Summary: A new study reveals elevated risks of ADHD diagnosis in grandchildren of women who took a synthetic estrogen drug, known as DES, between 1948 and 1971.
Source: Columbia University.
A study conducted by researchers at Columbia University’s Mailman School of Public Health and Harvard T.H. Chan School of Public Health reported elevated odds for attention deficit hyperactivity disorder (ADHD) in the grandchildren of users of diethylstilbestrol, a synthetic estrogen commonly known as DES prescribed between 1938 and 1971 to prevent pregnancy complications. This is the first study to provide evidence of the potential neurodevelopmental consequences of DES use across generations. The findings are published online in JAMA Pediatrics.
DES treatment for pregnant women was phased out after a 1953 study showed no benefit, and was banned in 1971 when DES was linked to vaginal adenocarcinomas in the daughters of women who had used DES during pregnancy. DES, which disrupts the body’s endocrine system, was later also linked to multiple other reproductive problems in DES daughters. Although the exact number of pregnant women that used DES is unknown, in the U.S. it is estimated to be between 5-10 million.
“Our aim was to explore the potential impact of DES use across generations, and specifically on third-generation neurodevelopment,” said Marianthi-Anna Kioumourtzoglou, ScD, assistant professor of Environmental Health Sciences at the Mailman School of Public Health. “To date, and to our knowledge, no epidemiologic study has assessed multigenerational impacts of DES – or any other endocrine disruptors – on neurodevelopment.”
The study was based on self-reported health information from 47,540 participants enrolled in the ongoing Nurses’ Health Study II, approximately 2 percent of whom had mothers who used DES while pregnant, as well as the 106,198 children born to nurses in the study.
Using DES was associated with 36 percent higher odds of ADHD among grandchildren of women who used DES compared to grandchildren women who did not use the drug during pregnancy. These results did not differ by the sex of the children.
“While DES is banned, pregnant women continue to be exposed to a large number of environmental endocrine disruptors,” said Marc Weisskopf, PhD, ScD, professor of Environmental and Occupational Epidemiology at the Harvard T.H. Chan School of Public Health, and senior author of the study. “And although current exposures are at a lower level and potency than seen with DES, cumulative exposures to these chemicals may be cause for concern and is deserving of further study.”
Funding: The study was supported by the National Institutes of Health (ES007069, ES000002, ES009089, CA176726), and the Escher Fund for Autism.
Co-authors are Brent Coull, Harvard T.H. Chan School of Public Health; Éilis O’Reilly, School of Public Health and Epidemiology, University College Cork, Ireland; and Alberto Ascherio, Harvard T.H. Chan School of Public Health, and Brigham and Women’s Hospital, Boston.
Source: Stephanie Berger – Columbia University
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Open access research for “Exposure to Diethylstilbestrol During Pregnancy and Multigenerational Neurodevelopmental Deficits” by Marianthi-Anna Kioumourtzoglou, ScD; Brent A. Coull, PhD; Éilis J. O’Reilly, ScD; Alberto Ascherio, MD, DrPH; and Marc G. Weisskopf, PhD, ScD in JAMA Pediatrics. Published May 21 2018.
Exposure to Diethylstilbestrol During Pregnancy and Multigenerational Neurodevelopmental Deficits
Importance Animal evidence suggests that endocrine disruptors affect germline cells and neurodevelopment. However, to date, the third-generation neurodevelopmental outcomes in humans have not been examined.
Objective To explore the potential consequences of exposure to diethylstilbestrol or DES across generations—specifically, third-generation neurodevelopment.
Design, Setting, and Participants This cohort study uses self-reported health information, such as exposure to diethylstilbestrol during pregnancy and attention-deficit/hyperactivity disorder (ADHD) diagnosis, from 47 540 participants enrolled in the ongoing 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).
Main Outcomes and Measures Participant- and mother-reported exposure to diethylstilbestrol during pregnancy and physician-diagnosed child ADHD.
Results The total number of women included in this study was 47 540. 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 diethylstylbestrol by F0 mothers was associated with an increased risk of ADHD among the F2 generation: 7.7% vs 5.2%, adjusted odds ratio (OR), 1.36 (95% CI, 1.10-1.67) and an OR of 1.63 (95% CI, 1.18-2.25) if diethylstilbestrol was taken during the first trimester of pregnancy. No effect modification was observed by the F2 children’s sex.
Conclusions and Relevance This study provides evidence that diethylstilbestrol exposure is associated with multigenerational neurodevelopmental deficits. The doses and potency level of environmental endocrine disruptors to which humans are exposed are lower than those of diethylstilbestrol, but the prevalence of such exposure and the possibility of cumulative action are potentially high and thus warrant consideration.