Role of Oral Zinc in Reducing Neonatal Indirect Hyperbilirubinemia

Unconjugated hyperbilirubinemia is one of the most common conditions in neonates. Although conventional treatment, phototherapy and/or exchange transfusion, is effective, both modalities are associated with several side effects. High levels of unconjugated hyperbilirubinemia causing direct serious brain injury, in the form of acute bilirubin encephalopathy which may progress to kernicterus (chronic bilirubin encephalopathy) with classically characterized permanently extrapyramidal movement disorders of dystonia, choreoathetosis or both, hearing loss due to auditory neuropathy spectrum, and oculomotor pareses. Treatment of unconjugated hyperbilirubinemia, such as phototherapy and blood exchange transfusion, is costly, takes a long time and can be dangerous. Phototherapy usage may associate with watery diarrhea, low serum calcium, retinal damage, skin rash, dehydration, and DNA mutation. Exchange transfusion can cause electrolyte imbalance, cardiac overload, air embolism, thrombophlebitis, thrombocytopenia, sepsis, necrotizing enterocolitis, transmission of blood-borne diseases, and portal vein thrombosis. These harmful adverse effects indicate the need to develop alternative therapeutic pharmacological strategies which aim to decrease the plasma concentration of unconjugated bilirubin by inhibiting production, stimulating hepatic clearance, or interrupting the enterohepatic circulation (EHC) of bilirubin. Studies have indicated that feeding inadequacy promotes EHC which is an important predictor for neonatal hyperbilirubinemia. Therefore, interruption of EHC is a potentially effective intervention. Various substances have been used to bind the bilirubin in intestinal lumen to prevent its absorption and disrupt enterohepatic circulation. These substances are such as oral agar, orlistat, active charcoal, cholestyramine, calcium phosphate or glucoronidase inhibitor like hydrolyzed casein; although the obtained results have been inconsistent.

Zinc is one of the critical trace elements which have a vital role in a wide range of biological activities in living organisms. Mendez-Sanchez et al., 2001 study was the first one which reported that zinc salts at physiological fluid media can be flocculated and almost completely adsorb unconjugated bilirubin from unsaturated micellar bile salt solutions. Vitek et al., 2005 studied the effect of zinc salts ingestion in hyperbilirubinemic rats and reported that oral zinc salts can decrease serum bilirubin levels efficiently, due to the probable enterohepatic circulation inhibition of bilirubin. Méndez-Sánchez et al., 2022 showed that administration of oral zinc sulphate can significantly decrease serum indirect bilirubin levels in adult patients with Gilbert´s syndrome.

Therefore, the anticipated role of zinc supplementation in neonatal jaundice seems to be an attractive issue for research. This study aimed to determine the role of oral zinc on treatment of neonates suffering from unconjugated hyperbilirubinemia with variable gestational ages, different levels of jaundice severity and different birth weight.

Inclusion criteria

• Neonates with total serum bilirubin (TSB) exceeding the 40th percentile track for age as per the hour-specific bilirubin nomogram of the American Academy of Pediatrics (AAP)
• Neonates who have indirect hyperbilirubinemia, not indicated for exchange transfusion.

Exclusion criteria

• Neonates submitted to blood transfusion.
• Neonates indicated for exchange transfusion
• Associated congenital anomalies.
• Co-morbidities such as sepsis, pneumonia or respiratory distress.
• Neonates whom their mothers received phenobarbitone during the third trimester