NCT04447742

Brief Summary

Background: Intestinal microbiota composition is fundamental to human health and undergoes critical changes within the first two years of life. Factors probably influencing the microbiota are the maternal microbiota and the general environment in Switzerland. However, the development of the intestinal microbiota is incompletely understood. Gaining knowledge of the trajectory of microbiota maturation is likely key to the understanding of the pathogenesis of many pathologies in childhood. Aims: The investigators aim for a deep understanding of the maturation of the healthy infant intestinal microbiota regarding composition, diversity and metabolic activities. The investigators aim for identifying parameters affecting microbiota maturation and effects of the microbiota on infant outcome. Methods: The investigators will recruit 250 pregnant mothers who will be followed as mother-baby pairs until 10 years of age. Infants will be followed clinically to determine adequate growth and development as well as pathology including abdominal pain. Epidemiological parameter and infant nutrition will be assessed. The investigators will collect biological samples such as stool, maternal milk, vaginal swaps and skin swaps. Species composition and diversity will be assessed by 16S sequencing. Metagenomic shotgun sequencing and bacterial messenger ribonucleic acid (mRNA) analysis will inform about metabolic potential and metabolic activity of the microbiota. Mass spectrometry will assess the small molecule content of stool and maternal milk samples. Network analysis will be used to assess the complex relationships between bacteria metabolic activities and small molecular content. Expected results: The investigators expect an increase in complexity and metabolic potential and activity with age. Microbiota parameters will differ according to nutrition and might predict infant outcomes such as growth and abdominal pain. Systematic analysis of sequential maternal and infant bacteria samples from stool, skin and maternal milk will help characterizing bacterial transfer from mother to infant Conclusion: The investigators propose an observational study of healthy Bern mother baby pairs with clinical characterisation and biological sampling. Advanced analysis tools will be used to characterise the microbiota and address mechanistic questions.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
250

participants targeted

Target at P75+ for all trials

Timeline
107mo left

Started May 2020

Longer than P75 for all trials

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress40%
May 2020Mar 2035

Study Start

First participant enrolled

May 7, 2020

Completed
12 days until next milestone

First Submitted

Initial submission to the registry

May 19, 2020

Completed
1 month until next milestone

First Posted

Study publicly available on registry

June 25, 2020

Completed
7.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

March 3, 2028

Expected
7 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 3, 2035

Last Updated

November 12, 2024

Status Verified

November 1, 2024

Enrollment Period

7.8 years

First QC Date

May 19, 2020

Last Update Submit

November 11, 2024

Conditions

Maturation of the Healthy Infant Intestinal MicrobiotaMicrobial ColonizationNutrition Disorder, InfantMilk Expression, BreastMental Health Disorder

Outcome Measures

Primary Outcomes (11)

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 0-3 days after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 10 days after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 6 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 10 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 14 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 24 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 36 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 48 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 96 weeks after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 5 years after birth

  • Maturation of a healthy infant intestinal microbiota regarding complexity of species composition and metabolic activities.

    The investigators are aiming for a deep understanding of the maturation of a healthy infant intestinal microbiota considering composition, diversity and metabolic activities. The investigators will characterise the composition, metabolic potential and activity at various time points by advanced techniques (16S sequencing, metagenomics shotgun sequencing and mRNA sequencing) and the metabolites present by mass spectrometry (see "detailed description") . Using this information, the investigators will estimate networks of metabolic activity of the microbiota. Network analysis can be informed by information regarding small molecules present. The trajectories shared by the microbiota of most healthy infants will be considered normal.

    Infant stool samples will be collected 10 years after birth

Secondary Outcomes (5)

  • Impact of variations of the normal environment in Switzerland on microbiota development.

    Enrolment, 0-3 days, 10 days, 6 weeks, 10 weeks, 14 weeks, 24 weeks, 36 weeks, 48 weeks, 96 weeks, 5 years and 10 years after birth.

  • Transfer of the maternal microbiota to the infant

    Enrolment, 0-3 days, 10 days, 6 weeks, 10 weeks, 14 weeks, 24 weeks, 36 weeks, 48 weeks, 96 weeks, 5 years and 10 years after birth.

  • Impact of the microbiota on child development and health.

    Enrolment, 0-3 days, 10 days, 6 weeks, 10 weeks, 14 weeks, 24 weeks, 36 weeks, 48 weeks, 96 weeks, 5 years and 10 years after birth.

  • Impact of low resources with poor nutrition and poor hygiene in developing countries on the maturation of the intestinal microbiota

    0-3 days, 10 days, 6 weeks, 10 weeks, 14 weeks, 24 weeks, 36 weeks, 48 weeks, 96 weeks, 5 years and 10 years after birth.

  • Effects of maternal microbiota on immunomodulatory properties of breast milk and immune maturation in the newborn

    Enrolment, 0-3 days, 10 days, 6 weeks, 10 weeks, 14 weeks, 24 weeks, 36 weeks, 48 weeks, 96 weeks, 5 years and 10 years after birth.

Eligibility Criteria

Age18 Years - 45 Years
Sexfemale(Gender-based eligibility)
Healthy VolunteersYes
Age GroupsAdult (18-64)
Sampling MethodNon-Probability Sample
Study Population

At recruitment: Healthy pregnant women in the area of Bern. On Follow-up: baby-mother pairs in the area of Bern

You may qualify if:

  • Signed informed consent.
  • Ability to understand and follow study procedures and understand informed consent
  • From week 20 of pregnancy until birth
  • General good health, i.e. absence of major severe medical/ surgical/ psychiatric condition requiring ongoing management. Minor well controlled conditions (e.g. medically controlled arterial hypertension, occupational asthma, gestational diabetes mellitus) may be present.
  • Absence of known severe embryonal pathology, expected normal pregnancy (e.g. minor conditions including twin/ triplet pregnancy, final pelvic position may be present)
  • Age 18-45 years.

You may not qualify if:

  • Participation in another clinical study interfering with study procedures.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University Hospital of Bern - Insel Spital

Bern, 3010, Switzerland

RECRUITING

Related Publications (1)

  • Cecchini L, Barmaz C, Cea MJC, Baeschlin H, Etter J, Netzer S, Bregy L, Marchukov D, Trigo NF, Meier R, Hirschi J, Wyss J, Wick A, Zingg J, Christensen S, Radan AP, Etter A, Muller M, Kaess M, Surbek D, Yilmaz B, Macpherson AJ, Sokollik C, Misselwitz B, Ganal-Vonarburg SC. The Bern Birth Cohort (BeBiCo) to study the development of the infant intestinal microbiota in a high-resource setting in Switzerland: rationale, design, and methods. BMC Pediatr. 2023 Nov 10;23(1):560. doi: 10.1186/s12887-023-04198-5.

    PMID: 37946167DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

* Maternal stool samples * Maternal milk samples * Maternal skin swabs * Maternal vaginal swabs (optional) * Infant stool samples infant skin swabs

MeSH Terms

Conditions

Communicable DiseasesInfant Nutrition DisordersBreast Milk ExpressionMental Disorders

Condition Hierarchy (Ancestors)

InfectionsDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNutrition DisordersNutritional and Metabolic DiseasesBreast FeedingFeeding BehaviorBehavior

Study Officials

  • Benjamin Misselwitz, Professor

    University Hospital of Bern - Insel Spital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Benjamin Misselwitz, Professor

CONTACT

+41 31 664 04 30benjamin.misselwitz@insel.ch

Stephanie Ganal-Vonarburg, Professor

CONTACT

‭+41 31 632 49 73stephanie.ganal@dbmr.unibe.ch

Study Design

Study Type
observational
Observational Model
COHORT
Time Perspective
PROSPECTIVE
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 19, 2020

First Posted

June 25, 2020

Study Start

May 7, 2020

Primary Completion (Estimated)

March 3, 2028

Study Completion (Estimated)

March 3, 2035

Last Updated

November 12, 2024

Record last verified: 2024-11

Locations

CH(1)