Increased Multigenerational ADHD Risk Linked to DES Exposure During Pregnancy

Monitoring AEDs and the Fetus
Monitoring AEDs and the Fetus
Investigators sought to investigate the association between the use of diethylstilbestrol during pregnancy on risk for ADHD in subsequent generations.

An association between diethylstilbestrol (DES) exposure during pregnancy and an increased risk of neurodevelopmental deficits, particularly attention-deficit/hyperactivity disorder (ADHD), across multiple generations was demonstrated in a study in JAMA Pediatrics. This study highlights the risk of exposure to endocrine disruptors during pregnancy, considering the observed association between these chemicals and neurodevelopmental issues in offspring.

The study cohort was first developed in 1989, when female registered nurses between the ages of 25 and 42 years (n=116,686, F1 generation) were administered a mailed questionnaire regarding lifestyle and risk factors, medication use, and major illnesses. Participants were born during a time period when DES was actively being prescribed. A follow-up questionnaire in 1993 asked 2742 participants from the original cohort about exposure to DES via the participants’ mothers (F0 generation). Investigators sought to identify the prevalence of ADHD among the exposed participants’ live-born children (F2 generation).

A total of 861 (1.8%) mothers in the F0 generation had used DES vs 46,679 (98.2%) who did not use this medication. Investigators found a higher rate of ADHD among the F2 generation who had grandmothers who used DES vs those who did not use the synthetic nonsteroidal estrogen (7.7% vs 5.2%, respectively; adjusted odds ratio [aOR], 1.36; 95% CI, 1.10-1.67; P =.004). Additionally, higher rates of ADHD were also observed among third-generation offspring of the F0 generation who took DES during the first trimester of pregnancy with mothers in the F1 generation (OR, 1.63; 95% CI, 1.18-2.25; P =.003).

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A limitation of this study is the potential for misclassification of DES as exposure data came from reports of their mothers’ previous exposure from participants in the F1 generation regarding.

The study investigators suggest that further research into lower exposure levels of endocrine-disrupting chemicals is warranted, considering that “the levels of a high number of endocrine-disrupting chemicals to which humans are daily exposed are lower than that of the prescribed diethylstilbestrol.”


Kioumourtzoglou M-A, Coull BA, O’Reilly ÉJ, Ascherio A, Weisskopf MG. Association of exposure to diethylstilbestrol during pregnancy with multigenerational neurodevelopmental deficits. JAMA Pediatr. 2018;172(7):670-677.