Intraventricular hemorrhage (IVH) results in significant neurodevelopmental handicap in preterm infants. Our multicenter, randomized, placebo-controlled trial demonstrated that indomethacin lowered the incidence of IVH in very low birth weight (VLBW) preterm infants. Reanalysis of our data revealed that the indomethacin-IVH effect occurred exclusively in males, reducing the IVH rate from 22% to 9%. Verbal test scores improved for all subjects. Male indomethacin subjects exhibited better verbal test scores during grade school than male placebo children, and a significant indomethacin x gender interaction was noted. To explore the suggestion that indomethacin, a neonatal intervention, may have a long-lasting effect on developing brain, the following hypotheses will be tested: (1.) Children randomized to indomethacin will continue to demonstrate a benefit in verbal and cognitive skills when compared to placebo subjects at ages 12 & 16 years; the effect of gender will be examined; (2.) Verbal skills will continue to improve during adolescence in VLBW preterm subjects compared to matched control teens; the effects of indomethacin, gender and MRI indices will be examined to assess the interactions of these critical variables; and (3.) Cortical maturation as assessed by MRI measures will differ between VLBW subject and term control teens between ages 12-16 years. Study participants will undergo assessment of verbal and cognitive skills at ages 12 and 16 years to compare subjects randomized to indomethacin and placebo; gender effects will be assessed. Serial assessments of cognitive/verbal function at ages 12 and 16 years will compare patterns of change in testing measures across time in preterm subjects and control teens; the effects of indomethacin, gender and MRI measures including volumetric analyses, gyrification indices, diffusion tensor imaging and functional MRI on cognitive outcome will be examined. Serial MRI scans will determine growth patterns of cortical regions across time.
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