Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial

Abstract

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.

Functional effects of human milk oligosaccharides (HMOs)

“…Equivalence in weight gain (primary endpoint), length, and head circumference gain of up to 17 weeks was also confirmed with the test formula. There were no statistically significant differences between the formula groups for regurgitation, vomiting, watery, or hard stools at any timepoint 151 . Ramirez-Farias and colleagues 153 examined extensively hydrolyzed formula (eHF) with 2′-FL (0.2 g/L) for growth, tolerance, and compliance in a non-randomized, single-group, multicenter study.…”

“… Higher secretory immunoglobulin A and lower alpha-1-antitrypsin ( p < 0.05) in the test group in comparison to SFG. Vandenplas et al 151 2020 2’-FL, 3’-GL, scGOS/lcFOS Belgium, Hungary, Poland, Spain Ukraine 215 fully formula fed infants≤14 days old Infant formula contained 26% fermented formula with postbiotics derived from the Lactofidus fermentation process (including 3′-GL), 0.8 g/100 mL scGOS/lcFOS (9:1), and 0.1 g/100 mL 2′-FL Standard infant formula containing the oligosaccharides scGOS/lcFOS (0.8 g/100 mL; 9:1), but no 2′-FL, postbiotics, or milk fat. Breastfed infants Until 17 weeks of age Equivalence in weight gain between the test formula and control infant formula up to 17 weeks of age Supported an adequate growth, was well-tolerated, and no safety concerns were revealed given the absence of clinically relevant differences in the number adverse event.s Nowak-Wegrzyn et al 168 2019 2‘FL + LNnT United States 2017–2018 64 children with CMPA Aged 2 months to 4 years Extensively hydrolyzed formula with 1 g/L 2’-FL and 0.5 g/L LNnT Extensively hydrolyzed formula without HMOs 7–9 days The study formula met the clinical hypoallergenicity criteria.…”

“…Vandenplas et al . 151 studied growth, safety, and tolerance in healthy infants consuming a partly fermented infant formula with postbiotics and the HMOs 3′–GL) and 2′-FL, and a specific prebiotic mixture of short-chain GOS (scGOS) and long-chain fructo-oligosaccharides (lcFOS). Equivalence in weight gain (primary endpoint), length, and head circumference gain of up to 17 weeks was also confirmed with the test formula.…”

The Link between Different Types of Prebiotics in Infant Formula and Infection Rates: A Review

“…In the study of Parschat et al, the infection rate was 32/113 vs. 28/112 (p = 0.54) [36]. In the study of Lasekan et al, the antipyretic use was comparable (4/128 and 4/126), as was the antibiotic use (4/128 vs. 4/126) [38]. However, the study of Lasekan was conducted during the COVID-19 pandemic, where the infection rates in infants were generally low (7.6% of included patients), which is likely to have had an impact on these observations.…”

“…We retained six publications on human milk oligosaccharides (HMOs) (Table 3) [28,[34][35][36][37][38] involving a total of 1571 infants, conducted in America, Europe, and Asia. Five studies included only healthy term infants, and one study examined the effects of HMOs on infants with cow's milk allergy (CMA).…”