Maternal alloimmunization to RBC antigens, whether from blood transfusion or exposure to fetal antigens during pregnancy, can lead to hemolytic disease of the fetus and newborn (HDFN). While routine administration of anti-D immune prophylaxis has decreased the incidence of HDFN, many other antigen families including ABO, Kell, Duffy, Kidd, and MNS may lead to HDFN. However, little is known about the prevalence and temporal trends of RBC alloimmunization in pregnant women in the U.S. Over 9.8 million initial obstetric blood samples (14.4% of total pregnancies) collected from 2010-2021 were screened at Quest Diagnostics. Overall, 1.5% (147,262) were positive for RBC antigens, and the estimated prevalence of maternal RBC alloimmunization was 1,518 per 100,000 pregnancies—nearly three quarters of which were to high-risk antibodies. The most common antibodies associated with maternal RBC alloimmunization were anti-D (586 per 100,000 pregnancies), anti-K (68 per 100,000 pregnancies), and anti-C (29 per 100,000 pregnancies). Interestingly, the prevalence of all three high-risk antibodies increased from 2010 to 2021 (p<0.001), and the prevalence of RBC alloimmunization in the U.S. was higher than in other high-income countries. Further research is needed to explore possible explanations for the rising prevalence of maternal RBC alloimmunization in the U.S.
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