Anti-U hemolytic disease of the fetus and newborn managed by multiple intrauterine transfusions: a case report and review of the literature

Abstract

: The U-antigen is part of the MNS blood group. Named for its almost universal expression, a U-negative phenotype is reported in ~1% of individuals of African descent. The spectrum of IgG-mediated anti-U hemolysis includes alloimmune disease of the fetus and newborn. The clinical presentation among affected newborns ranges from mild anemia to erythroblastosis fetalis. We present a case of maternal anti-U positivity and severe middle cerebral artery (MCA) Doppler concerning for anti-U hemolytic disease of the fetus and newborn managed by multiple intrauterine transfusions (IUTs). Uniquely, this case reports the lowest critical maternal anti-U titer to-date resulting in clinically significant fetal anemia. We also searched the literature using the general term “anti-U hemolytic disease” in PubMed to provide a review of case presentations, management methods, and outcomes. The maternal critical anti-U titer was initially 32 at 25 weeks and progressed to 64 by date of delivery. The initially normal fetus, at the 83rd growth percentile at 24 weeks, developed severe range MCA Doppler indices at 26 weeks [peak systolic velocity 59.9 cm/sec, 1.72 multiples of the median (MoM)]. The first percutaneous umbilical cord blood sampling (PUBS) at 26 5/7 weeks revealed a hemoglobin (Hgb) of 8.9 g/dL, 6.7% reticulocytes. IUTs were initiated for severe fetal anemia and predicted Hgb loss, four in total. Intrauterine growth restriction (<5%) developed by 36 weeks, prompting delivery by repeat cesarean section for non-reassuring fetal status. In conclusion, we successfully managed a case of severe anti-U-mediated fetal anemia by IUT performed via both fetal intravascular and intraperitoneal routes using donated U-negative blood. We identified 14 reports of anti-U hemolytic disease of the fetus and newborn that feature a broad range in clinical severity. Anti-U hemolytic disease of the fetus and newborn is a rare, but potentially serious condition and should be managed in accordance with Rh alloimmunization guidelines. Antibody titers are inconsistently associated with clinical severity of disease. Surveillance with MCA Doppler and IUT with donated U-negative blood have shown promising outcomes.