Antecedents of Cerebral Palsy in a Multicenter Trial of Indomethacin for Intraventricular Hemorrhage

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Abstract
To determine if cerebral palsy (CP) rates were lower in the active treatment group compared with the control group, as improved survival rates of very low-birth-weight infants are postulated to be the cause of the increased incidence of CP in preterm infants, to evaluate relationships between multiple prenatal, perinatal, and postnatal variables and CP to understand better its antecedents in very low-birth-weight infants in the era of surfactant replacement therapy, and to determine the usefulness of a cranial ultrasonographic (US) scan in predicting CP. Inception cohort follow-up study as part of a randomized controlled trial of low-dose indomethacin sodium for the prevention of intraventricular hemorrhage. Neonatal intensive care units at 3 medical centers. Infants with birth weights between 600 and 1250 g were eligible, and 505 infants were enrolled in the original study. Of these infants, 440 (87%) survived; neurologic examinations were completed on 381 infants (86%) at 36 months corrected age. Statistical analyses were performed to identify the antecedents of CP, including the results of frequent cranial US scans obtained throughout the newborn period. Cerebral palsy was found in 36 (9.5%) of 381 infants at 36 months corrected age (range, 33-39 months corrected age). Univariate analysis identified chorioamnionitis, treatment with surfactant, bronchopulmonary dysplasia, and abnormal cranial US findings as antecedents of CP. Periventricular leukomalacia and ventriculomegaly were associated with the highest detection rates for CP (37% and 30%, respectively) with acceptable false-positive rates. Multivariate analysis identified bronchopulmonary dysplasia and an abnormal cranial US scan showing grade 3 to 4 intraventricular hemorrhage, periventricular leukomalacia, or ventriculomegaly as independent predictors of CP. Odds ratios for the detection of CP using cranial US findings tabulated by hospital day were in the range of 7 to 26 beginning on day 2. The results suggest that cranial US findings are useful predictors of CP during a patient's stay in the hospital.