In-utero exposure to prescription stimulants is not associated with an increased risk for neurodevelopmental disorders in children.
Exposure to amphetamine/dextroamphetamine and methylphenidate in utero is not meaningfully associated with an increased risk for childhood neurodevelopmental disorders (NDDs), according to study results published in JAMA Psychiatry. These findings may help inform treatment for pregnant individuals who depend on prescription stimulants for daily functioning.
Stimulant medications cross the placenta and can increase the concentrations of norepinephrine and dopamine, which are known to play an important role in fetal neurodevelopment. However, it is unclear whether amphetamine treatment for pregnant individuals poses a risk for childhood NDDs. Therefore, researchers performed a cohort study using national Medicaid data from 2000 to 2018 and MarketScan data from 2003 to 2020.
The researchers identified pregnant individuals who filled prescriptions for amphetamine/dextroamphetamine and methylphenidate in the second half of pregnancy (week 19 to delivery) to assess the association between stimulant use for attention-deficit/hyperactivity disorder (ADHD) during pregnancy and neurodevelopmental outcomes. Children from these pregnancies were monitored from birth until their continuous enrollment ended, they developed a NDD, the study period ended, or they died (whichever came first). The primary outcome of any NDD was defined as a composite of autism spectrum disorder (ASD), ADHD, specific learning disorders, developmental speech or language disorder, developmental coordination disorder, intellectual disability, and behavioral disorder.
The analyses included 4,317,502 pregnancies from both the Medicaid and MarketScan cohorts, and pregnant individuals had a mean age of 25.2 (SD, 6.0) and 31.6 (SD, 4.6) years at enrollment, respectively. During the second half of pregnancy, 7065 individuals were exposed to amphetamine/dextroamphetamine and 1123 were exposed to methylphenidate.
Upon controlling for confounding variables, exposure to amphetamine/dextroamphetamine was not found to be significantly correlated with neurodevelopmental outcomes. The hazard ratios (HRs) were 0.80 (95% CI, 0.56-1.14) for ASD, 1.07 (95% CI, 0.89-1.28) for ADHD, and 0.91 (95% CI, 0.81-1.02) for any NDD. In the subset of patients with maternal ADHD diagnoses, risk elevation for these outcomes was not evident in either crude or adjusted analyses. Relative to individuals who ceased amphetamine use before pregnancy, the researchers observed no significant associations between amphetamines and ADHD and any NDD, while the adjusted HR for ASD was 1.35 (95% CI, 0.84-2.15) for early exposure and 1.81 (95% CI, 1.04-3.12) for late exposure. Overall, there were no meaningful associations between amphetamine exposure and ADHD and composite NDDs.
When examining pregnancies exposed to methylphenidate, initial estimates indicated a 2- to 3-fold increase in ASD, ADHD, and composite NDDs. However, these estimates were greatly reduced after adjusting for confounding factors. The adjusted HRs for exposure during late pregnancy were 1.06 (95% CI, 0.62-1.81) for ASD, 1.43 (95% CI, 1.12-1.82) for ADHD, and 1.15 (95% CI, 0.97-1.36) for NDD overall. The associations were even weaker in analyses that included only mothers with ADHD and those who discontinued methylphenidate use before pregnancy.
Study authors concluded, “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.”
These study findings may be limited by potential outcome misclassification and substantial attrition due to insurance disenrollment. Additionally, as prescription stimulants for ADHD can be used as needed, evidence of dispensing may not accurately indicate consumption.
This article originally appeared on Psychiatry Advisor
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