Banned pregnancy med still affecting daughters, grandchildren

The grandchildren of women who used a drug called diethylstilbestrol, or DES, during pregnancy have a higher risk of attention deficit hyperactivity disorder (ADHD), new research shows.

The study, published in the Journal of the American Medical Association Pediatrics, shows how significant exposure to an endocrine disruptor during pregnancy can affect brain development in later generations.

Endocrine-disruptors are chemicals that interfere with the body’s intricate hormone system, and have been associated with a number of neurological disorders, including ADHD. Increasing evidence suggests they can alter the epigenetic programming of reproductive cells. In other words, they can cause heritable changes in gene activity.

Animal studies show that endocrine disruptors, such as di(2ethylhexyl)phthalate (DEHP) and bisphenol A (BPA), are indeed linked with negative neurological effects in subsequent generations, but it was unknown if this was also the case for humans.

Researchers at Colombia and Harvard Universities in the US, and University College Dublin in Ireland, identified an opportunity to study the generational effects of one such disruptor by analysing data from the Nurses Study II, a long-term investigation of thousands of nurses in the US, which began in 1989. The study has primarily gathered diet, lifestyle and health data, but also collected information about the use of DES, a synthetic estrogen.

DES was prescribed to millions of women between 1938 and 1971, because it was thought to prevent miscarriage. However, a 1953 study showed it to be ineffective. Another study in 1971 revealed increased rates of vaginal cancer in the daughters of women who had taken it, and it was banned that same year.

DES, it turned out, was a potent endocrine disruptor.

The new research examined the self-reported health information of 47,540 participants enrolled in the ongoing study. Of these, nearly 2% had mothers who had used DES during pregnancy. Moreover, many of the nurses in the cohort had gone on to have children of their own.

“Our aim was to explore the potential impact of DES use across generations, and specifically on third-generation neurodevelopment,” says the study’s first-author, Marianthi-Anna Kioumourtzoglou of the Columbia University Mailman Institute 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 findings revealed that grandchildren of the women who had used DES were 36% more likely to have ADHD than grandchildren of women who had not used the drug, regardless of whether those grandchildren were male or female.

The findings provide evidence in humans that exposure to endocrine disruptors during pregnancy can alter neurodevelopment in later generations.

“While DES is banned, pregnant women continue to be exposed to a large number of environmental endocrine disruptors,” says co-author Marc Weisskopf of Harvard.

“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.”