Complete blood count-derived inflammatory biomarkers and neonatal cholestasis in preterm infants: a matched...

Inflammation has been implicated in neonatal cholestasis, but associations between complete blood count (CBC)-derived inflammatory biomarkers and cholestasis remain unclear. This study evaluated these associations in preterm infants. This retrospective 1:1 matched case-control study included 284 cholestatic cases and 284 matched controls. Eight biomarkers were evaluated: neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), neutrophil-plus-monocyte-to-lymphocyte ratio (NMLR), systemic inflammation response index (SIRI), systemic immune-inflammation index (SII), pan-immune-inflammation value (PIV), neutrophil-to-lymphocyte-to-platelet ratio (NLPR), and prognostic nutritional index (PNI). Conditional logistic regression, restricted cubic spline, subgroup, interaction, and sensitivity analyses were performed. In fully adjusted models, higher levels of NLPR, NLR, NMLR, PNI, and SIRI remained associated with an increased risk of cholestasis, whereas PLR was inversely associated with cholestasis risk. Specifically, each unit increase in NLR, NMLR, and SIRI was associated with a 28% (OR = 1.28, 95% CI: 1.07-1.53), 23% (OR = 1.23, 95% CI: 1.05-1.44), and 8% (OR = 1.08, 95% CI: 1.01-1.16) increase in cholestasis risk, respectively, whereas higher PLR was associated with a lower risk of cholestasis (OR = 0.99, 95% CI: 0.99-1.00). Tertile analyses showed higher odds of cholestasis in the highest NLPR tertile and lower odds in the higher PLR tertiles. Compared with the lowest tertile, infants in the highest tertile had a 2.19-fold higher risk of cholestasis for NLPR (OR = 2.19, 95% CI: 1.34-3.58). Conversely, higher tertiles of platelet-to-lymphocyte ratio (PLR) were associated with a reduced risk of cholestasis, with infants in the highest tertile showing significantly lower odds than those in the lowest tertile (T3 vs. T1: OR = 0.44, 95% CI: 0.27-0.72). Restricted cubic spline analyses revealed that PLR exhibited a L-shaped relationship with cholestasis risk. Subgroup and interaction analyses suggested that the observed associations were generally robust across clinical subgroups.

Several routinely available CBC-derived inflammatory biomarkers were associated with neonatal cholestasis in preterm infants. These findings are associational and require prospective validation before the biomarkers can be used for prediction or clinical decision-making.

• Systemic inflammation has been hypothesized to be involved in neonatal cholestasis, but its contribution to the development of cholestasis in preterm infants remains insufficiently established. • Evidence regarding the associations between complete blood count-derived inflammatory biomarkers and neonatal cholestasis is limited.

• Higher NLPR, NLR, NMLR, PNI, and SIRI levels were associated with higher odds of neonatal cholestasis, whereas PLR showed an inverse association. • These findings provide epidemiological support for the hypothesis that systemic inflammation may be involved in neonatal cholestasis, although causality cannot be established.