The ties that bind us to our ancestors might be even more influential than we knew, suggests a new study published in JAMA Pediatrics. It found that the grandchildren of women who took a certain hormone-mimicking drug before the 1970s were at higher risk of developing attention deficit hyperactivity disorder (ADHD) compared to children whose grandmothers didn't take the drug.
Diethylstilbestrol is a synthetic drug that mimics and, it was later shown, interferes with the effects of natural hormones, including estrogen. First created in 1938 and widely available on the market starting in the 1940s, it was prescribed to women as a treatment to prevent miscarriages and other pregnancy complications. But in 1971, a historic study in the New England Journal of Medicine confirmed what doctors had suspected for a while: Children whose mothers took DES while pregnant were more likely to develop rare genital cancers and other complications like infertility and genital defects. These children became known as DES daughters and DES sons.
Following publication of the 1971 study, DES was quickly taken off the shelves in many countries as a treatment for pregnant women. Ironically enough, an earlier clinical trial in the 1950s found that DES wasn't even good at its advertised job of preventing pregnancy problems. In DES daughters, it did the opposite, increasing the chances of these women experiencing their own miscarriages if they became pregnant.
In this latest study, researchers from Columbia University and elsewhere used self-reported data from one of the longest-run, ongoing population studies in the US, the Nurses Health Study II, to look at the children of these DES daughters. This study enrolled over 100,000 women nurses from the ages of 25 to 42 starting in 1989, and has kept track of their overall health through questionnaires mailed every two years.
The researchers looked at 47,540 women in the study who had kept in touch with researchers, as well as their combined 106,198 children. Around 2 per cent of these women had been born to mothers who took DES during their pregnancy. They found that children born to DES daughters were 36 per cent more likely to be diagnosed with ADHD compared to everyone else. These differences were the same regardless of the child's gender.
The study isn't the first to suggest that the long shadow of DES exposure can reach past one generation. Other research in humans has shown that DES grandchildren are more likely to be infertile, while animal studies have suggested it could raise the risk of cancer in third-generation children. The current study, the authors say, is the first to show DES can have a lasting negative impact on the brain.
It's thought that DES mostly causes epigenetic changes in the body. Rather than necessarily mutate a person's genes, DES alters how those genes are expressed and actually manifest in a person. Though most everything we experience in the world can tweak our epigenetics, our bodies do their best to wipe out any alterations in the respective egg and sperm cells that go on to become future children. But just like certain genetic mutations and traits, some epigenetic changes seem to be passed down.
Research has suggested that other factors, including prolonged starvation, childhood abuse, and smoking, might create these same sort of intergenerational effects. But epigenetic inheritance is still a relatively new and debated field of research, and there's still a lot we don't know about how exactly it might work. It's also hard to confirm these links exist, given how difficult it can be to spot epigenetic changes across generations (to say nothing of being able to keep track of them for decades).
But if these current findings do hold up to scrutiny, the authors warn they could have much greater implications.
"While DES is banned, pregnant women continue to be exposed to a large number of environmental endocrine disruptors," said study senior author Marc Weisskopf, professor of environmental and occupational epidemiology at the Harvard T.H. Chan School of Public Health, in a statement. "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."