Association Between Peripheral Blood Natural Killer Cells and Chromosomally Abnormal Spontaneous Abortion: A Retrospective Single-Center Study

Background Chromosomal abnormalities account for a significant proportion of spontaneous abortions (SA), yet the role of peripheral blood natural killer (pbNK) cells—especially across different karyotypes—remains unclear. Elucidating this relationship may reveal immune mechanisms underlying early pregnancy loss and identify actionable biomarkers. Methods This retrospective, single-center study included 1250 patients, comparing 294 early SA cases (classified as chromosomally normal or abnormal via CNV-seq) with 956 live births. Multivariable logistic regression and stratified analyses were used to assess the association between pbNK cell levels and chromosomally abnormal SA, as well as specific karyotypes. The diagnostic performance of pbNK cells was evaluated using receiver operating characteristic (ROC) curves. Results Multivariate analysis identified elevated pbNK cell levels as an independent risk factor for chromosomally abnormal SA (adjusted OR = 1.363, 95% CI: 1.033–1.797). Patients in the highest quartile of pbNK cells had a fourfold increased risk (OR = 4.123), with a linear dose-response relationship observed. Notably, SA cases associated with microdeletions showed the strongest association (OR = 10.807, 95% CI: 2.627–44.455), while trisomies demonstrated borderline significance. ROC analysis indicated moderate diagnostic utility (AUC = 65.1%, sensitivity = 52.1%, specificity = 74.8%). Conclusion These findings suggest that pbNK cell levels serve as a biomarker for chromosomally abnormal SA, particularly in microdeletion-related cases, and support a linear dose-response relationship between pbNK cell levels and SA risk.