A number of benefits of breastfeeding, particularly protection against child infections, may be, at least partially, related to the presence of human milk oligosaccharides (HMOs). Among others, the postulated effects of HMOs include prebiotic and antiadhesive/antimicrobial effects, modulation of intestinal epithelial cells, and immune modulation.

Progress in biotechnology nowadays allows the production of at least some HMOs. Two HMOs, 2-fucosyllactose (2’-FL) and lacto-N-neo-tetraose (LNnT), have recently been added to infant formula, either alone or in combination. We are at the beginning of a new era in infant nutrition which poses a number of clinical questions, the answers to which should be evidence-based.

Evidence-based medicine (EBM) relies on finding and critically appraising the relevant scientific literature with regard to the trustworthiness of the data reported and with the purpose of determining the merits of an intervention. This knowledge is then implemented in clinical care. The key elements of practicing EBM are formulation of an answerable question, finding the evidence, critical appraisal of the evidence, and applying the evidence. The extent to which one can draw conclusions from published clinical research depends on whether the data and results of the study are free of biases. If there are biases, the task is to consider how they might affect the results.

In the context of EBM, potential benefits, along with safety, should be considered when adding a new ingredient, such as an HMO, to formulas. Major databases were searched up to January 2019 for randomized controlled trials to review current evidence on HMO-supplemented formulas. The administration of currently evaluated HMO-supplemented formulas to healthy infants does not raise safety concerns with regard to growth and adverse effects. Some favorable clinical effects are possible; however, further high-quality randomized clinical trials are needed. These trials should assess outcomes over a longer period of time and use validated outcomes that are agreed on by experts in the field of infant nutrition. Future research should also examine the optimal composition and dosage for HMO interventions and consider effectiveness in different settings/populations. Stay tuned for future publications.