Objectives: Low-dose indomethacin has been shown to prevent intraventricular hemorrhage (IVH) in very low birth weight neonates, and long-term neurodevelopmental follow-up data are needed to validate this intervention. We hypothesized that the early administration of low-dose indomethacin would not be associated with adverse cognitive outcome at 36 months' corrected age (CA).
Methods: We enrolled 431 neonates of 600 to 1250 g birth weight with no IVH at 6 to 12 hours in a randomized, prospective trial to determine whether low-dose indomethacin would prevent 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 survived (192 [92%] of 209 infants receiving indomethacin versus 192 [86%] of 222 infants receiving saline), and 343 (89%) children were examined at 36 months' CA. Thirteen (8%) of the 166 infants who received indomethacin and 14 (8%) of 167 infants receiving the placebo were found to have cerebral palsy. There were no differences in the incidence of deafness or blindness between the two groups. For the 248 English-monolingual children for whom IQ data follow, the mean gestational age was significantly younger for the infants who received indomethacin than for those who received the placebo. None of the 115 infants who received indomethacin was found to have ventriculomegaly on cranial ultrasound at term, compared with 5 of 110 infants who received the placebo. The mean +/- SD Stanford-Binet IQ score for the 126 English-monolingual children who had received indomethacin was 89.6 +/- 18.92, compared with 85.0 +/- 20.79 for the 122 English-monolingual children who had received the placebo. Although maternal education was strongly correlated with Stanford-Binet IQ at 36 months' CA, there was no difference in educational levels between mothers of the infants receiving indomethacin and the placebo.
Conclusions: Indomethacin administered at 6 to 12 hours as prophylaxis against IVH in very low birth weight infants does not result in adverse cognitive or motor outcomes at 36 months' CA.