Admission platelet mass index in very preterm infants: independent association with mortality but limited clinical utility for hemodynamically significant patent ductus arteriosus – a multicenter retrospective cohort study

Platelet indices have been associated with inflammatory and thrombotic processes. However, findings remain inconsistent and most studies have focused on isolated platelet parameters. We aimed to investigate whether platelet mass index (PMI), an integrated marker reflecting both platelet quantity and activation, is independently associated with hemodynamically significant patent ductus arteriosus (hsPDA) and mortality in very preterm infants. This multicenter retrospective cohort study included 344 preterm infants born at ≤ 32 weeks’ gestation and ≤ 1,800 g. Platelet indices obtained from the first complete blood count at neonatal intensive care unit admission were analyzed according to clinical outcomes. Platelet count, mean platelet volume (MPV), platelet distribution width (PDW), plateletcrit (PCT), red cell distribution width-to-platelet ratio (RPR), and PMI were evaluated. Multivariable logistic regression and Cox proportional hazards regression analyses were performed to identify independent predictors of hsPDA and mortality, respectively. Receiver operating characteristic (ROC) curve analysis was used to evaluate the discriminatory performance of PMI. Non-survivors had significantly lower platelet count, PCT, and PMI values and higher RPR levels compared with survivors ( p < 0.05 for all), whereas none of the individual platelet indices, including PMI, differed significantly between infants with and without hsPDA in univariate analysis (PMI: 1650 vs. 1665, p = 0.209). In multivariable analyses, lower PMI remained independently associated with mortality (HR: 0.91 per 100 units, 95% CI: 0.87–0.96, p = 0.001; robust to a sensitivity analysis substituting gestational age for birth weight and to adjustment for early-onset sepsis) and showed a modest independent association with hsPDA after adjustment for gestational age, 5th-minute APGAR score, and oligohydramnios (OR: 0.96 per 100 units, 95% CI: 0.93–0.99, p = 0.015), whereas other platelet indices were not independently associated with either outcome; the PMI-mortality association was robust to sensitivity analyses adjusting for center, whereas the PMI-hsPDA association was not ( p = 0.384 after center adjustment, with center itself a strong predictor), indicating that the hsPDA finding likely reflects site-level heterogeneity rather than a generalizable association. Discriminatory performance of PMI alone was modest for mortality (AUC 0.626, 95% CI 0.540–0.711) and limited for hsPDA (AUC 0.540, 95% CI 0.480–0.599), and adding PMI to a baseline clinical model (gestational age, birth weight/oligohydramnios, and 5th-minute APGAR score) did not significantly improve discrimination for either outcome (DeLong p = 0.111 and p = 0.265, respectively). Lower admission PMI values were independently and robustly associated with mortality, including after sensitivity analyses adjusting for gestational age, early-onset sepsis, and treatment center. A modest independent association between PMI and hsPDA was present after adjustment for clinical covariates but was not robust to adjustment for center, whereas center itself was a strong predictor of hsPDA; PMI also did not differ between hsPDA groups in unadjusted comparisons and did not improve discrimination beyond routinely available clinical variables for either outcome. These findings support a role for PMI as a marker of platelet-related inflammatory and hemostatic dysregulation associated with mortality, but do not establish its utility as a standalone clinical biomarker; the hsPDA association in particular does not appear to be a reliable, generalizable finding and likely reflects site-level heterogeneity in diagnostic or treatment practice rather than a true biological relationship.