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Published on: February 8, 2022
Outcome of children in the indomethacin intraventricular hemorrhage prevention trial
1Department of Pediatrics, Yale University School of Medicine, New Haven, CT 06511, USA. laura.ment@yale.edu
Insights
Early low-dose indomethacin treatment in preterm infants did not increase neurodevelopmental issues at 4.5 years. This treatment for very low birth weight infants showed no adverse effects on cognitive or motor skills.
Area of Science:
- Neonatal care
- Pediatric neurology
- Pharmacology
Background:
- Intraventricular hemorrhage (IVH) in preterm infants is linked to poor neurodevelopmental outcomes.
- Early low-dose indomethacin treatment reduces IVH incidence and severity in very low birth weight preterm infants.
Purpose of the Study:
- To assess if early low-dose indomethacin administration increases neurodevelopmental handicap in children at 4.5 years.
- To evaluate the long-term neurodevelopmental effects of IVH prevention strategies.
Main Methods:
- Neurodevelopmental follow-up of 337 very low birth weight survivors from a randomized trial.
- Evaluations at 54 months corrected age included cognitive tests (WPPSI-R, PPVT-R) and neurologic examinations.
Main Results:
- Cerebral palsy incidence was similar in indomethacin (7%) and placebo (7%) groups.
- Indomethacin group showed significantly less mental retardation (IQ <70: 9% vs 17%) and better vocabulary skills (PPVT-R).
- No significant differences in WPPSI-R or PPVT-R overall scores between groups.
Conclusions:
- Early low-dose indomethacin therapy for preterm neonates is not associated with adverse neurodevelopmental outcomes at 54 months corrected age.
- This treatment appears safe for long-term neurodevelopmental function.
Background:
For preterm infants, intraventricular hemorrhage (IVH) may be associated with adverse neurodevelopmental outcome. We have demonstrated that early low-dose indomethacin treatment is associated with a decrease in both the incidence and severity of IVH in very low birth weight preterm infants. In addition, we hypothesized that the early administration of low-dose indomethacin would not be associated with an increase in the incidence of neurodevelopmental 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 Indomethacin IVH Prevention Trial. Three hundred thirty-seven children (88%) were evaluated at 54 months' corrected age, and underwent neurodevelopmental examinations, including the Wechsler Preschool and Primary Scale of Intelligence-Revised (WPPSI-R), the Peabody Picture Vocabulary Test-Revised (PPVT-R), and standard neurologic examinations.
Results:
Of the 337 study children, 170 had been randomized to early low-dose indomethacin therapy and 167 children had received placebo. Twelve (7%) of the 165 indomethacin children and 11 (7%) of the 158 placebo children who 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 received indomethacin than for those who received placebo. In addition, although 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 demonstrated significantly less mental retardation among those children randomized 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 less difficulty with vocabulary skills as assessed by the PPVT-R when compared with placebo children.
Conclusions:
These data suggest that, for preterm neonates, the early administration of low-dose indomethacin therapy is not associated with adverse neurodevelopmental function at 54 months' corrected age.
