Physicians at the the Royal Children’s Hospital the Royal Women’s Hospital in Australia have described their approach to issues encountered in the antenatal care of pregnancies at risk of hemolytic disease of the fetus and newborn (HDFN) in an article recently published in blood.
“We describe and highlight issues in the care of pregnant women with RBC alloimmunization, including monitoring for and management of fetal anemia caused by maternal RBC alloantibodies, but also considerations for transfusion support for the woman in the event of major bleeding,” the authors wrote.
HDFN is caused by maternal red blood cell (RBC) alloimmunization, the process by which a woman produces antibodies that target antigens in the membrane of RBCs. These antibodies can cross the placenta during pregnancy, causing anemia and fetal distress. Alloimmunization can occur after a pregnancy in which the fetus and the mother have different blood groups or after a transfusion of incompatible blood in the context of an emergency.
Learn more about HDFN treatment and care
Alloimmunization does not always lead to HFDN, the development of HDFN and its severity depend on factors such as which antigen the antibodies target. For example, immunization against the RhD antigen tends to lead to more severEHDFN. Furthermore the presence of antibodies is not relevant if the fetus does not carry the antigen these antibodies target.
Maternal blood typing for the Rh and ABO antigens and antibody testing should occur in the first trimester of pregnancy. A full history regarding blood transfusions and previous pregnancies should also be obtained, especially when the mother is Rh negative or is alloimmunized HDFN prevention through anti Rh immunoglobulin, is only effective against Rh alloimmunization.
If antibodies against RBC antigens are detected in sufficient quantity, the patient must be referred immediately to a specialist in fetal medicine. The possibility of the fetus carrying the antigen against which the antibody is directed must be predicted based on the blood type of the father or by NIPT, molecular typing of cell-free fetal DNA.
In cases of mild HDFN antibody concentration, fetal anemia must be frequently monitored using mid cerebral artery doppler sonography (MCAS). MCAS, although associated with a 15% false positive rate, can detect anemia before any severe complications such as heart failure arise. However, at the end of the third semester this measure can become unreliable and delivery must be scheduled around the 37th week of gestation.
Cases where there is a significant rise in antibody concentration or pathological changes in mid-cerebral artery monitoring require fetal blood sampling. Fetal blood sampling is necessary because it determines how much blood will need to be transfused through an intrauterine blood transfusion.
Both procedures involve administering a paralytic agent to the fetus and performing a needle puncture, which is associated with risks such as fetal loss in 0.6% of cases and emergency C-sections in 0.4%. Babies born immediately after a transfusion might require ventilatory assistance, as the respiratory musculature could still be paralyzed.
