Published online May 1, 2006
PEDIATRICS Vol. 117 No. 5 May 2006, pp. 1626-1631 (doi:10.1542/10.1542/peds.2005-1767)

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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

Steven P. Miller, MD^a,b, Eleanor E. Mayer, BA^c, Ronald I. Clyman, MD^d, David V. Glidden, PhD^e, Shannon E.G. Hamrick, MD^d and A. James Barkovich, MD^b

^a Departments of Neurology
^c Radiology
^d Pediatrics
^e Epidemiology and Biostatistics, University of California, San Francisco, California
^b Department of Pediatrics, University of British Columbia, Vancouver, British Columbia, Canada

OBJECTIVES. 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.

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Key Words: periventricular leukomalacia • MRI • brain injury • patent ductus arteriosus • indomethacin

Abbreviations: IVH—intraventricular hemorrhage • PMA—postmenstrual age • PDA— patent ductus arteriosus • CI—confidence interval • OR—odds ratio

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Accepted Oct 17, 2005.

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