What is the role of Lactobacillus rhamnosus (probiotic) in neonates?

Lactobacillus rhamnosus in Neonates

Primary Recommendation

In preterm neonates (<37 weeks gestational age) with low birth weight, use Lactobacillus rhamnosus ATCC 53103 in combination with Bifidobacterium species—not as monotherapy—to reduce necrotizing enterocolitis (NEC), sepsis, and all-cause mortality. 1

Evidence-Based Indications

Preterm, Low Birth Weight Infants

• Combination therapy with L. rhamnosus ATCC 53103 plus Bifidobacterium longum subspecies infantis significantly reduces all-cause mortality (OR 0.56; 95% CI 0.39-0.80) with high certainty of evidence. 1

• L. rhamnosus ATCC 53103 combined with various Bifidobacterium species (B. longum, B. bifidum, B. breve) reduces severe NEC (Bell's stage II or higher) compared to placebo. 1

• Combination regimens containing L. rhamnosus reduce time to full enteral feeds by approximately 2-3 days (MD -2.15 to -3.30 days) with low to high certainty of evidence. 1

• L. rhamnosus as part of multi-strain combinations does not increase sepsis risk in preterm infants, based on data from over 10,000 neonates. 1, 2

Specific Strain Identification

• Only L. rhamnosus ATCC 53103 (also known as LGG), ATC A07FA, or LCR 35 strains have moderate-to-high quality evidence supporting their use. 1

• The European Society for Paediatric Gastroenterology Hepatology and Nutrition provides a conditional recommendation specifically for L. rhamnosus GG ATCC 53103, acknowledging low certainty of evidence when used alone. 2

Critical Safety Considerations

Documented Risks

• L. rhamnosus GG supplementation has caused sepsis in at least 8 documented cases in newborns and children, establishing a cause-effect relationship in high-risk patients. 3

• Manufacturing contaminants have caused fatal infections (including gastrointestinal mucormycosis) in preterm infants, emphasizing the critical importance of pharmaceutical-grade product quality. 1, 4

Contraindications and High-Risk Populations

• Exercise extreme caution or avoid use in: 4

  • Immunocompromised infants
  • Critically ill patients with indwelling central venous catheters
  • Infants with cardiac valvular disease
  • Infants with short-gut syndrome

• Ensure local microbiology laboratories can routinely detect and identify Lactobacillus species to diagnose potential probiotic-associated sepsis. 2

• Verify products are devoid of transferable antibiotic resistance genes before administration. 2

Contraindications for Specific Clinical Scenarios

Term Infants with Acute Gastroenteritis

• Do NOT use L. rhamnosus ATCC 53103 for acute infectious gastroenteritis in children in North America—two large multicenter trials (943 and 827 children) showed no benefit. 1

• Studies from the Pediatric Emergency Care Applied Research Network and Pediatric Emergency Research Canada demonstrated no reduction in moderate-to-severe gastroenteritis duration with L. rhamnosus supplementation. 1

Optimal Implementation Strategy

Product Selection

1. Choose combination products containing L. rhamnosus ATCC 53103 with one or more Bifidobacterium species rather than L. rhamnosus monotherapy. 1

2. Prioritize pharmaceutical-grade products over dietary supplements to minimize contamination risk. 4

3. Verify specific strain identification on product labeling—generic "L. rhamnosus" without strain designation should not be used. 1

Target Population Verification

• Confirm gestational age <37 weeks at birth. 1, 4

• Confirm low birth weight status. 1, 4

• Assess for contraindications listed above before initiating therapy. 4, 2

Monitoring Requirements

• Monitor for signs of sepsis during probiotic administration, particularly in infants with central venous catheters. 3, 2

• If sepsis develops, obtain blood cultures and specifically request Lactobacillus identification from microbiology. 3, 2

• Consider discontinuing probiotics if unexplained clinical deterioration occurs. 3

Comparative Efficacy with Other Probiotics

• B. animalis subspecies lactis alone demonstrates superior reduction in hospitalization days (MD -13.00 days) compared to L. rhamnosus combinations. 1, 4

• Single-strain B. animalis subsp. lactis DSM 15954 reduces severe NEC (OR 0.31; 95% CI 0.13-0.74) with moderate-to-high quality evidence, potentially offering a safer alternative to L. rhamnosus-containing products. 4

• L. reuteri (DSM 17938 or ATCC 55730) shows comparable efficacy to L. rhamnosus combinations for reducing hospitalization duration (MD -7.89 days). 1

Clinical Context and Limitations

• Centers with robust donor breast milk feeding programs and already very low NEC rates may not derive additional benefit from probiotic supplementation. 1

• Optimal dosing, timing of initiation, and duration of L. rhamnosus administration remain undefined in current evidence. 1, 5

• Most efficacy data comes from studies outside North America, limiting generalizability to North American populations for conditions other than NEC prevention. 1