Fish Oil Supplementation During Pregnancy for Prevention of Asthma, Eczema and Allergies in Childhood

Fish Oil Supplementation During Pregnancy for Prevention of Asthma, Eczema and Allergies in Childhood: Interventional Trial in the COPSAC2010 (Copenhagen Studies on Asthma in Childhood) Birth Cohort

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Asthma; Allergy; Eczema
• Intervention / Treatment: Dietary supplement: n-3 fatty acid; Dietary supplement: olive oil

• Study Type: Interventional
• Enrollment (Estimated): 800
• Phase: Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Gentofte
    • Gentofte Municipality, Gentofte, Denmark, 2820
      • Copenhagen University Hospital of Copenhagen
  • Næstved
    • Næstved, Næstved, Denmark, 4700
      • Næstved Hospital, Pediatric Department

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria (mother):

• Pregnant women
• Living in Sealand, Denmark
• Fluent in Danish Language
• Willing to let the newborn child participate in the study

Exclusion Criteria (mother):

• Participating in other clinical trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; n-3 fatty acid	Dietary supplement: n-3 fatty acid; Oral intake of 4 capsules daily from week 24 of gestation to 1 week after delivery; Other Names: Incromega (Croda Nordica AB), Krossverksgatan 5 C, SE-216 16 Limhamn, Sweden
Placebo Comparator: 2; Olive oil	Dietary supplement: olive oil; Oral intake of 4 capsules (1 g) daily from 24 weeks of gestation to 1 week after delivery; Other Names: Pharmatech AS, Po 85, 1662 Rolvsøy, Norway

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Secondary Outcome Measures

Outcome Measure	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	Main analysis: • Number of lower respiratory tract infections registered in daily diaries Secondary analyses: Acute otitis media; Number of upper respiratory tract infections; Number of other infections; Total number of infections	0-3 years of age
Growth	Body composition (fat mass and bone mineral density) assessed by DEXA scan at 3 years of age; Development of BMI from birth to 3 years assesses longitudinally in the research clinic	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: Milestone development monitored prospectively by the parents using a registration form based on The Denver Development Index and WHO milestones registration (combined assessment by principal component analysis); Language development assessed at 1 and 2 years of age with the Danish version of The MacArthur Bates Communicative Developmental Inventory (CDI); The child´s general development (language, fine and gross motor, social and problem solving) at 3 years of age assessed with Ages and stages Questioner, third edition (ASQ-3)	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; Immune status at 18 months measured in stimulated whole blood as cytokine release (combined assessments by prinicipal component analyses) Secondary analyses; Composition of immune cell subsets in whole blood at birth and at 18 months of age	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

Other Outcome Measures

Outcome Measure	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.	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]
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
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]

Collaborators and Investigators

• Sponsor: Copenhagen Studies on Asthma in Childhood
• Investigators: Principal Investigator: Klaus Bønnelykke, MD, PhD, COPSAC / University of Copenhagen

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): November 26, 2008
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: November 25, 2008
• First Submitted That Met QC Criteria: November 25, 2008
• First Posted (Estimated): November 26, 2008

Study Record Updates

• Last Update Posted (Actual): June 5, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Asthma; Allergy; Eczema; Sensitization
• Additional Relevant MeSH Terms: Immune System Diseases; Respiratory Tract Diseases; Lung Diseases; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Skin Diseases; Skin Diseases, Eczematous; Dermatitis; Skin and Connective Tissue Diseases; Asthma; Hypersensitivity; Eczema; Fatty Acids; Lipids; Food; Diet, Food, and Nutrition; Physiological Phenomena; Food and Beverages; Fatty Acids, Unsaturated; Plant Oils; Oils; Dietary Fats; Fats; Dietary Fats, Unsaturated; Fish Oils; Fats, Unsaturated; Olive Oil; Fatty Acids, Omega-3
• Other Study ID Numbers: H-B-2008-093

Drug and device information, study documents

• product manufactured in and exported from the U.S.: No