If Rh immune globulin (RhIG) is not administered to Rh-negative mothers, HDFN due to anti-D typically develops as follows:
In the first pregnancy, Rh positive fetal red cells enter the maternal circulation during the pregnancy and/or at delivery. The mother has a 1o immune response in which mainly IgM antibody are produced, with lower levels of IgG anti-D produced. Thus the first infant is rarely affected because:
- Larger fetal bleeds occur at delivery and these are more likely to cause antibody production than smaller antenatal bleeds.
- Antibody is produced slowly and is mostly IgM.
In the second pregnancy, if the fetus is again D-positive, when fetal cells enter the mother, they cause a 2o immune response in which higher levels of IgG anti-D are produced. Depending on the antibody titer, the second child may suffer mild to severe HDN.
If a third or fourth pregnancy results in D-positive infants, these infants (by also bleeding into the mother) cause the production of even higher titers of IgG anti-D and offspring will be more severely affected, perhaps dying in utero or soon after birth.