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Brief Reports Indian Pediatrics 2001; 38: 165-168 |
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Neurological Prognosis in Term Newborns with Neonatal Indirect Hyperbilirubinemia |
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Neonatal indirect hyperbilirubinemia is a common problem in the neonatal period. Neurological disturbances such as athetoid-dystonic cerebral palsy, hearing loss, gaze palsy, developmental delay, and impairment of intelligence due to kernicterus are serious problems(1-4). Although neonatal indirect hyperbili-rubinemia (NIH) has long been a known entity, its management and outcome continue to be problematic. There are several studies relating bilirubin levels with neuro-developmental outcome, but the relationship between serum bilirubin levels and long term neurological outcome remains controversial and the limit of bilirubin for exchange transfusion are still unclear(5-11). This study was designed to investigate the neurological prognosis and related factors of NIH in term newborns.
Between January 1990 and December 1996, 1428 newborns were treated at our hospital for NIH. After excluding preterms and small for gestational age babies and patients with metabolic abnormalities, infec-tion, hypoxia-ischemia, congenital malforma-tions, and babies with any complication during or after exchange transfusion, there remained 755 healthy term newborns. The data on the jaundice in the neonatal period were obtained from the hospital records and documented. Features of indirect hyper-bilirubinemia such as the maximum serum indirect bilirubin (SIB) level, onset, duration, etiology, and management of jaundice were evaluated. STB levels during the newborn period had been measured every 4-12 hours using the method of Jendrassik. The duration of jaundice was determined as being the time from the onset of jaundice (according to the observation of the family) until the time when the SIB level decreased to 12 mg/dl. We attempted to reach each of these potential candidates for the study. The eighty-seven children we were able to reach (29 girls, 58 boys; mean age 32.6 ± 16.7 months; range: 10-72 months) participated in this study. There were no statistically significant differences between the available and lost cohort with regard to serum indirect bilirubin levels, duration of jaundice, and birth weight. None of the children had a history of any medical problem that could have interfered with his/her neurological or physical develop-ment before the last examination. All cases underwent complete physical and neurological examinations carried out by a pediatric neurologist who was blinded to the neonatal records of the patients. The develop-mental status was tested by the Denver II Developmental Screening Test. Hearing func-tion was investigated by clinical examination. The BERA (Brain Stem Evoked Response Auditory) test could only be performed in 5 cases. Neonatal risk factors for neurological sequalae such as the maximum serum indirect bilirubin levels, onset and duration of jaundice were evaluated using Student ‘t’ test, Mann Whitney-U test, and Fisher/Chi-square tests.
Neurological dysfunction was observed in 11.5% (10/87) of all cases. The Denver II developmental screening test was abnormal in three cases. Patients with maximum SIB levels of less than 20 mg/dl (n = 10) did not show any neurological abnormalities, where-as 9.3% (4/43) of the cases with bilirubin levels of 20-23.9 mg/dl had only dyscon-jugated gaze movements and 17.6% (6/34) of the cases with ³24 mg/dl SIB levels had neurological manifestations {dystonic athe-toid cerebral palsy (n = 2), pschosocial-motor retardation(n = 3), limitation of gaze move-ments (n = 2), mild hypotonia (n = 1), hear-ing loss (n = 1), ataxia-dysmetrie (n = 1)]. Table I compares neonatal risk factors in cases with and without neurologic abnormal-ity. Cases with neurological abnormality had significantly higher peak serum bilirubin levels and longer duration of jaundice than those who were neurologically normal.
There was no statistically significant relationship between the etiology of hyper-bilirubinemia and the neurological prognosis. The prevalence of neurological abnormality in cases with Rh incompatibility (n = 14), ABO incompatibility (n = 38) and non hemolytic jaundice (n = 35) were 21.4%, 10.5% and 8.6%, respectively. Similarly, there was no association of neurological abnormality with mode of treatment (11.4% treated with only phototherapy and 11.5% treated with exchange transfusion plus phototherapy).
Since kernicterus is a serious entity with severe neurological sequelae in survivors, criteria for treatment requires a high level of sensitivity. The critical level for intervention should be at or below the threshold level for bilirubin neurotoxicity. Since the earlier reports, the "20 mg/dl level" of serum bilirubin has been generally accepted as the limit value of exchange transfusions in full-term newborns with hemolytic disease(1,2). Despite traditional treatment based on vigintophobia (fear of 20), recent studies have proposed a new criterion for exchange transfusion; that is, bilirubin levels of 25 mg/dl in nonhemolytic and otherwise well babies(12,13). The serum bilirubin level which result in neuronal toxicity is not yet clear, and the management for term newborns with serum bilirubin concentrations of ³20 mg/dl has become controversial. In this study, there was a statistically significant relationship between the neurolo-gical outcome and bilirubin levels. However, neurologically disabled children with SIB levels of 20-23.9 mg/dl had only minor neurological dysfunction (dysconjugated gaze movements), whereas babies with SIB levels of ³24 mg/dl had moderate to severe neuro-logical sequelae, such as dystonicathetoid cerebral palsy, and psychomotor retardation. Several reports relating serum bilirubin levels to neurological outcome have been published, but some of these studies did not support the hypothesis that newborns with serum bilirubin levels between 20-24 mg/dl are at a greater risk of neurological abnormalities(5,12,13). Our results suggested that serum bilirubin levels >20 mg/dl increase the risk for neuro-logical abnormalities. The duration of exposure to hyperbili-rubinemia may be a more important predictor for bilirubin neurotoxicity than the peak bilirubin level alone. Nilsen et al. reported that cases with bilirubin levels higher than 15 mg/dl where the duration of the exposure to hyperbilirubinemia exceeded 5 days showed lower IQ scores(14). In a study by Ozmert et al., the mean duration of high bilirubin in children with prominent neurological abnor-malities was longer than that of those without neurological findings(15). Contrary to these results, Sheidt et al. reported that the duration of exposure to bilirubin was not associated with IQ scores, but the bilirubin levels of most patients were less than 20 mg/dl(16). In our study, the prevalance of neurological abnor-malities of cases with duration of jaundice above 4 days was 18.6%, whereas none of the cases in whom jaundice existed for 2 days or less had any neurological abnormality. These results suggest that patients in whom the duration of jaundice is longer are more likely to develop neurological abnormalities due to bilirubin neurotoxicity. Further studies consisting of a large number of series and long-term follow-up periods are needed to clarify reasonable and confirmatory criterion for the management of hyperbilirubinemia in healthy term newborns. Contributors: YY co-ordinated the study, examined the children neurologically and drafted the paper. LK participated in the documentation of the hospital records and collection of data. AS and FY were responsible for the management of babies in the newborn period. SDY helped in the collection of data.
Funding:
None.
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