Which maternal condition is most strongly associated with hemolytic disease of the fetus and newborn due to red blood cell incompatibility?

• A. ABO incompatibility
• B. Rh incompatibility
• C. Rh positive mother
• D. Fetal metabolic disorder

Answer: (B)

The central relationship is Rh(D) incompatibility between an Rh-negative mother and an Rh-positive fetus. When the mother becomes sensitized to the D antigen, she forms IgG anti-D antibodies that cross the placenta and bind fetal red cells, causing their destruction. This antibody-mediated hemolysis is what drives hemolytic disease of the fetus and newborn in these cases, and the risk is especially high in subsequent pregnancies with an Rh-positive fetus. ABO incompatibility can cause HDFN too, but it tends to be milder and can occur in a first pregnancy, whereas Rh incompatibility is the strongest, classic association. An Rh-positive mother cannot produce anti-D against its own RBCs, and fetal metabolic disorders do not cause this antibody-mediated hemolysis.