Background: Maternal underlying depression may confound previously reported associations between SSRI use and adverse pregnancy and neonatal outcomes.

Objective: To determine whether SSRI use during pregnancy is associated with an increased risk of pregnancy and neonatal complications after adjusting for indicators of maternal depression severity.

Study design: This population-based birth cohort study used data from national registers in Finland and included 1,272,587 singleton live births from 1996 to2018. Pregnancy outcome of women with two or more SSRI purchases during pregnancy (N=19,020) were compared to women with a diagnosis of depression but no antidepressant use (N=19,625), and women who discontinued SSRIs before pregnancy (n=3,145). Analyses included adjustment for several indicators of depression severity, and within-family sibling comparisons.

Results: After adjusting for confounders and comparing to women with depression who did not use antidepressants, maternal SSRI use was associated with an increased risk of gestational diabetes (OR 1.14; 95% CI 1.07–1.22), while the risk of caesarean section (CS), late (32–36+6 weeks’ gestation) and very preterm birth (<32 weeks’ gestation), small for gestational age (SGA), and low and very low birth weight was lower. Among SSRI-exposed infants, risk of a low (<7) 5-minute Apgar score (OR 2.02; 95% CI 1.78–2.30), breathing problems (OR 1.61; 95% CI 1.48–1.75), and neonatal care unit (NCU) treatment (OR 1.23; 95% CI 1.16–1.31) was higher, whereas the risk of hospital stay at 7 days and major congenital anomalies was lower. Third-trimester exposure further increased the risk of a low 5-minute Apgar score (OR 3.44; 95% CI 2.93–4.04). After adjustment for indicators of depression severity, the increased risk of gestational diabetes persisted (OR 1.20; 95% CI 1.09–1.32) as did the lower risk of CS, very preterm birth, and low and very low birth weight, and the risks of a low 5-minute Apgar score, breathing problems, and NCU treatment remained higher.

Compared to women who discontinued SSRI use before pregnancy, SSRI use was associated with lower risks of late preterm birth and low birth weight (OR 0.83; 95% CI 0.70–0.999 and OR 0.78; 95% CI 0.64–0.96, respectively), while the neonatal risks described above remained elevated.

In the sibling-pair analysis, SSRI use was associated with an increased risk of gestational diabetes and neonatal complications other than malformations, including an increased risk of needing hospital stay at 7 days of age.

Conclusions: SSRI use during pregnancy affects neonatal health beyond maternal depression by increasing symptoms related to delayed neonatal adaptation, although it may reduce the risk of preterm birth. The observed increase in the risk of gestational diabetes warrants further study.