Fetal safety of methylphenidate—A scoping review and meta analysis

While for decades attention deficit hyperactivity disorder (ADHD) was regarded as mostly a pediatric condition, it is apparent that many adults continue to be afflicted by this condition, and presently an estimated 30 %–40 % of patients continue with ADHD symptomatology into adulthood. With more adults using stimulants for ADHD, there is evidence of increased numbers using ADHD medications in pregnancy. Till recently the reports on ADHD medication safety have been sparse with insufficient power to address fetal safety. Methylphenidate has been a first line treatment for ADHD, with relatively large numbers of usage. We conducted a scoping review and meta-analysis of observational cohort studies that compared malformation rates among offspring exposed to methylphenidate during early pregnancy, to the rates in the general population. Meta- analysis of 4 cohort studies with almost 3000 women exposed to methylphenidate only, and almost 3 million unexposed controls, yielded an OR of 1.26(95 % confidence interval 1.05–1.51) for major malformations, and 1.59 (95 % confidence interval 1.02–2.49) for cardiac malformations. In conclusion, methylphenidate exposure in early pregnancy is associated with a small but significant increased risk for major malformations, which can be attributed mostly to increased risk of cardiac malformations. It may be advisable to consider fetal echocardiography in pregnant women using methylphenidate during pregnancy.