Effect of Time-Dependent Selective Serotonin Reuptake Inhibitor Antidepressants During Pregnancy on Behavioral, Emotional, and Social Development in Preschool-Aged Children

Objective: To evaluate the effect of prenatal exposure to selective serotonin reuptake inhibitors (SSRIs) on children's behavioral, emotional, and social development by age 5 years, and over time since age 1.5 years. Method: The prospective Norwegian Mother and Child Cohort Study was linked to the Medical Birth Registry of Norway. We included women who reported depressive/anxiety disorders before and/or during pregnancy. Children born to women who used SSRIs in early (weeks 0-16), mid- (weeks 17-28), or late (> week 29) pregnancy were compared to those who were unexposed. Children's internalizing and externalizing behaviors (Child Behavior Checklist) and temperament traits (Emotionality, Activity and Shyness Temperament Questionnaire) were measured at 1.5, 3, and 5 years. Mean scores were calculated and standardized. General linear marginal structural models were fitted to account for time-varying exposure and Qconfounders, and censoring; 3-level growth-curve models were used. Results: A total of 8,359 mother child dyads were included, and 4,128 children had complete outcome data at age 5 years. Children exposed to SSRIs in late pregnancy had an increased risk of anxious/depressed behaviors by age 5 years compared with unexposed children (adjusted beta = 0.50, 95% CI = 0.04, 0.96). Such risk was not evident for earlier timings of exposure. There was no evidence for a substantial prenatal SSRI effect on externalizing, social, and emotional problems. Conclusion: These findings suggest no substantial increased risk for externalizing, emotional, or social problems in preschool-aged children following prenatal SSRI exposure. Although the role of chance and potential unmeasured confounding cannot be ruled out, late-pregnancy SSRI exposure was associated with greater anxious/depressed behaviors in the offspring.