A pregnancy drug banned decades ago may have side effects that linger for generations. Grandchildren of women who took it have an increased risk of attention deficit hyperactivity disorder (ADHD), a new study suggests. The drug, a synthetic estrogen known as diethylstilbestrol (DES), was designed to prevent pregnancy complications like miscarriage and preterm delivery. As many as 10 million U.S. women may have used the drug between 1938 and 1971, when it was banned after being linked to vaginal cancers in daughters of women who used it. Now, a new study suggests that grandchildren of women how took DES during pregnancy are 36 percent more likely to be diagnosed with ADHD than other kids. And when women took DES during the first trimester of pregnancy, their grandchildren had 63 percent higher odds of developing ADHD, researchers report in JAMA Pediatrics. “An exposure during pregnancy has the potential to impact multiple generations if the fetus is female, because the oocytes (aka egg cells) that will develop into the grandchildren of the pregnant woman grow while their mother is in utero,” said lead study author Marianthi-Anna Kioumourtzoglou of the Mailman School of Public Health at Columbia University in New York City. “Use of DES during pregnancy or other endocrine disrupting chemicals could thus directly impact the third generation, leading to neurodevelopmental disorders, such as ADHD,” Kioumourtzoglou said by email. Chemicals known as endocrine disruptors can interfere with the body's endocrine, or hormone, system and produce negative developmental, reproductive, neurological and immune effects. These chemicals have been used to make a wide variety of consumer products over the years, including baby bottles, metal food cans, flame retardants, detergents, pesticides and cosmetics. A range of health problems including autism, ADHD, obesity, diabetes, heart and vascular disorders, and endometriosis have been linked to exposure to endocrine disruptors. DES in particular has been linked to delays in regular menstrual cycles for granddaughters of women who used the drug during pregnancy, researchers note. Grandsons of these women also have an increased risk of hypospadias, an abnormality that occurs when the opening of the urethra doesn't develop on the tip of the penis and instead forms on the shaft or on the scrotum. The new findings are drawn from 47,540 women in an ongoing study of U.S. nurses, including 861 women, or 1.8 percent, who used DES while pregnant. Overall, 7.7 percent of the grandchildren of women who used DES during pregnancy were diagnosed with ADHD, compared with 5.2 percent of other grandchildren in the study. This increased risk of ADHD was similar for male and female grandkids. The study wasn't a controlled experiment designed to prove whether or how DES exposure during pregnancy might cause ADHD generations later. Another limitation of the study is that researchers relied on survey data from one generation - the mothers - to assess DES use in grandmothers and ADHD diagnoses in grandchildren. It's possible mothers didn't know or recall whether the grandmothers used DES while they were pregnant, the authors note. Still, the results add to a growing body of evidence suggesting that exposure to DES and other endocrine disrupting chemicals may have effects that span generations, said Joel Nigg, author of an accompanying editorial and a psychiatry and neuroscience researcher at Oregon Health & Science University in Portland. “The entire class of hormone/endocrine disrupting medicines and chemicals have been known or suspected to interfere with offspring development for many years,” Nigg said by email. “What is new here is the demonstration of effects to grandchildren, and the possibility that this reflects an inherited epigenetic effect,” Nigg added. “That widens the sphere of possibilities for how kids' neurodevelopmental problems originate.”
Even though DES is no longer prescribed, other endocrine disruptors and so-called neurotoxic chemicals that alter fetal development can still get into women's bodies from pesticides on food, beauty products, and air pollution. Women may not always be able to avoid exposure, but reading product labels and eating organic fruits and vegetables can help minimize the risk, Nigg advised.
