This infant has erythroblastosis fetalis, which results when prior sensitization to a fetal blood cell antigen leads to alloantibodies in maternal blood that can cross the placenta. The Rh blood group system is most often implicated. The maternal antibody coats fetal RBCs, causing hemolysis. The Coombs test is positive. The fetal anemia leads to congestive heart failure and hydrops. Hemolysis results in a very high bilirubin level. A high maternal serum level of a-fetoprotein suggests a fetal neural tube defect; such defects are not associated with hydrops. Viral hepatitis is not a perinatal infection. Diminished glucocerebrosidase activity causes Gaucher disease, and this condition does not lead to perinatal liver failure or anemia. Listeriosis or other congenital infections may produce fetal hydrops and anemia, although not of the severity described in this case.