The prevalence of D alloimmunization complicating pregnancy ranges from 0.5 to 0.9 percent (Koelewijn, 2008; \1artin, 2005). Without anti-D immune globulin prophylaxis, a D-negative woman delivered of a D-positive, ABO-compatible newborn has a 16-percent likelihood of developing alloimmunization. Two percent will become sensitized by the time of delivery, 7 percent by 6 months postpartum, and the remaining 7 percent will be "sensibilized"-producing detectable antibodies only in a subsequent pregnancy (Bowman, 1985). If there is ABO incompatibility, the D alloimmunization risk approximates 2 percent without prophylaxis (Bowman, 2006). The reason for the difering rates relative to ABO blood type results from erythrocyte destruction of ABO-incompatible cells, which thereby limits sensitizing opportunities. D sensitization also may occur following irst-trimester pregnancy complications, prenatal diagnostic procedures, and maternal trauma (Table 15-2).
The C, c, E, and e antigens have lower immunogenicity than the D antigen but can cause hemolytic disease. Sensitization to E, c, and C antigens complicates approximately 0.3 percent of pregnancies in screening studies and accounts for about 30 percent of red cell alloimmunization cases (Howard, 1998; Koelewijn, 2008). Anti-E alloimmunization is the most common, but the need for fetal or neonatal transfusions is greater with anti-c alloimmunization than with anti-E or anti-C (de Haas, 2015; Hackney, 2004; Koelewijn, 2008).
The Grandmother Efect. In virtually all pregnancies, small amounts of maternal blood enter the fetal circulation. Realtime polymerase chain reaction (PCR) has been used to identiy maternal D-positive DNA in peripheral blood from pre term and full-term D-negative newborns (Lazar, 2006). hus, it is possible for a D-negative female fetus exposed to maternal D-positive red cells to develop sensitization. When such an individual reaches adulthood, she may produce anti-D antibodies even before or early in her irst pregnancy. This mechanism is called the grandmother eect or theory because the fetus in the current pregnancy is jeopardized by maternal antibodies that were initially provoked by his or her grandmothers erythrocytes.
Alloimmunization to Minor Antigens
Because routine administration of anti-D immunoglobulin prevents anti-D alloimmunization, proportionately more cases of hemolytic disease are caused by red cell antigens
TABLE 15-2. Causes of Fetomaternal Hemorrhage Associated with Red Cell Antigen Alloimmunizationa
Procedures Chorionic villus sampling Amniocentesis Fetal blood sampling Evacuation of molar pregnancy aFor each of the above, anti-D immune globulin is recom mended.
Expanded from American Academy of Pediatrics and
American College of Obstetricians and Gynecologists, 2017; American College of Obstetricians and
Gynecologists, 2017.
other than D (American College of Obstetricians and Gynecologists, 2016; Koelewijn, 2008). hese are also known as minor antigens. Kell antigens are among the most frequent. Other antigens with potential to cause severe alloimmunization include Duy group A_Fya, MNS, and Kidd-Jka (de Hass, 2015; Moise, 2008). Most cases of sensitization to minor antigens result from incompatible blood transfusions. However, if an IgG red cell antibody is detected and there is any doubt as to its significance, the clinician should err on the side of caution, and the pregnancy should be evaluated for hemolytic disease.