Effect Size and Dose-response in Fetal Alcohol Spectrum Disorders

Principal Investigators:  Drs. Joseph and Sandra Jacobsen, Wayne State University


Principal Investigator (Seattle site): Heather Carmichael Olson, Ph.D., University of Washington

Consultant: Therese Grant, Ph.D., University of Washington

Research Coordinator (Seattle site): Sandra Radin, Ph.D.

10/1/17 through 9/30/2021

Extensive evidence from experimental and epidemiological studies has linked prenatal alcohol exposure 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, and virtually no information is available regarding the levels of exposure associated with an increased risk of clinically meaningful adverse effects. This study will integrate extensive data collected from five large U.S. prospective longitudinal cohorts, including a cohort from the University of Washington Fetal Alcohol and Drug Unit, to better define the nature of the adverse effects associated with prenatal alcohol exposure 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 statistical approaches will be used to evaluate effect size in four domains: cognitive function, externalizing behavior problems, growth, and physical anomalies. In these analyses, we will also consider the degree to which (a) larger effect sizes are associated with greater average daily dose vs. dose/occasion; (b) effect sizes appear to be stable or to increase or attenuate across development; (c) effect sizes differ for different aspects of cognitive and behavioral function; and (d) effect sizes are moderated by maternal age at delivery, history of alcohol use disorders, and/or body mass index. With respect to dose-response relationships, 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 prenatal alcohol exposure 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 is being conducted by a team of leading fetal alcohol researchers in collaboration with an internationally respected expert statistician. Data from the study will be critically important to the further development and refinement of the diagnostic criteria proposed in the Diagnostic and Statistical Manual of Mental Disorders, 5th ed., recognizing FASD for the first time as a “condition in need of further study.”