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

Abstract

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 > 340 µmol/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). Forty-five 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.

Impact of bilirubin-induced neurologic dysfunction on neurodevelopmental outcomes

“…Similarly, there are some clinical data to suggest a link between neonatal hyperbilirubinemia and later decreased IQ. Most recently, a prospective cohort born 1971–1974 in Helsinki, Finland was followed for 30 years to determine neurobehavioral outcomes [12]. Within the larger overall cohort, the investigators identified 128 cases with neonatal hyperbilirubinemia, defined as TB > 340 mmol/L (20 mg/dL) or requiring exchange transfusion.…”

“…Deficits in executive function have been found in children with history of preterm birth [25–27], ADHD, autism, and learning disabilities [28,29]. Although studies on bilirubin neurotoxicity have not focused on executive functions per se, some studies have identified attention problems [7] and lower academic achievement in children with hyperbilirubinemia [12], two domains affected in other clinical populations at high risk for executive function impairment.…”

“…The Finnish birth risk cohort described above assessed a variety of outcomes, including symptoms of inattention and hyperactivity/impulsivity [12]. In this longitudinal study, children were assessed at ages 5 and 9 years with direct assessment as well as parent questionnaires; 15% had hyperactivity and attention deficit [12].…”

“…In this longitudinal study, children were assessed at ages 5 and 9 years with direct assessment as well as parent questionnaires; 15% had hyperactivity and attention deficit [12]. Children were classified as having (affected) or not having (unaffected) different developmental disorders at age 9 years in both the hyperbilirubinemia and control groups, and these dichotomized groups were used to evaluate risk associated with hyperbilirubinemia at age 30years in comparison with controls.…”

Descriptive epidemiology of prenatal and perinatal risk factors in a Chinese population with reading disorder

“…van Handel et al 24 reviewed that mild neonatal encephalopathy following perinatal asphyxia increased the risk of reading and spelling difficulties in children with norm intelligence quotient. Children who affected neonatal hyperbilirubinemia had persisting problems with reading, writing and mathematics in a prospective birth cohort25.…”