Early inflammatory markers for prediction of cholestasis in very-low-birth-weight infants.

Background: Neonatal cholestasis is associated with increased mortality and other adverse outcomes. There are no tools for prediction of infants at risk for cholestasis.

Objective: To determine if cholestasis in very-low-birth-weight (VLBW) infants is associated with alterations in cytokines or C-reactive protein (CRP) and, if so, whether inflammatory markers predict which infants will develop cholestasis.

Methods: VLBW infants expected to be on parenteral nutrition for >7 days were enrolled in this prospective cohort study. Infants with direct bilirubin ≥1.0 mg/dl were considered to have a high risk for cholestasis and were compared to infants who never developed direct bilirubin ≥1.0 mg/dl. Standard descriptive statistics were used to compare biomarkers over time. Multivariable models were used to estimate associations between early inflammatory markers and cholestasis.

Results: Of 63 infants enrolled, 29 were at risk for cholestasis. CRP was highly correlated with direct bilirubin. Infants in the high-risk group had significantly higher IL-1β, IL-6, IL-8, and IL-10 at 2, 4, and 6 weeks and CRP at 2 and 6 weeks. In logistic models, CRP (OR = 4.97, p = 0.02) or IL-1β (OR = 1.11, p = 0.008) at 2 weeks of age was predictive of cholestasis. In linear mixed-effects models, CRP (p < 0.001) or IL-6 (p = 0.02) and IL-8 (p < 0.001) were predictive of cholestasis.

Conclusion: Elevated CRP and cytokines are associated with cholestasis in VLBW infants. These inflammatory markers are candidates for further research into the pathogenesis, prediction, and prevention of cholestasis.