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. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health 2019. This work is written by (a) US Government employee(s) and is in the public domain in the US.