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 that are upregulated in the presence of placental inflammation.
Objective: To examine the relationship between histological 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 h and 30 h for cytokines and CRP, and at 72 h and 96 h for CRP. Placentas were examined for chorioamnionitis. The primary outcome was the administration of inhaled nitric oxide (iNO) therapy. Data were analysed using analysis of variance and χ2 analysis.
Results: 32 neonates with hypoxic respiratory failure and 25 controls were enrolled. 14/32 (44%) neonates with HRF required iNO, 9/32 (28%) required high-frequency ventilation and 3/32 (9%) required ECMO; 2/32 (6%) died. Neonates with HRF had more than threefold higher cord levels of interleukin 8 (IL8) than the controls (p<0.05). At 6 h and 30 h, serum IL6, IL8 and CRP were ⩾2.2-fold higher in neonates who received iNO (p<0.003). 23/32 (72%) infants with HRF had evidence of histological chorioamnionitis and/or funisitis compared with 5/25 (20%) controls (p<0.001).
Conclusion: Severe HRF, as defined by the need for iNO, is associated with raised blood levels of proinflammatory mediators and increased occurrence of histological chorioamnionitis and funisitis, suggesting that inflammation contributes to the severity of hypoxic failure.
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Competing interests: None.
Funding: These studies were in part supported by funds from the George L MacGregor Professorship in Pediatrics.
Ethics approval: The institution review board of the University of Texas Southwestern Medical Center at Dallas approved the study
Patient consent: Obtained.