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Fetal disorders may be acquired—such as alloimmunization; may be genetic—congenital adrenal hyperplasia; or may be sporadic—like many structural malformations. This chapter reviews fetal anemia and thrombocytopenia and immune and nonimmune fetal hydrops. Hydrops is perhaps the quintessential fetal disorder, as it can be a manifestation of severe illness from a wide variety of etiologies. Fetal structural malformations are reviewed in Chapter 15, genetic abnormalities in Chapters 16 and 17, and conditions amenable to medical or surgical fetal therapy in Chapter 19. Because congenital infections arise as a result of maternal infection or colonization, they are discussed in Chapters 67 and 68.


Anemia may result from alloimmunization, infection, genetic disorders, or fetomaternal hemorrhage. Red cell alloimmunization results from transplacental passage of maternal antibodies that destroy fetal red cells. Alloimmunization leads to overproduction of immature fetal and neonatal red cells—erythroblastosis fetalis—a condition now referred to as hemolytic disease of the fetus and newborn (HDFN). Congenital infections are also associated with fetal anemia, particularly parvovirus B19, discussed in Chapter 67 (p. 1191). In Southeast Asian populations, α0-thalassemia is a common cause of severe anemia and nonimmune hydrops. Rare genetic causes of anemia include red cell production disorders—such as Diamond-Blackfan anemia and Fanconi anemia; red cell enzymopathies—glucose-6-phosphate dehydrogenase deficiency and pyruvate kinase deficiency; red cell structural abnormalities—hereditary spherocytosis and elliptocytosis; lysosomal storage diseases—Gaucher disease, Niemann-Pick, and mucopolysaccharidosis VII; and myeloproliferative disorders—leukemias. Fetomaternal hemorrhage is discussed on page 357. Fetal anemia is typically identified through Doppler evaluation of the fetal middle cerebral artery (MCA) peak systolic velocity (p. 355).

Progressive fetal anemia from any cause leads to heart failure, hydrops fetalis, and ultimately death. Treatment with intrauterine transfusions can be lifesaving. 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; Mizuuchi, 2021; Zwiers, 2017).

Red Cell Alloimmunization

Currently, 36 different blood group systems and 360 erythrocyte antigens are recognized by the International Society of Blood Transfusion (Storry, 2019). Blood banks routinely screen for erythrocyte antigens. Some are immunologically and genetically important, but many are rare and of little clinical significance. An individual who lacks a specific erythrocyte antigen may produce antibodies against it when exposed to that antigen. Such antibodies can prove harmful if an individual receives an incompatible blood transfusion. During pregnancy, these antibodies may cross the placenta and lyse fetal red cells that contain the associated antigens, resulting in anemia.

The fetus typically inherits at least one erythrocyte antigen from the father that is lacking in the mother. The pregnant woman may become sensitized if enough fetal red cells reach her circulation to elicit an immune response. Importantly, alloimmunization is uncommon for the following reasons: (1) low prevalence of incompatible erythrocyte antigens; (2) insufficient ...

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