Timing of Antidepressant Use in Pregnancy and Preterm Birth: A Systematic Review and Meta-analysis

To evaluate the implication of timing of antidepressant exposure on preterm birth to better guide clinical counseling.

A systematic review and meta-analysis was conducted following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, using PubMed, MEDLINE Complete, EBSCO, CINAHL Plus, and ClinicalTrials.gov along with a manual search of references in relevant publications. The databases were searched between January 2000 and December 2022 with the following keywords: antidepressants, antidepressant medication, SSRI, selective serotonin reuptake inhibitors, TCA, or SNRI AND pregnancy, pregnant, prenatal, antenatal, perinatal, maternal AND trimester or timing AND preterm or premature.

The database search resulted in 162 studies. The 13 studies that met inclusion criteria compared preterm birth rates in pregnant patients exposed to antidepressants at a specified time in pregnancy (early, late, or throughout pregnancy) and a control group. Covidence was used for screening and data extraction. Excel and R were used for tabulation and statistical analysis, respectively.

Of the 13 studies, nine measured preterm birth rates with antidepressant use in early pregnancy, 10 in late pregnancy, and four throughout pregnancy. Separate random effects models were used to synthesize the effect sizes from studies that did not adjust for presence of maternal depression in the study sample and those that did. In each model, subgroup analysis was conducted to assess the effect of timing of antidepressant exposure on the odds of preterm birth. In the model unadjusted for depression, pooled odds ratios (ORs) for the association between use of antidepressants and preterm birth were 1.41 (95% CI, 1.10-1.81) in early pregnancy, 1.51 (95% CI, 1.26-1.82) in late pregnancy, and 2.79 (95% CI, 1.27-6.12) throughout pregnancy. After adjusting for depression, the pooled ORs were 1.04 (95% CI, 0.83-1.31) in early pregnancy, 1.26 (95% CI, 0.95-1.66) in late pregnancy, and 1.79 (95% CI, 0.54-5.91) throughout pregnancy. No significant effect of timing was found in either model.

Antidepressant use in pregnancy was not associated with preterm birth, regardless of timing of use. Pregnant patients with an established diagnosis of depression should receive individualized counseling regarding antidepressant use while taking into consideration their risk factors for preterm birth and the implications of untreated depression.

PROSPERO, CRD42023390136.