Cytokine levels in neonatal necrotizing enterocolitis and long-term growth and neurodevelopment

Acta Paediatr. 2010 Mar;99(3):338-43. doi: 10.1111/j.1651-2227.2009.01600.x. Epub 2009 Nov 18.


Objective: To investigate if circulating cytokines are related to growth and neurodevelopmental outcome following necrotizing enterocolitis (NEC).

Study design: Pro-inflammatory cytokine levels were measured prospectively in 40 neonates and compared with neurodevelopmental outcome. Cytokine levels were measured at the onset of feeding intolerance (Group II, n = 17) or NEC (Group III, n = 10) and at weeks 2-3 in control infants (Group I, n = 13). Neurodevelopmental outcome was assessed at the age of 24-28 months. Data were analysed using descriptive statistics, non-parametric tests and Student t-test.

Results: Median birth weights (range) in groups I, II and III were 1120 (525-1564) g, 1068 (650-1937) g and 1145 (670-2833) g, and median gestational ages (range) were 28 (24-35) weeks 28 (24-35) weeks and 28 (25-37) weeks respectively. NEC occurred in 10 infants. Serum IL-6 (interleukin-6) was elevated in group III, (p = 0.03). Significant developmental delay was found in 12% of the infants in Group II and 20% of the infants in Group III, but no infant in group I. Five infants in group III with NEC (50%), had head ultrasound abnormalities. At 1 year of age, growth, weight and head circumference were significantly different in Group III, however, at two years of age, only height was significantly different, p < 0.02. Although there was wide variation, neonatal cytokine levels tended to be greater in the infants later found to have abnormal cognitive and psychomotor outcomes.

Conclusion: This study suggests that increased serum levels of pro-inflammatory cytokines may play a role in the poor growth and neurodevelopment associated with this high-risk population.

MeSH terms

  • Cerebral Palsy / etiology
  • Child Development
  • Child, Preschool
  • Cytokines / blood*
  • Enterocolitis, Necrotizing / blood
  • Enterocolitis, Necrotizing / complications*
  • Enterocolitis, Necrotizing / physiopathology
  • Female
  • Growth Disorders / etiology*
  • Humans
  • Infant, Newborn
  • Infant, Premature / blood
  • Infant, Premature / growth & development*
  • Infant, Premature, Diseases
  • Infant, Very Low Birth Weight / blood
  • Infant, Very Low Birth Weight / growth & development*
  • Male
  • Nervous System / growth & development
  • Nervous System / physiopathology
  • Prospective Studies


  • Cytokines