Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Vitamin D | Active Comparator | Dietary supplement: 2400 IU Vitamin D3 (2 tablets of 1200 IU) from week 24 of gestation to 1 week after delivery |
|
| Placebo | Placebo Comparator | Placebo: 2 placebo tablets with no active substance, identical to the active tablets, from week 24 of gestation to 1 week after delivery |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Cholecalciferol D3 | Dietary Supplement | 2 tablets of 1200 IU daily from week 24 of gestation to 1 week after delivery |
|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Infections | Main analysis: • Number of lower respiratory tract infections registered in daily diaries Secondary analyses:
| 0 to 3 years of age |
| Allergic sensitization |
| Measure | Description | Time Frame |
|---|---|---|
| Asthma | Asthma diagnosed from age 3 to 10 years based on the same predefined algorithm of recurrent troublesome lung symptoms, response to treatment after withdrawal of treatment, which was used for persistent wheeze at age 0-3 in phase 1 of the study. Primary outcome in phase 2 is current asthma at specific visits till age 10 years, which is diagnosed in children fulfilling the persistent wheeze algorithm at any point during the first 10 years of life and still needing inhaled corticosteroids at specific visits (3, 4, 5, 6, 8 and 10 years of age) to control the symptoms. |
Inclusion Criteria:
Mother:
Exclusion Criteria:
Mother:
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Klaus Bønnelykke, MD, PhD | Copenhagen Studies on Asthma in Childhood | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Copenhagen University Hospital of Copenhagen | Gentofte Municipality | Gentofte | 2820 | Denmark | ||
| Næstved Hospital, Pediatric Department |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 42149595 | Derived | Frederiksen OF, Jepsen JRM, Brustad N, Vinding R, Rosenberg JB, Mohammadzadeh P, Hernandez-Lorca M, Schoos AM, Vahman N, Glenthoj BY, Fagerlund B, Bilenberg N, Bonnelykke K, Ebdrup BH, Aagaard K, Chawes B. High-Dose Vitamin D3 Supplementation During Pregnancy and Test-Based Cognitive Performance at Age 10 Years: A Post Hoc Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2026 May 1;9(5):e2611464. doi: 10.1001/jamanetworkopen.2026.11464. | |
| 40865727 |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D001249 | Asthma |
| D012135 | Respiratory Sounds |
| D007239 | Infections |
| D006967 | Hypersensitivity |
| D004485 | Eczema |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Placebo tablet | Other | 2 tablets containing no active substance |
|
|
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:
| 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 |
| 3-10 years of age |
| Lung function measurements | Spirometry measuring airflow assessed by FEV1, MMEF and FEV1/FVC ratio at age 5, 6, 8 and 10 years. | 5-10 years of age |
| Infections | Prescribed medicine for infections. Types and length of infections | 3-10 years of age |
| Growth | Anthropometrics: Clinical follow up on the development of weight in kg (calibrated digital weight scales), height in cm (Harpenden stadiometer), waist-, thorax- and head circumference in cm (using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic. | 3- 10 years of age |
| Eczema | Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria | 3-10 years of age |
| Allergic sensitization/atopy | Allergic sensitization at 6 and 10 years of age assessed by skin prick test (ALK-Abelló, Denmark) and specific IgE in blood (ImmunoCAP, PHarmacia Diagnostics AB, Sweden). | 6-10 years of age |
| Airway mucosal immune status | Immune status measured in airway mucosal lining fluid at 3, 6 and 10 years of age (combined assessments by principal component analyses for each age point). | 3-10 years of age |
| The diagnose allergic rhinitis | Allergic rhinitis will be diagnosed by combining allergic sensitization with symptom recording of troublesome congestion or sneezing or runny nose upon relevant exposure to allergens at age 3, 4, 5, 6, 8 and 10 years. | 3-10 years of age |
| Asthma exacerbations: | Age at onset and number of severe asthma exacerbation diagnosed by predefined criteria of acute severe asthma requiring oral/ high dose inhaled steroids or acute hospital contact | 3-10 years of age |
| Airway resistance | Measured by plethysmography (sRaw) at age 3, 4, 5, 6, 8 and 10 years. | 3-10 years of age |
| Airway resistance | Multiple breath wash-out using SF6 and N2 as inert gasses to determined LCI, Scond and Sacin at ages 3, 4 and 5 years. | 3-5 years of age |
| Bronchial reactivity: | Provocative dose of methacholine leading to a 20% drop in FEV1 from baseline (PD20 value) at age 6 years. | at 6 years of age |
| Body composition | Body composition measured as fat mass, lean mass, bone mineral content (BMC) and bone mineral density assessed (BMD) through DXA scans at 3, 6 and 13 years of age. Body impedance measurements at 10 years of age. | 3-13 years of age |
| Airway inflammation: | Measurement of fractional exhaled nitric oxide (FeNO) at age 6, 8 and 10 years | 6-10 years of age |
| Cognitive function | A 2,5 hours cognitive evaluation at 10 years of age. Cognitive functions from a broad spectrum of cognitive domains will be assessed with subtests both using paper pencil tests and Cambridge Neuropsychological Test Automated Battery . | 10 years of age |
| MRI scanning of the Brain | MRI scanning of the Brain | 10 years of age |
| Behavioral and psychopathological dimensions. | Questionnaires will be administered to the parents. | 6- 10 years of age |
| Behavioral and psychopathological dimensions. | Behavioral and psychopathological dimensions will be assessed at 10 years of age. The childrens' potential psychiatric diagnoses will be ascertained through the semi-structured clinical interview Schedule for Affective Disorders and Schizophrenia for School-Age Children - Present and Lifetime Version (K-SADS-PL) first with a parent and next with the child. | 10 years of age |
| Strength and Difficulties Questionnaire (SDQ)- Questionnaires | The Strengths and Difficulties Questionnaire (SDQ) is a brief behavioural screening questionnaire about 3-16 year olds. Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires in order validated methods | 6, 8 and 10 years of age |
| ADHD- RS- Questionnaires | The ADHD Rating Scale obtains parent ratings regarding the frequency of each ADHD symptom based on DSM criteria. Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods. | 8 and 10 years of age |
| Social Responsive Scale, Second version (SRS-2) | The SRS-2 identifies social impairment associated with autism spectrum disorders (ASDs) and quantifies its severity Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods. | 10 years of age |
| The Child Behavior Checklist school-age version (CBCL) | The Child Behavior Checklist (CBCL) is a widely used questionnaire to assess behavioral and emotional problems. Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology and behavior problems. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods. | 10 years of age |
| The Behavior Rating Inventory of Executive Function 2nd edition (BRIEF-2) | The BRIEF-2 is a set of questionnaires for parents and teachers , designed to evaluate executive function from multiple perspectives. Questionnaires will be administered to the parents to obtain their evaluation of their child's potential psychopathology. Scores will be calculated form the questionnaires. Scores will be calculated form the questionnaires in order validated methods. | 10 years of age |
| Bone fractures | Description: Assessed by medical record checks including all radiologically verified fractures of larger long bones (i.e. clavicle, radius, ulna, tibia, fibula, femur and humerus). Outcome analyses: total no. of fractures age 0-13 years. | 0-13 years of age |
| Næstved |
| Næstved |
| 4700 |
| Denmark |
| Derived |
| Brustad N, Wang T, Chen L, Kaiser H, Gomes B, Klein A, Vahman N, Skov L, Stokholm J, Schoos AM, Bonnelykke K, Chawes B. Effect of prenatal high-dose vitamin D on childhood atopic dermatitis is modified by maternal cotinine metabolome: A secondary analysis of a randomized clinical trial. J Am Acad Dermatol. 2026 Jan;94(1):88-95. doi: 10.1016/j.jaad.2025.08.044. Epub 2025 Aug 25. |
| 39077939 | Derived | Palacios C, Kostiuk LL, Cuthbert A, Weeks J. Vitamin D supplementation for women during pregnancy. Cochrane Database Syst Rev. 2024 Jul 30;7(7):CD008873. doi: 10.1002/14651858.CD008873.pub5. |
| 38072183 | Derived | Aagaard K, Mollegaard Jepsen JR, Sevelsted A, Horner D, Vinding R, Rosenberg JB, Brustad N, Eliasen A, Mohammadzadeh P, Folsgaard N, Hernandez-Lorca M, Fagerlund B, Glenthoj BY, Rasmussen MA, Bilenberg N, Stokholm J, Bonnelykke K, Ebdrup BH, Chawes B. High-dose vitamin D3 supplementation in pregnancy and risk of neurodevelopmental disorders in the children at age 10: A randomized clinical trial. Am J Clin Nutr. 2024 Feb;119(2):362-370. doi: 10.1016/j.ajcnut.2023.12.002. Epub 2023 Dec 9. |
| 36184023 | Derived | Brustad N, Yang L, Chawes BL, Stokholm J, Gurdeniz G, Bonnelykke K, Bisgaard H. Fish Oil and Vitamin D Supplementations in Pregnancy Protect Against Childhood Croup. J Allergy Clin Immunol Pract. 2023 Jan;11(1):315-321. doi: 10.1016/j.jaip.2022.09.027. Epub 2022 Sep 30. |
| 35105560 | Derived | Mohammadzadeh P, Rosenberg JB, Vinding R, Mollegaard Jepsen JR, Lindberg U, Folsgaard N, Erlang Sorensen M, Sulaiman D, Bilenberg N, Mitta Raghava J, Fagerlund B, Vestergaard M, Pantelis C, Stokholm J, Chawes B, Larsson H, Glenthoj BY, Bonnelykke K, Ebdrup BH, Bisgaard H. Effects of prenatal nutrient supplementation and early life exposures on neurodevelopment at age 10: a randomised controlled trial - the COPSYCH study protocol. BMJ Open. 2022 Feb 1;12(2):e047706. doi: 10.1136/bmjopen-2020-047706. |
| 33653805 | Derived | Knihtila HM, Kelly RS, Brustad N, Huang M, Kachroo P, Chawes BL, Stokholm J, Bonnelykke K, Pedersen CT, Bisgaard H, Litonjua AA, Lasky-Su JA, Weiss ST. Maternal 17q21 genotype influences prenatal vitamin D effects on offspring asthma/recurrent wheeze. Eur Respir J. 2021 Sep 23;58(3):2002012. doi: 10.1183/13993003.02012-2020. Print 2021 Sep. |
| 33289844 | Derived | Sass L, Vinding RK, Stokholm J, Bjarnadottir E, Noergaard S, Thorsen J, Sunde RB, McGrath J, Bonnelykke K, Chawes B, Bisgaard H. High-Dose Vitamin D Supplementation in Pregnancy and Neurodevelopment in Childhood: A Prespecified Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2020 Dec 1;3(12):e2026018. doi: 10.1001/jamanetworkopen.2020.26018. |
| 32091548 | Derived | Brustad N, Garland J, Thorsen J, Sevelsted A, Krakauer M, Vinding RK, Stokholm J, Bonnelykke K, Bisgaard H, Chawes BL. Effect of High-Dose vs Standard-Dose Vitamin D Supplementation in Pregnancy on Bone Mineralization in Offspring Until Age 6 Years: A Prespecified Secondary Analysis of a Double-Blinded, Randomized Clinical Trial. JAMA Pediatr. 2020 May 1;174(5):419-427. doi: 10.1001/jamapediatrics.2019.6083. |
| 31381020 | Derived | Norrisgaard PE, Haubek D, Kuhnisch J, Chawes BL, Stokholm J, Bonnelykke K, Bisgaard H. Association of High-Dose Vitamin D Supplementation During Pregnancy With the Risk of Enamel Defects in Offspring: A 6-Year Follow-up of a Randomized Clinical Trial. JAMA Pediatr. 2019 Oct 1;173(10):924-930. doi: 10.1001/jamapediatrics.2019.2545. |
| 29077711 | Derived | Wolsk HM, Chawes BL, Litonjua AA, Hollis BW, Waage J, Stokholm J, Bonnelykke K, Bisgaard H, Weiss ST. Prenatal vitamin D supplementation reduces risk of asthma/recurrent wheeze in early childhood: A combined analysis of two randomized controlled trials. PLoS One. 2017 Oct 27;12(10):e0186657. doi: 10.1371/journal.pone.0186657. eCollection 2017. |
| 26813208 | Derived | Chawes BL, Bonnelykke K, Stokholm J, Vissing NH, Bjarnadottir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdottir S, Arianto L, Hallas HW, Heickendorff L, Brix S, Rasmussen MA, Bisgaard H. Effect of Vitamin D3 Supplementation During Pregnancy on Risk of Persistent Wheeze in the Offspring: A Randomized Clinical Trial. JAMA. 2016 Jan 26;315(4):353-61. doi: 10.1001/jama.2015.18318. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D007154 | Immune System Diseases |
| D012818 | Signs and Symptoms, Respiratory |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |