Wang Hang Zhen, Hayles Elizabeth H, Fiander Michelle, Sinn John Kh, Osborn David A
Macquarie Medical School, Macquarie University, Sydney, Australia.
Department of Neonatology, Royal North Shore Hospital, The University of Sydney, St Leonards, Australia.
Cochrane Database Syst Rev. 2025 Jun 13;6(6):CD006475. doi: 10.1002/14651858.CD006475.pub3.
RATIONALE: This is an update of a Cochrane review first published in 2007. Allergic disease and food allergy are prevalent, and contribute to a significant burden of disease on the individual, their family and the healthcare system. Probiotics are live bacteria that colonise the gastrointestinal tract, and have been studied in many clinical trials for preventing allergic conditions. OBJECTIVES: To evaluate the benefits and harms of a probiotic, or a probiotic with added prebiotic ('synbiotic'), compared with control (placebo or no treatment) for preventing allergic diseases (asthma, eczema, allergic rhinitis) and dietary allergies in infants by two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase and trial registries in December 2023. We reviewed the reference lists of studies selected for inclusion in this review, and systematic reviews on similar topics. We manually searched conference abstracts. ELIGIBILITY CRITERIA: We included randomised controlled trials that compared a probiotic to a control, or a probiotic added to a prebiotic ('synbiotic'). We included enterally fed infants in the first six months of life without clinical evidence of allergic disease. We included probiotics added to human milk or infant formula, added in the manufacturing process or given separately. OUTCOMES: Infant incidence by two years of age and childhood incidence (up to 10 years of age or up to the age of latest report between 2 and 10 years) of specific allergic diseases, including: asthma, eczema, allergic rhinitis, immunoglobulin E (IgE)-mediated food allergy, IgE-mediated cow's milk protein allergy. Events of anaphylaxis and potential harms including adverse effects, harms or infection with probiotic bacteria. RISK OF BIAS: We used the Cochrane RoB 2 tool to assess bias in the studies. SYNTHESIS METHODS: We used the random-effects (Mantel-Haenszel) model for meta-analysis where possible. Where this was not possible due to the nature of the data, we synthesised and interpreted individual studies separately. We used GRADE to assess the certainty of evidence for each outcome. INCLUDED STUDIES: We included 24 studies (7077 mother-infant pairs). The studies were conducted in many parts of the world, including the USA, Europe, South Korea, Japan, Singapore and Australia, with most being conducted in Europe. Studies were published between 2001 and 2020. As some studies measured outcomes such as eczema using different criteria, we made assumptions to allow us to combine data. SYNTHESIS OF RESULTS: Probiotics may result in little to no difference in asthma (risk ratio (RR) 0.96, 95% confidence interval (CI) 0.65 to 1.44; 4 studies, 954 participants; low-certainty evidence), allergic rhinitis (RR 0.89, 95% CI 0.45 to 1.77; 5 studies, 1045 participants; low-certainty evidence) and IgE-mediated cow's milk protein allergy (RR 0.99, 95% CI 0.82 to 1.20; 4 studies, 259 participants; low-certainty evidence) by two years of age. Probiotics may result in a slight reduction in eczema by two years of age (RR 0.87, 95% CI 0.78 to 0.97; 18 studies, 3494 participants; low-certainty evidence); however, sensitivity analysis of the studies at low risk of bias showed little or no difference in eczema by two years of age (RR 0.86, 95% CI 0.69 to 1.07; 4 studies, 892 participants). Probiotic supplementation may have little to no effect on the incidence of food allergy by two years, but the evidence is very uncertain (RR 1.12, 95% CI 0.57 to 2.20; 3 studies, 857 participants; very low-certainty evidence). The evidence is very uncertain about the effect of synbiotics on eczema by two years of age (RR 0.88, 95% CI 0.52 to 1.47; 3 studies, 1235 participants; very low-certainty evidence). Synbiotics may result in little to no difference in food allergy by two years of age (RR 1.06, 95% CI 0.55 to 2.07; 1 study, 223 participants; low-certainty evidence). There were no data for the effect of synbiotics on asthma, allergic rhinitis and IgE-mediated cow's milk protein allergy by two years of age. Probiotic or synbiotic supplementation may result in little to no difference in potential harms including adverse effects, harms or infection with probiotic bacteria at any point during the study intervention by two years of age. There were no serious adverse events related to probiotics or synbiotics reported. We had some concerns about risk of bias for most studies, with only a few judged at low risk of bias. Some studies had a high risk of bias due to unclear randomisation, missing data and lack of prespecified intentions. Estimates were often imprecise, with wide CIs due to limited events. The limited data prevented subgroup analyses on infant risk factors and feeding methods for outcomes other than the effect of probiotics on eczema. Only three studies assessed synbiotic supplementation, leaving their role in allergic disease prevention uncertain. The included studies were mainly in high-income countries in many different areas of the world, but may have limited applicability to other regions. AUTHORS' CONCLUSIONS: There is insufficient evidence to make conclusions about the effect of probiotics and synbiotics on preventing the development of allergic diseases by two years of age and during childhood up to 10 years of age. Although there were no serious adverse events reported for the use of probiotics in infants, incorporating probiotics and synbiotics into routine practice requires further information to support their use. FUNDING: This Cochrane review had no dedicated funding. REGISTRATION: Protocol (2007) available via https://doi.org/10.1002/14651858.CD006475. Original review (2007) available via https://doi.org/10.1002/14651858.CD006475.pub2.
理由:这是对2007年首次发表的Cochrane系统评价的更新。过敏性疾病和食物过敏很常见,给个人、其家庭和医疗保健系统带来了重大疾病负担。益生菌是定殖于胃肠道的活细菌,已在许多临床试验中对预防过敏性疾病进行了研究。 目的:评估益生菌或添加益生元的益生菌(“合生元”)与对照(安慰剂或无治疗)相比,在预防2岁以下婴儿过敏性疾病(哮喘、湿疹、过敏性鼻炎)和食物过敏方面的益处和危害。 检索方法:我们于2023年12月检索了Cochrane系统评价数据库、医学期刊数据库、荷兰医学文摘数据库及试验注册库。我们查阅了纳入本系统评价的研究的参考文献列表,以及关于类似主题的系统评价。我们手动检索了会议摘要。 纳入标准:我们纳入了将益生菌与对照进行比较,或添加益生元的益生菌(“合生元”)的随机对照试验。我们纳入了出生后头六个月经肠道喂养且无过敏性疾病临床证据的婴儿。我们纳入了添加到母乳或婴儿配方奶粉中、在制造过程中添加或单独给予的益生菌。 结局指标:2岁时婴儿特定过敏性疾病的发病率以及儿童期(至10岁或至2至10岁间最新报告年龄)的发病率,包括:哮喘、湿疹、过敏性鼻炎、免疫球蛋白E(IgE)介导的食物过敏、IgE介导的牛奶蛋白过敏。过敏反应事件以及潜在危害,包括不良反应、危害或益生菌感染。 偏倚风险:我们使用Cochrane偏倚风险评估工具2(Cochrane RoB 2)来评估研究中的偏倚。 合成方法:我们尽可能使用随机效应(Mantel-Haenszel)模型进行荟萃分析。若因数据性质无法进行荟萃分析,我们则分别对各个研究进行合成和解读。我们使用GRADE评估每个结局指标的证据确定性。 纳入研究:我们纳入了24项研究(7077对母婴)。这些研究在世界许多地区进行,包括美国、欧洲、韩国、日本、新加坡和澳大利亚,其中大部分在欧洲进行。研究发表于2001年至2020年之间。由于一些研究使用不同标准测量湿疹等结局指标,我们做出了一些假设以便合并数据。 结果合成:益生菌可能对2岁时的哮喘(风险比(RR)0.96,95%置信区间(CI)0.65至1.44;4项研究,954名参与者;低确定性证据)、过敏性鼻炎(RR 0.89,95%CI 0.45至1.77;5项研究,1045名参与者;低确定性证据)和IgE介导的牛奶蛋白过敏(RR 0.99,95%CI 0.82至1.20;4项研究,259名参与者;低确定性证据)影响甚微或无差异。益生菌可能使2岁时的湿疹略有减少(RR 0.87,95%CI 0.78至0.97;18项研究,3494名参与者;低确定性证据);然而,对偏倚风险较低的研究进行敏感性分析显示,2岁时湿疹几乎无差异(RR 0.86,95%CI 0.69至1.07;4项研究,892名参与者)。补充益生菌可能对2岁时食物过敏的发病率影响甚微或无影响,但证据非常不确定(RR 1.12,95%CI 0.57至2.20;3项研究,857名参与者;极低确定性证据)。关于合生元对2岁时湿疹的影响,证据非常不确定(RR 0.88,95%CI 0.52至1.47;3项研究,1235名参与者;极低确定性证据)。合生元可能对2岁时食物过敏影响甚微或无差异(RR 1.06,95%CI 0.55至2.07;1项研究,223名参与者;低确定性证据)。关于合生元对2岁时哮喘、过敏性鼻炎和IgE介导的牛奶蛋白过敏的影响,没有数据。在研究干预的两年内,补充益生菌或合生元在潜在危害(包括不良反应、危害或益生菌感染)方面可能几乎无差异。没有报告与益生菌或合生元相关的严重不良事件。我们对大多数研究的偏倚风险存在一些担忧,只有少数研究被判定为低偏倚风险。一些研究由于随机化不明确、数据缺失和缺乏预先设定的意向而存在高偏倚风险。由于事件有限,估计值往往不精确,置信区间较宽。有限的数据妨碍了对除益生菌对湿疹影响之外的结局指标进行婴儿风险因素和喂养方法的亚组分析。只有三项研究评估了合生元补充剂,其在预防过敏性疾病中的作用尚不确定。纳入的研究主要在世界许多不同地区的高收入国家进行,但可能对其他地区适用性有限。 作者结论:没有足够的证据就益生菌和合生元对预防2岁及10岁以下儿童期过敏性疾病发展的影响得出结论。尽管在婴儿中使用益生菌未报告严重不良事件,但将益生菌和合生元纳入常规实践需要更多信息来支持其使用。 资助:本Cochrane系统评价没有专门的资助。 注册信息:方案(2007年)可通过https://doi.org/10.1002/14651858.CD006475获取。原始评价(2007年)可通过https://doi.org/10.1002/14651858.CD006475.pub2获取。
Cochrane Database Syst Rev. 2025-6-13
Cochrane Database Syst Rev. 2022-11-14
Cochrane Database Syst Rev. 2024-12-13
Cochrane Database Syst Rev. 2023-2-17
Cochrane Database Syst Rev. 2020-10-19
Cochrane Database Syst Rev. 2023-10-23
Cochrane Database Syst Rev. 2006-10-18
Cochrane Database Syst Rev. 2020-1-9
Cochrane Database Syst Rev. 2022-9-20
Cochrane Database Syst Rev. 2017-12-22
Nutrients. 2022-6-21
World J Clin Pediatr. 2022-5-9
Nutrients. 2021-6-24
Allergy Asthma Clin Immunol. 2021-4-17