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HDFN Diagnosis and Management

Maternal testing done routinely as part of perinatal testing programs vary from country to country and within countries. Recommended tests generally include:
  • ABO, Rh*, and antibody screen at first prenatal visit;
  • Test for weak D, if initial Rh typing appears to be D-negative (Optional -not mandated by blood safety standards). If weak-D testing is performed, antihuman globulin reagents that do not contain anti-complement activity would be recommended in order to avoid agglutination due to complement coating of maternal cells.
  • D-negative females: Tested again (ABO, Rh, and antibody screen) at ~ 28 weeks gestation prior to administration of RhIg (depending on the country) and again at delivery.
  • Antibody identification upon initial detection
  • Titration of anti-D at initial detection; repeated at 18-20 weeks and periodically thereafter.
    Other antibodies: Per institutional protocol.

*The mother, putative father, and fetus can be typed for D using DNA methods, if available.

Policies for typing fathers vary widely and usually testing is not done unless the mother develops anti-D or another clinically significant antibody. If a clinically significant antibody is identified, it is helpful to perform molecular testing on the father to determine if he has the corresponding antigen and, if so, whether he is homozygous or heterozygous. If the father is homozygous, the fetus will be positive for the antigen and at risk for HDFN. If the father is heterozygous, the fetal blood can be tested by PCR to determine genotype status. Test samples can be collected by amniocentesis, chorionic villus sampling, or cordocentesis. Molecular typing of the fetus can also be done on maternal blood later in the pregnancy.