To help answer that question, a cohort study published recently in the Journal of the American Medical Association Psychiatry included 7,065 pregnancies exposed to amphetamine/dextroamphetamine and 1,123 pregnancies exposed to methylphenidate in the second half of pregnancy. The study found that “neither medication was associated with autism spectrum disorder, attention-deficit/hyperactivity disorder, or a composite of any neurodevelopmental disorder in children after careful adjustment for confounding by indication through various design and analytic approaches.”
Researchers from Brigham and Women’s Hospital & Harvard Medical School and colleagues reported that their findings suggested that amphetamine/dextroamphetamine and methylphenidate exposure during pregnancy are not likely to meaningfully increase the risk of childhood neurodevelopmental disorders.
The article pointed out that use of medications for ADHD during pregnancy is increasing in the United States. It has been unknown, however, whether exposure to those medications in utero impacts the risk of neurodevelopmental disorders in children.
The study team sought to evaluate the association of childhood neurodevelopmental disorders with in-utero exposure to stimulant medications for ADHD. The cohort study included healthcare-utilization data from publicly insured (Medicaid data from 2000 to 2018) and commercially insured (MarketScan Commercial Claims Database data from 2003 to 2020) pregnant women aged 12 to 55 years in the U.S. They were followed from enrollment 3 months prior to pregnancy through 1 month after delivery. The offspring were monitored from birth until outcome diagnosis, disenrollment, death, or end of the study (December 2018 for Medicaid and December 2020 for MarketScan).
The women received amphetamine/dextroamphetamine or methylphenidate in the second half of pregnancy. The publicly insured cohort included 2.5 million stimulant-unexposed, 4,693 amphetamine/dextroamphetamine–exposed, and 786 methylphenidate-exposed pregnancies; the women had a mean (SD) age of 25.2 (6.0) years. The commercially insured cohort included 1.8 million stimulant-unexposed, 2,372 amphetamine/dextroamphetamine–exposed, and 337 methylphenidate-exposed pregnancies with a mean (SD) age of 31.6 (4.6) years.
The results indicated that in unadjusted analyses, amphetamine/dextroamphetamine and methylphenidate exposure were associated with a two- to threefold increased risk of the neurodevelopmental outcomes considered. “After adjustment for measured confounders, amphetamine/dextroamphetamine exposure was not associated with any outcome (autism spectrum disorder: hazard ratio [HR], 0.80; 95% CI, 0.56-1.14]; ADHD: HR, 1.07; 95% CI, 0.89-1.28; any neurodevelopmental disorder: HR, 0.91; 95% CI, 0.81-1.28),” the authors wrote. “Methylphenidate exposure was associated with an increased risk of ADHD (HR, 1.43; 95% CI, 1.12-1.82]) but not other outcomes after adjustment (autism spectrum disorder: HR, 1.06; 95% CI, 0.62-1.81; any neurodevelopmental disorder: HR, 1.15; 95% CI, 0.97-1.36).”
The researchers pointed out that the association between methylphenidate and ADHD did not persist in sensitivity analyses with stricter control for confounding by maternal ADHD.
Background information in the report stated that the prevalence of ADHD in adults is estimated to be approximately 5% in the U.S. “Multiple studies have shown an increase in the prevalence of adult ADHD diagnoses in recent years,” the authors explained. “Consequently, treatment with prescription medications for ADHD in adults has also markedly increased.”
In fact, the study advised that, among commercially insured female individuals of reproductive age in the U.S., stimulant medication use increased more than threefold between 2003 and 2015, from 0.8% to 3.9%, while nonstimulant ADHD medication use remained steady at approximately 0.2%. “Similar increases in use of ADHD medications have been observed among pregnant individuals in the US; by 2013, approximately 1.2% reported ADHD medication use,” the authors explained, adding that amphetamine/dextroamphetamine is by far the most commonly used stimulant medication for ADHD in adults in the U.S., followed by methylphenidate. Nonstimulant medications are less common, they added.
The researchers explain how stimulant medications cross the placenta and can increase the concentrations of norepinephrine and dopamine, which mighty play an important role in fetal neurodevelopment. Past studies have suggested that data were insufficient to draw conclusions as to the safety of stimulant medications and their effects on offspring, including neurodevelopmental outcomes. Studies of children exposed to illicit methamphetamine use in pregnancy have reported increased anxiety, depression, and emotional and developmental issues compared with unexposed children, although the potential for neurodevelopmental effects with prescription stimulant use for ADHD has been reported in only two studies.
Inconsistency in results “leaves a large gap in knowledge for pregnant individuals treated with amphetamines,” the researchers added.
The researchers pointed out that their study assessed the association between stimulant use for ADHD during pregnancy and neurodevelopmental outcomes in the offspring among publicly and commercially insured pregnancies, stratified by medication type and timing of exposure. “In addition to neurodevelopmental outcomes overall, we focus on autism spectrum disorder (ASD) and ADHD,” the researchers wrote.
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