DES Exposure During Pregnancy and Third-Generation Neurodevelopmental Deficits

Marianthi Kioumourtzoglou, ScD, Columbia University Presented at BeyondGenes.org conference, December 4, 2020 We investigated the potential consequences of diethylstilbestrol (DES)—a potent endocrine disruptor—use during pregnancy on third-generation neurodevelopment. We used information on 47,540 participants enrolled in the Nurses’ Health Study II. The 3 generations analyzed in this study were the participants (F1 generation), their mothers (F0 generation), and their live-born children (F2 generation). F0 DES use during her pregnancy with F1 was the exposure of interest and physician-diagnosed F2 attention-deficit/hyperactivity disorder (ADHD) was the outcome of interest. Of the 47,540 F0 mothers, 861 (1.8%) used diethylstilbestrol and 46,679 (98.2%) did not while pregnant with the F1 participants. Use of DES by F0 mothers was associated with an increased risk of ADHD among the F2 generation: We estimated an adjusted odds ratio (OR) of 1.36 (95% CI, 1.10-1.67) and an OR of 1.63 (95% CI, 1.18-2.25) if DES was used during the first trimester of pregnancy. We observed no effect modification by the F2 children’s sex. Our study provides evidence that DES use is associated with multigenerational neurodevelopmental deficits. Although the doses and potency level of environmental endocrine disruptors to which humans are exposed today are lower than those of DES, the prevalence of such exposure and the possibility of cumulative action are potentially high. Our findings, thus, have important implications for exposures to other environmental endocrine disruptors during pregnancy and third generation adverse health effects.