الفهرس 
FREE “UNBOUND” BILIRUBIN & BILIRUBIN TOXICITYOnly 14 pages are availabe for public view
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Abstract
The traditional view that kernicterus is a disease of the past, and that bilirubin toxicity causes only the classical clinical and pathological syndrome may be oversimplification of the effect of bilirubin toxicity on the nervous system.
Neonatal hyperbilirubinaemia is a very common entity in neonatal intensive care units and acute bilirubin encephalopathy, though is rare, but its resurgence recently in developed countries has made identification of infants at high risk for this condition essential.
The present study was conducted during the period from December 2002 to July 2004. Seventy jaundiced newborns were consecutively selected from Neonatal Intensive Care Unit of Maternity Hospital-Ain Shams University, and that of Nasser Institute for Research and Treatment.
Newborns who had growth retardation, sepsis, congenital malformation, liver disease, central nervous systems disorders, infant of diabetic mother, or severe respiratory distress were excluded.
Only 40 jaundiced newborns completed the study. They were twenty-three males and seventeen females. Their age ranged between one to ten days with a mean age of 4.03 ±2.5 days. They were subjected to thorough full history taking, physical examination (gestational age, APGAR, bruises, cephalhematomas, any sepsis signs), neurological examination using BIND-score system, and laboratory investigations including (complete blood picture, blood group, Retics, C-reactive protein, serum albumin, total and direct bilirubin, and free bilirubin was measured by a combined peroxidase-diazo method.
Studied jaundiced neonates were divided according to gestational age into two groups:
Group I: It included twenty-eight full term newborn infants. Fifteen newborns (53.6%) were males and thirteen (46.4%) were females. Their gestational age ranged from 37 to 40 weeks with a mean 38.9 ± 1.33 wks. Eleven newborns (39.3%) were delivered by cesarean section and seventeen (60.7%) were delivered vaginally. None of them had cephalhematomas or bruises.
Group II: It included only twelve preterm newborn infants. Eight (66.7%) were males and four (33.3%) were females. The small number of included preterm newborns was because prematurity was usually associated with other diseases that were excluded in the present study. Their gestational age ranged from 32 to 37 weeks at birth with a mean 34.5 ± 1.17 weeks. Eight (66.7%) were delivered by caesarean section and four (33.3%) were delivered vaginally.
The studied groups were compared to control group. That group included forty healthy non-jaundiced neonates that were selected from the delivery room at Maternity Hospital-Ain Shams University. Their gestational age ranged between 37 to 40 weeks with a mean of 38.9 ± 1.33 weeks. They were twenty-five males and fifteen females.
Results:
The present study revealed that full term newborns had significant higher mean total, direct, unbound bilirubin and B: A ratio, compared to preterm jaundiced neonates and controls. Preterm jaundiced neonates had statistically significant higher mean total, direct, and unbound bilirubin compared to control group.
Among full term neonates, thirteen (46.4%) were BIND-score zero, and fifteen (53.5 %) were BIND-score positive. Thirteen were BIND-score grade IA and two were BIND-score grade IB. Among preterm jaundiced neonates, eight (66.7 %) were BIND-score zero, three (25.0%) were BIND-core grade IA, and one patient (8.3 %) was BIND-score grade IB.
The present study confirmed that jaundiced full term neonates with bilirubin encephalopathy (positive BIND-score) had total bilirubin levels ≥ 20 mg/dl.
The present study revealed that etiology of jaundice, family history of previous sibling with jaundice, sex distribution, mode of delivery, and maternal age have no role in the occurrence of bilirubin encephalopathy (positive BIND-score). But the risk of bilirubin encephalopathy increased with decreased gestational age and decreased level of serum albumin, increased levels of total, indirect and free unbound bilirubin.
None of studied jaundiced newborns had clinical picture of classic kernicterus. All were treated with different types of phototherapy whether single, double, or triple. Among full term jaundiced neonates two were subjected to exchange transfusion and five were treated with phenobarbitone in addition to phototherapy. All studied newborns had no clinical signs of bilirubin encephalopathy after they were treated.
The choice of the type of phototherapy used in treatment of jaundiced neonates could depend on the level of total or indirect bilirubin concentration, while unbound bilirubin concentrations have a limited value.
After completion of phototherapy, there was no difference between different modes of phototherapy used in the treatment of jaundiced full term newborns as regard total, indirect, unbound bilirubin concentrations.
Unbound bilirubin levels correlated positively with each of Retics (r= 0.467), TLC (r=0.335), total bilirubin (r= 0.872); B: A ratio (r= 0.677), direct bilirubin (r= 0.711), and indirect bilirubin (r= 0.626), but unbound bilirubin had no statistically significant correlation with serum albumin levels (r=- 0.194, p>0.05).
Unbound bilirubin at the cut off point of 0.243 µg/dl, its sensitivity was 84.2% and its specificity was 85.7% for predicting the occurrence of encephalopathy. This means that unbound bilirubin can predict the occurrence of bilirubin encephalopathy in jaundiced neonate by 84.25% and can exclude the presence of bilirubin encephalopathy by 85.7%.
Stepwise regression analysis was performed for the most important factors in predicting the occurrence of bilirubin encephalopathy using a clinical score system (BIND-score). Unbound bilirubin level has the most significant effect on the occurrence of bilirubin encephalopathy, which detected clinically as positive BIND-score among the studied full term and preterm jaundiced neonates.