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Hemolytic disease of the fetus and newborn caused by maternal blood group immunization is an important cause of infant morbidity and mortality. The overall incidence of hemolytic disease of the newborn is10.6 cases per 10,000 total births, with most cases resulting from failure to use D (Rho[D]) immune globulin appropriately during the antepartum and postpartum periods. 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. ABO incompatibility is a common cause of subclinical and mild hemolytic disease of the newborn, but it does not cause severe erythroblastosis or death in utero. In fact, if ABO incompatibility exists, it is known to decrease significantly the risk of hemolytic disease for the fetus.
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.
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.
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, and abnormalities of pulsed Doppler.
Amniocentesis with spectrophotometric examination of amniotic fluid is the 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 as related to gestational age. Results are plotted on a graph described by Liley, which indicates the risk of erythroblastosis for given AOD450 values at specific gestational ages. Recently, some investigators have suggested that correlation.
If AOD450 is in Liley zone III, 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. If serial values remain in Liley zone I, the fetus is either antigen negative or so mildly affected that it can be delivered at term. However, when the AOD450 is in Liley zone II, the fetus is at a moderate to severe risk for deterioration in utero.
Prevention
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. Except in very rare circumstance in which a DU-positive mother carrying a D-positive fetus may be stimulated to form anti-D antibody, Du positive is the equivalent of D positive. Because there could be other reasons for a positive D~ test result, it is recommended that prophylaxis be given whenever the D type is in question. Prophylaxis should be given in the presence of any condition associated with maternal-fetal hemorrhage. The following obstetric situations result in sensitization and thus require prophylactic therapy:
• A D-negative woman has a slight chance of becoming sensitized in association with events that surround abortion or ectopic pregnancy. This is prevented almost completely by use of D immune globulin, adjusted based on gestational stage. Although a smaller dose may be sufficient for events that occur in the first trimester, most experts recommend the full dose of 300 ug.
• The risk of sensitization in association with amniocentesis is unknown. It is estimated that fetal-maternal hemorrhage occurs approximately 2.5% of the time. Prophylaxis with 300 mcg of D immune globulin.
Postpartum administration of 300 mcg 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 fetal-maternal hemorrhage at delivery has exceeded this amount. If 300 mcg of D immune globulin is administered, the risk of sensitization in association with a major fetal-maternal hemorrhage at term is very low, perhaps on the order of 1 per 8,000 D-incompatible pregnancies.