ObjectiveTo assess the efficacy of managing pregnancies complicated by anti-Kell isoimmunization using the methods developed for evaluating anti–Rh-D isoimmunization.MethodsWe reviewed 156 anti-Kell-positive pregnancies seen from 1959 to 1995, which were managed with serial maternal titers, amniotic fluid ΔOD450determination, and funipuncture. Data on maternal titers, paternal phenotypes, invasive fetal testing and therapies, and neonatal outcomes were collected and analyzed to determine whether severely affected pregnancies were identified in time for successful fetal and neonatal therapy.ResultsTwenty-one fetuses were affected, eight with severe disease, and two fetuses in this group died. All of the severely affected fetuses were associated with maternal serum titers of at least 1:32. A critical titer of 1:32 was found to be 100% sensitive for identifying the affected pregnancies. The affected group had significantly higher amniotic fluid ΔOD450values over the range of gestational ages than did the unaffected group (P< .001). The upper Liley curve was a specific discriminator for the diagnosis of affected fetuses, and the lower curve was specific for the diagnosis of unaffected or mild cases.ConclusionFetal anemia due to anti-Kell isoimmunization might be due in part to erythropoietic suppression, but it is still largely a hemolytic process. The methods based on a hemolytic process, including use of a critical maternal serum titer of 1:32, serial amniotic fluid analyses when the titer was exceeded, and liberal use of funipuncture, were successful in identifying severely affected fetuses.