title: Increasing F2-isoprostanes in the first month after birth predicts poor respiratory and neurodevelopmental outcomes in very preterm infants.
abstract: This study examined the association between increased early oxidative stress, measured by F2-isoprostanes (IsoPs), and respiratory morbidity at term equivalent age and neurological impairment at 12 months of corrected age (CA).
  
  
  
  Plasma samples were collected from 136 premature infants on days 14 and 28 after birth. All participants were infants born at ⩽28 weeks of gestational age enrolled into the Prematurity and Respiratory Outcomes Program (PROP) study. Respiratory morbidity was determined at 40 weeks of postmenstrual age (PMA) by the Respiratory Severity Index (RSI), a composite measure of oxygen and pressure support. Neurodevelopmental assessment was performed using the Developmental Assessment of Young Children (DAYC) at 12 months of CA. Multivariable logistic regression models estimated associations between IsoP change, RSI and DAYC scores. Mediation analysis was performed to determine the relationship between IsoPs and later outcomes.
  
  
  
  Developmental data were available for 121 patients (90% of enrolled) at 12 months. For each 50-unit increase in IsoPs, regression modeling predicted decreases in cognitive, communication and motor scores of -1.9, -1.2 and -2.4 points, respectively (P<0.001). IsoP increase was also associated with increased RSI at 40 weeks of PMA (odds ratio=1.23; P=0.01). RSI mediated 25% of the IsoP effect on DAYC motor scores (P=0.02) and had no significant impact on cognitive or communication scores.
  
  
  
  In the first month after birth, increases in plasma IsoPs identify preterm infants at risk for respiratory morbidity at term equivalent age and worse developmental outcomes at 12 months of CA. Poor neurodevelopment is largely independent of respiratory morbidity.
authors.affiliation: Department of Pediatrics, Division of Neonatal-Perinatal Medicine, University of Texas Health Science Center, Houston, TX, USA.
authors.forename: M A
authors.initials: MA
authors.lastname: Matthews
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.|Departments of Pediatrics and Obstetrics and Gynecology and Woman's Health, Albert Einstein College of Medicine of Montefiore Health and The Children's Hospital at Montefiore, Bronx, NY, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Aschner
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: A R
authors.initials: AR
authors.lastname: Stark
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: P E
authors.initials: PE
authors.lastname: Moore
authors.affiliation: Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: J C
authors.initials: JC
authors.lastname: Slaughter
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: S
authors.initials: S
authors.lastname: Steele
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: A
authors.initials: A
authors.lastname: Beller
authors.affiliation: Division of Clinical Pharmacology, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Milne
authors.affiliation: Department of Pediatrics, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: O
authors.initials: O
authors.lastname: Settles
authors.affiliation: Department of Pediatrics and the Center for Perinatal Research, Nationwide Children's Hospital, Columbus OH, USA.
authors.forename: O
authors.initials: O
authors.lastname: Chorna
authors.affiliation: Department of Pediatrics and the Center for Perinatal Research, Nationwide Children's Hospital, Columbus OH, USA.|Department of Hearing and Speech Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Maitre
mesh_terms: D001997:Bronchopulmonary Dysplasia / Q000097:blood* / Q000523:psychology*; D002657:Child Development; D003071:Cognition; D003142:Communication; D028441:F2-Isoprostanes / Q000097:blood*; D005260:Female; D005865:Gestational Age; D006801:Humans; D007223:Infant; D062071:Infant, Extremely Premature / Q000097:blood* / Q000254:growth & development; D007231:Infant, Newborn; D019102:Infant, Very Low Birth Weight / Q000097:blood* / Q000254:growth & development; D016015:Logistic Models; D008297:Male; D009048:Motor Skills; D015999:Multivariate Analysis; D011446:Prospective Studies; D012720:Severity of Illness Index; D013714:Tennessee
chemical_list: D028441:F2-Isoprostanes