Fetal safety of methylphenidate—A scoping review and meta analysis

Highlights

• Methylphenidate exposure in early pregnancy is associated with a small but significant increased risk for major malformations.

• These 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.

Abstract

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.

Introduction

ADHD is a common condition among children, reaching up to 10 % around the world [1]. Many of these children are chronically treated with central stimulants, with methylphenidate and amphetamines considered first line drugs [2] Over the last few decades it has become apparent that ADHD does not resolve in childhood, and presently, increasing numbers of adults receive these medications [3]. Not surprising then, exposure to methylphenidate in pregnancy has increased substantially, becoming a serious issue, dues to fetal exposure to a drug with insufficient record of fetal safety [4]. Over the last two decades increasing numbers of case reports and case series have been published, however, these have very limited power to endorse fetal safety [5]. Only during the last decade, observational cohort studies have begun to emerge, addressing the issue of fetal safety. However, most of them have been small studies, with limited numbers of methylphenidate-exposed offspring, and often lumping in the analysis different psychostimulants.

The objective of the present analysis was to estimate the fetal safety of methylphenidate using all existing cohort studies in which fetal malformation rates were compared among women exposed to the drug, to control groups of unexposed women. Such data are critical for women with ADHD; because half of all pregnancies are unplanned, many of them may unknowingly expose their unborn babies to the drug. In addition, increasing numbers of women who need methylphenidate for their health and well- being are asking teratology counseling services and obstetricians about the safety of using methylphenidate in early pregnancy.

The aim of this study was to conduct 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.