title: Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.
abstract: Reduced intake of n-3 long-chain polyunsaturated fatty acids (LCPUFAs) may be a contributing factor to the increasing prevalence of wheezing disorders. We assessed the effect of supplementation with n-3 LCPUFAs in pregnant women on the risk of persistent wheeze and asthma in their offspring.
  
  
  
  We randomly assigned 736 pregnant women at 24 weeks of gestation to receive 2.4 g of n-3 LCPUFA (fish oil) or placebo (olive oil) per day. Their children formed the Copenhagen Prospective Studies on Asthma in Childhood2010(COPSAC2010) cohort and were followed prospectively with extensive clinical phenotyping. Neither the investigators nor the participants were aware of group assignments during follow-up for the first 3 years of the children's lives, after which there was a 2-year follow-up period during which only the investigators were unaware of group assignments. The primary end point was persistent wheeze or asthma, and the secondary end points included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.
  
  
  
  A total of 695 children were included in the trial, and 95.5% completed the 3-year, double-blind follow-up period. The risk of persistent wheeze or asthma in the treatment group was 16.9%, versus 23.7% in the control group (hazard ratio, 0.69; 95% confidence interval [CI], 0.49 to 0.97; P=0.035), corresponding to a relative reduction of 30.7%. Prespecified subgroup analyses suggested that the effect was strongest in the children of women whose blood levels of eicosapentaenoic acid and docosahexaenoic acid were in the lowest third of the trial population at randomization: 17.5% versus 34.1% (hazard ratio, 0.46; 95% CI, 0.25 to 0.83; P=0.011). Analyses of secondary end points showed that supplementation with n-3 LCPUFA was associated with a reduced risk of infections of the lower respiratory tract (31.7% vs. 39.1%; hazard ratio, 0.75; 95% CI, 0.58 to 0.98; P=0.033), but there was no statistically significant association between supplementation and asthma exacerbations, eczema, or allergic sensitization.
  
  
  
  Supplementation with n-3 LCPUFA in the third trimester of pregnancy reduced the absolute risk of persistent wheeze or asthma and infections of the lower respiratory tract in offspring by approximately 7 percentage points, or one third. (Funded by the Lundbeck Foundation and others; ClinicalTrials.gov number, NCT00798226 .).
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Hans
authors.initials: H
authors.lastname: Bisgaard
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Jakob
authors.initials: J
authors.lastname: Stokholm
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Bo L
authors.initials: BL
authors.lastname: Chawes
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Nadja H
authors.initials: NH
authors.lastname: Vissing
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Elin
authors.initials: E
authors.lastname: Bjarnadóttir
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Ann-Marie M
authors.initials: AM
authors.lastname: Schoos
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Helene M
authors.initials: HM
authors.lastname: Wolsk
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Tine M
authors.initials: TM
authors.lastname: Pedersen
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Rebecca K
authors.initials: RK
authors.lastname: Vinding
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Sunna
authors.initials: S
authors.lastname: Thorsteinsdóttir
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Nilofar V
authors.initials: NV
authors.lastname: Følsgaard
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Nadia R
authors.initials: NR
authors.lastname: Fink
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Jonathan
authors.initials: J
authors.lastname: Thorsen
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Anders G
authors.initials: AG
authors.lastname: Pedersen
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Johannes
authors.initials: J
authors.lastname: Waage
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Morten A
authors.initials: MA
authors.lastname: Rasmussen
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Ken D
authors.initials: KD
authors.lastname: Stark
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Sjurdur F
authors.initials: SF
authors.lastname: Olsen
authors.affiliation: From COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen (H.B., J.S., B.L.C., N.H.V., E.B., A.-M.M.S., H.M.W., T.M.P., R.K.V., S.T., N.V.F., N.R.F., J.T., J.W., M.A.R., K.B.), and the Center for Fetal Programming, Statens Serum Institut (S.F.O.), Copenhagen, the Department of Pediatrics, Naestved Hospital, Naestved (J.S., E.B., T.M.P., R.K.V.), DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby (A.G.P.), and Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen (M.A.R.) - all in Denmark; the Department of Kinesiology, University of Waterloo, Waterloo, ON, Canada (K.D.S.); and the Department of Nutrition, Harvard School of Public Health, Boston (S.F.O.).
authors.forename: Klaus
authors.initials: K
authors.lastname: Bønnelykke
mesh_terms: D001249:Asthma / Q000453:epidemiology / Q000517:prevention & control*; D002675:Child, Preschool; D019587:Dietary Supplements; D004311:Double-Blind Method; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage* / Q000097:blood; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D055118:Medication Adherence; D000069463:Olive Oil / Q000008:administration & dosage; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D012135:Respiratory Sounds / Q000187:drug effects*; D012141:Respiratory Tract Infections / Q000453:epidemiology / Q000517:prevention & control; D012306:Risk
chemical_list: D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D000069463:Olive Oil