VItamin D in PregnanCy for PrevenTion of EaRlY Childhood Asthma

Phase 3

Recruiting

• Conditions: Croup; Fractures, Bone; Respiratory Tract Infections; Gastrointestinal Infection; Development, Child; Psychiatric Diagnosis; Asthma; Eczema; Allergy; Wheezing
• Interventions: Dietary Supplement: Cholecalciferol D3; Other: Olive oil

• Registration Number: NCT06570889
• Lead Sponsor: Professor Klaus Bønnelykke

Brief Summary

The overall aim of the study is to develop a nutritional preventive vitamin D supplementation strategy in pregnancy for early childhood asthma/persistent wheeze during the first three years of life as we hypothesize that supplementation in higher doses than recommended could reduce the risk of disease development.

Detailed Description

Randomization of 2000 pregnant women to vitamin D of high-dose (3200 IU/day) vitamin D vs placebo on top of the recommended 400 IU/day. Supplementation begins in gestational week 24 (22-26) until 1 week after delivery. Allocation to the trial will be determined based on the pre-interventional maternal blood levels of EPA+DHA with a dried blood screening test. Women with high levels (above 4.7% of total fatty acids) will be assigned to the vitamin D RCT. Maternal blood will be used for genetic, metabolomic and proteomic profiling. A 3-year follow-up of the children with longitudinal registration of parent reported symptoms, diagnoses, medication use, and hospitalizations will be performed. The primary outcome is persistent wheeze or asthma until age 3 years, with predefined analyses of effect modification by maternal genotypes. Secondary outcomes are lower respiratory tract infections, gastrointestinal infections, croup, troublesome lung symptoms, eczema, allergy, bone fractures, developmental milestones, mental health, cognition, and growth until age 3 years. A follow-up on both primary and secondary outcomes is planned after unblinding, from age 3 to 6 years.

Study Timeline

• Study First Submitted: 2024-08-20
• Study First Submitted QC: 2024-08-22
• Study First Posted: 2024-08-26
• Study Start: 2024-12-20
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-20
• Last Update Posted: 2025-03-24
• Primary Completion: 2026-10
• Study Completion: 2033-03

Recruitment & Eligibility

• Status: RECRUITING
• Sex: Female
• Target Recruitment: 2000

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Vitamin D3 (cholecalciferol) 3200 IU/day	Cholecalciferol D3	Oral intake of 1 capsule daily from week 22-26 of gestation until 1 week after delivery
Placebo Pearls with olive oil	Olive oil	Oral intake of 1 capsule daily from week 22-26 of gestation until 1 week after delivery

Primary Outcome Measures

Name	Time	Method
Early childhood asthma/persistent wheeze age 0-3 years	3 years	Defined as either a) parental report of a minimum of 2 wheeze episodes with at least 1 after the child's second birthday and redemption of at least 2 prescriptions of asthma controller medication with at least 1 being after the child's second birthday or b) a minimum of 2 ED visits or hospitalizations due to asthmatic symptoms, and at least 1 of these being after the child's second birthday or c) parental report of physician-diagnosed asthma age 0-3 years; Outcome analysis: risk (survival analysis) of persistent wheeze or asthma at age 0-3 years.

Secondary Outcome Measures

Name	Time	Method
Atopic/non-atopic wheeze or asthma age 0-3 years	3 years	Parental reports of physician diagnosed asthma in combination with eczema and/or allergic rhinitis.; Outcome analyses: asthma/persistent wheeze with/without eczema and/or allergic rhinitis (yes/no) by age 3 years. Each subtype is compared with children without asthma.
Troublesome lung symptoms age 0-3 years	3 years	Defined as cough, wheeze or dyspnea severely affecting the well-being of the child for at least 3 consecutive days based on parental reports.; Outcome analyses: total no. of episodes with symptoms age 0-3 years.
Wheeze episodes age 0-3 years	3 years	Parental reports of wheezing. Outcome analyses: total no. of episodes with wheeze age 0-3 years.
Inhaled bronchodilator use from parental reports age 0-3 years	3 years	Outcome analyses: total no. of days with bronchodilator use age 0-3.
Inhaled bronchodilator prescriptions from medical record checks age 0-3 years	3 years	Outcome analyses: total no. of prescriptions age 0-3.
Asthma controller medication use from parental reports age 0-3 years	3 years	Outcome analyses: total no. of days with use of asthma controller medication age 0-3.
Asthma controller medication prescriptions from medical record checks age 0-3 years	3 years	Outcome analyses: total no. of prescriptions age 0-3.
Asthma hospitalizations or emergency department visits age 0-3 years	3 years	Outcome analyses: total no. of episodes age 0-3 years.
Eczema age 0-3 years	3 years	Parental reports of physician-diagnosed eczema and prescribed topical antiinflammatory medication on medical record checks.; Outcome analyses: risk (survival analysis) of any eczema age 0-3 years and current eczema (yes/no) by age 3 years.
Allergic rhinitis age 0-3 years	3 years	Based on parental reports of physician-diagnosed allergic rhinitis.; Outcome analyses: allergic rhinitis (yes/no) by age 3 years.
Food allergy 0-3 years	3 years	Parental reports of physician-diagnosed food allergy.; Outcome analyses: any food allergy (yes/no) by age 3 years.
Lower respiratory tract infections age 0-3 years	3 years	Parental reports of physician-diagnosed bronchiolitis or pneumonia.; Outcome analysis: risk (survival analysis) of first lower respiratory tract infection and total no. of lower respiratory tract infections age 0-3 years.
Gastrointestinal infections age 0-3 years	3 years	Parental reports.; Outcome analyses: risk (survival analysis) of any gastroenteritis episode and total no. of gastroenteritis episodes age 0-3 years.
Croup age 0-3 years	3 years	Parental reports of physician diagnosed croup.; Outcome analysis: risk (survival analysis) of any croup episode and total no. of croup episodes age 0-3 years.
Fever episodes age 0-3 years	3 years	Based on parental reports.; Outcome analyses: total no. of episodes with symptoms age 0-3 years.
Absences from daycare age 0-3 years	3 years	Due to illnesses based on parental reports.; Outcome analyses: total no. of absence days age 0-3 years.
Bone fractures age 0-3 years	3 years	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 0-3 years.
Developmental milestones age 0-3 years	3 years	Monitored every 6 months until age 3 years by the parents using a registration form based on The Denver Development Index and WHO milestones registration.; Outcome analyses: combined assessment of age at achievement across milestones by principal component analysis.
Strength and difficulties at age 3 years	3 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.; Emotional symptoms: range 0-10, a low score means better outcome. Behavioral symptoms: range 0-10, a low score means better outcome. Hyperactivity/attention difficulties:range 0-10, a low score means better outcome.; Problems with children of the same age:range 0-10, a low score means better outcome.; Social strengths:range 0-10, a high score means better outcome. Impact on well-being and functioning: range 0-10, a low score means better outcome.; Outcome analyses: SDQ scores at age 3 years.
BMI age 0-3 years	3 years	From parental reports every 6 months.; Outcome analyses: development of BMI age 0-3 years and current BMI at age 3.
Waist circumference age 0-3 years	3 years	From parental reports every 6 months.; Outcome analyses: development of waist circumference age 0-3 years and current waist circumference at age 3.
Persistent wheeze or asthma age 0-6 years	6 years	Defined similarly to the primary outcome; Outcome analysis: risk (survival analysis) of persistent wheeze or asthma at age 0-6 years
Current asthma at age 6 years	6 years	Defined similarly to the primary outcome and with symptoms and/or asthma medication use in the last 12 months at age 6.; Outcome analyses: Current wheeze or asthma (yes/no) by age 6 years.
Asthma or wheeze yearly prevalence 0-6 years	6 years	Defined as in the primary outcome and current disease defined from parental reports of wheeze and/or asthma medication use.; Outcome analyses: Yearly prevalence of wheeze or asthma medication use (yes/no) 0-6 years.
Adaptive behavior at 3 years	3 years	Adaptive Behavior Assessment System, Third Edition (ABAS-3)is used to assess everyday, adaptive functioning.; Total score range: 0-645, a low score indicate poorer outcome.
Atopic/non-atopic asthma at age 6 years	6 years	Parental reports of physician diagnosed asthma in combination with eczema and/or allergic rhinitis.; Outcome analyses: Current asthma with/without eczema and/or allergic rhinitis (yes/no) by age 6 years. Each subtype is compared with children without asthma.
Asthma controller medication 0-6 years	6 years	From redeemed medication prescriptions (inhaled corticosteroids and leukotriene modifiers) based on medical record checks: Outcome analyses: total no. of prescriptions age 0-6 years.
Inhaled bronchodilators age 0-6 years	6 years	From redeemed inhaled bronchodilators based on medical record checks.; Outcome analyses: total no. of prescriptions age 0-6 years.
Asthma hospitalizations or emergency department visits age 0-6 years	6 years	Based on medical record checks.; Outcome analyses: total no. of episodes age 0-6 years.
Eczema age 0-6 years	6 years	Based on parental reports of physician diagnosed eczema.; Outcome analyses: risk (survival analysis) of any eczema age 0-6 years and current eczema (yes/no) by age 6 years.
Allergic rhinitis age 0-6 years	6 years	Based on parental reports of physician-diagnosed allergic rhinitis and on medical record checks.; Outcome analyses: allergic rhinitis (yes/no) by age 6 years.
Food allergy age 0-6 years	6 years	Based on parental reports of physician-diagnosed food allergy.; Outcome analyses: any food allergy (yes/no) by age 6 years.
Lower respiratory tract infections age 0-6 years	6 years	Based on parental reports of physician-diagnosed bronchiolitis or pneumonia.; Outcome analysis: risk (survival analysis) of first lower respiratory tract infection and total no. of lower respiratory tract infections age 0-6 years.
Gastrointestinal infections age 0-6 years	6 years	Based on parental reports.; Outcome analyses: risk (survival analysis) of any gastroenteritis episode and total no. of gastroenteritis episodes age 0-6 years.
Croup age 0-6 years	6 years	Based on parental reports of physician diagnosed croup.; Outcome analysis: risk (survival analysis) of any croup episode and total no. of croup episodes age 0-6 years.
Bone fractures age 0-6 years	6 years	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 0-6 years.
Strength and difficulties at age 6 years	6 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.; Emotional symptoms: range 0-10, a low score means better outcome. Behavioral symptoms: range 0-10, a low score means better outcome. Hyperactivity/attention difficulties:range 0-10, a low score means better outcome.; Problems with children of the same age:range 0-10, a low score means better outcome.; Social strengths:range 0-10, a high score means better outcome. Impact on well-being and functioning: range 0-10, a low score means better outcome.; Outcome analyses: SDQ scores at age 6 years.
ADHD symptoms at age 6 years	6 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children.; For attention symptoms: range: 0-27, a low score means better outcome. For impulsivity-hyperactivity: range: 0-27, a low score means better outcome. For behavioral problems: range: 0-24, a low score means better outcome.; Outcome analyses: ADHD symptom scores at age 6 years.
Psychopathology screening at age 6 years	6 years	From the Child Behavior Check List; a questionnaire for general screening of preschool psychopathology.; Total problem score: range 0-236, a low score means better outcome Internalizing problems score: range 0-64, a low score means better outcome Externalizing problems score: range 0-70, a low score means better outcome; Outcome analyses: Total syndrome scales at age 6 years.
BMI age 0-6 years	6 years	From parental reports every 6 months.; Outcome analyses: development of BMI age 0-6 years and current BMI at age 6.
Waist circumference age 0-6 years	6 years	From parental reports every 6 months.; Outcome analyses: development of waist circumference age 0-6 years and current waist circumference at age 6.
ADHD symptoms at age 3 years	3 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children.; For inattentive score: range: 0-27, a low score means better outcome. For impulsivity-hyperactivity: range: 0-27, a low score means better outcome.; Outcome analyses: ADHD symptom scores at age 3 years.
Social behavior assessment at age 3 years	3 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits: Total score range: 0-195, a low score indicates better outcome.; Outcome analyses: Total problem scores at age 3 years.
Social behavior assessment at age 6 years	6 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits.; Total score range: 0-195, low score indicates a better outcome.; Outcome analyses: Total problem scores at age 6 years.
Psychopathology screening at age 3 years	3 years	From the Child Behavior Check List 1,5-5 years; a questionnaire for general screening of preschool psychopathology.; Total problem score: range 0-198, a low score means better outcome; Outcome analyses: Total syndrome scales at age 3 years.
Adaptive behavior at 6 years	6 years	Adaptive Behavior Assessment System, Third Edition (ABAS-3)is used to assess everyday, adaptive functioning.; Total score range: 0-633, a low score indicate poorer outcome.
Cognitive assessment age 0-3 years	3 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions.; Total problem score: range 63-189, a low score means better outcome.; Outcome analyses: Index values at age 3 years.
Cognitive assessment age 0-6 years	6 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions.; Total problem score: range 60-180, a low score means better outcome.; Outcome analyses: Index values at age 6 years.

Trial Locations

Locations (1)

Copenhagen University Hospital of Copenhagen; 🇩🇰 Gentofte, Denmark