Effect of Probiotic Dose Escalation on Gut Microbiota and Clinical Outcomes in Preterm Infants-A Systematic Review.

Probiotics are known to decrease incidences of necrotising enterocolitis, feeding intolerance, late-onset sepsis, and mortality in preterm infants. Administering an adequate dose is important for optimizing the benefits and safety of probiotics. We conducted a systematic review to assess the effect of probiotic dose escalation on clinical outcomes and gut microbiota in preterm neonates. We searched PubMed, EMBASE, EMCARE, Medline, Cochrane Library, Google Scholar, and MedNar databases in July 2023. Three studies were included. In one of the randomized studies (n = 149, gestation 27 to 33 weeks), no significant differences in faecal Lactobacillus and Bifidobacterium counts and clinical outcomes were seen between the high- and low-dose groups. There was a trend towards increased Lactobacillus and Bifidobacterium counts in the high-dose group. In the other randomized study (n = 120, birth weight 500 to 2000 gm), smaller infants (500 to 1000 gm) required higher doses to display Lactobacillus in their faeces. The cohort study (n = 12, gestation < 33 weeks) showed a trend towards an increase in faecal abundance of bifidobacteria and bacterial diversity in the B. infantis group with increasing dose/time. Limited evidence suggests a higher dose might improve gut colonization in preterm infants. Further studies are urgently needed to address this gap in the knowledge considering the increasing use of probiotics for preterm infants.