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Probiotic Supplements Effect on Feeding Tolerance, Growth and Neonatal Morbidity in Extremely Preterm Infants: A
Sofia Söderquist Kruth1,2, Emma Persad1, Alexander Rakow1,3
1Department of Women's and Children's Health, Karolinska Institutet, 17177 Stockholm, Sweden.
Insights
Probiotic supplementation may reduce necrotizing enterocolitis (NEC) and mortality in extremely preterm infants. While not statistically significant, there was a trend toward improved feeding tolerance. Further research is needed for definitive conclusions on feeding and growth outcomes.
Area of Science:
- Neonatal Medicine
- Gastroenterology
- Microbiome Research
Background:
- Probiotic supplementation is explored for reducing necrotizing enterocolitis (NEC) and sepsis in preterm infants.
- Evidence is limited regarding feeding tolerance, growth, and extremely preterm infants (born before 28 weeks gestational age).
- This study investigates probiotic effects on feeding tolerance, growth, and morbidity in this high-risk population.
Purpose of the Study:
- To assess the impact of probiotic supplementation on feeding tolerance in extremely preterm infants.
- To evaluate the effect of probiotics on neonatal growth and morbidity, including NEC and mortality.
- To synthesize evidence from randomized controlled trials and non-randomized studies.
Main Methods:
- Comprehensive literature search across major databases (Medline, Embase, Cochrane CENTRAL, Web of Science, clinicaltrials.gov).
- Inclusion of extremely preterm infants from RCTs and non-randomized trials with concurrent control groups.
- Independent data extraction, risk of bias assessment (Risk of Bias 2 tool), and GRADE certainty assessment.
Main Results:
- Meta-analyses of 11 RCTs and 3 non-randomized studies (14,888 infants) showed no statistically significant improvement in days to full enteral feeds or duration of parenteral nutrition.
- Significant reductions were observed in necrotizing enterocolitis (NEC) (RR; 0.80) and all-cause mortality (RR; 0.56) in the probiotic group.
- All outcome evidence certainty was graded as low or very low.
Conclusions:
- Probiotic supplementation shows a trend towards reducing feeding intolerance in extremely preterm infants.
- A notable reduction in NEC and all-cause mortality risk was observed with probiotic use.
- Future randomized controlled trials are essential to confirm benefits for feeding intolerance and growth outcomes.
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.
