Between 1938 and 1971, an estimated five to 10 million U.S. women received the estrogen-receptor agonist diethylstilbestrol (DES) during pregnancy because it was thought to prevent pregnancy complications. The drug, shown as early as 1953 to be ineffective, was banned in 1971 after its use in pregnant women was linked to vaginal adenocarcinomas in their daughters. To examine the multigenerational neurodevelopmental effects of exposure during pregnancy to DES, a potent endocrine-disrupting chemical (EDC), researchers used data from the Nurses' Health Study II.

The nurses participating in the long-term Nurses' Health Study II, the reference cohort, were referred to as the F1 generation. Their parents were the F0 generation, and their children were the F2 generation. The nurses were mailed comprehensive questionnaires about their own and their families' health histories. Each participant answered questions about her mother's use of DES during her pregnancy with the participant and the occurrence of attention deficit-hyperactivity disorder (ADHD) in the participant's children.

Information on 47,540 F0 mothers was included in the analysis; 861 (1.8%) of these women had used DES while pregnant with the F1 participant. Among the participants' 106,198 children, 5,587 (5.3%) had been diagnosed with ADHD. The grandmothers of 137 (2.5%) F2 children with ADHD used DES while pregnant with the F1 participant.

Use of DES by grandmothers significantly increased the odds of ADHD among grandchildren. After adjustment for potential confounders, trimester-specific analysis showed that DES exposure during the first trimester was significantly associated with an increased risk of ADHD (odds ratio, 1.63).

The authors point out that we are exposed daily to environmental EDCs and that, even though the current levels are lower than those in women who were prescribed DES, because those exposures are ubiquitous, the possibility of cumulative effects must be considered.

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