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How do Rh-negative mothers become sensitized to Rh-positive fetal blood?

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Close-up illustration of multiple human red blood cells with their characteristic disc shape, floating against a red background. — blood group The major component of human blood is the red blood cell.

An Rh-negative mother becomes sensitized to Rh-positive fetal blood when fetal red blood cells, which carry the Rh factor (an antigen), cross the placental barrier and enter her bloodstream.1

This exposure typically occurs during labour, when a small amount of fetal blood enters the maternal circulation. Once these foreign antigens are detected, the mother’s immune system responds by producing anti-Rh antibodies. While this initial sensitization rarely affects the first pregnancy, these antibodies remain in the mother's system and can cross the placenta during subsequent pregnancies, attacking the red blood cells of an Rh-positive fetus and causing erythroblastosis fetalis.123

To prevent this, medical professionals administer Rh immunoglobulin (such as Rho-GAM) to the mother. This treatment effectively destroys any fetal red blood cells in the mother's bloodstream before her immune system can be stimulated to produce its own antibodies, thereby protecting future pregnancies.1432