OBJECTIVE:To study the effect of pregnancy on the frequency of neuromyelitis optica spectrum disorder (NMOSD) relapse and evaluate rates of pregnancy-related complications in an international multicenter setting. METHODS:We administered a standardized survey to 217 women with NMOSD from 7 medical centers and reviewed their medical records. We compared the annualized relapse rate (ARR) during a baseline period 2 years prior to a participant's first pregnancy to that during pregnancy and to the 9 months postpartum. We also assessed pregnancy-related complications. RESULTS:There were 46 informative pregnancies following symptom onset in 31 women with NMOSD. Compared to baseline (0.17), ARR was increased both during pregnancy (0.44; p = 0.035) and during the postpartum period (0.69; p = 0.009). The highest ARR occurred during the first 3 months postpartum (ARR 1.33). A total of 8 of 76 (10.5%) with onset of NMOSD prior to age 40 experienced their initial symptom during the 3 months postpartum, 2.9 times higher than expected. CONCLUSIONS:The postpartum period is a particularly high-risk time for initial presentation of NMOSD. In contrast to published observations in multiple sclerosis, in neuromyelitis optica, relapse rate during pregnancy was also increased, although to a lesser extent than after delivery.