Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years

Matteocci, Antonella; Rosa, Aline de Souza; Buffone, Elsa; Pierelli, Luca

doi:10.1111/tme.12512

Cited by 25 publications

(26 citation statements)

References 14 publications

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“…ABO blood group-caused hemolytic disease of the fetus and newborn (HDFN) is very frequent but only rarely severe [1][2][3][4][5][6][7][8][9]. The ABO blood group system is the only system in which natural IgM antibodies against the corresponding antigens are universally present from a young age, at approximately 4 months.…”

Section: Introductionmentioning

confidence: 99%

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Rieneck

Hother

Clausen

et al. 2020

Transfus Med Hemother

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Introduction: ABO blood group incompatibility between a pregnant woman and her fetus as a cause of morbidity or mortality of the fetus or newborn remains an important, albeit rare, risk. When a pregnant woman has a high level of anti-A or anti-B IgG antibodies, the child may be at risk for hemolytic disease of the fetus and newborn (HDFN). Performing a direct prenatal determination of the fetal ABO blood group can provide valuable clinical information. Objective: Here, we report a next generation sequencing (NGS)based assay for predicting the prenatal ABO blood group. Materials and Methods: A total of 26 plasma samples from 26 pregnant women were tested from gestational weeks 12 to 35. Of these samples, 20 were clinical samples and 6 were test samples. Extracted cell-free DNA was PCR-amplified using 2 primer sets followed by NGS. NGS data were analyzed by 2 different methods, FASTQ analysis and a grep search, to ensure robust results. The fetal ABO prediction was compared with the known serological infant ABO type, which was available for 19 samples. Results: There was concordance for 19 of 19 predictable samples where the phenotype information was available and when the analysis was done by the 2 methods. For immunized pregnant women (n = 20), the risk of HDFN was predicted for 12 fetuses, and no risk was predicted for 7 fetuses; one result of the clinical samples was indeterminable. Cloning and sequencing revealed a novel variant harboring the same single nucleotide variations as ABO*O.01.24 with an additional c.220C>T substitution. An additional indeterminable result was found among the 6 test samples and was caused by maternal heterozygosity. The 2 indeterminable samples demonstrated limitations to the assay due to hybrid ABO genes or maternal heterozygosity. Conclusions: We pioneered an NGS-based fetal ABO prediction assay based on a cell-free DNA analysis from maternal plasma and demonstrated its application in a small number of samples. Based on the calculations of variant frequencies and ABO*O.01/ABO*O.02 heterozygote frequency, we estimate that we can assign a reliable fetal ABO type in approximately 95% of the forthcoming clinical samples of type O pregnant women. Despite the vast genetic variations underlying the ABO blood groups, many variants are rare, and prenatal ABO prediction is possible and adds valuable early information for the prevention of ABO HDFN.

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Section: Introductionmentioning

confidence: 99%

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Rieneck

Hother

Clausen

et al. 2020

Transfus Med Hemother

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show abstract

“…[4][5][6][7][8][9][10] Interestingly, recent large retrospective analysis performed in Italy revealed a slightly higher incidence of ABO HDFN than formerly reported there, which is indicative of underreporting. 2 Such underreporting may have been more pronounced in low-resource settings, which is similar to the underreporting of RhD HDFN. 21 For example, the incidence of significant ABO HDFN is reported to be ∼3 times higher in black Africans, who also have a higher need for invasive treatment.…”

Section: Discussionmentioning

confidence: 88%

“…1 In European studies, these antibodies cause HDFN that needs neonatal treatment other than phototherapy (such as exchange transfusions or intravenous immunoglobulins) in ,1% of cases. 2 Fetal RBCs have not yet fully expressed A and B antigens, and the wide tissue distribution of the A and B antigens as histo-antigens on all cells and in the soluble phase absorbs the antibodies, which protects incompatible fetal RBCs from hemolysis. 3 In rare cases, IgG anti-A or anti-B antibodies cause more excessive hemolysis.…”

mentioning

confidence: 99%

Severe Fetal Hemolysis and Cholestasis Due to High-Titer Maternal IgG Anti-A Antibodies

Zonneveld¹,

Meer-Kapelle²,

Sylva

et al. 2019

Pediatrics

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ABO blood group incompatibility between mother and fetus can lead to hemolytic disease of the fetus and newborn (HDFN). We present the first case of severe O/A HDFN associated with extremely high-titer (1:32 000) immunoglobulin G anti-A antibodies in a Cameroon mother. Cord blood analysis revealed severe fetal hemolytic anemia and conjugated hyperbilirubinemia. After exclusion of an underlying disease and other risk factors, cholestasis resolved after treatment with ursodeoxycholic acid, a red blood cell transfusion, and intravenous immunoglobulins. This case is presented to create awareness for a more severe course of ABO HDFN in nonwhite and non-European mother-child pairs.

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“…Hemolytic disease of the newborn is caused by incompatibility in the maternal‐fetal blood group, especially in the Rh blood group and the ABO blood group. Since women with Rh‐negative blood groups are rare in Asia, HDN caused by ABO incompatibility, especially by group‐A/B babies of group‐O mothers, which is known as ABO hemolytic disease of the newborn (ABO‐HDN), is the most common hemolytic consequence in China . ABO‐HDN can lead to neonatal jaundice and polycythemia or even stillbirth or neonatal death.…”

Section: Introductionmentioning

confidence: 99%

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

et al. 2020

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Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotypeABO hemolytic disease of the newborn (ABO-HDN), which may cause neonatal jaundice and polycythemia, or even stillbirth or neonatal death, is widespread in China. Prenatal testing for the fetal ABO blood group can reduce unnecessary concerns or ensure prompt treatment. Herein, we presented a method to employ high-density silica microbeads (SiO 2 MBs) for capturing fetal nucleated red blood cells (fnRBCs) in maternal peripheral blood, and we detected the ABO genotype of the fetus using these captured cells. We evaluated 52 patients using the SiO 2 MBs. Among 26 pregnant women with type O blood, 8 (30.8%) of the fetuses had type A blood, 5 (19.2%) had type B blood, and 13 (50%) had type O blood. SRY genes were detected in all 27 male fetuses. This study represents a simple and effective method for noninvasive prenatal detection of the fetal ABO genotype. We believe that this method has great potential for noninvasive prenatal testing of the fetal Rh blood group and other fetal diseases as well.Abbreviations: ABO-HDN, ABO hemolytic disease of the newborn; CTCs, circulating tumor cells; fnRBCs, Fetal nucleated red blood cells; PCR-SSP, PCR with sequence specific primer; SiO 2 MBs, silica microbeads * These authors contributed equally.

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Retrospective analysis of HDFN due to ABO incompatibility in a single institution over 6 years

Cited by 25 publications

References 14 publications

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Next Generation Sequencing-Based Fetal ABO Blood Group Prediction by Analysis of Cell-Free DNA from Maternal Plasma

Severe Fetal Hemolysis and Cholestasis Due to High-Titer Maternal IgG Anti-A Antibodies

Silica microbeads capture fetal nucleated red blood cells for noninvasive prenatal testing of fetal ABO genotype

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