The use of methylphenidate by pregnant women is associated with a small increased risk of congenital cardiac malformations in newborns. However, a comparable increased risk is not found with intrauterine exposure to stimulants, according to a population-based cohort study published Dec. 13.

Krista F. Huybrechts, PhD , and her associates analyzed data from more than 1 million pregnancies in the United States. They found that the overall incidence of congenital malformations among the 1,813,894 pregnancies was 35 per 1,000 control infants, compared with 45.9 per 1,000 infants whose mothers used methylphenidate and 45.4 per 1,000 infants whose mothers used amphetamines.

For the subset of infants with cardiac malformations, the risk per 1,000 infants was 12.7 for controls, 18.8 for methylphenidate exposure, and 15.4 for amphetamine exposure. The researchers identified an adjusted relative risk of 1.11 for overall congenital abnormalities and 1.28 for cardiac abnormalities with methylphenidate exposure, compared with a relative risk of 1.05 for overall congenital abnormalities and 0.96 for cardiac abnormalities with stimulant exposure.

An analysis among 2,560,069 pregnancies in Denmark, Finland, Iceland, Norway, and Sweden yielded a similarly significant relative risk of 1.28 for cardiac malformations associated with methylphenidate exposure (JAMA Psychiatry 2017. doi: 10.1001/jamapsychiatry.2017.3644 ).

“We found a 28% increased prevalence of cardiac malformations after first-trimester exposure to methylphenidate,” wrote Dr. Huybrechts of Brigham and Women’s Hospital, Boston, and her associates. “Although the absolute risk is small, it is nevertheless important evidence to consider when weighing the potential risks and benefits of different treatment strategies for [attention-deficit/hyperactivity disorder] in young women of reproductive age and in pregnant women.”

The researchers had no financial conflicts to disclose. The study was supported in part by grants from the National Institutes of Mental Health, the Eunice Kennedy Shriver National Institute for Child Health & Human Development, and the Söderström König Foundation.