A comparison of in vitro tests for predicting the severity of haemolytic disease of the fetus and newborn.

Haemolytic disease of the newborn (HDN) is characterized by the presence of IgG antibodies in the maternal circulation which cause haemolysis in the fetus by crossing the placenta and sensitizing red cells for destruction by macrophages in the fetal spleen. Numerous serological, quantitative and cellular assays have been developed to predict the severity of HDN. These assays all measure and/or characterize alloantibodies in the maternal circulation. Quantitative assays which accurately measure antibody levels correlate with disease severity better than serological assays which are inherently less precise. Nevertheless, high antibody levels are found in some cases of mild HDN and relatively low antibody levels are found in some severe cases. This suggests that disease severity is influenced by factors in addition to antibody concentration. These factors remain to be fully elucidated but may include the subclass and glycosylation of maternal antibodies, the structure, site density, maturational development and tissue distribution of blood group antigens, the efficiency of IgG transport to the fetus, the functional maturity of the fetal spleen, polymorphisms which affect Fc receptor function, and the presence of HLA-related inhibitory antibodies. Cellular assays which are sensitive to factors affecting antibody function have therefore been developed in an attempt to improve the prediction of disease severity. Although these assays are cumbersome, there are now sufficient data to suggest that some cellular assays, when used as part of a structured approach to diagnostic testing, may provide clinically-useful information to complement serological and quantitative assays.