孕妇补充Omega-3可减少子代的哮喘


  【24drs.com】根据发表于12月29日新英格兰医学期刊的一篇新研究,孕妇在第三孕期时于饮食中补充摄取omega-3 (ω-3)脂肪酸,可能有助于子代在5岁前降低哮喘与气喘的风险。
  
  研究作者、丹麦哥本哈根大学医院「Copenhagen Prospective Studies on Asthma in Childhood (COPSAC)」的Hans Bisgaard医师等人写道,第三孕期补充ω-3 LCPUFA [long-chain polyunsaturated fatty acid(长链多元不饱合脂肪酸)]可以降低子代的持续哮喘或气喘、下呼吸道感染的绝对风险达将近7个百分点,或相当于三分之一。
  
  虽然越来越多的证据认为,怀孕期间摄取ω-3 LCPUFAs不足可能与子代的气喘及哮喘风险增加有关,但是,评估孕妇摄取ω-3 LCPUFA补充品之随机控制试验的结果各异。
  
  因此,Bisgaard医师等人进行了一篇双盲随机安慰剂控制试验,检视孕妇摄取高剂量ω-3 LCPUFA补充品对于子代持续哮喘与气喘之风险的效果。
  
  他们随机指定怀孕24周的736名孕妇接受每天2.4 g之ω-3 LCPUFA (ω-3多元不饱合脂肪酸EPA;鱼油)或安慰剂(橄榄油),这些妇女持续服用补充品直到产后一周。
  
  分娩后,这些子代组成「Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010)」世代,追踪综合临床表型直到3岁,接著是2年的追踪期。
  
  该研究的初级结果是持续哮喘或气喘,次级结果包括下呼吸道感染、气喘恶化、湿疹、过敏性致敏反应。
  
  研究者发现,第三孕期摄取高剂量ω-3 LCPUFA补充品可显著降低子代在5岁前的持续哮喘和气喘风险(16.9% vs 23.7%; 风险比[HR], 0.69; 95%信赖区间[CI], 0.49 - 0.97; P = .035)。他们指出,这相当于相对降低了30.7%。
  
  此外,摄取此补充品降低持续哮喘和气喘风险的效益,在那些开始使用补充品之前、血中ω-3 LCPUFAs值最低之三分之一的孕妇,其孩童的效益最高(17.5% vs 34.1%; HR, 0.46; 95% CI, 0.25 - 0.83; P = .011),这相当于相对降低了54.1%。
  
  孕妇使用ω-3 LCPUFA补充品也可降低孩童的下呼吸道感染比率(31.7% vs 39.1%; HR, 0.75; 95% CI, 0.58 - 0.98; P = .033),不过,并不会显著影响气喘恶化、湿疹或过敏性致敏反应的风险。
  
  作者们强调,因为该研究使用集中式的、纵向临床追踪、每日记录孩童的症状,并经常访视临床照护研究单位,而强化了研究发现。
  
  他们写道,COPSAC实际上是出生世代的初级健康照护中心,因而确保使用标准化的诊断和治疗方法,这种方法大幅提高了诊断的可靠性。
  
  在一篇编辑评论中,来自马里兰州Bethesda国家酒精滥用与酒瘾研究院、巴尔的摩国家老化研究院的Christopher E. Ramsden医师认可这项试验的主要优点,包括它是双盲随机安慰剂控制设计、中到大型样本数、低退出率、广泛使用临床表型。
  
  Ramsden医师强调,研究开始时的血中EPA和DHA值低孕妇的小孩,鱼油的预防效应最大,他指出,脂肪酸去饱和酶基因编码变异孕妇所生孩童的预防效果也是最大。脂肪酸去饱和酶和从饮食中的α-亚麻酸制造EPA(20:5ω-3)和DHA (22:6ω-3)的能力降低有关。
  
  他强调,总之,这些观察支持了研究结果的合理性,并指向一种精确医学方法,其中的因素包括血中脂肪酸值、基因型、以及双亲的气喘病史,这些因素可用来为那些最可能受益者修改介入方式。
  
  不过,Ramsden医师也指出,本试验使用的EPA加DHA之剂量(2.4 g/天)比美国的平均每日LCPUFAs摄取量高了约15-20倍。因此,在这些结果应用到临床实务之前,他强调,需要确保这种高剂量不会对行为或认知之长期结果有所影响。
  
  他结论指出,须进行后续研究,以确认较低的剂量是否有效、在其它人口是否可以复制这些结果。
  
  资料来源:http://www.24drs.com/
  
  Native link:Maternal Omega-3 Supplementation Reduces Wheeze in Offspring

Maternal Omega-3 Supplementation Reduces Wheeze in Offspring

By Nicola M. Parry, DVM
Medscape Medical News

Supplementing a mother's diet with omega-3 (n-3) fatty acids during the third trimester of pregnancy may decrease the risk for persistent wheeze and asthma during her child's first 5 years, according to a new study published in the December 29 issue of the New England Journal of Medicine.

"Supplementation with n-3 LCPUFA [long-chain polyunsaturated fatty acid] 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," write Hans Bisgaard, MD, DMSc, from Copenhagen Prospective Studies on Asthma in Childhood (COPSAC), Copenhagen University Hospital, Denmark, and colleagues.

Although increasing evidence has suggested that deficient maternal intake of n-3 LCPUFAs during pregnancy may be associated with increased risk for asthma and wheezing in the offspring, randomized controlled trials to evaluate the effect of maternal n-3 LCPUFA supplementation have shown conflicting results.

Dr Bisgaard and colleagues therefore conducted a double-blind, randomized, placebo-controlled trial to examine the effect of high-dose n-3 LCPUFA supplementation in pregnant women on the risk for persistent wheeze and asthma in the offspring.

They randomly assigned 736 pregnant women at 24 weeks of pregnancy to receive 2.4 g n-3 LCPUFA (n-3 polyunsaturated fatty acids eicosapentaenoic acid and docosahexaenoic acid; fish oil) or placebo (olive oil) per day. The women continued to take the supplements until 1 week after delivery.

After birth, the children then formed the Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010) cohort and were followed for the first 3 years of life with comprehensive clinical phenotyping, after which there was a 2-year follow-up period.

The study's primary outcome was persistent wheeze or asthma. Secondary outcomes included lower respiratory tract infections, asthma exacerbations, eczema, and allergic sensitization.

The researchers found that high-n-3 LCPUFA supplementation during the third trimester of pregnancy significantly reduced the child's risk for persistent wheeze and asthma during the first 5 years of life (16.9% vs 23.7%; hazard ratio [HR], 0.69; 95% confidence interval [CI], 0.49 - 0.97; P = .035). This corresponded to a relative reduction of 30.7%, they add.

In addition, the effect of supplementation on the risk for persistent wheeze and asthma was greatest among children of mothers whose blood levels of n-3 LCPUFAs were in the lowest third of the trial population before supplementation began (17.5% vs 34.1%; HR, 0.46; 95% CI, 0.25 - 0.83; P = .011). This corresponded to a relative reduction of 54.1%.

Maternal n-3 LCPUFA supplementation also reduced the rate of lower respiratory infections (31.7% vs 39.1%; HR, 0.75; 95% CI, 0.58 - 0.98; P = .033) in the children. However, it did not significantly affect their risk for asthma exacerbations, eczema, or allergic sensitization.

The authors emphasize that these findings are enhanced by the study's use of centralized, longitudinal clinical follow-up, daily recording of children's symptoms, and frequent visits to the clinical research unit for care.

"COPSAC served as the de facto primary health care center for the birth cohort, thereby ensuring the use of a standardized approach to diagnosis and treatment," they write. "This approach greatly improves the reliability of the diagnoses."

In an accompanying editorial, Christopher E. Ramsden, MD, from the National Institute on Aging, Baltimore, and the National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland, acknowledges the major strengths of this trial. These include its double-blind, randomized, placebo-controlled design, moderate to large sample size, low dropout rate, and extensive use of clinical phenotyping.

Dr Ramsden highlights the finding that the preventive effect of fish oil was driven almost exclusively by children of mothers with low baseline blood levels of eicosapentaenoic acid and docosahexaenoic acid. He adds that this preventive effect was also greatest in children of mothers with a variant of the gene encoding fatty acid desaturase, an enzyme associated with low ability to produce eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3) from their dietary alpha-linolenic acid.

"Together, these observations support the plausibility of the findings and point toward a precision-medicine approach in which factors such as blood levels of fatty acids, genotype, and parental history of asthma could potentially be used to tailor interventions to those most likely to benefit," he emphasizes.

However, Dr Ramsden also notes that the dose of eicosapentaenoic acid plus docosahexaenoic acid used in this trial (2.4 g/day) was about 15 to 20 times higher than the average American's dietary intake of these LCPUFAs. Before the results are applied to clinical practice, he therefore stresses the need to ensure that this high dose does not adversely affect long-term outcomes such as behavior or cognition.

"Future work is also needed to determine whether lower doses are effective and whether these results can be replicated in other populations," he concludes.

COPSAC has reported receiving core support from the Lundbeck Foundation, the Danish Ministry of Health, the Danish Council for Strategic Research, the Danish Council for Independent Research, and the Capital Region Research Foundation. One coauthor holds a Canada Research Chair in Nutritional Lipidomics and receives salary support from the Canada Research Chairs program. Another coauthor has reported receiving consulting fees from Chiesi Pharmaceuticals and Boehringer Ingelheim. Two coauthors are named on a pending patent related to the prevention of childhood asthma through FADS genotyping and the assessment of blood levels of eicosapentaenoic acid and docosahexaenoic acid in pregnant mothers. The editorialist has disclosed no relevant financial relationships.

N Engl J Med. 2016;26:2530-2539, 2596-2598.

    
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