AUTHOR=Hascoët Jean-Michel , Chevallier Marie , Gire Catherine , Brat Roselyne , Rozé Jean-Christophe , Norbert Karine , Chen Yipu , Hartweg Mickaël , Billeaud Claude 

TITLE=Use of a Liquid Supplement Containing 2 Human Milk Oligosaccharides: The First Double-Blind, Randomized, Controlled Trial in Pre-term Infants

JOURNAL=Frontiers in Pediatrics

VOLUME=10

YEAR=2022

URL=https://www.frontiersin.org/journals/pediatrics/articles/10.3389/fped.2022.858380

DOI=10.3389/fped.2022.858380

ISSN=2296-2360

ABSTRACT=<p>There is growing evidence supporting the benefit of human milk oligosaccharides (HMOs) on reducing risk of illnesses and improving immune function in newborn infants, but evidence in pre-term infants is lacking. This randomized, double-blind, placebo-controlled trial (NCT03607942) of pre-term infants evaluated the effects of HMO supplementation on feeding tolerance, growth, and safety in 7 neonatal units in France. Pre-term infants (27–33 weeks' gestation, birth weight &lt;1,700 g) were randomized early after birth to receive HMO supplement (<italic>n</italic> = 43) [2′-fucosyllactose (2′FL) and lacto-<italic>N</italic>-neotetraose (LNnT) in a 10:1 ratio (0.374 g/kg body weight/day)] or an isocaloric placebo (<italic>n</italic> = 43) consisting of only glucose (0.140 g/kg/day) until discharge from the neonatal unit. Anthropometric <italic>z</italic>-scores were calculated using Fenton growth standards. Primary outcome was feeding tolerance, measured by non-inferiority (NI) in days to reach full enteral feeding (FEF) from birth in HMO vs. placebo group (NI margin = 4+ days). Mean number of days on intervention prior to FEF was 8.9 and 10.3 days in HMO and placebo, respectively. Non-inferiority in time to reach FEF in HMO (vs. placebo) was achieved [LS mean difference (95% CI) = −2.16 (−5.33, 1.00); upper bound of 95% CI &lt; NI margin] in full analysis set and similar for per protocol. Adjusted mean time to reach FEF from birth was 2 days shorter in HMO (12.2) vs. placebo (14.3), although not statistically significant (<italic>p</italic> = 0.177). There was no difference in weight-for-age <italic>z</italic>-scores between groups throughout the FEF period until discharge. Length-for-age <italic>z</italic>-scores were higher in HMO at FEF day 14 [0.29 (0.02, 0.56), <italic>p</italic> = 0.037] and 21 [0.31 (0.02, 0.61), <italic>p</italic> = 0.037]. Head circumference-for-age <italic>z</italic>-score was higher in HMO vs. placebo at discharge [0.42 (0.12, 0.71), <italic>p</italic> = 0.007]. Occurrence of adverse events (AEs) was similar in both groups and relatively common in this population, whereas 2.3 and 14.3%, respectively, experienced investigator-confirmed, related AEs. HMO supplementation is safe and well-tolerated in pre-term infants. After 9 days of supplementation, the HMO group reached FEF 2 days earlier vs. placebo, although the difference was not statistically significant. In addition, HMO supplementation supports early postnatal growth, which may have a positive impact on long-term growth and developmental outcomes.</p>