Publication of recent study of pregnancy outcome after methylphenidate exposure

A collaborative study published in J Clin Psychiatry by ENTIS and MotherToBaby affiliated researchers did not suggest that first trimester in utero exposure be associated with increased risk of congenital malformations.


Methylphenidate is a central nervous system stimulant medicinally used in the treatment of attention deficit disorders. Data on its safety in human pregnancy are sparse. A recent prospective, comparative, multicenter, observational cohort study was published in 2016 in the Journal of Clinical Psychiatry [1].

The study was performed by four participating Teratology Information Services (Jerusalem, Berlin, Newcastle-upon-Tyne, and Toronto). Callers who contacted the services between 1996 and 2013 regarding methylphenidate exposure during pregnancy were prospectively collected and followed-up.

The outcome was compared to that of pregnancies from the same services after non-teratogenic exposure (NTE), matched by maternal age, gestational age, and year at initial contact. 382 methylphenidate-exposed pregnancies [90% in the first trimester] were followed-up. There was no significant difference in the overall rate of major congenital anomalies between the groups [10/309=3.2% (methylphenidate) vs. 13/358=3.6% (NTE), p=0.78]. After exclusion of genetic or cytogenetic anomalies and limiting methylphenidate exposure to the period of organogenesis (weeks 4-13 after the last menstrual period), the rates of major congenital anomalies [6/247=2.4% (methylphenidate) vs. 12/358=3.4% (NTE), p=0.51] and cardiovascular anomalies [2/247=0.8% (methylphenidate) vs. 3/358=0.8% (NTE), p=0.97] were similar. There was a higher rate of miscarriage and elective termination of pregnancy in the methylphenidate group. Using Cox proportional hazards model, significant predictors for miscarriage included methylphenidate exposure (adjusted HR=1.98, 95% CI 1.23-3.20, p=0.005) and past miscarriage (adjusted HR=1.35, 95% CI 1.18-1.55, p<0.001).

This study suggests, in accordance with previously published data, that methylphenidate use in the first trimester does not appear to increase the risk for major malformations. Due to limitations, including a high rate of early pregnancy therapy discontinuation and no comparison with a disease-matched group, further studies are required to fully establish the safety of methyphenidate during pregnancy.


[1] Diav-Citrin O, Shechtman S, Arnon J, Wajnberg R, Borisch C, Beck E, Richardson JL, Bozzo P, Nulman I, Ornoy A. Methylphenidate in pregnancy: a multicenter, prospective, observational study. J Clin Psychiatry 2016 May 24. [Epub ahead of print].