Selective Serotonin Reuptake Inhibitors and Persistent Pulmonary Hypertension of the Newborn: An Update Meta-Analysis

J Womens Health (Larchmt). 2019 Mar;28(3):331-338. doi: 10.1089/jwh.2018.7319. Epub 2018 Nov 8.


Background: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition associated with substantial mortality and morbidity. Previous studies have suggested a possible link between maternal selective serotonin reuptake inhibitor (SSRI) use and the risk of PPHN. This study aimed to provide an up-to-date review and meta-analysis of the topic.

Methods: Using the search terms [SSRI OR SSRIs OR selective serotonin reuptake inhibitors OR antidepressant OR Prozac OR fluoxetine OR Lexapro OR escitalopram] AND [pregnancy OR maternal OR newborn OR persistent pulmonary hypertension OR PPHN OR neonat* OR fet*], a preliminary search on the PubMed, Medline, EMBASE, Web of Science, and Google Scholar database yielded 7327 articles published in English between January 1, 1960 and October 1, 2017.

Results: A total of 9 cohort and case-control studies, with a total of 7,540,265 subjects were systematically reviewed. Random-effects meta-analysis of eight studies revealed a significantly increased risk of PPHN with maternal SSRI use during pregnancy, with a pooled OR of 1.516 (95% confidence interval: 1.035-1.997, p < 0.001). Overall, the absolute increase in risk of PPHN with SSRI use appears small, with an absolute risk difference of 0.619 per 1000 livebirths and a number needed to harm of 1615 women.

Conclusions: Current evidence suggests that there were significantly greater odds of PPHN with SSRI use during pregnancy. However, the clinical significance of this association remains modest and likely outweighed by the potential benefits of treatment of perinatal depression. The risk of PPHN associated with SSRI therapy might not warrant the recommendation to withdraw antidepressant therapy, as evidence from other studies show that untreated perinatal depression presents additional adverse maternal and fetal outcomes. Given the increasing prevalence of maternal depression and consequent use of antidepressant medications, further research with robust longitudinal or randomized, controlled studies and mechanistic investigations are needed.

Keywords: PPHN; SSRI; antenatal; antidepressant; pregnancy; pulmonary hypertension of the newborn.

Publication types

  • Meta-Analysis
  • Review

MeSH terms

  • Antidepressive Agents / adverse effects*
  • Antidepressive Agents / therapeutic use
  • Depression / drug therapy
  • Female
  • Humans
  • Infant, Newborn
  • Persistent Fetal Circulation Syndrome / epidemiology
  • Persistent Fetal Circulation Syndrome / etiology*
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Prenatal Exposure Delayed Effects
  • Risk Factors
  • Selective Serotonin Reuptake Inhibitors / adverse effects*
  • Selective Serotonin Reuptake Inhibitors / therapeutic use


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors