Selective serotonin reuptake inhibitor (SSRI) use during pregnancy and risk of preterm birth: a systematic review and meta-analysis

BJOG. 2016 Nov;123(12):1900-1907. doi: 10.1111/1471-0528.14144. Epub 2016 May 30.


Background: Depression is a prevalent condition in pregnancy affecting about 10% of women. Maternal depression has been associated with an increase in preterm births (PTB), low birthweight and fetal growth restriction, and postnatal complications. Available treatments for depressive disorders are psychotherapeutic interventions and antidepressant medications including selective serotonin inhibitors (SSRIs). SSRI use during pregnancy has been associated with several fetal and neonatal complications; so far, however, the risk of PTB in women using SSRIs during pregnancy is still a subject of debate.

Objective: To evaluate the risk of preterm birth (PTB) in cases of exposure to SSRIs during pregnancy.

Search strategy: Electronic databases (MEDLINE, Scopus,, the PROSPERO International Prospective Register of Systematic Reviews, EMBASE and the Cochrane Central Register of Controlled Trials) were searched from their inception until May 2015 with the use of a combination of the following text words 'depression', 'pregnancy', 'exposure', 'antidepressant', 'SSRI', 'selective serotonin reuptake inhibitor', 'preterm birth', 'small for gestational age' and 'prematurity'.

Selection criteria: We included studies evaluating the effect of SSRIs exposure in utero and pregnancy outcomes. All cohort and case-control studies were eligible to be included if they reported the incidence of PTB after any exposure to SSRIs and had a comparison group of unexposed pregnant women. Studies without a control group were excluded.

Data collection and analysis: The primary outcome was the incidence of PTB <37 weeks. Subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy were planned.

Main results: Eight studies (1 237 669 women) were included: 93 982 in the exposure group and 1 143 687 in the control group. After adjusting for confounders, the incidence of PTB was significantly higher in the group of women treated with SSRIs compared with controls (i.e. both women with depression but without SSRI exposure and women without depression) (adjusted OR (aOR) 1.24, 95% CI 1.09-1.41). In the subgroup analysis of studies in which controls were defined as women with depression but without SSRI exposure during pregnancy, an increased risk of PTB (6.8 versus 5.8%; OR 1.17, 95% CI 1.10-1.25) in the SSRI group was found compared with controls (i.e. depressed women treated with psychotherapy alone).

Conclusions: Women who received SSRIs during pregnancy had a significantly higher risk of developing PTB compared with controls. This higher risk remained significant even when comparing depressed women on SSRI with women not on SSRI.

Tweetable abstract: Selective serotonin reuptake inhibitors may be associated with preterm birth.

Keywords: Depression; drug; malformation; prematurity; preterm birth.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antidepressive Agents / administration & dosage*
  • Antidepressive Agents / adverse effects
  • Controlled Clinical Trials as Topic
  • Depression / drug therapy*
  • Depression / epidemiology
  • Evidence-Based Medicine
  • Female
  • Humans
  • Incidence
  • Pregnancy
  • Pregnancy Complications / chemically induced*
  • Pregnancy Complications / epidemiology
  • Premature Birth / chemically induced*
  • Premature Birth / epidemiology
  • Serotonin Uptake Inhibitors / administration & dosage*
  • Serotonin Uptake Inhibitors / adverse effects
  • United States / epidemiology


  • Antidepressive Agents
  • Serotonin Uptake Inhibitors