In the space of most paediatricians working lifetime, the spectrum of haemolytic disease of the newborn (HDN) has changed beyond recognition. Thirty years ago, HDN was almost synonymous with Rh D allo-immunisation and was a common neonatal problem. It was usually unmodified by antenatal therapy and caused overt fetal or neonatal haemolysis, leading to marked neonatal hyperbilirubinaemia and attendant anaemia. Affected neonates were commonly sick and unstable at birth, required multiple exchange transfusions, and suffered considerable neonatal morbidity and mortality. However, the introduction in the UK in the 1970s of routine postnatal prophylactic anti-D immunoglobulin for Rh D negative women has dramatically reduced this form of HDN, and as such this treatment ranks as one of the great success stories of modern perinatal care.

Although the clinical burden imposed on neonatal services by HDN has greatly reduced, it has not disappeared. Neonatal paediatricians continue to recognise a number of different presentations of neonatal haemolysis, many of which are considerably more subtle than the traditional “neonatal emergency” presentation of severe Rh D disease. In contemporary neonatal practice, HDN should be considered in the fetus or neonate where there is one or more of the following:

• rapidly developing or severe hyperbilirubinaemia not predicted by maternal antenatal antibody screening;

• positive maternal antenatal antibody screening and/or diagnosis of a severely anaemic/hydropic fetus;

• a positive direct anti-globulin test (DAT);

• haemolysis detected on blood film examination;

• prolonged hyperbilirubinaemia.

In addition to these various presentations of HDN, the spectrum of the disease has altered as new treatments, particularly improved phototherapy and/or intravenous immunoglobulin (IVIG), are being evaluated and introduced to reduce the need for exchange transfusion in the reduced number of severe cases. This review will aim to place HDN in the context of contemporary neonatal …