Association of Antidepressant Use During Pregnancy With Risk of Neurodevelopmental Disorders in Children

Abstract

ImportanceAntidepressant use during pregnancy has been associated with neurodevelopmental disorders in children in some studies. However, results may be explained by uncontrolled confounding by parental mental health status, genetics, and environmental factors.ObjectiveTo evaluate the association between antidepressant use in pregnancy and neurodevelopmental outcomes in children.Design, Setting, and ParticipantsThis cohort study of health care utilization data was separated into cohorts of publicly and privately insured pregnant individuals and their children nested in the Medicaid Analytic eXtract (MAX; 2000-2014) and the IBM MarketScan Research Database (MarketScan; 2003-2015). A total of 1.93 million pregnancies in MAX and 1.25 million pregnancies in MarketScan were recorded. Children were followed from birth until outcome diagnosis, disenrollment, death, or end of study (maximum 14 years). Analyses were conducted between August 2020 and July 2021.ExposuresDispensing of antidepressant medication from gestational week 19 until delivery, the period of synaptogenesis.Main Outcomes and MeasuresNeurodevelopmental disorders in children defined using validated algorithms. Early pregnancy exposure was considered in sensitivity analyses, and approaches to confounding adjustment included propensity score fine stratification, discontinuers comparison, and sibling analyses.ResultsAmong the individuals included in the analysis, there were 145 702 antidepressant-exposed and 3 032 745 unexposed pregnancies; the mean (SD) age among the antidepressant exposed and unexposed was 26.2 (5.7) and 24.3 (5.8) years in MAX and 32.7 (4.6) and 31.9 (4.6) years in MarketScan, respectively; and in MAX, which collected information on race and ethnicity, 72.4% of the antidepressant-exposed and 37.1% of the unexposed individuals were White. Crude results suggested up to a doubling in risk of neurodevelopmental outcomes associated with antidepressant exposure; however, no association was observed in the most fully adjusted analyses. When comparing antidepressant-exposed and unexposed siblings, hazard ratios were 0.97 (95% CI, 0.88-1.06) for any neurodevelopmental disorder, 0.86 (95% CI, 0.60-1.23) for autism spectrum disorder, 0.94 (95% CI, 0.81-1.08) for attention-deficit/hyperactivity disorder, 0.77 (95% CI, 0.42-1.39) for specific learning disorders, 1.01 (95% CI, 0.88-1.16) for developmental speech/language disorder, 0.79 (95% CI, 0.54-1.17) for developmental coordination disorder, 1.00 (95% CI, 0.45-2.22) for intellectual disability, and 0.95 (95% CI, 0.80-1.12) for behavioral disorders. Results were generally consistent for antidepressant classes and drugs and across exposure windows.Conclusions and RelevanceThe results of this cohort study suggest that antidepressant use in pregnancy itself does not increase the risk of neurodevelopmental disorders in children. However, given strong crude associations, antidepressant exposure in pregnancy may be an important marker for the need of early screening and intervention.

Antidepressants in pregnancy and neurodevelopmental disorders

“…It is worth noting that the reported rates of neurodevelopmental disorders in children in the study, even in the unexposed groups, were 30% and 15% 1. Although one estimate has suggested that the prevalence of neurodevelopmental impairments and conditions is around 3%–4% of children in England, it is difficult to find directly comparable data 2…”

“…This US cohort study investigated the association between antidepressant use during pregnancy with the risk of neurodevelopmental disorders in children 1. Pregnancy cohorts were identified from Medicaid healthcare records from 2000 to 2014, and private health insurance claims from 2003 to 2015.…”

“…Neurodevelopmental outcomes included autism spectrum disorder, attention-deficit/hyperactivity disorder (ADHD), speech/language disorders, developmental coordination disorder, intellectual disability and behavioural disorder. To adjust for confounding factors exposed individuals were compared with unexposed individuals, and analyses were adjusted for covariates including lifestyle factors, comorbidities, other medication, socioeconomic factors and demographics 1. The primary exposed group included those with at least one record of antidepressant prescribing from 127 days after the last menstrual period to delivery.…”

“…In the Medicaid cohort (mean age 25 years), there were 1 833 927 unexposed pregnancies and 93 069 pregnancies exposed to antidepressants 1. In the private health insurance cohort (mean age 32 years), there were 1 198 818 unexposed pregnancies and 52 633 pregnancies exposed to antidepressants.…”

“…A cohort study of more than 150 000 pregnancies that had been exposed to antidepressants found an increased risk of neurodevelopmental disorders in children exposed in utero, which was not statistically significant when the data was adjusted for confounding factors 1…”