Role of Oral Zinc in Reducing Neonatal Indirect Hyperbilirubinemia
Condition: Neonatal Jaundice
MeSH terms: Jaundice, Neonatal; Hyperbilirubinemia, Neonatal; Jaundice; Hyperbilirubinemia
Study type: Interventional
Phase: Phase 3

Summary: 
      This study aimed to determine the role of oral zinc in reducing the neonatal indirect
      hyperbilirubinemia if used concomitant with the standard phototherapy
    

Detailed description: 
      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.
    

Intervention name(s): Oral zinc sulfate and standard phototherapy
Intervention type(s): Drug
Intervention description(s): study the role of oral zinc sulfate in reducing level of indirect hyperbilirubinemia in neonates if used with standard phototherapy
Other intervention name(s): standard phototherapy alone
Intervention MeSH terms: Zinc Sulfate
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: This randomized clinical trial was carried out on 192 neonates with indirect hyperbilirubinemia, at neonatal intensive care unit (NICU) of Pediatric Department, National Liver Institute (NLI), Menoufia University from (June 2018- June 2019). Research Ethics Committee of NLI approved the study, NLI- Institutional Review Board (IRB) protocol number is (00136/2018). Neonates enrolled in the study were randomly assigned into two groups. Group (1) (zinc and phototherapy group) included 95 neonates receiving phototherapy and oral zinc sulfate with a dose of 5 mg every 12 hours using a calibrated dropper provided with the bottle, during the period of NICU admission on phototherapy. Group (2) (phototherapy group) included 97 neonates receiving phototherapy alone. Both groups receiving phototherapy based on the guidelines of American Academy of Pediatrics for the treatment of neonatal indirect hyperbilirubinemia. Any adverse effect were noted and recorded.
Masking: None (Open Label)
Primary purpose: Treatment