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The aim of this study is to prevent asthma and allergies in childhood by supplementation with fish oil (n-3 fatty acids) to the mother during pregnancy. Paticipants are mother and children participating in the ABC-(Asthma Begins in Childhood)cohort. Mothers are recruited during pregnancy and receive supplement with n-3 fatty acids or olive oil (placebo) from week 24 of gestation to 1 week after delivery. The child is followed with acute and planned visit at the research unit and diagnosis of disease is done in the research unit according to predefined algorithms.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Active Comparator | n-3 fatty acid |
|
| 2 | Placebo Comparator | Olive oil |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| n-3 fatty acid | Dietary Supplement | Oral intake of 4 capsules daily from week 24 of gestation to 1 week after delivery |
|
| Measure | Description | Time Frame |
|---|---|---|
| Persistent wheeze 0 to 3 years of age | 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 | 3 years |
| Measure | Description | Time Frame |
|---|---|---|
| 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 | 0-3 years |
| Infections |
| 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):
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| Name | Affiliation | Role |
|---|---|---|
| Klaus Bønnelykke, MD, PhD | COPSAC / University of Copenhagen | 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 |
|---|---|---|---|
| 41771441 | Derived | Rantala AK, Hakola L, Brustad N, Tapia G, Hard Af Segerstad EM, Lehtonen J, Thorsen J, Akerlund M, Parr CL, Magnus MC, Lund-Blix NA, Stokholm J, Knip M, Toppari J, Stordal K, Veijola R, Hyoty H, Virtanen SM, Bonnelykke K, Stene LC; HEDIMED Investigator Group. Marine n-3 Long-Chain Polyunsaturated Fatty Acid Intake in Pregnancy and Risk of Early Life Infections in 3 Nordic Cohorts: A HEDIMED Consortium Study. J Nutr. 2026 May;156(5):101456. doi: 10.1016/j.tjnut.2026.101456. Epub 2026 Feb 28. | |
| 39196551 |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| D004485 | Eczema |
| D006967 | Hypersensitivity |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D015525 | Fatty Acids, Omega-3 |
| D000069463 | Olive Oil |
| ID | Term |
|---|---|
| D004042 | Dietary Fats, Unsaturated |
| D004041 | Dietary Fats |
| D005223 | Fats |
| D008055 | Lipids |
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| olive oil | Dietary Supplement | Oral intake of 4 capsules (1 g) daily from 24 weeks of gestation to 1 week after delivery |
|
|
Main analysis:
• Number of lower respiratory tract infections registered in daily diaries
Secondary analyses:
| 0-3 years of age |
| Growth |
| 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 |
| Eczema | Age at onset of eczema diagnosed prospectively by research doctors according to predefined algorithm based upon Hanifin and Rajka criteria | 0-3 years |
| Allergic sensitization | Allergic sensitization at 6 and/or 18 months of age assessed by skin prick test and specific IgE in blood | 6 and 18 months of age |
| Systemic immune status | Main analysis
| 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 of age |
| 3-10 years of age |
| Infections | Prescribed medicine for infections. Types and length of infections | 3-10 years of age |
| Weight | Clinical follow up on the development of weight in kg (calibrated digital weight scales) at every visit till age 10 years assessed longitudinally in the research clinic. | 3-10 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 |
| MRI scanning of the brain | MRI scanning of the brain. The scanning procedure will take up to 1 hour. | 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). | 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 |
| 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 |
| Lung function measurements | Spirometry measuring airflow in liter. Compared with age and sex validated standards | [Time Frame: 5-10 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 |
| 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 | [Time Frame: 3-10 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. | [Time Frame: 3-13 years of age] |
| Airway resistance | sRaw measured by plethysmography at age 3, 4, 5, 6, 8 and 10 years. | [Time Frame: 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. | [Time Frame: 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. | 6 years of age. |
| Airway inflammation: | Measurement of fractional exhaled nitric oxide (FeNO) at age 6, 8 and 10 years | [Time Frame: 6-10 years of age] |
| Height | Clinical follow up on the development of height in cm (Harpenden stadiometer) at every visit till age 10 years assessed longitudinally in the research clinic. | [Time Frame: 3-10 years of age] |
| Waistcircumference | Clinical follow up on the development of waistcircumference in cm(using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic. | [Time Frame: 3-10 years of age] |
| Headcircumference | Clinical follow up on the development of headcircumference in cm(using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic. | [Time Frame: 3-10 years of age] |
| Thoraxcircumference | Clinical follow up on the development of thoraxcircumference in cm(using tape; 3 times each) at every visit till age 10 years assessed longitudinally in the research clinic. | [Time Frame: 3-10 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 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 |
| 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 |
| Allergic sensitization | Allergic sensitization assessed specific IgE in blood (ImmunoCAP, PHarmacia Diagnostics AB, Sweden). | 6 and 10 years of age |
| Næstved |
| Næstved |
| 4700 |
| Denmark |
| Derived |
| Chen L, Brustad N, Luo Y, Wang T, Ali M, Ebrahimi P, Schoos AM, Vahman N, Lovric M, Rasmussen MA, Kolmert J, Wheelock CE, Lasky-Su JA, Stokholm J, Bonnelykke K, Chawes B. Prenatal Fish Oil Supplementation, Maternal COX1 Genotype, and Childhood Atopic Dermatitis: A Secondary Analysis of a Randomized Clinical Trial. JAMA Dermatol. 2024 Oct 1;160(10):1082-1090. doi: 10.1001/jamadermatol.2024.2849. |
| 38569788 | Derived | Vinding RK, Sevelsted A, Horner D, Vahman N, Lauritzen L, Hagen CP, Chawes B, Stokholm J, Bonnelykke K. Fish oil supplementation during pregnancy, anthropometrics, and metabolic health at age ten: A randomized clinical trial. Am J Clin Nutr. 2024 Apr;119(4):960-968. doi: 10.1016/j.ajcnut.2023.12.015. Epub 2024 Feb 22. |
| 37696621 | Derived | Bisgaard H, Mikkelsen M, Rasmussen MA, Sevelsted A, Schoos AM, Brustad N, Eliasen AU, Thorsen J, Chawes B, Gurdeniz G, Morin A, Stark K, Stokholm J, Ober C, Pedersen CET, Bonnelykke K. Atopic and non-atopic effects of fish oil supplementation during pregnancy. Thorax. 2023 Dec;78(12):1168-1174. doi: 10.1136/thorax-2022-219725. Epub 2023 Sep 11. |
| 37380711 | Derived | Prince N, Kelly RS, Chu SH, Kachroo P, Chen Y, Mendez KM, Begum S, Bisgaard H, Bonnelykke K, Kim M, Levy O, Litonjua AA, Wheelock CE, Weiss ST, Chawes BL, Lasky-Su JA. Elevated third trimester corticosteroid levels are associated with fewer offspring infections. Sci Rep. 2023 Jun 28;13(1):10461. doi: 10.1038/s41598-023-36535-0. |
| 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. |
| 34927195 | Derived | Horner D, Hjelmso MH, Thorsen J, Rasmussen M, Eliasen A, Vinding RK, Schoos AM, Brustad N, Sunde RB, Bonnelykke K, Chawes BL, Stokholm J, Bisgaard H. Supplementation With Fish Oil in Pregnancy Reduces Gastroenteritis in Early Childhood. J Infect Dis. 2023 Feb 1;227(3):448-456. doi: 10.1093/infdis/jiab607. |
| 30418579 | Derived | Vinding RK, Stokholm J, Sevelsted A, Chawes BL, Bonnelykke K, Barman M, Jacobsson B, Bisgaard H. Fish Oil Supplementation in Pregnancy Increases Gestational Age, Size for Gestational Age, and Birth Weight in Infants: A Randomized Controlled Trial. J Nutr. 2019 Apr 1;149(4):628-634. doi: 10.1093/jn/nxy204. |
| 30181143 | Derived | Vinding RK, Stokholm J, Sevelsted A, Sejersen T, Chawes BL, Bonnelykke K, Thorsen J, Howe LD, Krakauer M, Bisgaard H. Effect of fish oil supplementation in pregnancy on bone, lean, and fat mass at six years: randomised clinical trial. BMJ. 2018 Sep 4;362:k3312. doi: 10.1136/bmj.k3312. |
| 28029926 | Derived | Bisgaard H, Stokholm J, Chawes BL, Vissing NH, Bjarnadottir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdottir S, Folsgaard NV, Fink NR, Thorsen J, Pedersen AG, Waage J, Rasmussen MA, Stark KD, Olsen SF, Bonnelykke K. Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. N Engl J Med. 2016 Dec 29;375(26):2530-9. doi: 10.1056/NEJMoa1503734. |
| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D007154 | Immune System Diseases |
| D003872 | Dermatitis |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D017443 | Skin Diseases, Eczematous |
| D005231 |
| Fatty Acids, Unsaturated |
| D005227 | Fatty Acids |
| D005395 | Fish Oils |
| D009821 | Oils |
| D005224 | Fats, Unsaturated |
| D010938 | Plant Oils |
| D005502 | Food |
| D000066888 | Diet, Food, and Nutrition |
| D010829 | Physiological Phenomena |
| D019602 | Food and Beverages |