title: Risk factors for parenteral nutrition–associated liver disease following surgical therapy for necrotizing enterocolitis: A Glaser Pediatric Research Network Study [corrected].
abstract: OBJECTIVE
  The aim of the study was to prospectively determine risk factors for the development of parenteral nutrition-associated liver disease (PNALD) in infants who underwent surgery for necrotizing enterocolitis (NEC), the most common cause of intestinal failure in children.
  
  
  METHODS
  : From February 2004 to February 2007, we diagnosed 464 infants with NEC, of whom 180 had surgery. One hundred twenty-seven patients were available for full analysis. PNALD was defined as serum direct bilirubin ≥ 2 mg/dL or ALT ≥ 2 × the upper limit of normal in the absence of sepsis after ≥ 14 days of exposure to PN.
  
  
  RESULTS
  Median gestational age was 26 weeks and 68% were boys. Seventy percent of the cohort developed PNALD and the incidence of PNALD varied significantly across the 6 study sites, ranging from 56% to 85% (P = 0.05). Multivariable logistic regression analysis identified small-bowel resection or creation of jejunostomy (odds ratio [OR] 4.96, 95% confidence interval [CI] 1.97-12.51, P = 0.0007) and duration of PN in weeks (OR 2.37, 95% CI 1.56-3.60, P < 0.0001) as independent risk factors for PNALD. Preoperative exposure to PN was also associated with the development of PNALD; the risk of PNALD was 2.6 (95% CI 1.5-4.7; P = 0.001) times greater in patients with ≥ 4 weeks of preoperative PN compared with those with less preoperative PN use. Breast milk feedings, episodes of infection, and gestational age were not related to the development of PNALD.
  
  
  CONCLUSIONS
  The incidence of PNALD is high in infants with NEC undergoing surgical treatment. Risk factors for PNALD are related to signs of NEC severity, including the need for small-bowel resection or proximal jejunostomy, as well as longer exposure to PN. Identification of these and other risk factors can help in the design of clinical trials for the prevention and treatment of PNALD and for clinical assessment of patients with NEC and prolonged PN dependence.
authors.affiliation: Division of GI/Nutrition, Children's Hospital, Boston, Harvard Medical School, Boston, MA, USA. dduro@med.miami.edu
authors.forename: Debora
authors.initials: D
authors.lastname: Duro
authors.forename: Paul D
authors.initials: PD
authors.lastname: Mitchell
authors.forename: Leslie A
authors.initials: LA
authors.lastname: Kalish
authors.forename: Cami
authors.initials: C
authors.lastname: Martin
authors.forename: Maggie
authors.initials: M
authors.lastname: McCarthy
authors.forename: Tom
authors.initials: T
authors.lastname: Jaksic
authors.forename: James
authors.initials: J
authors.lastname: Dunn
authors.forename: Mary L
authors.initials: ML
authors.lastname: Brandt
authors.forename: Kerilyn K
authors.initials: KK
authors.lastname: Nobuhara
authors.forename: Karl G
authors.initials: KG
authors.lastname: Sylvester
authors.forename: R Lawrence
authors.initials: RL
authors.lastname: Moss
authors.forename: Christopher
authors.initials: C
authors.lastname: Duggan
mesh_terms: D001663:Bilirubin / Q000097:blood; D020345:Enterocolitis, Necrotizing / Q000150:complications / Q000601:surgery*; D005260:Female; D005865:Gestational Age; D006801:Humans; D015994:Incidence; D007223:Infant; D007410:Intestinal Diseases / Q000209:etiology / Q000628:therapy; D007421:Intestine, Small / Q000601:surgery*; D007582:Jejunostomy / Q000009:adverse effects*; D008107:Liver Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D010288:Parenteral Nutrition / Q000009:adverse effects*; D011183:Postoperative Complications / Q000097:blood / Q000453:epidemiology*; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D001663:Bilirubin