Published online September 1, 2006
PEDIATRICS Vol. 118 No. 3 September 2006, pp. 961-970 (doi:10.1542/10.1542/peds.2005-2870)

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ARTICLE

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

Laura R. Ment, MD^a,b, Bradley S. Peterson, MD^c, Jed A. Meltzer, PhD^d, Betty Vohr, MD^e, Walter Allan, MD^f, Karol H. Katz, MS^a, Cheryl Lacadie, BS^d, Karen C. Schneider, MPH^a, Charles C. Duncan, MD^a,g, Robert W. Makuch, PhD^g and R. Todd Constable, PhD^d

^a Departments of Pediatrics
^b Neurology
^d Diagnostic Imaging Epidemiology and Public Health
^g Neurosurgery, Yale University School of Medicine, New Haven, Connecticut
^c Columbia College of Physicians and Surgeons and the New York State Psychiatric Institute, New York, New York
^e Department of Pediatrics, Brown Medical School, Providence, Rhode Island
^f Departments of Pediatrics and Neurology, Maine Medical Center, Portland, Maine

BACKGROUND. 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.

OBJECTIVE. 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.

METHODS. 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.

RESULTS. 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.

CONCLUSIONS. 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.

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Key Words: functional magnetic resonance imaging • premature • indomethacin • neurodevelopmental outcome

Abbreviations: IVH—intraventricular hemorrhage • VLBW—very low birth weight • CNS—central nervous system • fMRI—functional magnetic resonance imaging • PPVT—Peabody Picture Vocabulary Test • IQ—intelligence quotient • FSIQ—full-scale intelligence quotient • VIQ—verbal intelligence quotient • PIQ—performance intelligence quotient • IPL—inferior parietal lobule • IFG—inferior frontal gyrus • DLPF—dorsolateral prefrontal cortex • BA—Brodmann’s area

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Accepted Apr 10, 2006.

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