The major cause of immune hemolytic disease of the newborn (HDN) in developed countries is ABO incompatibility. HDN due to ABO incompatibility is considered a high risk condition because it leads to early onset hyperbilirubinemia, due to an acute and rapid rise in total serum bilirubin (TSB). There is conflicting evidence in the medical literature regarding reliable predictors to identify HDN. A number of investigators have suggested that cord blood TSB or early TSB in the sixth postnatal hour and maternal IgG anti-A and -B titers may be useful predictors to identify newborns at risk.
This prospective study investigated predictors of the risk of severe hyperbilirubinemia and kernicterus in ABO-incompatible neonates. The possible role of IgG anti-A and -B titers, used either as the primary predictor or combined with established factors such as the direct antiglobulin test and TSB was given special consideration. The study was conducted at a university hospital in Norway between 2004 and 2006. The patient population was 253 healthy neonates of mothers with blood group O who were born at a gestational age of ≥35 weeks. If a neonate had blood group A or B, a direct antiglobulin test was performed and IgG anti-A or -B were measured in the mother’s plasma. Blood group A or B infants with significant hyperbilirubinemia received phototherapy and those who developed severe hyperbilirubinemia also received invasive therapy (intravenous immunoglobulin [IVIG] treatment and/or exchange transfusion). The need for invasive treatment was the primary study outcome. Multiple logistic regression was used to identify predictors.
Of the 253 newborns enrolled, 155 were blood group O (61.3%), 75 blood group A (29.6%), and 23 blood group B (9.1%). Twenty of the 98 ABO incompatible neonates received at least one treatment with IVIG. Multivariate analysis showed that maternal antibody titers were the only significant predictors for IVIG treatment (P < 0.0001), exchange transfusions (P < 0.05), and duration of phototherapy (P < 0.0001). The number of newborns receiving IVIG treatment markedly increased for antibody titers ≥512 (P < 0.0001). Antibody titer levels below 512 had reduced risk for severe hyperbilirubinemia. Analysis of a receiver operating characteristic curve showed that the sensitivity and specificity of IgG antibody titers ≥512 for predicting the need for IVIG treatment was 90% and 73%, respectively.
These findings demonstrate that high maternal IgG anti-A or -B titers may be predictive for the need of invasive IVIG treatment for severe hyperbilirubinemia in ABO-incompatible neonates.