The Trajectory of Fetal Alcohol Spectrum Disorders (FASD) Across the Life Span: Continuing Prevention and Longitudinal Epidemiology
Phase: NA
Conditions: Fetal Alcohol Spectrum Disorders
Sponsor: University of North Carolina, Chapel Hill

 
The Trajectory of Fetal Alcohol Spectrum Disorders (FASD) Across the 
Life Span: Continuing Prevention and Longitudinal Epidemiology 
 
 
 
NCT number NCT04026620 
Document Date 07/26/2024 
 

PROTOCOL 
 
Complete Title: The Trajectory of Fetal Alcohol Spectrum Disorders (FASD) Across the Life Span: 
Continuing Prevention and Longitudinal Epidemiology 
 
 
 
 
Short Title: Motivational Enhancement Therapy  
Drug or Device Name(s): Not Applicable 
FDA IND/IDE (if applicable): Not Applicable 
Sponsor: National Institute on Alcohol Abuse and Alcoholism 
Protocol Date: July 26, 2024 
 
 
 
 
 
 
 
 
 
 
Sponsor 
National Institute on Alcohol Abuse and Alcoholism 
6700B Rockledge Drive 
Bethesda, MD 20892-6902 
United States 
Study Principal Investigator  
500 Laureate Way 
Kannapolis, NC 28081 
Phone 704-250-5000 
 
 
 
 

Page 2 of 9 
 
 
Table of Contents 
ABBREVIATIONS AND DEFINITIONS OF TERMS ...................................................................................... 3 
PROTOCOL SYNOPSIS .................................................................................................................................................................4 
BACKGROUND AND RATIONALE.............................................................................................................................................5 
STUDY OBJECTIVE .......................................................................................................................................................................5 
STUDY DESIGN ..............................................................................................................................................................................5 
DATA COLLECTION AND MANAGEMENT .............................................................................................................................6 
RECRUITMENT STRATEGY .......................................................................................................................................................6 
CONSENT PROCESS ......................................................................................................................................................................7 
ADDITIONAL SAFEGUARDS FOR PREGNANT INDIVIDUALS ...........................................................................................7 
ADDITIONAL SAFEGUARDS FOR NON-ENGLISH SPEAKING INDIVIDUALS ...............................................................7 
PARTICIPANT SAFETY, PROTECTION, AND CONFIDENALITY ......................................................................................7 
WITHDRAWL .................................................................................................................................................................................8 
STATISTICAL ANALYSIS PLAN .................................................................................................................................................8 
PLANS FOR PUBLICATION .........................................................................................................................................................8 
REFERENCES .................................................................................................................................................................................8 
 
 
 
 

Page 3 of 9 
 
Abbreviations and Definitions of Terms 
 
 
 
Abbreviation 
Definition 
AUDIT 
Alcohol Use Disorder Identification Test 
FASD 
Fetal alcohol spectrum disorders  
MET 
Motivational Enhancement Therapy  
PAE 
Prenatal Alcohol Exposure 
PEth 
Phosphatidyl ethanol 
SA       
South Africa 
USDTL                 United States Drug Testing Laboratories, Inc. 
  
 
 
 
 
 
 
 
 

Page 4 of 9 
 
 
PROTOCOL SYNOPSIS 
  
Study Title 
The Trajectory of Fetal Alcohol Spectrum Disorders (FASD) 
Across the Life Span: Continuing Prevention and Longitudinal 
Epidemiology  
Principal Investigator 
Philip A. May, PhD, UNC Nutrition Research Institute 
Funder 
National Institute on Alcohol Abuse and Alcoholism 
Clinical Phase 
N/A 
IND/IDE # 
N/A 
Investigational Drug 
N/A 
Study Rationale 
Alcohol is a known teratogen and can cause fetal alcohol spectrum 
disorders (FASD). Globally, FASD are a leading cause of 
development delays. The Western Cape Province of South Africa 
currently has the highest documented prevalence of FASD in the 
world. Effective prevention interventions are needed to reduce the 
number of individuals with prenatal alcohol exposure and/or who 
have a diagnosis within the FASD continuum.  
Study Objective(s) 
To determine whether there is a greater reduction in AUDIT scores 
from baseline to follow-up in the intervention group relative to the 
control group.  
Study Design 
 
Randomized trial comparing two behavioral interventions 
(Motivational Enhancement Therapy vs. Pamphlets Only) 
Subject Population 
key criteria for 
Inclusion and Exclusion: 
Inclusion Criteria 
1. Pregnant females, 15 - 44 years of age 
2. Gestation age <20 weeks 
3. At risk for an alcohol-exposed pregnancy 
 
Number Of Subjects  
 
Up to 400 pregnant women   
 
 
 
 
 
 
 
 

Page 5 of 9 
 
BACKGROUND AND RATIONALE 
 
 
         Alcohol is a known teratogen, and prenatal alcohol exposure (PAE) can lead to a variety of physical 
malformations and cognitive and behavioral impairments and/or delays. The broad range of physical and 
neurodevelopmental traits associated with prenatal alcohol exposure is captured under the umbrella term of 
fetal alcohol spectrum disorders (FASD). The prevalence of FASD has been found to be no lower than 1-5% 
in communities of the United States and 17 - 28% in the Western Cape Province of South Africa (SA).1–6 Yet 
there are few brief interventions designed to reduce or eliminate alcohol consumption during pregnancy in 
order to prevent and/or reduce the number of individuals who are diagnosed within the FASD continuum.    
Drinking during pregnancy in parts of the Western Cape Province of South Africa is 
frequently reported. Croxford and Viljoen (1999) reported that 43% of prenatal patients in Cape 
metropolitan areas drank during pregnancy.7 Concern about FASD has grown in South Africa.8–10 Studying 
characteristics of Western Cape Province mothers is useful for understanding high risk drinking and for 
designing prevention programs. FASD prevention programs in the Western Cape Province of SA can and 
must be built in this area.  
 
According to the US Surgeon General, there is no known safe amount of alcohol during pregnancy. 
The Host, Agent, and Environment model has guided our thinking from the start of SA research. This 
mainstream, utilitarian, analytic tool provides a distinctive, multivariate and multi-disciplinary understanding 
of prenatal alcohol exposure. Principles of Motivational Interviewing11 and Community-Reinforcement 
Approach12,13 have been shown efficacious in promoting behavior change (reduced alcohol consumption) in 
several settings.14–18 Ingersoll et al (2005) reported that a one-session motivational interview-based interview 
reduced risk for alcohol-exposed pregnancies compared to controls who received a pamphlet on women’s 
health. Others reported greater reduction in alcohol consumption following brief interventions.18 Potential 
benefits of this intervention include: women reduce or stop alcohol consumption during pregnancy which 
results in less or no prenatal alcohol exposure to the developing fetus. Therefore, the public health burden 
associated with prenatal alcohol exposure is reduced.  
 
STUDY OBJECTIVE 
 
The purpose of the study is to determine the efficacy of a one-session, motivational enhancement therapy 
intervention to reduce Alcohol Use Disorder Identification Test (AUDIT) scores compared to a comparison 
group which only receives pamphlets on the risks associated with alcohol consumption during pregnancy.  
Primary Objective: To determine whether there is a greater reduction (change) in AUDIT scores from 
baseline to follow-up in the intervention group relative to the comparison group.  
 
STUDY DESIGN 
 
Setting 
The study will be carried out in a single Municipal Area and surrounding rural areas in the Western 
Cape Province of SA. Afrikaans, English, and Xhosa are the dominate languages in the study area.  
 
 
 

Page 6 of 9 
 
Procedures 
Pregnant women who sought prenatal care at local clinics will be screened for study eligibility. To be 
eligible females must be 15-44 years of age, < 20 weeks gestation, and at risk for having an alcohol-exposed 
pregnancy (e.g., drank within the past 30 days). Up to 400 women will be enrolled into the intervention study. 
Enrolled pregnant participants will be randomly assigned to either an intervention group or a pamphlets-only 
comparison group.  
Intervention Group: a one-on-one session with a project officer using motivational interviewing to examine 
current lifestyle choices (regarding alcohol consumption) and develop a tailored change plan to identify steps 
the participant can take to change a current lifestyle choice. Once a participant enrolls into the Motivational 
Enhancement Therapy (MET) study and is randomized to the Intervention Group, each will be provided a 
brief MET session, provided a call in number, and monitored up to five times throughout the pregnancy. 
Comparison Group (pamphlets only): receive pamphlets on the dangers of alcohol consumption during 
pregnancy.  
Both Groups: Women in both groups will be interviewed at enrollment and 9 months follow-up. All mothers 
enrolled in the Intervention Group and Comparison Group will be asked to provide blood spot samples at 3 
time points: 1) on the same day the antenatal screening questionnaire is completed, 2) once during the third 
trimester of the pregnancy (between 30- and 34 weeks gestation), and 3) within 30 days after the birth of the 
baby. Obtaining the blood spot samples will take about 10-15 minutes and will be performed by an 
experienced research staff member. Blood spots will be collected by pricking the finger with a sterile safety 
lancet. The collector will wear latex free gloves and use universal precautions (five small drops of blood will 
be collected). Blood spots will be collected on de-identified, sterile blood spot collection cards and will be 
shipped to United States Drug Testing Laboratories, Inc (USDTL) for processing for detection of 
phosphatidylethanol (PEth) levels. Infants of both groups will be assessed with standard neurodevelopmental 
assessments (Bayley Scales of Infant Development)20 and standardized physical assessment for growth, 
development, and dysmorphology.21,22  
Randomization  
Random assignment numbers will be picked via a computerized random number selection program to 
indicate who is assigned to the Intervention Group and who is assigned to the Comparison Group. The 
randomization ratio will be 1:1. There is no blinding or masking.  
DATA COLLECTION AND MANAGEMENT  
Data collection will be carried out in person. Data will be recorded by hand in hard copy. Forms will 
be kept in locked file cabinets/offices. The offices have restricted access. As needed, data will be translated to 
English. Data will be entered into an electronic database. Electronic databases will be stored on password-
protected computers meeting University security requirements. Standard epidemiological record keeping 
methods will be used to protect confidentiality. Each participant will be given an identification number. 
Names and other identifiable information (telephone number, address) will not be included in databases.  
Intellectual property and data generated under this project will be administered in accordance with 
institutional policies, including the NIH Data Sharing Policy and Implementation Guidance. Materials 
generated under the project will be disseminated in accordance with participating institutional policies.  
  
RECRUITMENT STRATEGY 
All recruitment will be carried out in person. As the first step in this process, regular, screening for 
alcohol problems will occur at prenatal clinics, in the field, and at the local prevention office. Women will be 

Page 7 of 9 
 
asked in the screening if they would like to participate in a trial of brief Motivational Enhancement Therapy. 
Those females found to be in need of assistance with alcohol problems will be referred to the prevention staff 
for further assessment. A total of up to 400 women who screen positive for drinking will be asked if they want 
to be enrolled.  
CONSENT PROCESS 
 
 
The informed consent process will begin with the purpose of the study and a description of the study 
procedures. Study staff will review the consent form and orally explain the consent form to the participant. All 
participants will read and sign a standard consent form (in Afrikaans and/or English). A translator will be 
provided, if requested, at no cost to the participant. The consent process will occur in a private location (e.g., 
study office or another mutually agreed upon location). To ensure that participants comprehend the nature of 
the study, procedures, and risk/benefits, participants will be encouraged to ask questions and repeat back 
study expectations. A wavier of parental consent for pregnant females 15-17 is appropriate to keep the process 
of consent of this study consistent with South African standards of practice and regulations. Pregnant women 
ages 15-17 will sign the approved informed consent documents. Staff will be acquiring consent according to 
South African laws and regulations. No information will be withheld while obtaining consent or directing the 
progress of the study. 
 
ADDITIONAL SAFEGUARDS FOR PREGNANT INDIVIDUALS 
By definition, women are the major focus of this study as FASD is caused primarily by 
women consuming alcohol during the prenatal period. The research focuses on the general health 
and behavioral factors they possess which put a fetus at risk. Human subjects are protected by using standard 
and conservative protocols and the protection of privileged medical information. In the feedback process 
empathic communication is used at all times, and blaming is not allowed. Communication styles will be 
monitored by the research team. 
 
ADDITIONAL SAFEGUARDS FOR NON-ENGLISH-SPEAKING INDIVIDUALS 
 
All field staff will be bi-lingual in the two primary languages of the study community (Afrikaans and 
English). All study materials will be available in Afrikaans and English. If another language is requested by a 
study participant, a translator will be provided at no cost to the participant.  
 
PARTICIPANT SAFETY, PROTECTION, AND CONFIDENALITY  
 
The PI will be responsible for monitoring participant data for safety concerns, adverse events, and 
serious adverse events. Any unanticipated problems will be reported promptly in compliance with Good 
Clinical Practice. Staff will notify participants of new safety information as soon as possible. Women 
requiring additional medical attention will be given the contact information for local providers and guided to 
referrals by staff. 
 
There is no prospect of benefit for the woman or the fetus involved in this research, the risk to the 
fetus is not greater than minimal, and the purpose of the research is the development of important biomedical 
knowledge which cannot be obtained by any other means. The risks to the participants of this project will be 
minimal. The research focuses on the general health and behavioral factors that participants may possess 
which put a fetus at risk. When maternal interviews are carried out, a unique consent form is signed by the 
female interviewee. All information from the interview is confidential. Participants are protected by using 
standard conservative protocols and the protection of privileged information. Screening, confidential record 
reviews, and some of the research activities have strict record protection protocols. Communication styles will 
be monitored by the research team. Consent forms are signed emphasizing the voluntary nature of the 
services, that they are oriented to research, and that participants can disengage from the study at any time with 
no penalty. 
 
 

Page 8 of 9 
 
WITHDRAWL 
Participants may withdraw from the study at any point. Participants who voluntarily withdraw may 
keep previously given incentive amount.  
STATISTICAL ANALYSIS PLAN 
 
 
Primary Endpoint: Change in Alcohol Use Disorder Identification Test (AUDIT) score. 
Data Analysis Plan: The primary outcome is the change in AUDIT score from baseline to 9 months follow-
up. Between-group mean differences and standard deviations will be compared. Data analysis will include 
traditional statistical analyses for group differences.  
Power Analysis: The primary test is that women in the Intervention Group should show greater reduction of 
alcohol consumption over time than women in the Comparison Group. Main effects of time are expected 
because alcohol consumption should be reduced as a result of first contact. Therefore, a group (between) 
effect, time (within) effect, and a group by time interaction will be explored. With a sample size of 400, 
alpha = .05, power of 0.95, there is power to detect an effect size (f) of .09. With a sample size of 200, there 
is power to detect an effect size of .13.  
Data Integrity: Data will be subjected to standard quality control and assurance measures.  
 
PLANS FOR PUBLICATION 
 
Aggregate, anonymous data will be presented in standard scientific publications and conferences. The 
utilization of final publication information only in anonymous and aggregate form protects the identity of 
both individuals and communities. Groups and/or subgroups will not be small enough to allow individuals to 
be deductively identified.  
  
REFERENCES 
 
1. 
May, P. A. et al. Prevalence of Fetal Alcohol Spectrum Disorders in 4 US Communities. J Am Med 
Assoc 319, 474–482 (2018). 
2. 
May, P. A. et al. Approaching the Prevalence of the Full Spectrum of Fetal Alcohol Spectrum 
Disorders in a South African Population-Based Study. Alcohol Clin Exp Res 37, 818–830 (2013). 
3. 
May, P. A. et al. The Continuum of Fetal Alcohol Spectrum Disorders in a Community in South 
Africa: Prevalence and Characteristics in a Fifth Sample. Drug Alcohol Depend 168, 274–286 (2016). 
4. 
May, P. A. et al. The Prevalence, Child Characteristics, and Maternal Risk Factors for the Continuum 
of Fetal Alcohol Spectrum Disorders: A sixth Population-Based Study in the Same South African 
Community. Drug Alcohol Depend 218, 108408 (2021). 
5. 
May, P. A. et al. The Continuum of Fetal Alcohol Spectrum Disorders in Four Rural Communities in 
South Africa: Prevalence and Characteristics. Drug Alcohol Depend 159, 207–218 (2016). 
6. 
May, P. A. et al. Replication of High Fetal Alcohol Spectrum Disorders Prevalence Rates, Child 
Characteristics, and Maternal Risk Factors in a Second Sample of Rural Communities in South Africa. 
Int J Environ Res Public Health 14, 522 (2017). 

Page 9 of 9 
 
7. 
Croxford, J. & Viljoen, D. Alcohol consumption by pregnant women in the Western Cape. South 
African Medical Journal 89, 962–965 (1999). 
8. 
Viljoen, D. L. & Hymbaugh, K. Fetal Alcohol syndrome---South Africa, 2001. Morbidity and 
Mortality Weekly Report 52, 660–662 (2003). 
9. 
Olivier, L., Urban, M., Chersich, M., Temmerman, M. & Viljoen, D. Burden of Fetal Alcohol 
Syndrome in a Rural West Coast Area of South Africa. S Afr Med J 103, 402–405 (2013). 
10. 
Adebiyi, B. O., Mukumbang, F. C., Cloete, L. G. & Beytell, A. M. Exploring service providers’ 
perspectives on the prevention and management of fetal alcohol spectrum disorders in South Africa: A 
qualitative study. BMC Public Health 18, 1–18 (2018). 
11. 
Miller, W. R. & Rollnick, S. Motivational Interviewing. (Guilford Press, New York, NY, 2002). 
12. 
Miller, W. R., Meyers, R. J. & Hiller-Sturmhöfel, S. The community-reinforcement approach. in 
Psychosocial Treatments (2003). doi:10.4324/9780203503508. 
13. 
Meyers, R. J. & Smith, J. E. Clinical Guide to Alcohol Treatment: The Community Reinforcement 
Approach. (Guilford Press, New York, NY, 1995). 
14. 
Ingersoll, K. et al. A Pilot RCT of an Internet Intervention to Reduce the Risk of Alcohol-Exposed 
Pregnancy. Alcohol Clin Exp Res 42, 1132–1144 (2018). 
15. 
Farrell-Carnahan, L. et al. Feasibility and promise of a remote-delivered preconception motivational 
interviewing intervention to reduce risk for alcohol-exposed pregnancy. Telemed J E Health 19, 597–
604 (2013). 
16. 
Joya, X. et al. Segmental hair analysis to assess effectiveness of single-session motivational 
intervention to stop ethanol use during pregnancy. Drug Alcohol Depend 158, 45–51 (2016). 
17. 
Ingersoll, K. S. et al. Reducing alcohol-exposed pregnancy risk in college women: initial outcomes of a 
clinical trial of a motivational intervention. J Subst Abuse Treat 29, 173–180 (2005). 
18. 
Feldstein Ewing, S. et al. Randomized controlled trial of motivational interviewing for alcohol and 
cannabis use within a predominantly Hispanic adolescent sample. Exp Clin Psychopharmacol 30, 287–
299 (2022). 
19. 
Nutrition Coordinating Center University of Minnesota. Nutrition Data System for Research (NDSR). 
Preprint at http://www.ncc.umn.edu/products/. 
20. 
Bayley, N. Bayley Scales of Infant and Toddler Development, 3rd Edition. Preprint at (2006). 
21. 
Hoyme, H. E. et al. A Practical Clinical Approach to Diagnosis of Fetal Alcohol Spectrum Disorders: 
Clarification of the 1996 Institute of Medicine Criteria. Pediatrics 115, 39–47 (2005). 
22. 
Hoyme, H. E. et al. Updated Clinical Guidelines for Diagnosing Fetal Alcohol Spectrum Disorders. 
Pediatrics 138, e20154256 (2016).