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Alloimmune hemolytic disease of the fetus and newborn (HDFN) is caused by the action of transplacentally transmitted maternal immunoglobulin (Ig) G antibodies on paternally inherited antigens present on fetal red cells but absent on the maternal red cells. Maternal IgG antibodies bind to fetal red cells, causing hemolysis or suppression of erythropoiesis. As a consequence, anemia, extramedullary hematopoiesis, and neonatal hyperbilirubinemia may result, with severe cases resulting in fetal loss or neonatal death or disability. Collaboration among maternal–fetal medicine specialists, hematologists, transfusion medicine physicians, radiologists, and neonatologists has substantially reduced perinatal mortality and morbidity resulting from hemolytic disease of the fetus and newborn. Antenatal diagnostic methods identify at risk fetuses and assess disease severity in affected fetuses. After birth, phototherapy and exchange transfusions prevent serum bilirubin from rising to levels that could produce bilirubin encephalopathy and resultant brain damage (kernicterus), remove maternal antibody, and replace circulating fetal red blood cells with those negative for the implicated antigen(s). Rho(D) immunoglobulin (RhIg) has successfully prevented alloimmune hemolytic disease resulting from rhesus D sensitization in many at risk infants, but there is not enough RhIg available to distribute to all women at risk worldwide, and no prophylactic therapy exists as of this writing to prevent alloimmune hemolytic disease resulting from other red cell antibodies. Advances in immunohematology and molecular biology may offer new avenues for prevention and treatment in the future.

Acronyms and Abbreviations:

ΔOD450, change in optical density at 450 nm; AABB, American Association of Blood Banks; AMIGO, Antigen Matching Influence on Gestational Outcomes; AAP, American Academy of Pediatrics; anti-D, antibody against D antigen; CAP, College of American Pathologists; ccff-DNA, circulating cell-free fetal DNA; DAT, direct antiglobulin test; ddPCR, droplet digital polymerase chain reaction; FFP, fresh-frozen plasma; FMH, fetomaternal hemorrhage; HDFN, hemolytic disease of the fetus and newborn; HDN, hemolytic disease of the newborn; HLA, human leukocyte antigen; IAT, indirect antiglobulin test; Ig, immunoglobulin; IUT, intrauterine transfusion; IVIG, intravenous immunoglobulin G; LOTUS, Long-Term follow up after intra-Uterine transfusionS; MALDI-TOF MS, matrix-assisted laser desorption ionization/time of flight mass spectrometry; NEC, necrotizing enterocolitis; QT-PCR, quantitative polymerase chain reaction; RBC, red blood cell; Rh, rhesus; rHuEPO, recombinant human erythropoietin; RhIg, Rho(D) immunoglobulin; RT-PCR, real-time quantitative polymerase chain reaction; SGA, small for gestational age; TBV, total blood volume; TSB, total serum bilirubin; WB, whole blood.

Alloimmune hemolytic disease of the fetus and newborn (HDFN) is a disorder in which the life span of fetal and/or neonatal red cells is shortened as a result of binding of transplacentally transferred maternal immunoglobulin (Ig) G antibodies on fetal red blood cell (RBC) antigens foreign to the mother, inherited by the fetus from the father. The resulting hemolysis or suppression of erythropoiesis may cause fetal and/or neonatal anemia and significant neonatal jaundice. There are three main classes of alloimmune HDFN, based on the antigen(s) involved: Rh (rhesus), minor red cell antigens (ie, Kell, Duffy, Kidd antigens), and ABO.

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