Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer

Krog, Grethe Risum; Donneborg, Mette Line; Hansen, Bo Moelholm; Lorenzen, Henriette; Clausen, Frederik Banch; Jensen, Kristian V.; Kjærbye‐Thygesen, Anette; Albertsen, Per; Ebbesen, Finn; Bergholt, Thomas; Smed, Mette Kiel; Dziegiel, Morten Hanefeld

doi:10.1038/s41390-020-01232-5

Cited by 11 publications

(26 citation statements)

References 22 publications

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“…This study is a further investigation of a previously published case–control study, and details of inclusion criteria of the subjects are given there [6]. Briefly, blood group O‐mothers and their incompatible newborns (group A or B) born gestational age ≥ 35 weeks were eligible for the study.…”

Section: Methodsmentioning

confidence: 99%

“…The maternal anti‐A/‐B IgG titre is predictive of the risk of developing severe hyperbilirubinaemia, however, with a modest accuracy of 73%–80% [4, 5]. We have previously reported an association measured by two different methods: the solid phase red cell adherence assay (SPRCA) with an accuracy of 80% and the column agglutination technology method with an accuracy of 79% [6].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2021

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“…Maternal anti-A and anti-B IgG titers are predictive of neonatal requirement for treatment of hyperbilirubinemia [47,48]. However, we found the positive predictive values both in the 1st trimester (65%) and perinatally (73-76%) to be too low to be used clinically for routine screening and we aim for enhancement of predictive values [49] by on-going research.…”

Section: Maternal Abo Antibodiesmentioning

confidence: 96%

“…In pregnancies with identified maternal high-titer IgG anti-A and anti-B or a history of a previous pregnancy where maternal anti-A/B was responsible for HDFN, the anti-A and anti-B IgG titer is determined in the 1st trimester as well as at GA 32 weeks. For the methods described a common cut-off value of 512 was initially found for anti-A/B [49]. However, additional studies (in preparation) showed that distinct cut-off values for anti-A and anti-B increased accuracy.…”

Section: Laboratory Monitoring Anti-a and Anti-bmentioning

confidence: 99%

Laboratory Monitoring of Mother, Fetus, and Newborn in Hemolytic Disease of Fetus and Newborn

Dziegiel¹,

Krog²,

Hansen³

et al. 2021

Transfus Med Hemother

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Background: Laboratory monitoring of mother, fetus, and newborn in hemolytic disease of fetus and newborn (HDFN) aims to guide clinicians and the immunized women to focus on the most serious problems of alloimmunization and thus minimize the consequences of HDFN in general and of anti-D in particular. Here, we present the current approach of laboratory screening and testing for prevention and monitoring of HDFN at the Copenhagen University Hospital in Denmark. Summary: All pregnant women are typed and screened in the 1st trimester. This serves to identify the RhD-negative pregnant women who at gestational age (GA) of 25 weeks are offered a second screen test and a non-invasive fetal RhD prediction. At GA 29 weeks, and again after delivery, non-immunized RhD-negative women carrying an RhD-positive fetus are offered Rh immunoglobulin. If the 1st trimester screen reveals an alloantibody, antenatal investigation is initiated. This also includes RhD-positive women with alloantibodies. Specificity and titer are determined, the fetal phenotype is predicted by non-invasive genotyping based on cell-free DNA (RhD, K, Rhc, RhC, RhE, ABO), and serial monitoring of titer commences. Based on titers and specificity, monitoring with serial peak systolic velocity measurements in the fetal middle cerebral artery to detect anemia will take place. Intrauterine transfusion is given when fetal anemia is suspected. Monitoring of the newborn by titer and survival of fetal red blood cells by flow cytometry will help predict the length of the recovery of the newborn.

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“…Light emission within a wavelength range of 460-490 nm in the bluegreen range, maximum exposure to the infant's body, and adequate irradiance all contribute to this modality of treatment. 29,31,32 Hyperbilirubinemia caused by HDN is mostly treated with phototherapy and, on rare occasions, exchange transfusion. In a 2004 research by pediatricians (AAP), recommendations were made that HDN was possible for children with the following birth weights: 2000g, 2000 to 2499 g, and bilirubin level > 171 umol/L (10 mg/ dL), 2500 g, and 222 umol/L (13 mg/dL) respectively.…”

mentioning

confidence: 99%

Hemolytic Disease of the Newborn: A Review of Current Trends and Prospects

Myle¹,

Al-Khattabi

2021

PHMT

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Hemolytic disease of the newborn (HDN), also known as Erythroblastosis fetalis, is a hemolytic condition that predominantly affects rhesus-positive fetuses and infants born to rhesus-negative mothers. The pathophysiology of HDN begins with maternal antibodies attacking fetal red blood cells following alloimmunization due to rhesus or ABO incompatibility between the maternal and fetal blood. Previously, HDN was known to cause fetal death in 1% of all pregnancies, but with the advent of immunoprophylactic therapies, the condition can be currently fairly well managed with fewer complications if diagnosed early. Diagnosis calls for extensive history taking, physical examination, serological studies, and imaging modalities such as pelvic ultrasound scans. To prevent the disease, earlier intravenous immunoglobulin (IVIG) should be given to pregnant Rh-women who have not been sensitized. It is also vital to understand prospective complications such as severe hyperbilirubinemia and develop appropriate remedies. Because of its great incidence and nature, HDN has been thoroughly explored, and more studies are being conducted each year, revealing new insights about the condition. This review covers the disorder's etiology, diagnosis, and management, including the most current findings as of 2021, as well as trends and prospects, to help in future research and evidence-based medical practice.

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Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer

Cited by 11 publications

References 22 publications

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

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

Laboratory Monitoring of Mother, Fetus, and Newborn in Hemolytic Disease of Fetus and Newborn

Hemolytic Disease of the Newborn: A Review of Current Trends and Prospects

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