Objective: Prenatal antidepressant use is widespread. Observational studies have investigated the neonatal effects of prenatal antidepressant exposure with inconclusive results. We aimed to comprehensively investigate the associations between prenatal antidepressant exposure and the most commonly studied adverse neonatal outcomes: preterm birth, birthweight, poor neonatal adaptation, persistent pulmonary hypertension of the neonate (PPHN), neonatal admission and congenital malformations. Methods: We included 45,590 singletons (born 1997-2015) whose mothers used antidepressants within one year before pregnancy. Children were categorised into two groups: continuation (antidepressant use before and during pregnancy) or discontinuation (antidepressant use before but not during pregnancy). We applied random-effects logistic and linear regressions, adjusting for covariates. Results: After adjusting for confounders, prenatal antidepressant exposure was associated with a 2.3 day (95% CI −2.9; −2.0) decrease in gestational age and a 51 g (95% CI −62g; −41 g) decrease in birthweight. The continuation group was at increased risk for moderate-to-late preterm birth (32–37 weeks) (aOR = 1.43; 95%CI 1.33; 1.55), moderately low birthweight (1500–2499 g) (aOR = 1.28; 95%CI 1.17; 1.41), postnatal adaptation syndrome (aOR = 2.59; 95%CI 1.87; 3.59) and neonatal admission (aOR = 1.52; 95%CI 1.44; 1.60) compared to the discontinuation group. Conclusion: Prenatal antidepressant exposure was associated with small decreases in gestational age and birthweight, as well as higher risk for moderate-to-late preterm birth, moderately low birthweight, neonatal admission and postnatal adaptation syndrome. No differences in risk were found for PPHN, or congenital malformations. The causality of the observed associations cannot be established due to the potential for unmeasured residual confounding linked to the underlying disease.
Bibliographical noteFunding Information:
This study is supported by the National Institute of Mental Health (NIMH) (R01MH122869). Dr Liu is also supported by the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 891079. Dr Munk-Olsen is also supported by iPSYCH, the Lundbeck Foundation Initiative for Integrative Psychiatric Research (R155-2014-1724), the Lundbeck Foundation (R313-2019-569), AUFF NOVA (AUFF-E 2016-9-25), and Fabrikant Vilhelm Pedersen og Hustrus Legat. The funders of the study had no role in study design, data analysis, data interpretation, writing, or submission for publication. [Correction added on 18 March 2022, after first online publication: The first sentence of Methods in the abstract and Table 2 has been corrected.]
© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.