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Alloimmune hemolytic disease of the fetus and newborn 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. As a consequence of the hemolytic process, anemia, extramedullary hematopoiesis, and neonatal hyperbilirubinemia sometimes result in fetal loss or neonatal death or disability. Collaboration among maternal–fetal medicine specialists, hematologists, radiologists, and neonatologists has substantially reduced perinatal mortality and morbidity resulting from this condition. Antenatal diagnostic methods identify fetuses at risk for developing hemolysis 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). Severely affected fetuses who in the past died before birth, secondary to severe anemia and hydrops, now are saved by vigilant antenatal monitoring and intrauterine transfusions. Antibody against D antigen prophylaxis protocols have successfully prevented alloimmune hemolytic disease resulting from rhesus D sensitization, but alloimmune hemolytic disease resulting from other red cell antibodies still occurs. Advances in immunohematology and molecular biology may offer new avenues for prevention and treatment in the future.

Acronyms and Abbreviations

Acronyms and abbreviations that appear in this chapter include: anti-D, antibody against D antigen; DAT, direct antiglobulin test; ΔOD450, change in optical density at 450 nm; FMH, fetal–maternal hemorrhage; HDFN, alloimmune hemolytic disease of the fetus and newborn; Ig, immunoglobulin; IUT, intrauterine transfusion; IVIg, intravenous immunoglobulin G; RBC, red blood cell; Rh, rhesus.

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 cell antigens foreign to the mother, inherited by the fetus from the father. The resulting hemolysis may cause fetal and neonatal anemia and significant neonatal jaundice. There are three main classes of alloimmune HDFN, based on the antigen(s) involved: Rh (rhesus), ABO, and other red cell antigens.

Prior to the development of medical interventions in the 1950s, almost half of all newborn infants with Rh HDFN died or were severely handicapped. Although the clinical condition was described in newborn infants as early as the 1600s, it was only in the 1930s and 1940s that the pathophysiology of Rh HDFN was uncovered. In 1932, Diamond and colleagues1 recognized that the clinical syndromes of stillbirth with unusual erythroblastic activity in the extramedullary sites and blood, fetal hydrops, anemia in the newborn, and “icterus gravis neonatorum” were closely related and likely had the same pathophysiology in the hematopoietic system. In 1938, Ruth Darrow, a pathologist who lost a baby to kernicterus, postulated that hemolysis of fetal red blood cells was a result of maternal antibody produced in response to fetal hemoglobin.2 The ...

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