2.1. Cohort Description
CMPA, EHF
SECONDARY
The study cohort comprised 194 non-breastfed infants aged between 2 weeks and 6 months (mean age 3.2 months) from 7 countries in Europe and Singapore with symptoms suggestive of CMPA. Participants were randomized to receive either an EHF supplemented with 2′-FL and LNnT (test formula) or the same EHF without HMO (control formula) until 12 months of age. The protein content of the test formula was slightly lower than that of the control formula (2.5 g/100 kcal vs. 2.2 g/100 kcal). The first 4 months of the study were conducted as a growth trial (principal study period). The introduction of a complementary solid diet was allowed from 4 months of age. Infants were followed to 12 months of age (secondary study period). Demographics of the study cohort, clinical details, and study outcomes (growth, tolerability, and safety) were previously published [Of the 194 participants, 151 (79 test, 72 control) completed the 4-month growth trial without major protocol deviations (per protocol cohort). Of these, 142 (71 test, 71 control) remained in the trial until 12 months of age (visit 6). The microbiome and metabolomic analyses were limited to the per-protocol cohort and performed at baseline (visit 0), after 1 month (visit 1), and 3 months (visit 3) of study formula intake, and during follow-up at 12 months of age (visit 6). The microbiome composition and fecal metabolomic signature were strongly influenced by the infant’s age in both feeding groups (