Chapter 48  Neonatal Jaundice and Liver Disease 1455

Hemolytic conditions in the newborn are generally divided hypoxia, and capillary leak. Anemia with resultant poor myo-
into two major etiologic groups: immune and nonimmune. cardial function may further exacerbate the hydrops by caus-
ing congestive cardiac failure and venous congestion.154
Isoimmunization Elevated COHb levels, detected in blood obtained by cor-
The hallmark of isoimmunization is a positive DAT, also docentesis in affected fetuses of nonsmoking isoimmunized
known as the Coombs test. This is indicative of maternally mothers, demonstrate that destruction of erythrocytes begins
produced antibody that has traversed the placenta and is now in utero.254 However, the primary manifestation of the in
found within the fetus. The test is termed direct if the anti- utero hemolysis is that of anemia. Although large amounts of
globulin is adhered to the RBCs. An indirect test refers to the bilirubin are produced concomitantly, erythroblastotic in-
antibody being detected in the serum. fants are not severely icteric at birth. TB concentrations are
usually kept below 5 mg/dL (86 mmol/L) by transfer of un-
Rh DISEASE conjugated bilirubin across the placenta. Jaundice may ap-
In past decades, Rh hemolytic disease was the most com- pear, however, within 30 minutes after delivery. Classically,
mon cause of severe hemolytic hyperbilirubinemia and a the serum bilirubin is all indirect reacting, although small
frequent cause of kernicterus. However, maternal prophy- amounts of conjugated bilirubin have been noted. After some
laxis with high-titer anti-D immunoglobulin G (RhoGAM), days of excessive bilirubin load, the excretory system may
combined with aggressive fetal surveillance and intrauter- become overwhelmed with efflux of conjugated bilirubin
ine blood transfusions, has greatly reduced the incidence into the serum, and an increasing conjugated bilirubin frac-
and severity of this disease. Mothers sensitized before the tion is not uncommonly seen. Hepatic conjugation may ma-
development of immune serum prophylaxis are no longer ture more rapidly than excretory function as a result of
commonly encountered. Those without access to preventive stimulation by chronic exposure to high concentrations of
treatment, immigrants from countries in which prophylaxis bilirubin in utero. Furthermore, hepatic excretory function
was not widely available, or those who did not receive pro- may also be adversely affected by development of hepatic
phylaxis following abortion or invasive procedures may congestion secondary to heart failure and swelling caused by
continue to deliver affected infants. extramedullary hepatic hematopoiesis, anemia, and poor
The Rh blood group proteins are a highly antigenic hepatic perfusion.
group of proteins capable of causing severe isoimmuniza-
tion with a high risk for fetal hydrops and death. Although ABO HETEROSPECIFICITY
several systems of nomenclature exist, the CDE system is With the reduction of the incidence of Rh isoimmunization
most commonly used. These three loci each contain two by immune prophylaxis, DAT-positive ABO incompatibility
major alleles (C,c; D,d; E,e) and several minor alleles. The is now the single most prominent cause of immune hemo-
D antigen may produce maternal sensitization with a feto- lytic disease in the neonate. The clinical picture is usually
maternal hemorrhage as small as 0.1 mL. Whereas C and E milder than that of Rh disease, although infrequently severe
alleles are relatively uncommon causes of isoimmunization, hemolysis with hyperbilirubinemia may occur.
they can, on occasion, lead to severe hemolysis and hyper- By ABO blood group heterospecificity, we refer to the situ-
bilirubinemia. Rh disease in pregnancy is highly associated ation in which a blood group A or B baby is born to a group
with both intrauterine hemolysis and severe hemolytic dis- O mother, a setup occurring in about 12% of pregnancies. In
ease following delivery. Untreated, the condition can lead to some instances, women with blood group O have a high titer
intrauterine anemia and severe hydrops fetalis, with rapid of naturally occurring anti-A or anti-B antibodies. High titers
postnatal evolvement of hyperbilirubinemia with the poten- of anti-A or anti-B antibodies can sometimes be found in
tial of kernicterus. blood group O women even before their first pregnancy. This
The immunization process may begin if an Rh-negative contrasts to Rh isoimmunization, in which immune sensiti-
woman, usually D negative, is exposed to a D antigen. This zation occurs progressively with subsequent pregnancies.90
usually occurs by antepartum or intrapartum transplacental In contradistinction to blood group A or B individuals, in
fetomaternal transfusion of fetal RBCs containing a D anti- whom their respective anti-B or anti-A antibodies are IgM
gen, or by transfusion of Rh-positive RBCs during abortion, molecules with limited ability to cross the placenta, the re-
blood administration, or procedures including amniocente- spective antibodies of blood group O individuals are pre-
sis, chorionic villus sampling, or fetal blood sampling. Fol- dominantly smaller IgG molecules and may cross the pla-
lowing exposure to the D antigen on the fetal RBCs, the centa. Attachment to corresponding fetal RBCs may follow,
mother’s immune system responds by forming anti-D immu- provided these cells have the A or B antigen. Extravascular
noglobulin G (IgG) antibodies. The IgG then crosses the hemolysis of the IgG-coated RBCs is thought to be mediated
placenta and adheres to fetal RBCs containing the D antigen. within the reticuloendothelial system by Fc-receptor–bearing
The subsequent antigen-antibody interaction leads to hemo- cells. As with Rh isoimmunization, the immune process may
lysis and anemia. The immune response may become more commence in utero. However, unlike the Rh situation, there
severe and more rapid with progressive pregnancies. Resul- is little danger of severe hyperbilirubinemia, anemia, or hy-
tant anemia causes bone marrow stimulation, with increased drops in utero, and prenatal intervention is not indicated.
numbers of immature RBCs appearing in the circulation Infants may sometimes be born with moderate anemia. After
(erythroblastosis) and extramedullary hematopoiesis. Fetal delivery, there is a potential danger of hyperbilirubinemia.
hydrops, a condition characterized by generalized tissue About one third of blood group A or B neonates born
edema and pleural, pericardial, and peritoneal effusions, to a blood group O mother will have a positive direct Coombs
may result from a combination of hypoproteinemia, tissue test.175 Measurements of endogenous formation of CO,