Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood

Study Overview
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Brief Summary
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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.

Official Title
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Vitamin D Supplementation During Pregnancy for Prevention of Asthma in Childhood: An Interventional Trial in the ABC (Asthma Begins in Childhood) Cohort

Conditions
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Asthma

Intervention / Treatment
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* Dietary Supplement: Cholecalciferol D3
* Other: Placebo tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vitamin D<br>Dietary supplement: 2400 IU Vitamin D3 (2 tablets of 1200 IU) from week 24 of gestation to 1 week after delivery | Dietary Supplement: Cholecalciferol D3<br>* 2 tablets of 1200 IU daily from week 24 of gestation to 1 week after delivery<br>* Other names: Vitamin D from Camette, Denmark;|
| Placebo Comparator: Placebo<br>Placebo: 2 placebo tablets with no active substance, identical to the active tablets, from week 24 of gestation to 1 week after delivery | Other: Placebo tablet<br>* 2 tablets containing no active substance<br>* Other names: Placebo tablets from Camette, Denmark;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Persistent wheeze | 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 | 0 to 3 years of age | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Infections | 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 | 0 to 3 years of age | 
| Allergic sensitization | Allergic sensitization at 6 and/or 18 months assessed by skin prick test and specific IgE in blood | 6 and 18 months of age | 
| Eczema | Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria | 0 to 3 years of age | 
| Mothers levels of 25-OH-Vitamin D, PTH, Calcium, alkaline phosphatase |  | 1 week after delivery | 
| Growth |  | 0 to 3 years of age | 
| Asthma exacerbations | 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 | 0 to 3 years of age | 
| Neurological development | 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) | 0-3 years | 
| Growth | 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 clinic | 0-3 years | 
| Systemic immune status | 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 | 18 months | 
| Airway mucosal immune status | 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) | 4 weeks and 2 years | 
| 17q21 genotype and sphingolipid metabolites | 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. | 6 months | 
| Dental health | Caries and enamel defects (molar incisor hypomineralization, MIH) determined at a dental examination at age 6 years. | 6 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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wheeze, infections, allergy, eczema, vitamin D