The Utility of a Critical Antibody Titer in Anti-K Alloimmunized Pregnancies: A Systematic Review and Meta-Analysis of Diagnostic Test Accuracy

Jeremy W. Jacobs, Department of Pathology, Microbiology, & Immunology, Vanderbilt University Medical Center, Nashville, TN, USA
Ronan P. Sugru, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Duke University School of Medicine, Durham, NC, USA.
Jerome Jeffrey Federspiel, Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Duke University School of Medicine, Durham, NC, USA; Department of Population Health Sciences, Duke University School of Medicine, Durham, NC, USA; Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Melissa C. Funaro, Harvey Cushing/John Hay Whitney Medical Library, Yale University, New Haven, CT, USA.
Brian D. Adkins, Department of Pathology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Garrett S. Booth, Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, TN, USA.
Christopher Haas, Department of Internal Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Masja de Hass, Department of Haematology, Leiden University Medical Center, Leiden, The Netherlands; Department of Immunohematology Diagnostics, Sanquin Diagnostic Services, Sanquin, Amsterdam, The Netherlands.
Jia Jennifer Ding, Department of Obstetrics, Gynecology, and Reproductive Sciences, Division of Maternal-Fetal Medicine, Yale School of Medicine, New Haven, CT, USA.
Danijela Drndarevic, Department of Transfusion, Health Center Užice, Užice, Serbia.
Sejal Kabre, Department of Obstetrics and Gynecology, Bridgeport Hospital/Yale University, Bridgeport, CT, USA.
Shengxin Liu, Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Yolentha M. Slootweg, Department of Obstetrics, Leiden University Medical Center, Leiden, The Netherlands; Department of Clinical Transfusion Research, Sanquin Research, Leiden, The Netherlands.
Elenor Tiblad, Department of Medicine Solna, Clinical Epidemiology Division, Karolinska Institutet, Stockholm, Sweden.
Kenneth J. Moise, Department of Women's Health, Dell Medical School, UT Health Austin, and the Comprehensive Fetal Center, Dell Children's Medical Center, Austin, Texas.
Elizabeth A. Abels, Department of Obstetrics and Gynecology, Bridgeport Hospital/Yale University, Bridgeport, Connecticut, USA.

Document Type

Article

Publication Title

Transfusion Medicine Reviews

Abstract

Anti-Kell (anti-K) alloimmunization is a known cause of severe hemolytic disease of the fetus and newborn (HDFN), yet the utility of a critical maternal antibody titer in guiding clinical management remains debated. We conducted a systematic review and meta-analysis to evaluate the diagnostic accuracy of a maternal anti-K titer threshold of ≥8 for predicting the need for intrauterine intervention due to severe anti-K–mediated HDFN. In parallel, we characterized all reported cases of severe HDFN occurring in the setting of low maternal anti-K titers (<8). Studies were excluded if they lacked reported titers, did not include K-positive or K-unknown fetuses, failed to report fetal outcomes, or included interventions that could lower maternal alloantibody levels. Studies that assessed all alloimmunized patients meeting inclusion criteria were incorporated into a diagnostic test accuracy (DTA) meta-analysis; all eligible studies were included in a qualitative synthesis. Fifty-four studies, comprising 582 fetuses, met inclusion criteria. Of these, 6 studies (350 fetuses) were included in the DTA analysis, which demonstrated a pooled sensitivity of 97.0% (95% CI, 88.7%–99.2%) and specificity of 33.1% (95% CI, 27.9%–38.8%) for an anti-K titer ≥8. Among fetuses affected by severe HDFN, 98.6% (204/207) were associated with maternal anti-K titers ≥8. These findings suggest that severe disease is uncommon in the setting of low anti-K titers and support the use of a critical titer threshold to inform antenatal surveillance. Reevaluation of current clinical guidelines may be warranted in light of these data.

DOI

10.1016/j.tmrv.2025.150895

Publication Date

4-10-2025

Comments

Conflict of interest statement

Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: ET receives consultancy fees for membership in advisory boards and committees in Janssen Pharmaceutical HDFN program. KJM serves as the overall principal investigator for the phase 2 trial of nipocalimab (UNITY); has received funding from Momenta Pharmaceuticals, Inc paid on his behalf to the McGovern Medical School – UT Health and from Janssen Pharmaceuticals, Inc paid on his behalf to Dell Medical School at The University of Texas at Austin for a clinical trial on a monoclonal antibody for the treatment of HDFN; has served on the steering committees and advisory boards for clinical studies for Momenta Pharmaceuticals, Inc., and Janssen Pharmaceuticals but has not received funding for these activities; receives royalty funding from UpToDate, Inc. for authorship on various chapters, consulting fees from Health Management Associates, Inc. for consultation on the formation of fetal centers, consulting fees from BillionToOne, Inc. paid on his behalf to Dell Medical School at The University of Texas at Austin, honoraria from GLC Healthcare, Inc for podcast content on HDFN; and serves as a nonpaid consultant for Immunology for Janssen Pharmaceuticals, Inc. JF was supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development of the National Institutes of Health under award K12HD103083. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. All other authors report no relevant disclosures.

References

40253764

e-ISSN

1532-9496

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