Causes and outcomes of prenatally unexplained fetal anemia

Despite advances in diagnostic approaches, fetal anemia of unknown etiology continues to be observed in rare cases. This study aimed to assess the incidence of unexplained fetal anemia and to evaluate the associated perinatal outcomes.We conducted an observational retrospective cohort study of all fetuses that underwent fetal blood sampling (FBS) due to an MCA-PSV>1.5 MoM at a tertiary center between 2007 and 2024. Fetuses were included if they had moderate or severe anemia defined as a hemoglobin (Hgb) deviation of more than 20g/L below a gestational age adjusted mean, with a negative anemia workup. Prenatal and postnatal outcomes were obtained.Among 376 fetuses that underwent fetal blood sampling for anemia, 361 (96%) had an identified cause, while 15 (4%) had moderate to severe anemia of unknown etiology. Seven fetuses presented with non-immune hydrops and eight with other major structural anomalies not typically associated with anemia. Eleven (73%) of the 15 fetuses with unexplained anemia had thrombocytopenia, with platelets below 100000/µL in 8 cases and below 50000/µL in 6 cases. Seven cases (47%) resulted in perinatal death. Rare causes of anemia were elucidated in only 5 cases (33%) postnatally despite extensive investigations.Unexplained fetal anemia is uncommon and is associated with poor neonatal outcomes warranting close pre- and postnatal surveillance.