Prenatal exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors and risk for persistent pulmonary hypertension of the newborn: a systematic review, meta-analysis, and network meta-analysis

Background: There is a marked increase in the use of selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors in the last decade. Many newborns are likely to be exposed during pregnancy and labor.

Objective: We aimed to evaluate the association between exposure to selective serotonin reuptake inhibitors and serotonin norepinephrine reuptake inhibitors during pregnancy and the risk for persistent pulmonary hypertension of the newborn. We sought to compare the risk for persistent pulmonary hypertension of the newborn between specific selective serotonin reuptake inhibitor agents.

Study design: MEDLINE, Embase, and Cochrane were searched up to July 2017. No language restrictions were applied. Search key words included: "SSRI," "SNRI," "pregnancy," "risk," "new-born," and "pulmonary hypertension." Retrospective cohort studies and case-control studies reporting the risk for persistent pulmonary hypertension of the newborn in the offspring of women exposed to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy, were extracted. Two independent researchers identified relevant data. Random effects meta-analysis was used to pool results. Odds ratios were calculated with subsequent 95% confidence intervals. Network meta-analysis was conducted, incorporating direct and indirect comparisons among different selective serotonin reuptake inhibitors. The primary outcome was risk for persistent pulmonary hypertension of the newborn after exposure to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy.

Results: A total of 11 studies were identified. A total of 156,978 women and their offspring were exposed to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy. Persistent pulmonary hypertension of the newborn was detected among 452 exposed offspring, representing an incidence rate of 2.9 cases per 1000 live births and a number needed to harm of 1000. The risk for persistent pulmonary hypertension of the newborn was significantly increased in the analysis of exposure to selective serotonin reuptake inhibitor/serotonin norepinephrine reuptake inhibitor in any trimester (odds ratio, 1.82; 95% confidence interval, 1.31-2.54; I² = 72%), as well as in analysis restricted to exposure week >20 (odds ratio, 2.08; 95% confidence interval, 1.44-3.01; I² = 76%). In network meta-analysis, sertraline was ranked most likely to have the lowest risk for persistent pulmonary hypertension of the newborn among the different selective serotonin reuptake inhibitors (P = .83).

Conclusion: Exposure to selective serotonin reuptake inhibitors or serotonin norepinephrine reuptake inhibitors during pregnancy is associated with an increased risk for persistent pulmonary hypertension of the newborn. According to our findings, sertraline ranked as most likely to have the lowest risk for persistent pulmonary hypertension of the newborn compared to other selective serotonin reuptake inhibitors, suggesting it may have the best safety profile for use in pregnancy in this regard. Further studies are needed to fully establish these results.