1. Introduction

  • Definition: Live microorganisms which, when administered in adequate amounts, confer a health benefit on the host.
  • Goal: To establish a healthy microbiome (commensal flora) in the preterm gut to prevent dysbiosis.

2. Mechanism of Action

  • Barrier Enhancement: Strengthens epithelial tight junctions, reducing permeability (“leaky gut”).
  • Competitive Inhibition: Competes with pathogens for nutrients and mucosal receptor sites.
  • Immunomodulation: Upregulates anti-inflammatory cytokines (IL-10) and downregulates pro-inflammatory cytokines (TNF-α, IL-6).
  • Trophic Effects: Increases mucin production and production of Short Chain Fatty Acids (SCFAs) which nourish colonocytes.

3. Evidence and Indications (VLBW Infants)

Current evidence (Cochrane/systematic reviews) supports use in Very Low Birth Weight (VLBW) <1500g infants.

  • Necrotizing Enterocolitis (NEC): Significant reduction in NEC (Stage II or higher). Number Needed to Treat (NNT) is approx 20–25.
  • Mortality: Significant reduction in all-cause mortality in VLBW infants.
  • Late-Onset Sepsis (LOS): Modest reduction in culture-proven sepsis (fungal and bacterial).
  • Feed Tolerance: Reduces time to reach full enteral feeds.

4. Strains and Dosage

  • Common Strains:
    • Bifidobacterium species (e.g., B. lactis, B. infantis) - Dominant in breastfed infants.
    • Lactobacillus species (e.g., L. acidophilus, L. rhamnosus GG).
    • Saccharomyces boulardii (Yeast) - Generally avoided in central line patients due to fungemia risk.
  • Protocol:
    • Dose: Typically CFU/day.
    • Timing: Start with initiation of enteral feeds; continue until 34–36 weeks PMA or discharge.
    • Combination: Multi-strain probiotics are generally considered more effective than single strains.

5. Contraindications and Safety

  • Absolute Contraindications:
    • Known intestinal anomaly (e.g., Gastroschisis, Omphalocele).
    • Short bowel syndrome (risk of D-lactic acidosis with certain strains).
    • Immunodeficiency disorders.
  • Relative Contraindications/Caution:
    • Extreme prematurity (<750g or <26 weeks) - Safety data limited; use with caution.
    • Hemodynamic instability/Acute phase of NEC.
  • Adverse Events: Probiotic sepsis (bacteremia/fungemia) is the main concern but is extremely rare in reported trials.

6. Summary of Recommendations

  • Routine use of probiotics is recommended for preterm infants <32 weeks or <1500g.
  • Should be used as an adjunct to breast milk/donor milk.
  • Standard quality control is essential as commercial preparations vary in purity.