Clinical Manifestations of Hemolytic Disease of Newborn Caused by Rh Incompatibility

The Rh antigenic determinants are genetically transmitted from each parent, determine the Rh type, and direct the production of a number of blood group factors (C, c, D, d, E, and e). Each factor can elicit a specific antibody response under suitable conditions; 90% are due to D antigen and the remainder to C or E.

A wide spectrum of hemolytic disease occurs in affected infants born to sensitized mothers, depending on the nature of the individual immune response.

The severity of the disease may range from only laboratory evidence of mild hemolysis (15% of cases) to severe anemia with compensatory hyperplasia of erythropoietic tissue leading to massive enlargement of the liver and spleen. When the compensatory capacity of the hematopoietic system is exceeded, profound anemia occurs and results in pallor, signs of cardiac decompensation (cardiomegaly, respiratory distress), massive anasarca, and circulatory collapse. This clinical picture of excessive abnormal fluid in two or more fetal compartments (skin, pleura, pericardium, placenta, peritoneum, amniotic fluid), termed hydrops fetalis, frequently results in death in utero or shortly after birth. With the use of RhoGAM to prevent Rh sensitization, nonimmune (nonhemolytic) conditions have become frequent causes of hydrops . The severity of hydrops is related to the level of anemia and the degree of reduction in serum albumin (oncotic pressure), which is due in part to hepatic dysfunction. Alternatively, heart failure may increase right heart pressure, with the subsequent development of edema and ascites. Failure to initiate spontaneous effective ventilation because of pulmonary edema or bilateral pleural effusions results in birth asphyxia; after successful resuscitation, severe respiratory distress may develop. Petechiae, purpura, and thrombocytopenia may also be present in severe cases as a result of decreased platelet production or the presence of concurrent disseminated intravascular coagulation.

Jaundice may be absent at birth because of placental clearance of lipid-soluble unconjugated bilirubin, but in severe cases, bilirubin pigments stain the amniotic fluid, cord, and vernix caseosa yellow. Jaundice is generally evident on the 1st day of life because the infant’s bilirubin-conjugating and excretory systems are unable to cope with the load resulting from massive hemolysis. Indirect-reacting bilirubin therefore accumulates postnatally and may rapidly reach extremely high levels and present a significant risk of bilirubin encephalopathy. The risk of kernicterus developing from hemolytic disease is greater than from comparable nonhemolytic hyperbilirubinemia, although the risk in an individual patient may be affected by other complications (anoxia, acidosis). Hypoglycemia occurs frequently in infants with severe isoimmune hemolytic disease and may be related to hyperinsulinism and hypertrophy of the pancreatic islet cells in these infants.

Infants born after intrauterine transfusion for prenatally diagnosed erythroblastosis may be severely affected because the indications for transfusion are evidence of already severe disease in utero (hydrops, fetal anemia). Such infants usually have very high (but extremely variable) cord levels of bilirubin, which reflects the severity of the hemolysis and its effects on hepatic function. Infants treated with intra-umbilical vein transfusions in utero may also have a benign postnatal course if the anemia and hydrops resolve before birth. Anemia from continuing hemolysis may be masked by the previous intrauterine transfusion, and the clinical manifestations of erythroblastosis may be superimposed on various degrees of immaturity resulting from spontaneous or induced premature delivery.