulsiveness and risk-taking because these measures

have empirical support for predictive substance abuse. We suggest that

investigators carefully examine all the measures discussed above.

SUMMARY

As a guide to the selection of process and outcome measurement in

interventions with drug-abusing women, we have offered a model of

fundamental coping processes. Three coping processes-reinforcer

management, challenge management, and affect management-appear

critical to women’s competence and physical hardiness. When these

processes go awry, substance abuse is a likely result. For successful recovery

from substance abuse, good fortune or purposeful intervention must promote

these coping processes, To measure the impact of any intervention with drugabusing women, methods of assessing fundamental coping processes during

intervention (process measures) and repeatedly after intervention (outcome

measures) are needed.

333
We have described multiple methods of measuring fundamental coping

processes from diverse vantage points: self-report, behavioral observation,

biochemistry, and physiology. We have discussed how these measures relate

to the theoretical model. Finally, we have indicated measures favored and used

in our longitudinal and intervention research on adolescent and perinatal

substance abuse.

The final set of measures, as summarized in the list of recommended process

and outcome measures on pages 324-325, is somewhat lengthy because the

process of intervention is complex. Given the financial and structural limitations

of research in drug treatment settings, it may not be possible for a single

investigator to employ all the recommended measures. An adequate research

design would employ two measures from each of the domains outlined. If

resources allow, more extensive measurement procedures would be possible.

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ACKNOWLEDGMENT

Preparation of this chapter was supported by National Institute on Drug Abuse

grants DA-06360 (EAB) and DA-05950 (TAW) and U.S. Department of

Education grant S184A00035 (TAW).

AUTHORS

Elaine A. Blechman, Ph.D.

Professor

Department of Psychology

University of Colorado at Boulder

Boulder, CO 80309-0345

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Thomas A. Wills, Ph.D.

Associate Professor of Psychology, Epidemiology, and Social Medicine

Ferkauf Graduate School of Psychology and Department of Epidemiology and

Social Medicine

Albert Einstein College of Medicine

1300 Morris Park Avenue

Bronx, NY 10461

Vera Adler, M.S.

Research Associate

Department of Psychiatry and Medicine

State University of New York

Health Sciences Center at Brooklyn

450 Clarkson Avenue

Brooklyn, NY 11203

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Discussion: Dilemmas in Research in

Perinatal Addiction-Intervention

Issues

Loretta P. Finnegan

In their chapters, Brown and Blechman and colleagues present much useful

information about several aspects of intervention. Both encouraging and

distressing comments were heard at the technical review. Of concern are

such statements as the following: “We do not know what treatment is” and

“We do not know what works and what does not.” Researchers do know what

works. They need to utilize sound principles of patient management (e.g., a

good medical, social, and family history; physical examination; and psychiatric

evaluation) and then make a diagnosis or diagnoses. Subsequent to this,

a treatment plan can be developed, and intervention into the multitude of

physical, psychological, and sociological issues that pregnant drug-dependent

women experience can begin. It is not easy, but it is feasible. Many basic

problems will complicate interventions. For example, in Philadelphia,

Kaltenbach and Finnegan (1989) found that 80 percent of the women enrolling

in treatment had one or two parents who were addicted to alcohol or other

drugs. Moreover, 70 percent of the women had been sexually abused by

age 16.

Extensive information is available in the literature so that individuals interested

in research in the area of perinatal addiction can develop a sound knowledge

base. The first responsibility of any individual interested in pursuing the

treatment or intervention aspects of perinatal substance abuse is to understand

the accumulated knowledge in this and related fields. Knowledge of the

following areas is essential: perinatal medicine, neonatology, genetics,

pharmacology, drug abuse treatment, child development assessment,

psychiatry, sociology, and human immunodeficiency virus and other infectious

diseases. These are the foundations of the knowledge base.

In her chapter, Brown comments that social interactions between men and

women are extremely important to treatment outcome. The research team also

needs to recognize the heterogeneity of women in general and the important

impact of ethnicity. The team must realize that women encounter tremendous

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barriers when seeking treatment. Equivalent professional services should be

provided for white and black women. When looking at the mean age of the

women enrolled in treatment research programs, it is clear that they have been

addicted for a long time. What happened when they were adolescents,

frequently pregnant, taking drugs, and involved with delinquent activities?

Where were the pediatricians, nurses, and social workers?

As indicated earlier, the researcher interested in this area must be familiar with

many disciplines and carefully review what he or she reads. Reading the

abstracts of articles is not enough. One must analyze and assess the literature

to ascertain any bias that may have been presented in an article. A good

example of bias is described by Koren and colleagues (1989) in a report titled

“Bias Against the Null Hypothesis: The Reproductive Hazards of Cocaine” that

examined whether studies showing no adverse effects of cocaine in pregnancy

have a different likelihood of being accepted for presentation by the Society for

Pediatric Research. The abstracts reviewed were those submitted between

1985 and 1989. There were 58 abstracts on fetal outcome after gestational

exposure to cocaine. Of the 9 abstracts showing no adverse effect, only 1 (11

percent) was accepted, whereas 28 of the 49 positive ones were accepted (57

percent), a significant difference. Moreover, one could argue that the studies

with negative outcomes were stronger than those with positive outcomes. The

negative studies tended to verify cocaine use more often and to have more

cocaine and control cases. Of the 8 rejected negative studies and the 21

rejected positive studies, significantly more negative studies verified cocaine

use and predominantly reported cocaine use rather than use of other drugs.

The investigators concluded that this bias against the null hypothesis may lead

to distorted estimation of the teratogenic risk of cocaine and that it may cause

women who have used cocaine to terminate their pregnancies unjustifiably.

Another dilemma with regard to clinical research studies is illustrated in a paper

authored by Doering and colleagues (1989) titled “Effects of Cocaine on the

Human Fetus: A Review of Clinical Studies.” This paper reviews the published

studies of pregnancy outcome in cocaine-abusing mothers with a special focus

on structural malformations and other neonatal risks. In their review of 14

clinical studies, the researchers contrasted the differences in the literature with

regard to congenital malformations, neurological outcome, and sudden infant

death syndrome (SIDS). They concluded that, given the limitations of studying

any drug in pregnant women, the absolute risk of maternal cocaine intake may

never be known; however, they did make some meaningful conclusions about

the fetal risk associated with maternal cocaine use from these clinical studies. It

was clear that placental dysfunction due to vascular compromise probably

increases the fetal risk for growth retardation or prematurity. Fetal loss due to

abruptio placentae also may occur. Cocaine-induced neuroexcitation can

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cause neonatal behavioral abnormalities (e.g., increased startle response,

abnormal sleep patterns, and jitteriness), but it is not clear if these behavioral

effects are lastlng. Although there may be an increased risk for fetal structural

abnormalities due to disruption of in utero events possibly related to the

vasoactive properties of cocaine, this result is not consistent across studies.

Several other articles look at the differences in studies regarding SIDS

(Bauchner et al. 1988; Chavez et al. 1979; Kandall et al. 1991). Because of the

differences in results, one must think critically in terms of risk. A review of fetal

and maternal risk factors and neurological outcome studies (Jones and Lopez

1990) indicates much is still unclear. In addition, epidemiological studies are

needed before the risk for structural fetal abnormalities is defined more

precisely.

One of the few epidemiological studies reporting on congenital malformations

from maternal use of cocaine during pregnancy is published by Chavez and

colleagues (1989) at the Centers for Disease Control. They were able to

observe urogenital anomalies at a statistically significant level. In the 1970s

and 1980s many researchers were concerned about the potential hazards of

methadone on child development. Using then-current methodology, no

significant effects of methadone on infant development were found using the

Bayley Scales of Infant Development.

A recent study by Rodning and colleagues (1989) on a few children has

demonstrated that those age 1 1/2 to 2 years who are exposed to a polydrug

environment in utero do not function as well as those who have not been

exposed. The investigators postulate that this may indicate an early sign of

future problems. Clearly, longitudinal followup in these and other children is

essential to confirm this hypothesis.

In studying human populations, there is another vital consideration. Although

researchers may be interested in evaluating the symptomatology of an infant

who is undergoing narcotic abstinence or the neurobehavioral effects on the

child exposed to cocaine, they must be cognizant of what is going on with the

mother of this child and consider interventions with the mother. She needs help

from a medical and psychological standpoint, and research goals will not be

accomplished without her.

There are many who say, “Can addiction truly be cured?” It is clear that it

cannot in every case, but have researchers tried hard enough? Has a

nourishing environment been established for the baby and for the baby’s

mother? Many researchers did not plan to become involved with the treatment

of drug-addicted mothers; however, in the process of researching the issues

around perinatal substance abuse, concerned clinicians saw that the small, very

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ill neonates arriving in intensive care nurseries did not exist in a vacuum. It was

clear that, to help these babies and to learn more about the effects of drugs in

utero, in the neonatal period, and in infancy, efforts had to be initiated when

they were in the uterus, and the mother also had to be considered. The

problems seen in the current literature, the controversies and the dilemmas, are

inherent in research in humans. Because researchers are not dealing with an

animal population that can be well controlled, the rules surrounding research

must be complex and varied.

The best advice for those interested in perinatal addiction research is not to be

a “research litterbug.” Each researcher must critically assess the work of others

and his or her own work and not rush to publish after studying just a few

subjects but consider collaborating with other centers that have similar patients.

The National Institute on Child Health and Human Development has developed

an effective mechanism called the Neonatal Network. Under cooperative

agreements, multiple centers are looking at the same research questions, This

provides a large subject pool and offsets the many confounding variables found

in human populations.

In summary, from reading the chapters in this monograph, it is clear that

researchers in the field of perinatal substance abuse must surround themselves

with knowledgeable people. No one knows or ever will know everything about

the multitude of areas that assist with the development of the appropriate

methodology for the research as well as the appropriate treatment aspects for

the maternal-infant dyad. The Nation is faced with a tragedy, and the impact of

perinatal addiction must be thoroughly studied. Turf issues must be forgotten.

This country’s needs and the individual needs of drug-dependent pregnant

women must be placed above personal gain. If all the superb information

presented in this monograph is utilized, many fewer children would suffer from

the effects of perinatal substance abuse.

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Chavez, G.F.; Mulinare, J.; and Cordero, J.F. Maternal cocaine use during

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Kaltenbach, K.A., and Finnegan, L.P. Prenatal narcotic exposure: Perinatal

and developmental effects. Neurotoxicology 10:597-604, 1989.

Kandall, S.R.; Damus, K.; Gaines, J.J.; and Habel, L. Maternal substance use

and sudden infant death syndrome (SIDS) in offspring. Pediatr Res 29:92A,

1991.

Koren, G.; Graham, K.; Shear, H.; and Elinarson, T. Bias against the null

hypothesis: The reproductive hazards of cocaine. Lancet 2(8677):1440-

1442, 1989.

Rodning, C.; Beckwith, L.; and Howard, J. Prenatal exposure to drugs and its

influence on attachment. Ann N Y Acad Sci 562:352-354, 1989.

AUTHOR

Loretta P. Finnegan, MD.

Senior Adviser on Women’s Issues

National Institute on Drug Abuse

Associate Director for Medical and Clinical Affairs

Office for Substance Abuse Prevention

Alcohol, Drug Abuse, and Mental Health Administration

Department of Health and Human Services

Rockwall II, Suite 615

5600 Fishers Lane

Rockville, MD 20857

Professor of Pediatrics, Psychiatry, and Human Behavior

Jefferson Medical College

Thomas Jefferson University

Philadelphia, PA 19107

348
Alcohol- and Drug-Dependent

Pregnant Women: Laws and Public

Policies That Promote and Inhibit

Research and the Delivery of Services

Ellen Marie Weber

INTRODUCTION

Significant public attention has focused on the urgent need to deal with

maternal alcohol and other drug dependence. Alcohol and other drug

dependence clearly leads to physical, mental, and developmental problems in

women and children, including the increased risk of human immunodeficiency

virus disease and the destabilization of families.

Yet, in the face of this crisis, appropriate drug and alcohol prevention and

treatment services for all women, particularly pregnant women, have been

grossly inadequate. In addition, essential social and health services needed

to support poor families who are affected by substance abuse have been

inadequate. Public response to this crisis has ranged from efforts to increase

prevention, treatment, and health services for drug- and alcohol-dependent

pregnant women, to mandating treatment for pregnant women, to removing

children from families, to criminally prosecuting pregnant women.

Although there is disagreement about the appropriate response to this thorny

issue, no one disputes that women must be encouraged to enter treatment

early-before alcohol and other drug use affects their children-and that

effective treatment services must be expanded dramatically to care for the

women who seek rehabilitation. Early entrance of women into treatment

programs is also crucial for conducting research that is needed to develop and

study effective treatment models for pregnant women.

This chapter examines the laws and recent public policies that encourage

women to enter treatment or deter them from doing so. It first examines the

Federal statutes and regulations that provide for confidentiality of alcohol and

other drug information about individuals who seek or enter treatment. Second,

349
it examines recent trends to use criminal law to prosecute women who use

alcohol and other drugs during pregnancy and to amend State child abuse and

neglect reporting laws to mandate reporting of infants who are exposed

prenatally to or born dependent on drugs and alcohol. Finally, it examines how

the trend toward punitive measures and expanded reporting requirements may

affect treatment programs and the mission of researchers who work with those

programs.

CONFIDENTIALITY OF DRUG AND ALCOHOL PATIENT RECORDS

Several Federal laws and two sets of Federal regulations provide for

confidentiality of information about individuals who are in alcohol and other

drug treatment programs and who are the subjects of research. The most

comprehensive protections are found in the two Federal statutes and the set of

implementing regulations known as the Confidentiality of Alcohol and Drug

Abuse Patient Records regulations (hereinafter referred to as confidentiality

regulations).1

 The other Federal law and set of regulations, which overlap the

confidentiality regulations in some respects, permit researchers who obtain a

Confidentiality Certificate to withhold information about research subjects2

Confidentiality Regulations

The Federal confidentiality laws and regulations guarantee strict confidentiality

for persons who have sought or received treatment or diagnosis for alcohol and

other drug-related problems. Congress enacted extremely strict confidentiality

protections to protect clients’ privacy rights because it recognized that

alcoholism and other drug dependence are stigmatizing illnesses and that

the disclosure of such conditions can lead to harsh results such as loss of

employment or children. Thus, Congress feared that individuals would not enter

treatment or benefit from it fully unless their identities as alcohol and/or other

drug users and information about their treatment were protected by strict

confidentiality.

Accordingly, the confidentiality regulations protect virtually all information about

a woman if she has applied for or received any alcohol-or-other-drug-related

services, including diagnosis, treatment, or referral for treatment, from a

covered program. The restrictions on disclosure apply to virtually all

information, recorded or not, that would identify the woman as an alcohol and/or

other drug user, either directly or by implication. Thus, for example, a treatment

program that is subject to the regulations cannot disclose the identity of a

patient or even confirm that an individual is receiving alcohol or other drug

treatment unless the request for information falls within one of the limited

exceptions recognized by the regulations.

350
Virtually all treatment programs are covered by the confidentiality regulations.

The regulations govern any federally assisted individual or program that

specializes, in whole or in part, in providing treatment, counseling, and/or

assessment and referral services for women with alcohol and other drug

problems. The regulations define Federal assistance broadly, so as to include

direct Federal funding, State and local funding that originates with the Federal

Government, and indirect Federal funding such as having a tax-exempt status.

Programs that are not technically covered under the regulations may choose

nonetheless to comply with the standards.

The regulations prohibit a covered program from disclosing patient-identifying

information3

 to a third party unless certain conditions have been met. The

regulations also prohibit redisclosure by the recipient of information without

compliance with the same conditions. The most common way that a program

may permissibly disclose information is with the client’s consent,4 but there are

several circumstances in which patient-identifying information can be released

without the client’s consent. Two exceptions to the nondisclosure rule that are

particularly relevant to research on drug- and alcohol-dependent women are

those relating to research and child abuse reporting.

Scientific Research. The exception to the nondisclosure rule most relevant to

the National Institute on Drug Abuse’s (NIDA) research mission is the research

exception. Under these regulations, a program may, but is not required to,

disclose patient-identifying information to researchers without patient consent,

provided certain safeguards are met.5

The program may release information only to researchers who the program

director determines are qualified. This decision depends on the

appropriateness of the particular researcher for the research to be conducted.

Researchers also must have a protocol ensuring that information will be stored

securely and will not be redisclosed except as allowed by the regulations.

The researcher must provide a written statement that the protocol has been

reviewed by an independent group of three or more individuals who have

determined that the rights of patients would be adequately protected and that

the potential benefits of the research outweigh any potential risks to patient

confidentiality posed by the disclosure of records.

With the sole exception mentioned in the next paragraph, researchers who

receive patient-identifying information are strictly prohibited from redisclosing

any patient information to anyone outside the treatment program. Research

reports may not identify a patient either directly or indirectly.6

 Finally, no

patient-identifying information obtained by a researcher may be used to conduct

any criminal investigation of a patient, even in response to a Federal or State

court order.7

351
Thus, for example, a scientist who wishes to conduct research on effective

treatment modalities or detoxification procedures for pregnant women can

obtain patient-identifying information if the treatment program authorizes such

research upon determining that the researcher is qualified to conduct the

research and will protect the confidentiality of the patients. However, the

researcher cannot disclose any patient-identifying information in any report or to

anyone not involved with the research project other than the program. The sole

exception to this rule is that the researcher may make an initial report of child

abuse or neglect if State or local law requires it.8,9 However, the researcher

cannot be compelled to disclose information about a woman’s criminal activity

or abuse or neglect of her children to prosecutors.10

Special precautions also must be taken if the researcher seeks to conduct longterm or followup studies of former patients. A researcher may attempt to

contact a woman only if it can be done without disclosing to a third party her

relationship to the treatment program. Accordingly, no inquiries-whether to

relatives, friends, employers, or others-designed to locate a former patient

may be conducted unless they can be carried out in a way that will not reveal

the individual’s status as a former drug or alcohol abuse patient or unless the

patient has signed a proper consent form under the regulations.

Child Abuse and Neglect Reporting. The Federal law and regulations

specifically provide that the regulation’s “restrictions on disclosure and use [of

patient-identifying information] do not apply to the reporting under State law of

incidents of suspected child abuse and neglect to the appropriate State or local

authorities.”11 Thus, all covered alcohol and other drug treatment programs and

scientific researchers who work in such programs must, to the extent mandated

by the State’s child abuse statute, comply with the provisions of the mandatory

reporting laws.

However, this exemption for child abuse reporting applies only to the initial

reports of child abuse or neglect. The exemption does not apply to followup

requests or subpoenas for additional information or records, even if the records

are sought for use in civil or criminal proceedings resulting from the program’s

or researcher’s initial child abuse report. Thus, patient files and information

about patients must be withheld from child protection agencies absent an

appropriate court order12 or patient consent. And, as noted above, the

information obtained by researchers never can be disclosed for purposes of a

criminal investigation or prosecution for child abuse or neglect even if a court

orders such disclosure.

The legislative history of the provision permitting reporting of child abuse makes

clear that reporting is permitted only when there is danger or harm to the child

352
and is not permitted merely because a parent has abused alcohol or other

drugs. According to one of the authors of the provision:

The amendment should be applied so it does not dissuade

persons from coming forward for drug or alcohol abuse

treatment, especially since the children of untreated substance

abusers are among the most common victims of child abuse.

The amendment is not intended to suggest that substance

abuse by itself is a condition that must be reported as child

abuse or neglect. As under current practice, there must be

some reason to suspect actual or imminent harm to the child

(Edwards 1986). (emphasis added)

This guiding principle is extremely important to women who need treatment and

to treatment programs because a requirement that all substance-abusing

parents be reported would deter individuals from entering treatment for fear of a

child abuse investigation and ultimately would result in the closing of many

treatment programs. The sponsors of the amendment permitting child abuse

reporting emphasized that confidentiality is extremely important even in the face

of suspected child abuse. “The amendment is not intended to relieve treatment

providers of the continued responsibility of insuring that the interests of patient

confidentiality are protected to the fullest” (Edwards 1986).

Confidentiality Certificates

A second source of confidentiality specifically protects individuals who are the

subject of research. This law permits researchers engaged in biomedical,

behavioral, clinical, or other research, including research on the use and effect

of alcohol and other psychoactive drugs, to obtain authorization from the

Secretary of the Department of Health and Human Services13 to withhold the

names or other identifying characteristics of research subjects from all persons

not connected with the research. If a researcher is issued a Confidentiality

Certificate, he or she may not be compelled in any Federal, State, or local civil,

criminal, administrative, legislative, or other proceedings to identify such

individuals.14

This law is both broader and narrower than the Federal confidentiality

regulations. It has a more expansive reach because all researchers may

seek authorization to protect the privacy of research subjects.15 Since the

confidentiality regulations only apply to programs that receive Federal

assistance, a researcher may not be bound by the confidentiality regulations if

the program in which he or she conducts research is not federally assisted. On

the other hand, the confidentiality regulations restrict voluntary and compelled

353
disclosures, while a Confidentiality Certificate only protects a researcher from

being compelled to disclose identifying information, Theoretically, a researcher

who had such a certificate could, if not bound by the confidentiality regulations,

voluntarily release information about research subjects.16

Thus, with regard to child abuse and neglect reporting, researchers who work

with drug and alcohol programs that are bound by the Federal regulations must

comply with those regulations to obtain patient information and conduct their

work. All other researchers may wish to obtain a Confidentiality Certificate to

assure women who are the subjects of the research that their confidentiality will

be protected to the greatest extent possible. Such assurances probably will be

necessary to encourage alcohol- and drug-dependent women to participate in

such projects.

PUNITIVE MEASURES AGAINST ALCOHOL- AND DRUG-DEPENDENT

PREGNANT AND POSTPARTUM WOMEN

One alarming response to the crisis of maternal drug and alcohol dependence

has been the criminal prosecution and incarceration of women for alleged drug

use during pregnancy. A second response has been for States to amend their

child abuse and neglect reporting laws to require reporting of infants who have

been exposed prenatally to and/or are dependent on drugs and, in some cases,

alcohol. These legal measures have had and continue to have an impact on

the willingness of women to obtain prenatal care and drug treatment. They also

will affect the scientific community’s ability to conduct research in this area.

Criminal Prosecutions

Seventeen States have arrested and criminally prosecuted at least 45 women

for drug use during pregnancy. These States generally have relied on four

criminal charges. The first and most commonly used charge is distribution of

drugs to a newborn.17 Prosecutors have brought charges based on the theory

that the woman has distributed drugs to the newborn through the umbilical cord

during the brief period—60 to 90 seconds-after birth and before the cord was

clamped or severed.18

A second charge is that of child abuse and endangerment, which usually is

based on a newborn’s positive toxicology test at birth.19 In many cases, these

charges have been dismissed because the State’s child abuse statute was not

intended to cover fetal abuse.20 However, in at least one case, a judge in South

Carolina sentenced a 21-year-old woman to 3 1/2 years in prison, suspended to

5 years probation, on child neglect charges because of her cocaine use during

pregnancy (Plazza 1989).

354
Criminal charges for use or possession of drugs also are being brought against

women based on a newborn’s positive toxicology test. In South Dakota, a

woman who was charged with ingestion of drugs on the basis of the infant’s

toxicology test was arrested 7 months after the birth of her child. The woman

pled guilty and was given the maximum possible sentence even though she had

participated successfully in a treatment program after the birth of her child.21 In

Indiana, a woman was charged with possession of cocaine based on findings

that her child was born addicted to cocaine. The charge grew out of the

hospital’s child abuse report made pursuant to Indiana’s statute that requires a

report of newborns who exhibit signs of drug or alcohol addiction.22

Finally, some courts, in an effort to prevent drug use for the duration of the

pregnancy, have sent pregnant women convicted of non-drug-related criminal

charges to jail. In most cases, these women would have been sentenced to

probation were it not for their status as pregnant drug users. In one highly

publicized case, United States v. Vaughn,23 the judge sentenced a woman

convicted of second-degree theft to a prison term rather than to the usual

sentence of probation when he determined that she was 7 months pregnant

and used cocaine. In imposing the sentence, the judge noted that other judges

of the Superior Court of the District of Columbia had similarly incarcerated

pregnant drug abusers. It is relevant to note that the defendant in this case

received no drug treatment or prenatal care while she was incarcerated.

These cases represent an alarming trend for several reasons. First, and

most important, many experts are warning that punitive measures are

counterproductive and result in deterring women from seeking prenatal care

and treatment (American Society of Addiction Medicine 1990; Chavkin 1990a,

1990b).

Second, in many cases, evidence of drug use and possession is being gathered

from the results of drug tests that are conducted on newborns and women—

often without notice, informed consent, or probable cause to believe the woman

has used or possessed drugs. These practices violate women’s constitutional

rights to due process and to be free from unreasonable searches and seizures.

Many commentators have pointed out that tests conducted without notice and

consent are performed more often by public hospitals on poor and minority

women.

Finally, these cases also raise privacy issues. The U.S. Supreme Court has

held that women are entitled to protections from government intrusions during

pregnancy, although those protections may vary depending on the trimester

involved (Roe v. Wade).24 Criminal prosecutions against drug-dependent

pregnant women penalize a woman solely for her decision to continue a

355
pregnancy. Therefore, they may send the unfortunate message that if you

are drug-dependent and choose to continue your pregnancy you can be

prosecuted, but if you abort you will not be.25

Often, criminal cases have been brought with the goal of deterring other

pregnant women from using drugs during pregnancy, but such prosecutions will

have little deterrent effect. The criminal law appears to have little effect on drug

abuse in general. The proposition that it somehow will have a greater effect

with pregnant women is unsupported by any evidence. Alcohol and other drug

dependence are diseases that must be treated to halt the behavior.26 The sad

fact is that pregnant women seeking treatment are often unable to obtain it

(Chavkin 1990b). The real danger is that criminal prosecutions will deter

women from seeking help for fear they will be punished for exposing their

addiction.

Child Abuse Reporting Statutes

States also have begun to amend their child abuse and neglect statutes

to expand the definition of abuse and neglect to encompass a newborn’s

dependence on or exposure to alcohol and/or other drugs. These statutes raise

significant concerns for drug and alcohol treatment programs and researchers

because treatment providers may be required in some cases to make abuse

and neglect reports solely on the basis of a woman’s prenatal drug or alcohol

use. As noted above, this requirement conflicts with the principle guiding child

abuse reporting under the Federal confidentiality regulations (see section

above).

Nine States have amended their statutes to deal specifically with prenatal drug

and/or alcohol use. Florida, Indiana, Massachusetts, Nevada, Oklahoma, and

Utah mandate reports if a child is born dependent on or addicted to a controlled

substance or addictive drug.27 In addition, Indiana, Nevada, and Utah also

require reporting of children born with fetal alcohol syndrome (FAS).28 Three

other States—Illinois, Minnesota, and Wisconsin-require reports of infants who

have been exposed to drugs.29 In addition, Minnesota requires a physician

to report the nonmedical use of a controlled substance by a woman during

pregnancy and, when there are medical indications of possible use of a

controlled substance, to administer toxicology tests and report positive results

that are found.

Although each State law varies as to which individuals are required to report

suspected child abuse and neglect, some of the above laws may require

treatment programs and researchers to do so.30 In such States, reporting most

likely will be required when the program or researcher works with a child who

356
demonstrates signs of alcohol or other drug dependence or gathers sufficient

information from parents to form a suspicion that a child was born drug- or

alcohol-dependent.

For example, in Florida, any person with knowledge or reasonable suspicion

that a child was born dependent on drugs must make a report. Thus, a

treatment program or a researcher working directly with a drug-dependent infant

in a residential program may be obligated to make a report. Similarly, in

Indiana, any individual, including health care providers, who have reason to

believe that a child was born with FAS or drug addiction must report. The

statutes in Nevada and Minnesota are also sufficiently broad to trigger the

obligation to report if the treatment program or researcher has reason to

believe that a child is suffering from alcohol or other drug dependence.

These laws represent a new trend in child abuse reporting. In addition, States

that have not specifically amended their child abuse statutes may impose an

obligation to report under their case law when evidence of maternal drug use

and infant exposure to drugs exists.31 Because State law interpretations vary

dramatically and change constantly, treatment programs and researchers

should seek legal advice on the scope of their obligations.

IMPACT OF MANDATORY REPORTING LAWS AND CRIMINAL

PROSECUTIONS ON TREATMENT PROGRAMS AND RESEARCHERS

To further the goal of curtailing maternal drug and alcohol dependence, it must

be determined what impact punitive actions will have on the wiilingness of

women to come forward for treatment and, consequently, the ability of

researchers to conduct their work. Clearly, without research, it will not be

possible to develop and implement effective intervention and treatment

programs for women and their children.

Many experts have warned that punitive measures may deter women from

seeking prenatal care and treatment (for example, see American Society of

Addiction Medicine 1990; Chavkin 1990a, 1990b), and anecdotal information

supports this prediction. Moreover, interviews of 22 recipients of demonstration

grants from the Office for Substance Abuse Prevention for Model Projects for

Pregnant and Post-Partum Women and Their Children revealed that 15

programs believed that these measures were indeed deterring women from

coming forward for treatment, 3 programs did not see a deterrent effect, and 4

did not have sufficient information to respond.32

Efforts to criminalize addiction during pregnancy also threaten to change the

role of treatment providers and researchers in that treatment professionals may

357
be transformed from health care providers and advocates for patients to what

one commentator coined, “pregnancy police” (McNulty 1987-88). It seems clear

that this is a dangerous trend that will not result in either healthier mothers or

babies.

CONCLUSION

The Federal confidentiality regulations establish a logical scheme that carefully

balances the privacy rights of women and men in treatment against the public’s

need to protect children against harm. These protections are necessary to

ensure that women and men will enter alcohol and other drug treatment,

recover, and provide a stable life for their children. These protections also

ensure that scientists will be able to develop the most effective intervention and

treatment programs for women and children.

This careful balance is being threatened by efforts to criminally prosecute

women and report them for child abuse based on their conduct during

pregnancy. Such “quick-fix” solutions raise serious legal questions and are not

likely to achieve what is most needed for women and children: services to

recover and create stable families.

NOTES

1.

2.

3.

4.

The statutory protections are set forth in the Comprehensive Alcohol

Abuse and Alcoholism Prevention, Treatment, and Rehabilitation Act of

1970, 42 U.S.C. 290dd-3, and the Drug Abuse Prevention, Treatment,

and Rehabilitation Act, 42 U.S.C. 290ee-3. The Federal regulations are

found at 42 C.F.R. Part 2.

The statute is found at 42 U.S.C. § 241 (d), and the regulations on

Protection of Identity-Research Subjects are found at 42 C.F.R. Part 2a.

42 C.F.R. Section 2.11 of the regulations defines “patient-identifying

information” as the name, address, social security number, photograph,

or similar information by which the identity of a patient-one who has

sought or received alcohol or other drug services-can be determined

with reasonable accuracy and speed either directly or by reference to

other publicly available information.

42 C.F.R. Section 2.31 of the regulations sets forth a specific format for

the client’s consent and provides that the consent form is not valid unless

it contains all the required information. The consent form must be in

writing and contain the following nine elements the name of the program

358
5.

6.

7.

8.

9.

10.

11.

12.

making the disclosure; the name of the individual or organization that will

receive the disclosed information; the name of the patient; the purpose

for the disclosure; how much and what kind of information will be

disclosed; a statement that the patient may revoke the consent at any

time, except to the extent that the program already has acted in reliance

on it; the date or condition on which the consent expires if not previously

revoked; the client’s signature; and the date the consent was signed.

All information provided via a client’s consent must be accompanied by a

written prohibition on redisclosure stating that the information disclosed is

protected by Federal law and that the recipient cannot make any further

disclosure of it unless permitted by the regulations.

See 42 C.F.R. Section 2.52. This exception to the nondisclosure rule

was created to ensure that research to advance drug and alcohol

treatment could be conducted effectively. At the same time, the

regulations sought to balance the researcher’s need for information

against the patient’s right to privacy by imposing strict protections against

the subsequent disclosure and use of all patient-identifying information.

Research reports can discuss a client’s case as long as the report does

not contain any information that could be used to accurately and quickly

identify the client. Reports also can describe aggregate data about the

research subjects since that type of information is not patient identifying.

See 42 C.F.R. Section 2.62.

See 42 C.F.R. Section 2.62.

See 42 C.F.R. Section 2.12(c)(6). The Federal laws were amended in

1986 to remove any restrictions on compliance with State laws

mandating the reporting of child abuse and neglect.

See 42 C.F.R. Section 2.62.

See 42 C.F.R. Section 2.12(c)(6). The Federal laws were amended in

1986 to remove any restrictions on compliance with State laws

mandating the reporting of child abuse and neglect.

Subpart E of the regulations allows a court to issue an order permitting

the program to make a disclosure of information and records that

otherwise would be prohibited. The regulations require the court to follow

special procedures before it issues an order. In contrast to most

359
situations in which records are sought, a subpoena or search warrant,

even when signed by a judge, is not sufficient, standing alone, to require

or even permit a program to make a disclosure. See 42 C.F.R. Section

2.61 (b).

In short, if additional records are sought to conduct a civil investigation or

proceeding against a patient for child abuse or neglect, a motion must be

made for a hearing on the issue, and the program and the patient (or his

or her representative) must be notified that a hearing will be held and

must be given an opportunity to appear in person or file a responsive

statement. See 42 C.F.R. Section 2.64(b).

To issue an authorizing court order, at the required hearing the court

must find that “good cause” exists to issue the order (Section 2.64(d)).

The regulations provide that

[t]o make this [good cause] determination the court must

find that:

1. Other ways of obtaining the information are not

available or would not be effective; and

2. The public interest and need for the disclosure

outweigh the potential injury to the patient, the

physician-patient relationship and the treatment

services.

The Federal regulations also limit the type of material that a court may

order a program to release. Section 2.63 provides that a court may not

order any disclosure of confidential communications made by a patient

unless (1) the disclosure is necessary to protect against an existing threat

to life or of serious bodily injury (including circumstances that constitute

suspected child abuse and neglect); (2) the disclosure is necessary in

connection with the investigation or prosecution of a serious crime such

as homicide or rape; or (3) the patient already has offered evidence

about confidential communications. In addition, Section 2.64(e) provides

that an order must “limit disclosure to those parts of the patient’s record

which are essential to fulfill the objective of the order” and that only those

persons having a need for the information may receive patient records.

To criminally investigate a patient for child abuse or to bring criminal

charges, the court must also find that (1) the crime involved is extremely

360
serious, such as an act causing or threatening to cause death or serious

injury (including child abuse); (2) the records sought are likely to contain

information of significance to the investigation or prosecution; (3) there is

no other practical way to obtain the information; (4) the public interest in

disclosure outweighs any actual or potential harm to the patient, the

doctor-patient relationship, and the ability of the program to provide

services to other patients; and (5) when law enforcement personnel seek

the order, the program has an opportunity to be represented by

independent counsel.

A complete description of the court order procedure is contained in the

Legal Action Center’s publication Confidentiality: A Guide to the New

Federal Regulations.

13. Under the regulations, the Directors of NIDA, the National Institute on

Alcohol Abuse and Alcoholism, and the National Institute of Mental

Health issue confidentiality certificates upon application by the

researcher. See 42 C.F.R. § 2a.3.

14. See 42 U.S.C. § 241 (d).

15. See 42 C.F.R. § 2a.1.

16. See 42 C.F.R. § 2a.4(j)(4) and § 2a.7(c).

17. Florida, Illinois, Georgia, Massachusetts, Michigan, and North Carolina

have charged and prosecuted women on this basis.

18. Women have been convicted in at least two cases. In State of Florida v.

Black, No. 89-5325 (Cir. Ct. Escambia County, Jan 3, 1989), a woman

who admitted to using cocaine twice during pregnancy to induce labor

was sentenced to 18 months in prison and 3 years probation for passing

cocaine to her baby through the umbilical cord. In State of Florida v.

Johnson, No. E89-890-CFA (Fla. Cir. Ct. Jul 13, 1989), appeal docketed,

No. 89-1765 (Fla. Dist. Ct. App. Aug 31, 1989), a woman was found

guilty on two counts of delivery and sentenced to 15 years probation

during which she is prohibited from using drugs or alcohol, going to bars,

or associating with people who use drugs or alcohol.

19. Florida, Michigan, Nevada, Ohio, South Carolina, South Dakota, Texas,

and Wyoming have sought prosecutions on this basis.

361
20. See, for example, Reyes v. Superior Court, 75 Cal.App.3d 214 (Ct. App.

1977); State of California v. Stewart, No. M508197 (Municipal Ct. County

of San Diego, Feb 26,1987) (A woman was arrested under a child

support statute and charged with “falling to follow her doctor’s advice to

stay off her feet, refrain from sexual intercourse, refrain from taking street

drugs, and seek immediate medical attention if she experienced

difficulties with her pregnancy.” The court dismissed the charges finding

that the statute did not apply to the actions of a pregnant woman and did

not create a legal duty of care owed by a pregnant woman to her fetus.);

State of Florida v. Gethers, No. 89-4454 CF10A (Cir. Ct. for Broward

County, Nov 6, 1989); State of Ohio v. Andrews, No. JU 68459 (Ct. C.P.

of Stark County, Jun 19, 1989); State of Ohio v. Gray, No. (CR88-7406

(Ct. of C.P. of Lucas County, Jul 13, 1989); and State of Wyoming v.

Osmus, 276 P.2d 469 (Wyo. 1954) (State child abuse statute not

intended to apply to an unborn child).

21. See State of South Dakota v. Christenson, No. CRI. 90 (S.D. Cir. Ct. Mar

12,1990).

22. State of Indiana v. Yurchak, No. 64 D01-8901-CF-181B (Porter County

Super. Ct. filed Oct 2, 1989).

23. No. F-2172-88B (Super. Ct. of D.C., Aug 23, 1988).

24. 410 U.S. 959 (1973).

25. In addition, many criminal prosecutions have involved an expansion of a

criminal statute to encompass conduct that was never intended to be

proscribed by the statute invoked. For example, some women have been

charged with delivery of a drug to a minor for ingesting a drug during

pregnancy and passing it to their fetuses through the umbilical cord.

26. Indeed, the U.S. Supreme Court held in 1962 that criminal conviction for

being addicted to the use of narcotics violated the Eighth and Fourteenth

Amendments because addiction is a disease. The Court in Robinson

emphasized that drug addiction is a disease:

It is unlikely that any state at this moment in history would

attempt to make it a criminal offense for a person to be

mentally ill, or a leper, or to be afflicted with a venereal

disease... [l]n light of contemporary human knowledge, a law

which made a criminal offense of such a disease would

doubtless be universally thought to be an infliction of cruel

362
27.

and unusual punishment in violation of the Eighth and

Fourteenth Amendments...[T]he prosecution is aimed at

penalizing an illness, rather than at providing medical care

for it. We would forget the teachings of the Eighth

Amendment if we allowed sickness to be made a crime and

permitted sick people to be punished for being

sick . . . . (Robinson v. California, 370 U.S. 660, 1962).

Fla. S. § 415.503(9)(a)(2) (1989) (abuse or neglect includes “physical

dependency of a newborn infant upon any drug controlled [under state

law]” with the exception of those used for detoxification or medically

approved treatment); Ind. Ann. Code § 31-6-4-3.1 (Burns 1987) (child in

need of services includes “child...born with fetal alcohol syndrome or an

addiction to a controlled substance”); Mass. Gen. Law Ann. § 51A (West

Supp. 1990) (mandatory report of child “who is determined to be

physically dependent upon an addictive drug at birth”); Nev. Rev. Stat.

§ 432B.330 (child in need of protection if “he is suffering from congenital

drug addiction or the fetal alcohol syndrome, because of the faults or

habits of a person responsible for his welfare”); Okla. Stat. Ann. Q 646

(West Supp. 1990) (“child born in a condition of dependence on a

controlled substance” must be reported); Utah Code Ann. Q 78-36-3.5

(Cum. Supp. 1989) (“child born with fetal alcohol syndrome or dependent

on a controlled substance” must be reported).

26. Depending on the State’s definition of “addictive drug,” the

Massachusetts statute (see endnote 27) also could encompass

dependence on alcohol.

29. Ill. Rev. Stat. ch. 23, § 2053 (Smith-Hurd 1990) (neglected or abused

minor includes “any newborn infant whose blood or urine contains any

amount of a controlled substance as defined [in state law] or a metabolite

of a controlled substance” with the exception of controlled substances

whose presence results from medical treatment to the mother or

newborn); Minn. Stat. § 626.556 (“neglect includes prenatal exposure to

a controlled substance, as defined [under state law], used by the mother

for a nonmedical purpose, as evidenced by withdrawal symptoms in the

child at birth, results of a toxicology test performed on the mother at

delivery or the child at birth, or medical effects or developmental delays

during the child’s first year of life that medically indicate prenatal

exposure to a controlled substance.”); Wisc. Sess. Laws § 146.0255

(West 1989-90) (infant who has a controlled substance in bodily fluids

must be reported).

363
30.

31.

32.

Several reporting statutes are structured so that treatment programs or

the researchers working with them would not be required to make a

report. For example, in Illinois and Wisconsin, a report is triggered by a

finding of controlled substances in the newborn’s body fluids. Treatment

programs probably would not be responsible for conducting such tests;

and indeed, in Wisconsin that responsibility is given to physicians who

must obtain parental consent prior to testing. In Utah, the obligation to

report rests with medical personnel who attend the birth or care for a

child who is born with fetal alcohol syndrome or dependent on drugs.

Only hospital-based drug and alcohol professionals and researchers who

serve these functions and are deemed to be medical personnel would be

obligated under this statute to make a report. Finally, in Oklahoma, the

duty to report is on those who attend the birth of the child.

See, for example, In the Matter of Stefanel Tyesha C., 157 A.D. 2d

322,556 N.Y.S.2d 280, 1990 W.L. 69335 (N.Y.A.D. 1st Dept., May 29,

1990).

The interviews were conducted by the Treatment Committee of the

Coalition on Alcohol and Drug Dependent Women and Their Children

between February and June 1990. Copies of the interviews are on file at

the National Council on Alcoholism and Drug Dependence, 1511 K

Street, N.W., Washington, DC 20005.

REFERENCES

American Society of Addiction Medicine (ASAM). “Policy Statement on

Chemically Dependent Women and Pregnancy.” Adopted by ASAM Board,

New York, September 25, 1969.

Chavkin, W. American Academy of Pediatrics. Testimony before the U.S.

House of Representatives Select Committee on Children, Youth, and

Families, Washington, DC, May 17, 1990a.

Chavkin, W. Drug addiction and pregnancy: Policy crossroads. Am J Public

Health 80:483-487, 1990b.

Edwards, D. Congressional Rec, August 4, 1986. p. H5362.

McNulty, M. Pregnancy police: The health policy and legal implications of

punishing pregnant women for harm to their fetuses. Rev Law Soc Change

16:277-319, 1987-88.

Plazza, R. “Addicted Baby’s Mother Charged.” Piedmont News, August 16,

1989.

364
AUTHOR

Ellen Marie Weber, J.D.

Legislative Counsel

Legal Action Center

236 Massachusetts Avenue, N.E.

Washington, DC 20002

365
Mandatory Reporting of Child Abuse

and Research on the Effects of

Prenatal Drug Exposure*

Douglas J. Besharov

INTRODUCTION

Research on the effects of prenatal drug exposure raises several serious legal

issues. Many of these issues, such as informed consent and human subjects

protection, have been explored extensively elsewhere and are not discussed

here.1

 Instead, this chapter examines one important question that arises in this

specific context, namely: Does prenatal drug exposure fall under mandatory

child abuse reporting laws? Or to put it more directly, must researchers report

the prenatal drug abuse revealed in their studies? A review of the applicable

laws and court decisions indicates that, in most States, the answer is a qualified

yes.

MANDATORY REPORTING LAWS

All States have laws that require an array of professionals to report suspected

child abuse and neglect. Most professionals who serve children are required to

report. In every State, those required to report include physicians, nurses,

emergency room personnel, coroners, medical examiners, dentists, mental

health professionals (sometimes specified as “psychologists” or “therapists”),

social workers, teachers and other school officials, day-care or child-care

workers, and law enforcement personnel. In some States those required

to report include pharmacists, foster parents, clergy, attorneys, day-care

licensing inspectors, film or photograph processors (largely to detect cases

of sexual exploitation), substance abuse counselors, counselors and staff

at children’s camps, family mediators, staff and volunteers in child abuse

information and referral programs, and “religious healers” (usually Christian

Science practitioners) (Besharov 1990, p.24). Each year other professions

are added to the list.

*SOURCE: Adapted from Besharov 1990

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Everyone must report in some States. About 20 States require a report from

any person who has reason to believe that a child is a victim of abuse or

neglect, regardless of their professional status or relation to the child. This

would include researchers. According to the National Center on Child Abuse

and Neglect, as of 1988, the States that required all persons to report were

Connecticut, Delaware, Florida, Idaho, Indiana, Kentucky, Maryland, Minnesota,

Mississippi, Nebraska, New Hampshire, New Jersey, New Mexico, North

Carolina, Oklahoma, Rhode Island, Tennessee, Texas, Utah, and Wyoming.*

Of course, even those persons not legally required to report may do so. In

all States, anyone may report suspected child abuse or neglect. Anonymous

reports also are accepted in all States.

Reporting is an individual as well as an institutional responsibility. Most

reporting laws do not lift the reporting obligations of staff members when they

notify their superior of suspected child maltreatment. Therefore, staff members

still may be civilly and criminally liable for not reporting if they knew or should

have known that no report was made. Staff members who are falsely told that a

report was made will have a defense against liability unless they knew or should

have known that this was untrue.

REPORTABLE SITUATIONS

All forms of child maltreatment must be reported. The Federal Child Abuse

Prevention and Treatment Act of 1974 requires States to provide for the

reporting of all forms of maltreatment to receive special grants3 The act

provides that “child abuse and neglect” means the physical or mental injury,

sexual abuse or exploitation, negligent treatment, or maltreatment of a child

...under circumstances which indicate that the child’s health or welfare is

harmed or threatened thereby . . .”4

This definition makes reportable any parental act or omission that harms a child

or threatens to do so. As a result, just about every State now requires the

reporting of all forms of physical, sexual, and emotional maltreatment.

Reportable child maltreatment includes:

Physical abuse: physical assaults (such as striking, kicking, biting, throwing,

burning, or poisoning) that caused or could have caused serious physical

injury to the child

Sexual abuse: vaginal, anal, or oral intercourse; vaginal or anal

penetrations; and other forms of inappropriate touching or exhibitionism for

sexual gratification

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Sexual exploitation: use of a child in prostitution, pornography, or other

sexually exploitative activities

Physical deprivation: failure to provide basic necessities (such as food,

clothing, hygiene, and shelter) that caused or over time would cause serious

physical injury, sickness, or disability

Medical neglect: failure to provide the medical, dental, or psychiatric care

needed to prevent or treat serious physical or psychological injuries or

illnesses

Physical endangerment: reckless behavior toward a child (such as leaving a

young child alone or placing a child in a hazardous environment) that caused

or could have caused serious physical injury

Abandonment: leaving a child alone or in the care of another under

circumstances that suggest an intentional abdication of parental

responsibility

Emotional abuse: physical or emotional assaults (such as torture and close

confinement) that caused or could have caused serious psychological injury

Emotional neglect (or “developmental deprivation”): failure to provide the

emotional nurturing and physical and cognitive stimulation needed to prevent

serious developmental deficits

Failure to treat a child’s psychological problems: indifference to a child’s

severe emotional or behavioral problems or parental rejections of

appropriate offers of help

Improper ethical guidance: grossly inappropriate parental conduct or

lifestyles that pose a specific threat to a child’s ethical development or

behavior

Educational neglect: chronic failure to send a child to school (Besharov

1990, p. 30)

The Federal Child Abuse Act contains an important limitation: Reportable

situations are those in which “the child’s health or welfare is harmed or

threatened thereby.” The injury must be sufficiently serious so that there is a

danger to the child’s health or welfare.5 This limitation is meant to protect the

rights of parents to exercise their best judgment about how to raise children and

to protect regional, religious, cultural, and ethnic differences in such beliefs. It

368
means, for example, that parents who allow their children to watch hours of

television are not considered neglectful, although many people think that the

children would be better off doing something else. It also means that, absent

specific legislation, a parent who is abusing drugs should not be reported

unless there is reason to believe that the child is or will be seriously harmed

thereby. Thus, for example, use of marijuana on weekends-in a way that does

not seem to affect the child-is not generally reportable. (The few States that

seem to require reports of such casual or recreational drug use are discussed

below.)6

“Threatened harm” must be reported. Society does not wait until a child is

seriously injured before taking protective action. The Federal Child Abuse Act

states that reports and authorizes agency and court intervention to prevent

future harm. Although statutory provisions vary, they commonly require action if

a child “lacks proper parental care,” is “without proper guardianship,” has

parents “unfit to properly care” for him or her, or is in an “environment injurious

to his welfare.” Such provisions authorize intervention before the child has

been seriously injured, and even before he or she has been abused or

neglected. Hence, injury is not a prerequisite to a report; abuse must be

reported to the authorities if children are in danger of serious injury.

Only “reasonable suspicion” is needed for a report. Because of the difficulty in

obtaining information about a child’s maltreatment, reporting laws do not require

potential reporters to be certain that a child is being abused or neglected or to

have absolute proof of maltreatment. In all States, reports are to be made when

there is “reasonable cause to suspect” or “reasonable cause to believe” that a

child is abused or neglected.7

Requiring only reasonable suspicions of abuse relieves potential reporters of

the need to make a final or definitive diagnosis of maltreatment, which usually

requires a home visit, interviews with parents, and further investigation. After a

report is made, the child protective agency is responsible for determining the

child’s true situation and, if protective intervention is needed, for taking

appropriate action.

LIABILITY FOR FAILURE TO REPORT

Almost all States have a specific law making it a crime nor to report suspected

child abuse and neglect. Even in those that do not, the failure to report may

be a crime under general criminal laws.8

 The criminal penalty is usually of

misdemeanor level, with the potential fine ranging from $100 up to $1,000 and/

or imprisonment ranging from 5 days up to 1 year in jail. Criminal prosecutions

for not reporting have been brought against doctors9 psychiatrists,10

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318-164 0 - 92 - 13 : QL 3
psychologists,” teachers (in one case, a nun),12 social workers13 spouses,14

and friends of the family.15

There is also civil liability for failing to report. A specific statute may establish

civil liability for the failure to report. Under the common law, the violation of a

statutory duty, in this instance the required reporting of suspected abuse and

neglect, may be “negligence per se.” No legislation specifically creating civil

liability is needed: the failure to comply with a statutory mandate establishes the

negligence.16 In other situations, the negligent failure to report may be

considered professional malpractice.

Criminal and civil liability can be based on circumstantial evidence, such as

the child’s “suspicious” or “apparently inflicted” injuries. In Los Angeles, for

example, a doctor-who apparently knew that a 3-year-old child previously had

been removed from her mother’s custody-was prosecuted for not reporting

repeated evidence of severe abuse. According to court documents, the doctor

did not report evidence of abuse, which included “old burns on the chest and

left leg, and the absence of the nasal . . . septum.” His defense was that he

wanted to “give the mother a chance” to avoid further contact with social service

workers, and that he had attempted to treat the child in his office and at her

home. “Thirteen days after [he] began treating her, she died of a massive chest

infection resulting from pneumonia.”17 The doctor entered a no contest plea to

involuntary manslaughter.”18

Liability can be extensive and long-lived. Whatever theory of liability is applied,

when the person who allegedly failed to report was employed by an agency or

organization, the agency or organization also may be sued—and invariably is.19

Most nonlawyers know that there is a statute of limitations to the bringing of

lawsuits. Generally, an action must be filed within 3 or 5 years of when the

harm was done. In all but a few States, however, the statute of limitations

usually does not take effect against minor plaintiffs until they reach age 18.20

Thus, the failure to report the suspected maltreatment of an infant may result in

a lawsuit up to 21 years later. Of course, an action may be initiated on behalf of

a child who is still a minor if it is brought by a legal representative or a duly

appointed guardian.

LEGAL IMMUNITY

All States explicitly grant immunity from civil and criminal liability to persons

who report. Except in two or three States, immunity applies only to reports

made in good faith.21 There is no protection for reports made maliciously

because of prejudice or personal bias or because of reckless or grossly

370
negligent decisionmaking. To reassure potential reporters even more, about

half the States have laws that establish a presumption of good faith.

ABROGATION OF PROFESSIONAL CONFIDENTIALITY

Physicians and many social service or mental health professionals, including

drug treatment counselors, who are most likely to see abused and neglected

children are subject to statutory privileges making their conversations with

patients or clients confidential. Ordinarily, they are prohibited from divulging

anything told to them within the scope of the privilege, unless the protected

person gives permission or the communication involves information about a

crime that will be committed in the future.22 A professional who violates such

privileges may be sued by the protected person. Thus, unless the privilege is

lifted, many abused children could not be reported.

Professional confidentiality is not a bar to reporting. A legal mandate to report

presumably overrides any other law creating a privileged communication—

especially if the reporting law was enacted after the law creating the privilege.

Nevertheless, to remove any question, most State reporting laws contain

specified clauses abrogating statutorily created privileges. Some statutes

abrogate only the privileges governing professionals required to report; others

abrogate all privileges, even if the professionals involved are not required to

report. In addition, almost every jurisdiction has a specific provision abrogating

all or some privileges for the purpose of participating in judicial proceedings

relating to abuse or neglect.

Federal laws also make some conversations and records confidential for

schools,23 drug treatment programs,24 and alcohol treatment programs.25 For

each, exceptions have been made for reporting suspected child maltreatment.

For example, the statutes concerning drug and alcohol treatment programs

specify that “the prohibitions of this section do not apply to the reporting under

State law of incidents of suspected child abuse and neglect to the appropriate

State or local authorities.”26

However, the rules concerning the release of information under these statutes

are complex and vary from community to community.27 (For further information

on this subject, contact the local child protective agency, the particular Federal

agency involved, or the US National Center on Child Abuse and Neglect.)

Families already in treatment must be reported. Some mental health and

social service professionals feel that reporting parents already in treatment

violates their ethical obligations toward the parents because, throughout their

professional training and careers, great emphasis was placed on guarding the

371
privacy of their clients, They also fear that reporting the parents to a child

protective agency and testifying against them in court may reinforce the

insecurity and hostility many abusive and neglectful parents feel and may

disrupt the treatment already in progress.

Three or four States give mandated professionals limited discretion not to report

but only under extremely restricted circumstances.28 In all the rest, persons

mandated to report have no discretion; they must break confidentiality to report

suspected child maltreatment.

EXPLICIT REQUIREMENTS TO REPORT PRENATAL DRUG EXPOSURE

Researchers conducting studies of prenatal drug exposure are likely to belong

to the professional groups legally required to report suspected child abuse

and neglect. Moreover, in about 20 States, all persons-regardless of any

professional status-are required to report. So if the researcher is mandated to

report, the question is: Must prenatal drug exposure be reported? Depending

on the State, the answer is a qualified yes.

In a growing number of States, prenatal drug exposure or parental drug use is

explicitly made subject to mandatory child abuse reporting statutes. Of those

States having a law, the largest number require reporting of newborns who

have been exposed to drugs.29 In general, these States limit reporting to

exposure to illegal substances. Sometimes prescription drugs or drugs taken

pursuant to chemical dependency treatment programs are expressly excluded

from reporting mandates, but most often the exclusion is accomplished by

referencing the State’s controlled substance statutes.30 In all States, this

apparently includes marijuana,31 although child protective agencies rarely

accept jurisdiction in such cases. One exception to these general rules is fetal

alcohol syndrome, now required to be reported in about four States.

The specified condition of an infant that establishes the duty to report varies

among States. Some States require signs of dependence or physical addiction

before invoking reporting mandates.32 This requirement is problematic because

of debate about the addictive qualities of cocaine. Others merely require a

positive toxicology,33 which can occur without any signs of dependency. A

new development (enacted in one State and pending in others) is a statutory

requirement that physicians perform toxicology screens on infants whom they

suspect were exposed to drugs.34

Parental drug use is the focus of other State laws. Many States have enacted

or are considering statutes that identify parental substance abuse as evidence

of child abuse or neglect and, therefore, require a report to child protective

372
agencies.35 Apparently, no State requires reports of all levels of drug use, no

matter how minor. Minnesota, though, requires a physician to:

administer a toxicology test to a pregnant woman under the

physician’s care to determine whether there is evidence that she

has ingested a controlled substance, if the woman has obstetrical

complications that are a medical indication of possible use of a

controlled substance for a non-medical purpose. If the test results

are positive, the physician shall report the results under Section 5.

A negative test result does not eliminate the obligation to report

under Section 5, if other evidence gives the physician reason to

believe the patient has used a controlled substance for nonmedical purposes.36

Even if statutory mandates do not exist, many States have court decisions that

hold that parental substance abuse is evidence of child abuse and neglect37

A growing number of States will accept a report before the child is born to give

child protective authorities time to mobilize. At least one State requires such

reporting.38

IMPLICIT REQUIREMENTS TO REPORT PRENATAL DRUG EXPOSURE

Most States do not have legislation that explicitly addresses reporting of

prenatal drug exposure. Even in these States, though, legal analysis

indicates that reports of prenatal drug exposure are required when the

exposure suggests that the parent is seriously addicted to a debilitating drug.39

(The phrase “legal analysis” is used deliberately because there are few court

decisions on the subject, and the practice seems to vary even within the same

community.)

As described above, a mandated reporter must report when there is reasonable

cause to suspect that “the child’s health or welfare is harmed or threatened.”

Thus, the operative legal question becomes: Does prenatal drug exposure

create reasonable cause to suspect that the child has been seriously harmed or

is threatened thereby? The evidence is clear that, at least sometimes, the

answer is yes.

Severe parental drug or alcohol abuse is a reportable condition because it can

so strikingly impair a parent’s judgment and ability to cope that serious harm to

the child becomes likely. Parents suffering from such severe drug habits that

they cannot care for themselves also cannot care for their children.40 Moreover,

there is evidence that drug use can make parents more violent toward their

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children, A Ramsey County Minnesota Department of Human Services report,

after reviewing 70 cases of “cocaine-attached” households in mid-1988, found

that these parents are “extremely volatile with episodes of ‘normal’ behavior

interspersed with episodes of unpredictable, dangerous and even violent

behavior.”41

In the absence of suitable arrangements for the children of these parents, State

intervention is essential no matter how caring such parents may seem. A report

should be made, even if the child is not yet harmed and even if the parent has

never had custody of the child.42 To wait until the child shows signs of abuse or

neglect would unreasonably endanger many children and, as this chapter

describes, may expose the professional to civil or criminal penalties.

There are many degrees of parental incapacity, however, and a prediction of

future serious harm to the child—and, therefore, a report—is justified only in

cases of regular or continuous drug or alcohol abuse that so severely impairs

the parent’s judgment or ability to function that future abuse or neglect is likely.

Thus, in a statutory construction used in several States, the New York Family

Court Act provides that:

proof that a person repeatedly uses a drug, or drugs or alcoholic

beverages, to the extent that it has or would ordinarily have the

effect of producing in the user thereof a substantial state of stupor,

unconsciousness, intoxication, hallucination, disorientation, or

incompetence, or a substantial impairment of judgment, or a

substantial manifestation of irrationality, shall be prima facie

evidence that a child [is neglected].43

Except in those States where any level of drug addiction must be reported, the

parents’ participation in a treatment or counseling program does not establish

that a report should be made;44 the parent, perhaps with outside help, may be

adequately caring for the child.

Some States consider the harm or threatened harm to the fetus as a form of

reportable child abuse. A pregnant woman who continues illicit drug or alcohol

use may give birth to a child with severe problems. Untreated neonatal

addiction to heroin, for example, can be fatal. The dangers encountered by

heroin babies were described 20 years ago in a New York City case:

[The] baby was born normally without apparent symptoms until 24

hours after birth, [when] the baby began to exhibit unmistakable

narcotic withdrawal symptoms; preconvulsive tremors,

hyperactivity, incessant crying, ravenousness alternating with

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vomiting. . . . Sedatives (phenobarbital), dark and quiet were

required for seven days before the child became physically well.

Without careful therapy, the child might have suffered convulsions

and death.45

Neonatal exposure to heroin and methadone, if treated properly, appears to

leave no lasting damage. However, cocaine is different because it constricts

the blood vessels in the placenta and the fetus, thus cutting off the flow of

oxygen and nutrients and creating a higher probability of miscarriages,

stillbirths, and premature and low-birth-weight babies, often with various

physical and neurological problems. Some cocaine-exposed babies have

deformed hearts, lungs, digestive systems, or limbs: others have what amounts

to a disabling stroke while in the womb.46 Death rates may be twice as high for

these babies as for others.

For these reasons, courts have held that prenatal exposure is a form of child

neglect because it results in “actual impairment” of the children.47 As one court

held: “A new-born baby having withdrawal symptoms is prima facie a neglected

baby.”48

Basing reports on harm (or threatened harm) to the fetus makes many people

uncomfortable because it comes so close to the abortion issue. Hence, it is

important to mention that there is a second legal basis for reporting prenatal

exposure to drugs: Prenatal exposure can be circumstantial evidence of severe

drug use, which, in turn, would be reportable because of the threat of serious

harm to the baby when he or she goes home with the addicted mother. Thus,

prenatal use of dangerous drugs is probative of future neglect.49 The reasoning

behind such a conclusion is that:

To give rise to such symptoms, the mother must have been

regularly using large quantities of heroin (as she substantiated by

her history) for considerable time before [the child’s birth]; the

placenta permits ready transfer of heroin from mother to fetus.

Had she injected heroin not habitually but only shortly before

child’s birth, massive doses may have killed her and the new-born

child, or the baby would have been sedated instead of hyperactive

and suffering withdrawal. Only a high tolerance (a strong and

perhaps sufficient basis for a finding of narcotic addiction without

additional history) for both mother and baby would cause the

medically observed course of events found here.50

Not all babies born to heavy drug users exhibit withdrawal symptoms; anywhere

from 30 to 50 percent do not. Although medical studies have yet to develop

375
specific measures of prediction, it appears that the existence and severity of

withdrawal symptoms is a function of the type, dosage, and regularity of drug

use. Hence, if there are other reasons to suspect that drug use renders the

parent(s) unable to care for the infant, a report should be made.

Demonstrated parental inability to care for a newborn should be reported.

Certain specific parental behaviors in the maternity ward provide additional

reasons for a report. What parents are unable to do in the hospital, where they

have help, they are unlikely to be able to do alone at home. Concrete examples

of parental inability to care for a newborn should be reported (see Besharov

1990, pp. 131-133).

The requirement to report “reasonable suspicions” means that there need not

be a definitive determination of either the parent’s drug abuse or its harmful

effect on the child. Some people point to the uncertainty that exists about

parental drug use and its effect on children as a reason for not reporting.

However, there have been several court cases holding professionals legally

culpable for not reporting their reasonable suspicions and, instead, seeking

absolute proof of child abuse before making a report.51 It may be only a matter

of time before some local prosecutor or plaintiff in a civil damage suit will use

these precedents in a prenatal drug exposure case.

CONCLUSION

In many States, researchers probably are required to report at least some of the

prenatal drug exposure revealed in their studies to child protective agencies.

First, a growing number of States have laws that expressly require such reports.

Second, in many other States, the general child abuse reporting law implicitly

requires such reports—at least when there is reasonable cause to suspect that

a parent is seriously addicted to a dangerous or debilitating drug.

The existence of this requirement to report, though, does not mean that

researchers and clinicians should ignore the trusting relationship they may have

developed with parents. Unless it appears that doing so will endanger the child,

they should prepare the parents for the consequences of the report. The

necessity of the report, and the nature of the investigation that will follow,

should be described honestly and supportively. If appropriate, the parents

should be encouraged to report themselves to the child protective agency.

Reporting child abuse, moreover, does not necessarily mean that the child will

be removed from parental custody. In many cases, supportive services

provided by the child protective agency or another public or private agency may

enable the parents to care for their children. Moreover, researchers can take

376
steps, such as developing cooperative agreements with child protective

agencies, to increase the likelihood that a report will result in the provision of

services to the family rather than the child’s removal.

However, State laws vary, and they change almost constantly; therefore, it is

impossible to provide definitive guidance here. And, although the State or local

child protective agency may be of help in planning a response to child abuse

reporting responsibilities, the issues are sufficiently complex, State laws

sufficiently ambiguous, and the cost of a wrong decision sufficiently high that

prudence dictates an early consultation with an attorney specializing in such

matters.

NOTES

1.

2.

3.

4.

E.g., Applebaum, P.S. Informed Consent: Legal Theory and Clinical

Practice. New York: Oxford University Press, 1987; Morrissey, J.M.

Consent and Confidentiality in the Health Care of Children and

Adolescents: A Legal Guide. New York: Free Press, 1986; Barber, B.

informed Consent in Medical Therapy and Research. New Brunswick,

NJ: Rutgers University Press, 1980; Rosoff, A.J. Informed Consent: A

Guide for Health Care Providers. Rockville, MD: Aspen Systems Corp.,

1980; Sharpe, S. B. Informed Consent: Its Basis in Traditional Legal

Principles. Toronto: Butterworths, 1979; Ludlam, J.E. Informed

Consent. Chicago: American Hospital Association, 1978; Annas, G.J.

Informed Consent to Human Experimentation: The Subject’s Dilemma.

Cambridge, MA: Ballinger, 1977; Hershey, N. Human Experimentation

and the Law. Germantown, MD: Aspen Systems Corp., 1976.

Clearinghouse on Child Abuse and Neglect Information. State Statutes

Related to Child Abuse and Neglect: 1988, passim. U.S. Department of

Health and Human Services, Office of Human Development Services,

Administration for Children, Youth and Families, Children’s Bureau, and

National Center on Child Abuse and Neglect. June 1989.

See generally Besharov, D. The need to narrow the grounds for state

intervention. In: Besharov, D. Protecting Children from Abuse and

Neglect: Policy and Practice. Springfield, IL: Charles C. Thomas, 1988.

pp. 47, 50 et seq.

Child Abuse Prevention and Treatment Act of January 31, 1974, codified

as amended at 42 U.S.C. § 5102(1) (Suppl.1989).

377
5. For the definitive exposition of how severity of injury affects—and should

affect—child protective decisionmaking, see Giovannoni, J.M., and

Becerra, R.M. Defining Child Abuse. New York: Free Press, 1979.

Reflecting the need to specify the level of severity, the National Center on

Child Abuse and Neglect provides the following definitions: (1) “Physical

injury” means death, or permanent or temporary disfigurement or

impairment of any bodily organ or function and (2) “mental injury” means

an injury to the intellectual or psychological capacity of a child as

evidenced by an observable and substantial impairment in his ability to

function within his normal range of performance and behavior, with due

regard to his culture. National Center on Child Abuse and Neglect. Child

Protection: A Guide for State Legislation, subsections 4(h) and (i) (Draft

1983).

6. See the text at note 38, infra.

7. Although there is a small, technical difference between the two phrases,

most legal authorities have concluded that they are fundamentally

equivalent and have the same impact on reporting decisions. [E.g.,

Op.lll.Attorney General, S-1298 (October 6, 1977); Op.Mass.Attorney

General 74/75-66 (June 16, 1975).] Since “reasonable cause to suspect”

is the more common phraseology, it is adopted in this chapter.

8. For example, the failure to report may be misprision of a felony. Cf. Pope

v. State, 38 Md.App.520, 382 A.2d 880 (1978); modified, 284 Md.309,

396 A.2d 1054 (1979) dismissed because the state’s child abuse law did

not apply and because there was no crime of misprision of felony in

Maryland.

9. “Doctor, Parents Charged in Death of Abused L.A. Child.” Los Angeles

Times, December 3, 1983. Pt. 1, p. 1, col. 5; “MD Charged With Not

Reporting Child Abuse.” Toronto Star, June 2, 1983. p. A16, col. 1.

10. E.g., Groff v. State, 390 So.2d 361 (Fla. Dist.Ct.App. 1980), State v.

Groff 409 So.2d 44 (Fla. Dist.Ct. App. 1981), ultimately dismissed on the

grounds that the Florida reporting mandate was limited to “any person ...

serving children,” and, therefore, did not apply to the defendant

psychiatrist who was treating the father, not the child and, in fact, had

never met her.

11. People v. Poremba, 7 Family Law Repotter p. 2142 (1/1/81) (Denver

County Court 12/17/80).

378
12.

13.

14.

15.

16.

17.

18.

19.

20.

21. See Besharov, supra n. 3, p. 46.

E.g., People v. Sok (for punching and pushing two children) and People

v. Molitor (for not reporting the abuse) mentioned in, “Monk Seeks $60

Million Damages for Lawsuit’s Allegations of Racism.” Los Angeles

Times, June 23, 1982. Pt. 2, p. 12, col. 1. According to the Los Angeles

District Attorney, both cases resulted in convictions.

E.g., “People v. Noshay.” NASW News, February 1984. p. 21, and April

1984, p. 7, a case, later dismissed, charging the social worker for failing

to report “immediately” because she worked with the victim’s family for 5

weeks before a report was made by the family.

E.g., “2 Found Guilty of Not Reporting Child-Abuse Case.” Providence

Journal, December 4, 1981. p. A-3, col. 3. On appeal, the case was

dismissed on procedural grounds. (The case was tried in the wrong

court.) State v. Boucher and Flinkfelt, 468 A.2d 1227 (R.I. 1983).

E.g., Pope v. State, supra n. 8.

See Keeton, W.P., and Prosser, W.L. Prosser and Keeton on Torts. 5th

ed. St. Paul/Minneapolis: West, 1984. p. 220.

All information and quotations from “Doctor, Parents Charged in Death of

Abused L.A. Child,” supra n. 10.

Metro section, Los Angeles Times, December 1, 1984. p. 1.

Such vicarious liability is based on the legal doctrine of “respondeat

superior,” under which the tortious conduct of a staff member may be

imputed to the employer. See generally Keeton and Prosser, supra n.

16, at Chapter 12, p. 499, “Imputed Negligence.” See also Note,

“Agency: Liability of a hospital for negligent acts of a physician—

employee,” Oklahoma Law Rev 18:77, 1965; annotation, American Law

Reports 2d 69:30, 1960.

A full discussion of these issues can be found in: Horowitz, R. “The

Child Litigant.” In: The Legal Rights of Children § 3.04; “Statutes of

Limitation” (Horowitz, R., and Davidson, H., eds., 1984); American

Jurisprudence 2d ed., “Limitations of Actions,” 51:§§ 181-185 (1970 and

Suppl. 1981).

379
22. See generally Wigmore on Evidence 8:§ 2380 (Suppl. 1981);

McCormick’s Handbook of the Law of Evidence § 95 (2d ed., E. Cleary

1972).

23. Family Educational Rights and Privacy Act of 1974 (FERPA), codified at

20 U.S.C. § 1232g(b)(1)(l) (1978).

24. Public Health Service Act, § 527, codified at 42 U.S.C.§ 290ee-3 (1988

and Suppl. 1990).

25. Public Health Service Act, § 523, codified at 42 U.S.C.§ 290dd-3 (1988

and Suppl. 1990).

26. 42 U.S.C. § 290dd-3(e); 42 U.S.C. § 290ee-3(e).

27. For a further discussion of these issues, see U.S. Public Health Service,

Proposed regulations on confidentiality of alcohol and drug abuse patient

records, Fed Register 48:38758, 38767 et seq, 1983, codified at 42

C.F.R. 2 (1985); National Center on Child Abuse and Neglect, Impact of

Federal Law on Provision of Child Protective and Related Services, p. 16

et seq. (DHHS 1981); “Iowa Attorney General Issues Opinion On

Dilemma In Child Abuse Reporting,” 10 Family Law Reporter 1123

(January 3, 1984), discussing Iowa Attorney General’s Opinion No. 83-

11-3, November 9, 1983.

28. Maine mandates reports from therapists but requires the child protective

agency to meet with the therapist and to consider the abuser’s

willingness to seek treatment before deciding what to do. [Me. Rev. Stat.

Ann. tit. 22, § 4011 (1-A)(C) (Suppl. 1988).] Note that, before deciding

not to report, the professional must determine that there is “little threat of

serious harm to the child,” a difficult decision in many cases and one that

creates the threat of criminal and civil liability for not reporting. Maryland

exemption is limited to health practitioners who specialize in psychiatric

treatment of pedophilia. A report is not required if the report would be

based solely on the statement of an abuser made while in treatment for

past abuse. [Md. Fam. Law Code Ann. § 5-704 (Suppl. 1988).] See also

Or. Rev. Stat. § 418.750 (1987), where mental health professionals,

clergy, and attorneys are not required to report if such a report would

disclose privileged communications, and Utah Code Ann. § 78-3c-4

(1987), abrogating the privilege between a victim and a sexual assault

counselor at the counselor’s discretion as established by statutory

guidelines.

380
29. Generally, reports are required for any suspected child abuse or neglect,

as defined in each state’s statute; these statutes then specifically mention

drug exposure in their definitions. E.g., Fla. Stat. Ann. § 415.503(7)(a)

(Suppl. 1988). (Child abuse or neglect includes “physical dependency

of a newborn infant upon any drug controlled in Schedule II of §

893.03 . .. .”); Hawaii Rev. Stat. § 587-2 (1985). (Abuse includes “any

case where the child is provided with dangerous, harmful, or detrimental

drugs as defined by § 712-1240.”); Ill. Rev. Stat. ch. 23, § 2053 (SmithHurd 1990). (Neglected children include “any newborn infant whose

blood or urine contains any amount of a controlled substance as defined

in subsection (9 of Section 102 of the Illinois Controlled Substance Act . .

. .”); Ind. Code Ann. § 31-6-4-3.1 (Burns 1987). (A child is in need of

services if he or she is “born with fetal alcohol syndrome or an addiction

to a controlled substance or a legend drug .. . .”); Mass. Gen. Laws Ann.

ch. 119, § 51A (West Suppl. 1988). (A report is mandated for any infant

 “. . . who is determined to be physically dependent upon an addictive

drug at birth.”); Minn. Stat. Ann. § 626.556(4)(2) (1988). (“Neglect

includes prenatal exposure to a controlled substance ...”); Okla. Stat.

tit. 21, § 846(A) (Suppl. 1989). (A report must be made for “a child who

appears to be a child born in a condition of dependence on a controlled

dangerous substance . . . .”); Utah Code Ann. § 78-36-3.5 (Cum. Suppl.

1989). (A report is mandated when a child “at the time of birth, has a

fetal alcohol syndrome or fetal drug dependency.“)

30. E.g., Hawaii Rev. Stat. § 587-2 (1985). (Harm to a child occurs in “any

case where the child is provided with dangerous, harmful, or detrimental

drugs, as defined by Section 712-1240 . . . .”); Ill. Ann. Stat. ch. 37,

§ 802-3(1) (Smith-Hurd 1989). (Neglected children include “any newborn

infant whose blood or urine contains any amount of a controlled

substance as defined in subsection (9 of Section 102 of the Illinois

Controlled Substance Act . . . .”)

31. Ind. Code Ann. § 31-6-4-3 (Burns 1987). (A child is in need of services

if “the child is born with fetal alcohol syndrome . . . . ”); Nev. Rev. Stat.

§ 201.090 (1987). (A child is neglected if he or she “habitually uses

intoxicating liquors . . . .”); Utah Code Ann, § 78-3b-8 (1),(6) (1987).

(The agency shall investigate “an oral or written report of alleged abuse,

neglect, fetal alcohol syndrome, or dependency . . . .”)

32. Fla. Stat. Ann. § 415.503(8)(a)(2) (West Suppl. 1988). (“physical

dependency of a newborn infant”); Mass. Gen. Laws Ann, Ch. 119 § 51A

(West Suppl. 1989). (“physically dependent on an addictive drug at

birth”): Okla. Stat. Ann. tit 21, § 846(A) (West Suppl. 1988). (“born in a

381
condition of dependence on a controlled substance”): Utah Code Ann.

§ 78-36-3.5 (Cum. Suppl. 1989). (“at the time of birth has a fetal alcohol

syndrome or fetal drug dependency”.)

33. III. Ann. Stat. ch. 37, § 802-3(1) (1990). (“any newborn infant whose

blood or urine contains any amount of a controlled substance . . . or

metabolite of a controlled substance, with the exception of. . . such

substances, the presence of which in the newborn infant is the result of

medical treatment administered to the mother or the newborn infant.“);

Minn. Stat. Ann. § 626.5562(2) (West Suppl. 1990). (Physicians are

required to report as neglect the positive results of any toxicology tests.)

34. Minn Stat. Ann. § 626.5562(6)(2) (1988). This section also requires a

physician to report to the child protective agency even when the drug test

is negative, if “other medical evidence of prenatal exposure to a

controlled substance” exists.

35. Minn. Stat. Ann. § 626.5562(1) (West Suppl. 1990). (A report is required

if “a woman is pregnant and uses a controlled substance for a nonmedical purpose. . . .”); R.I. Gen. Laws § 40-11-2 (2), (3) (Suppl. 1988).

(Evidence of an abused or neglected child includes parental “use of a

drug, drugs or alcohol to the extent, that the parent . . . loses his ability or

is unwilling to properly care for the child . . . .”); Nev. Rev. Stat. § 128.106

(1987). (“In determining neglect by or unfitness of a parent, the court

shall consider. . . excessive use of intoxicating liquors, controlled

substances or dangerous drugs which renders the parent consistently

unable to care for the child.”); N.Y. Fam. Ct. Act § 1012(e) (McKinney

1983 and Suppl. 1989). (A parent may neglect his child “by misusing a

drug, or drugs; or by misusing alcoholic beverages to the extent that he

loses self-control of his actions.“)

36. Minn. Stat. Ann. § 626.5562(1) (1989).

37. In Re Baby X, 293 N.W.2d 736, 97 Mich. App. 111 (1980); In Re Troy D.

215 Cal. App. 3d 889, 263 Cal. Rptr. 869 (Ct. App. 1989); In Re Stefanel

C., N.Y. App. Div. 1st Dept., May 29, 1990; NYLJ May 31, 1990.

Additional cases exist in Illinois, Alaska, Georgia, South Dakota,

Montana, and Nevada. See Horowitz, R. Testimony before

Subcommittee on Human Resources, Committee on Ways and Means,

U.S. House of Representatives, April 3, 1990.

38. Minn. Stat. Ann. § 626.5561 (1989). (Physicians must report any

pregnant women whom they suspect of using drugs. Child abuse

382
includes “prenatal exposure to a controlled substance used by the mother

for a non-medical reason . . . .”); (Delaware has a similar bill pending,

H.B. 571, which would require reporting of “any woman suspected of

using a controlled substance during pregnancy.“)

39. See generally English, A. Prenatal drug exposure: Grounds for

mandatory child abuse reports?” Youth Law News X1(1):3-8, 1990.

40. E.g., Ward, P., and Krone, A. Deadly deals: Child abuse and chemically

dependent families. Focus on Chemically Dependent Families 10(6):16-

17, 34-35, 1987; Coleman, E. Family intimacy and chemical abuse: The

connection. J Psychoactive Drugs 14(1-2):153-158, 1982; Jones, C., and

Lopez, R. “Direct and Indirect Effects on the Infant of Maternal Drug

Use.” In: Component Report on Drug Abuse. Expert Panel on Prenatal

Care. U.S. Department of Health and Human Services and the National

Institutes of Health. Pub. No. 7161M, July 15, 1988; Finnegan, L.P.;

Oehlberg, S.M.; Regan, D.O.; and Rudrauff, M.E. “Evaluation of

Parenting, Depression and Violence Profiles in Methadone Maintained

Women.” Paper presented at the Third International Congress on Child

Abuse and Neglect, 1981.

41. Clement, D. Babies in trouble. Minnesota Monthly March:49, 1989.

42. E.g., Roberts v. State, 941 Ga. App.268, 233 S.E.2d 224 (1977) where a

baby born to a mentally retarded, 14-year-old mother was placed in foster

care immediately after birth. Despite the absence of any “history of

deprivation,” the court held that, under the circumstances, parental rights

could be terminated on the grounds that the child would suffer deprivation

if the mother were given custody of him.

43. N.Y. Fam. Ct. Act § 1046(a)(iii)(McKinney 1988) (emphasis added).

44. E.g., N.Y. Fam. Ct. Act § 1012(e) (McKinney 1983 and Suppl. 1989)

(‘Where the respondent is voluntarily and regularly participating in a

rehabilitative program, evidence that the respondent has repeatedly

misused a drug or drugs or alcoholic beverages to the extent that he

loses self-control of his actions shall not establish that the child is a

neglected child in the absence of evidence that the child’s physical,

mental or emotional condition has been impaired or is in imminent danger

of becoming impaired . . . .”)

45. In the Matter of John Children, 61 Misc.2d 347, 353, 306 N.Y.S.2d 797,

805 (Fam.Ct., N.Y.Co., 1969).

383
46.

47.

48.

49.

50.

51.

E.g., Zuckerman, B.; Frank, D.; Hingson, R.; Amaro, H.; Levenson, S.;

Parker, S.; Vinci, R.; Aboagye, K.; Fried, L.; Cabral, H.; Timperi, R.; and

Bauchner, H. Effects of maternal marijuana and cocaine use on fetal

growth. N Engl J Med 320:762-768, 1989.

ln Re Stefanel C., N.Y. App. Div. 1st Dept; May 29, 1990, NYLJ May 31,

1990; see also In Re Ruiz, 500 N.E.2d 935 (Ohio Ct. Comm. Pls. 1986).

In the Matter of Vanesa F., 76 Misc.2d 617,620,351 N.Y.S.2d 337,340

(Surr.Ct., N.Y.Co. 1974).

In Re Troy D., 215 Cal. App. 3d 889, 263 Cal. Rptr. 869 (Ct. App. 1989),

basing its decision on “prognostic deprivation”; In Re Baby X., 293

N.W.2d 736, 739, 97 Mich. App. 111 (1980), stating that “prenatal

treatment can be considered probative of a child’s neglect.”

In the Matter of John Children, supra n. 46, 61 Misc.2d at 354, 306

N.Y.S.2d at 805.

Confidential material on file with the author.

REFERENCE

Besharov, D. Recognizing Child Abuse: A Guide for the Concerned. New

York: Free Press, 1990.

ACKNOWLEDGMENT

Elizabeth Fish, a legal policy analyst at the American Enterprise Institute, and

Barbara Gill, an intern, performed legal research in the preparation of this

chapter.

AUTHOR

Douglas J. Besharov, J.D., LL.M.

Resident Scholar

American Enterprise Institute

1150 17th Street, N.W.

Washington, DC 20036

384
Discussion: Effect of Legal

Stipulations on the Conduct of

Treatment and Prevention Research

Judy Howard

INTRODUCTION

This chapter discusses the divergent viewpoints expressed by Ellen Marie

Weber, Legislative Counsel for the Legal Action Center of New York City, Inc.,

in her chapter (this volume) “Alcohol and Drug-Dependent Pregnant Women:

Laws and Public Policies That Promote and Inhibit Research and the Delivery of

Services,” and by Douglas J. Besharov, Resident Scholar at the American

Enterprise Institute for Public Policy Research, in his chapter (this volume)

“Mandatory Reporting of Child Abuse and Research on the Effects of Prenatal

Drug Exposure.” The issues addressed by these two legal experts span a

continuum that ranges from protecting the privacy rights of women and men in

drug treatment to reporting suspected child abuse and neglect in instances

where parents are chronic substance abusers. Both authors express the need

to balance treatment for substance-abusing parents with the provision of an

environment for their children that is safe from harm.

The two views expressed in these chapters regarding the need to report

prenatally substance-exposed infants and to maintain confidentiality of

information related to parental chemical dependency reflect the controversies

and issues that professionals and policymakers must face and resolve if

treatment programs for chemically dependent families are to be improved and

legislation enacted that is appropriately guided by research findings. It is my

belief that only through close collaboration-in which clinicians and researchers

from the fields of health, social services, and alcohol and other drug treatment

work together with legislators and policymakers-can meaningful public policy

be enacted that will benefit this population.

As a developmental pediatrician based at a university medical center, I have

been involved since 1981 in clinical and research programs serving chemically

dependent parents and their offspring. In addition, I have served as medical

365
director of the University of California, Los Angeles (UCLA) Suspected Child

Abuse and Neglect (SCAN) Team and chair of the hospital’s Child Abuse Policy

Committee for 8 years. Within UCLA Medical Center, the SCAN Team

functions as a consulting resource for mandated reporters of suspected child

abuse and neglect, and since 1977, SCAN Team members have formally

reviewed all such cases occurring in the Medical Center. This interdisciplinary

team is composed of university professionals from the fields of medicine,

nursing, social work, pharmacology, dentistry, law, and law enforcement. in our

work with families at UCLA Medical Center we routinely collaborate with a range

of community-based professionals in Los Angeles County from child protective

services, public health nursing, alcohol and other drug treatment, the office of

the county counsel (representing the child in the civil courts), and the office of

the district attorney (prosecuting the alleged perpetrator in the criminal courts).

Last year, 277 cases of suspected child abuse and neglect were reviewed.

Approximately 23 percent (64) of these cases involved infants with prenatal

drug exposure, and 42 percent (116) involved parental substance abuse.

Thus, this discussion of the issues raised by Weber and Besharov is based

on a decade of experience in both research and clinical intervention with

chemically dependent women and their children. However, whether one

approaches the issue of perinatal substance abuse from a purely clinical

stance or from that of a researcher, it is true that there has been a paucity of

prevention and treatment efforts on behalf of chemically dependent pregnant

women and women with children. It is also true that-despite a lack of

information regarding the effectiveness of various treatment methods, a lack

of thoughtful, organized approaches to developing programs for rehabilitating

chemically dependent pregnant women or women with young children, and a

lack of existing treatment resources overall-there appears to be a widespread

trend toward criminalizing the act of using drugs during pregnancy.

It is within this emotionally charged arena—in which the reporting of suspected

child abuse and neglect remains controversial—that clinicians and researchers

are asked to maintain subject confidentiality and to protect children from harm.

Weber and Besharov raise four issues that influence the ability to meet both

these requirements while simultaneously providing effective clinical services

and conducting meaningful research. The issues identified relate to

confidentiality, whether child abuse laws deter women from seeking treatment,

the question of serious harm, and the effect of reporting on research paradigms.

CONFIDENTIALITY

The critical issue of confidentiality is acknowledged by both authors. As Weber

notes, when a suspected child abuse or neglect report is made by a scientific

386
researcher or by an alcohol and other drug treatment program staff member,

Federal regulations regarding the exemption for confidentiality apply only to the

initial report and not to requests for followup information. This regulation

presents several potential conflicts for research projects that incorporate the

provision of clinical services. Initially, there is the potential for discord between

researchers and community agencies if the researchers appear to be

withholding requested followup information on cases that already have been

reported. Over time, lack of availability of information or unwillingness to share

information may foster a climate of distrust, since it is possible that community

agency representatives would perceive such action on the part of the research

staff to be uncooperative. In turn, for the researcher it could become difficult to

recruit future study subjects who are involved with these community systems.

At UCLA, compliance with basic requests for information relevant to a child’s

situation always has been considered necessary, and a recent California Court

of Appeals decision’ seems to support this position. In this case, it was

determined that a mandated reporter could provide followup information to the

county counsel and to child protective services. The UCLA programs have

incorporated within the research design provisions for a carefully monitored

exchange of information to ensure safety for the child and to develop a more

appropriate and realistic intervention plan for the entire family.

DETERRENT TO TREATMENT

A second area of concern for Weber and Besharov relates to potentially

adverse consequences when strict confidentiality is not maintained-specifically

to the possibility that reporting of alcohol or other drug use by pregnant women

may be a deterrent to their obtaining prenatal care and/or drug treatment for

their chemical dependency.

Because health care behaviors are influenced by multiple factors, to understand

deterrents to care, more information and research are needed regarding those

specific variables that facilitate the chemically dependent woman’s seeking

and following through with prenatal care and chemical dependency treatment

programs, In fact, pregnant, substance-abusing women may have a variety

of reasons for not making and keeping appointments. Although these reasons

may include fear of losing their children, they also may be related to the lack

of a user-friendly environment in which to receive care, long waits before

appointments, the scarcity of child care facilities for other children during

prenatal visits, the insensitivity of some health care professionals, and difficulty

in arranging transportation to and from appointments. Just as important, the

effects of chronic and severe addiction may interfere with the chemically

dependent woman’s ability to plan ahead and to keep scheduled appointments.

387
Furthermore, just as researchers lack information about what deters women

from seeking prenatal care, information also is lacking relative to the impact of

child abuse reporting. No solid data are available indicating that the potential

referral to child protective services agencies at the time of birth has deterred a

significant number of women from either seeking prenatal care or entering drug

treatment programs. In fact, the opposite may be true. Indeed, at UCLA many

pregnant women have entered and complied with drug treatment and prenatal

care programs specifically to increase their chances of keeping their babies

should child protective services agencies become involved.

In two research projects at UCLA, one involving 20 and the other 41 families,

clients have been tracked over a course of 3 years. These projects have

involved a home-based intervention component staffed by a competent, caring

professional staff of social workers, public health nurses, and/or early childhood

specialists. At the time of subject recruitment, each client was informed that a

referral to child protective services would be filed in the event that the newborn

demonstrated symptoms of prenatal substance exposure and/or had a positive

urine toxicology screen or if there was any subsequent evidence of child abuse

or neglect. In addition, it was made clear that the project staff would continue to

provide services and advocate on behalf of the mother’s and infant’s needs

even if child protective services should become involved. We believe this

forthright approach helped build trust and establish clear expectations for the

client’s behavior.

In following subjects over the course of 3 years, we have made reports to child

protective services for approximately 30 percent of these families in cases

where we believed a child was in imminent harm or had been abused or

neglected. Admittedly, some mothers became angry and threatened to leave

the project or even personally threatened project staff members. However, a

skillful, consistent, patient, and unambivalent stance can be effective in these

situations. When staff members are honest with families about the reasons for

making a report and when they continue to follow and maintain contact with

families after a report has been filed, the families can learn that they will not be

abandoned and that they can trust the staff from the research project to help

them weather the crisis We stay in touch with the family throughout the

investigative and dispositional process and advocate for services as indicated.

The attrition rate in both these projects has been less than 5 percent.

When the health care and research team operates under the assumption

that addiction is a chronic, relapsing disease characterized by denial, the

identification of a chemically dependent client has the goal of providing the

substance-abusing mother with the structure and the impetus that she is unable

to provide for herself. From a child neglect standpoint, as Dr. Donald Bross has

388
stated in the Denver University Law Review, “. . . in cases in which the parent

suffers from mental illness, it is appropriate to view drug addiction or alcoholism

as a capacity issue, rather than one of blame. Since the civil court process

involves determining the child’s status, ‘guilt’ or ‘innocence’ of the parent is not

at issue” (Bross 1988).

Rather than supporting criminal sanctions, this view advocates treatment for

children and families that is backed by the legal clout of the civil court. In the

Harvard Mental Health Letter, Richard S. Schottenfeld stated that there is

considerable evidence that some kind of leverage almost always is needed to

counter the denial that is frequently present in drug and alcohol addiction.

“Coercion at the start often helps drug and alcohol abusers realize they need

treatment” (Schottenfeld 1990).

Thus, at UCLA Medical Center, we do not view the reporting of suspected childendangering situations as punitive-to continue to permit a mother to endanger

her own health and that of her child would be a terrible disservice. Indeed, my

staff members and I have seen children permanently removed from their

mothers’ custody without any real attempt made to effect family reunification,

and we have seen children receive serious injuries or even die while in their

mothers’ care. If constructive intervention can be made before such irreversible

damage occurs, then everyone’s best interest—the parent’s, the child’s, and

society’s—will be better served.

SERIOUS HARM

Besharov and Weber agree that mandatory reporting of suspected child abuse

and neglect in cases of prenatal substance abuse appears to be contingent on

ability to demonstrate harm. In the absence of specific legislation, Besharov

notes that chemically dependent parents should not be reported unless there is

reason to believe “that the child is or will be seriously harmed thereby.” He

goes on to comment that chronic, severe substance abuse interferes with the

adult’s alert state, and if there is a dependent child within the home, imminent

harm to the child is a real consideration.

In a recent California appellate decision, specific testimony by one expert

witness detailed the cycle of parental addiction, which included a description of

the behavioral effects of a drug on the adult’s alert state and a description of

how the parents, who used drugs together, “would be out of commission

frequently at the same time.” According to this testimony, the ability of

chemically dependent parents to prioritize their children’s needs over their own

“literally disappears as the length of time between the last dosage and what is

currently needed by the individual increases.”2

339
However, for those engaged in research with chemically dependent families,

it is often difficult to draw the line between what constitutes chronic, severe

substance abuse and occasional, recreational use of illegal substances. It is

well known that chemically dependent adults tend not to be reliable historians

in reporting their own substance abuse patterns. Besharov states that such

differentiation is necessary to help interpret correctly the child abuse reporting

law as it pertains to perinatal substance abuse, but how does a researcher

make educated, informed decisions about the frequency and nature of drug use

or even about the specific substances abused?

RESEARCH PARADIGMS

Conducting research with chemically dependent families is complicated by

statutory regulations, legal requirements, and professional ethics. However,

the decision regarding whether to make a referral of suspected child abuse or

neglect to a child protective services agency is only one facet of conducting

research with this population. Once a chemically dependent family has been

identified and it has been determined that the children are in imminent danger

and/or have been abused, professionals involved in the care of these families—

whether through research projects or clinical programs—need to recognize

that the family is part of a much larger system over which the researcher

has minimal control. For instance, the child protective services worker, in

conjunction with the juvenile court, may recommend special programs to

address the unique needs of the immediate family as well as of the extended

family members and foster parents who may be caring for the children. Thus,

the experimental and control groups within a research project may swell in size

and in complexity of required services: conversely, group sizes may diminish

because some children will be moved to distant locations.

Conforming to a research paradigm, which usually is not a difficult task with

non-substance-abusing families, can become a real challenge in studying this

population. Because the legal disposition of a given case cannot be predicted

or controlled, research studies have to be carefully and flexibly designed to

allow for multiple contingencies. Attachment behaviors, parenting skills, and

the effects of prenatal drug exposure on a child’s long-term development are

all difficult to determine in a “moving target” population involving multiple

caretaking environments for the child, multiple drug treatment programs for the

parent, and in some cases, episodes of parental incarceration.

In designing a research project, professionals have the option to study

populations who are participating in the program voluntarily or populations

whose participation is mandated by the court. If a decision is made to solicit

subjects who have been mandated to enroll in a treatment program to maintain

390
custody of their children or to regain custody, it has been our experience that

this official court order may create the crisis that motivates a family toward

change. Over time, as skilled staff members have worked with families whose

participation has been mandated, the majority of them have remained in our

projects, even after the initial order has been terminated, as a result of the

positive relationships that have been established with the project staff. On

the other hand, those chemically dependent parents who have participated

voluntarily in our research projects have been easier to engage in program

services and have been more open about their substance abuse and family

problems, Yet, over the long haul, they can prove as resistant to significant

change as families who are mandated to participate. Finally, because the

voluntary or mandated status of a subject may change during the course of a

longitudinal research project, the research staff needs to understand this

possibility, be knowledgeable about dealing with either contingency, and be

aware of how this affects the research design.

When recruiting pregnant, substance-abusing women or chemically dependent

mothers of young children into a study, the research staff has the responsibility

to describe to the subjects the manner in which cases of suspected child

abuse and neglect will be reported. As previously stated, an unambiguous,

informed, and caring approach to this topic on the part of the professional staff

is essential. Also, it may be useful to include on the project staff those

professionals who are familiar with community services that may be required

in the event a child abuse report is made. In addition, whether project services

will be ongoing in the event a child is removed from parental custody should be

made clear at the onset.

Furthermore, it may be helpful for research projects involving chemically

dependent families to have two professional staffs: one to serve the clinical

needs of the families and a second to perform the research activities. It has

been our experience that such a staffing pattern can help alleviate the extra

burden placed on the researcher who may be unfamiliar with the multiple

agencies and systems that become involved with these families once a report

of suspected child abuse or neglect has been filed.

Finally, when designing research that involves chemically dependent parents, it

seems imperative that each participant—whether assigned to the experimental

or the control group—receive care that is at least at the level of “standard of

practice” within the community. Under such circumstances, randomization of

subjects into experimental or control groups will not jeopardize a subject’s

ethical right and access to treatment. If the proposed research is designed to

compare a new treatment approach to an established one, the control subjects

still will receive the “standard of practice” care.

391
CONCLUSION

Longitudinal research is possible with this difficult-to-follow population of

chemically dependent families, and it can be conducted in compliance with the

child abuse reporting law. However, a successful project depends to a great

extent on staff knowledge and expertise in the area of child abuse and neglect.

To retain subjects who have been reported, staff members not only need to be

comfortable with and unambivalent about the need for reporting but also need

to stand by the family throughout the process. Furthermore, the research

design needs to have the flexibility to deal with a population of families in which

there are frequent changes in status with regard to caretaking responsibility,

family residence, and legal involvement. In those situations when information

deemed confidential must be shared to observe the law and protect a child from

harm, this process need not be viewed as a punitive measure but rather as part

of the early intervention and treatment plan for the family. The child abuse

reporting law need not be viewed as an obstacle to conducting research with

this population. Rather, one can simultaneously comply with the law, protect

children, retain subjects in a study, and increase knowledge in the field of

substance abuse.

NOTES

1. John Ferraro et al., Plaintiffs-Appellants, v. David L. Chadwick, M.D., et al.,

Defendants-Respondents. 90 Daily Journal Daily Appellate Report 6582.

CA Courts of Appeal, 14 June 1990.

2. In re: Stephen, W., a Person Coming Under the Juvenile Court Law. Butte

County Child Protective Services, Petitioner and Respondent, v. Rayla, W.,

Defendant and Appellant. Daily Opinion Service. CA Courts of Appeal, 22

June 1990.

REFERENCES

Bross, D. Medical diagnosis as a gateway to the child welfare system: A legal

review for physicians, lawyers, and social workers. Denver University Law

Rev 65(2-3):213-253, 1988.

Schottenfeld, R.S. How effective is coercive treatment for alcohol and drug

dependence? Harvard Ment Health Left 7(1):8, 1990.

AUTHOR

Judy Howard, M.D.

Professor of Clinical Pediatrics

392
Intervention Program

Department of Pediatrics

University of California, Los Angeles School of Medicine

Rehabilitation Center, Room 23-10

1000 Veteran Avenue

Los Angeles, CA 90024-1797

393
While limited supplies last, single copies of the monographs may be obtained

free of charge from the National Clearinghouse for Alcohol and Drug

Information (NCADI). Please contact NCADI also for information about

availability of coming issues and other publications of the National Institute on

Drug Abuse relevant to drug abuse research.

Additional copies may be purchased from the U.S. Government Printing Office

(GPO) and/or the National Technical Information Service (NTIS) as indicated.

NTIS prices are for paper copy; add $3 handling charge for each order.

Microfiche copies are also available from NTIS. Prices from either source are

subject to change.

Addresses are:

NCADI

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P.O. Box 2345

Rockville, MD 20852

(301) 468-2600

(800) 729-6686

GPO

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For information on availability of NIDA Research Monographs 1 through 70

(1975-1986) and others not listed, write to NIDA, Community and Professional

Education Branch, Room 10A-54, 5600 Fishers Lane, Rockville, MD 20857.

394
71 OPIATE RECEPTOR SUBTYPES AND BRAIN FUNCTION. Roger M.

Brown, Ph.D.; Doris H. Clouet, Ph.D.; and David P. Friedman, Ph.D., eds.

GPO out of stock NTIS PB #89-151955/AS $31

72 RELAPSE AND RECOVERY IN DRUG ABUSE. Frank M. Tims, Ph.D.,

and Carl G. Leukefeld, D.S.W., eds.

GPO Stock #017-024-01302-1 $6 NTIS PB #89-151963/AS $31

73 URINE TESTING FOR DRUGS OF ABUSE. Richard L. Hawks, Ph.D., and

C. Nora Chiang, Ph.D., eds.

GPO Stock #017-024-01313-7 $3.75 NTIS PB #89-151971/AS $23

74 NEUROBIOLOGY OF BEHAVIORAL CONTROL IN DRUG ABUSE.

Stephen I. Szara, M.D., D.Sc., ed.

GPO Stock #017-024-01314-5 $3.75 NTIS PB #89-151989/AS $23

75 PROGRESS IN OPIOID RESEARCH. PROCEEDINGS OF THE 1986

INTERNATIONAL NARCOTICS RESEARCH CONFERENCE. John W.

Holaday, Ph.D.; Ping-Yee Law, Ph.D.; and Albert Herz, M.D., eds.

GPO out of stock NCADI out of stock

Not available from NTIS

76 PROBLEMS OF DRUG DEPENDENCE, 1986: PROCEEDINGS OF THE

48TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO out of stock NCADI out of stock

NTIS PB #88-208111/AS $53

77 ADOLESCENT DRUG ABUSE: ANALYSES OF TREATMENT

RESEARCH. Elizabeth R. Rahdert, Ph.D., and John Grabowski, Ph.D., eds.

GPO Stock #017-024-01348-0 $4 NCADI out of stock

NTIS PB #89-125488/AS $23

78 THE ROLE OF NEUROPIASTICITY IN THE RESPONSE TO DRUGS.

David P. Friedman, Ph.D., and Doris H. Clouet, Ph.D., eds.

GPO out of stock NTIS PB #88-245683/AS $31

79 STRUCTURE-ACTIVITY RELATIONSHIPS OF THE CANNABINOIDS.

Rao S. Rapaka, Ph.D., and Alexandros Makriyannis, Ph.D., eds.

GPO out of stock NTIS PB #89-109201/AS $31

395
80 NEEDLE SHARING AMONG INTRAVENOUS DRUG ABUSERS:

NATIONAL AND INTERNATIONAL PERSPECTIVES. Robert J. Battjes,

D.S.W., and Roy W. Pickens, Ph.D., eds.

GPO out of stock NTIS PB #88-236138/AS $31

81 PROBLEMS OF DRUG DEPENDENCE, 1987: PROCEEDINGS OF THE

49TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S Harris, Ph.D., ed.

GPO Stock #017-024-01354-4 $17 NTIS PB #89-109227/AS

Contact NTIS for price

82 OPIOIDS IN THE HIPPOCAMPUS. Jacqueline F. McGinty, Ph.D., and

David P. Friedman, Ph.D., eds.

GPO out of stock NTIS PB #88-245691/AS $23

83 HEALTH HAZARDS OF NITRITE INHALANTS. Harry W. Haverkos, M.D.,

and John A. Dougherty, Ph.D., eds.

GPO out of stock NTIS PB #89-125496/AS $23

84 LEARNING FACTORS IN SUBSTANCE ABUSE. Barbara A. Ray, Ph.D.,

ed.

GPO Stock #017-024-01353-6 $6 NTIS PB #89-125504/AS $31

85 EPIDEMIOLOGY OF INHALANT ABUSE: AN UPDATE. Raquel A. Crider,

Ph.D., and Beatrice A. Rouse, Ph.D., eds.

GPO Stock #017-024-01360-9 $5.50 NTIS PB #89-123178/AS $31

86 COMPULSORY TREATMENT OF DRUG ABUSE: RESEARCH AND

CLINICAL PRACTICE. Carl G. Leukefeld, D.S.W., and Frank M. Tims, Ph.D.,

eds.

GPO Stock #017-024-01352-8 $7.50 NTIS PB #89-151997/AS $31

87 OPIOID PEPTIDES: AN UPDATE. Rao S. Rapaka, Ph.D., and Bhola N.

Dhawan, M.D., eds.

GPO Stock #017-024-01366-8 $7 NTIS PB #89-158430/AS $45

88 MECHANISMS OF COCAINE ABUSE AND TOXICITY. Doris H. Clouet,

Ph.D.; Khursheed Asghar, Ph.D.; and Roger M. Brown, Ph.D., eds.

GPO Stock #017-024-01359-5 $11 NTIS PB #89-125512/AS $39

89 BIOLOGICAL VULNERABILTY TO DRUG ABUSE. Roy W. Pickens,

Ph.D., and Dace S. Svikis, B.A., eds.

GPO Stock #017-022-01054-2 $5 NTIS PB #89-125520/AS $23

396
90 PROBLEMS OF DRUG DEPENDENCE, 1988: PROCEEDINGS OF THE

50TH ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01362-5 $17

91 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION DATA.

Steven W. Gust, Ph.D., and J. Michael Walsh, Ph.D., eds.

GPO Stock #017-024-01384-6 $10 NTIS PB #90-147257/AS $39

92 TESTING FOR ABUSE LIABILITY OF DRUGS IN HUMANS. Marian W.

Fischman, Ph.D., and Nancy K. Mello, Ph.D., eds.

GPO Stock #017-024-01379-0 $12 NTIS PB #90-148933/AS $45

93 AIDS AND INTRAVENOUS DRUG USE: FUTURE DIRECTIONS FOR

COMMUNITY-BASED PREVENTION RESEARCH. C.G. Leukefeld, D.S.W.;

R.J. Battjes, D.S.W.; and Z. Amsel, D.Sc., eds.

GPO Stock #017-024-01388-9 $10 NTIS PB #90-148941/AS $39

94 PHARMACOLOGY AND TOXICOLOGY OF AMPHETAMINE AND

RELATED DESIGNER DRUGS. Khursheed Asghar, Ph.D., and Errol De

Souza, Ph.D., eds.

GPO Stock #017-024-01386-2 $11 NTIS PB #90-148958/AS $39

95 PROBLEMS OF DRUG DEPENDENCE, 1989: PROCEEDINGS OF THE

51 ST ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01399-4 $21 NTIS PB #90-237660JAS $67

96 DRUGS OF ABUSE: CHEMISTRY, PHARMACOLOGY, IMMUNOLOGY,

AND AIDS. Phuong Thi Kim Pham, Ph.D., and Kenner Rice, Ph.D., eds.

GPO Stock #017-024-01403-6 $8 NTIS PB #90-237678/AS $31

97 NEUROBIOLOGY OF DRUG ABUSE: LEARNING AND MEMORY. Lynda

Erinoff, Ph.D., ed.

GPO Stock #017-024-01404-4 $8 NTIS PB #90-237686/AS $31

98 THE COLLECTION AND INTERPRETATION OF DATA FROM HIDDEN

POPULATIONS. Elizabeth Y. Lambert, M.S., ed.

GPO Stock #017-024-01407-9 $4.75 NTIS PB #90-237694/AS $23

99 RESEARCH FINDINGS ON SMOKING OF ABUSED SUBSTANCES.

C. Nora Chiang, Ph.D., and Richard L. Hawks, Ph.D., eds.

GPO Stock #017-024-01412-5 $5 NTIS PB #91-141119 $23

397
100 DRUGS IN THE WORKPLACE: RESEARCH AND EVALUATION DATA.

VOL. II. Steven W. Gust, Ph.D.; J. Michael Walsh, Ph.D.; Linda B. Thomas,

B.S.; and Dennis J. Crouch, M.B.A., eds.

GPO Stock #017-024-01458-3 $8

101 RESIDUAL EFFECTS OF ABUSED DRUGS ON BEHAVIOR. John W.

Spencer, Ph.D., and John J. Boren, Ph.D., eds.

GPO Stock #017-024-01426-7 $6 NTIS PB #91-172858/AS $31

102 ANABOLIC STEROID ABUSE. Geraline C. Lin, Ph.D., and Lynda Erinoff,

Ph.D., eds.

GPO Stock #017-024-01425-7 $8 NTIS PB #91-172866/AS $31

103 DRUGS AND VIOLENCE: CAUSES, CORRELATES, AND

CONSEQUENCES. Mario De La Rosa, Ph.D.; Elizabeth Y. Lambert, M.S.;

and Bernard Gropper, Ph.D., eds.

GPO Stock #017-024-01427-3 $9 NTIS PB #91-172841/AS $31

104 PSYCHOTHERAPY AND COUNSELING IN THE TREATMENT OF

DRUG ABUSE. Lisa Simon Onken, Ph.D., and Jack D. Blaine, M.D., eds.

GPO Stock #017-024-01429-0 $4 NTIS PB #91-172874/AS $23

105 PROBLEMS OF DRUG DEPENDENCE, 1990: PROCEEDINGS OF THE

52ND ANNUAL SCIENTIFIC MEETING, THE COMMITTEE ON PROBLEMS

OF DRUG DEPENDENCE, INC. Louis S. Harris, Ph.D., ed.

GPO Stock #017-024-01435-4 $22

106 IMPROVING DRUG ABUSE TREATMENT. Roy W. Pickens, Ph.D.; Carl

G. Leukefeld, D.S.W.; and Charles R. Schuster, Ph.D., eds.

GPO Stock #017-024-01439-7 $12

107 DRUG ABUSE PREVENTION INTERVENTION RESEARCH:

METHODOLOGICAL ISSUES. Carl G. Leukefeld, D.S.W., and William J.

Bukoski, Ph.D., eds.

GPO Stock #017-024-01446-0 $9

108 CARDIOVASCULAR TOXICITY OF COCAINE: UNDERLYING

MECHANISMS. Pushpa V. Thadani, Ph.D., ed.

GPO Stock #017-024-01446-0 $7

396
109 LONGITUDINAL STUDIES OF HIV INFECTION IN INTRAVENOUS

DRUG USERS: METHODOLOGICAL ISSUES IN NATURAL HISTORY

RESEARCH. Peter Hartsock, Dr.P.H., and Sander G. Genser, M.D., M.P.H.,

eds.

GPO Stock #017-024-01445-1 $4.50

110 THE EPIDEMIOLOGY OF COCAINE USE AND ABUSE. Susan Schober,

Ph.D., and Charles Schade, M.D., M.P.H., eds.

GPO Stock #017-024-01456-7 $11

111 MOLECULAR APPROACHES TO DRUG ABUSE RESEARCH:

VOLUME I. Theresa N.H. Lee, Ph.D., ed.

112 EMERGING TECHNOLOGIES AND NEW DIRECTIONS IN DRUG

ABUSE RESEARCH. Rao S. Rapaka, Ph.D.; Alexandros Makriyannis, Ph.D.;

and Michael J. Kuhar, Ph.D., eds.

GPO Stock #017-024-01455-9

113 ECONOMIC COSTS, COST-EFFECTIVENESS, FINANCING, AND

COMMUNITY-BASED DRUG TREATMENT. William S. Cartwright, Ph.D.,

and James M. Kaple, Ph.D., eds.

Not for sale at GPO

114 METHODOLOGICAL ISSUES IN CONTROLLED STUDIES ON

EFFECTS OF PRENATAL EXPOSURE TO DRUG ABUSE. M. Marlyne Kilbey,

Ph.D., and Khursheed Asghar, Ph.D., eds.

GPO Stock #017-024-01459-1

115 METHAMPHETAMINE ABUSE: EPIDEMIOLOGIC ISSUES AND

IMPLICATIONS. Marissa A. Miller, D.V.M., M.P.H., and Nicholas J. Kozel,

M.S., eds.

GPO Stock #017-024-01460-5 $4

116 DRUG DISCRIMINATION: APPLICATIONS TO DRUG ABUSE

RESEARCH. Richard A. Glennon, Ph.D., and Jerry Frankenheim, Ph.D., eds.

399

U.S. GOVERNMENT PRINTING OFFICE : 1992 0 - 318-164 : QL 3
DHHS Publication No. (ADM) 92-1881

Alcohol, Drug Abuse, and Mental Health Administration

Printed 1992