Flashcards in Management of Alloimmunization During Pregnancy Deck (13):
Most of the cases of Rh alloimmunization causing transfusion reactions or serious hemolytic disease in the fetus and newborn are the result of incompatibility with respect to the D antigen. For this reason, the designation Rh positive usually indicates the presence of the D antigen and Rh negative indicates the absence of D antigen on erythrocytes.
The incidence of Rh incompatibility varies by race and ethnicity. Approximately 15% of whites are Rh negative, compared with only 5–8% of African Americans and 1–2% of Asians and Native Americans. Among whites, an Rh-negative woman has an approximate 85% chance of mating with an Rh-positive man, 60% of whom are heterozygous and 40% of whom are homozygous at the D locus.
Several obstetric procedures may lead to fetomaternal hemorrhage and, in turn, maternal alloimmunization. These include chorionic villus sampling, pregnancy termination, amniocentesis, and external cephalic version (16–18).
The usefulness of maternal serum antibody titers is determined by the patient's reproductive history. For a woman with a history of a previously affected fetus or neonate, serial titer assessment is inadequate for surveillance of fetal anemia. Titer values are reported as the integer of the greatest tube dilution with a positive agglutination reaction. Variation in titer results from different laboratories is not uncommon, so titers should be obtained in the same laboratory when monitoring a patient, and a change of more than one dilution is significant. A critical titer is that titer associated with a significant risk for severe erythroblastosis fetalis and hydrops, and in most centers this is between 1:8 and 1:32. If the initial antibody titer is 1:8 or less, the patient may be monitored with titer assessment every 4 weeks. For patients with alloimmunization involving antigens other than D, similar titer levels should be used to guide care except in Kell-sensitized patients because Kell antibodies do not correlate with fetal status (19).
The initial management of a pregnancy involving an alloimmunized patient is determination of the paternal erythrocyte antigen status. If the father is negative for the erythrocyte antigen in question (and it is certain that he is the father of the fetus), further assessment and intervention are unnecessary.
In cases of Rh-D alloimmunization in which the father is Rh positive, the probability that he is heterozygous for the D antigen can be reliably estimated by using Rh-D antisera to determine his most likely genotype. This involves mixing antisera, containing antibodies to the D antigen, with the father's cells to determine if the D antigen is present. A positive result is determined by agglutination caused by the cross-linking of the antibody with the corresponding antigen. If the father is homozygous for the D antigen, all his children will be Rh positive; if he is heterozygous, there is a 50% likelihood that each pregnancy will have an Rh-negative fetus that is not at risk of anemia.
The fetal antigen type should be assessed when the paternal genotype is thought to be heterozygous or is unknown. Amniocentesis is the primary modality used to determine fetal blood type using polymerase chain reaction (PCR) on uncultured amniocytes in 2 mL of amniotic fluid. The sensitivity and specificity of PCR typing are reported as 98.7% and 100%, respectively, with positive and negative predictive values of 100% and 96.9% (20). Chorionic villus biopsy also has been employed for this purpose, but its use should be discouraged because disruption of the villi may result in unnecessary fetomaternal hemorrhage and worsening alloimmunization
If the fetus is found to be negative for the erythrocyte antigen in question, further testing may not be warranted (20). Although the false-negative rate is low (1–3%), periodic noninvasive assessment may be warranted (20).
the history and antenatal studies indicate only mild fetal hemolysis, it is reasonable to proceed with delivery by induction of labor at 37–38 weeks of gestation. Induction may be considered earlier if fetal pulmonary maturity is documented by amniocentesis.
With severely sensitized pregnancies requiring multiple invasive procedures, the risks of continued cord blood sampling and transfusions must be considered and compared with those neonatal risks associated with early delivery. Given that the overall neonatal survival rate after 32 weeks of gestation in most neonatal intensive care nurseries is greater than 95%, it is prudent to time procedures so that the last transfusion is performed at 30–32 weeks of gestation, with delivery at 32–34 weeks of gestation after maternal steroid administration to enhance fetal pulmonary maturity
In a center with trained personnel and when the fetus is at an appropriate gestational age, Doppler measurement of peak systolic velocity in the fetal middle cerebral artery is an appropriate noninvasive means to monitor pregnancies complicated by red cell alloimmunization.
The initial management of a pregnancy involving an alloimmunized patient is determination of the paternal erythrocyte antigen status.
paternal erythrocyte antigen status.