Background. This study was designed to examine whether there is an increased risk for major malformations following the use of fluoxetine during the first trimester of pregnancy.

Methods. Published and unpublished reports were identified through computerized and manual searches of bibliographical databases, reference lists from primary articles, and letters to editors, agencies, foundations and content experts. Meta-analysis was undertaken of prospective controlled and uncontrolled studies on the use of fluoxetine during first trimester of pregnancy.

Results. The pooled relative risk and 95% confidence interval for major malformations does not suggest an association between the use of fluoxetine during the first trimester and an increased risk of major malformations. Combination of controlled and uncontrolled studies shows a weighted risk of 2·6% (95% CI 1–4·2%). The summary odds ratio from the two controlled studies (OR = 1·33, 95% CI 0·49–3·58) was not significant. Homogeneity testing shows that the effect sizes are similar throughout all studies. Power analysis indicates that 26 controlled studies of similar size, would be required, to reverse this finding.

Conclusions. The use of fluoxetine during the first trimester of pregnancy is not associated with measurable teratogenic effects in human.