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Translating Basic Research

on Drugs and Pregnancy

Into the Clinical Setting

James R. Woods, Jr., M.D.

INTRODUCTION

Drug abuse has become a major problem within the field of obstetrics and gynecology. At the University of Rochester, investigators in

the fields of obstetrics and pediatrics surveyed the community and found

about a 5.5-percent incidence of cocaine use, but when neonatologists

selectively screened high-risk babies, the positivity rate for cocaine was

more than 20 percent (Ryan et al. 1994). Perhaps no other condition

in high-risk obstetrics is more prevalent. Drug abuse should be a topic

in which all obstetricians are interested.

Great changes have occurred in this field in the past 10 years.

Drug abuse is not just a condition of underserved populations or any

particular minority group; it involves all segments of society.

COMMUNITIES AT RISK

Drug abuse and pregnancy is a complex area. Although drug abuse

is the main concern, many pregnant women live in communities where

fear, sexual and other physical abuse (including rape), and poverty are

interwoven. Certain drugs were believed to have disappeared in these

communities, but they have returned. In the recent past, University of

Rochester Medical Center (URMC) obstetric residents had experience

with patients who were using heroin and methadone, but during the

past year in Rochester, snorted heroin appeared at a purity rate of around

50 percent, unlike the 4 or 5 percent previously used in intravenous (IV)

injections of heroin.

This new trend has rekindled old questions that were never answered. Should pregnant women who are on heroin be detoxified during

pregnancy? How should the fetus be monitored? What aspects of fetal

health should be monitored? The author’s laboratory has generated

interesting observations about cocaine’s actions in pregnancy, and the
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author and colleagues have collaborated with other researchers to study

obstetrics and drug abuse. The laboratory has shown that the animal

model is an important resource for mechanistically evaluating the effects

of illicit drugs on the developing fetus.

LABORATORY FINDINGS

In the laboratory, clinical observations have been used to develop

specific hypotheses. The studies that test these hypotheses can assist

in making more astute clinical observations and posing valid clinical

questions. This interaction between the basic science laboratory and

the clinical setting must be strengthened. Data from several laboratories

have created a picture of how cocaine interacts with the maternalplacental-fetal unit. For example, during pregnancy, cocaine stimulates

the maternal heart and causes reduced uterine blood flow through

constriction of the uterine blood vessels. Because the uterine vessels are

normally widely dilated, with a high blood flow rate, this vascular bed

is a prime target for cocaine’s actions in pregnancy. Thus, cocaine

produces a decrease in uterine blood flow while the maternal heart rate,

blood pressure, and cardiac output increase (Woods et al. 1987, 1994).

Unfortunately, this cocaine-induced blood pressure increase is

transmitted into the delicate blood vessels within the placenta. In

sheep, these findings are consistent with an early report of an increase

in miscarriage with cocaine use (Chasnoff et al. 1985). Numerous

incidents of abruptio placentae have occurred as a result of cocaine use

among pregnant women in the U.S. population.

Cocaine also decreases oxygen delivery to the fetus, resulting in

the release of norepinephrine and epinephrine. However, cocaine passes

so quickly across the placenta that within 2 minutes, the cocaine level

in the fetus is comparable to that in the mother (Woods et al. 1989).

Unfortunately, cocaine blocks the normal removal of norepinephrine

in the fetus, just as it does in the adult. Consequently, the fetus exhibits

hypertension that is even greater than if the fetus were made hypoxic

in the absence of cocaine exposure.

Cocaine also affects the fetus in other ways. Owiny and colleagues

(1991) have shown that fetal lambs exposed to maternal cocaine demonstrated an increase in adrenocorticotropic hormone and cortisol.

Chan and associates (1992) have demonstrated that norepinephrine is
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released by the fetus during cocaine exposure, a process that explains

the rise in blood pressure. Epinephrine is released more slowly and

probably accounts for the delayed increase in heart rate. Hurd and

colleagues have written several papers that address the issue of cocaineinduced preterm labor (e.g., Hurd et al. 1993; Smith et al. 1995).

Chronic cocaine exposure may either downregulate beta receptors in

the uterus or unbalance the relationship between adrenergic receptors.

Many institutions use beta agonists as the primary drug to stop preterm

labor, but in pregnant cocaine users, the uterus may respond poorly to

that type of drug.

The fetus is not the only target for cocaine; maternal risks also are

significant. Cardiac arrhythmias occur in pregnant sheep administered

IV cocaine (Woods and Plessinger 1990). The normal heart rhythm

suddenly exhibits atrioventricular disassociation and ventricular

tachycardia before returning to a sinus rhythm. These cardiac changes

in sheep do not differ significantly from the electrocardiogram findings

in human adult cocaine addicts as reported by Isner and colleagues

(1986). Of even greater concern is that pregnancy may predispose the

mother to enhanced cardiotoxicity from cocaine that is not apparent

in the nonpregnant state (Woods et al. 1994). These findings suggest

that hormones during pregnancy may interact to enhance cocaine’s

cardiovascular actions.

If cocaine produces a rise in maternal epinephrine and norepinephrine that increases the heart rate and blood pressure, this may increase

myocardial oxygen demand as well. However, if, as has been shown in

nonpregnant animals, cocaine restricts coronary blood flow that normally

would increase to meet the needs of increased myocardial function, this

impaired response, coupled with cocaine’s ability to block sodium channels, may lead to arrhythmia and even death.

The author and colleagues found that fetal exposure to cocaine is

not simply through maternal-to-fetal transfer. Sandberg and Olsen

(1992) administered cocaine subcutaneously to guinea pigs every day

for 10 days and sampled the amniotic fluid, fetal plasma, and maternal

plasma on the last day. Cocaine concentrations in amniotic fluid were

significantly higher than in maternal and fetal plasma.

As a followup to these findings, the author and coworkers administered cocaine directly into the amniotic fluid of animals that had not

been previously exposed (Mahone et al. 1994), which demonstrated
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that cocaine can enter the fetal circulatory system at about 3 to 5 percent

of the concentrations in the amniotic fluid. When the trachea was

occluded in some of these fetuses, detectable fetal blood levels were still

found. Cocaine’s entry into the fetus was not simply from swallowing;

cocaine in the amniotic fluid appeared to enter the fetal circulation

through the placental vessels or the umbilical cord. Amniotic fluid

may act as a drug reservoir to consistently expose the fetus to drugs,

even after the mother demonstrates a drug-free state.

CONTRADICTORY FINDINGS?

Researchers disagree about the risks of cocaine use during pregnancy.

Dixon and Bejar (1989) suggested that cocaine-exposed babies were

being diagnosed with brain lesions in as much as 20 to 25 percent of

cases, but later studies failed to confirm these findings. Laboratory

observations are only a starting place to ask general questions. Cocaineexposed babies likely are not neurologically impaired to the degree

initially reported, even when they are exposed throughout most of the

pregnancy. However, there is still reason for concern. Case reports

show that cocaine has other lethal effects. For example, Burkett and

colleagues (1990) described a 26-year-old woman, 7 months pregnant,

who came to the emergency room unconscious, without blood pressure

or respiration. An electrocardiogram showed severe bradycardia. After

an unsuccessful attempt at resuscitation, doctors performed a cesarean

section, and a placental abruption was noted. Analysis of maternal

plasma levels demonstrated the presence of cocaine. The mother died.

A report by Pollock and coworkers (1991) indicated that 75 percent

more cocaine-related deaths were reported to the Drug Abuse Warning

Network (DAWN) than to the Centers for Disease Control and

Prevention’s National Center for Health Statistics (NCHS). From 1983

to 1988, NCHS data from 25 metropolitan areas indicated that there

were 3,466 cocaine-related deaths, whereas 6,057 cocaine-related deaths

were reported to DAWN. Underreporting may even understate the

problem: There may be no way to measure accurately the increase in

deaths associated with cocaine because of the inaccuracy of the reporting

systems.
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ONE CASE STUDY

For any research study of pregnant cocaine addicts, fetal heart rate

tracing is an important tool. Such a fetal heart rate and uterine contraction pattern were obtained from a cocaine-addicted woman at URMC

when she came in for delivery. When the baseline uterine activity

began to increase, she underwent an emergency cesarean section and

demonstrated a ruptured uterus. Fortunately, the baby was delivered

safely and was put in the nursery. This kind of premature newborn

appears in neonatology units all too often, in association with not only

cocaine but also alcohol and heroin; this consequence of illicit drug use

during pregnancy also consumes large numbers of health care dollars.

PSYCHOSOCIAL v. MEDICAL ISSUES

In many cases of drug abuse, the psychosocial needs of patients

obscure the benefits of current medical resources. For example, the

following scenario could happen in any labor and delivery. A 29-yearold pregnant woman had a history of alcohol, heroin, and cocaine abuse.

She had no prenatal care except a visit in the first trimester. When

she presented at 35 weeks to her family physician, the fetal ultrasound

showed the baby was very small, with decreased amniotic fluid.

The patient left immediately and was lost to followup for 24 hours.

She suddenly appeared in the URMC labor and delivery suite 8 centimeters dilated and quickly delivered a baby who was undergrown and

who tested positive for cocaine and opioids. The mother missed her

6-week postpartum followup exam. Unfortunately, there is more to this

story that illustrates why medical care failed. In 1990 she delivered at

home a cocaine-positive baby who is now in foster care. The woman

lives with an unemployed father, has only cereal and macaroni to eat,

and admits to cocaine and heroin use five times a week and beer four

times a week. She has been in rehab five times since 1990, the longest

time for 10 months.

On February 16 her first ultrasound took place at Planned Parenthood, but she could not stay for the physical examination. A couple of

months later, she appeared in the office intoxicated. She had not filled

out the New York State Department of Social Services application. She

applied for a new card and was referred to the Food Cupboard but did

not go.
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On July 14 the social worker’s note said, “Still on cocaine, heroin,

alcohol, marijuana. Refuses rehab.” On July 15 the patient was seen

(intoxicated) in the emergency room because she had shoved her arm

through a window. On July 29 her social worker called her mother, but

the phone had been disconnected. On July 30 extensive outreach efforts

were made by both the New York State Department of Health and Baby

Love (an outreach program), and the social worker’s note for that date

stated, “Still trying to assist.”

On August 9 the young woman visited her family physician, and

the next day she came into URMC in labor, 8 centimeters dilated, and

delivered. Many resources were used to try to address this woman’s

concerns, but medical efforts were paralyzed by her psychosocial problems.

Addressing the psychosocial problems of these patients is paramount

because the best medical care will make no difference if it cannot be

delivered.

PSYCHOSOCIAL ISSUES

The medical challenges of fetal monitoring, drug screening, and

prenatal care have undergone many advances, but these issues may be

only the tip of the iceberg. There are broader hurdles for these patients.

Although the medical issues are important, the real targets should be

the issues of poverty, rape, fear, distrust, and use of nicotine, alcohol,

and other drugs. In addressing these issues, outreach programs can make

contributions that complement available medical care. Health care

practitioners need to understand how patients think: that they must hit

bottom to seek help; that their self-esteem is low and is gone when they

shoot up; that they hate the chaotic nature of clinics; and that they want

to see the same person each time—a forceful example of the need for

continuity of care.

According to patients, their patterns of living include timing their

drug use around clinic visits, having no telephone and no transportation,

and their greatest fear, losing custody of their children. No wonder they

fear the involvement of researchers and health care workers in their care.

Obstetricians must learn how to utilize community resources when

the answer to the question, “Do you use drugs?” is yes. Communities

have many resources that could collaborate to help pregnant addicts—

the prison system, settlement houses, residential and outpatient alcohol
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and other drug treatment programs, schools, and sexually transmitted

disease clinics.

Every community should develop a network that links obstetric

activities to residential drug treatment programs and mental health

programs that include intensive day treatment, outpatient care, and

pediatric support. After delivery, the patient must be able to reenter

the network educated about proper contraceptive care so that she can

choose when to become pregnant. Much energy needs to go into

outreach programs, because their participants serve as role models for

other women, and the programs build trust, facilitate care, and follow

through.

Health care providers need to be educated about the needs of these

patients. Getting angry at them because they cannot follow the rules or

becoming frustrated about having to fit them into clinic schedules is

nonproductive. For patients who come in late and are told they have

to reschedule, accountability is important but must be balanced with

flexibility. A single mother who must travel across town with three

children and make three bus transfers may arrive late for her clinic

appointment. Clinics with strict rules that require her to reschedule

serve no one’s purpose. Drug screening is another issue. Although

improved techniques for screening cocaine and other drugs exist,

screening’s most valuable function is that of challenging social workers

to answer three questions: (1) Is the family functional and the home

environment safe enough to let the baby return? (2) Is the newborn at

risk from prenatal drug exposure? and (3) Can this woman enter drug

treatment to improve her quality of living? When these questions are

asked, screening is being done properly.

CONCLUSION

Some final questions that must be resolved are, Are we really in a

drug war? Is drug abuse a crime, or is drug abuse a chronic relapsing

disease like diabetes mellitus and chronic hypertension? As a result of

progress that has been made in understanding drug abuse in pregnancy

and the biology of drug abuse, more opportunities now exist to network

within communities to bring together the fields of obstetrics, drug abuse

prevention, and mental health. Through that kind of consortium,

health care professionals can make a difference.
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Chan, K.; Dodd, P.A.; Day, L.; Kullama, L.; Ervin, M.G.; Padbury, J.; and Ross,

M.G. Fetal catecholamines, cardiovascular and neurobehavioral responses

to cocaine. Am J Obstet Gynecol 167:1616-1623, 1992.

Chasnoff, I.J.; Burns, W.J.; Schnoll, S.H.; and Burns, K.A. Cocaine use in

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Woods, J.R.; Plessinger, M.A.; Scott, K.; and Miller, R.K. Prenatal cocaine

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AUTHOR

James R. Woods, Jr., M.D.

Professor

Obstetrics and Gynecology

Director

Maternal-Fetal Medicine

Strong Memorial Hospital

601 Elmwood Avenue, Box 668

Rochester, NY 14642-8668

(716) 275-7824 (Tel)

(716) 273-4167 (Fax)

jwoods@obgyn.rochester.edu (E-mail)