妊娠女性服用鱼油有助降低后代发生哮喘和下呼吸道感染的风险
2016年12月29日，美国麻省（马萨诸塞）医学会官方期刊《新英格兰医学杂志》正式发表丹麦哥本哈根大学、海莱乌和根措夫特医院、奈斯坦德医院、丹麦技术大学、加拿大滑铁卢大学、美国哈佛大学公共卫生学院的哥本哈根儿童哮喘前瞻研究（COPSAC），发现妊娠女性在妊娠的最后三个月内服用鱼油补充剂，有助降低后代发生哮喘和下呼吸道感染的风险。
该研究将736位妊娠女性随机分为两组，从妊娠第24周起每天服用2.4g的鱼油（n-3长链多不饱和脂肪酸）或橄榄油（安慰剂），她们的后代组成哥本哈根儿童哮喘前瞻研究（COPSAC）队列，随后进行广泛临床表型分析。随访前3年，研究者和参与者都不知分组（双盲），之后2年随访期间，仅研究者不知分组（单盲）。共有695位儿童入组，95.5%完成3年双盲随访期。主要观察终点为持续哮鸣或哮喘，次要观察终点包括下呼吸道感染、哮喘加重、湿疹、变应性致敏。
结果发现，随访至3～5岁时，治疗组、对照组儿童的持续哮鸣或哮喘风险分别为16.9%、23.7%（风险比：0.69，95%置信区间：0.49～0.97，P=0.035），相对风险降低30.7%。从出生随访至5岁时，治疗组儿童的持续哮鸣或哮喘风险降低32%（风险比：0.68，95%置信区间：0.49～0.95，P=0.024），每年持续哮鸣或哮喘发生率降低32%（比值比：0.68，95%置信区间：0.47～0.98，P=0.038）。
预设亚组分析表明，服用鱼油对随机分组时血液二十碳五烯酸（EPA）和二十二碳六烯酸（DHA）水平最低三分之一研究人群女性的儿童最有效，持续哮鸣或哮喘风险降低54%（17.5%比34.1%，风险比：0.46，95%置信区间：0.25～0.83，P=0.011）。
次要观察终点分析显示，补充鱼油可使下呼吸道感染风险显著降低25%（31.7%比39.1%，风险比：0.75；95%置信区间：0.58～0.98，P=0.033），但是与哮喘急性加重、湿疹、变应性致敏之间无统计学显著相关性。
因此，作者认为妊娠女性在妊娠的最后三个月内服用鱼油补充剂，有助降低后代发生哮喘和下呼吸道感染的风险。
该研究由丹麦的灵北基金会和丹麦卫生部等机构赞助，部分作者拥有通过母亲基因和血液检测预防哮喘的未决专利。
对此，美国国家卫生研究院的学者发表同期述评：鱼油有助于呼吸——预防哮喘的新方法？认为该研究结果非常有前途，鱼油补充剂对于有哮喘家族史的女性是合理的，特别由于其价格较低，而且未见严重不良反应。但是，该研究每天2.4g的鱼油剂量是美国人每天从食物中摄入量的15～20倍，故在推荐妊娠女性服用鱼油预防后代哮喘之前，还要研究如此大的剂量是否会对行为、思维能力或健康产生不良影响，此外也需了解小剂量鱼油是否有效，以及该研究结果能否在其他人群中重复。
此外，美国国家卫生研究院、哈佛医学院布莱根女子医院、南澳大利亚健康医学研究所的学者还发表了同期病例讨论：妊娠期间是否应该补充鱼油？对其利弊进行了辩论。
N Engl J Med. 2016 Dec 29;375(26):2530-9.
Fish Oil-Derived Fatty Acids in Pregnancy and Wheeze and Asthma in Offspring.
Bisgaard H, Stokholm J, Chawes BL, Vissing NH, Bjarnadóttir E, Schoos AM, Wolsk HM, Pedersen TM, Vinding RK, Thorsteinsdóttir S, Folsgaard NV, Fink NR, Thorsen J, Pedersen AG, Waage J, Rasmussen MA, Stark KD, Olsen SF, Bonnelykke K.
COPSAC (Copenhagen Prospective Studies on Asthma in Childhood), Herlev and Gentofte Hospital, University of Copenhagen; Center for Fetal Programming, Statens Serum Institut, Copenhagen, Naestved Hospital, Naestved, DTU Bioinformatics, Technical University of Denmark, Kongens Lyngby, Faculty of Science, Chemometrics and Analytical Technology, University of Copenhagen - all in Denmark; University of Waterloo, Waterloo, ON, Canada; Harvard School of Public Health, Boston.
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 Childhood 2010 (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.
Funded by the Lundbeck Foundation and others.
ClinicalTrials.gov number: NCT00798226
PMID: 28029926
DOI: 10.1056/NEJMoa1503734
N Engl J Med. 2016 Dec 29;375(26):2596-8.
Breathing Easier with Fish Oil - A New Approach to Preventing Asthma?
Ramsden CE.
National Institute on Aging, in Baltimore, National Institute on Alcohol Abuse and Alcoholism, in Bethesda, MD.
PMID: 28029914
DOI: 10.1056/NEJMe1611723
N Engl J Med. 2016 Dec 29;375(26):2599-2601.
Fish Oil Supplementation in Pregnancy.
Ramaswami R, Serhan CN, Levy BD, Makrides M.
National Institute of Allergy and Infectious Diseases, Bethesda, MD; Brigham and Women's Hospital, Harvard Medical School, Boston; South Australian Health and Medical Research Institute, North Adelaide, SA, Australia.
PMID: 28029929
DOI: 10.1056/NEJMclde1614333