Anna-Sophie Rommel1, Natalie C Momen2, Nina Maren Molenaar1, Esben Agerbo2,3,4, Veerle Bergink1,5,6, Trine Munk-Olsen2,7, Xiaoqin Liu2. 1. Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 2. NCRR-The National Centre for Register-based Research, Aarhus University, Aarhus, Denmark. 3. CIRRAU - Centre for Integrated Register-Based Research at Aarhus University, Aarhus, Denmark. 4. iPSYCH-Lundbeck Foundation Initiative for Integrative Psychiatric Research, Aarhus, Denmark. 5. Department of Psychiatry, Erasmus Medical Centre Rotterdam, Rotterdam, The Netherlands. 6. Department of Obstetrics, Gynecology and Reproductive Science, Icahn School of Medicine at Mount Sinai, New York, New York, USA. 7. Department of Clinical Research, University of Southern Denmark, Odense, Denmark.
Abstract
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.
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.
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