The biology of bilirubin production: detection and inhibition (original) (raw)
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Newborn Jaundice Technologies: Unbound Bilirubin and Bilirubin Binding Capacity in Neonates
Seminars in Perinatology, 2011
Neonatal jaundice (hyperbilirubinemia), extremely common in neonates, can be associated with neurotoxicity. A safe level of bilirubin has not been defined in either premature or term infants. Emerging evidence suggest that the level of unbound (or "free") bilirubin has a better sensitivity and specificity than total serum bilirubin for bilirubin-induced neurotoxicity. Although recent studies suggest the usefulness of free bilirubin measurements in managing high-risk neonates including premature infants, there currently exists no widely available method to assay the serum free bilirubin concentration. To keep pace with the growing demand, in addition to reevaluation of old methods, several promising new methods are being developed for sensitive, accurate, and rapid measurement of free bilirubin and bilirubin binding capacity. These innovative methods need to be validated before adopting for clinical use. We provide an overview of some promising methods for free bilirubin and binding capacity measurements with the goal to enhance research in this area of active interest and apparent need. Keywords Free bilirubin; total binding capacity; reserve binding capacity; binding affinity I. Bilirubin Induced Neurotoxicity Unconjugated hyperbilirubinemia, or jaundice, is one of the most common problems for neonates, including premature infants. Jaundice may lead to neurotoxicity including but not limited to sensori-neural deafness, auditory neuropathy, athetoid cerebral palsy, supranuclear gaze palsy, neonatal seizures, and apnea. (1-3) However, despite extensive research, the total serum bilirubin (TSB) level, the traditional parameter to evaluate and manage jaundice, has not been useful as a sensitive and specific predictor of neurological outcomes. (1, 4-9) This is not surprising because several biochemical and physiological factors are involved in the pathogenesis of bilirubin-induced neurotoxicity.(10)
Correlation of cord blood bilirubin and neonatal hyperbilirubinemia in healthy newborns
International Journal of Contemporary Pediatrics, 2016
Background: Jaundice is one of the commonest problems that can occur in a newborn. During the first week of life all new-borns have increased bilirubin levels by adult standards, with approximately 60% of term babies 1 and 85% of preterm babies having visible jaundice. This physiological rise in bilirubin causes indirect hyperbilirubinemia after 24 hours of birth, rises progressively with age and resolves gradually with no intervention in majority of cases. A small percentage may however require phototherapy or exchange transfusion when the bilirubin levels exceed the normal range.
Cord bilirubin as a predictor for development of hyperbilirubinemia in term neonates
Pediatric Review: International Journal of Pediatric Research, 2016
Introduction: Hyperbilirubinemia is a common problem among term newborns. Cord bilirubin level has been found to correlate well with day 3 bilirubin level. We studied whether cord bilirubin could predict risk of development of significant hyperbilirubinemia among term neonates. Methodology: Prospective study from October 2009-July 2010. All newborns between 37 weeks-42weeks, birth weight > 2500 gram, Apgar score > 7 at 1 st & 5 th minute of life were included in the study. Cord blood, day 3 & day 5 bilirubin was collected. Maternal data & bilirubin values were collected & analyzed using SPSS software. Results: About 115 babies were studied. There was no significant difference in cord bilirubin & day 3 bilirubin between babies born to mothers < 30 years &> 30 years. There was no significant difference in bilirubin values bassed on mode of delivery. About 29.6% babies developed clinical jaundice & received phototherapy. Cord bilirubin levels had significant association with need of phototherapy. Cord bilirubin >/= 2.1 mg/dl predicted need for phototherapy with PPV of 90.3%. Maternal age, sex of baby, birth weight & gestational age had no significant effect on cord bilirubin levels. Cord bilirubin >/= 2.1 mg/dl predicted day 3 serum bilirubin > 15 mg/dl with sensitivity of 88 % & PPV of 77.49 %. The likelihood ratio with cord bilirubin > 2.1 mg/dl & day 3 serum bilirubin > 15 mg/dl was 9.316. Conclusion: Cord bilirubin is predictive of need of phototherapy & correlated well with day 3 bilirubin levels which would facilitate early management of neonatal hyperbilirubinemia.
The Journal of Pediatrics, 2008
Objective-To estimate the effect of phototherapy and other predictors on the risk of total serum bilirubin (TSB) ≥ 25 mg/dL in infants with a TSB of 17 to 22.9 mg/dL at age ≥ 48 hours. Study design-From a cohort of 285295 infants ≥ 34 weeks gestation and ≥ 2000 g born between 1995 and 2004 in northern California Kaiser hospitals, we identified 17 986 with a TSB of 17 to 22.9 mg/dL at age ≥ 48 hours. All infants exhibiting a TSB ≥ 25 mg/dL were selected as cases for the study. Four randomly selected controls were matched to each case based on the difference between their qualifying TSB and the American Academy of Pediatrics' phototherapy threshold. Results-A total of 62 cases were identified (0.4%). Six of these (10%) received inpatient phototherapy within 8 hours, along with 101 controls (41%) (adjusted odds ratio [AOR] 0.15; 95% confidence interval [CI] 0.06 to 0.40). Cases more often had lower gestational age (AOR 3.24; 95% CI 1.24 to 8.47 for 38 to 39 weeks and AOR = 3.70; 95% CI 0.61 to 22.4 for 34 to 37 weeks compared with ≥ 40-week infants), bruising, (AOR 2.52; 95% CI 1.16 to 5.50), exclusive breastfeeding (AOR 2.09; 95% CI 1.05 to 4.03), and TSB increase of ≥ 6 mg/dL/day (AOR 2.39; 95% CI 1.18 to 4.85). Conclusions-Phototherapy was 85% effective in preventing TSB ≥ 25 mg/dL. The strongest predictors of TSB ≥ 25 mg/dL were gestational age, bruising, family history, and rapid rise in TSB. Clinicians caring for newborns often must decide how to manage those presenting with jaundice in the first few days after birth. If the infant's total serum bilirubin level (TSB) is well above or below the American Academy of Pediatrics (AAP) jaundice treatment guidelines (based on age [in hours] and TSB level), 1 then management decisions are simple. But marked variability exists in the treatment of infants with TSB levels within a few mg/dL of the AAP's age-specific phototherapy threshold. 2 A physician may choose to admit the infant for inpatient phototherapy, implement interventions at home (home phototherapy, supplementation with formula), or follow the TSB level with serial measurements. Because TSB levels in this range often peak below 25 mg/dL without receiving treatment, it may be reasonable to observe an infant and repeat the test. In addition, even though many consider inpatient phototherapy a benign intervention, it does have some drawbacks, including
Bilirubin binding in jaundiced newborns: from bench to bedside?
Pediatric research, 2018
Bilirubin-induced neurologic dysfunction (BIND) is a spectrum of preventable neurological sequelae in jaundiced newborns. Current total plasma bilirubin (B) concentration thresholds for phototherapy and/or exchange transfusion poorly predict BIND. The unbound (free) bilirubin (B) measured at these B thresholds provides additional information about the risk for BIND. B can be readily adapted to clinical use by determining B population parameters at current B thresholds. These parameters can be established using a plasma bilirubin binding panel (BBP) consisting of B, B, and two empiric constants, the maximum B (B) and the corresponding equilibrium association bilirubin constant (K). B and K provide the variables needed to accurately estimate B at B < B to obtain B at threshold B in patient samples. Once B population parameters are known, the BBP in a newborn can be used to identify poor bilirubin binding (higher B at the threshold B compared with the population) and increased ri...