Methylphenidate use during pregnancy not linked to malformations overall

Methylphenidate use during pregnancy was not linked to an increased risk for malformations overall in a nationwide registry-based study with information on both prenatal and postnatal diagnoses published in Journal of Clinical Psychiatry.

“A 2018 meta-analysis of [eight] cohort studies did not find an association of exposure to any ADHD medication during pregnancy and any major malformation (risk ratio [RR] = 1.05; 95% CI, 0.96–1.16) or cardiac malformations (RR = 1.08; 95% CI, 0.92–1.27),” Line Kolding, MD, PhD, of the department of obstetrics and gynecology at Aarhus University Hospital in Denmark, and colleagues wrote. “However, methylphenidate was associated with an increased risk [for] cardiac malformations (RR=1.27; 95% CI, 0.99–1.63), with the result nearly solely based on data from a large study from the United States and the Nordic countries that included 3,474 methylphenidate-exposed pregnancies.”

Further, data is currently lacking on malformations resulting in pregnancy loss, which may thus lead to underestimation of the occurrence of malformations and potential survivor bias if only data are available for liveborn children, the researchers noted. Thus, in the current study, Kolding and colleagues analyzed data of both prenatal and postnatal diagnoses of major malformations. Specifically, they included 364,012 singleton pregnancies in Denmark between Nov. 1, 2007, and Feb. 1, 2014. They obtained exposures to ADHD medication from redeemed prescriptions from the Danish Health Services Prescription Database. Prenatally diagnosed malformations from the Danish Fetal Medicine Database, as well as postnatally diagnosed malformations from the Danish National Patient Registry, were used as outcome data. Major malformations overall served as the primary outcome and malformations of the central nervous system and cardiac malformations as secondary outcomes. Pregnancies with no redeemed prescriptions for ADHD medication was the comparison group. The investigators defined severe cardiac malformations as “concurrent diagnoses of a cardiac malformation with miscarriage, termination, stillbirth, postnatal death or cardiac surgery within 1 year of birth.”

Results showed an increase in the prevalence of first-trimester exposure to ADHD medication from 0.05% in 2008 to 0.27% in 2013. Most of the exposures were to methylphenidate. The researchers noted 5.1% malformations overall and 2.1% cardiac malformations among the exposed vs. 4.6% and 1%, respectively, among those who were not exposed. The adjusted prevalence ratios for methylphenidate were 1.05 (95% CI, 0.7-1.55) for malformations overall and 1.65 (95% CI, 0.89-3.05) for any cardiac malformations, with septum defects in 10 of 12 cases. Kolding and colleagues reported a prevalence ratio of 2.74 (95% CI, 1.03-7.28) for ventricular septal defect and 2.59 (95% CI, 0.98-6.9) for severe cardiac malformations.

“We believe that the results add important information regarding safety of ADHD medication given the rapidly increasing use of ADHD medications during pregnancy and among women of reproductive age who may become pregnant inadvertently,” the researchers wrote.