Cause

Rh sensitization can occur when a person with Rh-negative blood is exposed to Rh-positive blood. About 90% of women who become sensitized do so during childbirth, when their blood mixes with the Rh-positive blood of their fetus.¹ After being exposed, a mother's immune system produces antibodies against Rh-positive red blood cells. For more information about events and procedures that can put you at high risk for Rh sensitization, see the What Increases Your Risk section of this topic.

The minimum amount of blood mixing that causes sensitization is not known. But many women become sensitized during pregnancy or childbirth after being exposed to as little as 0.1 mL of Rh-positive fetal blood.¹ Fortunately, Rh sensitization can almost always be prevented with the Rh immune globulin injection.

When an Rh-negative person's immune system is first exposed to Rh-positive blood, it takes several weeks to develop immunoglobulin M, or IgM, antibodies. IgM antibodies are too large to cross the placenta. So the Rh-positive fetus that first triggers maternal sensitization is usually not harmed.

A previously Rh-sensitized immune system rapidly reacts to Rh-positive blood, as during a second pregnancy with an Rh-positive fetus. Usually within hours of Rh-positive blood exposure, smaller immunoglobulin G, or IgG, antibodies are formed. IgG antibodies can cross the placenta and destroy fetal red blood cells. This causes Rh disease, which is dangerous for the fetus.

Some Rh-negative people never become sensitized, even after exposure to large amounts of Rh-positive blood. The reason for this is not known.