OBJECTIVE: The use of methylphenidate to treat attention-deficit/hyperactivity disorder has risen dramatically in Western countries, and it is increasingly used by adults, including women of childbearing age. Very little is known about potential hazards of in utero exposure to methylphenidate. We conducted this study to estimate the risk of major congenital malformations following first-trimester in utero exposure to methylphenidate.

METHOD: Data from 2005 to 2012 were extracted from the Danish National Patient Register, the Danish National Prescription Registry, the Medical Birth Registry, and the Danish Civil Registration System. Exposure was defined as having redeemed 1 or more prescriptions for methylphenidate within a time window defined as 14 days before the beginning of the first trimester up to the end of the first trimester. Each exposed subject was propensity score-matched to 10 unexposed subjects with respect to maternal age, smoking status, body mass index, length of education, calendar year of completion of pregnancy, and concomitant use of antipsychotics, antidepressants, anxiolytics, and nonsteroidal anti-inflammatory drugs.

RESULTS: We included 222 exposed and 2,220 unexposed pregnancies in the analysis. There was no statistically significant increase in major malformations (point prevalence ratio = 0.8; 95% CI, 0.3-1.8) or cardiac malformations (point prevalence ratio = 0.9; 95% CI, 0.2-3.0). Sensitivity analyses using different definitions of exposure or previous users of methylphenidate as the unexposed comparison cohort yielded comparable results.

CONCLUSIONS: First-trimester in utero exposure to methylphenidate does not appear to be associated with a substantially (ie, more than 2-fold) increased overall risk of major congenital malformations.