Rh isoimmunization typically occurs during delivery or bleeding events because this is when fetal Rh-positive red blood cells can enter the maternal circulation. The maternal immune system then recognizes these cells as foreign and produces antibodies against the Rh antigen. This sensitization usually does not occur during early pregnancy, unless there is a bleeding episode. Once sensitized, these antibodies can cross the placenta in subsequent pregnancies, risking hemolytic disease of the fetus/newborn. Therefore, the timing of exposure to Rh-positive fetal blood is critical for isoimmunization.

Reference: Williams Obstetrics, Cunningham et al., 25th Edition.