# Dose and Pattern of Adverse Effects in the Diagnosis of Fetal Alcohol Spectrum Disorders: A Secondary Analysis of Data from Five Cohorts

> **NIH NIH R01** · WAYNE STATE UNIVERSITY · 2020 · $488,543

## Abstract

Extensive evidence from animal model and epidemiological studies has linked prenatal alcohol exposure
(PAE) to a broad range of cognitive and behavioral deficits, growth impairment, and physical anomalies.
However, to date there has been no systematic attempt to use sophisticated meta-analytic techniques to
integrate data across studies to improve identification of affected individuals, and virtually no information is
available regarding the levels of exposure associated with an increased risk of clinically meaningful adverse
effects. The aim of this study is integrate extensive data collected from five large prospective longitudinal
cohorts to better define the nature of the adverse effects associated with PAE and to derive more reliable and
robust estimates of effect size and critical dose. Although these five studies were conducted independently,
there was substantial convergence in the approaches used to measure exposure and developmental
outcomes. Three complementary approaches—Bayesian hierarchical meta-analysis, structural equation
modeling, and growth curve modeling—will be used to evaluate effect size in four domains: cognitive function,
externalizing behavior problems, growth, and physical anomalies. These analyses will also consider the degree
to which (a) larger effect sizes are associated with greater average daily dose vs. dose/occasion; (b) larger
effect sizes are associated with drinking earlier vs. later in pregnancy; (c) effect sizes within these domains are
stable or increase or attenuate across development; (d) effect sizes differ for different aspects of cognition
(e.g., IQ, learning and memory, executive function) and behavioral function (e.g., aggression, social problems);
and (e) effect sizes are moderated by maternal age at delivery, history of alcohol use disorders, and/or body
mass index. In addition, we will (a) examine the shape of the dose-response curves to identify nonlinearities
and inflection points that may suggest threshold effects; (b) use benchmark dose analysis to determine critical
doses of PAE at which there is an increased likelihood of clinically significant adverse effects; and (c) evaluate
the sensitivity and specificity of critical doses suggested by these analyses for predicting a range of
developmental outcomes. This project will be conducted by a team of leading fetal alcohol researchers in
collaboration with an internationally respected biostatistician. The proposal is responsive to NIAAA PAR-14-
338, Secondary Analyses of Existing Alcohol Epidemiology Data, which highlights the application “of new
analytic techniques and statistical methods for alcohol research” to “currently available data sets” to “help
develop accurate measurement of…risk relationship and outcomes of alcohol consumption [and] to establish
reliable and plausible thresholds.” Data from the proposed study will be critically important to the further
development and refinement of the new tentative diagnostic criteria proposed in th...

## Key facts

- **NIH application ID:** 9965642
- **Project number:** 5R01AA025905-04
- **Recipient organization:** WAYNE STATE UNIVERSITY
- **Principal Investigator:** SANDRA W. JACOBSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $488,543
- **Award type:** 5
- **Project period:** 2017-09-20 → 2023-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9965642

## Citation

> US National Institutes of Health, RePORTER application 9965642, Dose and Pattern of Adverse Effects in the Diagnosis of Fetal Alcohol Spectrum Disorders: A Secondary Analysis of Data from Five Cohorts (5R01AA025905-04). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9965642. Licensed CC0.

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