Effects of prenatal alcohol exposure in humans are impossible to study via controlled experiments; we are limited to observational studies. Although alcohol is considered a teratogen, there is a lack of clarity about the nature of the association between prenatal alcohol exposure, particularly low-level exposure, and offspring development in part because of the potential for unmeasured factors to play a role. In this issue of the Journal, an article by Lees and colleagues (1) leverages data from a large, representative sample, the Adolescent Brain Cognitive Development (ABCD) Study, to examine prenatal alcohol exposure in relation to adolescents' neurodevelopmental outcomes based on behavioral assessments, maternal report of psychopathology, and imaging data, with multiple statistical methods to control for other variables. However, review of this article in the context of other studies in the broader field studying the developmental origins of health and disease demonstrates that different research approaches addressing development beginning before birth can lead to divergent conclusions and highlights the importance of considering prenatal exposures in concert with other environmental factors.The study by Lees et al. follows a behavioral teratology model, focusing on alcohol with the goal of isolating its effects by controlling statistically for other potentially confounding variables that could explain child outcomes-an approach that the large sample of nearly 10,000 participants permits. This model dominates prenatal alcohol exposure research, which began in the 1970s when "fetal alcohol syndrome" was first described in a small study of alcoholic mothers whose infant offspring were assessed to determine the consequences of having an alcoholic mother (2). Research has progressed substantially since, beginning with preclinical models establishing high levels of alcohol as teratogenicalthough not before guidelines promoting abstinence from alcohol during pregnancy were swiftly implemented and became commonly accepted. In contrast to other neurodevelopmental disorders, fetal alcohol spectrum disorders, the umbrella term for a range of fetal alcohol exposure effects, including fetal alcohol syndrome, have a unique etiology in that the causal factor (i.e., alcohol) is integral to the diagnosis.The field of the developmental origins of health and disease, which has come to the fore in developmental