Anti-RH1 alloimmunization: At what maternal antibody threshold is there a risk of severe fetal anemia?
anti-RH1 alloimmunization
in utero transfusion
severe fetal anemia
titration
weight determination
Journal
Transfusion
ISSN: 1537-2995
Titre abrégé: Transfusion
Pays: United States
ID NLM: 0417360
Informations de publication
Date de publication:
03 2023
03 2023
Historique:
revised:
16
12
2022
received:
20
06
2022
accepted:
27
12
2022
pubmed:
4
2
2023
medline:
23
3
2023
entrez:
3
2
2023
Statut:
ppublish
Résumé
To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI). We conducted a retrospective study of patients followed for anti-RH1 AI at the Lille University Hospital. The first group, severe anemia, included patients who received one or more in utero transfusions (IUT) or who were induced before 37 weeks of pregnancy for suspected severe fetal anemia. The second group, absence of severe anemia, corresponded to patients without intervention during pregnancy related to AI. Sensitivities, specificities, and positive and negative predictive values for screening for severe fetal anemia were calculated for the antibody thresholds of 3.5 and 5 IU/ml for the quantification. Between 2000 and 2018, 207 patients were included 135 in the severe anemia group and 72 in the no severe anemia group. No severe anemia was observed for an antibody titer below 16. For an antibody threshold of 3.5 IU/ml, the sensitivity was 98.2%, with 30.2% false positives. All severe anemias were detected in the second trimester; two cases of severe anemia were not detected in the third trimester. For an antibody threshold of 5 IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected. The antibody threshold of 3.5 IU/ml for the quantification and 16 for the titration allow targeting patients requiring close monitoring by an experienced team in case of anti-RH1 AI.
Sections du résumé
BACKGROUND
To define a threshold of maternal antibodies at risk of severe fetal anemia in patients followed for anti-RH1 alloimmunization (AI).
STUDY, DESIGN, AND METHODS
We conducted a retrospective study of patients followed for anti-RH1 AI at the Lille University Hospital. The first group, severe anemia, included patients who received one or more in utero transfusions (IUT) or who were induced before 37 weeks of pregnancy for suspected severe fetal anemia. The second group, absence of severe anemia, corresponded to patients without intervention during pregnancy related to AI. Sensitivities, specificities, and positive and negative predictive values for screening for severe fetal anemia were calculated for the antibody thresholds of 3.5 and 5 IU/ml for the quantification.
RESULTS
Between 2000 and 2018, 207 patients were included 135 in the severe anemia group and 72 in the no severe anemia group. No severe anemia was observed for an antibody titer below 16. For an antibody threshold of 3.5 IU/ml, the sensitivity was 98.2%, with 30.2% false positives. All severe anemias were detected in the second trimester; two cases of severe anemia were not detected in the third trimester. For an antibody threshold of 5 IU/ml, the sensitivity was lower at 95.6%, with five cases of severe anemia not detected.
CONCLUSION
The antibody threshold of 3.5 IU/ml for the quantification and 16 for the titration allow targeting patients requiring close monitoring by an experienced team in case of anti-RH1 AI.
Substances chimiques
Isoantibodies
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
629-637Informations de copyright
© 2023 AABB.
Références
Collège National des Gynécologues et Obstétriciens Français. J Gynecol Obstet Biol Reprod. 2005;34(5):513.
Branger B, Winer N. Epidemiology of anti-D Allo-immunization during pregnancy. J Gynecol Obstet Biol Reprod. 2006;35(1 Suppl):1S87-81S92.
Webb J, Delaney M. Red blood cell Alloimmunization in the pregnant patient. Transfus Med Rev. 2018;32(4):213-9.
Ghesquière L, Garabedian C, Coulon C, Verpillat P, Rakza T, Wibaut B, et al. Management of red blood cell alloimmunization in pregnancy. J Gynecol Obstet Hum Reprod. 2018;47(5):197-204.
Carbonne B, Castaigne V, Cynober E, Levy R, Cortey A, Mailloux A, et al. Le point sur le suivi des allo-immunisations érythrocytaires. Gynecol Obstet Fertil. 2010;38(3):205-13.
Gottvall T, Hildén JO. Concentration of anti-D antibodies in Rh(D) alloimmunized pregnant women, as a predictor of anemia and/or hyperbilirubinemia in their newborn infants. Acta Obstet Gynecol Scand. 1997;76(8):733-8.
Walsh CA, Doyle B, Quigley J, McAuliffe FM, Fitzgerald J, Mahony R, et al. Reassessing critical maternal antibody threshold in RhD alloimmunization: a 16-year retrospective cohort study. Ultrasound Obstet Gynecol. 2014;44(6):669-73.
Philip J, Jain N. Antenatal maternal serum IAT titer and fetal outcome in Rh Isoimmunized pregnancies. Indian J Hematol Blood Transfus. 2015;31(1):137-41.
Nicolaides KH, Rodeck CH. Maternal serum anti-D antibody concentration and assessment of rhesus isoimmunisation. BMJ. 1992;304(6835):1155-6.
Gottvall T, Hildén JO, Selbing A. Evaluation of standard parameters to predict exchange transfusions in the erythroblastotic newborn. Acta Obstet Gynecol Scand. 1994;73(4):300-6.
Bowell P, Wainscoat JS, Peto TE, Gunson HH. Maternal anti-D concentrations and outcome in rhesus haemolytic disease of the newborn. Br Med J (Clin Res Ed). 1982;285(6338):327-9.
Morley G, Gibson M, Eltringham D. Use of discriminant analysis in relating maternal anti-D levels to the severity of haemolytic disease of the newborn. Vox Sang. 1977;32(2):90-8.
Filbey D, Berseus O, Sandström B, Wesström G. The evaluation of maternal anti-D concentrations during pregnancy. Early Hum Dev. 1987;15(1):1-9.
Toly-Ndour C, Mourtada H, Huguet-Jacquot S, Maisonneuve E, Friszer S, Pernot F, et al. Clinical input of anti-D quantitation by continuous-flow analysis on autoanalyzer in the management of high-titer anti-D maternal alloimmunization. Transfusion. 2018;58(2):294-305.
Mari G, Deter RL, Carpenter RL, Rahman F, Zimmerman R, Moise KJ, et al. Noninvasive diagnosis by Doppler ultrasonography of fetal anemia due to maternal red-cell alloimmunization. Collaborative Group for Doppler Assessment of the blood velocity in anemic fetuses. N Engl J Med. 2000;342(1):9-14.
Garabedian C, Vaast P, Behal H, Coulon C, Duahamel A, Thomas D, et al. Management of severe fetal anemia by Doppler measurement of middle cerebral artery: are there other benefits than reducing invasive procedures? Eur J Obstet Gynecol Reprod Biol. 2015;192:27-30.
Garabedian C, Philippe M, Vaast P, Wibaut B, Salleron J, Delsalle A, et al. Is intrauterine exchange transfusion a safe procedure for management of fetal anaemia? Eur J Obstet Gynecol Reprod Biol. 2014;179:83-7.
Guilbaud L, Garabedian C, Cortey A, Rakza T, Carbonne B, Houfflin-Debarge V. In utero treatment of severe fetal anemia resulting from fetomaternal red blood cell incompatibility: a comparison of simple transfusion and exchange transfusion. Eur J Obstet Gynecol Reprod Biol. 2016;201:85-8.
Garabedian C, Rakza T, Drumez E, Poleszczuk M, Ghesquiere L, Wibaut B, et al. Benefits of delayed cord clamping in red blood cell Alloimmunization. Pediatrics. 2016 Mar;137(3):e20153236.
Garabedian C, Rakza T, Thomas D, Wibaut B, Vaast P, Subtil D, et al. Neonatal outcome after fetal anemia managed by intrauterine transfusion. Eur J Pediatr. 2015;174(11):1535-9.
Flesiopoulou I, Pouliakis A, Politou M, Dourouki A, Damaskos C, Koutsouri T, et al. Red blood cell alloantibody titration - does the titration method matter? Clin Lab. 2020;66(6). https://doi.org/10.7754/Clin.Lab.2019.191021
Brossard Y, Parnet-Mathieu F, Larsen M. Diagnostic et suivi prénatals des allo-immunisations érythrocytaires. Feuill Biol. 2002;43(245):11-7.
Cortey A, Mailloux A, Huguet-Jacquot S, Castaigne-Meary V, Macé G, N'Guyen A, et al. Incompatibilités fœtomaternelles érythrocytaires. EMC - Pédiatr Mal Infect. 2012;7(3):1-22.
Li S, He Z, Mo C, Ji Y, Luo Y, Fang Q, et al. Hyporegenerative anemia in anti-M-associated hemolytic disease of the fetus. Transfusion. 2021;61(6):1908-15.
Wikman A, Edner A, Gryfelt G, Jonsson B, Henter JI. Fetal hemolytic anemia and intrauterine death caused by anti-M immunization. Transfusion. 2007;47(5):911-7.
Markham KB, Rossi KQ, Nagaraja HN, O'Shaughnessy RW. Hemolytic disease of the fetus and newborn due to multiple maternal antibodies. Am J Obstet Gynecol. 2015;213(1):68.e1-5.
Spong CY, Porter AE, Queenan JT. Management of isoimmunization in the presence of multiple maternal antibodies. Am J Obstet Gynecol. 2001;185(2):481-4.
Nordvall M, Dziegiel M, Hegaard HK, Bidstrup M, Jonsbo F, Christensen B, et al. Red blood cell antibodies in pregnancy and their clinical consequences: synergistic effects of multiple specificities. Transfusion. 2009;49(10):2070-5.
Walsh CA, Russell N, McAuliffe FM, Higgins S, Mahony R, Carroll S, et al. Relationship between maternal antibody type and antenatal course following intrauterine transfusion for red cell alloimmunisation. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):235-9.
Phung TV, Houfflin-Debarge V, Ramdane N, Ghesquière L, Delsalle A, Coulon C, et al. Maternal red blood cell alloimmunization requiring intrauterine transfusion: a comparative study on management and outcome depending on the type of antibody: alloimmunization according to the antibody. Transfusion. 2018;58(5):1199-205.