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

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.

Duke Scholars

Author Jerome Jeffrey Federspiel Obstetrics and Gynecology, Maternal Fetal Medicine