Invited Commentary: The Disillusionment of Developmental Origins of Health and Disease (DOHaD) Epidemiology.

The developmental origins of health and disease (DOHaD) model promises a greater understanding of early development but has left unresolved the balance of risks and benefits to offspring of medication use during pregnancy. Masarwa et al. (Am J Epidemiol. 2018;187(8):1817-1827) conducted a meta-analysis of the association between in utero acetaminophen exposure and risks of attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). A challenge of meta-analyzing results from observational studies is that summary measures of risk do not correspond to well-defined interventions when the individual studies adjusted for different covariate sets, which was the case here. This challenge limits the usefulness of observational meta-analyses for inferences about etiology and treatment planning. With that limitation understood, Masarwa et al. reported a 20%-30% higher risk of ADHD and ASD following prenatal acetaminophen exposure. Surprisingly, most of the original studies did not report diagnoses of ADHD or ASD. As a result, their summary estimates of risk are not informative about children's likelihood of ADHD and ASD diagnoses. The long-term promise of DOHaD remains hopeful, but more effort is needed in the short-term to critically evaluate observational studies suggesting risks associated with medications used to treat conditions during pregnancy that might have adverse consequences for a developing fetus.