ABO haemolytic disease of the newborn: Improved prediction by novel integration of causative and protective factors in newborn and mother

Grethe Risum Krog*, Henriette Lorenzen, Frederik Banch Clausen, Anne Todsen Hansen, Mette Line Donneborg, Morten Hanefeld Dziegiel

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

4 Citations (Scopus)


Background and Objectives: Prediction of haemolytic disease of the foetus and newborn (HDFN) caused by maternal anti-A/-B enables timely therapy, thereby preventing the development of kernicterus spectrum disorder. However, previous efforts to establish accurate prediction methods have been only modestly successful. Materials and Methods: In a case–control study, we examined 76 samples from mothers and 76 samples from their newborns; 38 with and 38 without haemolysis. The IgG subclass profile of maternal anti-A and anti-B was determined by flow cytometry. Samples from newborns were genetically analysed for the A2 subgroup, secretor and FcγRIIa receptor alleles. Results: Surprisingly, we found a correlation between the newborn secretor allele and haemolysis (p = 0.034). No correlation was found for FcγRIIa alleles. The A2 subgroup was found only in newborns without haemolysis. Unexpectedly, different reaction patterns were found for maternal anti-A and anti-B; consequently, the results were treated separately. For the prediction of haemolysis in A-newborns, the maternal IgG1 subclass determination resulted in an accuracy of 83% at birth. For B-newborns, an accuracy of 91% was achieved by the maternal IgG2 subclass determination. Conclusion: We improved the prediction of ABO-HDFN by characterizing maternal anti-A and anti-B by flow cytometry and we presented genetic traits in newborns with correlation to haemolysis. We propose a new understanding of A- and B-substances as immunogens that enhance the maternal immune response and protect the newborn, and we suggest that the development of ABO-HDFN is different when caused by maternal anti-A compared to maternal anti-B.

Original languageEnglish
JournalVox Sanguinis
Issue number3
Pages (from-to)415-423
Number of pages9
Publication statusPublished - Mar 2022

Bibliographical note

Publisher Copyright:
© 2021 International Society of Blood Transfusion


  • blood groups
  • genotyping
  • haemolytic disease of the foetus and newborn
  • RBC antigens and antibodies
  • serological testing


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