Fluoxetine and congenital malformations: a systematic review and meta-analysis of cohort studies

To investigate the safety of fluoxetine use during pregnancy, and to better understand the relationship between maternal fluoxetine use during the first trimester and congenital malformations in infants.

PubMed and Web of Science databases were systematically searched from inception to 21 March 2016. Additional studies were identified in a manual search of the reference lists. Two reviewers independently extracted data. A third reviewer checked the data. Estimates were pooled using a random-effects model to calculate the summarized relative ratios (RR) and 95% confidence intervals (CI).

Among 1918 initially identified articles, 16 cohort studies were included. The offspring of pregnant women exposed to fluoxetine during the first trimester had a statistically increased risk of major malformations (RR = 1.18, 95% CI = 1.08-1.29), cardiovascular malformations (RR = 1.36, 95% CI = 1.17-1.59), septal defects (RR = 1.38, 95% CI = 1.19-1.61), and non-septal defects (RR = 1.39, 95% CI = 1.12-1.73) with low heterogeneity in infants. There were no significant observations of other system-specific malformations in the nervous system, eye, urogenital system, digestive system, respiratory system, or musculoskeletal system, respectively. There was no indication of publication bias.

The results of this meta-analysis indicate maternal fluoxetine use is associated with a slightly increased risk of cardiovascular malformations in infants. Health care providers and pregnant women must weigh the risk-benefit potential of these drugs when making decisions about whether to treat with fluoxetine during pregnancy.