Probiotic Supplements Effect on Feeding Tolerance, Growth and Neonatal Morbidity in Extremely Preterm Infants: A Systematic Review and Meta-Analysis.

2025-04-01
Nutrients 17(7)

PubMed: 40218986
DOI: 10.3390/nu17071228

Study Design

Type: Meta-Analysis
Sample size: n = 14
Population: extremely preterm infants
Methods: A literature search was conducted in Medline, Embase, Cochrane CENTRAL, Web of Science, and clinicaltrials.gov for ongoing trials. We included extremely preterm infants from randomized controlled trials and non-randomized trials with a concurrent control group. Two authors independently performed screening, data extraction and risk of bias assessment using the Risk of Bias 2 tool from Cochrane. The certainty of the evidence was assessed using GRADE.

Rigorous Journal

Background/objectives

Probiotic supplementation has been actively investigated in preterm populations to reduce the risk of necrotizing enterocolitis (NEC) and late-onset sepsis. Despite this, few studies have focused on clinically relevant feeding tolerance and growth outcomes, and there is an alarming lack of evidence surrounding extremely preterm infants (defined as birth before 28 weeks gestational age), those most at risk of severe comorbidities. We aimed to investigate whether probiotics improve feeding tolerance, neonatal growth and neonatal morbidity among extremely preterm infants.

Methods

A literature search was conducted in Medline, Embase, Cochrane CENTRAL, Web of Science, and clinicaltrials.gov for ongoing trials. We included extremely preterm infants from randomized controlled trials and non-randomized trials with a concurrent control group. Two authors independently performed screening, data extraction and risk of bias assessment using the Risk of Bias 2 tool from Cochrane. The certainty of the evidence was assessed using GRADE.

Results

Eleven RCTs and three non-randomized studies with a concurrent control group were included, analyzing a total of 14,888 extremely preterm infants. Meta-analyses revealed lower mean days to full enteral feeds (mean difference 1.1 days lower; 95% CI, 7.83 lower to 5.56 higher) and lower duration of parenteral nutrition (mean difference 2.4 days lower; 95% CI, 7.44 lower to 2.58 higher) in infants treated with probiotics; however, this was not statistically significant. There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) and all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group. All outcomes were graded at low or very low certainty of evidence.

Conclusions

The findings indicate a trend towards a potential beneficial effect of probiotic supplementation in reducing feeding intolerance and a notable reduction of risk of NEC and all-cause mortality in infants receiving probiotics. Future RCTs will focus on feeding intolerance, and growth outcomes are warranted.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bifidobacterium bifidum HA-132	—	Improved Feeding Tolerance	Beneficial	Small	View source Meta-analyses revealed lower mean days to full enteral feeds ... and lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium bifidum HA-132	—	Reduced All-Cause Mortality	Beneficial	Moderate	View source There was a significant reduction in ... all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group.
Bifidobacterium bifidum HA-132	—	Reduced Necrotising Enterocolitis	Beneficial	Moderate	View source There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) in the probiotic group.
Bifidobacterium breve Bb-18	—	Improved Feeding Tolerance	Beneficial	Small	View source Meta-analyses revealed lower mean days to full enteral feeds ... and lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium breve Bb-18	—	Reduced All-Cause Mortality	Beneficial	Moderate	View source There was a significant reduction in ... all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group.
Bifidobacterium breve Bb-18	—	Reduced Duration of Parenteral Nutrition	Beneficial	Small	View source Meta-analyses revealed ... lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium breve Bb-18	—	Reduced Necrotising Enterocolitis	Beneficial	Moderate	View source There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) in the probiotic group.
Bifidobacterium breve HA-129	—	Improved Feeding Tolerance	Beneficial	Small	View source Meta-analyses revealed lower mean days to full enteral feeds ... and lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium breve HA-129	—	Reduced All-Cause Mortality	Beneficial	Moderate	View source There was a significant reduction in ... all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group.
Bifidobacterium breve HA-129	—	Reduced Necrotising Enterocolitis	Beneficial	Moderate	View source There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) in the probiotic group.
Bifidobacterium infantis HA-116	—	Improved Feeding Tolerance	Beneficial	Small	View source Meta-analyses revealed lower mean days to full enteral feeds ... and lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium infantis HA-116	—	Reduced All-Cause Mortality	Beneficial	Moderate	View source There was a significant reduction in ... all-cause mortality (RR; 0.56, 95% CI; 0.33, 0.93) in the probiotic group.
Bifidobacterium infantis HA-116	—	Reduced Duration of Parenteral Nutrition	Beneficial	Small	View source Meta-analyses revealed ... lower duration of parenteral nutrition ... in infants treated with probiotics; however, this was not statistically significant.
Bifidobacterium infantis HA-116	—	Reduced Necrotising Enterocolitis	Beneficial	Moderate	View source There was a significant reduction in NEC (RR; 0.80, 95% CI; 0.68, 0.93) in the probiotic group.