Abstract
Background
Hemolysis in fetus/newborns is often caused by maternal antibodies. There are currently no established screening procedures for maternal ABO antibodies harmful to fetus/newborn. We investigated the clinical significance, and predictive value of maternal anti-A/B titer for hyperbilirubinemia in ABO-incompatible newborns.
Methods
We conducted a case–control study of blood group O mothers and their ABO-compatible (O) vs. -incompatible (A/B) newborns receiving phototherapy, and of ABO-incompatible newborns receiving phototherapy vs. no phototherapy. Newborn data and treatment modalities were recorded, and total serum bilirubin and hemoglobin were measured. Maternal anti-A/B immunoglobulin-γ (IgG) titers were measured prenatally and perinatally, and negative and positive predictive values (NPV, PPV) were calculated to assess the risk of developing hyperbilirubinemia requiring phototherapy.
Results
We found a significantly higher maternal IgG antibody titer in the case group (p < 0.001). Maternal anti-A/B titers at first trimester had modest predictive values: NPV = 0.82 and PPV = 0.65 for neonatal hyperbilirubinemia; titers at birth improved the predictive values: NPV = 0.93 and PPV = 0.73. Newborn hemoglobin was significantly lower in incompatibles compared to compatibles (p = 0.034). Furthermore, increased anti-A/B IgG production during pregnancy was associated with hyperbilirubinemia and hemolysis in incompatible newborns.
Conclusions
There was a significant association between maternal anti-A/B IgG titer and hyperbilirubinemia requiring treatment.
Impact
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Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn.
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Increased IgG anti-A/B production throughout pregnancy in mothers to ABO-incompatible newborns developing hyperbilirubinemia contrasts a constant or reduced production in mothers to newborns not developing hyperbilirubinemia.
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Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B.
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Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.
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Acknowledgements
We thank laboratory technologists at the Serology Laboratory at the Department of Clinical Immunology, Rigshospitalet. We also thank the staff, social, and health care assistants, as well as midwives and nurses, at the maternity ward and the obstetric department at both Aalborg and Copenhagen University Hospital. Special thanks to the leading laboratory scientist, Jane Vad, for her invaluable help with blood grouping of newborns and handling of samples from Aalborg University Hospital. We would also like to thank the nurses and doctors at the including departments at Rigshospitalet, Herlev Hospital, Hvidovre Hospital, Nordsjællands Hospital, and Aalborg University Hospital for their help with the recruitment of patients.
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G.R.K. conceptualized and designed the study, collected the data, performed the statistical analyses, drafted the initial manuscript, and reviewed and revised the manuscript. M.L.D. conceptualized and designed the study, included patients, reviewed thoroughly the statistical analyses and clinical aspect, and revised the manuscript. B.M.H. conceptualized and designed the study, included patients, reviewed thoroughly the clinical aspect, and revised the manuscript. H.L. designed tables, reviewed thoroughly the statistical analyses, and reviewed and revised the manuscript. K.V.J., A.K.-T., P.A., and T.B. included patients, and reviewed and revised the manuscript. F.B.C., F.E., M.K.S., and M.H.D. conceptualized and designed the study, and reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work. This work was supported by grants from Rigshospitalet’s and dbio’s Research Foundations.
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Krog, G.R., Donneborg, M.L., Hansen, B.M. et al. Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer. Pediatr Res 90, 74–81 (2021). https://doi.org/10.1038/s41390-020-01232-5
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DOI: https://doi.org/10.1038/s41390-020-01232-5
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