Karen Harris

Karen Harris is a professional writer and editor with more than two decades of experience in research-driven nonfiction writing. With a background in journalism and a Master's degree in English, she brings a meticulous approach to fact-finding, source evaluation, and clear communication of complex topics. Her work spans health, lifestyle, and consumer education, always with a focus on accuracy and readability.

Context

Human milk oligosaccharides (HMOs) are a major bioactive component of breast milk, believed to support immune development and gut health in early infancy. Standard cow's milk-based formulas contain very little of these compounds. This randomized controlled trial - the primary safety and efficacy trial for 2′FL and LNnT supplementation - evaluated whether adding two HMOs to infant formula affects growth, tolerability, and illness rates during the first year of life.

Study Overview

Design: Randomized, double-blind, controlled, multicenter trial (RCT)


Population: 175 healthy, full-term formula-fed infants, enrolled at 0–14 days of age (Italy & Belgium)


Follow-up: 12 months


Funding: Fully funded by Société des Produits Nestlé SA; most authors are Nestlé employees


Evidence Certainty (GRADE): Not formally GRADE-rated; secondary morbidity outcomes are exploratory


Comparison:

  • Test group (n = 88): Whey-predominant cow's milk formula + 1.0 g/L 2′FL + 0.5 g/L LNnT (replacing equivalent lactose), from enrollment to 6 months
  • Control group (n = 87): Identical formula without HMOs, from enrollment to 6 months
  • Both groups switched to the same standard follow-up formula without HMOs from 6 to 12 months
  • Complementary foods allowed from 4 months onward

Key Findings

Growth (Primary Outcome — met non-inferiority):

  • Weight gain from 0–4 months was equivalent between groups (test: 29.84 g/day vs. control: 30.15 g/day; difference −0.30 g/day, 95% CI −1.94 to 1.34), well above the pre-specified non-inferiority margin of −3 g/day.
  • All anthropometric z-scores (weight, length, head circumference, BMI) tracked closely with WHO 2006 growth standards through 12 months, with no significant differences between groups at any visit.

Gastrointestinal Tolerance & Behavior:

  • Overall GI symptoms (flatulence, spitting-up, vomiting) were similar between groups.
  • HMO group had significantly softer stools at 2 months (p = 0.021), a pattern similar to breastfed infants; this difference did not persist beyond 2 months.
  • Fewer nighttime wake-ups were reported in the HMO group at 2 months (p = 0.036); did not persist thereafter.
  • Among Caesarean-born infants specifically, colic at 4 months was reported significantly less in the HMO group (p = 0.035).

Morbidity & Medication Use (Secondary, Exploratory):

  • Bronchitis rates were significantly lower in the HMO group at 4 months (2.3% vs. 12.6%), 6 months (6.8% vs. 21.8%), and 12 months (10.2% vs. 27.6%).
  • Lower respiratory tract infections were less frequent in the HMO group through 12 months (19.3% vs. 34.5%).
  • Antibiotic use was significantly lower in the HMO group at 6 months (34.1% vs. 49.4%) and 12 months (42.0% vs. 60.9%).
  • Antipyretic use was significantly lower at 4 months (15.9% vs. 29.9%), but not at later time points.
  • Effects on bronchitis and lower respiratory tract infections were especially pronounced in the Caesarean-born subgroup.
  • No significant differences were found for GI-related illnesses (e.g., gastroenteritis), upper respiratory tract infections, or otitis media.
  • Morbidity and medication differences persisted through 12 months, i.e., 6 months after HMO supplementation ended.

Limitations

  • The trial was powered solely for the primary growth/safety outcome — all morbidity findings are exploratory secondary endpoints and must be interpreted accordingly.
  • All illness and medication data were based entirely on parental reporting via diary; no independent clinical verification of diagnoses.
  • No breastfed reference group was included in this primary trial.
  • Study conducted at only two European sites (Italy and Belgium), limiting geographic generalizability.
  • The dropout rate was ~25% by the primary outcome visit, as anticipated and accounted for in the sample size calculation.
  • The morbidity differences observed at 12 months (6 months post-intervention) raise questions about mechanism that cannot be answered by this trial design alone.
  • Fully industry-funded; several authors are Nestlé employees, with potential for bias in design, analysis, and interpretation.
  • No stool volume or weight data collected, so osmotic effects of HMO supplementation cannot be ruled out.

Neutral Interpretation

This RCT robustly demonstrates that formula supplemented with 2′FL and LNnT supports normal infant growth and is well tolerated - the primary safety objective was clearly met. The secondary findings of reduced bronchitis, lower respiratory tract infections, and antibiotic use are biologically plausible given preclinical evidence on HMO immune-modulating properties, and the magnitude of differences is notable. However, these outcomes were not the primary focus of a trial powered for growth, relied on parental reporting rather than clinical verification, and come from a study entirely funded and largely conducted by the manufacturer. These findings are hypothesis-generating and warrant confirmation in larger, independently funded trials with morbidity as a pre-specified primary endpoint.

Full Citation

Puccio G, Alliet P, Cajozzo C, et al. Effects of Infant Formula With Human Milk Oligosaccharides on Growth and Morbidity: A Randomized Multicenter Trial. J Pediatr Gastroenterol Nutr. 2017;64(4):624–631. 

PMID: 28107288. 

Available at: https://pubmed.ncbi.nlm.nih.gov/28107288/

Disclosure

This summary is based on the published study. It is provided for informational purposes only and does not constitute medical advice.