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

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.