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.