Human milk oligosaccharides and early-life outcomes: A systematic review and meta-analysis

Human milk oligosaccharides (HMOs) are key bioactive components of breast milk that support infant growth and gut microbiome development. This study evaluated the effects of HMO-enriched infant formula compared with non-HMO formula on clinical outcomes in healthy infants. This systematic review followed PRISMA guidelines and was registered with PROSPERO (CRD420251148484). Multiple databases were searched. Anthropometric outcomes showed no significant differences between groups. However, HMO supplementation over 6 and 12 months reduced the risk of lower respiratory tract infections (RR 0.61; 95% CI: 0.38–0.97 at 6 months; RR 0.59; 95% CI: 0.43–0.82 at 12 months) and was associated with decreased antibiotic use (RR 0.74; 95% CI: 0.64–0.86). Common HMOs included 2′-FL, LNnT, LNFP I, and LDFT. Early initiation (<3 months) was associated with increased Bifidobacterium abundance. HMO supplementation may improve early-life outcomes and supports its potential role in infant formula fortification.