Neurodevelopment of Preterm Infants: Neonatal Neurosonographic and Serum Bilirubin Studies

Abstract

In this study of 249 preterm infants of less than 34 weeks's gestation, the relationships between maximal serum total bilirubin concentrations during the neonatal period, neonatal cranial ultrasonographic abnormalities, and severe neurodevelopmental sequelae are described. The subjects, who were selected on the basis of serial cranial ultrasonographic findings, had repeated neurologic and developmental examinations during late infancy and early childhood that established the presence (n = 45) or absence (n = 204) of spastic forms of cerebral palsy. Of the 204 subjects without cerebral palsy, 23 scored abnormally low on standardized developmental testing during early childhood. All but seven of the subjects with cerebral palsy had grade III/IV intracranial hemorrhage or moderate to severe periventricular echogenicity or both, ultrasonographic abnormalities that probably reflect a disruption in the blood-brain barrier as well as extravasation of blood into brain tissue; however, analysis of the data did not suggest that these cranial ultrasonographic abnormalities increased either the maximum serum bilirubin concentration during the neonatal period or the susceptibility of the subjects to neurologic damage from hyperbilirubinemia. Also, there was no evidence to suggest that bilirubinemia in the range studied (2.3 to 22.5 mg/100 mL total serum bilirubin) was causally related to cerebral palsy, early developmental delay, or the development of periventricular cysts in this population of preterm infants. Univariate analyses revealed that Apgar scores were significantly lower, while grade III/IV intracranial hemorrhage, large periventricular cysts, moderate to severe periventricular echodensity, ventriculomegaly, assisted ventilation, and bronchopulmonary dysplasia occurred significantly more often in infants with cerebral palsy than in those without cerebral palsy; however, a stepwise logistic regression revealed that of these clinical variables only large periventricular cysts, moderate to severe periventricular echodensity, and the need for assisted ventilation were associated with the occurrence of cerebral palsy at a statistically significant level. Apgar scores and average birth weight were significantly lower, and duration of assisted ventilation was significantly longer, but neurosonographic findings did not differ in the 23 developmentally delayed infants compared with the normal group.