Maternal grandmothers’ prepregnancy BMI may impact grandkids’ risk for ADHD

Maternal grandmothers who were underweight before becoming pregnant were more likely to have a grandchild diagnosed with ADHD than women in other BMI categories, a cohort study showed.

“There is growing evidence from animal research that peripregnancy exposures can have effects that are passed on to more than just the next generation,” Marc Weisskopf, PhD, ScD, a professor of environmental epidemiology and physiology at the Harvard T.H. Chan School of Public Health, told Healio. “But this is very hard research to do in humans because of the need to collect data from, and follow, multiple generations.”

The researchers analyzed information from 19,835 grandmother-mother dyads and 44,720 grandchildren in the Nurses’ Health Study II, “one of the few available with the appropriate data” to meet their study’s needs, Weisskopf said. Among the entire cohort, 97.6% were white and before becoming pregnant, 10.7% of them were underweight and 7% were overweight or obese, according to the researchers.

Weisskopf and colleagues reported that 8% of the grandchildren were diagnosed with ADHD. The odds of this diagnosis were higher among grandchildren whose grandmother was underweight before becoming pregnant compared with healthy weight grandmothers (adjusted OR = 1.25; 95% CI, 1.1-1.42). Conversely, the maternal grandmother’s weight gain during pregnancy was not significantly associated with a grandchild’s ADHD diagnosis (aOR for weight gain of 20 pounds or fewer = 1.06; 95% CI, 0.96-1.16; aOR for weight gain of 29 pounds or more = 1.01; 95% CI, 0.91-1.13). In addition, compared with mothers who had a normal weight before becoming pregnant, those who were obese were more likely to have a child diagnosed with ADHD (aOR = 1.27; 95% CI, 1.07-1.49) as were those who were overweight (aOR = 1.13; 95% CI, 1.02-1.26).

“The positive association between grandmother prepregnancy underweight and ADHD risk among the grandchildren remained unchanged after further adjustment for potential mediators,” the researchers wrote in JAMA Network Open.

The results left the researchers “a little surprised,” according to Weisskopf.

“We had thought we might see grandmother overweight/obesity to be associated with grandchild ADHD because of the effects of obesity on endocrine function and DNA methylation,” he said. “But that is not what we saw.”

The researchers said a limitation of the study was that ADHD case ascertainment was based on nurses’ reports, rather than on medical records. “However, maternal reports of ADHD diagnoses in their children have been found to be reliable,” they wrote.

Since healthy weight discussions should already be occurring during patient visits, changes to clinical practice based on the results are “probably” premature, Weisskopf said. He added that the study is among those “shedding light on the issue of exposures to germline cells.”

“These cells are largely not considered in regulatory deliberations, but they may in fact be particularly important to consider given the potential for multigenerational effects,” Weisskopf said.