hemolytic disease of the newborn

HDN occurs when an Rh-negative mother is sensitized to Rh-positive fetal blood (typically during a prior pregnancy, delivery, miscarriage, or abortion), leading to production of maternal IgG anti-D antibodies. Unlike IgM, IgG can cross the placenta. In subsequent pregnancies with an Rh-positive fetus, these antibodies attack fetal RBCs, causing extravascular hemolysis in the fetal spleen. This results in fetal anemia, compensatory extramedullary hematopoiesis (hepatosplenomegaly), and in severe cases, high-output cardiac failure leading to hydrops fetalis (generalized edema, effusions, ascites). After birth, continued hemolysis causes unconjugated hyperbilirubinemia; because the neonatal liver is relatively immature in bilirubin conjugation, there is risk of kernicterus (bilirubin deposition in basal ganglia causing irreversible neurologic damage).

ABO incompatibility (mother type O, fetus type A or B) can also cause a milder form of HDN, often in the first pregnancy, due to naturally occurring IgG anti-A/anti-B antibodies, but usually results in a less severe clinical picture.

Diagnosis involves the indirect Coombs test (detects maternal antibodies) and direct Coombs test (detects antibody-coated fetal/neonatal RBCs). Management includes intrauterine transfusions for severe fetal anemia, phototherapy, and exchange transfusion for neonatal hyperbilirubinemia.

Prevention is key: Rh-negative mothers receive anti-D immunoglobulin (RhoGAM) at 28 weeks gestation and within 72 hours postpartum (if the infant is Rh-positive), as well as after any sensitizing event (e.g., miscarriage, amniocentesis, trauma). RhoGAM works by binding fetal Rh-positive RBCs that enter maternal circulation, preventing maternal immune recognition and sensitization.