4.7 Article

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

期刊

PEDIATRICS
卷 117, 期 5, 页码 1626-1631

出版社

AMER ACAD PEDIATRICS
DOI: 10.1542/peds.2005-1767

关键词

periventricular leukomalacia; MRI; brain injury; patent ductus arteriosus; indomethacin

资金

  1. NCRR NIH HHS [5 M01 RR-01271] Funding Source: Medline
  2. NHLBI NIH HHS [HL466911, HL56061] Funding Source: Medline
  3. NINDS NIH HHS [NS40117, NS35902, NS046432] Funding Source: Medline

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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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