OBJECTIVE: To investigate the effect of intrauterine selective serotonin reuptake inhibitor (SSRI) exposure on pregnancy outcomes. DESIGN: Prospective cohort study. SETTING: Department of Obstetrics, Aarhus University Hospital, Aarhus, Denmark. PARTICIPANTS: Pregnant women receiving prenatal care in our hospital from 1989 to 2006. MAIN EXPOSURE: Maternal SSRI use during pregnancy. OUTCOME MEASURES: Gestational age, birth weight, head circumference, 5-minute Apgar score, and admission to the neonatal intensive care unit. RESULTS: Three hundred twenty-nine pregnant women reported treatment with SSRIs, 4902 were not treated with SSRIs but had a history of psychiatric illness, and 51 770 reported no history of psychiatric illness. Gestational age was 5 days (95% confidence interval [CI], -6 to -3) shorter and the odds ratio (OR) for preterm birth was 2.0 (95% CI, 1.3-3.2) in the women exposed to SSRIs compared with women with no history of psychiatric illness. In utero-exposed newborns had increased risk of admission to the neonatal intensive care unit (OR, 2.4; 95% CI, 1.7-3.4) and of 5-minute Apgar scores of less than 8 (OR, 4.4; 95% CI, 2.6-7.6) compared with those not exposed. Head circumference and birth weight did not differ between infants in the exposed and unexposed groups. The results were similar when compared with infants of women with a psychiatric history. CONCLUSIONS: Exposure to SSRIs during pregnancy was associated with an increased risk of preterm delivery, a low 5-minute Apgar score, and neonatal intensive care unit admission, which was not explained by lower Apgar scores or gestational age. The study justifies increased awareness to the possible effects of intrauterine exposure to antidepressants.