Fetal disorders may be acquired—such as alloimmunization, they may be genetic—congenital adrenal hyperplasia or α4-thalassemia, or they may be sporadic developmental abnormalities—like many structural malformations. Reviewed in this chapter are fetal anemia and thrombocytopenia, along with 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 10; genetic abnormalities are reviewed in Chapters 13 and 14; and other conditions amenable to fetal medical and surgical treatment are reviewed in Chapter 16. Because congenital infections arise as a result of maternal infection or colonization, they are considered in Chapters 64 and 65.
Of the many causes of fetal anemia, the most common 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 fetalis–a condition now referred to as hemolytic disease of the fetus and newborn (HDFN). Several congenital infections are also associated with fetal anemia, particularly parvovirus B19, discussed in Chapter 64 (Hantaviruses). In Southeast Asian populations, α4-thalassemia is a common cause of severe anemia and nonimmune hydrops. Fetomaternal hemorrhage occasionally creates severe fetal anemia and is discussed on Fetomaternal Hemorrhage. 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 as described in Chapter 14 (Chorionic Villus Sampling (CVS)) or by Doppler evaluation of the fetal middle cerebral artery (MCA) peak systolic velocity as described on Middle Cerebral Artery Doppler Velocimetry.
Progressive fetal anemia from any cause leads to heart failure, hydrops fetalis, and ultimately death. Fortunately, the prevention of Rh D alloimmunization with anti-D immune globulin, and the identification and treatment of fetal anemia with MCA Doppler studies and intrauterine transfusions, respectively, have dramatically changed the prevalence and course of this otherwise devastating disorder. Severely anemic fetuses transfused in utero have survival rates exceeding 90 percent, and even in cases of hydrops fetalis, survival rates approach 80 percent (Lindenburg, 2013; van Kamp, 2001).
Red Cell Alloimmunization
There are currently 30 different blood group systems and 328 red cell antigens recognized by the International Society of Blood Transfusion (Storry, 2011). Although some of these are immunologically and genetically important, many are so rare as to be of little clinical significance. 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 ...