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辅助生殖技术与儿童癌症之间的累积时间关联:一项观察性研究的系统评价和荟萃分析

Cumulative temporal association between assisted reproductive technology and childhood cancer: a systematic review and meta-analysis of observational studies.

作者信息

Jiang Yanjie, Dai Qiangqiang, Zhang Shipeng, Wang Hanyu, He Xingyi, Fu Rui, Tan Junwen, Fu Qinwei, Zhang Qinxiu, Lu Yan

机构信息

Neurology Department, Nanjing Hospital of Chinese Medicine Affiliated to Nanjing University of Chinese Medicine, Nanjing, China.

Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, China.

出版信息

Front Oncol. 2025 May 20;15:1555420. doi: 10.3389/fonc.2025.1555420. eCollection 2025.


DOI:10.3389/fonc.2025.1555420
PMID:40463883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12129972/
Abstract

OBJECTIVE: Assisted reproductive technology (ART) has contributed to the birth of over 10 million children worldwide; however, its long-term health impacts, especially the potential risk of childhood cancer, continue to be a subject of debate. This study aims to examine the most current risk associations between ART and childhood cancer. METHODS: We conducted a comprehensive search across PubMed, Embase, Web of Science, and Cochrane Library databases up to August 1, 2024. These studies aimed to explore the association between ART and childhood cancer risk, covering overall cancers, haematological malignancies, neural tumors, other solid tumors, and 11 specific cancers. Pooled analyses of risk estimates and 95% confidence intervals were conducted using random effects models, while cumulative meta-analyses were conducted to provide a time-based summary of the evidence. The study was prospectively registered on PROSPERO (CRD42024547262). RESULTS: Sixteen large sample observational studies were included. Our findings showed a 21% increased risk of overall cancer in children conceived via ART (relative risk [RR] = 1.21, 95% CI, 1.11-1.33), with elevated risks also noted for haematological malignancies (RR = 1.16, 95% CI, 1.05-1.28), neural tumors (RR = 1.19, 95% CI, 1.07-1.32), and other solid tumors (RR = 1.48, 95% CI, 1.26-1.73). Six specific cancer types also demonstrated higher risks. The direction and magnitude of the effects remained relatively constant over time, while the degree of precision increased as data from newer studies were incorporated. Sensitivity analyses confirmed the robustness of these findings, and no publication bias was found. CONCLUSIONS: Our findings suggest a potential risk association between ART and childhood cancer, raising concerns regarding the future application of ART. These findings are critical in informing infertile couples considering ART about the potential risks involved. CLINICAL TRIAL REGISTRATION: https://www.crd.york.ac.uk/prospero/, identifier CRD42024547262.

摘要

目的:辅助生殖技术(ART)已助力全球超过1000万儿童诞生;然而,其对健康的长期影响,尤其是儿童患癌的潜在风险,仍是一个备受争议的话题。本研究旨在探讨ART与儿童癌症之间最新的风险关联。 方法:截至2024年8月1日,我们对PubMed、Embase、Web of Science和Cochrane图书馆数据库进行了全面检索。这些研究旨在探究ART与儿童癌症风险之间的关联,涵盖总体癌症、血液系统恶性肿瘤、神经肿瘤、其他实体肿瘤以及11种特定癌症。使用随机效应模型对风险估计值和95%置信区间进行汇总分析,同时进行累积荟萃分析以提供基于时间的证据总结。该研究已在PROSPERO(CRD42024547262)上进行前瞻性注册。 结果:纳入了16项大样本观察性研究。我们的研究结果显示,通过ART受孕的儿童患总体癌症的风险增加了21%(相对风险[RR]=1.21,95%置信区间,1.11 - 1.33),血液系统恶性肿瘤(RR = 1.16,95%置信区间,1.05 - 1.28)、神经肿瘤(RR = 1.19,95%置信区间,1.07 - 1.32)和其他实体肿瘤(RR = 1.48,95%置信区间,1.26 - 1.73)的风险也有所升高。六种特定癌症类型的风险也更高。随着时间推移,效应的方向和大小保持相对稳定,而随着纳入更新研究的数据,精确程度有所提高。敏感性分析证实了这些研究结果的稳健性,且未发现发表偏倚。 结论:我们的研究结果表明ART与儿童癌症之间可能存在风险关联,引发了对ART未来应用的担忧。这些结果对于告知考虑采用ART的不孕夫妇其中涉及的潜在风险至关重要。 临床试验注册:https://www.crd.york.ac.uk/prospero/,标识符CRD42024547262。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a9e/12129972/c9301b073bd5/fonc-15-1555420-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a9e/12129972/55b6a053f7c9/fonc-15-1555420-g003.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a9e/12129972/c9301b073bd5/fonc-15-1555420-g005.jpg

相似文献

[1]
Cumulative temporal association between assisted reproductive technology and childhood cancer: a systematic review and meta-analysis of observational studies.

Front Oncol. 2025-5-20

[2]
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Cochrane Database Syst Rev. 2022-2-1

[3]
Assisted Reproductive Technology and Risk of Childhood Cancer Among the Offspring of Parents With Infertility: Systematic Review and Meta-Analysis.

JMIR Cancer. 2025-3-12

[4]
The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

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[5]
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Environ Int. 2024-9

[6]
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JMIR Res Protoc. 2025-5-12

[7]
Cancer risk among children conceived by fertility treatment.

Int J Cancer. 2019-1-3

[8]
Quantifying the association of sperm DNA fragmentation with assisted reproductive technology outcomes: An umbrella review.

BJOG. 2024-8

[9]
Sex differences in childhood cancer risk following ART conception: a registry-based study.

Hum Reprod. 2025-2-1

[10]
Asthma and allergies in offspring conceived by ART: a systematic review and meta-analysis.

Hum Reprod Update. 2021-12-21

本文引用的文献

[1]
Cancer Risk Among Children Born After Fertility Treatment.

JAMA Netw Open. 2024-5-1

[2]
Medically Assisted Reproduction and Risk of Cancer Among Offspring.

JAMA Netw Open. 2024-5-1

[3]
Investigation of inherited noncoding genetic variation impacting the pharmacogenomics of childhood acute lymphoblastic leukemia treatment.

Nat Commun. 2024-5-1

[4]
Long-term health risk of offspring born from assisted reproductive technologies.

J Assist Reprod Genet. 2024-3

[5]
Assisted reproductive technology and imprinting errors: analyzing underlying mechanisms from epigenetic regulation.

Hum Fertil (Camb). 2023-10

[6]
ART in Europe, 2019: results generated from European registries by ESHRE†.

Hum Reprod. 2023-12-4

[7]
Cancer risk in children, adolescents, and young adults conceived by ART in 1983-2011.

Hum Reprod Open. 2023-6-1

[8]
Long-term outcomes for children conceived by assisted reproductive technology.

Fertil Steril. 2023-9

[9]
The risks of birth defects and childhood cancer with conception by assisted reproductive technology.

Hum Reprod. 2022-10-31

[10]
Cancer in children born after frozen-thawed embryo transfer: A cohort study.

PLoS Med. 2022-9

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