Learn The BasicsHemolytic disease of the fetus and newborn (HDFN) is caused by a mismatch between the blood of a pregnant mother and her fetus. It occurs when the mother’s blood and the baby’s blood mix and the mother’s body makes antibodies against factors in the blood of the baby. The mixing can happen at birth, when the placenta breaks away, during a miscarriage or during prenatal testing.
Blood types and Rh factors
Mismatches that cause HDFN can be between the blood types (A, B and O) and/or Rhesus (Rh) factors, a protein that can be found on the surface of red blood cells.
ABO incompatibility
ABO incompatibility occurs when the blood type of the mother and that of the baby do not match. It is usually less severe than Rh incompatibility.
Most commonly, a mother who has the O blood type also has antibodies against A or B blood types. If the baby has the A, B or AB blood type, the anti-A and/or anti-B antibodies from the mother can attack the blood cells of the fetus. The anti-A and anti-B antibodies are immunoglobulin G (IgG) and can cross the placenta, affecting the developing fetus.
Rh incompatibility
Incompatibility in Rh factors between the mother and the baby, also called Rh disease, is more common and usually requires more monitoring.
There are many Rh antigens, or a substance that is capable of stimulating an immune response. Rh incompatibility is most commonly triggered by the Rh-D antigen. Other antigens that may also be problematic include the c, C, E and e antigens.
Other types of incompatibility
In rare cases, antibodies against antigens of the Kell blood group such as anti-K and anti-k, Kidd blood group such as anti-Jka and anti-Jkb and Duffy blood group such as anti-Fya can cause HDFN. MNS and s blood group antibodies can cause HDFN.
An increased risk in second pregnancies
Normally, the blood of the mother and the baby do not mix during pregnancy. However, the baby’s red blood cells cross to the mother’s body when the placenta detaches at delivery. This can also happen in cases of miscarriage, abortion or prenatal testing. The entry of fetal blood into the circulation of the mother is called fetomaternal hemorrhage.
At that moment, the mother’s body starts producing antibodies against the Rh-positive red blood cells of the baby and keeps these antibodies in case the “foreign” cells are encountered again. This is called Rh sensitization. The next time the mother becomes pregnant with an Rh-positive baby, her immune system can quickly produce IgG antibodies against the Rh antigen, which can cross the placenta and attack the red blood cells of the developing fetus, destroying them.
HDFN risk factors
The Rh-negative blood type is more common among certain races and ethnicities than others. It is most common in white populations–among white women, a woman who is Rh-negative has an 85% chance of mating with an Rh-positive man, increasing the risk of HDFN.
HDFN occurs in around 15% of white populations, compared to 5% to 8% of African-American populations and 1% to 2% of Asian and Native American populations.
Reviewed by Hasan Avcu, M.D., on September 26, 2023
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