Abstract
Aquaporin-4-immunoglobulin G (AQP4-IgG)-positive neuromyelitis optica spectrum disorder (NMOSD) and acetylcholine receptor-IgG (AchR-IgG)-positive generalized myasthenia gravis (gMG) are complement-mediated neurological diseases that affect women of childbearing age and are associated with disease activity during pregnancy and postpartum. Disease relapses during these periods can result in substantial maternal morbidity, making treatment continuation an important clinical consideration. Complement-targeting monoclonal antibodies, eculizumab and ravulizumab, have demonstrated significant efficacy in reducing disease activity in both conditions. However, evidence regarding their safety during pregnancy remains limited as pregnant women are routinely excluded from clinical trials. This review synthesizes evidence on the safety of complement-targeting monoclonal antibodies during pregnancy in NMOSD and gMG and contextualizes these findings with systemic complement-mediated diseases (paroxysmal nocturnal hemoglobinuria [PNH] and atypical hemolytic uremic syndrome [aHUS]). Available reports in NMOSD and gMG include a small number of pregnancies exposed to eculizumab or ravulizumab, with no consistent pattern of major maternal or fetal adverse outcomes identified across the reported cases. Larger cohort studies in PNH and aHUS with eculizumab use in pregnancy demonstrate live birth rates ranging from 66 to 100% and maternal outcomes comparable to the general population. Although these findings contribute to the available pregnancy safety data, important biological and clinical differences between neurological and hematological complement-mediated diseases limit direct extrapolation. In the absence of prospective data and disease-specific studies, complement inhibition during pregnancy may be considered in women with high-risk disease requiring sustained control, following individualized risk-benefit assessment. Multidisciplinary management and infection risk mitigation are essential.