孕婦補充Omega-3可減少子代的哮喘


  【24drs.com】根據發表於12月29日新英格蘭醫學期刊的一篇新研究,孕婦在第三孕期時於飲食中補充攝取omega-3 (ω-3)脂肪酸,可能有助於子代在5歲前降低哮喘與氣喘的風險。
  
  研究作者、丹麥哥本哈根大學醫院「Copenhagen Prospective Studies on Asthma in Childhood (COPSAC)」的Hans Bisgaard醫師等人寫道,第三孕期補充ω-3 LCPUFA [long-chain polyunsaturated fatty acid(長鍊多元不飽合脂肪酸)]可以降低子代的持續哮喘或氣喘、下呼吸道感染的絕對風險達將近7個百分點,或相當於三分之一。
  
  雖然越來越多的證據認為,懷孕期間攝取ω-3 LCPUFAs不足可能與子代的氣喘及哮喘風險增加有關,但是,評估孕婦攝取ω-3 LCPUFA補充品之隨機控制試驗的結果各異。
  
  因此,Bisgaard醫師等人進行了一篇雙盲隨機安慰劑控制試驗,檢視孕婦攝取高劑量ω-3 LCPUFA補充品對於子代持續哮喘與氣喘之風險的效果。
  
  他們隨機指定懷孕24週的736名孕婦接受每天2.4 g之ω-3 LCPUFA (ω-3多元不飽合脂肪酸EPA;魚油)或安慰劑(橄欖油),這些婦女持續服用補充品直到產後一週。
  
  分娩後,這些子代組成「Copenhagen Prospective Studies on Asthma in Childhood2010 (COPSAC2010)」世代,追蹤綜合臨床表型直到3歲,接著是2年的追蹤期。
  
  該研究的初級結果是持續哮喘或氣喘,次級結果包括下呼吸道感染、氣喘惡化、濕疹、過敏性致敏反應。
  
  研究者發現,第三孕期攝取高劑量ω-3 LCPUFA補充品可顯著降低子代在5歲前的持續哮喘和氣喘風險(16.9% vs 23.7%; 風險比[HR], 0.69; 95%信賴區間[CI], 0.49 - 0.97; P = .035)。他們指出,這相當於相對降低了30.7%。
  
  此外,攝取此補充品降低持續哮喘和氣喘風險的效益,在那些開始使用補充品之前、血中ω-3 LCPUFAs值最低之三分之一的孕婦,其孩童的效益最高(17.5% vs 34.1%; HR, 0.46; 95% CI, 0.25 - 0.83; P = .011),這相當於相對降低了54.1%。
  
  孕婦使用ω-3 LCPUFA補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),不過,並不會顯著影響氣喘惡化、濕疹或過敏性致敏反應的風險。
  
  作者們強調,因為該研究使用集中式的、縱向臨床追蹤、每日記錄孩童的症狀,並經常訪視臨床照護研究單位,而強化了研究發現。
  
  他們寫道,COPSAC實際上是出生世代的初級健康照護中心,因而確保使用標準化的診斷和治療方法,這種方法大幅提高了診斷的可靠性。
  
  在一篇編輯評論中,來自馬里蘭州Bethesda國家酒精濫用與酒癮研究院、巴爾的摩國家老化研究院的Christopher E. Ramsden醫師認可這項試驗的主要優點,包括它是雙盲隨機安慰劑控制設計、中到大型樣本數、低退出率、廣泛使用臨床表型。
  
  Ramsden醫師強調,研究開始時的血中EPA和DHA值低孕婦的小孩,魚油的預防效應最大,他指出,脂肪酸去飽和酶基因編碼變異孕婦所生孩童的預防效果也是最大。脂肪酸去飽和酶和從飲食中的α-亞麻酸製造EPA(20:5ω-3)和DHA (22:6ω-3)的能力降低有關。
  
  他強調,總之,這些觀察支持了研究結果的合理性,並指向一種精確醫學方法,其中的因素包括血中脂肪酸值、基因型、以及雙親的氣喘病史,這些因素可用來為那些最可能受益者修改介入方式。
  
  不過,Ramsden醫師也指出,本試驗使用的EPA加DHA之劑量(2.4 g/天)比美國的平均每日LCPUFAs攝取量高了約15-20倍。因此,在這些結果應用到臨床實務之前,他強調,需要確保這種高劑量不會對行為或認知之長期結果有所影響。
  
  他結論指出,須進行後續研究,以確認較低的劑量是否有效、在其他人口是否可以複製這些結果。
  
  資料來源: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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