What are the risks of giving Lactobacillus reuteri (probiotic) to a preterm infant for 110 days or more?

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Extended Duration of L. reuteri in Preterm Infants: Safety Assessment

Based on the available evidence, giving Lactobacillus reuteri DSM 17938 for 110 days or more to a preterm infant appears safe with no documented adverse effects, though the typical studied duration is until 36 weeks postmenstrual age (approximately 60-90 days depending on gestational age at birth). 1

Evidence on Extended Duration Safety

The longest well-documented study administered L. reuteri DSM 17938 to extremely low birthweight infants (<1,000 g) born at <28 weeks gestational age from birth until 36 weeks postmenstrual age (PMA), which translates to approximately 56-84 days of supplementation. 1 This multi-site randomized controlled trial found:

  • No adverse effects were reported during the entire supplementation period 1
  • The probiotic effects were transient and beneficial, with increased alpha-diversity and reduced pathogenic bacteria in early weeks 1
  • At 2 years follow-up, no substantial differences in microbiome composition existed between probiotic and control groups, indicating the effects normalized after discontinuation 1
  • Positive long-term outcomes included improved head growth at 36 weeks PMA and weight gain at 2 years 1

What Happens After Standard Duration

The evidence shows that L. reuteri colonization is transient by nature - the relative and absolute abundance of Lactobacillaceae gradually decreases over time, even during active supplementation. 1 This means:

  • Extending beyond typical duration (36 weeks PMA) is unlikely to cause harm because the probiotic doesn't permanently colonize the gut 1
  • The microbiome naturally transitions toward a more mature state regardless of continued supplementation 1
  • No evidence suggests accumulation of adverse effects with prolonged use 1

Safety Profile Across Multiple Studies

Multiple studies using L. reuteri DSM 17938 in preterm infants have consistently reported:

  • No adverse effects noted in studies ranging from 25 days to discharge 2, 3, 4
  • Safe reduction in feeding intolerance, improved growth parameters, and shorter hospital stays 2, 3, 4
  • Potential reduction in late-onset sepsis and necrotizing enterocolitis without safety concerns 3, 4

Critical Safety Considerations (Regardless of Duration)

Product quality is paramount - manufacturing contaminants have caused fatal infections in preterm infants, making pharmaceutical-grade products essential over dietary supplements. 5, 6

High-risk populations requiring extreme caution include: 5, 7

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

Practical Guidance for 110+ Days

If your infant has already received L. reuteri for 110 days or more:

  • Monitor for signs of infection (fever, lethargy, feeding intolerance), though these would be related to product contamination rather than duration 5, 6
  • Verify the product is pharmaceutical-grade and not a dietary supplement 5, 6
  • Consider discontinuation if the infant has reached term-equivalent age or beyond, as the evidence supports use primarily during the preterm period 1
  • No specific intervention is needed if the infant is thriving without complications, as extended duration has not been associated with harm 1, 2

Comparison to Combination Products

Consider that combination products may offer superior benefits - L. rhamnosus ATCC 53103 combined with Bifidobacterium species reduces mortality and NEC with higher certainty of evidence than L. reuteri alone. 5 However, this doesn't indicate L. reuteri is unsafe at extended durations. 1

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Lactobacillus reuteri DSM 17938 Improves Feeding Intolerance in Preterm Infants.

Pediatric gastroenterology, hepatology & nutrition, 2019

Guideline

Lactobacillus rhamnosus in Preterm Neonates

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Bifidobacterium animalis Safety and Efficacy in Preterm Neonates

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Safety of Probiotics During Pregnancy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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