Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood
- Conditions
- Asthma
- Interventions
- Other: Placebo tabletDietary Supplement: Cholecalciferol D3
- Registration Number
- NCT00856947
- Lead Sponsor
- Copenhagen Studies on Asthma in Childhood
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- Female
- Target Recruitment
- 600
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
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo tablet Placebo: 2 placebo tablets with no active substance, identical to the active tablets, from week 24 of gestation to 1 week after delivery Vitamin D Cholecalciferol D3 Dietary supplement: 2400 IU Vitamin D3 (2 tablets of 1200 IU) from week 24 of gestation to 1 week after delivery
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase 1 week after delivery 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
Dental health 6 year Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years.
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 infectionsAsthma 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
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 ageEczema 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
Growth 0-3 years Main analysis:
• Body composition (fat mass and bone mineral density) assessed by DEXA scan at 3 years of age
Secondary analysis
• Development of BMI from birth to 3 years assesses longitudinally in the research clinicNeurological 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.
Trial Locations
- Locations (2)
Copenhagen University Hospital of Copenhagen
🇩🇰Gentofte, Denmark
Næstved Hospital, Pediatric Department
🇩🇰Næstved, Denmark