Milk Free From A1-Type β-Casein With Human Milk Oligosaccharides on Gut Health, Immunity, Cognitive Development, and Temperament in Toddlers

The aim of the study is to compare the effects of HMOs in A1-type β-casein-free formula on gut health, immunity, inflammation, gut microflora, cognitive development, and temperament compared with HMOs in conventional formula in toddlers aged 24-30 months.

Inclusion Criteria: * (24±3) months of age at enrolment/randomisation Singleton birth Born full-term (37-42 weeks gestation) * Birth weight of 2500-4500 g * Habitually consume any cow's milk * Parent or guardian of toddler agrees not to enrol toddler in another interventional clinical trial while participating in this trial * Parent or guardian agrees to exclusively feed the toddler the assigned toddler formula, as per the randomisation schedule Exclusion Criteria: * Toddler with inborn malformation and with hereditary and/or chronic and/or inborn diseases that could interfere with the trial * Toddlers born after in vitro fertilisation (IVF) * Diseases that may have jeopardised intrauterine growth * Toddler whose mother had gestational diabetes, and other metabolic and/or chronic diseases at the time of pregnancy (for example, gestational hypertension, thyroid dysfunction, autoimmune diseases, and pre-existing diabetes mellitus.) * Known or increased risk of cows' milk protein allergy (i.e., one of the biological parents and/or siblings diagnosed with allergy, asthma, hayfever, etc.) * Toddlers currently using, or who have ever used, specialty formula or growing-up milk (GUM), such as hypoallergenic, lactose-free, or anti-regurgitation formulas * Toddlers with functional gastrointestinal disorders; e.g., gastroparesis * Toddlers with an acute infection or gastroenteritis at the time of randomisation * Evidence of milk/formula intolerance, such as vomiting or poor intake at the time of randomisation * Participation in another clinical trial * Investigator uncertainty about the willingness or ability of the parents to comply with the protocol requirements * Use of antibiotics at the time of screening, or during the 2 weeks before enrolment * Toddlers with known cognitive or developmental disorders