Using health care utilization data and controlling for confounding by indication, environment, and genetics, findings from a recently published study of nearly 150,000 antidepressant-exposed pregnancies showed that use of these medications during pregnancy itself does not increase the risk of neurodevelopmental disorders (NDDs) in children. However, this may indicate the need to screen and intervene early, as there are strong associations.1
The defined pregnancy groups were nested in both the Medicaid Analytic eXtract(MAX), which contains health care utilization data for Medicaid beneficiaries nationwide, 2000-2014, and the MarketScan Commercial Claims Database which contains private health insurance claims data, 2003-2015. The total number of pregnancies exposed to antidepressants at late pregnancy was 93,069, 52,633 and 1,833,927 respectively.
Led by Elizabeth A. Suarez, PhD, MPH, pharmacoepidemiologist, Rutgers Institute for Health, Health Care Policy and Aging Research, the study followed children from birth until outcome diagnosis, disenrollment, death, or end of study (maximum, 14 years). Neurodevelopmental outcomes included diagnosis of autism spectrum disorder (ASD), attention defect disorder (ADHD), certain learning disorders, developmental speech/language disorders, developmental coordination disorder or intellectual disability and any NDD (presence any of the 7 specific disorders).
Children of antidepressant-exposed parents had a higher incidence of NDDs. At 12 years old, 46.8% (95%CI, 45.6-48.1), and 24.9% (95%CI, 23.0-26.9) of the MAX cohort had experienced any type of NDD. This was compared to 31.4% (95%CI, 31.1-31.6) or 15.1% (95%CI, 14.7-15.4) for unexposed children in the same cohorts. ADHD was the most common individual outcome in NDD. There were 33.3% (95%CI), 32.2-34.5 and 20.3% (95%CI), 20.0-20.9) incidence rates for those who took antidepressants in MAX or MarketScan. These rates were lower than the 17.6% (95%CI), 15.8-19.5) and 9.6% (95%CI), 9.3-10.0 for unexposed individuals.
The incidence of ASD was similarly higher in antidepressant-exposed children and publicly insured children. At 12 years, 4.1% (95% CI, 3.5-4.7) and 2.1% (95% CI, 2.0-2.1) of antidepressant-exposed children developed ASD vs 2.9% (95% CI, 2.4-3.6) and 1.6% (95% CI, 1.4-1.7) of those unexposed to treatment in the same cohorts, respectively. Crude HRs of all NDD outcomes indicated an increase in risk. HRs ranged between 1.32 and 2.02 for ADHD in children exposed to antidepressants during pregnancy compared to those who were not. After adjusting to measure covariates and proxy for unmeasured variables, HRs for all NDDS were significantly reduced, ranging between 1.01 for certain learning disorders and 1.20 for ADHD.
The sibling design was not subject to sensitivity analysis. These analyses did not show that there were any carryover effects from the first pregnancy’s exposure to the outcome of the second. The study included several antidepressants, but no one therapy was found to significantly increase the risk of NDD. The adjusted HRs for escitalopram across all outcomes was comparable to those for other drugs and classes. Results were also similar for all ages regardless of whether they were exposed in the late or early stages of pregnancy when NDD risk was calculated based on antidepressant timing.
