NEURODEVELOPMENTAL OUTCOME AT 36 MONTHS CORRECTED AGE OF PRETERM INFANTS IN THE MULTICENTER INDOMETHACIN INTRAVENTRICULAR HEMORRHAGE PREVENTION TRIAL

Objectives. Low-dose indomethacin has been shown to prevent intraventr icular hemorrhage (IVH) in very low birth weight neonates, and long-te rm neurodevelomental follow-up data are needed to validate this interv ention. We hypothesized that the early administration of low-dose indo methacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA). Methods. We enrolled 431 neonates of 600 t o 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, pr ospective trial to determine whether low-dose indomethacin would preve nt IVH. A priori, neurodevelopmental follow-up examinations, including the Stanford-Binet Intelligence Scale and Peabody Picture Vocabulary Test-Revised, and standard neurologic examinations were planned at 36 months' CA. Results. Three hundred eighty-four of the 431 infants surv ived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examine d at 36 months' CA. Thirteen (8%) of the 166 infants who received indo methacin and 14 (8%) of 167 infants receiving the placebo were found t o have cerebral palsy. There were no differences in the incidence of d eafness or blindness between the two groups. For the 248 English-monol ingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than f or those who received the placebo. None of the 115 infants who receive d indomethacin was found to have ventriculomegaly on cranial ultrasoun d at term, compared with 5 of 110 infants who received the placebo. Th e mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared wi th 85.0 +/- 20.79 for the 122 English-monolingual children who had rec eived the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in e ducational levels between mothers of the infants receiving indomethaci n and the placebo. Conclusions. Indomethacin administered at 6 to 12 h ours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.