Final answer:
Hemolytic disease of the newborn is most likely to occur in an Rh-negative mother with an Rh-positive fetus, especially during or after a second pregnancy with an Rh-positive child due to the mother's immune system producing antibodies against the fetus's Rh-positive red blood cells.
Step-by-step explanation:
Hemolytic disease of the newborn (HDN), also known as erythroblastosis fetalis, can occur when there is an incompatibility between the blood types of the mother and the fetus concerning the Rh factor. A Rh-negative mother with an Rh-positive fetus is at risk for developing HDN, particularly in the circumstance that the mother has been previously sensitized to the Rh-positive antigen. This sensitization typically occurs when a Rh-negative woman carries an Rh-positive fetus in a previous pregnancy; she may generate antibodies that can cross the placenta in subsequent pregnancies and attack the red blood cells of a Rh-positive fetus, causing anemia and other complications.
In the first pregnancy, an Rh-negative mother's exposure to Rh-positive red blood cells may not lead to significant problems because it takes time for her to produce antibodies. However, upon a second exposure with a subsequent Rh-positive pregnancy, the already formed antibodies readily cross the placenta and cause hemolysis in the fetal blood. To prevent this, women identified as Rh-negative are given Rho(D) immune globulin injections during pregnancy to stop the formation of anti-Rh antibodies.