Perinatal Outcomes of ADHD Medication Use During Pregnancy

Source: di Giacomo E, Confalonieri V, Tofani F, et al. Methylphenidate and atomoxetine in pregnancy and possible adverse fetal outcomes: a systematic review and meta-analysis. JAMA Netw Open. 2024;7(11):e2443648; doi: 10.1001/jamanetworkopen.2024.43648.Investigators from the University of Milano-Bicocca, Monza, Italy, conducted a meta-analysis to assess the association between receiving treatment for attention-deficit/hyperactivity disorder (ADHD) with methylphenidate and/or atomoxetine during pregnancy and risk of congenital anomalies and miscarriage. A systematic process was used to identify published observational studies that compared the rate of congenital anomalies or miscarriage in the offspring of women with ADHD who were treated with methylphenidate and/or atomoxetine during pregnancy (exposed group) with those with ADHD who were not receiving these medications (unexposed group), or with women without ADHD (general population). The location, year of publication, and results were abstracted from the identified publications. Meta-analyses were conducted to determine the risk of congenital anomalies and miscarriage in the exposed ADHD group and those in the unexposed ADHD group and in the general population. A secondary meta-analysis was performed to compare these outcomes among offspring of women in the unexposed ADHD group and the general population.Ten studies met eligibility criteria and were included in the meta-analysis. Data from a total of 16,621,481 pregnant women, 30,830 with ADHD, were analyzed. The identified studies were conducted in 6 countries, and all were published after 2014. Five studies assessed prenatal exposure to methylphenidate, 4 with exposure to methylphenidate and atomoxetine, and 1 to atomoxetine alone. The risk of congenital anomalies among offspring of ADHD exposed and unexposed women was assessed in 5 studies; there was not a significantly increased risk associated with exposure to methylphenidate and/or atomoxetine (odds ratio [OR], 1.14; 95% CI, 0.83, 1.55). Similarly, no difference in risk of miscarriage among women in the ADHD exposed or ADHD unexposed group was found in the meta-analysis of 3 studies (OR, 1.01; 95% CI, 0.70, 1.47). Compared to the general population of pregnant women without ADHD, prenatal exposure to methylphenidate and/or atomoxetine was not associated with an increased risk of congenital anomalies (OR, 1.19; 95% CI, 0.93, 1.53) or miscarriages (OR, 1.05; 95% CI, 0.81, 1.37). When the risk of congenital anomalies or miscarriage was compared among women in the ADHD unexposed group and the general population of pregnant women, no increased risk for either outcome was found (OR, 1.23; 95% CI, 0.58, 2.63 and OR, 0.88; 95% CI, 0.71, 1.09, respectively).The authors conclude that the risk of congenital anomalies or miscarriages was not increased in women with ADHD receiving methylphenidate and/or atomoxetine during pregnancy.Dr Goyal has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.In recent decades, there has been a significant increase in the prevalence of diagnosed ADHD among pregnant women, as well as an increase in the use of ADHD medications during pregnancy.1,2 Importantly, ADHD in pregnancy warrants screening and attention to associated comorbid conditions, including substance use disorder and mood disorders,3 and the safety of using psychotropic medications during pregnancy is a frequent concern. Two commonly used treatments for ADHD in pregnancy are methylphenidate (a norepinephrine-dopamine reuptake inhibitor) and atomoxetine (a selective norepinephrine reuptake inhibitor). Both are classified by the US Food and Drug Administration as “pregnancy category C,” indicating that there is insufficient research, but benefits may outweigh risks.4The current investigators found no significantly increased risk of congenital anomalies or miscarriages with methylphenidate and/or atomoxetine for ADHD treatment during pregnancy. While an overall reassuring finding, other potential outcomes of fetal exposure to these medications, including neurodevelopmental and longer-term cardiovascular conditions, were outside the scope of this study and are methodologically more challenging to study with observational data. Concomitant use with other psychotropic medications also was not evaluated. Still, these results can help inform shared decision making for pregnant women with ADHD, for whom the balance of benefits and risks of treatment will vary depending on clinical factors, values, and preferences.Use of methylphenidate and/or atomoxetine for ADHD during pregnancy does not appear to increase the risk of congenital anomalies or miscarriage. (See AAP Grand Rounds. 2023;49[3]:29.)5