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.


CONCLUSIONS
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.
Department of Pediatrics, The Children's Hospital of Philadelphia, Pennsylvania Hospital and the University of Pennsylvania, Philadelphia, PA 19104, USA. demauro@email.chop.edu
Sara B
SB
DeMauro
Laurie E
LE
Kilpatrick
Jeffrey S
JS
Gerdes
Soraya
S
Abbasi
D001663:Bilirubin / Q000097:blood; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D016022:Case-Control Studies; D002779:Cholestasis / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D042241:Early Diagnosis; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D007235:Infant, Premature, Diseases / Q000097:blood / Q000175:diagnosis*; D019102:Infant, Very Low Birth Weight / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000175:diagnosis; D018836:Inflammation Mediators / Q000032:analysis* / Q000097:blood; D008297:Male; D009035:Mothers; D011237:Predictive Value of Tests; D011379:Prognosis
D015415:Biomarkers; D018836:Inflammation Mediators; D001663:Bilirubin