Depression and antidepressant use in pregnancy and adverse maternal and offspring outcomes: a systematic review and meta-analysis.

Abstract

Objective: Antidepressant use during pregnancy has been increasing in the last few decades. A substantial body of evidence has indicated the increased risks of adverse health outcomes for both pregnant women and their offspring. The association may be biased by uncontrolled confounding of maternity depression or mental health status. We performed a systematic review and meta-analysis to generate comprehensive estimates of the association between depression, antidepressants, and reproductive outcomes.

Methods: The PubMed and Embase were searched from database inception to Jul 29, 2025, for longitudinal cohort studies of pregnant women with exposure to antidepressant or depression. The Newcastle-Ottawa Scale was used for assessing the methodological quality of included studies. Pooled estimates of risk ratio (RR) were calculated by comparing adverse outcomes between antidepressant-exposed pregnancies and unexposed pregnancies. Subsequently, we analyzed the risks of antidepressant-treated, untreated antenatal depression by adjusting for disease factors. Totally, 20 adverse health outcomes including 6 maternal and 14 children's outcomes were accessed.

Results: A total of 166 studies with 51,596,405 participants were included. When antidepressant-exposed pregnancies were compared to all unexposed pregnancies (with and without depression), an increased risk for the majority (16/20) of the focused adverse outcomes was found. After adjusting for depression, results shows that certain adverse outcomes remained significant among untreated pregnancies. However, compared with untreated depressed women, the treated by antidepressant for depressed women during pregnancy was associated with the increased risk for limited outcomes of preterm birth and NICU admission.

Conclution: The findings indicated that many of the adverse outcomes observed with medication may be attributable to the underlying depression itself rather than of antidepressants. More attention should be paid to depression, and health professionals should estimate the risk of depression and antidepressant comprehensively during counseling and prenatal health care.