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The most recent version of this article was published on 1 November 2008

Arch. Dis. Child. Fetal Neonatal Ed.. Published Online First: 11 January 2008. doi:10.1136/adc.2007.124503
Copyright © 2008 BMJ Publishing Group Ltd & Royal College of Paediatrics and Child Health.

Original articles

Severe neonatal hypoxic respiratory failure correlates with histologic chorioamnionitis and elevated concentrations of IL-6, IL-8 and CRP

Mesfin Woldesenbet 1*, Charles R. Rosenfeld 2, Octavio Ramilo 2, Sarah Johnson-Welch 2 and Jeffrey M. Perlman 3

1 Pediatrix Medical Group of Texas, United States
2 University of Texas- Southwestern Medical Center at Dallas, United States
3 New York Presbyterian Hospital-Weil Cornell Medical College, United States

* To whom correspondence should be addressed. E-mail: mesfin_w{at}yahoo.com.

Accepted 3 January 2008


Abstract

Background: The mechanisms contributing to hypoxic respiratory failure (HRF) in term infants are multifactorial. Recent evidence suggests a potential pathogenetic role for inflammation. Nitric oxide (NO), a pulmonary vasodilator, is inhibited by inflammatory mediators which are upregulated in the presence of placental inflammation.

Objective: To examine the relationship between histologic chorioamnionitis and/or funisitis, serum concentrations of inflammatory mediators and severity of HRF.

Methods: Prospective observational study involving term neonates with HRF and normal controls. Blood samples were taken at birth from mixed cord blood, at 6 and 30 h for cytokines and CRP, and at 72 and 96h for CRP. Placentas were examined for chorioamnionitis. The primary outcome was the administration of inhaled nitric oxide (iNO) therapy. Data were analyzed by ANOVA and chi-square analysis.

Results: 32 neonates with hypoxic respiratory failure and 25 controls were enrolled. 14/32 (44%) neonates with HRF required iNO, 9/32(28%) hi-frequency ventilation and 3/32(9%) ECMO; 2/32 (6%) died. Neonates with HRF had >3-fold higher cord levels of IL-8 than controls (p<0.05). At 6 and 30h, serum IL-6, IL-8 and CRP were 2.2-fold higher in neonates who received iNO (p<0.003). 23/32 (72%) infants with HRF had evidence of histologic chorioamnionitis and/or funisitis compared to 5/25 (20%) controls (p<0.001).

Conclusion: Severe hypoxic respiratory failure, as defined by the need for iNO, is associated with elevated blood proinflammatory mediators and increased occurrence of histologic chorioamnionitis and funisitis, suggesting that inflammation contributes to the severity of hypoxic failure.

Keywords: Chorioamnionitis, Funisitis, Hypoxic Respiratory Failure, Inflammation, Nitric Oxide


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