Division of Obstetrics and Gynaecology, University of Western Australia, Perth, Western Australia, Australia.
Department of Obstetrics and Gynaecology, King Edward Memorial Hospital, Perth, Western Australia, Australia.
Hum Reprod Update. 2021 Dec 21;28(1):132-148. doi: 10.1093/humupd/dmab031.
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.
背景:目前,在澳大利亚出生的儿童中,每 25 个就有 1 个是通过体外受精(IVF)和卵胞浆内单精子注射(ICSI)等辅助生殖技术(ART)受孕的。全世界已有超过 800 万儿童通过 ART 出生。有证据表明,这些儿童先天畸形、早产、低出生体重和新生儿发病率的风险增加。然而,关于 ART 后受孕的后代的长期健康结果的研究还很缺乏。特应性疾病,如哮喘、特应性皮炎和各种过敏,在社会中越来越普遍,人们担心 ART 会增加后代患特应性疾病的风险。
目的和理由:本研究的目的是系统地总结和量化与未经 ART 受孕的儿童相比,ART 受孕的后代患特应性疾病的风险。
检索方法:根据 PRISMA 指南进行了系统综述。在以下国际数据库中进行了几次系统搜索:Medline、Embase、Cinahl、PsychINFO、AMED、全球健康和 ISI Web of Science。使用的检索词是所有与 ART、IVF、ICSI、哮喘、特应性皮炎和过敏相关的术语。检索期为 1978 年至 2021 年。纳入的观察性研究报告了 ART 受孕后代的哮喘或过敏的主要结局,并与未经 ART 受孕的对照组进行了比较。使用纽卡斯尔-渥太华量表(NOS)对个体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 受孕后代的哮喘情况。虽然 10 项研究,包括两项最大的基于人群的研究,报告了 ART 受孕后代哮喘风险显著增加(调整后的优势比(aOR)范围:1.20-2.38),但 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,ART 受孕的后代哮喘风险显著增加[风险比(RR)1.28(1.08-1.51)]。尽管这些 14 项研究的异质性很高(I2=85%),但去除离群值和高权重研究显著降低了异质性(I2=0%和 I2=34%),同时仍然显示出显著增加的风险[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 项研究中的 9 项中,ART 受孕后代的过敏率没有增加(aOR 范围 0.60-1.30)。总之,这项系统综述和荟萃分析的结果表明,ART 受孕后代患哮喘的风险有增加的趋势,但并非过敏。哮喘研究中没有证据表明存在发表偏倚,过敏研究中只有微小的证据表明存在发表偏倚(均 P>0.05)。
意义:哮喘给个人和社会的生活质量带来了相当大的负担。因此,阐明潜在的因果途径非常重要。虽然 ART 的使用很普遍,但需要了解其长期健康影响,以便为考虑使用 ART 的夫妇提供循证建议,并警惕 ART 后受孕的后代可能出现任何不良健康影响。
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