Up to 40 percent of D-negative pregnant women carry a D-negative fetus. he presence of anti-D antibodies relects maternal sensitization but does not indicate whether the fetus is D-positive. If a woman became sensitized in a prior pregnancy, her antibody titer might rise to high levels during the current pregnancy even if the current fetus is D-negative, due to an amnestic response. In a non-Hispanic white couple in which the woman is D-negative, there is an 85-percent chance that the man is D-positive. But, in 60 percent of these cases, he will be heterozygous at the D-Iocus. And, if he is heterozygous, then half of his children will be at risk for hemolytic disease.
Transfusion history is relevant. Alloimmunization to a red cell transfusion in the past, and if that antigen is not present on paternal erythrocytes, the pregnancy is not at risk.
Initial evaluation of alloimmunization begins with determining the paternal erythrocyte antigen status. Provided that paternity is certain, if the father is negative for the red cell antigen to which the mother is sensitized, the pregnancy is not at risk. In a D-alloimmunized pregnancy in which the father is D-positive, it is helpful to determine paternal zygosity for the D antigen using DNA-based analysis. If the father is heterozygous-or if paternity is not known-the woman should be ofered assessment of fetal genotype. Traditionally, this was done with amniocentesis and PCR testing of uncultured amniocytes, which has a positive-predictive value of 100 percent and negative-predictive value of approximately 97 percent (American College of Obstetricians and Gynecologists, 2016; Van den Veyver, 1996). Fetal testing for other antigens-such as E/e, C/c, Duy, Kell, Kidd, and �1/N-is also available with this method. Chorionic villus sampling is not recommended because of greater risk for fetomaternal hemorrhage and subsequent worsening of alloimmunization.
Noninvasive fetal D genotyping has been performed using cell-free DNA (cfDNA) from maternal plasma (Chap. 13, p. 273). The reported sensitivity exceeds 99 percent, the speciicity exceeds 95 percent, and positive-or negative-predictive values are similarly very high (de Haas, 2016; Johnson, 2017; Moise, 2016; Vivanti, 2016). Fetal D genotyping with cDNA is routinely used in parts of Europe. There are two potential indications in D-negative pregnant women: (1) in women with D alloimmunization, testing can identiY fetuses that are also D-negative and do not require anemia surveillance, and (2) in women without D alloimmunization, anti-D immune globulin might be withheld if the fetus is D negative. In the case of the latter, the American College of Obstetricians and Gynecologists (2017) does not recommend routine cDNA screening in D-negative pregnancies until it becomes cost-efective.
Management of the alloimmunized pregnancy is individualized and may consist of maternal antibody titer surveillance, sonographic monitoring of the fetal MCA peak systolic velocity, amnionic luid bilirubin studies, or fetal blood sampling. Accurate pregnancy dating is critical. The gestational age at which fetal anemia developed in prior pregnancies is important because anemia tends to occur earlier and be sequentially more severe.