title: Prolonged indomethacin exposure is associated with decreased white matter injury detected with magnetic resonance imaging in premature newborns at 24 to 28 weeks' gestation at birth.
abstract: OBJECTIVE
  Newborns delivered before 28 weeks' gestation commonly have white matter lesions on MRI that are associated with adverse neurodevelopmental outcomes. Our objective was to determine the risk factors for MRI-detectable white matter injury in infants delivered before 28 weeks' gestation who were treated with prophylactic indomethacin.
  
  
  METHODS
  This was a prospective cohort study conducted at the intensive care nursery at University of California San Francisco Children's Hospital. Patients included 57 premature newborns between 24 and 27 (+6 days) weeks' gestation at birth (October 1998 to October 2004). We identified perinatal and neonatal risk factors associated with moderate-severe "white matter injuries" (T1 signal abnormalities >2 mm or >3 areas of T1 abnormality) and moderate-severe "brain abnormality" (moderate-severe white matter injuries, any degree of ventriculomegaly, or severe intraventricular hemorrhage) on MRI. Infants were studied with MRI at 31.1 weeks' postmenstrual age (median).
  
  
  RESULTS
  Moderate-severe white matter injuries were detected in 12 (21%) of 53 preterm newborns, and 20 (35%) of 57 had moderate-severe brain abnormality. Prolonged indomethacin exposure was the only risk factor independently associated with a lower risk of white matter injury or brain abnormality, even when adjusting for the presence of a hemodynamically significant PDA, gestational age at birth, prenatal betamethasone, systemic infection, and days of mechanical ventilation.
  
  
  CONCLUSIONS
  In this observational study, a longer duration of indomethacin exposure was associated with less white matter injury in infants delivered before 28 weeks' gestation. A randomized trial of prolonged indomethacin treatment is needed to determine whether indomethacin can decrease white matter injury and neurodevelopmental abnormalities.
authors.affiliation: Department of Neurology, University of California, San Francisco, California, USA. millerst@neuropeds.ucsf.edu
authors.forename: Steven P
authors.initials: SP
authors.lastname: Miller
authors.forename: Eleanor E
authors.initials: EE
authors.lastname: Mayer
authors.forename: Ronald I
authors.initials: RI
authors.lastname: Clyman
authors.forename: David V
authors.initials: DV
authors.lastname: Glidden
authors.forename: Shannon E G
authors.initials: SE
authors.lastname: Hamrick
authors.forename: A James
authors.initials: AJ
authors.lastname: Barkovich
mesh_terms: D001921:Brain / Q000187:drug effects / Q000473:pathology*; D001925:Brain Damage, Chronic / Q000175:diagnosis / Q000517:prevention & control*; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage*; D004374:Ductus Arteriosus, Patent / Q000517:prevention & control; D005865:Gestational Age; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000175:diagnosis / Q000517:prevention & control*; D008279:Magnetic Resonance Imaging
chemical_list: D016861:Cyclooxygenase Inhibitors; D007213:Indomethacin