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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. An additional follow-up visit will be conducted at 48 months of age to repeat microbiome analysis, determine adiposity, and perform cognitive development assessment.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | 400 mg of lactose daily for 12 weeks |
|
| Supplement | Experimental | 400 mg of betaine daily for 12 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Betaine | Dietary Supplement | The intervention with supplement will start during the first 48h after birth and will last for 12 weeks |
|
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Breast milk microbiota composition | DNA from breast milk samples will be sequenced to quantify abundance of the different bacterial groups. | 1 and 3 months |
| Breast milk metabolome | Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of breast milk samples |
Inclusion Criteria:
Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital Sant Joan de Deu | Barcelona | Barcelona | 08950 | Spain |
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| ID | Term |
|---|---|
| D050177 | Overweight |
| D009765 | Obesity |
| ID | Term |
|---|---|
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
| D001835 | Body Weight |
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| ID | Term |
|---|---|
| D001622 | Betaine |
| ID | Term |
|---|---|
| D050337 | Trimethyl Ammonium Compounds |
| D000644 | Quaternary Ammonium Compounds |
| D000588 | Amines |
| D009930 | Organic Chemicals |
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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. An additional follow-up will be performed at 48 months of age.
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| Placebo | Dietary Supplement | The intervention with supplement will start during the first 48h after birth and will last for 12 weeks |
|
Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.
| Birth and 12 months |
| Change from birth weight-for-length z score at 48 months | Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores. | Birth and 48 months |
| Infant Body composition | Total body and abdominal fat mass measured by DXA scan | 3, 12 and 48 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, 12 and 48 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 |
| 1 and 3 months |
| Child development (ASQ-3 questionnaire) | Developmental progress will be evaluated with the parental reported ASQ-3 questionnaires | 1, 3, 6, and 12 months |
| Child development: Vineland Adaptive Behavior Scales-Third Edition (Vineland-3)- Parent/Caregiver | Respondents: Parents/caregivers This evaluation is used to assist in the diagnosis of intellectual and developmental disabilities and measure the adaptive behaviors of individuals. 9 subdomains 3 domains and a overall ABCa. Motor Skills (77). Maladaptive Behavior (44) items. Total 502 items. The main domains are: Communication, Daily Living Skills, Socialization, Motor Skills, and Maladaptive Behavior (optional). The domain scores yield an adaptive behavior composite. A scaled score typically tells us how well a child did on a specific sub-test, and a standard score typically tells us how well a child did on a broad domain (which is often made of sub-tests). Scaled Scores have a score range of 0 - 19 points, with an average score of 10 points. | 48 months |
| Child development: Behavior Rating Inventory of Executive Function, Preschool Version (BRIEF-P) | Respondents: Parents/teachers. Information about a child's behaviour that is directly relevant to an understanding of that child's executive functioning. 63 items that measure various aspects of executive functioning: Inhibit, Shift, Emotional Control, Working Memory, and Plan/Organize. A Likert-type scale with "never," "sometimes," and "often" options for rating behavior. The raw scores for the clinical scales and composite indexes are converted into standardized T-scores. Higher scores on BRIEF-P clinical scales and composite indexes indicate greater difficulties with executive functions, while lower scores suggest fewer problems. Interpretation should consider clinical norms and the overall profile to assess the significance of the child's performance. | 48 months |
| Child development: The Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV) | Respondents: childs, in direct interaction with the examiner. Is an individually administered, standardized assessment designed to evaluate the intelligence of young children. The age range of the WPPSI-IV is divided into two age bands, ages 2:6-3:11 and ages 4:0-7:7. WPPSI-IV (ages 2:6-3:11) can be interpreted at three levels: FSIQ (Full Scale Quotient), Primary Indexes (VCI=Verbal Comprehension Index, VSI=Visual Spatial Index, WMI=Working Memory Index), and Ancillary Indexes (VAI=Verbal Acquisition Index, NVI=Nonverbal Index, GAI=General Ability Index). WPPSI-IV scores can be calculated manually or via software. Subtest raw scores convert to scaled scores (M=10, SD=3), which sum into composite scores (M=100, SD=15, e.g., FSIQ). Age-based percentiles are available. Practitioners can analyze discrepancies between composites and identify cognitive strengths and weaknesses. Higher scaled or composite scores indicate better performance on that subtest or domain. | 48 months |
| Child development: Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI) | Respondents: Childs. Age range: 2:0-99:11. Copying geometric figures of increasing complexity to assess visual-motor integration. Helps assess the extent to which individuals can integrate their visual and motor abilities. Poor performance on the Beery VMI is associated with difficulties in spatial organization of written text and maths. Some studies propose a cut-off below the 25th percentile to identify below-average motor performance. This treshold is higher than the 15th and 16th percentile cut-offs used in research to indicate severe difficulties with motor coordination affecting daily life. Raw scores on the Beery VMI can range from 1 to 27, with a higher score reflecting a better performance. Raw scores can be converted into norm scores, which are adjusted for age. | 48 months |
| D012816 |
| Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D009861 |
| Onium Compounds |