Adjunctive screening and risk stratification performance of neutrophil-to-lymphocyte ratio for gestational diabetes mellitus: A systematic review and meta-analysis.

Abstract

The neutrophil-to-lymphocyte ratio (NLR) is an inexpensive inflammatory marker with uncertain value for gestational diabetes mellitus (GDM) risk assessment. This systematic review and meta-analysis evaluated NLR for first-trimester risk stratification and second-trimester adjunctive screening of GDM. PubMed, Embase, Web of Science, and the Cochrane Library were searched from inception to April 15, 2026. Risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Sensitivity and specificity were pooled separately by trimester, and summary receiver operating characteristic curves were fitted using the Moses-Littenberg method. Eleven studies comprising 12 independent datasets used the oral glucose tolerance test (OGTT) as the reference standard. Pooled sensitivity, specificity, and area under the curve (AUC), with 95% confidence intervals (CIs), were 0.702 (0.660-0.742), 0.426 (0.401-0.452), and 0.694 (0.559-0.828), respectively, in the first trimester and 0.665 (0.632-0.697), 0.644 (0.618-0.670), and 0.798 (0.723-0.873) in the second trimester. At cutoffs ≤ 3.0, exploratory AUC estimates were 0.845 and 0.850, respectively, but subgroup differences were not formally tested. All studies were at high risk of index-test bias from post hoc threshold selection, seven used case-control designs, and heterogeneity was substantial. NLR may have an adjunctive role in GDM risk assessment but should not replace OGTT or serve as a standalone screening test. No clinical cutoff can be recommended; prospective studies with prespecified thresholds and independent validation cohorts are required.