Effects of Saccharomyces boulardii on Neonatal Hyperbilirubinemia: A Randomized Controlled Trial

Abstract

Objective Since probiotics modulate intestinal functions and enterohepatic circulation; they might have an effect on neonatal hyperbilirubinemia treatment. The objective of this study was to investigate the efficacy of Saccharomyces boulardii supplementation on hyperbilirubinemia.

Study Design A prospective, double-blind, placebo controlled trial was performed on 35 to 42 gestational weeks' neonates. They were randomized either to receive feeding supplementation with S. boulardii 125 mg every 12 hours or placebo during phototherapy. Serum bilirubin levels were measured at 0, 24th, 48th, 72nd, and 96th hour of phototherapy.

Results A total of 119 infants (61 in the control group and 58 in the study group) were enrolled. The duration of phototherapy (2 [1–3] vs. 2 [1–3], p: 0.22) was not different between groups. The levels of bilirubin during phototherapy ([24th hour; 14.1 {12.8–15.7} vs. 13.5 {12.4–14.9}, p: 0.085]; [48th hour; 14.1 {12–15.3} vs. 13.4 {12.4–14.5}, p: 0.41]; [72nd hour; 13.9 {12.2–15.6} vs. 13.5 {12.5–14.5}, p: 0.41]; [96th hour; 14.7 {11.4–15.5} vs. 13.4 {10.7–14.1}, p: 0.24]) or the duration of rebound phototherapy (1 [1–1] vs. 1.5 [1–2], p: 0.40) were lower in the study group than in the controls, but none of the values were statistically significant.

Conclusion S. boulardii did not influence the clinical course of hyperbilirubinemia significantly.

Keywords

neonatal hyperbilirubinemia - phototherapy - probiotic - Saccharomyces boulardii

Note

The full trial protocol can be accessed where the trial was approved (Central ethical committee in Ankara, Turkey). This trial was registered by IRCT with ID as IRCT 2012123010279N2.

• References

• 1 Sgro M, Campbell D, Shah V. Incidence and causes of severe neonatal hyperbilirubinemia in Canada. CMAJ 2006; 175 (6) 587-590
• 2 Bhutani VK, Johnson LH. Urgent clinical need for accurate and precise bilirubin measurements in the United States to prevent kernicterus. Clin Chem 2004; 50 (3) 477-480
• 3 Bhutani VK, Johnson LH, Keren R. Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week. Pediatr Clin North Am 2004; 51 (4) 843-861 , vii
• 4 Bhutani VK, Johnson L, Sivieri EM. Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns. Pediatrics 1999; 103 (1) 6-14
• 5 Ip S, Chung M, Kulig J , et al; American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. An evidence-based review of important issues concerning neonatal hyperbilirubinemia. Pediatrics 2004; 114 (1) e130-e153
• 6 Joint Commission on Accreditation of Healthcare Organizations. Kernicterus threatens healthy newborns. Sentinel Event Alert 2001; (18) 1-4
• 7 Bisceglia M, Indrio F, Riezzo G, Poerio V, Corapi U, Raimondi F. The effect of prebiotics in the management of neonatal hyperbilirubinaemia. Acta Paediatr 2009; 98 (10) 1579-1581
• 8 Burke BL, Robbins JM, Bird TM, Hobbs CA, Nesmith C, Tilford JM. Trends in hospitalizations for neonatal jaundice and kernicterus in the United States, 1988-2005. Pediatrics 2009; 123 (2) 524-532
• 9 Havenaar R, Huis in't Veld JHJ. Probiotics: a general view. In: Wood BJB, , ed. The Lactic Acid Bacteria in Health and Disease. The Lactic Acid Bacteria Vol. 1. New York, NY: Chapman and Hall; 1992: 209-224
• 10 Husebye E, Hellström PM, Sundler F, Chen J, Midtvedt T. Influence of microbial species on small intestinal myoelectric activity and transit in germ-free rats. Am J Physiol Gastrointest Liver Physiol 2001; 280 (3) G368-G380
• 11 Banasaz M, Norin E, Holma R, Midtvedt T. Increased enterocyte production in gnotobiotic rats mono-associated with Lactobacillus rhamnosus GG. Appl Environ Microbiol 2002; 68 (6) 3031-3034
• 12 van Meer H, Boehm G, Stellaard F , et al. Prebiotic oligosaccharides and the enterohepatic circulation of bile salts in rats. Am J Physiol Gastrointest Liver Physiol 2008; 294 (2) G540-G547
• 13 Floch MH. Bile salts, intestinal microflora and enterohepatic circulation. Dig Liver Dis 2002; 34 (Suppl. 02) S54-S57
• 14 Usman HA, Hosono A. Effect of administration of Lactobacillus gasseri on serum lipids and fecal steroids in hypercholesterolemic rats. J Dairy Sci 2000; 83 (8) 1705-1711
• 15 Costalos C, Skouteri V, Gounaris A , et al. Enteral feeding of premature infants with Saccharomyces boulardii. Early Hum Dev 2003; 74 (2) 89-96
• 16 American Academy of Pediatrics Subcommittee on Hyperbilirubinemia. Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation. Pediatrics 2004; 114 (1) 297-316
• 17 Kaplan M, Merlob P, Regev R. Israel guidelines for the management of neonatal hyperbilirubinemia and prevention of kernicterus. J Perinatol 2008; 28 (6) 389-397
• 18 Blackburn S. Hyperbilirubinemia and neonatal jaundice. Neonatal Netw 1995; 14 (7) 15-25
• 19 Bin-Nun A, Bromiker R, Wilschanski M , et al. Oral probiotics prevent necrotizing enterocolitis in very low birth weight neonates. J Pediatr 2005; 147 (2) 192-196
• 20 Deshpande GC, Rao SC, Keil AD, Patole SK. Evidence-based guidelines for use of probiotics in preterm neonates. BMC Med 2011; 9: 92
• 21 Wang WJ, Zheng YJ. Clinical application of probotics in China. Chin J Microecol 2009-01
• 22 Liu L, Bao LY, Zhang L, Cui YL. The observation on effect of Clostridium butyricum powder in treatment of breast milk jaundice. Chin J Microecol 2009; 21 (3) 260-261
• 23 Demirel G, Celik IH, Erdeve O, Dilmen U. Impact of probiotics on the course of indirect hyperbilirubinemia and phototherapy duration in very low birth weight infants. J Matern Fetal Neonatal Med 2013; 26 (2) 215-218
• 24 Serce O, Benzer D, Gursoy T, Karatekin G, Ovali F. Efficacy of saccharomyces boulardii on necrotizing enterocolitis or sepsis in very low birth weight infants: a randomised controlled trial. Early Hum Dev 2013; 89 (12) 1033-1036
• 25 Ng E, Shah VS. Erythromycin for the prevention and treatment of feeding intolerance in preterm infants. Cochrane Database Syst Rev 2008; 16 (3) CD001815