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-1ß, 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.
Subject(s)
Bronchodilator Agents/therapeutic use , Infant, Premature, Diseases/drug therapy , Nitric Oxide/therapeutic use , Respiratory Insufficiency/drug therapy , Administration, Inhalation , Bronchodilator Agents/administration & dosage , Female , Fetal Membranes, Premature Rupture , Humans , Hypoxia , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/physiopathology , Nitric Oxide/administration & dosage , Nitric Oxide/biosynthesis , Pregnancy , Respiratory Insufficiency/epidemiology , Respiratory Insufficiency/metabolism , Risk FactorsABSTRACT
OBJECTIVE: To evaluate the influence of chorioamnionitis (CA) on plasma cytokines and the cytokine-associated risk of bronchopulmonary dysplasia (BPD) during the perinatal period. STUDY DESIGN: Eleven cytokines from 128 very low gestational age infants were analyzed from cord blood and from plasma at ages 1 day and 7 days after birth. The diagnosis of CA was based on histology of the placenta, fetal membranes, and umbilical cord. Neonatal risk factors were recorded. RESULTS: In the 48 infants born with CA, high concentrations of inflammatory cytokines in cord blood decreased during the first postnatal day. Inflammatory cytokines in cord blood was associated with the severity of CA. At 1 day after birth, the concentration of interleukin (IL)-8 predicted the risk of BPD. For the 75 infants born without CA, cytokine concentrations increased after birth. For the 128 infants born with or without CA, at 1 day after birth, the concentrations of IL-8, granulocyte colony-stimulating factor, and anti-inflammatory IL-10 were associated with the risk of BPD, after adjustment for the duration of gestation and severity of respiratory distress during the first day. CONCLUSIONS: In infants exposed to CA, insufficient inhibition of high fetal inflammatory cytokine response shortly after birth may increase the risk of BPD.