BACKGROUND Currently, 1 in 25 children born in Australia are conceived through ARTs such as IVF and ICSI. Worldwide over 8 million children have been born after ART. There is evidence that these children are at an increased risk of congenital malformations, preterm birth, low birth weight and neonatal morbidity. However, studies on long-term health outcomes of offspring conceived after ART are lacking. Atopic disorders, such as asthma, atopic dermatitis and various allergies are increasingly common within society, and concerns have been raised that ART increases the risk of atopy amongst offspring. OBJECTIVE AND RATIONALE The aim of this study was to systematically summarise and quantify the risk of atopic disorders in offspring conceived with ART compared to those conceived without ART. SEARCH METHODS A systematic review was conducted according to the PRISMA guidelines. Several systematic searches were performed in the following international databases: Medline, Embase, Cinahl, PsychINFO, AMED, Global Health and ISI Web of Science. Search terms utilised were all terms pertaining to ART, IVF, ICSI, asthma, atopic dermatitis and allergies. The search period was 1978–2021. Included observational studies stated a primary outcome of asthma or allergies in offspring conceived after ART, with a comparison group conceived without ART. Individual studies were scored on quality and risk of bias, using the Newcastle-Ottawa scale (NOS). OUTCOMES There were 26 studies which met the inclusion criteria; of these, 24 studies investigated asthma in offspring conceived after ART. While 10 studies, including the two largest population-based studies, reported a significantly increased risk of asthma in offspring conceived after ART (adjusted odds ratio (aOR) range: 1.20–2.38), 14 smaller cohort studies found no difference (aOR range 0.70–1.27). In the meta-analysis of the 14 highest-quality studies (NOS ≥ 7), a modest yet significantly increased risk of asthma was demonstrated in offspring conceived after ART [risk ratio (RR) 1.28 (1.08–1.51)]. Although heterogeneity in these 14 studies was high (I2 = 85%), the removal of outliers and high weight studies significantly reduced heterogeneity (I2 = 0% and I2 = 34% respectively) while still demonstrating a significantly increased risk [RR 1.19 (1.10–1.28) and RR 1.31 (1.03–1.65), respectively]. The increased asthma risk was also observed in most subgroup and sensitivity analyses. The allergy rates were not increased in offspring conceived after ART in 9 of 12 studies (aOR range 0.60–1.30). In summary, the findings of this systematic review and meta-analysis suggest a trend towards a significantly increased risk of asthma, but not allergies, in offspring conceived after ART. There was no evidence of publication bias in the asthma studies and minimal evidence of publication bias in the allergy studies (both P > 0.05). WIDER IMPLICATIONS Asthma brings considerable burden to the quality of life of individuals and to society. Hence, it is of great importance to untangle potential causal pathways. Although ART use is common, knowledge about its long-term health effects is required to provide evidence-based advice to couples considering ART, and to be vigilant for any potential adverse health effects on offspring conceived after ART.

中文翻译：

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ART 孕育后代的哮喘和过敏：系统评价和荟萃分析

背景 目前，在澳大利亚出生的每 25 名儿童中，就有 1 名是通过 IVF 和 ICSI 等 ART 受孕的。全世界有超过 800 万儿童在接受 ART 后出生。有证据表明，这些儿童发生先天性畸形、早产、低出生体重和新生儿发病率的风险增加。然而，缺乏对 ART 后受孕后代的长期健康结果的研究。特应性疾病，如哮喘、特应性皮炎和各种过敏症在社会中越来越普遍，人们担心 ART 会增加后代患特应性的风险。目的和基本原理 本研究的目的是系统地总结和量化接受 ART 与未接受 ART 的后代患特应性疾病的风险。搜索方法 根据 PRISMA 指南进行了系统评价。在以下国际数据库中进行了几次系统搜索：Medline、Embase、Cinahl、PsychINFO、AMED、Global Health 和 ISI Web of Science。使用的搜索词是与 ART、IVF、ICSI、哮喘、特应性皮炎和过敏有关的所有词。搜索期为 1978-2021 年。纳入的观察性研究表明，ART 后受孕的后代的主要结果是哮喘或过敏，而对照组则未接受 ART。使用纽卡斯尔-渥太华量表（NOS）对个别研究的质量和偏倚风险进行评分。结果 有 26 项研究符合纳入标准；其中，24 项研究调查了 ART 后受孕后代的哮喘。虽然有 10 项研究，包括两项最大的基于人群的研究报告称，ART 后受孕的后代患哮喘的风险显着增加（调整优势比 (aOR) 范围：1.20-2.38），14 项较小的队列研究发现没有差异（aOR 范围 0.70-1.27）。在对 14 项最高质量研究 (NOS ≥ 7) 的荟萃分析中，在 ART 后受孕的后代中，哮喘风险适度但显着增加 [风险比 (RR) 1.28 (1.08–1.51)]。尽管这 14 项研究的异质性很高（I2 = 85%），但去除异常值和高权重研究显着降低了异质性（分别为 I2 = 0% 和 I2 = 34%），同时仍显示出显着增加的风险 [RR 1.19 (1.10 –1.28) 和 RR 1.31 (1.03–1.65)]。在大多数亚组和敏感性分析中也观察到哮喘风险增加。在 12 项研究中有 9 项（aOR 范围 0.60-1.30）中，ART 后受孕的后代的过敏率没有增加。总之，这项系统评价和荟萃分析的结果表明，ART 后受孕的后代患哮喘的风险显着增加，但过敏风险没有显着增加。哮喘研究中没有发表偏倚的证据，过敏研究中发表偏倚的证据也很少（均 P > 0.05）。更广泛的影响 哮喘给个人和社会的生活质量带来了相当大的负担。因此，理清潜在的因果关系非常重要。虽然 ART 的使用很普遍，但需要了解其长期健康影响，以便为考虑 ART 的夫妇提供基于证据的建议，