Adult neurobehavioral outcome of hyperbilirubinemia in full term neonates – a 30 year prospective follow-up study

Background. Neonatal hyperbilirubinemia (HB) may cause severe neurological damage, but serious consequences are effectively controlled by phototherapy and blood exchange transfusion. HB is still a serious health problem in economically compromised parts of the world. The long term outcome has been regarded favorable based on epidemiological data, but has not been confirmed in prospective follow-up studies extending to adulthood.Methods. We studied the long term consequences of HB in a prospective birth cohort of 128 HB cases and 82 controls. The cases are part of a neonatal at-risk cohort (n=1196) that has been followed up to 30 years of age. HB cases were newborns ≥ 2500 g birth weight and ≥ 37 weeks of gestation who had bilirubin concentrations > 340µmol/l or required blood exchange transfusion. Subjects with HB were divided into subgroups based on the presence (affected HB) or absence (unaffected HB) of diagnosed neurobehavioral disorders in childhood, and compared with healthy controls. Subjects were seen at discharge, 5, 9 and 16 years of life and parent’s and teacher’s assessments were recorded. At 30 years they filled a questionnaire about academic and occupational achievement, life satisfaction, somatic and psychiatric symptoms including a ADHD self-rating score. Cognitive functioning was tested using ITPA, WISC, and reading and writing tests at 9 years of life. Results. Compared to controls, the odds for a child with HB having neurobehavioral symptoms at 9 years was elevated (OR=4.68). Fortyfive per cent of the HB group were affected by cognitive abnormalities in childhood and continued to experience problems in adulthood. This was apparent in academic achievement (p<0.0001) and the ability to complete secondary (p<0.0001) and tertiary (p<0.004) education. Also, the subgroup of affected HB reported persisting cognitive complaints e.g. problems with reading, writing and mathematics. Childhood symptoms of hyperactivity/impulsivity (p<0.0001) and inattention (p<0.02) were more common in HB groups, but in adulthood the symptoms were equal. The affected HB had lower scores in parameters reflecting life satisfaction, less controlled drinking, but not increased substance abuse. Discussion. Our results indicate that neonatal HB has negative consequences in adult age. A prospectively collected cohort with strict inclusion criteria enables to control most of the bias factors involved with retrospective data. The control and HB groups were remarkably similar at birth in terms of medical data, and the growth environment of the children, as well as the parents’ social groups, education, size of family, type of housing at birth and at 9 years of age. Our findings bear resemblance to disorders of the fronto-striatal network, and also symptoms of the ADHD spectrum were frequent in the HB group suggesting a link of HB to other neurodevelopmental disorders.