Asthma
Conditions
Keywords
wheeze, infections, allergy, eczema, vitamin D
Brief summary
The aim of this study is to prevent asthma symptoms (recurrent wheeze) in childhood by supplementation with high dose vitamin D to the mother during pregnancy. Participants are mothers and children of the ABC (Asthma Begins in Childhood) cohort. Mothers are recruited during pregnancy and receive daily supplement with 2400 IU of Vitamin D3 or placebo from week 24 og gestation to 1 week after delivery. In addition all mothers are advised to take the recommended dose of 400 IU vitamin D daily. The mothers in ABC also participate in an interventional trial with fish oil supplementation, and the vitamin D randomization is stratified by fish oil treatment group. The child is followed with acute and planned vits at the research unit, and wheeze is diagnosed according to predefined algorithms.
Interventions
DIETARY_SUPPLEMENTCholecalciferol D3
2 tablets of 1200 IU daily from week 24 of gestation to 1 week after delivery
OTHERPlacebo tablet
2 tablets containing no active substance
Sponsors
Copenhagen Studies on Asthma in Childhood
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
Mother: * Pregnant in week 22-26 of gestation * Participating in the ABC-cohort * Living in Sealand, Denmark * Fluent in Danish * Willing to let the child participate in the study
Exclusion criteria
Mother: * Intake of more than 400 IU of vitamin D during the last 6 months * Endocrinological disease such as calcium metabolic disorder, parathyroid disorder, thyroid disorder or Diabetes type 1 * Tuberculosis * Sarcoidosis * In need of diuretics or heart medication including calcium channel blockers
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Persistent wheeze | 0 to 3 years of age | Age at onset of persistent wheeze diagnosed according to predefined algorithm of recurrent troublesome lung symptoms, response to treatment and relapse after withdrawal of treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Infections | 0 to 3 years of age | Main analysis: • Number of lower respiratory tract infections registered in daily diaries Secondary analyses: * Acute otitis media * Number of upper respiratory tract infections * Number of other infections * Total number of infections |
| Allergic sensitization | 6 and 18 months of age | Allergic sensitization at 6 and/or 18 months assessed by skin prick test and specific IgE in blood |
| Eczema | 0 to 3 years of age | Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria |
| Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase | 1 week after delivery | — |
| Growth | 0 to 3 years of age | — |
| Asthma exacerbations | 0 to 3 years of age | Age at onset of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/high dose inhaled steroids or acute hospital contact |
| Neurological development | 0-3 years | Main analysis: • Cognitive development assessed at 2½ years using the cognitive part of Bayley Scales of Infant and Toddler Development, third edition Secondary analyses: * Milestone development monitored prospectively by the parents using a registration form based on The Denver Development Index and WHO milestones registration (combined assessment by principal component analysis) * Language development assessed at 1 and 2 years of age with the Danish version of The MacArthur Bates Communicative Developmental Inventory (CDI) * The child´s general development (language, fine and gross motor, social and problem solving) at 3 years of age assessed with Ages and stages Questioner, third edition (ASQ-3) |
| Airway mucosal immune status | 4 weeks and 2 years | Immune status measured in airway mucosal lining fluid at 4 weeks and 2 years of age (combined assessments by prinicipal component analyses for each age point) |
| 17q21 genotype and sphingolipid metabolites | 6 months | In a secondary analyses, we will determine the effect of 17q21 genotype on the efficacy of vitamin D supplementation in the prevention of asthma/wheeze. We will compute hazard ratios for the reduction in asthma/wheeze risk associated with prenatal supplementation, stratified by rs12936231. rs12936231 is a functional SNP influencing expression of ORMDL3, and given the role of ORMDL3 as a key sphingolipid biosynthesis regulator, we will subsequently investigate the relative abundance of sphingolipids between those in the vitamin D Intervention arm and those in the placebo group, stratified by 17q21 genotype. Finally we will identify interactions between prenatal vitamin D supplementation, rs12936231 genotype and sphingolipid metabolism in the risk of asthma/wheeze by age three. |
| Systemic immune status | 18 months | Main analysis Immune status at 18 months measured in stimulated whole blood as cytokine release (combined assessments by prinicipal component analyses) Secondary analyses Composition of immune cell subsets in whole blood at birth and at 18 months of age |
| Dental health | 6 year | Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years. |
Countries
Denmark
Contacts
PRINCIPAL_INVESTIGATORKlaus Bønnelykke, MD, PhD
Copenhagen Studies on Asthma in Childhood
Outcome results
None listed