Does Antidepressant Use During Pregnancy Increase Risk of Neurodevelopmental Disorders in Children?
Does Antidepressant Use During Pregnancy Increase Risk of Neurodevelopmental Disorders in Children?
Lauren Ostlund, PharmD
North Memorial St. Anthony Clinic
Background: Researchers have attempted to understand the safety of prenatal antidepressant use for many years, with a particular focus on neurodevelopmental disorders (NDD) in children exposed to these medications during pregnancy. Evidence has been conflicting which has kept the topic controversial, despite 6-8% of pregnant women in the United States taking antidepressants (correlating to approximately 280,000 births yearly). Many studies across the world have looked at this issue, but outcomes have been too heterogeneous to draw conclusions. This study looked closer at confounding variables within prenatal antidepressant use to further tease out potential for risk of NDDs.
Purpose: This trial sought to determine whether antidepressant use in pregnancy is associated with neurodevelopmental outcomes in children.
Study Design: Approximately 3.18 million patients aged 12 to 55 years with live birth deliveries were collected through Medicaid Analytic eXtract (nationwide Medicaid beneficiaries; 2000-2014) or MarketScan Claims Database (private commercial health insurance; 2003-2015). In order to be eligible, patients had to have insurance for at least three months prior to their last menstrual period and until one month after delivery. The exposed patients were also required to have at least one antidepressant dispensed between the 19th week of gestation to delivery. Confounding factors that were collected when available were: antidepressant indication, genetics, demographics (age, race, ethnicity, state, delivery year), healthcare visits (to aid in assessment of severity of mental health conditions), lifestyle factors (substance use), other medications, comorbidities, prenatal care, socioeconomic indicators, and dispensed outpatient prescriptions. The control group consisted of individuals who met the population criteria but were not exposed to antidepressants at least 90 days prior to pregnancy and up until the day prior to delivery. There was also a secondary study of siblings who were not exposed to antidepressants to compare to siblings who were exposed.
Of the approximately 3.18 million pregnancies, 198,496 of the patients had early-pregnancy exposure to antidepressants (dispensing in the first half of pregnancy; included in a secondary analysis), 145,702 of the patients had late-pregnancy exposure to antidepressants, and 3,032,745 patients were unexposed. The children were followed until diagnosis of collected NDD*, disenrollment, death, or end of 14 year study period. Analysis was then completed from August 2020 to July 2021. After weighting, characteristics were balanced.
*Collected NDDs: autism spectrum disorder, attention deficit/hyperactivity disorder, specific learning disorders, developmental speech/language disorder, developmental coordination disorder, intellectual disability, behavioral disorder; validated via claims algorithms
Results: By age 12, 46.8% of children (95% CI, 45.6% to 48.1%) in the Medicaid cohort and 24.9% (95% CI, 23.0% to 26.9%) in the commercial cohort with antidepressant exposure had any NDD, compared with 31.4% (95% CI, 31.1% to 31.6%) and 15.1% (95% CI, 14.7% to 15.4%), respectively, among unexposed individuals. Crude HRs (hazard ratios) for all NDD outcomes suggested an increase in risk, with HRs ranging from 1.32 (95% CI, 1.16 to 1.47) for specific learning disorders to 2.02 (95% CI, 1.96 to 2.08) for ADHD, among children exposed versus unexposed. These outcomes were further broken down into the specific type of NDD at age 12; crude data suggested increased risk with antidepressant use, but when other variables were accounted for, this did not persist.
Taking confounding factors into account, individuals in the experimental group were overall older and had more medication use. Cumulative incidence for all NDDs was higher in the Medicaid population compared to commercial health insurance groups.
Results for each exposure window were similar whether antidepressant exposure occurred only in early pregnancy or only in late pregnancy. Composite outcome of any NDD showed no significant increased risk for any drug class or specific medication (except potentially escitalopram, which showed slightly higher HRs; more research needed).
Conclusions: Rather than interpreting results in a typical significant versus non-significant lens, they used a qualitative approach to express the results as meaningful or not meaningful increases in risks. It initially appeared that children exposed to antidepressants during pregnancy had an increased risk of having a NDD compared to children not exposed to antidepressants during pregnancy. However, after adjusting for potential confounders, the results shifted away from this association. The comparison shifted even more towards no-difference when comparing to people who discontinued antidepressants prior to pregnancy or compared to unexposed sibling comparisons. There is a possibility that the increased risk is more related to the indication for taking an antidepressant and the environment during pregnancy than to the medication itself. The confounding factors were shown to carry an impact on the outcomes, which is what has largely been unexplored prior to this study.
Key Point: In this trial, children born after exposure to common antidepressant medications during gestation were not at higher risk for neurodevelopmental disorders after controlling for various confounding factors.
Reference:
- Suarez EA, Bateman BT, Hernández-Díaz S, et al. Association of antidepressant use during pregnancy with risk of neurodevelopmental disorders in children. JAMA Intern Med. 2022;182(11):1149-1160. doi:10.1001/jamainternmed.2022.4268.