Published online June 29, 2009
PEDIATRICS Vol. 124 No. 1 July 2009, pp. 277-284 (doi:10.1542/peds.2008-0877)
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ARTICLE

Carbon Monoxide is a Significant Mediator of Cardiovascular Status Following Preterm Birth

Michael J. Stark, PhD, MRCPa,b, Vicki L. Clifton, PhDa,b and Ian M.R. Wright, FRACPa,c

a Mother and Babies Research Centre, Hunter Medical Research Institute, University of Newcastle, Newcastle, Australia
b Department of Paediatrics and Reproductive Health, University of Adelaide, Adelaide, Australia
c Neonatal Intensive Care Unit, John Hunter Children's Hospital, Newcastle, Australia

OBJECTIVE: With male gender as a strong predictor of cardiovascular instability, we hypothesized that gender-specific differences in circulating carbon monoxide levels contributed to dysregulated microvascular function in preterm male infants.

METHODS: Infants born at 24 to 34 weeks of gestation (N = 84) were studied in a regional tertiary neonatal unit. Carboxyhemoglobin levels were measured through spectrophotometry in umbilical arterial blood and at 24, 72, and 120 hours after birth. Microvascular blood flow was determined through laser Doppler flowmetry.

RESULTS: Carboxyhemoglobin levels demonstrated a strong inverse relationship with gestational age (r = –0.636; P < .001) and were higher in boys (P = .032). Repeated-measures analysis of variance showed a significant decrease in arterial carboxyhemoglobin levels over time (P < .001), with significant between-subjects effects for gestational age (P = .011) and gender (P = .025). Positive correlations with microvascular blood flow at 24 hours of age (r = 0.495; P < .001) and 120 hours of age (r = 0.548; P < .001) were observed. With controlling for gestational age, carboxyhemoglobin levels at 72 hours were greater for infants who died in the first week of life (P = .035).

CONCLUSIONS: The gestational age- and gender-specific differences in carboxyhemoglobin levels and the relationship with dysregulated microvascular blood flow, a state related to greater illness severity and hypotension, are novel findings not confined solely to sick preterm infants. Both inducible heme oxygenase-dependent and non–heme oxygenase-dependent pathways may initially play a central role in carbon monoxide production, inducing pathophysiologic processes in a gender-specific manner.

Key Words: carbon monoxide • microcirculation • cardiovascular physiology • vasodilation • gender

Abbreviations: CO—carbon monoxide • NO—nitric oxide • cGMP—guanosine 3',5'-cyclic monophosphate • RDS—respiratory distress syndrome

Accepted Mar 30, 2009.


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eLetters:

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Carbon Monoxide and the Male Disadvantage
David K. Stevenson, et al.
Pediatrics Online, 12 Oct 2009 [Full text]