Colic, Eczema Atopic Dermatitis, Healthy Infants
Conditions
Keywords
Preventive effect, Limosilactobacillus reuteri, L. reuteri, crying, colic, healthy infants, newborns
Brief summary
This study aims to demonstrate that a dietary supplement, which contains two strains of the probiotic L. reuteri is safe, well tolerated and able to reduce the incidence of colic and excessive crying/fussiness in healthy infants. Additionally, the study aims to investigate if children with this probiotic supplement have better stool characteristics and a more beneficial composition of the fecal and skin flora than children given a placebo during the first 3 months of life.
Detailed description
This study is a double-blind, randomized, placebo-controlled trial conducted at UZ Brussel to evaluate the safety and preventive efficacy of a dietary supplement containing two probiotic strains of Limosilactobacillus reuteri on excessive crying and the development of infantile colic in healthy newborns. Recent systematic reviews and meta-analyses have shown that supplementation with certain strains of L. reuteri significantly reduces crying and fussing time in infants. A novel formulation combining those strains was developed to achieve a potentially enhanced effect on infant distress symptoms. This study investigates whether early supplementation, initiated within the first week of life, is safe and effective during the first three months of life. Healthy, full-term infants (≥37 weeks' gestation) aged 1-14 days at inclusion are eligible. Participants are randomized to receive either placebo plus vitamin D (400 IU) or L. reuteri plus vitamin D (400 IU) for a maximum of 98 days, until approximately 3 months of age. Study visits include a baseline visit (day 1-14), a midway visit at 6 weeks, an end-of-intervention visit at 3 months, and a long-term follow-up at 1 year. Additional telephone contacts are triggered by infant day diaries. The primary outcomes are peak crying and fussing time at 6 weeks of age and the occurrence of infantile colic during the first 3 months of life. Secondary outcomes include infant quality of life (ITQOL™), parental stress, parental satisfaction, crying and fussiness patterns, and the presence of atopic dermatitis. Exploratory outcomes assess changes in the intestinal microbiome, stool characteristics, biomarkers, growth, and allergy-related parameters. The primary hypothesis is that daily supplementation with the two strains of L. reuteri reduces the incidence of infantile colic and peak crying time at 6 weeks. Secondary hypotheses propose microbiome modulation leading to reduced distress, improved infant quality of life, and lower parental stress.
Interventions
DIETARY_SUPPLEMENTTwo probiotic Limosilactobacillus reuteri strains
Each participant in this intervention group gets 5 drops per day, containing the two probiotic Limosilactobacillus reuteri strains and 400 IU of Vitamin D
DIETARY_SUPPLEMENTPlacebo
Each participant in this intervention group gets 5 drops per day, containing only 400 IU of Vitamin D.
Sponsors
Universitair Ziekenhuis Brussel
BioGaia AB
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
Prospective, double-blind, parallel, randomized, placebo-controlled superiority trial.
Eligibility
Sex/Gender
ALL
Age
1 Days to 14 Days
Healthy volunteers
Yes
Inclusion criteria
1. Infant is born at the maternity ward of UZ Brussel with a gestational age of ≥37 weeks. 2. Infant is healthy at the time of pre-examination. 3. Infant is aged between 1 and 14 days old at the time of inclusion. 4. Legal guardian(s) are able and willing to follow the study instructions 5. Infant is suitable for participation in the study according to the investigator/ study personnel 6. Legal guardian(s) willing to refrain products containing probiotics for their infant, from baseline (visit 1) throughout the study period (visit 3). 7. Informed written consent given by parent / legal guardian
Exclusion criteria
1. No legal guardian's command of any local language 2. Infant with a major congenital anomaly (i.e. anal atresia, trisomy 21) or suspicion of any chronic disorder or disease (i.e. Hirschsprung's disease, metabolic disorder) 3. Infant is suffering from congenital or acquired immunodeficiency 4. Infant is suffering from an infection at the time of pre-examination or previous 7 days 5. Infant is admitted post-partum to the neonatal intensive care unit 6. Infant is not suitable for participation in the study according to the study personnel´s opinion
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Peak measured crying time | 6 weeks | Peak measured crying time at 6 (±1) weeks according to the prospectively kept baby day diary |
| The occurrence of infant colic at any time in the first 3 months of life. | 3 months | The criteria for infant colic are: * Recurrent and prolonged periods of infant crying, fussing, or irritability reported by caregivers that occur without obvious cause and cannot be prevented or resolved by caregivers. Fussing refers to intermittent distressed vocalization and refers to behavior that is not quite crying but not awake and content either. * Caregiver reports infant has cried or fussed for 3 or more hours/day during 3 or more days in a given week. * Total 24-hour crying plus fussing in the selected group of infants is confirmed to be 3 hours or more when measured by at least one, prospectively kept, 24-hour behavior diary. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Peak measured fussiness time | 6 weeks | Peak measured fussiness time at the age of 6 (±1) weeks according to the prospectively kept baby day diary. |
| Overall crying and/or fussiness time | 3 months | Overall (estimated + measured) crying and/or fussiness time in the first 3 months (±1 week) of life. |
| Overall unconsolable crying time | 3 months | Overall measured and/or estimated unconsolable crying time in the first 3 months (±1 week) of life |
| Parental stress | 3 months | Parental stress as measured by the Parental Stress Scale (PSS) at 6 (±1) weeks and 3 months (±1 week) of both (if applicable) caregivers. Parents can indicate the degree to which they agree or disagree with the statements in this questionnaire, ranging from strongly disagree (1 point) to strongly agree (5 points). Total scores range from 18 points (low score signify a low level of stress) to 90 points (high score signify a high level of stress). |
| Quality of Life score | 12 months | Infant and toddler quality of life questionnaire(ITQOL™) at 3 months (±1 week) and of 12 months (±2 weeks) age. ITQOL is scored on a scale from 0 to 100, where higher scores mean better health/quality of life. |
| Parental satisfaction | 3 months | Parental satisfaction scale measured by a 5-point Likert scale at 6 (±1) weeks and 3 months (±1 week). A scale where parents indicate how satisfied they are with their baby's current level of crying and fussing, with a minimum score of 2 and maximum score of 10. Parents who are very dissatisfied have a low score, while parents who are very satisfied have a high score. |
| Atopic dermatitis | 12 months | Presence and degree of atopic dermatitis (AD, measured via SCORAD) at 3 months (±1 week) and 12 months (±2 weeks) of age. The score ranges from 0 to 103 and is used to determine the stages of AD severity. Where a score lower than 25 is seen as mild state, 25-50 is a moderate state and \>50 is a severe state. |
Countries
Belgium
Contacts
CONTACTKoen Huysentruyt, Pediatric Gastroenterologist
CONTACTLeontien Depoorter, Resident Pediatric Pulmonology
PRINCIPAL_INVESTIGATORKoen Huysentruyt, Pediatric Gastroenterologist
Universitair Ziekenhuis Brussel
Outcome results
None listed