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

Abstract

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.

Secretor status of blood group O mothers is associated with development of ABO haemolytic disease in the newborn

“…The secretor genotype ( FUT2 ) was determined for blood group O mothers to newborns with or without haemolysis. The median semi‐quantitative level of anti‐A and anti‐B IgG1, 2, 3 subclasses and the total IgG titre, determined in earlier studies, were included for comparison [2, 6]. We found evidence that the maternal secretor status was significantly associated with haemolysis in the newborn induced by ABO IgG antibodies.…”

“…The maternal secretor status was determined by genotyping a single nucleotide polymorphism (SNP) in FUT2 , rs601338 (c.428G>A), using KASP chemistry as previously described [6].…”

“…In a previous study, we determined semi‐quantitatively the level of maternal IgG1, 2, 3 anti‐A and anti‐B using a flowcytometric method and included the data in the present study [6].…”

“…We have previously reported an association between the frequency of the foetal secretor allele and newborn haemolysis [6]. Since this association was found only at the allele level and not with the phenotype, we hypothesized that the association might reflect an effect exerted by the maternal secretor status [6].…”

“…We have previously reported an association between the frequency of the foetal secretor allele and newborn haemolysis [6]. Since this association was found only at the allele level and not with the phenotype, we hypothesized that the association might reflect an effect exerted by the maternal secretor status [6]. Furthermore, a previous study found an effect of secretor status on the level of anti‐B, where the level was found considerably lower in non‐secretors than in secretors [5].…”