ADHD More Common in Grandchildren of Women Who Used DES During Pregnancy Interview with:

Marianthi-Anna Kioumourtzoglou ScD Assistant Professor Environmental Health Sciences Mailman School of Public Health Columbia University 

MarianthiAnna Kioumourtzoglou ScD
Assistant Professor
Environmental Health Sciences
Mailman School of Public Health
Columbia University What is the background for this study?

Response: The prevalence of neurodevelopmental disorders, like attention deficit/hyperactivity disorder (ADHD) has been increasing. One of the hypothesized risk factors for increased risk for neurodevelopmental disorders is a class of chemicals known as endocrine disrupting chemicals (EDCs). These chemicals are known to interfere with the endocrine system, i.e. the system that uses hormones to control and coordinate metabolism, reproduction and development. Several high production volume chemicals, ubiquitously present in commercial products, are known or suspected endocrine disruptors. Because of their widespread use in consumer products, the population-wide exposure to known and suspected EDCs is very high.

Recently, there has been increased attention in the potential effects of EDCs on neurodevelopment that span multiple generations. Animal studies have provided evidence that exposure to EDCs, such as phthalates and bisphenol A (BPA), alter the behavior and social interactions in mice in three to five generations after exposure. However, evidence of such multi-generational impacts of EDC exposure on neurodevelopment in humans is unavailable, likely because of the lack of detailed information on exposures and outcomes across generations.

For this study we leveraged information from a nationwide cohort, the Nurses’ Health Study II (NHSII), to investigate the potential link between exposure to diethylstilbestrol (DES) and third generation ADHD, i.e. ADHD among the grandchildren of the women who used DES while pregnant. DES is a very potent endocrine disruptor that was prescribed between 1938 and 1971 to pregnant women thought to prevent pregnancy complications. In the United States, between 5 and 10 million women are estimated to have used DES, although the exact number is not known. DES was banned in 1971, when was linked to vaginal adenocarcinomas (a rare cancer of the reproductive system) in the daughters of the women who had used it during pregnancy. Since then, DES has been also linked to multiple other reproductive outcomes in DES daughters, as well as with some reproductive outcomes in the grandchildren of the women who used it, such as hypospadias and delated menstrual regularization. However, to our knowledge, no study to date has evaluated the association between DES, or any other EDC, and multigenerational neurodevelopment.   What are the main findings?

Response: We used information from 47,540 NHSII participants who reported on their mother’s DES use during pregnancy and on their children’s ADHD diagnosis. Among the 47,540 NHSII mothers, approximately 2% had used DES when pregnant, and among the 106,198 children, 5,587 had been diagnosed with ADHD.

We observed a 36% increase in the odds of ADHD among the grandchildren of women who had used DES during pregnancy compared to the grandchildren of women who had not. This association was not different by the sex of the grandchildren. Grandchildren of women who used DES during their first trimester of pregnancy, furthermore, had 63% increased odds of ADHD compared to grandchildren of women who did not use DES. What should readers take away from your report?

Response: In our study, we found evidence in humans of increased ADHD risk in the third generation following DES use during pregnancy. Although the levels and potency of DES are much higher than those of any single EDC to which humans are daily exposed, the ubiquity of environmental EDC exposure, suggesting a very high prevalence, and the possibility of cumulative consequences must be considered. What recommendations do you have for future research as a result of this work?

Response: Because this was the first ever study to investigate the association between exposure to a potent EDC and third-generation neurodevelopment, our findings should be interpreted with caution. More human studies are warranted to evaluate the same association, as well as the association with environmental EDCs to which humans are daily exposed. 

Nothing to disclose.


Kioumourtzoglou M, Coull BA, O’Reilly ÉJ, Ascherio A, Weisskopf MG. Association of Exposure to Diethylstilbestrol During Pregnancy With Multigenerational Neurodevelopmental Deficits. JAMA Pediatr. Published online May 21, 2018. doi:10.1001/jamapediatrics.2018.0727 

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Last Updated on May 21, 2018 by Marie Benz MD FAAD