Fish Oil in PREgnancY for Personalized Prevention of Early Childhood Asthma

Phase 3

Recruiting

• Conditions: Asthma; Gastrointestinal Infection; Croup; Psychiatric Diagnosis; Wheezing; Respiratory Tract Infections; Eczema; Allergy; Fractures, Bone; Development, Child
• Interventions: Dietary Supplement: n-3 fatty acid; Other: Rape seed oil

• Registration Number: NCT06560255
• Lead Sponsor: Professor Klaus Bønnelykke

Brief Summary

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

Detailed Description

Randomization of 2000 pregnant women to fish oil of 2.4 g/day (55% EPA and 37% DHA) in triacylglycerol form vs placebo. 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 low levels (below 4.7% of total fatty acids) will be assigned to the fish oil 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: 2024-08-15
• Study First Submitted QC: 2024-08-15
• Study First Posted: 2024-08-19
• 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
n-3 fatty acid of 2.4 g per day	n-3 fatty acid	Oral intake of 4 capsules daily from week 22-26 of gestation until 1 week after delivery
Rape seed oil	Rape seed oil	Oral intake of 4 capsules 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
ADHD symptoms at age 3 years	3 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children.; Outcome analyses: ADHD symptom scores at age 3 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.; Outcome analyses: Total syndrome scales at age 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.
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.
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.
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 hospitalizations or emergency department visits age 0-3 years	3 years	Outcome analyses: total no. of episodes age 0-3 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.
Social behavior assessment at age 3 years	3 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits: Outcome analyses: Total problem scores at age 3 years.
Cognitive assessment age 0-3 years	3 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions.; Outcome analyses: Index values at age 3 years.
BMI and waist circumference age 0-3 years	3 years	From parental reports every 6 months.; Outcome analyses: development of BMI and waist circumference age 0-3 years and current BMI and waist circumference at age 3.
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 controller medication prescriptions from medical record checks age 0-3 years	3 years	Outcome analyses: total no. of prescriptions age 0-3.
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.
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.
Strength and difficulties at age 3 years	3 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.; Outcome analyses: SDQ scores at age 3 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.
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.
Inhaled bronchodilator prescriptions from medical record checks age 0-3 years	3 years	Outcome analyses: total no. of prescriptions age 0-3.
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.
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.
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.
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
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.
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.
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.
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.
Strength and difficulties at age 6 years	6 years	From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.; Outcome analyses: SDQ scores at 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.
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.
ADHD symptoms at age 6 years	6 years	From the ADHD rating scale-IV preschool, a dimensional questionnaire for ADHD symptoms in preschool children.; Outcome analyses: ADHD symptom scores at age 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.
Social behavior assessment at age 6 years	6 years	From the Social Responsiveness Scale, Second Edition; a questionnaire for screening for autistic traits.; Outcome analyses: Total problem 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.; Outcome analyses: Total syndrome scales at age 6 years.
Cognitive assessment age 0-6 years	6 years	From Behavior Rating Inventory of Executive Function in preschool children; a measurement of executive functions.; Outcome analyses: Index values at age 6 years.
BMI and waist circumference age 0-6 years	6 years	From parental reports every 6 months.; Outcome analyses: development of BMI and waist circumference age 0-6 years and current BMI and waist circumference at age 6.

Trial Locations

Locations (1)

Copenhagen University Hospital of Copenhagen; 🇩🇰 Gentofte, Denmark