Maternal ADHD drug use not tied to neurodevelopmental disorders, autism in children

Key takeaways:

• Amphetamine/dextroamphetamine exposure was not linked to autism, ADHD or any neurodevelopmental disorder.
• Methylphenidate exposure was tied to ADHD risk, but not autism or any other neurodevelopmental disorder.

In utero exposure to amphetamine/dextroamphetamine or methylphenidate was not associated with increased risks for neurodevelopmental disorders in children, according to cohort study results published in JAMA Psychiatry.

“By 2013, approximately 1.2% [of pregnant individuals in the U.S.] reported ADHD medication use. Amphetamine/dextroamphetamine is by far the most commonly used stimulant medication for ADHD in adults in the U.S. followed by methylphenidate, whereas nonstimulant medications are less common,” Elizabeth A. Suarez, MPH, PhD, an instructor of epidemiology at the Center for Pharmacoepidemiology and Treatment Science at the Rutgers Institute for Health, Health Care Policy and Aging Research and the department of biostatistics and epidemiology at the Rutgers School of Public Health, and colleagues wrote. “Stimulant medications cross the placenta and can increase the concentrations of norepinephrine and dopamine, which may play an important role in fetal neurodevelopment.”

Suarez and colleagues conducted a cohort study using health care utilization Medicaid data from 2000 to 2018 and MarketScan Commercial Claims Database data from 2003 to 2020 to identify insured pregnant individuals aged 12 to 55 years in the U.S. All individuals were enrolled within 3 months before their pregnancy through 1 month after delivery. Researchers monitored offspring from birth until outcome diagnosis, disenrollment, death or the end of the study period for both publicly and commercially insured mothers and children.

The primary outcome was ADHD and a composite of any neurodevelopmental disorder observed in offspring of individuals who used ADHD medications during pregnancy.

The Medicaid cohort consisted of 2,496,771 stimulant-unexposed, 4,693 amphetamine/dextroamphetamine-exposed and 786 methylphenidate-exposed pregnancies (mean maternal age, 25.2 years), and the MarketScan cohort consisted of 1,773,501 stimulant-unexposed, 2,372 amphetamine/dextroamphetamine-exposed and 337 methylphenidate-exposed pregnancies (mean maternal age, 31.6 years).

Amphetamine/dextroamphetamine and methylphenidate exposures were associated with a twofold to threefold increased risk for neurodevelopmental outcomes in unadjusted analyses. However, after adjusting for measured confounders, amphetamine/dextroamphetamine exposure was not associated with autism (HR = 0.8; 95% CI, 0.56-1.14), ADHD (HR = 1.07; 95% CI, 0.89-1.28) or any neurodevelopmental disorder (HR = 0.91; 95% CI, 0.81-1.28).

In addition, methylphenidate exposure was associated with an increased ADHD risk (HR = 1.43; 95% CI, 1.12-1.82), but was not associated with autism (HR = 1.06; 95% CI, 0.62-1.81) or any neurodevelopmental disorder (HR = 1.15; 95% CI, 0.97-1.36) after adjusting for confounders.

Researchers noted that the association observed between methylphenidate and ADHD was not consistent in sensitivity analyses when controlling for confounding for maternal ADHD.

“Given the recent rise in use of stimulant medications for ADHD in adults and during pregnancy, these results are reassuring for patients who depend on these medications throughout pregnancy for control of debilitating ADHD symptoms that interfere with daily functioning,” the researchers wrote.