ERYTHROBLASTOSIS FETALIS (RH SENSITIZATION)
Isoimmunization of the mother to any dissimilar fetal blood group not possessed by the mother is possible. Historically the most common example is the Rh (D) factor. Erythroblastosis fetalis (hemolytic disease of the newborn) is characterized by sustained destruction of the fetal erythrocytes by speciﬁc maternal antibodies (IgG), which cross the placenta to the fetus. What was once a common cause for fetal death has largely been eradicated by prophylactic maternal administration of immune globulin against the Rh (D) factor to those at risk.
Human red blood cells contain a complex group of inherited antigens, one of which is the Rhesus CDE antigen system. The genes for the CDE blood groups are inherited separately from the ABO groups and are located on the short arm of chromosome 1. One of the more important antigens of this group is Rh (D) factor. About 85% of all individuals are Rh (D)-positive whereas 15% are Rh (D)-negative. Any process that exposes the woman to blood carrying the D antigen including blood transfusion, miscarriage, ectopic or normal pregnancy, trauma during pregnancy, amnio-centesis, and others can result in anti-Rh agglutinins being formed. The IgG antibodies can cross the placenta into the fetal circulation and result in the destruction of the Rh-positive fetal blood. Other isoimmunizations (most frequently Kell, or Duffy antigens) can also result in similar effects on the fetus.
The three principal features of the disease are hemolytic anemia, icterus, and hydrops. The predominance of one or another of these manifestations in a given case depends mainly upon the degree of immunity in the mother’s blood. When antibody titers are 1:8, no clinical intervention is required. When titers are 1:16 in albumin or 1:32 by an indirect Coombs test, amnio-centesis, umbilical cord blood sampling, or Doppler velocimetry of the middle cerebral arteries should be considered. In severely affected fetuses, intrauterine transfusion may be required to prevent the full spectrum of hemolytic disease and hydrops.
In hydrops fetalis, the most severe form of the disease, the fetus often is born dead and macerated. Fluids accumulate in the serous cavities and body tissues. In severe cases marked hemolytic anemia may develop. The nucleated red cells may far outnumber the white blood cells. The viscera present many foci of extramedullary erythropoiesis, which is most character-istically seen in the lungs where the blood vessels in alveolar septa are ﬁlled with large erythroblasts.
In less severe cases the infant is born alive with less edema and milder anemia. Because the placenta is no longer available to transport bilirubin away, within a few hours icterus may develop as the red cells are destroyed, liberating hemoglobin for transformation into bilirubin more rapidly than the pigment can be eliminated by the liver. Icterus and anemia may gradually subside or may increase to cause death within a few days. In other cases with fewer agglutinins in the infant’s blood, the icterus may be mild, and only anemia (congenital anemia) may be manifested clinically. Most of these cases recover when exchange transfusion therapy is applied.
In severe cases, the placenta is very large, excessively lobulated, pale, and edematous. Microscopically, the villi are swollen, edematous, and generously covered with trophoblasts, including occasional cytotrophoblastic cells even at term. The fetal blood is loaded with erythroblasts and other nucleated red blood cells. Intra-placental clots are frequent.
All patients should have their Rh type established and be tested for isoimmunization (indirect Coombs test) at the ﬁrst prenatal visit. Those who are Rh-negative should receive D immune globulin after delivery, amniocentesis, fetal demise, miscarriage, ectopic pregnancy, or any other time exposure to Rh-positive cells may have occurred. Prophylactic administration between 28 and 30 weeks of gestation is also standard. With prophylaxis, he risk of isoimmunization is estimated to be 0.3%.