Recurrent postnatal infections are associated with progressive white matter injury in premature infants

OBJECTIVE. Our objective was to identify clinical predictors of progressive white matter injury. METHODS. We evaluated 133 infants of < 34 weeks of gestation at birth from 2 university hospitals. Infants underwent MRI twice, initially when in stable condition for transport and again at term-equivalent age or before transfer or discharge. Two neuroradiologists who were blinded to the clinical course graded MRI white matter injury severity by using a validated scale. Potential risk factors were extracted from medical charts. RESULTS. Twelve neonates (9.0%) had progressive white matter injury. In the unadjusted analysis of 10 newborns without Candida meningoencephalitis, recurrent culture-positive postnatal infection and chronic lung disease were associated with progressive white matter injury. Exposure to multiple episodes of culture-positive infection significantly increased the risk of progressive white matter injury. Of the 11 neonates with > 1 infection, 36.4% (4 infants) had progressive injury, compared with 5.0% (6 infants) of those with <= 1 infection. Of the 35 infants with chronic lung disease, 17.1% (6 infants) had progressive injury, compared with 4.3% (4 infants) of those without chronic lung disease. After adjustment for gestational age at birth, the association between infection and white matter injury persisted, whereas chronic lung disease was no longer a statistically significant risk factor. CONCLUSIONS. Recurrent postnatal infection is an important risk factor for progressive white matter injury in premature infants. This is consistent with emerging evidence that white matter injury is attributable to oligodendrocyte precursor susceptibility to inflammation, hypoxia, and ischemia.