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NCT Number: NCT06560255

Fish Oil in pREgnancY for Personalized Prevention of Early Childhood Asthma

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.

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Key information

About this study

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.

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

  • Pregnant Danish women before week 26 with blood levels of EPA+DHA below 4.7% of total fatty acids
  • No planned use of fish oil supplementations
  • No endocrine-, heart-, kidney- or auto-immune disorders
  • No disorders requiring treatment with blood thinning medication

Treatment and study plan

n-3 fatty acid

Dietary Supplement

Oral intake of 4 capsules per day from week 22-26 in pregnancy to 1 week after delivery

Other names: GoldenOmega, PharmaNord, DK

Rape seed oil

Other

Oral intake of 4 capsules per day from week 22-26 in pregnancy to 1 week after delivery

Other names: Placebo capsules, PharmaNord, DK

Primary outcomes

  1. Early childhood asthma/persistent wheeze age 0-3 years

    Time frame: 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 outcomes

  1. Atopic/non-atopic wheeze or asthma age 0-3 years

    Time frame: 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.

  2. Troublesome lung symptoms age 0-3 years

    Time frame: 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.

  3. Wheeze episodes age 0-3 years

    Time frame: 3 years

    Parental reports of wheezing.

    Outcome analyses: total no. of episodes with wheeze age 0-3 years.

  4. Inhaled bronchodilator use from parental reports age 0-3 years

    Time frame: 3 years

    Outcome analyses: total no. of days with bronchodilator use age 0-3.

  5. Inhaled bronchodilator prescriptions from medical record checks age 0-3 years

    Time frame: 3 years

    Outcome analyses: total no. of prescriptions age 0-3.

  6. Asthma controller medication use from parental reports age 0-3 years

    Time frame: 3 years

    Outcome analyses: total no. of days with use of asthma controller medication age 0-3.

  7. Asthma controller medication prescriptions from medical record checks age 0-3 years

    Time frame: 3 years

    Outcome analyses: total no. of prescriptions age 0-3.

  8. Asthma hospitalizations or emergency department visits age 0-3 years

    Time frame: 3 years

    Outcome analyses: total no. of episodes age 0-3 years.

  9. Eczema age 0-3 years

    Time frame: 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.

  10. Allergic rhinitis age 0-3 years

    Time frame: 3 years

    Based on parental reports of physician-diagnosed allergic rhinitis.

    Outcome analyses: allergic rhinitis (yes/no) by age 3 years.

  11. Food allergy 0-3 years

    Time frame: 3 years

    Parental reports of physician-diagnosed food allergy.

    Outcome analyses: any food allergy (yes/no) by age 3 years.

  12. Lower respiratory tract infections age 0-3 years

    Time frame: 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.

  13. Gastrointestinal infections age 0-3 years

    Time frame: 3 years

    Parental reports.

    Outcome analyses: risk (survival analysis) of any gastroenteritis episode and total no. of gastroenteritis episodes age 0-3 years.

  14. Croup age 0-3 years

    Time frame: 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.

  15. Fever episodes age 0-3 years

    Time frame: 3 years

    Based on parental reports.

    Outcome analyses: total no. of episodes with symptoms age 0-3 years.

  16. Absences from daycare age 0-3 years

    Time frame: 3 years

    Due to illnesses based on parental reports.

    Outcome analyses: total no. of absence days age 0-3 years.

  17. Bone fractures age 0-3 years

    Time frame: 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.

  18. Developmental milestones age 0-3 years

    Time frame: 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.

  19. Strength and difficulties at age 3 years

    Time frame: 3 years

    From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.

    Outcome analyses: SDQ scores at age 3 years.

  20. ADHD symptoms at age 3 years

    Time frame: 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.

  21. Social behavior assessment at age 3 years

    Time frame: 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.

  22. Psychopathology screening at age 3 years

    Time frame: 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.

  23. Cognitive assessment age 0-3 years

    Time frame: 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.

  24. BMI and waist circumference age 0-3 years

    Time frame: 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.

  25. Persistent wheeze or asthma age 0-6 years

    Time frame: 6 years

    Defined similarly to the primary outcome

    Outcome analysis: risk (survival analysis) of persistent wheeze or asthma at age 0-6 years

  26. Current asthma at age 6 years

    Time frame: 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.

  27. Asthma or wheeze yearly prevalence 0-6 years

    Time frame: 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.

  28. Atopic/non-atopic asthma at age 6 years

    Time frame: 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.

  29. Asthma controller medication 0-6 years

    Time frame: 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.

  30. Inhaled bronchodilators age 0-6 years

    Time frame: 6 years

    From redeemed inhaled bronchodilators based on medical record checks.

    Outcome analyses: total no. of prescriptions age 0-6 years.

  31. Asthma hospitalizations or emergency department visits age 0-6 years

    Time frame: 6 years

    Based on medical record checks.

    Outcome analyses: total no. of episodes age 0-6 years.

  32. Eczema age 0-6 years

    Time frame: 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.

  33. Allergic rhinitis age 0-6 years

    Time frame: 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.

  34. Food allergy age 0-6 years

    Time frame: 6 years

    Based on parental reports of physician-diagnosed food allergy.

    Outcome analyses: any food allergy (yes/no) by age 6 years.

  35. Lower respiratory tract infections age 0-6 years

    Time frame: 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.

  36. Gastrointestinal infections age 0-6 years

    Time frame: 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.

  37. Croup age 0-6 years

    Time frame: 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.

  38. Bone fractures age 0-6 years

    Time frame: 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.

  39. Strength and difficulties at age 6 years

    Time frame: 6 years

    From the Strengths and Difficulties Questionnaire (SDQ), which is a brief behavioral screening questionnaire.

    Outcome analyses: SDQ scores at age 6 years.

  40. ADHD symptoms at age 6 years

    Time frame: 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.

  41. Social behavior assessment at age 6 years

    Time frame: 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.

  42. Psychopathology screening at age 6 years

    Time frame: 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.

  43. Cognitive assessment age 0-6 years

    Time frame: 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.

  44. BMI and waist circumference age 0-6 years

    Time frame: 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Klaus Bønnelykke, PhD

CONTACT

[email protected]

+45 38677360

Ulrik Ralfkiaer, PhD

CONTACT

[email protected]

+45 38674164

Sponsors and collaborators

Lead sponsor

Professor Klaus Bønnelykke

Other

Registry information

Official study title

Fish Oil in pREgnancY for Personalized Prevention of Early Childhood Asthma (FREYA)

Acronym: FREYA

Important dates

Study start
2024
Primary completion
2026
Study completion
2033
First posted
Aug 19, 2024
Registry last updated
Sep 30, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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