Early end-tidal carbon monoxide levels and neurodevelopmental outcome at 3 years 6 months of age in preterm infants

Dev Med Child Neurol. 2011 Dec;53(12):1113-8. doi: 10.1111/j.1469-8749.2011.04110.x. Epub 2011 Sep 20.


Aim: Increased end-tidal carbon monoxide (ETCOc) and cytokines in preterm infants are related to bronchopulmonary dysplasia and intraventricular haemorrhages. The aim was to study the predictive value of ETCOc and cytokine levels for long-term outcome.

Methods: This study comprised 105 very preterm infants (57 males, 48 females; gestational age range 25 wks 5d-31 wks 4d; birthweight 610-2100 g) who were admitted to a neonatal intensive care unit between 1 February and 31 December 2002. ETCOc, plasma tumour necrosis factor alpha (TNF-α) and interleukins (IL) 6 and 8, and malondialdehyde (MDA, a marker of lipid peroxidation), were measured at days 1, 3, and 5 of life and related to outcome at 3 years 6 months of age (Griffiths Mental Developmental Scales).

Results: Of the 105 infants, 69 were eligible for follow-up (37 males; 32 females; bronchopulmonary dysplasia, n = 12). ETCOc at 0 to 24 hours was higher in infants with adverse outcome (Griffiths developmental quotient <85, n = 15) compared with favourable outcome (2.7SD 0.7 vs 2.0SD 0.5; p < 0.05). MDA and cytokines did not differ between groups. Regression analysis with bootstrapping of independent variables (gestational age, birthweight, ETCOc, TNF-α, IL-6, IL-8, and bronchopulmonary dysplasia) showed that ETCOc was the only parameter that correlated with outcome. The sensitivity and negative predictive value of ETCOc for adverse outcome were 93% and 85% respectively.

Interpretation: Adverse neurodevelopmental outcome is associated with increased endogenous carbon monoxide. ETCOc less than 2.0 ppm during the first day indicates a favourable outcome.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Breath Tests
  • Carbon Monoxide / metabolism*
  • Child Development / physiology*
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Humans
  • Infant, Newborn
  • Infant, Premature / metabolism*
  • Male
  • Predictive Value of Tests
  • Prognosis
  • Tidal Volume


  • Carbon Monoxide