What is the role of Rhesus (Rh) typing in hemolytic disease of the fetus and newborn assessment?

Updated: Aug 01, 2018
  • Author: Victoria K Gonsorcik, DO; Chief Editor: Jun Teruya, MD, DSc, FCAP  more...
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Evaluation of hemolytic disease of the fetus and newborn (HDFN) that is associated with Rh incompatibility involves multiple steps. HDFN occurs when a fetus has antigens on his or her red cells that the mother's immune system does not recognize as her own (usually an Rh-negative woman carrying an Rh-positive fetus). A small percentage of fetal blood may come into direct contact with the maternal blood circulation through fetal maternal hemorrhage (eg, amniocentesis, trauma, miscarriage/abortion, or placental abnormalities).

Certain antigens on fetal blood cells, like those of the Rh system, are more fully developed and are present in greater numbers than others. This allows the mother's immune system to easily recognize them and produce antibodies that may cause hemolysis. Anti-Rh antibodies are mainly immunoglobulin (Ig) G. The mother's IgG antibodies, because of their smaller structures, are able to cross the placenta and attack fetal red blood cells carrying the Rh antigens, causing fetal hemolysis. Once the mother's Rh antibody is identified, titers and a score are used to assess the amount of antibody present in the mother's plasma and to evaluate its strength/avidity. Clinicians then use this information to predict the risk of fetal hemolysis.

Titers and scores are performed in a blood bank reference laboratory. A sample of the mother's blood is centrifuged to separate her plasma (which contains the antibody) from her red blood cells. The plasma is then serially diluted and combined with reagent Rh-antigen–positive red cells. Agglutination or lack of agglutination is visually assessed. A score is then determined based on the strength of agglutination associated with each dilution.

In order to prevent HDFN arising from an Rh-negative mother in the first place, several steps can be taken. In the United States, when fetal Rh(D) status is unknown, Rh-negative pregnant women are given a form of Rh(D) immunoglobulin (ie, RhoGam or WinRho) at approximately 28 weeks’ gestation. Additional doses are administered after any procedures and at the time of delivery. Clinicians can also use amniocentesis samples to verify fetal Rh(D) status to predict current or future risk for HDFN due to Rh(D) incompatibility.

A less-invasive molecular genotyping procedure has been tested and used in portions of Europe. Throughout pregnancy, particularly during the second and third trimesters, fetal DNA is present in the pregnant woman's plasma. A blood sample from the pregnant woman is taken and separated via centrifugation. If the fetus is Rh-positive, the fetal RH DNA can be amplified and detected by polymerase chain reaction (PCR). The genotyping results assist in determining the fetal Rh(D) status. If the fetus is deemed Rh-negative, the pregnant woman may not need to receive the Rh(D) immunoglobulin to prevent antibody formation.

In a review of the literature from European centers that implemented large-scale nationwide noninvastive fetal RHD typing in the second trimester for targeted Rh(D) immunoglobulin administration, investigators found that depending on patients' ethnic backgrounds and the medical institution, fetal RHD typing using a duplex real-time PCR can safely and cost-effectively guide the administration of Rh(D) immunoglobulin to prevent D-alloimmunization during pregnancy. [11]  They calculated the unnecessary administration of 40% of antenatal Rh(D) immunoglobulin could be avoided, and cord blood serology could be omitted.

This molecular testing has undergone review in the United States. If implemented, there will not only be a decrease of more invasive techniques but also a decrease of unnecessary exposure to Rh(D) immunoglobulin. [9]

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