Probiotics and Preterm Infants: Clinical Evidence

Risk, Impact, Benefits

PRETERM NEONATES ARE AT HIGH RISK FOR DYSBIOSIS

Preterm infants face challenges that adversely affect the developing microbiome1-3

  • Underdeveloped gut immunity
  • Use of antibiotics and other medications
  • Use of non-human milk feeding products
  • Delayed enteral feeding
  • Sterile neonatal intensive care unit (NICU) environment
  • Exposure to hospital environment

DYSBIOSIS CAN ADVERSELY IMPACT THE DEVELOPMENT OF A HEALTHY MICROBIOME4-6

Dysbiosis: consequences and long-reaching implications

  • Pathogenic vs beneficial bacterial colonization
  • Delayed intestinal barrier maturation
  • Less-developed immune system
  • Inflammation
  • Feeding intolerance

Reducing the risk of dysbiosis5

  • Antibiotic stewardship
  • Human milk
  • Probiotics

 

PROBIOTICS IN THE NICU: CLINICAL EVIDENCE

Probiotics have shown to significantly improve outcomes, based on more than 25 reviews and meta-analyses of randomized, controlled trials (RCTs) involving nearly 12,000 infants7

  • All-cause mortality
  • Necrotizing enterocolitis (NEC)
  • Late-onset sepsis
  • Feeding tolerance

Benefits of probiotics on NEC5

  • Probiotics significantly reduced incidence of NEC in clinical studies
  • Based on 35 randomized controlled trials (RCTs) with over 10,000 infants

Benefits of probiotics on feeding intolerance8

  • Probiotics significantly reduced feeding intolerance as well as time to full enteral feeds (TFEFs) (P < 0.00001) in clinical studies

Position Paper

Objective

Design

Population

Probiotic Used

Results

Athalye-Jape, et al 2014

Determine effects of probiotics on all-cause mortality, morbidity, and feeding intolerance

Over 25 systematic reviews and meta-analysis of RCTs and non-RCTs

≈12,000 premature infants*

* From RCTs.

Varied according to study and included both single and multiple strains

Significant reduction on risk of all-cause mortality, NEC, late onset sepsis, and feeding intolerance

 

PROBIOTICS AND NEC: A SAMPLE OF CLINICAL EVIDENCE9-12

Study results showed a significant reduction in NEC using different strains.

Study

Objective

Design

Clinical characteristics

Probiotic used

Results

Hoyos 1999

Determine effect of probiotics on incidence of NEC

Observational, interventional study

1237 newborns <37 completed weeks’ gestation and weighing <2750 g

Bifidobacterium infantis, Lactobacillus acidophilus; containing half a billion colony-forming units (CFU) given daily

Significant decrease in NEC

Bin-Nun, et al 2005

Determine effect of probiotics on incidence and severity of NEC

Prospective, randomized, controlled study

145 preterm neonates <30 weeks’ gestation and weighing <1500 g

Bifidobacterium infantis, Streptococcus thermophilis, Bifidobacterium lactis; containing 1 billion CFU given daily

Significant reduction in both incidence and severity of NEC

Jacobs, et al 2013

Determine effect of probiotics on NEC and late-onset sepsis

Prospective multicenter, double-blind, placebo-controlled, randomized trial

1099 infants born at <32 completed weeks’ gestation and weighing <1500 g

Bifidobacterium infantis, Streptococcus thermophilis, Bifidobacterium lactis; containing 1 billion CFU given daily

Significant reduction in late-onset sepsis and significant decrease of NEC

Hartel, et al 2014

Determine effect of probiotics on outcome data

Observational cohort study using infants from German Neonatal Network

5351 infants born at <30 completed weeks’ gestation and weighing <1060 g

Lactobacillus cidophilus, Bifidobacterium infantis

Significant reduction in NEC surgery and any abdominal surgery

References: 1. Underwood M, et al. Pediatr Res. 2014;76:326-332. 2. Groer M, et al. Microbiome. 2014;2:38. 3. Denning N, et al. Molecular Medicine. 2018;24:42018. 4. Underwood MA. J Pediatr Surg. 2019;54:405-412. 5. Patel RM, et al. Semin Pediatr Surg. 2018;27:39-46. 6. Yuan Z, et al. PLoS One. 2019;14:e0210609. 7. Athalye-Jape G, et al. Microb Biotechnol. 2019;12:249-253. 8. Athalye-Jape G, et al. Am J Clin Nutr. 2014;100:1508-1519. 9. Hoyos A. Int J Infect Dis. 1999;3:197-202. 10. Bin-Nun A, et al. J Pediatr. 2005;147:192-196. 11. Jacobs S, et al. Pediatrics. 2013;132:1055-1062. 12. Hartel C, et al. J Pediatr. 2014;165:285-289.