Prenatal typing of fetal DNA in cases of potential alloimmune haemolytic disease of the newborn: clinical benefit outweighs disadvantage.
Haemolytic disease of the newborn (HDN) is caused by the action of maternal antibodies on paternally derived antigens present on fetal erythrocytes. In its most severe form it may lead to death in utero. Although the introduction of anti-D prophylaxis has greatly reduced the incidence of the disease, a significant number of cases appear each year. Current antenatal management aims to predict whether the fetus will be severely affected, correct the fetal anaemia if present and deliver the baby at the optimal time. Indirect methods include antibody quantitation performed on maternal blood samples, and amniocentesis to determine bilirubin levels in the amniotic fluid. Fetal blood sampling offers a direct method to determine the antigen status of the fetus, and enables measurement of fetal haemoglobin and haematocrit if appropriate. Both fetal blood sampling and amniocentesis are invasive procedures and have the potential to produce further antibody stimulation which can compound existing problems and compromise the pregnancy. The ultimate aim is to develop an accurate, non-invasive technique for fetal DNA typing which can be carried out in the first trimester. Research methods outlined here suggest that this is feasible. Pinpointing those pregnancies where further intervention is not required will reduce the demand on NHS resources.