A Functional Magnetic Resonance Imaging Study of the Long-term Influences of Early Indomethacin Exposure on Language Processing in the Brains of Prematurely Born Children

Abstract

Previous studies have demonstrated that indomethacin lowers the incidence and decreases the severity of intraventricular hemorrhage, as well as improves the cognitive outcome, in prematurely born male infants. The purpose of this work was to use functional magnetic resonance imaging to test the hypothesis that neonatal indomethacin treatment would differentially affect brain activation across genders in school-aged, prematurely born children during performance of a language task. Forty-seven prematurely born children (600-1250-g birth weight) and 24 matched term control subjects were evaluated using a functional magnetic resonance imaging passive language task and neurodevelopmental assessments that included the Wechsler Intelligence Scale for Children-III and the Peabody Picture Vocabulary Test-Revised. Neural activity was assessed during both phonologic and semantic processing in the functional magnetic resonance imaging protocol. Neurodevelopmental assessments demonstrated significant differences in full-scale, verbal, and performance intelligence quotient, as well as Peabody Picture Vocabulary Test scores, between the preterm and term control subjects. Rates of perinatal complications did not differ significantly across preterm treatment groups, but male preterm subjects randomly assigned to saline tended to have lower Peabody Picture Vocabulary Test-Revised scores than did all of the other preterm groups. During phonological processing, a significant treatment-by-gender effect was demonstrated in 3 brain regions: the left inferior parietal lobule, the left inferior frontal gyrus (Broca's area), and the right dorsolateral prefrontal cortex. These data demonstrate a differential effect of indomethacin administration early in postnatal life on the subsequent development of neural systems that subserve language functioning in these male and female preterm infants.