Weng Shiue-Shan, Huang Yen-Tsung, Huang Yi-Ting, Li Yi-Ping, Chien Li-Yin
Institute of Public Health, National Yang Ming Chiao Tung University, Yang-Ming Campus, Taipei City, Taiwan.
Institute of Statistical Science, Academia Sinica, Taipei City, Taiwan.
JAMA Netw Open. 2022 Aug 1;5(8):e2230157. doi: 10.1001/jamanetworkopen.2022.30157.
The number of children born through the use of assisted reproductive technology (ART) has been increasing. These children may have higher risks for epigenetic alteration and adverse perinatal outcomes, which may be associated with childhood cancers.
To determine the associations between different modes of conception and childhood cancers and potential mediation by preterm birth and low birth weight.
DESIGN, SETTING, AND PARTICIPANTS: This nationwide, population-based cohort study included registry data from 2 308 016 eligible parents-child triads in Taiwan from January 1, 2004, to December 31, 2017. A total of 1880 children with incident childhood cancer were identified. Data were analyzed between September 1, 2020, and June 30, 2022.
Mode of conception, defined as (1) natural conception, (2) subfertility and non-ART (ie, infertility diagnosis but no ART-facilitated conception), or (3) ART (ie, infertility diagnosis and ART-facilitated conception).
Diagnosis of childhood cancer according to the International Classification of Childhood Cancers, Third Edition.
The mean (SD) paternal and maternal ages were 33.28 (5.07) and 30.83 (4.56) years, respectively. Of the 2 308 016 children, 52.06% were boys, 8.16% were born preterm, and 7.38% had low birth weight. During 14.9 million person-years of follow-up (median, 6 years [IQR, 3-10 years]), ART conception was associated with an increased risk of any type of childhood cancers compared with natural conception (hazard ratio, 1.58; 95% CI, 1.17-2.12) and subfertility with non-ART conception (hazard ratio, 1.42; 95% CI, 1.04-1.95). The increased cancer risk of children conceived with ART was mainly owing to leukemia and hepatic tumor. The increased cancer risk associated with ART conception was not mediated by preterm birth or low birth weight.
In this cohort study, children conceived via ART had a higher risk of childhood cancers than those conceived naturally and those born to parents with an infertility diagnosis did not use ART. The increased risk could not be explained by preterm birth or low birth weight.
通过辅助生殖技术（ART）出生的儿童数量一直在增加。这些儿童可能面临更高的表观遗传改变风险和不良围产期结局，这可能与儿童癌症有关。
确定不同受孕方式与儿童癌症之间的关联，以及早产和低出生体重的潜在中介作用。
设计、设置和参与者：这项基于全国人口的队列研究纳入了2004年1月1日至2017年12月31日台湾地区2308016对符合条件的父母-子女三联体的登记数据。共识别出1880例患儿童癌症的儿童。数据于2020年9月1日至2022年6月30日进行分析。
受孕方式，定义为（1）自然受孕，（2）亚生育力且未使用ART（即诊断为不育但未通过ART辅助受孕），或（3）ART（即诊断为不育且通过ART辅助受孕）。
根据《国际儿童癌症分类》第三版诊断儿童癌症。
父亲和母亲的平均（标准差）年龄分别为33.28（5.07）岁和30.83（4.56）岁。在2308016名儿童中，52.06%为男孩，8.16%早产，7.38%出生体重低。在1490万人年的随访期间（中位数为6年[四分位间距，3 - 10年]），与自然受孕相比，ART受孕与任何类型儿童癌症的风险增加相关（风险比，1.58；95%置信区间，1.17 - 2.12），与亚生育力且未使用ART受孕相比也相关（风险比，1.42；95%置信区间，1.04 - 1.95）。ART受孕儿童癌症风险增加主要归因于白血病和肝肿瘤。ART受孕相关的癌症风险增加并非由早产或低出生体重介导。
在这项队列研究中，通过ART受孕的儿童患儿童癌症的风险高于自然受孕的儿童以及父母诊断为不育但未使用ART的儿童。风险增加无法用早产或低出生体重来解释。
