Effect of probiotics on necrotizing enterocolitis in preterm infants: a network meta-analysis of randomized controlled trials.

2025-03-27
BMC pediatrics 25(1)
- Yu Dai
- Qinlei Yu
- Fan Zhang
- Ke Ma
- Xiangyun Yan
- Wenjuan Chen
- Xiaohui Chen
- Shushu Li
- Shuping Han

PubMed: 40140789
DOI: 10.1186/s12887-025-05469-z

Study Design

Type: Systematic Review
Sample size: n = 661
Population: preterm infants
Methods: network meta-analysis of 51 randomized controlled trials involving 11,661 participants

Background

Previous studies have suggested that probiotics may have potential benefits for preterm infants. Their efficacy seems to depend on the particular species or combinations used.

Methods

To further investigate the effects of probiotics in preventing necrotizing enterocolitis (NEC) and other related outcomes in preterm infants, we conducted a network meta-analysis of 51 randomized controlled trials involving 11,661 participants.

Results

Our study revealed that most probiotics can effectively reduce the incidence of NEC (at or beyond Bell's stage II). Lactobacillus (RR, 0.59; 95% CI: 0.29, 0.98), the combination of Bifidobacterium and Lactobacillus (RR, 0.47; 95% CI: 0.20, 0.87), and the combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR, 0.17; 95% CI: 0.00, 0.84) were the only treatments that significantly reduced all-cause mortality compared to placebo. Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81) and reaching full enteral feeding (MD, -2.15; 95% CI: -3.70, -0.64).

Conclusions

The combination of Bifidobacterium, Lactobacillus, and Enterococcus was the most efficacious in reducing the mortality and incidence of NEC (Bell II or above) in preterm infants. Both prebiotics and Lactobacillus alone were found to be highly effective in reducing the length of hospitalization and the time needed to achieve full enteral feeding. No evidence suggests that probiotics affect sepsis risk.

Trial registration

The study protocol was registered with PROSPERO (CRD42023460231) on March 10, 2023.

Research Insights

Bifidobacterium bifidum HA-132→Reduced All-Cause Mortality
Lactobacillus (RR, 0.59; 95% CI: 0.29, 0.98), the combination of Bifidobacterium and Lactobacillus (RR, 0.47; 95% CI: 0.20, 0.87), and the combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR, 0.17; 95% CI: 0.00, 0.84) were the only treatments that significantly reduced all-cause mortality compared to placebo.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium bifidum HA-132→Reduced Incidence of Necrotizing Enterocolitis
Most probiotics can effectively reduce the incidence of NEC (at or beyond Bell's stage II).
Effect
Beneficial
Effect size
Moderate
Bifidobacterium bifidum HA-132→Reduced Length of Hospital Stay
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81).
Effect
Beneficial
Effect size
Small
Bifidobacterium bifidum HA-132→Reduced Time to Full Enteral Feeding
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81) and reaching full enteral feeding (MD, -2.15; 95% CI: -3.70, -0.64).
Effect
Beneficial
Effect size
Small
Bifidobacterium infantis HA-116→No Change in Sepsis Risk
No evidence suggests that probiotics affect sepsis risk.
Effect
Neutral
Effect size
Small
Bifidobacterium infantis HA-116→Reduced All-Cause Mortality
Lactobacillus (RR, 0.59; 95% CI: 0.29, 0.98), the combination of Bifidobacterium and Lactobacillus (RR, 0.47; 95% CI: 0.20, 0.87), and the combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR, 0.17; 95% CI: 0.00, 0.84) were the only treatments that significantly reduced all-cause mortality compared to placebo.
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis HA-116→Reduced Incidence of Necrotizing Enterocolitis
Most probiotics can effectively reduce the incidence of NEC (at or beyond Bell's stage II).
Effect
Beneficial
Effect size
Moderate
Bifidobacterium infantis HA-116→Reduced Length of Hospital Stay
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81).
Effect
Beneficial
Effect size
Small
Bifidobacterium infantis HA-116→Reduced Time to Full Enteral Feeding
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81) and reaching full enteral feeding (MD, -2.15; 95% CI: -3.70, -0.64).
Effect
Beneficial
Effect size
Small
Lactobacillus→Reduced All-Cause Mortality
Lactobacillus (RR, 0.59; 95% CI: 0.29, 0.98), the combination of Bifidobacterium and Lactobacillus (RR, 0.47; 95% CI: 0.20, 0.87), and the combination of Bifidobacterium, Lactobacillus, and Streptococcus (RR, 0.17; 95% CI: 0.00, 0.84) were the only treatments that significantly reduced all-cause mortality compared to placebo.
Effect
Beneficial
Effect size
Moderate
Lactobacillus→Reduced Length of Hospitalization
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81)
Effect
Beneficial
Effect size
Moderate
Lactobacillus→Reduced Time to Full Enteral Feeding
Lactobacillus can be effective in reducing the time preterm infants spend in the hospital (MD, -4.23; 95% CI: -7.62, -0.81) and reaching full enteral feeding (MD, -2.15; 95% CI: -3.70, -0.64).
Effect
Beneficial
Effect size
Small