Figure 62-1 Differential diagnosis of neonatal anemia. The physician obtains information from the family, maternal and labor and delivery histories, and laboratory tests, including hemoglobin, reticulocyte count, blood type, direct Coombs test, peripheral smear, red blood cell (RBC) indices, and bilirubin concentration. DIC, Disseminated intravascular coagulation; FTA, fluorescent treponemal antibody test; G6PD, glucose-6-phosphate dehydrogenase; HIV, human immunodeficiency virus; KB, Kleihauer-Betke; PCN, penicillin; RPR, rapid plasma reagin tests; TORCH, toxoplasmosis, other, rubella, cytomegalovirus, herpes simplex. (From Ohls RK: Anemia in the neonate. In Christensen RD, editor: Hematologic problems of the neonate, Philadelphia, 2000, Saunders, p 162.) maternal circulation, such as first-trimester abortion, ectopic pregnancy, amniocentesis, manual extraction of the placenta, version (external or internal) procedures, or normal pregnancy.
ABO incompatibility with sensitization usually does not cause fetal disease other than extremely mild anemia. It may produce hemolytic disease of the newborn, which is manifested as significant anemia and hyperbilirubinemia. Because many mothers who have blood group O have IgG antibodies to A and B before pregnancy, the firstborn infant of A or B blood type may be affected. In contrast to Rh disease, ABO hemolytic disease does not become more severe with subsequent pregnancies. Hemolysis with ABO incompatibility is less severe than hemolysis in Rh-sensitized pregnancy, either because the anti-A or anti-B antibody may bind to nonerythrocytic cells that contain A or B antigen or because fetal erythrocytes have fewer A or B antigenic determinants than they have Rh sites. With the declining incidence of Rh hemolytic disease, ABO incompatibility has become the most common cause of neonatal hyperbilirubinemia requiring therapy—currently accounting for approximately 20% of clinically significant jaundice in the newborn.
Erythroblastosis fetalis classically is caused by Rh bloodgroup incompatibility. Most Rh-negative women have noanti-Rh antibodies at the time of their first pregnancy. TheRh antigen system consists of five antigens: C, D, E, c, and e; the d type is not antigenic. In most Rh-sensitized cases, theD antigen of the fetus sensitizes the Rh-negative (d) mother,resulting in IgG antibody production during the first pregnancy. Because most mothers are not sensitized to Rh antigens at the start of pregnancy, Rh erythroblastosis fetalis isusually a disease of the second and subsequent pregnancies.The first affected pregnancy results in an antibody response inthe mother, which may be detected during antenatal screening with the Coombs test and determined to be anti-D antibody. The first affected newborn may show no serious fetaldisease and may manifest hemolytic disease of the newbornonly by the development of anemia and hyperbilirubinemia.Subsequent pregnancies result in an increasing severity of response because of an earlier onset of hemolysis in utero. Fetal anemia, heart failure, elevated venous pressure, portal vein obstruction, and hypoalbuminemia result in fetal hydrops, which is characterized by ascites, pleural and pericardial effusions, and anasarca (see Chapter 60). The risk offetal death is high.