Commentary

Methylphenidate for ADHD in early pregnancy


 

It is estimated that 30%-70% of children diagnosed with attention-deficit/hyperactivity disorder will continue to experience symptoms as they grow older. The prevalence of the disorder in adults is thought to be 3%-4%.

For these reasons, therapeutic use of stimulants to treat attention-deficit/hyperactivity disorder (ADHD) among adults has increased sharply in recent years. This leads to the increasing possibility that pregnant women will either intentionally or inadvertently be treated with ADHD medications during some period of gestation (J. Clin. Psychiatry 2014;75:e88-93); (Can. Fam. Physician 2007;53:1153-5). Yet, there are limited human data regarding the use of these medications with respect to fetal safety.

Dr. Christina D. Chambers

Of the various medications currently marketed for the treatment of ADHD, the stimulant medication methylphenidate is the single drug with the largest amount of published human pregnancy safety data. The Swedish Medical Birth Register holds reports on 104 children exposed to methylphenidate in early pregnancy. Three children had congenital malformations (two to three expected), all of which were heart defects (Basic Clin. Pharmacol. Toxicol. 2013;112:73-6).

Another register-based study, conducted in Denmark between 1998 and 2010, identified 480 pregnancies in which women had redeemed at least one prescription for an ADHD medication; 81.9% of these prescriptions were for methylphenidate (Pharmacoepidemiol. Drug Saf. 2014 Mar 4 [doi: 10.1002/pds.3600]). Women treated with an ADHD medication in pregnancy were more likely to be younger, single, less educated, and primiparous, and to have used other psychotherapeutic medications. Methylphenidate-exposed women were more likely to experience an induced or spontaneous abortion than other pregnant women in the population, but no more likely to have a child with a congenital anomaly (adjusted odds ratio, 0.48; 95% confidence interval, 0.15, 1.53).

A third study, also from Denmark, identified 240 pregnancies with a prescription dispensed for methylphenidate in the first trimester and linked them to live birth outcomes between 2005 and 2012. It is unclear how much overlap there was with the pregnancies reported in the previously mentioned Danish study from the same data source. Methylphenidate-exposed pregnancies in this analysis were compared with propensity score–matched pregnancies presumed to be unexposed to the drug, to address confounding by age, education, tobacco, and other drug use that differed between the groups. Among the exposed, 3.2% of pregnancies resulted in a child with a major malformation, which is within the expected range in the population. The point prevalence ratio for major birth defects comparing the methylphenidate-exposed women to the matched controls was 0.8 (95% confidence interval, 0.3-1.8) (J. Clin. Psychiatry 2014;75:e88-93).

Finally, a study from Israel (published as an abstract only) identified 54 methylphenidate-exposed pregnancies of which 52 were exposed in the first trimester and compared outcomes with 54 unexposed pregnancies. There were no congenital malformations reported in the exposed group; there were no significant differences in abortion rates, and no significant differences in gestational age at delivery or mean birth weight between the groups (Reprod. Toxicol. 2011;31:267).

Other than the concern for pregnancy loss, which could be explained in part by other characteristics of the mothers who were taking methylphenidate early in pregnancy, the limited data to date have been generally reassuring, with no suggestion of an overall increased risk for major congenital malformations or a specific pattern of defects. However, the number of exposed pregnancies followed in controlled studies that have been published in the literature to date are too few to allow firm conclusions. Additional data are needed for this drug as well as alternative stimulant and nonstimulant medications used to treat ADHD, particularly in light of the fact that it is evident that an increasing number of women will continue to be treated into their reproductive years.

Dr. Chambers is professor of pediatrics and family and preventive medicine at the University of California, San Diego. She is director of the California Teratogen Information Service and Clinical Research Program. Dr. Chambers is a past president of the Organization of Teratology Information Specialists and past president of the Teratology Society. She said that she had no relevant financial disclosures. To comment, e-mail her at obnews@frontlinemedcom.com.

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