Clinical Question

Does maternal exposure to an antidepressant in the first trimester of pregnancy increase the risk of preterm birth, small for gestational age (SGA), autism spectrum disorder (ASD), or attention-deficit/hyperactivity disorder (ADHD) in offspring?

Bottom Line

This study found that maternal antidepressant use during the first trimester of pregnancy is associated with an increased risk of preterm birth, but not SGA, ASD, or ADHD. Another study in the same issue (Brown HK, et al. JAMA. 2017;317(15):1544–1552) also reported no increased risk of ASD with in utero exposure to selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors. (Level of Evidence = 2b –)

Synopsis

These investigators analyzed data obtained from multiple registries in Sweden that link first-trimester exposure to any antidepressant medication with the risk of preterm birth, SGA, ASD, or ADHD in offspring. Various registries also provided information related to potential confounding variables, including parity, year of birth, maternal and paternal age at childbirth, level of completed education, history of criminal conviction, and history of severe psychiatric illnesses. Maternal exposure was defined by self-report and pharmacy dispensation records. “First-trimester exposure” was defined as having at least one medication dispensation between 90 days before and 90 days after the estimated date of conception. “Use before pregnancy only” was defined as having at least one medication dispensation between 270 days and 90 days before estimated conception and no dispensations during pregnancy or during the first 180 days after pregnancy. Birth outcomes were assessed using standard international diagnostic criteria. To account for shared genetic and early environmental influences, a sibling comparison model evaluated anti-depressant exposure and outcomes within families with siblings born to the same mother.

The final cohort of eligible offspring (N = 1,580,629) included those born between 1996 and 2012. Of these, 1.4% (n = 22,544) of the offspring were exposed to any antidepressant during the first trimester, with 82% (n = 18,470) of those exposed to selective serotonin reuptake inhibitors. Median follow-up time for neuro-developmental disorders (ASD and ADHD) in offspring was approximately nine years for the unexposed group and six years for the exposed group. When compared with unexposed offspring, exposed offspring had a higher probability of preterm birth, SGA, ASD, and ADHD overall. However, in the sibling comparison models, although first-trimester exposure was significantly associated with preterm birth, it was not significantly associated with SGA, ASD, or ADHD. Likewise, when comparing maternal antidepressant first-trimester exposure with before-pregnancy exposure only, a significant association occurred with an increased risk of preterm birth, but not for any of the other outcomes, including SGA, ASD, or ADHD. Finally, antidepressant use during the second or third trimester was also not associated with ASD or ADHD.

Study design: Cohort (retrospective)

Funding source: Government

Setting: Population-based

Reference:SujanACRickertMEObergASet alAssociations of maternal antidepressant use during the first trimester of pregnancy with preterm birth, small for gestational age, autism spectrum disorder, and attention-deficit/hyperactivity disorder in offspring. JAMA2017;317(15):1553–1562.