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
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%.