Transient defect in nitric oxide generation after rupture of fetal membranes and responsiveness to inhaled nitric oxide in very preterm infants with hypoxic respiratory failure

J Pediatr. 2012 Sep;161(3):397-403.e1. doi: 10.1016/j.jpeds.2012.03.008. Epub 2012 May 1.

Abstract

Objective: To study antenatal risk factors and inflammatory responses during hypoxic respiratory failure (HRF) in infants of very low gestational age (VLGA, ≤32.0 weeks).

Study design: Of a cohort of 765 VLGA infants, 144 required mechanical ventilation. Airway specimens from these patients were prospectively studied. Infants who developed HRF (oxygenation index >25) with echocardiographic diagnosis of pulmonary hypertension were treated with inhaled nitric oxide (iNO). Three gestation comparison groups were formed on the basis of specific antenatal complications: prolonged preterm rupture of membranes (PPROM), spontaneous preterm birth, and preeclampsia. Chest radiographs were studied and airway specimens were analyzed for concentrations of tumor necrosis factor-α, interleukin (IL)-6, IL-8, IL-10, IL-12p70, IL-1β, and nitrite + nitrate over 4 days.

Results: Seventeen (2.2% of all VLGA infants) developed HRF. In all 17 cases, PPROM complicated the antenatal course; these infants responded to iNO, regardless of infection or PPROM. The chest radiographs of HRF and non-HRF PPROM infants were similar. Airway proinflammatory cytokines and nitrite + nitrate levels were low in infants with HRF, but they increased during iNO treatment and remained elevated after discontinuation of iNO. Each of the 3 comparison groups had different and characteristic patterns of airway cytokines and nitrite + nitrate levels.

Conclusions: Seven percent of VLGA infants with preterm rupture of membranes and 15% of those with PPROM developed HRF, characterized by pulmonary hypertension that acutely responds to iNO. These infants may have a transient deficiency in the inflammatory response, including a defect in nitric oxide generation in airspaces.

MeSH terms

  • Administration, Inhalation
  • Bronchodilator Agents / administration & dosage
  • Bronchodilator Agents / therapeutic use*
  • Female
  • Fetal Membranes, Premature Rupture
  • Humans
  • Hypoxia
  • Infant, Newborn
  • Infant, Premature
  • Infant, Premature, Diseases / drug therapy*
  • Infant, Premature, Diseases / physiopathology
  • Nitric Oxide / administration & dosage
  • Nitric Oxide / biosynthesis
  • Nitric Oxide / therapeutic use*
  • Pregnancy
  • Respiratory Insufficiency / drug therapy*
  • Respiratory Insufficiency / epidemiology
  • Respiratory Insufficiency / metabolism
  • Risk Factors

Substances

  • Bronchodilator Agents
  • Nitric Oxide