DES Exposure and Third Generation Attention Deficit/ Hyperactivity Disorder

Abstract

Introduction: Diethylstilbestrol (DES) is a synthetic estrogen that was given to pregnant women (G0) between 1938—1971 to prevent miscarriages and pre-term births. DES prescription was banned when in utero DES exposures were linked to adverse reproductive outcomes in female offspring (G1). Although some reports have suggested adverse health effects among children of G1 women, such as hypospadias, third generation (G2) effects due to DES exposure have not yet been widely examined. Methods: Among 69,619 G1 women in the Nurses’ Health Study II with a live born G2 child, we examined whether the nurses’ report of G1 in utero exposure to DES (i.e. use of DES by G0) was associated with G2 Attention Deficit/Hyperactivity Disorder (ADHD). We employed logistic regression models adjusting for potential confounders, including race, G0 socioeconomic status, education and smoking during pregnancy. Results: We observed a positive association between G1 in utero DES exposure and G2 ADHD. Specifically, we observed an adjusted odds ratio (OR) = 1.21 (95% Confidence Interval (CI): 1.02—1.44) if DES exposure was at any point during gestation (160 exposed cases). This association was stronger when DES exposure was during the first trimester (OR = 1.36; 95% CI: 1.09—1.70) (97 exposed cases). In a subset of 25,151 participants, DES exposure was reported directly by the G0 women. Results of analyses among these women did not change. Conclusions: Our results show an association between exposure when pregnant to a strong endocrine disruptor and third generation neurodevelopment. Our findings have important implications for exposures to other environmental endocrine disruptors during pregnancy and third generation adverse health effects.