Role of Serum (B/A) Ratio Compared to (TSB) for Early Prediction of Bilirubin-induced Neurological Dysfunction (BIND).

Introduction Neonatal hyperbilirubinemia is a common problem in neonates. Approximately 60% of term and 80% of preterm babies develop jaundice in the first week of life and about 10% of breastfed babies are still jaundiced at 1 month.

Jaundice due to either indirect (unconjugated) or direct (conjugated) bilirubin within the first 24 h of life should be taken seriously. Early identification and proper management are needed to prevent the serious neurological complications .

When the total serum bilirubin (TSB) rises above the 95th percentile for age (high-risk zone), entry of unconjugated bilirubin into the brain can cause both short-term and long-term neurological dysfunctions (bilirubin encephalopathy) . The increased level of bilirubin is detrimental for nervous system, especially damage the basal ganglia, cerebellum, and brainstem, thus, resulting in bilirubin-induced neurological dysfunction (BIND) .

Bilirubin-induced neurologic dysfunction (BIND) is the term applied to the spectrum of neurologic abnormalities associated with hyperbilirubinemia. It can be further divided into characteristic signs and symptoms that appear in the early stages (acute) and those that evolve over a prolonged period (chronic) . Signs and symptoms of BIND include tone abnormalities such as hypotonia, hypertonia, retrocollis and opisthotonos, in association with varying degrees of drowsiness, lethargy, decreased feeding and irritability .

BIND was also associated with Kernicterus leading to devastating disability including athetoid cerebral palsy, speech and hearing impairment. BIND in neonates is a significant cause of death or lifelong disability, including cerebral palsy (CP) and auditory disorders .

The earliest signs and symptoms of BIND are nonspecific therefore may be easily missed thus an early diagnostic tool is required. BIND score is a scoring system, in which characteristics of mental state, muscle tone, and cry are grouped into three levels of increasing abnormality: stage IA, minimal signs; stage IB, progressive but reversible with treatment; stage II, advanced and largely irreversible, but may be significantly decreased by treatment .

The pathogenesis of BIND is multifactorial and includes interaction between the level of unconjugated bilirubin, free bilirubin, bilirubin bound to albumin, bilirubin passed through brain blood barrier and nerves damage. Although 99.9% of unconjugated bilirubin in the circulation is bound to albumin, a relatively small fraction (only less than 0.1%) remains unbound (free bilirubin) and it can go into the brain across an intact blood brain barrier (BBB) .

There is currently no method available for measuring free bilirubin concentrations accurately in plasma or serum; therefore, adjunct measurements of albumin concentration and bilirubin albumin ratio (B/A) may provide more insight into the likelihood of bilirubin-induced encephalopathy. The B/A ratio is considered a surrogate parameter for free bilirubin and an interesting additional parameter in the management of hyperbilirubinemia. Few studies suggested the utilization of B/A ratios as a predictor for bilirubin-induced neurotoxicity .

• Avoidance of complications of severe neonatal jaundice [Time frame: baseline]