title: 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.
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).
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, University of Oulu, Oulu, Finland.
authors.forename: Outi
authors.initials: O
authors.lastname: Aikio
authors.forename: Juhani
authors.initials: J
authors.lastname: Metsola
authors.forename: Reetta
authors.initials: R
authors.lastname: Vuolteenaho
authors.forename: Marja
authors.initials: M
authors.lastname: Perhomaa
authors.forename: Mikko
authors.initials: M
authors.lastname: Hallman
mesh_terms: D000280:Administration, Inhalation; D001993:Bronchodilator Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005322:Premature Rupture of Fetal Membranes; D006801:Humans; D000860:Hypoxia; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000188:drug therapy* / Q000503:physiopathology; D009569:Nitric Oxide / Q000008:administration & dosage / Q000096:biosynthesis / Q000627:therapeutic use*; D011247:Pregnancy; D012131:Respiratory Insufficiency / Q000188:drug therapy* / Q000453:epidemiology / Q000378:metabolism; D012307:Risk Factors
chemical_list: D001993:Bronchodilator Agents; D009569:Nitric Oxide