Once anti-D antibodies are detected the father’s RhD type should be determined. Significant hemolysis does not occur with anti-D concentrations ≤≤ 4 iu/ml and there is no need for intervention. Antibody testing should be repeated monthly to 28 weeks and fortnightly thereafter. Above 4 iu/ml there is a risk of anemia but this is not accurately predicted by anti-D concentration; between 4 and 15 iu/ml mild to moderate anemia, requiring postnatal transfusion, may occur but severe anemia (hemoglobin < 7 g/dl) is uncommon. Above 15 iu/ml, and particularly in the presence of rapidly rising levels, the risk of severe anemia has been reported to be as high as 50%. Where there is a risk of significant hemolysis and the partner is heterozygous for the RhD antigen, the fetal RhD genotype can be predicted using real-time PCR on cell-free fetal DNA within the maternal circulation.

In women with anti-D > 4 iu/ml and an RhD-positive fetus, the risk of fetal anemia is assessed by ultrasonographic measurement of cerebral peak systolic blood flow; the sensitivity of an increased peak velocity of systolic blood flow for severe fetal anemia is ∼100% with a FPR of 12% (positive LR 8.5, 95% CI 4.7–15.6, negative LR 0.02, 95% CI 0.00– 0.25). This increase in peak velocity is likely to be a result of increased cardiac output and/or reduced blood visocity.

The management of increased peak systolic velocity (i.e. > 1.5 Multiples of the Median [MoMs]) at gestations < 33 weeks is cordocentesis to measure the fetal hematocrit (or hemoglobin). The risk of increased sensitization, especially with transplacental passage of the needle, and fetal death suggests that fetal blood sampling should be reserved for fetuses perceived to be at highest risk. Intravascular transfusions are begun when the fetal hematocrit declines below > 30% (less than the 2.5th centile after 20 weeks). The timing of subsequent blood sampling in fetuses with a hematocrit > 30% is determined by the strength of the positive direct antiglobulin test and the fetal reticulocyte count. Compatible (RhD negative), fresh, leukocyte depleted blood, resuspended in saline to a hematocrit of ∼70–75%, is transfused into either the umbilical vein (at the placental cord insertion) or the intrahepatic vein. The volume of blood required to attain the desired hematocrit (typically 40–50%) can be estimated from the initial fetal and donor hematocrits together with the estimated fetoplacental blood volume. The second transfusion is arbitrarily undertaken 2 weeks after the first, or at a time when the peak systolic velocities increase beyond the treatment threshold. The timing of subsequent transfusions is then determined from the fall in hematocrit, which becomes more consistent over time (typically ∼1%/d) as fetal erythropoiesis is suppressed and only donor blood is circulating. Intraperitoneal transfusion is less effective and associated with a greater risk of fetal death compared with intravascular transfusion

Source: Forfar and Arneil’s Textbook of Pediatrics, 7E