Effect of a Multinutrient-Optimized Infant Formula Supplemented With Human Milk Oligosaccharides on Infant Growth and Development: A Multicenter, Randomized, Controlled Trial

Effect of Adding Breast Milk Oligosaccharides and Multinutrient Optimized Infant Formula on the Growth and Development of Infants Aged 0 to 1 Years: a Multicenter, Double-blind, Randomized, Controlled Trial

This study aims to learn about a newly developed infant formula that adds two special ingredients found in breast milk (human milk oligosaccharides, HMOs) and improves other nutrients. We will compare the effects of this new formula, a currently available standard formula, and breastfeeding on babies' growth and development during their first year of life. We plan to enroll about 240 healthy newborn babies, who will be divided into three groups: about 80 babies will be fed the new formula with added breast milk ingredients, about 80 will receive the standard infant formula, and about 80 will be breastfed by their mothers. Assignment to the formula groups will be done randomly by computer, while families who wish to and are able to breastfeed will join the breastfeeding group. The study will last about 12 months, during which our research team will have 4 visits with the babies at 28 days, 3 months, 6 months, and 12 months of age. At these visits, we will measure the baby's growth (like height, weight, and head size), use internationally recognized tests to check mental and motor development, collect small samples of stool and blood to understand gut health and immune function, and ask parents to fill out short questionnaires about feeding, sleep, fussiness, and the baby's health. Both formulas used in the study meet national food safety standards, and the entire study follows strict ethical rules to protect the privacy and rights of babies and families. Families in the formula groups will receive all study formula for free and receive regular health check-ups from a professional team. The results will help scientists and doctors better understand how to improve infant formula to support healthy baby growth.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Human Milk Oligosaccharide-Supplemented, Multi-Nutrient Optimized Infant Formula; Dietary supplement: Commercially Available Standard Formula; Dietary supplement: Breast Milk Feeding

Detailed Description

This multicenter, randomized, double-blind, controlled, parallel-group clinical trial is designed to evaluate the effects of an investigational infant formula. The formula is supplemented with two key human milk oligosaccharides (HMOs), and further optimized with a nutrient profile, comparing its effects against a standard infant formula. A breastfed reference cohort is included for contextual comparison. The primary objective is to compare the test and control formulas' impact on infant gut health, specifically assessed through gut microbiota composition (via 16S rRNA sequencing) and short-chain fatty acid profiles in stool samples. Secondary objectives involve comparing groups across a range of outcomes: growth parameters (weight, length, head circumference); immune function (serum hsCRP, lymphocyte subsets; fecal sIgA); bone development markers (osteocalcin, alkaline phosphatase); cognitive development (Bayley Scales of Infant and Toddler Development, 4th Edition); metabolic markers (serum amino acids, albumin); and measures of gastrointestinal tolerance, sleep patterns, fussiness, and the incidence of diarrhea and upper respiratory infections. The study will enroll 240 healthy, term infants aged 0-28 days, with key eligibility criteria including singleton birth, gestational age of 37-42 weeks, and birth weight of 2500-4000g. Of these, 160 infants will be centrally randomized (1:1, stratified by site and infant sex) to receive either the test or control formula under double-blind conditions, while the remaining infants will form a non-randomized, open-label breastfed group. The intervention period spans 360 days, with protocol-defined minimum daily feeding requirements for each group. Outcomes will be assessed during scheduled visits at Day 28, Day 90±3, Day 180±5, and Day 360±7, encompassing anthropometry, neurodevelopmental testing (final visit), biosample (stool/blood) collection, and questionnaires.

• Study Type: Interventional
• Enrollment (Actual): 240
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100010
      • Seventh Medical Center, Chinese PLA General Hospital
  • Jiangsu
    • Changzhou, Jiangsu, China, 213000
      • Changzhou Second People's Hospital
    • Nanjin, Jiangsu, China, 211100
      • Nanjing Medical University
    • Nanjing, Jiangsu, China, 210003
      • The Second Affiliated Hospital of Nanjing Medical University
  • Shandong
    • Linyi, Shandong, China, 276016
      • Linyi City Maternal and Child Health Care Hospital
  • Tianjin Municipality
    • Tianjin, Tianjin Municipality, China, 300381
      • The First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria： Breastfed Group

Infants eligible for the breastfed reference group must meet all of the following criteria:

• Aged 0 to 28 days after birth (inclusive).
• Singleton birth.
• Gestational age between 37 and 42 weeks (inclusive).
• Birth weight between 2500 and 4000 grams (inclusive).
• Parent(s) or legal guardian(s) agree that the infant will not participate in any other interventional clinical studies for the duration of this trial.
• Parent(s) or legal guardian(s) agree to feed the infant according to the trial protocol (i.e., breastfeeding).

Formula-fed Group

Infants eligible for the randomized formula-fed groups must meet all of the following criteria:

• Aged 0 to 28 days after birth (inclusive).
• Singleton birth.
• Gestational age between 37 and 42 weeks (inclusive).
• Birth weight between 2500 and 4000 grams (inclusive).
• Parent(s) or legal guardian(s) agree that the infant will not participate in any other interventional clinical studies for the duration of this trial.
• Parent(s) or legal guardian(s) agree to feed the infant according to the trial protocol.
• For objective or subjective reasons, the mother is unable to provide exclusive breastfeeding.

Exclusion Criteria：

Infants will be excluded from the trial if they meet any of the following criteria:

• Conceived through assisted reproductive technology.
• Maternal history of any condition during pregnancy known to compromise intrauterine growth.
• Maternal history of gestational diabetes, significant metabolic disease, or chronic disease during pregnancy.
• Presence of congenital malformations, genetic disorders, chronic diseases, or congenital conditions that could interfere with the study participation or outcome assessments.
• Known IgE-mediated cow's milk protein allergy, or presence of factors that increase the risk of cow's milk protein allergy.
• Active acute infection or gastroenteritis at the time of enrollment.
• History of functional gastrointestinal disorders, such as gastroparesis.
• Concurrent participation in another clinical trial.
• Any condition that, in the investigator's judgment, could compromise the parent's willingness or ability to comply with the protocol requirements.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: control group; Feeding with regular infant formula milk powder	Dietary supplement: Commercially Available Standard Formula; A commercially available standard infant formula, administered as the control. It does not contain the human milk oligosaccharides (HMOs) or other specific nutrient optimizations present in the investigational formula.
Active Comparator: Breastfeeding group; Breastfeeding with breast milk	Dietary supplement: Breast Milk Feeding; Participants are breastfed by their mothers, receiving human breast milk as the sole or primary source of nutrition. It serves as a natural benchmark for comparing growth, development, and health outcomes against infants fed the investigational or standard formulas.
Experimental: experimental group; Intervention with a novel infant formula containing added human milk oligosaccharides and a multi-nutrient optimized profile	Dietary supplement: Human Milk Oligosaccharide-Supplemented, Multi-Nutrient Optimized Infant Formula; This is an investigational infant formula designed to be closer to the nutritional and functional composition of breast milk. It is distinguished by the addition of a specific, proprietary blend of human milk oligosaccharides (HMOs) and a comprehensively optimized nutrient profile. The optimization encompasses multiple key nutrient categories (including proteins, lipids, prebiotics/probiotics, and micronutrients) aimed at supporting infant gut health, immune development, and overall growth.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intestinal indicators	16s rRNA	day 28,180
Intestinal indicators	SCFAs	day 28,180

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory markers	serum hsCRP	day 180,360
Nutritional indicators	serum albumin	day 180,360
Immune indicators	blood lymphocyte subsets	day 180,360
Growth and development indicators	height	day 28,90,180,360
Growth and development indicators	weight	day 28,90,180,360
Growth and development indicators	head circumference	day 28,90,180,360
Growth and development indicators	chest circumference	day 28,90,180,360
Bone development indicators	osteocalcin	day 180,360
Bone development indicators	alkaline phosphatase	day 180,360
Tolerance indicators	investigation of infant gastrointestinal comfort：In the past week, the average daily number of reflux .The minimum number is 0, and there is no limit to the maximum number.	day 28,90,180,360
Tolerance indicators	investigation of infant sleep crying：In the past week, the average daily crying time.The minimum time is 0 hours and the maximum time is 24 hours.	day 28,90,180,360
Tolerance indicators	investigation of infant sleep crying：In the past week, the average daily crying frequency.The minimum number of times is 0, and the maximum number of times is unlimited.	day 28,90,180,360
Tolerance indicators	investigation of infant sleep crying：In the past week, the average daily crying severity. The severity of crying is divided into no crying, mild crying, moderate crying, very crying, and extreme crying.	day 28,90,180,360
Tolerance indicators	investigation of infant sleep crying：In the past week, the average daily crying daytime and nighttime sleep duration. The minimum time is 0 hours and the maximum time is 12 hours.	day 28,90,180,360
Tolerance indicators	investigation of infant sleep crying：In the past week, sleep problems of infants.Sleep problems are divided into no problem, minor problem, moderate problem, major problem, and extreme problem.	day 28,90,180,360
Tolerance indicators	investigation of infant diarrhea and upper respiratory tract infections：The severity of diarrhea and upper respiratory tract infections (colds) in infants from birth until now. The severity level is classified as no problem, minor problem, moderate problem, major problem, and maximum problem.	day 28,90,180,360
Cognitive Development	Serum Amino Acids	day 180,360
Immune indicators	fecal sIgA	day 28,180
Tolerance indicators	Infant Gastrointestinal Comfort Score：A score assessing the comfort level related to gastrointestinal symptoms over the past week.The minimum score is 0, and the maximum score is 10.	day 28,90,180,360
Tolerance indicators	Bristol stool classification of infant feces	day 28,180
Cognitive Development	Bailey Infant Development Scale (Version IV) Score（130 or above, very excellent; 120-129, excellent; 110~119, upper middle; 90-109, moderate; 80-89, below average; 70-79, critical state; Below 69, developmental delay）	day 360

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
adverse event	adverse event	From enrollment until the end of the study (Day 360), up to 12 months
Serious adverse events	Serious adverse events	From enrollment until the end of the study (Day 360), up to 12 months

Collaborators and Investigators

• Sponsor: Heilongjiang Feihe Dairy Co. Ltd.
• Investigators: Study Chair: Zhixu Wang, Nanjing Medical University

Study record dates

Study Major Dates

• Study Start (Actual): January 11, 2024
• Primary Completion (Actual): December 16, 2025
• Study Completion (Actual): December 16, 2025

Study Registration Dates

• First Submitted: August 7, 2024
• First Submitted That Met QC Criteria: August 21, 2024
• First Posted (Actual): August 26, 2024

Study Record Updates

• Last Update Posted (Actual): July 21, 2026
• Last Update Submitted That Met QC Criteria: July 17, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: infants; Milk oligosaccharides; multiple nutrients
• Other Study ID Numbers: CTS-MP-2023-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No