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Despite dramatic progress in the management and prevention of hemolytic disease of the fetus and newborn caused by maternal blood group immunization, it continues to be an important cause of infant morbidity and mortality in the United States isoimmunization. In 1970, the incidence of hemolytic disease in newborns was approximately 45 per 10,000 births. In 1986, the Centers for Disease Control and Prevention reported the overall incidence of 10.6 cases per 10,000 total births, with most cases resulting from failure to use D (Rho[D]) immune globulin appropriately during the antepartum period.
Isoimmune hemolytic disease of the fetus and newborn is due to fetal-maternal blood group incompatibility and is caused by production of maternal antibodies against a fetal blood group antigen. Despite widespread use of D immune globulin, anti-D immunization remains the most common cause of erythroblastosis fetalis; however, a significant number of cases are the result of incompatibility with other erythrocyte antigens such as Kell, c, E, C, Fya (Duffy), Jka (kidd), s, M, and rarer erythrocyte antigens, both public and private. ABO incompatibility is a common cause of subclinical and mild hemolytic disease of the newborn, but it does not cause severe erythroblastosis or death.
Prenatal Screening
At the first prenatal visit, each patient's blood should be tested for ABO and CDE (Rh) types as well as screened for the presence of antibodies by an indirect Coombs test (antibody screen). Any erythrocyte antibody present must be specifically identified, and appropriate titers must be obtained to determine whether there is a risk to the fetus. Antibodies formed in response to the D antigen are of the IgG immunoglobulin class, which can cross the placenta and hemolyze fetal erythrocytes. Conversely, antibodies of the IgM class, such as the Lewis antigen, are of no clinical significance because they cannot cross the placenta. Kell antibodies, also of the IgG class, can produce severe erythroblastosis fetalis and are often due to prior transfusion of Kell-incompatible blood. Kell antibody titer has been reported to correlate poorly with the severity of fetal anemia.
Management
In sensitized patients who have never had an infant affected with erythroblastosis, the maternal antibody titer should be determined at the first prenatal visit. Follow-up evaluations should be made at 20 weeks of gestation and approximately every 4 weeks thereafter. When the titer is 1:8 or less, whether directed to D or another paternal antigen capable of causing hemolytic disease, no intervention is necessary. If the titer is 1:16 or greater by a technique using albumin or 1:32 or greater by the indirect Coombs technique, amniocentesis or PUBS should be considered.
When hydrops is detected on an ultrasound examination, fetal anemia is severe. Possible signs of worsening fetal anemia include an increase in the size of the fetal liver, an increase in placental thickness, pericardial effusion, polyhydramnios, thickening of the bowel wall.
Since the mid-1960s, amniocentesis with spectrophotometric examination of amniotic fluid has been the accepted method of assessing the severity of erythroblastosis in utero. Amniotic fluid bilirubin is most likely derived from fetal tracheal and pulmonary secretions. This approach evaluates the difference in optical density between observed absorption of amniotic fluid bilirubin at 450 nm (AOD450) and extrapolated baseline absorption.
Interpretation of AOD450 results is relatively straightforward. If a value is in Liley zone llI, there is a high probability of fetal death within 7-10 days, and either delivery or intrauterine transfusion is indicated, depending on the gestational age.
Prevention
From a public health standpoint, prevention is the most important aspect of the management of hemolytic disease. D isoimmunization is the only situation for which a preventive strategy is currently available. The process of prevention begins with the identification of each newly pregnant patient's major blood group and D type in early pregnancy. Those patients at risk for isoimmunization should be given D immune globulin prophylaxis.
Postpartum administration of 300 :g of D immune globulin will almost completely prevent sensitization. This dosage will effectively neutralize the antigenic load of 30 mL of fetal whole blood or 15 mL of fetal erythrocytes that have entered the maternal circulation. Kleihauer-Betke or the rosette test frequently is used to determine whether fe-tal-maternal hemorrhage at delivery has exceeded this amount.