Healthy, Healthy Nutrition
Conditions
Keywords
Microbiota, Gastrointestinal Microbiome, Probiotics, Bifidobacterium longum subspecies infantis, Paediatrics, Infant, Child, Immunology, Infections, Inflammation, Growth and Development, Colic, Respiratory Tract Diseases, Metabolism
Brief summary
The goal of The BEGIN Study, a randomized controlled double-blinded intervention trial, is to learn if probiotics, with Bifidobacterium longum subspecies infantis Bifin02 (B. infantis), given to healthy newborns can affect various health outcomes and to explore impacts of the infant gastrointestinal microbiome. The main questions it aims to answer are: * Does B. infantis probiotics impact immune function and does it lower the number of bacterial infections and use of antibiotics? * Does B. infantis probiotics impact overall health, development, growth and wellbeing? * Does B. infantis probiotics impact inflammatory diseases, allergies and autoimmune diseases Researchers will compare B. infantis probiotics to a placebo (a look-alike substance that contains no probiotic) to see if B. infantis colonization impact the human immunesystem and various clinical and biochemical health markers. Participants (parents) will * Orally administrate the B. infantis probiotic to their newborn child daily in three weeks from 7 days of age. * Answer baseline and follow up questionnaires in a study app * Take five stool samples from the child and one stool sample from the mother * Collect a 4 week of passive dust sample at home (Electrostatic Dust fall Collector) * Donate one dried bloodspot and one blood sample from their child
Interventions
DIETARY_SUPPLEMENTB. infantis
1000 newborn children are randomized 50/50 to receive either B. infanits or placebo in a dietary supplement, for daily oral administration in three weeks from 7 days of age.
DIETARY_SUPPLEMENTPlacebo
Identical looking placebo (without any probiotics/B. infantis) for double-blinded daily oral administration in three weeks from 7 days of age.
Sponsors
Aarhus University Hospital
Gødstrup Hospital
Regionshospitalet Horsens
Technical University of Denmark
Statens Serum Institut
University of Copenhagen
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Randomised controlled double-blinded intervention trial
Eligibility
Sex/Gender
ALL
Age
1 Days to 7 Days
Healthy volunteers
Yes
Inclusion criteria
* Infants born at term (above gestational week 37) * Infants born in Region Midtjylland Denmark receiving a Danish CPR number. * Parents age is above 18 * At least one parent holds a smartphone (for study app) and is able to fill out Danish questionaries * Both legal parents are willing and able to provide written informed consent prior to participation, regarding both themselves and their future child.
Exclusion criteria
* Multiple pregnancy * Child diagnosed with immune deficiency, renal, gastrointestinal, hepatic, or endocrine diseases * Parents expecting to give other probiotics
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Prescriptions of antibiotics | First assessment at 1 year and up to 18 years follow-up | Number of prescriptions of antibiotics among participants, as a measure of bacterial infections. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Antibiotic resistance genes (ARGs) | 1 year | Amount of Antibiotic resistance genes (ARGs) in participants microbial community in stool samples. Identification with shutgun metagenomics. Assessing the microbial composition and diversity. |
| Colic | 3 months | Parents' observations registered in study app. Duration of crying in the first three months of life. Defined as Wessels criteria: Crying for three or more hours a day, three or more days a week, for three or more weeks. |
| Bowel function, stool consistency | 3 months | Parents' observations registered in study app, related to their infant child's stool consistency measured at the Infant Stool Scale |
| Bowel function, stool frequency. | 3 months | Parents' observations of their infant child's frequency of stool passings, registered in study app |
| Bowel function, laxatives | 3 months | Parents' reported use of medical laxatives for their infant child, registered in study app and reported as amount of days using the laxative. |
| High sensitive C-reactive protein (hs-CRP) | 1 year | Blood biomarker: Low-grade systemic inflammation. Unit of measurement: mg/l |
| Cluster of Differentiation 163 (CD163) | 1 year | Blood biomarker: Macrophage-mediated inflammation and insulin-sensitivity. Unit of measurement: mg/l |
| The intestinal microbiota and B. infantis colonization | 1 year | Stool samples collected during the first year of life and tested with shutgun metagenomics, assessing the microbial composition.. |
| Allergies, Immunoglobulin E (IgE) | 1 year | Blood marker: Allergies. Specific IgE against the 11 most common inhalation allergens and IgE directed against Egg white, cow's milk, codfish, wheat, peanut and soybean. Unit of measurement: IU/l |
| Allergies | 1 year | Self reported allergy symptoms |
| Growth, weight gain | First assessment at 1 year and up to 18 years follow-up | Measured as weight gain in kilograms |
| Growth | First assessment at 1 year and up to 18 years follow-up | Growth velocity and weight-for-length z-scores, measured in kilograms and centimeters and combined for Z-scores. |
| Growth, IGF-1 (Insulin-like Growth Factor-1) | 1 year | Blood biomarker: Mediating the growth-promoting effects of growth hormone. Unit of measurement: µg/l |
| Body composition | 3 months | Measured by air displacement plethysmography (ADP) (Pea Pod) estimating body fat |
| Plasma Calprotectin | 1 year | Blood biomarker: Intestinal inflammation. Unit of measurement: µg/l |
Other
| Measure | Time frame | Description |
|---|---|---|
| Mother HMO-secretor status | 1 month | The type of Human Milk Oligosaccharides (HMO) section in mothers' breastmilk, will be determined to exploratively study the relationship between types of HMO's, mothers HMO-secretor status and effects of B.infantis. |
| Atopic disease (adjusted SCORAD grading) | First assessment at 1 year | Atopic symptoms, eczema, registered in study-app with description of episodes of atopic dermatitis (adjusted SCORAD grading). Disease intensity is calculated based on six characteristics: erythema, edema, oozing/crusts, excoriations, lichenification, and dryness. Each characteristic is given a score between 0 and 3, where 0 is absent and 3 is severe. The scores for each characteristic are added together for a total intensity score of up to 18. |
| Atopic disease, local steroids | First assessment at 1 year and up to 18 years follow-up | Number of participants with prescriptions of local steroids to treat eczema. |
| Asthma | up to 18 years follow-up | Number of participants with prescriptions of medicine for asthma |
| Hospital admissions | First assessment at 1 year and up to 18 years follow-up | Number of hospital admissions. Registered at Landspatientregistret |
| Febrile episodes | 1 year | Number of days with a fever during the last month. A febrile episode is characterized as a body temperature at 38 degrees Celsius or above. Self-reported in a monthly questionnaire in study app. |
| Asthma Control Test | 1 year, possible later follow-up | Participants reporting symptoms of astma or astmatic bronkitis, will be asked to complete the Asthma Control Test. The scores range from 5 (poor control of asthma) to 25 (complete control of asthma), with higher scores reflecting greater asthma control. An ACT score \>19 indicates well-controlled asthma. |
| Asthmatic Bronchitis, prescriptions | First assessment at 1 year | Number of prescriptions of medicine for asthmatic bronchitis; Ventoline, Airomir, Flixotide, Aerobec, Montelukast / Singulair. |
| Asthmatic bronchitis, hospitalization | First assessment at 1 year | Number of hospitalizations due to asthmatic bronchitis. |
| Diaper rash | 1 year | Atopic skin symptoms in diaper area. Self-reported by the childs parents as affected red skin, distribution in centimeters . |
| Rhinoconjunctivitis | 1 year | Measured as Mini Rhinoconjunctivitis quality of life questionnaire Mini RQLQ, adjusted to infants. 14 questions in five domains (activity limitation, practical problems, nose symptoms, eye symptoms, and non-nose/ eye symptoms), scores for each question is ranging from 0 to 6, with 0 reflecting no affection and 6 reflecting maximum affection. |
| Obesity | 18 years | Measured as number of participants diagnosed with Obesity |
| Metabolic syndrome | 18 years | Measured as number of participants diagnosed with Metabolic syndrome |
| Diabetes | 18 years | Measured as number of participants diagnosed with Diabetes |
| Inflammatory bowel disease | 18 years | Measured as number of participants diagnosed with of Morbus Crohn and/or Colitis Ulcerosa. |
| Dried blood spot for metabolomics | 3 months and 1 year | The metabolomic method measures and compares large numbers of metabolites (for example shot chained fatty acids) present in the dried blood sample. |
| Bloodsample analyzed with Singlecell PBMC method | 1 year | Single cell sequencing is a method profiling the peripheral blood mononuclear cells (PBMC), by isolating memory B, T and B-cells |
| Child stool sample | 1 year | Stool samples collected at week 1, 4, 13, 28 and 52 will by qPCR or shutgun metagenomics examine the gut microbiome. |
| Mother stool sample | 1 month | A stool sample from the pregnant mother, preferably prior to or during birth. To analyze mothers microbial colonization, that may be transferred to the child, e.g during vaginal birth. |
Countries
Denmark
Contacts
Primary ContactMarie T Philipsen, MD, PhD.stud
Backup ContactMia E Sjørring, MD, PhD.stud
Outcome results
None listed