Maternal Betaine Supplementation During Breastfeeding

Study Overview
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Brief Summary
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Developing more efficient and cost-effective prevention strategies to slow down the worldwide epidemic of obesity and chronic metabolic disease has become a public health imperative. Our previous results in humans demonstrate that lower breast milk betaine levels were associated with faster infant postnatal growth, a strong and potentially modifiable risk factor of future obesity. Betaine is a trimethylated derivative of glycine, which is present in multiple foods and occurs naturally in breast milk. In this study, we will perform a double-blind randomized placebo-controlled pilot clinical study, in which maternal diet will be supplemented with betaine for 3 months during breastfeeding; infant's growth and adiposity will be monitored until 12 months of age, and breast milk composition and gut microbiota analyzed.

Official Title
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Maternal Betaine Supplementation During Breastfeeding

Conditions
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Overweight and Obesity

Intervention / Treatment
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* Dietary Supplement: Betaine
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Maternal Pre-pregnancy BMI between 25 and 40. Willing to exclusively breastfeed for ≥ 3 months Infant gestational age at birth > 37 weeks Infant birth weigth > -1 standard deviations Absence of infant disease or malformations at birth Exclusion Criteria: Multiple pregnancy Lactose intolerance CBS deficiency (inherited disease)

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized placebo-controlled study with maternal dietary supplementation (betaine or placebo) for 3 months starting at infant birth and follow-up until 12 months of age.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>400 mg of lactose daily for 12 weeks | Dietary Supplement: Placebo<br>* The intervention with supplement will start during the first 48h after birth and will last for 12 weeks<br>|
| Experimental: Supplement<br>400 mg of betaine daily for 12 weeks | Dietary Supplement: Betaine<br>* The intervention with supplement will start during the first 48h after birth and 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 from birth weight-for-length z score at 1 month | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | Birth and 1 month | 
| Change from birth weight-for-length z score at 3 months | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | Birth and 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from birth weight-for-length z score at 6 months | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | Birth and 6 months | 
| Change from birth weight-for-length z score at 12 months | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | Birth and 12 months | 
| Infant Body composition | Total body and abdominal fat mass measured by DXA scan | 3 and 12 months | 
| Breast milk concentration of betaine and related metabolites | We will quantify betaine and related metabolites in maternal breast milk samples | 1 and 3 months | 
| Maternal circulating concentration of betaine and related metabolites | We will quantify betaine and related metabolites in maternal plasma samples | 1 and 3 months | 
| Infant urine concentration of betaine and related metabolites | We will quantify betaine and related metabolites in infant urine samples | 1, 3, and 6, and 12 months | 
| Infant gut microbiome composition | DNA from infant fecal samples will be sequenced to quantify abundance of the different bacterial groups. | 1, 3, 6, and 12 months | 
| Maternal gut microbiome composition | DNA from maternal fecal samples will be sequenced to quantify abundance of the different bacterial groups. | 1 and 3 months |