DEPRESSION AND ANTIDEPRESSANT USE IN PREGNANCY AND ADVERSE MATERNAL AND FETAL/CHILDREN OUTCOMES: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Bao *Yanping , Liu Tingting , Zeng Na , Xu Yingying , Fan Tengteng , Ni Shuyu , Zhao Yimiao , Mei Huan , Wu Shuilin , Shi Jie , Lu Lin 
Published: February 2025

Abstract

Background
Antidepressant use during pregnancy has been increasing in the last few decades. Many evidences have indicated the high risks of adverse health outcomes for both pregnant women and their offspring.

Aims & Objectives
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 precise estimates of the association between depression, antidepressants, and reproductive outcomes.

Methods
The PubMed and Embase were searched from database inception to Sep 23, 2022, for longitudinal cohort studies of pregnant women with exposure to antidepressants or depression, we assessed the risk of adverse maternal and children outcomes. The Newcastle-Ottawa Scale was used for assessing the methodological quality of included studies. Pooled estimates of risk ratio (RR) were conducted by random effects or fixed effects model by comparing adverse pregnant outcomes in women who took antidepressants versus those who did not, or in women with or without a depressive disorder. Further investigations were conducted to compare the effects of depression (pregnant women with untreated depression compared with control women without depression) and antidepressant use (only in women with depression) on 19 adverse pregnancy outcomes including six maternal and fetal outcomes during eight newborn and five childhood or adolescent period. And association were examined in subgroups stratified by different study designs and income levels.

Results
A total of 134 studies with 40,864,148 participants were included. Compared with pregnant women who did not take antidepressants, those who were exposed had a higher risk for the 16 majority of the focused adverse outcomes in our study, such as abortion (RR,1.33; 95%CI, 1.18-1.49), gestational diabetes (1.24, 1.13- 1.35), 5-minute Apgar score &lt;7 (RR,2.07; 95%CI, 1.95-2.20), ASD (1.69, 1.58-1.80), ADHD (1.30, 1.15- 1.48), depression (2.61, 1.59-4.28), and anxiety (1.74, 1.16-2.61) etc. Compared with women without depression disorder, depressed pregnancy was also associated with increased risks of 8 adverse outcomes, such as low birth weight (LBW) (1.74, 1.24-2.43), preterm birth (1.53, 1.30-1.80), abortion (1.52, 1.45-1.60),. However, when comparing women exposed to antidepressants with those not exposed in the participants of depressed pregnancy, the risks of 2 adverse outcome including preterm birth (1.14, 1.12-1.17) and admission to NICU (1.44,1.33-1.56) were found to be significantly increased.

Discussion & Conclusion
The adverse outcome of antidepressant use manly come from perinatal depression, which was associated with adverse reproductive outcomes, but antidepressants use in depressed pregnancy did not cause more adverse events except for preterm birth and admission to NICU. Higher risks of most adverse outcomes of antidepressants are mainly associated by the onset of depression itself. 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.