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NCT Number: NCT04633044

Maternal Betaine Supplementation During Breastfeeding

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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This study is active but is not currently recruiting participants.

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Key information

Age range

20 year–42 year

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hospital Sant Joan de Deu

Barcelona, 08950, Spain

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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 weight > -1 standard deviations
  • Absence of infant disease or malformations at birth

Exclusion criteria

  • Multiple pregnancy
  • Lactose intolerance
  • CBS deficiency (inherited disease)

Treatment and study plan

Betaine

Dietary Supplement

The intervention with supplement will start during the first 48h after birth and will last for 12 weeks

Placebo

Dietary Supplement

The intervention with supplement will start during the first 48h after birth and will last for 12 weeks

Primary outcomes

  1. Change from birth weight-for-length z score at 1 month

    Time frame: Birth and 1 month

    Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.

  2. Change from birth weight-for-length z score at 3 months

    Time frame: Birth and 3 months

    Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.

Secondary outcomes

  1. Change from birth weight-for-length z score at 6 months

    Time frame: Birth and 6 months

    Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.

  2. Change from birth weight-for-length z score at 12 months

    Time frame: Birth and 12 months

    Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.

  3. Change from birth weight-for-length z score at 48 months

    Time frame: Birth and 48 months

    Weight and length will be measured at different time-points and combined to calculate weight-for-length z scores.

  4. Infant Body composition

    Time frame: 3, 12 and 48 months

    Total body and abdominal fat mass measured by DXA scan

  5. Breast milk concentration of betaine and related metabolites

    Time frame: 1 and 3 months

    We will quantify betaine and related metabolites in maternal breast milk samples

  6. Maternal circulating concentration of betaine and related metabolites

    Time frame: 1 and 3 months

    We will quantify betaine and related metabolites in maternal plasma samples

  7. Infant urine concentration of betaine and related metabolites

    Time frame: 1, 3, and 6, and 12 months

    We will quantify betaine and related metabolites in infant urine samples

  8. Infant gut microbiome composition

    Time frame: 1, 3, 6, 12 and 48 months

    DNA from infant fecal samples will be sequenced to quantify abundance of the different bacterial groups.

  9. Maternal gut microbiome composition

    Time frame: 1 and 3 months

    DNA from maternal fecal samples will be sequenced to quantify abundance of the different bacterial groups.

Other outcomes

  1. Breast milk microbiota composition

    Time frame: 1 and 3 months

    DNA from breast milk samples will be sequenced to quantify abundance of the different bacterial groups.

  2. Breast milk metabolome

    Time frame: 1 and 3 months

    Liquid chromatography coupled to mass spectrometry will be used to obtain a comprehensive metabolic profile of breast milk samples

  3. Child development (ASQ-3 questionnaire)

    Time frame: 1, 3, 6, and 12 months

    Developmental progress will be evaluated with the parental reported ASQ-3 questionnaires

  4. Child development: Vineland Adaptive Behavior Scales-Third Edition (Vineland-3)- Parent/Caregiver

    Time frame: 48 months

    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.

  5. Child development: Behavior Rating Inventory of Executive Function, Preschool Version (BRIEF-P)

    Time frame: 48 months

    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.

  6. Child development: The Wechsler Preschool and Primary Scale of Intelligence - Fourth Edition (WPPSI-IV)

    Time frame: 48 months

    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.

  7. Child development: Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery VMI)

    Time frame: 48 months

    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.

Sponsors and collaborators

Lead sponsor

Fundació Sant Joan de Déu

Other

Registry information

Acronym: BetMilk

Important dates

Study start
2021
Primary completion
2023
Study completion
2026
First posted
Nov 18, 2020
Registry last updated
Mar 24, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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