Modulating Early-life Nutrition for Childhood Obesity Prevention

Study Overview
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Brief Summary
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In this study, betaine intake will be increased in formula-fed infants through formula milk supplementation. To do this, a double-blind randomized study has been designed with the supplementation group (infant formula supplemented with betaine) and control group (unsupplemented infant formula). The main objectives of the study are to determine the safety of supplementation and to assess whether there are changes in infant growth.

Detailed Description
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Childhood obesity is one of the main public health concerns worldwide. Previous results have linked a nutrient called betaine (trimethylglycine) to the risk of childhood obesity. Betaine is a modified amino acid with osmotic properties that participates in the methionine cycle as a methyl group donor. Specifically, previous data demonstrate a link between breast milk betaine content, postnatal growth, and long-term metabolic health, suggesting that betaine supplementation may be an effective strategy for regulating growth trajectories and preventing childhood obesity. This study will assess the effects of increasing betaine intake in formula-fed infants through formula milk supplementation. To do this, a double-blind randomized study has been designed where participants will be randomly assigned to the control group or the supplementation group. The main objectives of the study are to determine the safety of supplementation and to assess whether there are changes in infant growth. Additionally, potential changes in the intestinal microbiome induced by the increase in betaine intake will be analyzed.

Official Title
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Modulating Early-life Nutrition for Childhood Obesity Prevention

Conditions
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Infant Growth, Childhood Overweight

Intervention / Treatment
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* Dietary Supplement: Betaine supplementation in infant formula
* Dietary Supplement: Regular infant formula


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal age between 17 and 42 years Maternal pre-pregnancy BMI equal or higher than 25 Gestational age at birth > 37 weeks No exclusive breastfeeding at time of recruitment Exclusion Criteria: Presence of disease or malformations in the infant Infant birth weight < -1 SD (standard deviations) Multiple pregnancy Elective c-section

Ages Eligible for Study
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Minimum Age: 0 Weeks
Maximum Age: 4 Weeks

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Control group<br>Use of unmodified infant formula for 12 weeks | Dietary Supplement: Regular infant formula<br>* Regular (unmodified) infant formula . The intervention will last for 12 weeks.<br>|
| Experimental: Betaine supplementation group<br>Use of infant formula supplemented with betaine (final concentration of 100 µmol/L) for 12 weeks | Dietary Supplement: Betaine supplementation in infant formula<br>* Infant formula will be supplemented with betaine to provide a final concentration of 100 µmol/L in the reconstituted milk. The intervention will last for 12 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in weight-for-length z score | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | From start to the end of treatment at 12 weeks and at 12 months of follow-up | 
| Changes in fecal microbiota composition | Differences in features associated with a healthy mucosal layer and metabolic state (e.g. Bifidobacteria and Akkermansia relative amount). Stool samples will be processed to isolate the bacterial DNA. Microbiome composition will be determined by DNA sequencing. | At 4 weeks and 12 weeks end of treatment, and at 12 months of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infant body composition | Total body and abdominal fat mass measured by dual energy x-ray absorptiometry (DXA) scan | At 12 months of follow-up | 
| Urine one-carbon metabolite concentration | Urine samples will be analyzed to quantify betaine content as well as related metabolites (including dimethylglycine, the product of the betaine demethylation reaction | At 4 weeks and 12 weeks after start of treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infant formula, childhood obesity risk, infant growth, one-carbon metabolism, Betaine