Hematologic Ratios as Early Biomarkers for Preterm Premature Rupture of Membranes: A Prospective Cohort Study

Preterm premature rupture of membranes (PPROM) is a leading cause of preterm birth and is associated with substantial neonatal morbidity and mortality. Subclinical inflammation and immune dysregulation play a central role in the pathogenesis of PPROM, yet reliable, inexpensive early predictors remain limited. Hematologic indices derived from routine complete blood counts, including platelet distribution width (PDW) and leukocyte-based inflammatory ratios, may reflect early systemic inflammation and serve as potential biomarkers for PPROM risk stratification. This study was conducted to find out if readily available hematologic indices may serve as inexpensive markers of systemic inflammation and potential predictors of PPROM.

This prospective cohort study enrolled 500 healthy pregnant women between 7 and 12 weeks of gestation at a tertiary care center in eastern India and followed them until delivery. Complete blood counts were obtained during the first and second trimesters. Platelet indices (platelet count, mean platelet volume [MPV], PDW) and inflammatory ratios, including neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR), were calculated. Participants were classified into PPROM (n = 218) and non-PPROM (n = 282) groups based on pregnancy outcomes. Group comparisons were performed using the Mann-Whitney U test. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive performance of each parameter.

Women who developed PPROM demonstrated significantly higher PDW, NLR, and LMR values in both the first and second trimesters compared with those without PPROM (all p < 0.001). Platelet count, MPV, and PLR showed no statistically significant differences between groups. ROC analysis revealed perfect discriminatory performance for PDW, NLR, and LMR in both trimesters, each achieving an area under the curve (AUC) of 1.000 with 100% sensitivity and 100% specificity at optimal cutoff values. In contrast, traditional clinical and hematologic parameters, including gestational age, platelet count, MPV, and PLR, demonstrated poor predictive ability (AUC < 0.60). PPROM was strongly associated with preterm delivery, occurring in 197 (90.4%) of pregnancies compared with 40 (14.2%) in the non-PPROM group (p < 0.001). However, the observation of perfect diagnostic accuracy (AUC = 1.000 with 100% sensitivity and specificity) across multiple biomarkers warrants cautious interpretation. Such findings raise the possibility of overfitting, cohort-specific effects, or unrecognized methodological influences, particularly in the absence of independent external validation. Therefore, these results should be considered preliminary and hypothesis-generating rather than definitive.

Elevated PDW, NLR, and LMR in early pregnancy appear to be promising markers associated with subsequent PPROM. While these inexpensive and routinely available hematologic indices may have potential utility for early risk stratification, further multicentric studies with robust validation and external replication are essential before clinical implementation can be recommended.