Of the many causes of fetal anemia, one of the most frequent is red cell alloimmunization, which results from transplacental passage of maternal antibodies that destroy fetal red cells. Alloimmunization leads to overproduction of immature fetal and neonatal red cells-erythroblastosis etalis-a condition now referred to as hemoytic disease of the etus and newborn (HDFN).
In addition, several congenital infections are also associated with fetal anemia, particularly parvovirus B19, discussed in Chapter 64 (p. 1216). In Southeast Asian populations, x4-thalassemia is a common cause of severe anemia and nonimmune hydrops. Fetomaternal hemorrhage occasionally creates severe fetal anemia and is discussed on page 306. Rare causes of anemia include red cell production disorders-such as Blackfan-Diamond anemia and Fanconi anemia; red cell enzymopathies-glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency; red cell structural abnormalities-hereditary spherocytosis and elliptocytosis; and myeloproliferative disorders-leukemias. Anemia may be identified through fetal blood sampling, described in Chapter 14 (p. 294), or by Doppler evaluation of the fetal middle cerebral artery (MCA) peak systolic velocity, described on page 303.
Progressive fetal anemia from any cause leads to heart failure, hydrops fetalis, and ultimately death. Fortunately, the prevalence and the course of this otherwise devastating disorder have been dramatically changed by prevention and treatment. Prevention ofD alloimmunization is with anti-D immune globulin. Identiication and treatment of fetal anemia is with MCA Doppler studies and intrauterine transfusions, respectively. Severely anemic fetuses transfused in utero have survival rates exceeding 90 percent, and even in cases of hydrops fetalis, survival rates approach 80 percent (Lindenberg, 2013; Zwiers, 2017).
Currently, 33 diferent blood group systems and 339 red cell antigens are recognized by the International Society of Blood Transfusion (Storry, 2014). Although some of these are immunologically and genetically important, many are so rare as to be of little clinical signiicance. Any individual who lacks a specific red cell antigen may produce an antibody when exposed to that antigen. Such antibodies can prove harmful to that individual if she receives an incompatible blood transfusion. Accordingly, blood banks routinely screen for erythrocyte antigens. hese antibodies may also be harmful to a mother's fetus during pregnancy. As noted, maternal antibodies formed against fetal erythrocyte antigens may cross the placenta to cause fetal red cell lysis and anemia.
Typically, a fetus inherits at least one red cell antigen from the father that is lacking in the mother. hus, the mother may become sensitized if enough fetal erythrocytes reach her circulation to elicit an immune response. Even so, alloimmunization is uncommon for the following reasons: (1) low prevalence of incompatible red cell antigens; (2) insuicient transplacental passage of fetal antigens or maternal antibodies; (3) maternalfetal ABO incompatibility, which leads to rapid clearance of fetal erythrocytes before they elicit an immune response; (4) variable antigenicity; and (5) variable maternal immune response to the antigen.
In population-based screening studies, the prevalence of red cell alloimmunization in pregnancy approximates 1 percent (Bollason, 2017; Koelewijn, 2008). Most cases of severe fetal anemia requiring antenatal transfusion are attributable to anti-D, anti-Kell, anti-c, or anti-E alloimmunization (de Haas, 2015).