Women who take a class of stimulants used to treat attention deficit hyperactivity disorder (ADHD) during pregnancy are 28 percent more likely to have a baby with cardiac malformations, according to a study in JAMA Psychiatry.

Krista F. Huybrechts, MS, PhD, with Brigham and Women’s Hospital and Harvard Medical School, and colleagues studied 1.8 million publicly insured women who gave birth in the U.S. and replicated their findings in a cohort of 2.5 million live births from Nordic countries.

Both populations showed a risk-adjusted increase in cardiac defects after a mother’s exposure to methylphenidate—commonly known by brand names Ritalin and Concerta—when compared to women not taking the stimulants. The absolute increase in complications is relatively small: about three additional infants are born with congenital cardiac malformations for every 1,000 women who receive methylphenidate during the first trimester of pregnancy, according to the researchers.

The risk of overall congenital malformations associated with methylphenidate wasn’t statistically significant and no increased risk of overall malformations or congenital defects was detected for amphetamines, another class of stimulant used in treating ADHD.

“This information is important when weighing the risks and benefits of alternative treatment strategies for attention-deficit/hyperactivity disorder in women of reproductive age and during early pregnancy,” Huybrechts et al. wrote.

The authors pointed out the use of these ADHD medications has risen substantially in recent years, including in women of reproductive age. For this reason, they wrote, it is important for women to understand their safety in cases of both planned and unplanned pregnancy.

Huybrechts and colleagues divided the study cohorts into exposure groups for each class of stimulant and compared them to the unexposed population. A woman was considered unexposed if she hadn’t filled a prescription for any ADHD medication from three months before her last menstrual period until the end of her first trimester.

Among the approximately 1.8 million pregnancies in the U.S. cohort, 2,072 women (0.11 percent) filled a prescription for methylphenidate and 5,571 women (0.31 percent) filled a prescription for an amphetamine.

In a related editorial, William O. Cooper, MD, MPH, said the researchers’ use of a validation cohort and sensitivity analyses substantiates their findings. And even though the absolute risk increase associated with methylphenidate was small, “any study that sheds light on the many unknowns related to prescription medication use during pregnancy is a welcome addition to the literature,” Cooper wrote.

“Because nearly half of pregnancies are unplanned, women could be taking a prescription medication and become pregnant without being aware of the concomitant risks,” he added. “Thus, it is important to provide information to women who use any medication and who are pregnant or likely to become pregnant. In the clinical setting, where a pregnant woman can be prescribed a different medication or medication can be temporarily avoided, information on risks can be particularly important to guide decision making.”