Safety of fluoxetine during the first trimester of pregnancy: a meta-analytical review of epidemiological studies

Background. This study was designed to examine whether there is an increase d risk for major malformations following the use of fluoxetine during the f irst trimester of pregnancy. Methods. Published and unpublished reports were identified through computer ized and manual searches of bibliographical databases, reference lists from primary articles, and letters to editors, agencies, foundations and conten t experts. Meta-analysis was undertaken of prospective controlled and uncon trolled studies on the use of fluoxetine during first trimester of pregnanc y. Results. The pooled relative risk and 95 % confidence interval for major ma lformations does not suggest an association between the use of fluoxetine d uring the first trimester and an increased risk of major malformations. Com bination 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 studi es (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 analy sis 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.