Laboratory assays for predicting the severity of haemolytic disease of the fetus and newborn.

Haemolytic disease of the fetus and newborn (HDFN) is characterised by the presence of IgG antibodies in the maternal circulation which cause haemolysis in the fetus by crossing the placenta and sensitising red cells for destruction by macrophages in the fetal spleen. Serological, quantitative and cellular assays have all been developed to predict the severity of HDFN. These assays measure and/or characterise 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 HFDN 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 provide clinically useful information to complement serological and quantitative assays.