Alloimmunization Part II: Management

What to do with a positive antibody screen?

• First, obtain a antibody titer: a value of dilution at which the antibody screen remains positive.

  • So a 1:32 titer is more significant than a 1:4 titer.

  • A critical titer is one that carries risk for hydrops, which is generally between 1:8 - 1:32, depending on the lab.

    • Additionally, a change in titer of more than one dilution is considered significant. 

  • For titers less than 1:8, titers should be obtained every 4 weeks to reassess.

    • Exception: anti-Kell antibodies, as these titers do not correlate with fetal status. 

• Assess paternal genotype.

  • If the infant can’t get the antigen that the mother is sensitized to (i.e., dad has no Kell antigen for mom’s anti-Kell antibodies to attack), then there’s no need for assessment.

  • If the father does carry an offending antigen, DNA testing can be utilized to determine if the father is heterozygous or homozygous. 

• Assess fetal DNA.

  • Can be employed when paternal status is unknown, or carries risk.

  • Amniocentesis is the gold-standard methodology for fetal blood typing; CVS can also be employed, but carries a higher risk of de novo alloimmunization than amniocentesis.

  • Rh (D) antigen carriage can also be determined by cell free fetal DNA assays.

Monitoring the Alloimmunized Pregnancy

• Historically: serial amniocentesis

  • The concentration of bilirubin in amniotic fluid is assessed by spectral analysis through 450 nm light (OD450)

• Currently: middle cerebral artery (MCA) Doppler ultrasonography

  • Studies have correlated the relationship between peak systolic velocity 1.5 times the median for gestational age with moderate-to-severe fetal anemia, with 100% sensitivity.

    • However, this monitoring should be done by those with experience in the technique, as even with good technique the false positive rate approaches 12%.

• For minor blood group antigen sensitization, protocols may be different.

  • Anti-Kell in particular has a less predictable course and often results in more severe fetal anemia than alloimmunization due to other blood antigens. 

• If severe anemia is suspected, periumbilical cord blood sampling (PUBS, aka cordocentesis) can be used to measure the fetal hemoglobin directly.

  • An intrauterine transfusion (IUT) can be performed to transfuse the fetus as well. 

Interventions and delivery

• Delivery timing is controversial:

  • ACOG recommends if only mild hemolysis is suspected, induction can be considered at 37-38 weeks.

  • With more severely sensitized pregnancies, the risk of repeated cord blood sampling and intrauterine transfusion has to be compared to that of early delivery, and this is often dependent on the center and their experience.