Outcome of children in the indomethacin intraventricular hemorrhage prevention trial

Background. For preterm infants, intraventricular hemorrhage (IVH) may be a ssociated with adverse neurodevelopmental outcome. We have demonstrated tha t early low-dose indomethacin treatment is associated with a decrease in bo th the incidence and severity of IVH in very low birth weight preterm infan ts. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of n eurodevelopmental handicap at 4.5 years of age in our study children. Methods. To test this hypothesis, we provided neurodevelopmental follow-up for the 384 very low birth weight survivors of the Multicenter Randomized I ndomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopment al examinations, including the Wechsler Preschool and Primary Scale of Inte lligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PP VT-R), and standard neurologic examinations. Results. Of the 337 study children, 170 had been randomized to early low-do se indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children wh o underwent neurologic examinations were found to have cerebral palsy. For the 233 English-monolingual children for whom cognitive outcome data follow , the mean gestational age was significantly younger for the children who r eceived indomethacin than for those who received placebo. In addition, alth ough there were no differences in the WPPSI-R or the PPVT-R scores between the 2 groups, analysis of the WPPSI-R full-scale IQ by function range demon strated significantly less mental retardation among those children randomiz ed to early low-dose indomethacin (for the indomethacin study children, 9% had an IQ <70, 12% had an IQ of 70-80, and 79% had an IQ >80, compared with the placebo group, for whom 17% had an IQ <70, 18% had an IQ of 70-80, and 65% had an IQ >80). Indomethacin children also experienced significantly l ess difficulty with vocabulary skills as assessed by the PPVT-R when compar ed with placebo children. Conclusions. These data suggest that, for preterm neonates, the early admin istration of low-dose indomethacin therapy is not associated with adverse n eurodevelopmental function at 54 months' corrected age.