CONGENITAL NONHEMOLYTIC UNCONJUGATED HYPERBILIRUBINEMIA WITH GLUCURONYL TRANSFERASE DEFICIENCY IN NEONATES: BIOCHEMICAL, HAEMATOLOGICAL AND PHARMACOLOGIC EVIDENCE FOR HETEROGENEITY AND THE ROLE OF PHENOBARBITOL

Abstract

Background: Congenital non-haemolytic unconjugated hyperbilirubinemia, commonly known as Gilbert syndrome, is a common genetic condition characterized by mild, fluctuating elevations of unconjugated bilirubin in the blood without evidence of haemolysis.

Objective: To evaluate the biochemical and pharmacologic heterogeneity of congenital non-haemolytic unconjugated hyperbilirubinemia in neonates with deficiency of glucuronyl transferase and evaluate the effectiveness of phenobarbital in lowering levels of bilirubin.

Methodology: This prospective cohort study was conducted at District Head Quarter Hospital in Karak, Khyber Pakhtunkhwa, Pakistan, from January 2023 to January 2024, involving 195 neonates with congenital nonhemolytic unconjugated hyperbilirubinemia and glucuronyl transferase deficiency (UGT1A1 gene mutation). Neonates aged 0-28 days meeting inclusion criteria were treated with phenobarbital (5-10 mg/kg orally, once or twice daily).

Results: 195 neonates diagnosed with congenital non-hemolytic unconjugated hyperbilirubinemia and glucuronyl transferase deficiency were included in the study. Treatment with phenobarbitol led to a significant lowering of serum bilirubin levels from a mean of 16.2 mg/dL to 8.1 mg/dL (p < 0.023). Initially, none of the neonates had bilirubin levels below 10 mg/dL; however, 145 neonates reached this goal after treatment (p < 0.032). All neonates had bilirubin levels greater than 15 mg/dL before treatment, but none after treatment (p < 0.001). The incidence of kernicterus decreased from 15 cases at baseline to zero after treatment (p < 0.012).

Conclusion: Phenobarbital is highly effective in the management of congenital non-haemolytic unconjugated hyperbilirubinemia in neonates with deficiency of glucuronyl transferase. Baseline bilirubin levels were significantly lowered from an average of 16.2 mg/dL to 8.1 mg/dL post-treatment, with a noticeable decline in the number of neonates with bilirubin levels above 15 mg/dL and an attainment of target bilirubin levels below 10 mg/dL in 145 neonates. Additionally, the kernicterus cases dropped to zero after management highlighting its importance.