PEDIATRICS Vol. 89 No. 3 March 1992, pp. 359-364
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Hyperbilirubinemia in Low Birth Weight Infants and Outcome at 5 Years of Age

Margot van de Bor MD, PhD1, Martina Ens-Dokkum MD1, Anneke M. Schreuder MD1, Sylvia Veen MD1, Ronald Brand PhD1, and S. Pauline Verloove-Vanhorick MD, PhD1

1 From the Collaborative Project on Preterm and Small for Gestational Age Infants in the Netherlands, Departments of Pediatrics and Medical Statistics, University Hospital Leiden, Leiden, The Netherlands

The collaborative national survey on morbidity and mortality in preterm and small for gestational age infants in the Netherlands enrolled initially 1338 infants born in 1983. The relationship between maximal serum total bilirubin concentration in the neonatal period and neurodevelopmental outcome in the survivors of this cohort was studied. This relationship at the corrected age of 2 years was previously reported. A dose-response relationship between maximal serum total bilirubin concentration and risk of adverse outcome was observed in the 831 surviving children. The present study reassessed the relationship at the age of 5 years in 814 children. There was no significant difference in mean maximal serum total bilirubin concentration between the children with and without a handicap. This was confirmed by logistic regression analysis. After correction for seven suspected confounding factors (gestational age, birth weight, intracranial hemorrhage, ventriculomegaly, seizures, bronchopulmonary dysplasia, and socioeconomic status) the estimated odds ratio was 1.2 (confidence interval 0.89, 1.43) per 50 µmol/l increase of total bilirubin. However, in this analysis an interaction between bilirubin and intracranial hemorrhage was observed. Therefore, the cohort was divided into two groups according to the absence or presence of an intracranial hemorrhage. Logistic regression analysis including four suspected confounding factors (gestational age, ventriculomegaly. seizures, and socioeconomic status) was then again applied. In children who had suffered from an intracranial hemorrhage in the neonatal period the estimated odds ratio was 1.84 (confidence interval 1.08, 3.15) per 50 µmol/l increase of bilirubin. Similar results were obtained treating bilirubin as a categorized exposure. The odds ratio in children without a hemorrhage was 1.05 (confidence interval 0.80, 1.38), probably because of the small number of surviving handicapped children.

Key Words: hyperbilirubinemia • jaundice • preterm • neurodevelopmental outcome

Submitted on February 11, 1991
Accepted on September 5, 1991




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