Clinical Management of Hemolytic Disease of the Newborn and Fetus

Abstract

Hemolytic disease of the fetus and newborn (HDFN) is caused by maternal alloantibodies directed against antigens present in fetal red cells. Paternally inherited antigens of the Rh system, which differ to those from the mother, are present on fetal red cells and when the maternal immune system makes contact with a significant number of these cells create an immune response with antibodies against these antigens. This may happen because of fetomaternal transplacental bleeding (in traumatic events during pregnancy, obstetric procedures, labor, cesarean section) or by events unrelated with pregnancy, such as transfusion, contamination by needle use, etc. Maternal antibodies (IgG) can cross the placenta and activate macrophages in the fetal spleen which cause fetal red cell destruction with subsequent hemolytic anemia. This leads to jaundice and kernicterus in the newborn or hydrops and death in the fetus. Before the 70’s, HDFN was a major obstetric problem, that had a large impact on fetal and neonatal morbidity and mortality. Today, without an appropriate programme, up to 50% of untreated HDFN will result in death or severe brain damage. In developing countries, especially those lacking an efficient prophylactics progamme, this causes an important public health problem. In fact, it has been estimated that more than 50 thousand fetuses could be affected by this condition every year in India (Zipursky and Paul, 2010). With the established use of post-natal anti-D prophylaxis for rhesus (Rh) negative women, together with its increasing use for routine antenatal prophylaxis, the incidence of Rh-D sensitization has dramatically fallen (Hughes RG et al., 1994). Nevertheless, 15-17% of the Caucasian population in Europe and North America is D negative (Ubarkian S, 2002). With the sensitization against other red cell antigens such as Kell RhC/c, RhE/e, this pathology could still affect a large number of pregnancies every year, with significant health and financial implications (Abdel-Fattah SA et al., 2002; Illanes S and Soothill P, 2009). In England and Wales, about 520 fetuses develop HDFN each year, of which about 37 would die in the fetal or neonatal period and 28 would present developmental problems (Daniels G et al., 2004, NICE 2008). On the other hand, in fetus affected by HDFN, survival rates can exceed 90 percent if anemia is diagnosed and treated with intrauterine blood transfusions in a timely manner (Van Kamp IL et al., 2001). Women with rising red cell antibody levels are usually referred to tertiary fetal medicine units for specialized management. The main challenge facing fetal medicine