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.
