Comparison of Stool Colonization in Premature Infants by Three Dose Regimes of a Probiotic Combination: A Randomized Controlled Trial

Abstract

Objective To compare stool colonization among premature infants receiving high-dose probiotics versus standard dose.

Study Design This blinded, randomized, placebo-controlled trial was conducted in a Level III neonatal unit. Eligibility criteria were gestational age 27–33 weeks, age < 96 hours, tolerating milk ≥ 15 mL/kg/day and availability for follow-up. Gastro-intestinal/life-threatening malformations and necrotizing enterocolitis/sepsis were exclusions. A total of 149 subjects were randomly allocated to groups A through D (received 12-hourly probiotic supplements of 10¹⁰ cells for 21 days, 10¹⁰ cells for 14 days, 10⁹ cells for 21 days and placebo, respectively). Key outcome was stool colonization by a probiotic organism at 28 days.

Results Colonization with Lactobacillus and Bifidobacterium was significantly higher in groups A, B, and C versus placebo respectively, but groups A through C did not differ from each other. There were trends toward more colony forming unit (cfu) of Lactobacillus and Bifidobacterium per milliliter of stool in group A versus B and B versus C. Groups A and B and spontaneous preterm labor (SPL) independently predicted high Lactobacillus counts on day 28; groups A, B, and C and SPL predicted high Bifidobacterium counts.

Conclusion Proportion of infants colonized with probiotic species was similar with high-dose and standard dose regimes.

Keywords

probiotics - dose - colonization - preterm

• References

• 1 Alfaleh K, Anabrees J, Bassler D, Al-Kharfi T. Probiotics for prevention of necrotizing enterocolitis in preterm infants. Cochrane Database Syst Rev 2011; (3) CD005496
• 2 Deshpande G, Rao S, Patole S, Bulsara M. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010; 125 (5) 921-930
• 3 Beattie LM, Hansen R, Barclay AR. Probiotics for preterm infants: confounding features warrant caution. Pediatrics 2010; 126 (3) e742-e743 , author reply e743–e745
• 4 Neu J. Routine probiotics for premature infants: let's be careful!. J Pediatr 2011; 158 (4) 672-674
• 5 Soll RF. Probiotics: are we ready for routine use?. Pediatrics 2010; 125 (5) 1071-1072
• 6 Bennet R, Nord CE, Zetterström R. Transient colonization of the gut of newborn infants by orally administered bifidobacteria and lactobacilli. Acta Paediatr 1992; 81 (10) 784-787
• 7 Kitajima H, Sumida Y, Tanaka R, Yuki N, Takayama H, Fujimura M. Early administration of Bifidobacterium breve to preterm infants: randomised controlled trial. Arch Dis Child Fetal Neonatal Ed 1997; 76 (2) F101-F107
• 8 Millar MR, Bacon C, Smith SL, Walker V, Hall MA. Enteral feeding of premature infants with Lactobacillus GG. Arch Dis Child 1993; 69 (5 Spec No): 483-487
• 9 Reuman PD, Duckworth DH, Smith KL, Kagan R, Bucciarelli RL, Ayoub EM. Lack of effect of Lactobacillus on gastrointestinal bacterial colonization in premature infants. Pediatr Infect Dis 1986; 5 (6) 663-668
• 10 Agarwal R, Sharma N, Chaudhry R , et al. Effects of oral Lactobacillus GG on enteric microflora in low-birth-weight neonates. J Pediatr Gastroenterol Nutr 2003; 36 (3) 397-402
• 11 Sharma N, Chdhry RB. Effect of continuous probiotic treatment on stool microbial patterns in very low-birth-weight infants. Pediatr Res 2000; 47: 168A
• 12 Adlerberth I. Establishment of a normal intestinal microflora in the newborn infant. In: Hanson LA, Yolken RH, , eds. Probiotics, Other Nutritional Factors and Intestinal Microflora. Philadelphia, PA: Lippincott-Raven; 1999: 63-78
• 13 Candela M, Perna F, Carnevali P , et al. Interaction of probiotic Lactobacillus and Bifidobacterium strains with human intestinal epithelial cells: adhesion properties, competition against enteropathogens and modulation of IL-8 production. Int J Food Microbiol 2008; 125 (3) 286-292
• 14 Collado MC, Gueimonde M, Hernández M, Sanz Y, Salminen S. Adhesion of selected Bifidobacterium strains to human intestinal mucus and the role of adhesion in enteropathogen exclusion. J Food Prot 2005; 68 (12) 2672-2678
• 15 Ostad SN, Salarian AA, Ghahramani MH, Fazeli MR, Samadi N, Jamalifar H. Live and heat-inactivated lactobacilli from feces inhibit Salmonella typhi and Escherichia coli adherence to Caco-2 cells. Folia Microbiol (Praha) 2009; 54 (2) 157-160
• 16 Miles AA, Misra SS, Irwin JO. The estimation of the bactericidal power of the blood. J Hyg (Lond) 1938; 38 (6) 732-749
• 17 Walsh MC, Kliegman RM, Fanaroff AA. Necrotizing enterocolitis: a practitioner's perspective. Pediatr Rev 1988; 9 (7) 219-226
• 18 Mohan R, Koebnick C, Schildt J , et al. Effects of Bifidobacterium lactis Bb12 supplementation on intestinal microbiota of preterm infants: a double-blind, placebo-controlled, randomized study. J Clin Microbiol 2006; 44 (11) 4025-4031
• 19 Butel MJ, Suau A, Campeotto F , et al. Conditions of bifidobacterial colonization in preterm infants: a prospective analysis. J Pediatr Gastroenterol Nutr 2007; 44 (5) 577-582
• 20 Cilieborg MS, Boye M, Mølbak L, Thymann T, Sangild PT. Preterm birth and necrotizing enterocolitis alter gut colonization in pigs. Pediatr Res 2011; 69 (1) 10-16
• 21 Timmerman HM, Koning CJ, Mulder L, Rombouts FM, Beynen AC. Monostrain, multistrain and multispecies probiotics—A comparison of functionality and efficacy. Int J Food Microbiol 2004; 96 (3) 219-233
• 22 Tsai CC, Liang HW, Yu B , et al. The relative efficacy of different strain combinations of lactic acid bacteria in the reduction of populations of Salmonella enterica Typhimurium in the livers and spleens of mice. FEMS Immunol Med Microbiol 2011; 63 (1) 44-53