Antidepressant Use During Pregnancy and Birth Outcomes: Analysis From the UK , Norway, and Sweden

PURPOSE: Although antidepressant use during pregnancy has been linked to adverse birth outcomes such as stillbirth and preterm delivery, existing evidence is conflicting and rarely presents absolute risk estimates. We aimed to assess the association between antidepressant use during pregnancy and birth outcomes, alongside estimates of absolute risk to aid clinical interpretation. METHODS: We conducted a multi-country cohort study using data from the UK Clinical Practice Research Datalink (1996-2018), Norwegian Medical Birth Registry (2009-2020), and Swedish Medical Birth Register (2006-2020). Discordant sibling analyses and paternal negative controls were used to investigate associations with stillbirth, neonatal death, gestational age, size for gestational age, and Apgar score < 7 at 5-min among pregnancies delivered at ≥ 22 weeks' gestation. RESULTS: Among 120 209 (4.8%) pregnancies exposed to antidepressants, maternal use was associated with stillbirth (adjusted pooled odds ratio [aOR] 1.16, 95% CI 1.05-1.28), preterm delivery (aOR 1.26, 95% CI 1.23-1.30), and low Apgar score (aOR 1.83, 95% CI 1.75-1.91). Associations persisted in sibling analyses with greater uncertainty. The predicted absolute risk of stillbirth was 0.34% among unexposed pregnancies and 0.40% among exposed. When restricting to mothers with depression or anxiety, the association with stillbirth attenuated (aOR 1.07, 95% CI 0.94-1.21). Paternal antidepressant use was modestly associated with preterm delivery and low Apgar score. CONCLUSIONS: Maternal antidepressant use during pregnancy may be associated with increased risks of preterm delivery and low Apgar score, though absolute risks remain low. Residual confounding related to parental mental health is likely to explain part of these associations.