A newborn girl is admitted to the neonatal intensive care unit with jaundice, hepatomegaly, and generalized edema. She was born by vaginal delivery to a 32-year-old woman, gravida 2, para 2, who received minimal prenatal care. The infant's laboratory results show a hemoglobin level of 6 g/dL and a positive direct Coombs test. A peripheral blood smear shows many nucleated erythrocytes. The infant has significant respiratory distress due to pleural effusions and ascites and dies soon after birth. Autopsy shows areas of extramedullary hematopoiesis in many tissues. Which of the following is the most likely cause of this patient's condition?

Question

A newborn girl is admitted to the neonatal intensive care unit with jaundice, hepatomegaly, and generalized edema.  She was born by vaginal delivery to a 32-year-old woman, gravida 2, para 2, who received minimal prenatal care.  The infant's laboratory results show a hemoglobin level of 6 g/dL and a positive direct Coombs test.  A peripheral blood smear shows many nucleated erythrocytes.  The infant has significant respiratory distress due to pleural effusions and ascites and dies soon after birth.  Autopsy shows areas of extramedullary hematopoiesis in many tissues.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_37cf_f727_9249_ffb32efbc21c_MD0001_00 Hemolytic disease of the newborn (erythroblastosis fetalis) results from the destruction of fetal red blood cells by maternal antibodies directed against fetal erythrocyte antigens. These antibodies are IgG antibodies, the only class of antibody able to cross the placenta. Erythroblastosis fetalis is most commonly caused by Rhesus (Rh) incompatibility (particularly the D antigen). Rh sensitization can occur in an Rh(D)− mother during pregnancy with an Rh(D)+ fetus due to small amounts of fetal blood crossing the placenta and entering the maternal circulation. These erythrocytes are viewed as foreign by the maternal immune system and induce the production of anti-Rh(D) IgG antibodies. In subsequent pregnancies with an Rh(D)+ fetus, these antibodies cross the placenta and opsonize fetal erythrocytes, causing hemolysis. This results in a positive direct Coombs test (indicating autoimmune hemolysis), profound anemia, jaundice (possibly leading to kernicterus), and generalized edema (hydrops fetalis due to accumulation of interstitial fluid). The severe anemia also stimulates release of immature, nucleated erythrocytes and leads to persistent extramedullary hematopoiesis in the liver, spleen, and other tissues (hepatosplenomegaly). (Choice A) Sickle cell anemia causes vasoocclusion due to abnormal hemoglobin polymerization. It is asymptomatic in the fetus/neonate due to high levels of fetal hemoglobin that are not replaced by hemoglobin S until age 3-12 months. (Choice B) Fetuses with homozygous alpha-thalassemia (hemoglobin Barts) have no alpha globin chains and therefore form gamma-4 tetramers with very high oxygen affinity. The consequence is severe functional anemia and tissue hypoxia, which results in high-output heart failure and nonimmune hydrops fetalis (negative Coombs test). (Choice D) Glucose-6-phosphate dehydrogenase deficiency can cause prolonged neonatal jaundice (beyond 2 weeks) due to increased erythrocyte breakdown and immaturity of the newborn liver. However, the associated anemia is rarely severe. (Choice E) Infants are born with an immature immune system; their humoral defense during the first 6 months of life comes primarily from maternal circulating IgG that is received transplacentally prior to birth and from mucosal IgA received via breastfeeding. Therefore, fetal antibody-mediated red blood cell lysis is an unlikely etiology. Educational objective: Hemolytic disease of the newborn most commonly occurs from maternal sensitization to Rh antigens during a prior pregnancy with an Rh(D)+ fetus. In subsequent Rh(D)+ pregnancies, maternal anti-Rh(D) IgG antibodies cross the placenta and cause a severe autoimmune hemolytic anemia in the fetus and life-threatening hydrops fetalis. __________ References: Hemolytic disease of the fetus and newborn: managing the mother, fetus, and newborn. (http://www.ncbi.nlm.nih.gov/pubmed/26637714) Etiology of non-immune hydrops fetalis: An update. (http://www.ncbi.nlm.nih.gov/pubmed/25712632)

A Newborn Girl Is Admitted to the Neonatal Intensive Care