A Partly Fermented Infant Formula with Postbiotics Including 3′-GL, Specific Oligosaccharides, 2′-FL, and Milk Fat Supports Adequate Growth, Is Safe and Well-Tolerated in Healthy Term Infants: A Double-Blind, Randomised, Controlled, Multi-Country Trial

Abstract

This study investigated growth, safety, and tolerance in healthy infants consuming a partly fermented infant formula (IF) with postbiotics, 2′-linked fucosyllactose (2′-FL), a specific prebiotic mixture of short-chain galacto-oligosaccharides (scGOS) and long-chain fructo-oligosaccharides (lcFOS), and milk fat. This double-blind, controlled trial randomised 215 fully IF-fed infants ≤ 14 days of age to either: Test Group (IF) containing 26% fermented formula with postbiotics derived from Lactofidus fermentation process (including 3′-Galactosyllactose; 3′-GL), 0.8 g/100 mL scGOS/lcFOS (9:1), 0.1 g/100 mL 2′-FL, and milk fat), or Control group (IF with 0.8 g/100 mL scGOS/lcFOS (9:1)) until 17 weeks of age. Fully breastfed infants were included as a reference. Anthropometric measures, gastrointestinal symptoms, and safety were assessed monthly. Equivalence in weight gain (primary outcome) between the Test and Control groups was confirmed (difference in means −0.08 g/day; 90% CI (−1.47;1.31)) with estimated mean weight gain (SE) of 31.00 (0.59) g/day and 31.08 (0.60) g/day, respectively, (PP population, n = 196). Equivalence in length and head circumference gain between the randomised groups was also confirmed. No statistically significant differences were observed in adverse events or gastrointestinal tolerance between randomised IF groups. A partly fermented IF with postbiotics, specific oligosaccharides, 2′-FL, and milk fat supports adequate infant growth and is safe and well-tolerated in healthy term infants.

Clinical Evaluation of 16-Week Supplementation with 5HMO-Mix in Healthy-Term Human Infants to Determine Tolerability, Safety, and Effect on Growth

“…We observed no significant difference in weight gain between the 5HMO-Mix and IF groups, indicating that the 5HMO-Mix was noninferior to the IF lacking HMOs. The observed mean values for daily weight gain of ~28.7 g/day were similar to those reported in studies comparing IF with 2′-FL plus GOS [ 42 ], 2′-FL plus LNnT [ 45 ], or 2′-FL plus 3′-GL and GOS/FOS [ 46 ]. When comparing the daily weight gain in the two formula groups to the BM group, we observed a slightly higher increase from baseline to V6 for 5HMO-Mix vs. BM (2.1 ± 0.9 g/day, p = 0.0199) compared to IF vs. BM (1.6 ± 0.9 g/day, p = 0.0674) in the FAS ( n = 300), but this effect was not seen in the PPS ( n = 239).…”

“…When comparing the daily weight gain in the two formula groups to the BM group, we observed a slightly higher increase from baseline to V6 for 5HMO-Mix vs. BM (2.1 ± 0.9 g/day, p = 0.0199) compared to IF vs. BM (1.6 ± 0.9 g/day, p = 0.0674) in the FAS ( n = 300), but this effect was not seen in the PPS ( n = 239). Faster weight gain has previously been reported for infants bottle-fed with formula [ 46 , 55 , 56 , 57 ]. However, this may be associated with loss of the infant’s self-regulation of energy intake due to early bottle feeding and is also observed when human breast milk is fed by bottle [ 56 , 57 , 58 ].…”

“…Over the last two decades, efforts have been made to synthesize HMOs and add them to formula products, but only a limited number of HMOs not representing all structural classes have been tested in the clinic. These earlier studies investigated the safety, tolerability, and effect on growth of 2′-FL [ 42 , 43 , 44 ], 2′-FL plus LNnT [ 45 , 54 ], or 2′-FL plus 3′-galactosyllactose (3′-GL) [ 46 ], typically combined with other prebiotics [ 42 , 43 , 46 ] such as galacto-oligosaccharides (GOS) and fructo-oligosaccharides (FOS) or probiotics [ 46 , 54 ].…”

“…However, AEs causally linked to the formula products occurred at a similar frequency in both groups. Gastrointestinal disorders are generally the most common AEs in studies of infant formulae [ 46 , 63 ]. However, caregivers in the 5HMO-Mix group were less likely to need healthcare interventions during the study than those in the IF group.…”

“…Thus, in this study, we chose concentrations of HMOs that reflected an average of reported physiological HMO concentrations in human breast milk, with a slightly increased proportion of LNT to promote growth of beneficial intestinal bacteria. Thus far, clinical studies have been carried out with 2′-FL or mixtures of two HMOs [ 42 , 43 , 44 , 45 , 46 ], but to the best of our knowledge there have been no clinical studies published on the tolerance and safety of HMO mixtures containing multiple HMOs from all three classes.…”