Effects of oral zinc sulfate on hyperbilirubinemia in low-birth-weight neonates

• Main Authors: Ashraf Mohammadzadeh, Ahmadshah Farhat, Ahmad Ghasemian, Mohammad Ramezani, Habibullah Esmaily, Bibi Marziyeh Musavi
• Format: Article
• Language: English
• Published: Mashhad University of Medical Sciences 2016-06-01
• Series: Iranian Journal of Neonatology
• Subjects: Hyperbilirubinemia, LBW, Neonate, Zinc Sulfate1. Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinemia in the newborn. In: Kliegman RM, Stanton B, Geme JS, Schor NF, Behrman RE, editors. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: WB Saunders; 1. Stoll BJ, Kliegman RM. Jaundice and hyperbilirubinemia in the newborn. In: Kliegman RM, Stanton B, Geme JS, Schor NF, Behrman RE, editors. Nelson Textbook of Pediatrics. 17th ed. Philadelphia: WB Saunders; 2004. P. 562-96; 2. Boskabadi H, Maamouri G, Mafinejad S. The effect of traditional remedies (Camel's Thorn, Flixweed and Sugar Water) on idiopathic neonatal jaundice. Iran J Pediatr. 2011; 21(3):325-30; 3. Boskabadi H, Maamouri G, Mafinejad S, Rezagholizadeh F. Clinical course and prognosis of hemolytic jaundice in neonates in north east of Iran. Maced J Med Sci. 2011; 4(4):403-7; 4. Maisels MJ, Pathak A, Nelson NM, Nathan DG, Smith CA. Endogenous production of carbon monoxide in normal and erythroblastotic newborn infants. J Clin Invest. 1971; 50(1):1-8; 5. Ambalavarna N, Carlo WA. Jaundice and hyperbilirubinemia. In: Kliegman RM, Stanton B, Geme JS, Schor NF, Behrman RE, editors. Nelson Textbook of Pediatrics. 19th ed. Philadelphia: WB Saunders; 2011. P. 603-12; 6. Kaplan M, Wong RJ, Sibley E, Stevenson DK. Neonatal jaundice and liver disease. In: Martin RJ, Fanaroff AA, Walsh MC, editors. Fanaroff and Martin's Neonatal-Perinatal Medicine. 9th ed. Amsterdam: Elsevier /Mosby; 2011. P. 1443-96; 7. Jahnson LH, Brown AK, Bhutani VK. System-based approach to management of neonatal jaundice and prevention of kernicterus. J Pediatr. 2002; 140(4):396-403; 8. Maisels MJ. Jaundice. In: MacDonald MG, Seshia MM, Mullett MD, editors. Avery’s Neonatology: Pathophysiology and Management of the Newborn. 6th ed. Philadelphia: Lippincott Williams & Wilkins; 2005. P. 768-846; 9. Kawade N, Onishi S. The prenatal and postnatal development of UDP-glucuronyltransferase activity toward bilirubin and the effect of premature birth on this activity in the human liver. Biochem J. 1981; 196(1):257-60; 10. Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin's neonatal-perinatal medicine: diseases of the fetus and infant. New York: Elsevier Health Sciences. 10th ed. 2015; P.1621-23; 11. Méndez-Sánchez N, Roldán-Valadez E, Flores MA, Cárdenas-Vázquez R, Uribe M. Zinc salts precipitate unconjugated bilirubin in vitro and inhibit enterohepatic cycling of bilirubin in hamsters. Eur J Clin Invest. 2001; 31(9):773-80; 12. Mendez-Sanchez N, Martinez M, Gonzalez V, Roldan-Valadez E, Flores MA, Uribe M. Zinc sulfate inhibits the enterohepatic cycling of unconjugated bilirubin in subjects with Gilbert's syndrome. Ann Hepatol. 2002; 1(1):40-3; 13. Maisels MJ, Ostrea EM Jr, Touch S, Clune SE, Cepeda E, Kring E, et al. Evaluation of a new transcutaneous bilirubinometer. Pediatric. 2004; 113(6):1628-35; 14. Lathe GH, Ruthven CR. Factors affecting the rate of coupling of bilirubin and conjugated bilirubin in the van de Bergh reaction. J Clin Pathol. 1958; 11(2):155-61; 15. Martin RJ, Fanaroff AA, Walsh MC. Fanaroff and Martin's neonatal-perinatal medicine: diseases of the fetus and infant. 9th ed. New York: Elsevier Health Sciences; 2011. P. 1476; 16. Mohammadzade A, Farhat AS, Amiri R, Esmaely H, Bagheri S. Treatment effect of clofibrate in jaundiced low birth weight neonates. Int J Hematol Oncol. 2009; 19(2):100-5; 17. Rana N, Mishra S, Bhatnagar S, Paul V, Deorari AK, Agarwal R. Efficacy of zinc in reducing hyperbilirubinemia among at-risk neonates: a randomized, double-blind, placebo-controlled trial. Indian J Pediatr. 2011; 78(9):1073-8; 18. Mohammadzadeh A, Khorakian F, Ramezani M. Prophylactic effect of zinc sulfate on hyperbilirubinemia in premature very low birth weight neonates: a randomized clinical trial. Iran J Neonatol. 2015; 5(4):6-10; 19. Maamouri G, Boskabadi H, Mafinejad S, Bozorgnia Y, Khakshur A. Efficacy of oral zinc sulfate intake in prevention of neonatal jaundice. Iran J Neonatol. 2013; 4(4):11-6; 20. Patton DR, Sukadi A. Effect of oral zinc on hyperbilirubinemia in full term neonates. Paediatr Indones. 2011; 51(2):107-10; 21. Strand TA, Chandyo RK, Bahl R, Sharma PR, Adhikari RK, Bhandari N, et al. Effectiveness and efficacy of zinc for the treatment of acute diarrhea in young children. Pediatrics. 2002; 109(5):898–903; 22. Bahl R, Bhandari N, Saksena M, Strand T, Kumar GT, Bhan MK, et al. Efficacy of zinc fortified oral rehydration solution in 6- to 35-month-old children with acute diarrhea. J Pediatr. 2002; 141(5):677–82; 23. Fischer C, Harvey P. Low risks of adverse effects from zinc supplementation. Arlington: The USAID Micronutrient Program; 2005
• Online Access: http://ijn.mums.ac.ir/article_7107_02600b3def0bb821be8318c42f2499b5.pdf

Background: Hyperbilirubinemia is one of the most common and persistent problems encountered in preterm newborns. This condition in preterm infant is more likely to be associated with neurological damage rather than terms. So far, no major studies have precisely assessed the effects of zinc sulfate on hyperbilirubinemia in low-birth-weight (LBW) neonates. Therefore, in this study, we aimed to evaluate these effects in LBW infants. Methods: This randomized, double-blind, clinical trial (IRCT201401041162N22) was performed on 61 icteric LBW neonates, hospitalized in the neonatal intensive care unit (NICU) of Imam Reza Hospital in Mashhad, Iran from May 24, 2014 to May 24, 2015. The neonates were randomly divided into case and control groups, and the total serum bilirubin (TSB) level was measured at 0, 24, 48, 72, 96, and 120 h after treatment. The subjects received either 10 mg of zinc sulfate or placebo twice per day for five days (or by the end of treatment). The termination point of phototherapy was defined as a bilirubin level below 50% of the starting point. The collected data were analyzed, using SPSS version 20. Chi-square, t-test, and repeated measures ANOVA were carried out to compare the findings between the two groups. Results: The mean TSB level was 14.87±2.65 and 14.73±3.22 mg/dl in the control and case groups. The mean decline in TSB level was only significant at 24 h after the treatment (2.71 and 2.13 mg/dl in the case and control groups, respectively; P=0.04), while being statistically insignificant on other days of the assessment. Also, similar findings were reported regarding the duration of treatment in the case and control groups (58.84±14.97 and 65.60±16.59 h in the case and control groups, respectively). Conclusion: The present study showed that administration of oral zinc sulfate in icteric LBW infants could significantly reduce TSB level only at 24 h following the treatment.