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

Aikio O et al. – Seven percent of VLGA infants with preterm rupture of membranes and 15% of those with prolonged preterm rupture of membranes (PPROM) developed hypoxic respiratory failure (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.

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.

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.

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