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First trimester ADHD drug exposure increases risk for congenital heart defects
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Intrauterine exposure to methylphenidate during pregnancy was associated with a small increase in the risk for cardiac malformations; however, this association was not seen with amphetamines, according to data published in JAMA Psychiatry.
“Data regarding the safety of stimulant medications in early pregnancy are limited,” Krista F. Huybrechts, PhD, from the division of pharmacoepidemiology and pharmacoeconomics in the department of medicine at Brigham and Women’s Hospital, and colleagues wrote. “Given the rapidly increasing use of stimulant medications during pregnancy and among women of reproductive age who may become pregnant inadvertently, there is a need to better understand their safety.”
Researchers examined the risk for congenital malformations and a subgroup of cardiac malformations associated with intrauterine exposure to methylphenidate and amphetamines during the first trimester. They assessed data from 1,813,894 publicly-insured pregnancies in the U.S. enrolled in the 2000 to 2013 U.S. Medicaid Analytic eXtract, with follow-up of safety signals detected in 2,560,069 singleton pregnancies in Nordic Health registries from 2003 to 2013. Relative risk estimates accounted for underlying psychiatric disorders and other potential confounders.
Of the pregnancies evaluated in the U.S. data, 35 per 1,000 infants not exposed to stimulants had congenital malformations compared with 45.9 per 1,000 infants exposed to methylphenidate and 45.4 per 1,000 exposed to amphetamines. The risks for cardiac defects were 12.7 per 1,000 infants not exposed to stimulants (95% CI, 12.6-12.9), 18.8 per 1,000 infants for methylphenidate (95% CI, 13.8-25.6), and 15.4 per 1000 infants for amphetamines (95% CI, 12.5-19).
“If pregnant women take methylphenidate during the first trimester of pregnancy, they have a small increased risk of having a baby born with a cardiac malformation. No such increase in risk was seen for amphetamines,” Huybrechts told Healio Psychiatry. “This is important evidence to consider for pregnant women and for young women of reproductive age when weighing the potential risks and benefits of different treatment strategies for ADHD.”
After adjusting for confounders, relative risks for methylphenidate were 1.11 (95% CI, 0.91-1.35) for any malformation and 1.28 (95% CI, 0.94-1.74) for cardiac malformations, but there were no increased risks observed for amphetamines. Examination of the Nordic data used to replicate the analyses for methylphenidate yielded a relative risk of 1.28 (95% CI, 0.83-1.97) for cardiac malformations, resulting in a pooled estimate of 1.28 (95% CI, 1-1.64). Sensitivity analyses confirmed these findings.
“We do want to emphasize, however, that cardiac malformations are a serious but rare outcome. They affect approximately 10 per 1,000 births. With use of methylphenidate, this risk appears to increase to about 13 per 1,000 births,” Huybrechts said. “This risk would have to be weighed against the risks associated with discontinuing treatment during pregnancy when symptoms are severe and interfere significantly with daily functioning.”
In a related editorial, William O. Cooper, MD, MPH, from the departments of pediatrics and health policy at Vanderbilt University School of Medicine, wrote that these findings offer much-needed information on the risks of prescription medication use during pregnancy.
“While the absolute increase in cardiac malformation risk associated with methylphenidate in the study was small, these results make an important contribution to the question of the safety of methylphenidate and amphetamine use during pregnancy,” Cooper wrote. “The innovative approaches used by the authors add additional contributions to future questions of pregnancy-related medication safety.” – by Savannah Demko
Disclosures: The authors report no relevant financial disclosures.