Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial

Giuseppe Puccio, Philippe Alliet, Cinzia Cajozzo, Elke Janssens, Giovanni Corsello, Norbert Sprenger, Susan Wernimont, Delphine Egli, Laura Gosoniu, Philippe Steenhout, Giuseppe Puccio, Philippe Alliet, Cinzia Cajozzo, Elke Janssens, Giovanni Corsello, Norbert Sprenger, Susan Wernimont, Delphine Egli, Laura Gosoniu, Philippe Steenhout

Abstract

Objectives: The aim of the study was to evaluate the effects of infant formula supplemented with 2 human milk oligosaccharides (HMOs) on infant growth, tolerance, and morbidity.

Methods: Healthy infants, 0 to 14 days old, were randomized to an intact-protein, cow's milk-based infant formula (control, n = 87) or the same formula with 1.0 g/L 2'fucosyllactose (2'FL) and 0.5 g/L lacto-N-neotetraose (LNnT) (test, n = 88) from enrollment to 6 months; all infants received standard follow-up formula without HMOs from 6 to 12 months. Primary endpoint was weight gain through 4 months. Secondary endpoints included additional anthropometric measures, gastrointestinal tolerance, behavioral patterns, and morbidity through age 12 months.

Results: Weight gain was similar in both groups (mean difference [95% confidence interval] test vs control: -0.30 [-1.94, 1.34] g/day; lower bound of 95% confidence interval was above noninferiority margin [-3 g/day]). Digestive symptoms and behavioral patterns were similar between groups; exceptions included softer stool (P = 0.021) and fewer nighttime wake-ups (P = 0.036) in the test group at 2 months. Infants receiving test (vs control) had significantly fewer parental reports (P = 0.004-0.047) of bronchitis through 4 (2.3% vs 12.6%), 6 (6.8% vs 21.8%), and 12 months (10.2% vs 27.6%); lower respiratory tract infection (adverse event cluster) through 12 months (19.3% vs 34.5%); antipyretics use through 4 months (15.9% vs 29.9%); and antibiotics use through 6 (34.1% vs 49.4%) and 12 months (42.0% vs 60.9%).

Conclusions: Infant formula with 2'FL and LNnT is safe, well-tolerated, and supports age-appropriate growth. Secondary outcome findings showing associations between consuming HMO-supplemented formula and lower parent-reported morbidity (particularly bronchitis) and medication use (antipyretics and antibiotics) warrant confirmation in future studies.

Trial registration: ClinicalTrials.gov NCT01715246.

Figures

FIGURE 1
FIGURE 1
Flow of study participants. Ninety-five infants (47 control, 48 test) were enrolled at the site in Belgium; 80 infants (40 control, 40 test) were enrolled at the site in Italy. HMOs = human milk oligosaccharides; ITT = intention-to-treat; PP = per-protocol.
FIGURE 2
FIGURE 2
Anthropometric z scores for weight-for-age (A), length-for-age (B), head circumference-for-age (C) and BMI-for-age (D) from enrollment to 12 months of age based on the 2006 World Health Organization Child Growth Standards. Triangles/dashed line = control; Circles/solid line = test. BMI = body mass index.
FIGURE 3
FIGURE 3
OR (with 95% CI) for parent-reported adverse events identified a priori and medication use in the test group compared with the control group. Analyzed using Fisher's exact test: ∗P < 0.05, ∗∗P ≤ 0.01. †Refers to parent-reported morbidity or medication use. AE = adverse event; CI = confidence interval; LRTI = lower respiratory tract infection; OR = odds ratio.

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Source: PubMed

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