Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

Hans Bisgaard; Jakob Stokholm; Bo L Chawes; Nadja H. Vissing; Elín Bjarnadóttir; Ann-Marie Malby Schoos; Helene M Wolsk; Tine M Pedersen; Rebecca Kofod Vinding; Sunna Thorsteinsdóttir; Nilofar V Følsgaard; Nadia R Fink; Jonathan Thorsen; Anders G. Pedersen; Johannes Waage; Morten Arendt Rasmussen; Ken D Stark; Sjurdur F Olsen; Klaus Bønnelykke

doi:10.1056/nejmoa1503734

Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

Hans Bisgaard, Jakob Stokholm, Bo L Chawes, Nadja H. Vissing, Elín Bjarnadóttir, Ann-Marie Malby Schoos, Helene M Wolsk, Tine M Pedersen, Rebecca Kofod Vinding, Sunna Thorsteinsdóttir, Nilofar V Følsgaard, Nadia R Fink, Jonathan Thorsen, Anders G. Pedersen, Johannes Waage, Morten Arendt Rasmussen, Ken D Stark, Sjurdur F Olsen, Klaus Bønnelykke

204 Citations (Scopus)

Abstract

BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

Original language	English
Journal	New England Journal of Medicine
Volume	375
Issue number	26
Pages (from-to)	2530-2539
Number of pages	10
ISSN	0028-4793
DOIs	https://doi.org/10.1056/nejmoa1503734
Publication status	Published - 29 Dec 2016

Keywords

Asthma
Child, Preschool
Dietary Supplements
Double-Blind Method
Fatty Acids, Omega-3
Female
Fish Oils
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Male
Medication Adherence
Olive Oil
Pregnancy
Pregnancy Trimester, Third
Respiratory Sounds
Respiratory Tract Infections
Risk
Journal Article
Randomized Controlled Trial

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Bisgaard, H., Stokholm, J., Chawes, B. L., Vissing, N. H., Bjarnadóttir, E., Schoos, A.-M. M., Wolsk, H. M., Pedersen, T. M., Vinding, R. K., Thorsteinsdóttir, S., Følsgaard, N. V., Fink, N. R., Thorsen, J., Pedersen, A. G., Waage, J., Rasmussen, M. A., Stark, K. D., Olsen, S. F., & Bønnelykke, K. (2016). Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring. New England Journal of Medicine, 375(26), 2530-2539. https://doi.org/10.1056/nejmoa1503734

Bisgaard, H, Stokholm, J, Chawes, BL, Vissing, NH, Bjarnadóttir, E, Schoos, A-MM, Wolsk, HM, Pedersen, TM, Vinding, RK, Thorsteinsdóttir, S, Følsgaard, NV, Fink, NR, Thorsen, J, Pedersen, AG, Waage, J, Rasmussen, MA, Stark, KD, Olsen, SF & Bønnelykke, K 2016, 'Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring', New England Journal of Medicine, vol. 375, no. 26, pp. 2530-2539. https://doi.org/10.1056/nejmoa1503734

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abstract = "BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.",

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year = "2016",

month = dec,

day = "29",

doi = "10.1056/nejmoa1503734",

language = "English",

volume = "375",

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TY - JOUR

T1 - Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

AU - Bisgaard, Hans

AU - Stokholm, Jakob

AU - Chawes, Bo L

AU - Vissing, Nadja H.

AU - Bjarnadóttir, Elín

AU - Schoos, Ann-Marie Malby

AU - Wolsk, Helene M

AU - Pedersen, Tine M

AU - Vinding, Rebecca Kofod

AU - Thorsteinsdóttir, Sunna

AU - Følsgaard, Nilofar V

AU - Fink, Nadia R

AU - Thorsen, Jonathan

AU - Pedersen, Anders G.

AU - Waage, Johannes

AU - Rasmussen, Morten Arendt

AU - Stark, Ken D

AU - Olsen, Sjurdur F

AU - Bønnelykke, Klaus

PY - 2016/12/29

Y1 - 2016/12/29

N2 - BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

AB - BACKGROUND 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. METHODS 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. RESULTS 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. CONCLUSIONS 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.

KW - Asthma

KW - Child, Preschool

KW - Dietary Supplements

KW - Double-Blind Method

KW - Fatty Acids, Omega-3

KW - Female

KW - Fish Oils

KW - Follow-Up Studies

KW - Humans

KW - Kaplan-Meier Estimate

KW - Male

KW - Medication Adherence

KW - Olive Oil

KW - Pregnancy

KW - Pregnancy Trimester, Third

KW - Respiratory Sounds

KW - Respiratory Tract Infections

KW - Risk

KW - Journal Article

KW - Randomized Controlled Trial

U2 - 10.1056/nejmoa1503734

DO - 10.1056/nejmoa1503734

M3 - Journal article

C2 - 28029926

SN - 0028-4793

VL - 375

SP - 2530

EP - 2539

JO - New England Journal of Medicine

JF - New England Journal of Medicine

IS - 26

ER -

Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring

Abstract

Keywords

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