ObjectiveTo determine whether first-trimester exposure to fluoxetine, a selective serotonin reuptake inhibitor commonly used to treat depression and obsessive-compulsive disorders, is associated with increased frequency of fetal malformations.MethodsWe evaluated outcomes of all pregnancies identified prospectively with confirmed first-trimester fluoxetine exposure contained in the Eli Lilly and Company worldwide fluoxetine pregnancy registry. These outcomes were compared with historic reports of newborn surveys.ResultsOutcomes were available for 796 pregnancies, 37 from fluoxetine clinical trials and 759 from spontaneous reports. Spontaneous abortions were reported in 110 of the 796 (13.8%) pregnancies. Of the remaining 686, malformations, deformations, and disruptions, including those identified after the perinatal period, were reported in 34 (5.0%). No consistent or recurring pattern of abnormalities was observed.ConclusionBased on comparison with historic reports of newborn surveys, it is unlikely that maternal fluoxetine use during the first trimester of pregnancy results in increased risk of fetal malformations.