The Influence by Dietary Human Milk Oligosaccharide in Low Birth Weight Infants

Study Overview
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Brief Summary
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This study aims to investigate the concentration of various growth factors and cytokines in blood, and to examine the gut microbiota of low birth weight infants fed with formulas with or without Human Milk Oligosaccharide (HMO) supplement. Eligible low birth weight infants are allocated to two groups, Investigational formula (with HMO) or Control formula (without HMO). The subjects are taking the assigned formula when they need to be supplemented with formula. After the informed consent was obtained and eligibility was confirmed, the intervention period begins, and ends at the one-month-old medical check-up with the assessment of the various blood growth factors and cytokines, and the gut microbiota.

Official Title
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An Investigation of the Influence by Dietary Human Milk Oligosaccharide on Growth Factors and Cytokines in Blood, and Gut Microbiota in Low Birth Weight Infants (a Non-blinded Pilot Clinical Study)

Conditions
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Low Birth Weight Infants

Intervention / Treatment
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* Dietary Supplement: Infant formula with Human Milk Oligosaccharide
* Dietary Supplement: Infant formula without Human Milk Oligosaccharide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 1-1) For infants i. Low birth weight infants (defined as a birth weight ≥1,500 g and <2,500 g) during hospitalization and may require milk powder formula as supplement. 1-2) For mothers i. Mothers who do not find serious viral infection ii. Mothers who are willing to provide consent for provision of study required information and specimen(s) from both mothers and infants iii. Mothers who are willing to provide consent as infant's legally acceptable representative (LAR) Exclusion Criteria: 2-1) For infants i. Infants who receive any formulas before Informed Consent. ii. Infants with serious infections. iii. Infants with necrotizing enteritis. iv. Infants with gastrointestinal perforation. v. Infants whom the PI determines inappropriate as a study subject (e.g. inflammatory, metabolic abnormalities and difficulty in enteral feeding). 2-2) For mothers i. Mothers the PI determines inappropriate as a study subject ii. Mothers under 18 years old. Withdrawal criteria: A subject must be discontinued from treatment with test formula if any of the following apply: i. If the mother, who is a subject of the study as well as infant's LAR , asks for withdrawal from the study or withdraws consent. ii. When a serious adverse event occurs. iii. When an adverse event occurs, and the PI or co-investigator determines that the study should be discontinued. iv. If it is decided that there is a risk of compromising the safety of the study subject. v. If a subject is found to be ineligible after the start of the study. vi. If it is found that there is a serious or continued non-compliance with the study protocol by a study subject. vii. In addition, if the PI decides to end the study.

Ages Eligible for Study
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Maximum Age: 1 Month

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The number of anticipated participants is 60 mother-infant pairs. The 30 first enrolled mother-infant pairs are assigned to the investigational formula group, and the next 30 enrolled mother-infant pairs are assigned to the control formula group.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Investigational formula<br>Infant formula with Human Milk Oligosaccharide | Dietary Supplement: Infant formula with Human Milk Oligosaccharide<br>* Although breastfeeding is encouraged, the shortage is supplemented with the investigational formula. After obtaining the informed consent, the investigational formula is administered to infants under the doctor's direction until a medical check-up at one-month-old.<br>|
| Placebo Comparator: Control formula<br>Infant formula without Human Milk Oligosaccharide | Dietary Supplement: Infant formula without Human Milk Oligosaccharide<br>* Although breastfeeding is encouraged, the shortage is supplemented with the control formula. After obtaining the informed consent, the control formula is administered to infants under the doctor's direction until a medical check-up at one-month-old.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Growth factors concentration in infant's plasma | The concentration of NGF-beta (pg/mL), BDNF (pg/mL), etc. in infant's plasma will be measured by immunoassay. | At one-month-old | 
| Cytokines concentration in infant's plasma | The concentration of IFN-gamma (pg/mL), IL-1alpha (pg/mL), etc. in infant's plasma will be measured by immunoassay. | At one-month-old | 
| Infant's gut microbiota occupancy | Total bacterial counts and bifidobacterial counts in stool will be measured by RT-PCR (copy/g wet feces). Occupancy of microbiota in infant's stool will be comprehensively analyzed by DNA/RNA Sequencing (percent). | At one-month-old |