Meta-analysis highlights health benefits of probiotics and prebiotics in premature infants

1. Overall mortality, NEC morbidity, sepsis morbidity, time to enteral feeding, and length of hospital stay were decreased in premature infants receiving any two of Lactobacillus, Bifidobacterium, and prebiotic.

2. Use of a single probiotic was inferior to using combinations of probiotics or a probiotic plus a prebiotic.

Evidence Rating Level: 1 (Excellent)

Study Rundown: Necrotizing enterocolitis (NEC) and sepsis are significant causes of morbidity and mortality in premature infants. Imbalance of the preterm gut microbiome has long been considered a predisposing factor to NEC, and many studies have reported mortality reduction in those infants that receive probiotic supplementation. This meta-analysis was the first to compare efficacy of different probiotics, prebiotics, and synbiotics (combinations of the two) in premature infants. It found that rates of mortality, NEC morbidity, sepsis morbidity, time to full enteral feeding, and length of hospital stay, may be reduced with a combination of any two of Lactobacillus, Bifidobacterium, and prebiotic. However, only two studies included infants with extremely low birth weight (<1000g), preventing any elucidation of the potential sepsis risk of probiotics in this tenuous patient population. Overall, these findings provide useful guidance to clinicians on the use of specific combinations of probiotics and prebiotics to reduce morbidity and mortality in premature infants.

Click to read the study in Pediatrics

Click to read an accompanying editorial in Pediatrics

Relevant Reading: The microbiome in early life: implications for health outcomes

In-Depth [meta-analysis]: This meta-analysis included 45 randomized controlled trials (RCTs) performed between 2002 and 2018 comparing 14 different probiotics versus placebo in infants with a gestational age < 37 weeks or birth weight < 2500 grams. 12,320 infants were included in the trials (intervention group n = 6577, placebo group n = 5743). Infants who received a combination of Bifidobacterium plus Lactobacillus had lower rates of mortality (RR 0.56; 95% CI 0.34-0.84) and NEC morbidity (RR 0.47; 95% CI 0.27-0.79) compared to placebo. Bifidobacterium plus prebiotic and Bifidobacterium plus Lactobacillus were superior to placebo in the time to reach full enteral feeding and length of hospitalization. Furthermore, infants who received Lactobacillus plus prebiotic had the lowest rates of NEC morbidity (RR 0.06; 95% CI 0.01-0.41). In an adjusted model (using the Markov chain Monte Carlo method), infants who received Bifidobacterium plus prebiotic had the lowest risk of overall death (surface under the cumulative ranking curve (SUCRA) 83.94%) compared to Lactobacillus plus prebiotic (SUCRA 79.69%) and Bifidobacterium plus Lactobacillus (SUCRA 73.81%). Lactobacillus and prebiotic were most likely to have the lowest rates of NEC and sepsis (SUCRA 95.62% and 98.85%, respectively). Bifidobacterium plus Lactobacillus had the highest probability of being the most effective in reducing the time to reach full enteral feeding (SUCRA 89.41%) and length of hospitalization (SUCRA 82.13%).

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