Effects of Breast Milk Simulated Infant Formula

Study Overview
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Brief Summary
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Objective：The aim of this trial is to assess effects of Kieember and Yashili infant formula on body growth, behavior development, intestinal comfort, infectious diseases, allergic diseases, the absorption of nutrients and gut microbiota as compared to breast-milk in term infants aged 0-3 months. Participants：195 healthy term infants at the age of 0-14 days at entry to study. Study Design: A open-label, quasi-randomized, controlled trial. Random allocation is performed between the two infant formula groups. Arms, Groups, and Intervention: (1) Breast milk-fed group: fed with human breast milk; (2) Breast Milk Simulated Formula Group：fed with breast milk simulated infant formula (Ruibuen®Kieember, Phase I); (3) Traditional Formula Group: fed with traditional infant formula (Ruibuen®Yashili, Phase I). Random allocation is performed between the two formula groups. Intervention Duration: 12 weeks. Visits: 2 (baseline), 6 and 12 weeks old. Outcome measures: (1)Biochemical detection of feces (total fat, fatty acids, calcium, nitrogen);(2)Stool characteristics (frequency, color, volume, and stool consistency);(3)Anthropometric parameters (body length, body weight, and head circumferences);(4)Temperament and adaptive behavior;(5)Gut microbiota;(6)General health and wellbeing;(7)concomitant medications and adverse events.

Official Title
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Effects of Breast Milk Simulated Infant Formula: A 3-month Randomized Controlled Trial

Conditions
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Infant Formula, Breast Milk

Intervention / Treatment
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* Other: Breast milk
* Other: Kieember Infant formula, Ruibuen®
* Other: Yashili Infant formula, Ruibuen®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Term infant: Born at 37-42 gestation weeks Birth weight: 2500-4000g (appropriate for gestational age) The infant is in good health and Apgar after 5 minutes >7 The mother had unequivocally decided not to breastfeed (for formula fed infants) or to breastfeed (for human milk fed infants) age at the enrollment: less than 14 days Exclusion Criteria: The mother is unable to take care of her infant on account of health condition (psychological or physical) or socioeconomic problems The infant is born with a congenital malformation or chromosome abnormality with a clinical significance The infant suffers from a disease requiring mechanical ventilation or medication in the first week of life (not including applying phototherapy of blue to cure neonatal jaundice) The infant whose feeding or normal metabolism is affected by any suspected or unknown metabolic factors or physical limitations The infant has been breastfed for more than 2 weeks (for formula fed infants) Twins or multiple births

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Breast Milk-Fed Group<br>The infants will be breastfed during the study. | Other: Breast milk<br>* Breast milk: Human breast milk, provided and fed by the corresponding infant's mother<br>|
| Experimental: Breast Milk Simulated Formula Group<br>Kieember Infant formula, Ruibuen®: Infants will be fed Kieember infant formula(Phase I) from baseline (about 0-14 days) to 12 weeks old. | Other: Kieember Infant formula, Ruibuen®<br>* Kieember Infant formula, Ruibuen®: a type of Phase I infant formula for 0-6 month infants, with a trademark of Ruibuen®. The formula is characterized by (1) OPO structured lipid of the third generation; and (2) Breast Milk Simulated complete structured lipid UPU. It was produced by Yashili New Zealand Dairy Co., Limited<br>|
| Experimental: Traditional Formula Group<br>Yashili Infant formula, Ruibuen®: Infants will be fed Yashili infant formula (Phase I) from baseline (about 0-14 days) to 12 weeks old. | Other: Yashili Infant formula, Ruibuen®<br>* Yashili Infant formula, Ruibuen®: a type of Phase I infant formula for 0-6 month infants, with a trademark of Ruibuen®. The formula is characterized by(1) lactoferrin and(2) lutein . It was produced by Yashili International Holdings Ltd.,China<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change Rate of Gut Microbiota Pattern Score from Baseline at 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in gut microbiota pattern score from 16S RNA sequencing. | 0, 6, 12 weeks | 
| Average Change Rate of Fecal Residual Fatty Acid from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in Fecal Residual Fatty Acid. | 0, 6, 12 weeks | 
| Average Change Rate of Fecal Residual Nitrogen from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in Fecal Residual Nitrogen. | 0, 6, 12 weeks | 
| Average Change Rate of Fecal Residual Calcium from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in fecal residual calcium. | 0, 6, 12 weeks | 
| Average Change Rate of body length from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in body length. | 0, 6, 12 weeks | 
| Average Change Rate of body weight from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in body weigh. | 0, 6, 12 weeks | 
| Average Change Rate of head circumferences from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in head circumferences. | 0, 6, 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Average Change Rate of Stool Characteristic Index from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in Stool Characteristic Index: calculated by using stool color (using sample pictures), stool shape (using sample pictures), and frequency. | 0, 6, 12 weeks | 
| Average Change Rate of an Index of General health and wellbeing from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in Index of General health and wellbeing, calculated from diseases (cold, diarrhea,infectious diseases), doctor visits, concomitant medications,etc. | 0, 6, 12 weeks | 
| Average Change Rate of Temperament Score from Baseline to 6 and 12 weeks | Slope of change at 0, 6 and 12 weeks in Temperament Score assessed by the Early Infant Temperament Scale | 0, 6, 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiota, temperament, body growth, fecal residual nutrient