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Alloimmunization and Hemolytic Disease—What Are Infant Outcomes?

May 24, 2024

In an article entitled, “Neonatal and Obstetrical Outcomes of Pregnancies Complicated by Alloimmunization,” which is being early released this week in Pediatrics, Dr. Timothy M. Bahr and colleagues from the University of Utah, Intermountain Health in Salt Lake City, and the University of Arizona present a retrospective review, focused on fetal and neonatal outcomes of all births, January 1, 2017–December 30, 2022, to mothers who had a positive red blood cell antibody screen (alloimmunization) during pregnancy (10.1542/peds.2023-064604).

The authors aimed to:

  • Calculate the frequency of alloimmunization among pregnant persons in their health system,
  • Describe the relative frequency of each antibody type detected, and
  • Summarize the prenatal and postnatal outcomes of those pregnancies with respect to antibody type and titer and clinical features.

By reviewing both maternal and infant charts, the authors were able to present a complete picture of an otherwise complex clinical situation.

Of the 233,227 neonates delivered in the health system’s 21 hospitals, 707 infants were born after a positive maternal antibody screen:

  • For 31 infants, the positive screen was due only to maternal receipt of Rhesus* immune globulin (RhIG).
  • Of the rest, 466 infants had a direct antigen test (DAT), and 174 (37%) DATs were positive, and
  • Antigen-positivity best predicted anemia and hyperbilirubinemia in the infant, but
  • Neonatal hemolytic disease was most severe with DAT positive anti-Rh antibodies (c, C, D, e, E).
  • No neonatal red blood cell transfusions or exchange transfusions occurred in infants born to mothers with anti-M, anti-S, anti-Duffy, anti-Kidd A, or anti-Lewis.

Thus, amazingly, even with the introduction of RhIG in 1968, which (when administered during pregnancy to Rh(D) negative unsensitized women who are likely carrying an Rh(D) positive fetus) permits prevention of Rh alloimmunization, Rh group antibodies still caused a majority of the severe neonatal hemolytic disease in this large series.

One additional take-home point the authors emphasize is that their study supports the AAP recommendation to obtain a DAT for all infants whose mothers had a positive or unknown pregnancy antibody screen. Given the risk conferred by positivity, this information is key for neonatal clinicians.

There is so much more information tucked into this excellent study that it’s hard to stop the blog right here. Enjoy!

*For context, I had to remind myself about the origins of “Rhesus”—in 1939 a mother delivered a stillborn due to non-ABO alloimmunization. After the stillborn birth, she was given a needed transfusion from her husband, and had a hemolytic transfusion reaction after exposure to the same paternal antigen as had affected the infant; this was mistakenly likened to antibodies produced in various animals' serum in response to red blood cells from the Rhesus monkey. The new antigen was ultimately abbreviated from Rhesus to Rh blood group! For more background information on Rh Blood Groups, read in the National Library of Medicine here.

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