Transfer of nutrients, proteins, and antibodies between the mother and fetus generally occurs across the placenta without direct transfer of blood. Although the maternal and fetal blood supplies are separated from each other, they are, of necessity, in relative proximity and can, under certain circumstances, come into contact with each other. Under these circumstances, exposure to foreign proteins may elicit an immune response with potential health effects for either the mother or fetus.

Rh isoimmunization represents a serious maternal–fetal complication. All red blood cells are produced with a variety of surface antibodies that serve to identify one’s own red cells from those of others. The presence of red blood cells from an outside source will elicit an immune response with subsequent hemolysis/removal of the foreign cells. This response may be relatively minor or may represent a significant medical complication.

The primary surface proteins serve to identify blood within the ABO blood type categories. Exposure to immunologically incompatible blood types within the ABO category will result in significant hematological complications. A second set of proteins (rhesus factor) also provide significant identification. Rh-negative ([Rh−] those without Rh factor) patients exposed to blood containing Rh factor (Rh positive [Rh+]) will produce an antibody response to that blood. It is this incompatibility that results in the complications of Rh isoimmunization. An initial exposure will lead to development of antibodies. Subsequent exposures will yield a significant antibody response and an associated reaction.

Pregnant Rh-negative patients exposed to fetal Rh-positive blood may also develop such an antibody response (approximately 20 % will isoimmunize if not treated). Because such antibodies can cross the placenta and reach the fetus, all subsequent pregnancies that involve Rh-positive fetuses will potentially result in hemolysis and in complications for the fetus.

Rh factor is a genetically inherited trait with an autosomal-dominant inheritance pattern. An Rh-negative mother is, by definition, homozygous (Rh−/Rh−). An Rh-positive father may be homozygous (Rh+/Rh+) or heterozygous (Rh+/Rh−). As all children will receive one Rh-negative gene from such mothers, the Rh status of the child is dependent on the Rh status of the father. All children of homozygous Rh-positive fathers will be Rh positive. One-half of all children of heterozygous fathers will be Rh positive.