ABSTRACT
Plasma protein levels of 3-nitrotyrosine and 3-chlorotyrosine were measured by LC-MS/MS at 0 and 72 h after the initiation of inhaled nitric oxide (INO) at 20 ppm in 22 prematurely born infants with clinically documented bronchopulmonary dysplasia. Infants were classified at the time of hospital discharge as either "off mechanical ventilation," "on mechanical ventilation," or "expired/organ failure." These outcomes were tested for association with changes in plasma levels of 3-nitrotyrosine and 3-chlorotyrosine and selected clinical risk factors. Infants whose 3-nitrotyrosine levels decreased over the 72 h period were more likely to wean off of mechanical ventilation (p =.03). There was no significant association between changes in 3-chlorotyrosne levels and outcome. After controlling for other variables, an odds ratio of 8.3 (95% CI: 1.3-54.4) for improved outcomes was observed if the 3-nitrotyrosine levels decreased. These data suggest that nitrative and oxidative stress may be related to the severity of lung disease and, consequentially, the overall outcome in this select group of infants with severe bronchopulmonary dysplasia.
Subject(s)
Bronchopulmonary Dysplasia/blood , Bronchopulmonary Dysplasia/drug therapy , Nitric Oxide/administration & dosage , Nitric Oxide/therapeutic use , Tyrosine/analogs & derivatives , Tyrosine/blood , Administration, Inhalation , Birth Weight , Chromatography, High Pressure Liquid , Female , Gestational Age , Humans , Infant , Infant, Newborn , Logistic Models , Male , Mass Spectrometry , Risk Factors , Time Factors , Treatment Outcome , Ventilators, MechanicalABSTRACT
OBJECTIVE: Determine whether the increased neonatal mortality following repeated courses of antenatal corticosteroids (ANCS), observed in the Thyrotropin-Releasing Hormone (TRH) Trial, was related to confounding maternal risk factors or specific preterm morbidities. STUDY DESIGN: A post hoc analysis of 595 TRH trial neonates, 26 to 32 weeks' gestation, studied the association between > or =3 courses ANCS and mortality. Potential confounding maternal factors and preterm morbidities were evaluated using logistic regression and log likelihood modeling. RESULTS: Mortality was 9.2% after > or =3 courses (13/141) vs. 4.8% after 1 or 2 courses (22/454). This association was not explained by maternal factors, or other common preterm morbidities. However, 15/141 infants receiving > or =3 courses (10.6%) had early severe lung disease (ESLD) with 10 deaths, compared to 16/454 of the 1- to 2-course infants (3.5%) with 7 deaths (odds ratio 3.5, p<0.001). CONCLUSIONS: ESLD, but not maternal risk factors, was associated with increased mortality in preterm infants after > or =3 courses ANCS.