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

Grethe Risum Krog; Mette L. Donneborg; Bo M. Hansen; Henriette Lorenzen; Frederik B. Clausen; Kristian V. Jensen; Anette Kjærbye-Thygesen; Per Albertsen; Finn Ebbesen; Thomas Bergholt; Mette K. Smed; Morten H. Dziegiel

doi:https://doi.org/10.1038/s41390-020-01232-5

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

Grethe Risum Krog, Mette L. Donneborg, Bo M. Hansen, Henriette Lorenzen, Frederik B. Clausen, Kristian V. Jensen, Anette Kjærbye-Thygesen, Per Albertsen, Finn Ebbesen, Thomas Bergholt, Mette K. Smed, Morten H. Dziegiel

Publikation: Bidrag til tidsskrift › Tidsskriftsartikel › Forskning › peer review

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.

Originalsprog	Engelsk
Tidsskrift	Pediatric Research
Vol/bind	90
Udgave nummer	1
Sider (fra-til)	74-81
Antal sider	8
ISSN	0031-3998
DOI	https://doi.org/10.1038/s41390-020-01232-5
Status	Udgivet - jul. 2021

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Krog, G. R., Donneborg, M. L., Hansen, B. M., Lorenzen, H., Clausen, F. B., Jensen, K. V., Kjærbye-Thygesen, A., Albertsen, P., Ebbesen, F., Bergholt, T., Smed, M. K., & Dziegiel, M. H. (2021). Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer. Pediatric Research, 90(1), 74-81. https://doi.org/10.1038/s41390-020-01232-5

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

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: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn.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.Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B.Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.",

keywords = "pregnant women",

author = "Krog, {Grethe Risum} and Donneborg, {Mette L.} and Hansen, {Bo M.} and Henriette Lorenzen and Clausen, {Frederik B.} and Jensen, {Kristian V.} and Anette Kj{\ae}rbye-Thygesen and Per Albertsen and Finn Ebbesen and Thomas Bergholt and Smed, {Mette K.} and Dziegiel, {Morten H.}",

note = "Publisher Copyright: {\textcopyright} 2020, International Pediatric Research Foundation, Inc.",

year = "2021",

month = jul,

doi = "https://doi.org/10.1038/s41390-020-01232-5",

language = "English",

volume = "90",

pages = "74--81",

journal = "Pediatric Research",

issn = "0031-3998",

publisher = "Lippincott Williams and Wilkins Ltd.",

number = "1",

}

Krog, GR, Donneborg, ML, Hansen, BM, Lorenzen, H, Clausen, FB, Jensen, KV, Kjærbye-Thygesen, A, Albertsen, P, Ebbesen, F, Bergholt, T, Smed, MK & Dziegiel, MH 2021, 'Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer', Pediatric Research, bind 90, nr. 1, s. 74-81. https://doi.org/10.1038/s41390-020-01232-5

TY - JOUR

T1 - Prediction of ABO hemolytic disease of the newborn using pre- and perinatal quantification of maternal anti-A/anti-B IgG titer

AU - Krog, Grethe Risum

AU - Donneborg, Mette L.

AU - Hansen, Bo M.

AU - Lorenzen, Henriette

AU - Clausen, Frederik B.

AU - Jensen, Kristian V.

AU - Kjærbye-Thygesen, Anette

AU - Albertsen, Per

AU - Ebbesen, Finn

AU - Bergholt, Thomas

AU - Smed, Mette K.

AU - Dziegiel, Morten H.

PY - 2021/7

Y1 - 2021/7

N2 - 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: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn.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.Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B.Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

AB - 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: Maternal anti-A/B IgG titer in the first trimester and at birth is predictive of hemolytic disease of the ABO-incompatible newborn.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.Screening tools available in most immunohematology laboratories can identify clinically important IgG anti-A/B.Use of maternal samples taken at birth yielded NPV = 0.93 and PPV = 0.73.

KW - pregnant women

UR - http://www.scopus.com/inward/record.url?scp=85095757633&partnerID=8YFLogxK

U2 - https://doi.org/10.1038/s41390-020-01232-5

DO - https://doi.org/10.1038/s41390-020-01232-5

M3 - Journal article

SN - 0031-3998

VL - 90

SP - 74

EP - 81

JO - Pediatric Research

JF - Pediatric Research

IS - 1

ER -

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

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