Allergy, Asthma, Cognition Disorders in Children, Croup, Development, Child, Eczema, Fractures, Bone, Gastrointestinal Infection, Psychiatric Diagnosis, Respiratory Tract Infections, Wheezing
Conditions
Keywords
Childhood, Asthma, Infections, Eczema, Allergy, Development, Psychiatry, Bone development, Cognition, Growth
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.
Interventions
DIETARY_SUPPLEMENTCholecalciferol D3
Oral intake of 1 capsule per day from week 22-26 in pregnancy to 1 week after delivery
OTHEROlive oil
Oral intake of 1 capsule per day from week 22-26 in pregnancy to 1 week after delivery
Sponsors
Professor Klaus Bønnelykke
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 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Pregnant Danish women before week 26 with blood levels of EPA+DHA above 4.7% of total fatty acids * No current vitamin D intake above the recommended 400 IU/day * No endocrine-, heart-, kidney- or auto-immune disorders * No disorders requiring treatment with blood thinning medication
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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 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. |
| 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. |
| 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. |
Countries
Denmark
Contacts
Primary ContactKlaus Bønnelykke, PhD
Backup ContactUlrik Ralfkiaer, PhD
Outcome results
None listed