University College London, Great Ormond Street Institute of Child Health, London WC1 1EH, UK.
National Perinatal Epidemiology Unit, University of Oxford, Oxford OX3 7LF, UK.
Hum Reprod. 2018 Jan 1;33(1):140-146. doi: 10.1093/humrep/dex333.
Do children born after donor ART have an increased risk of developing childhood cancer in comparison to the general population?
This study showed no overall increased risk of childhood cancer in individuals born after donor ART.
Most large population-based studies have shown no increase in overall childhood cancer incidence after non-donor ART; however, other studies have suggested small increased risks in specific cancer types, including haematological cancers. Cancer risk specifically in children born after donor ART has not been investigated to date.
STUDY DESIGN, SIZE, DURATION: This retrospective cohort study utilized record linkage to determine the outcome status of all children born in Great Britain (1992-2008) after donor ART. The cohort included 12 137 members who contributed 95 389 person-years of follow-up (average follow-up 7.86 years).
PARTICIPANTS/MATERIALS, SETTING, METHODS: Records of all children born in Great Britain (England, Wales, Scotland) after all forms of donor ART (1992-2008) were linked to the UK National Registry of Childhood Tumours (NRCT) to determine the number who subsequently developed cancer by 15 years of age, by the end of 2008. Rates of overall and type specific cancer (selected a priori) were compared with age, sex and calendar year standardized population-based rates, stratifying for potential mediating/moderating factors including sex, age at diagnosis, birth weight, multiple births, maternal previous live births, assisted conception type and fresh/ cryopreserved cycles.
In our cohort of 12 137 children born after donor ART (52% male, 55% singleton births), no overall increased risk of cancer was identified. There were 12 cancers detected compared to 14.4 expected (standardized incidence ratio (SIR) 0.83; 95% CI 0.43-1.45; P = 0.50). A small, significant increased risk of hepatoblastoma was found, but the numbers and absolute risks were small (<5 cases observed; SIR 10.28; 95% CI 1.25-37.14; P < 0.05). This increased hepatoblastoma risk was associated with low birthweight.
Although this study includes a large number of children born after donor ART, the rarity of specific diagnostic subgroups of childhood cancer results in few cases and therefore wide CIs for such outcomes. As this is an observational study, it is not possible to adjust for all potential confounders; we have instead used stratification to explore potential moderating and mediating factors, where data were available.
This is the first study to investigate cancer risk in children born after donor ART. Although based on small numbers, results are reassuring for families and clinicians. The small but significant increased risk of hepatoblastoma detected was associated with low birthweight, a known risk factor for this tumour type. It should be emphasized that the absolute risks are very small. However, on-going investigation with a longer follow-up is needed.
STUDY FUNDING/COMPETING INTEREST(S): This work was funded by Cancer Research UK (C36038/A12535) and the National Institute for Health Research (405526) and supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London. The work of the Childhood Cancer Research Group (CCRG) was supported by the charity CHILDREN with CANCER UK, the National Cancer Intelligence Network, the Scottish Government and the Department of Health for England and Wales. There are no competing interests.
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与普通人群相比,接受供体 ART 后出生的儿童患儿童癌症的风险是否增加?
本研究显示,接受供体 ART 后出生的个体患儿童癌症的总体风险没有增加。
大多数基于人群的大型研究表明,非供体 ART 后儿童癌症总体发病率没有增加;然而,其他研究表明,某些癌症类型(包括血液癌症)的风险略有增加。迄今为止,尚未调查供体 ART 后出生的儿童的癌症风险。
研究设计、大小和持续时间:这项回顾性队列研究利用记录链接来确定英国(1992-2008 年)所有接受供体 ART 后出生的儿童的结局状态。该队列包括 12137 名成员,他们提供了 95389 人年的随访(平均随访 7.86 年)。
参与者/材料、设置、方法:链接英国所有接受供体 ART(1992-2008 年)后出生的儿童(英格兰、威尔士、苏格兰)的记录,以确定截至 2008 年底 15 岁以下随后发生癌症的人数。通过年龄、性别和日历年标准化人群发病率,比较总体和特定类型癌症(预先选择)的发病率,分层分析潜在的中介/调节因素,包括性别、诊断时的年龄、出生体重、多胎、母亲既往活产、辅助受孕类型和新鲜/冷冻周期。
在我们的 12137 名接受供体 ART 后出生的儿童队列中(52%为男性,55%为单胎出生),未发现癌症总体风险增加。检测到 12 例癌症,预期为 14.4 例(标准化发病率比(SIR)0.83;95%CI 0.43-1.45;P=0.50)。发现肝母细胞瘤的风险略有增加,但数量和绝对风险很小(<5 例观察病例;SIR 10.28;95%CI 1.25-37.14;P<0.05)。这种增加的肝母细胞瘤风险与低出生体重有关。
尽管这项研究包括大量接受供体 ART 后出生的儿童,但儿童癌症的特定诊断亚组的罕见性导致病例较少,因此此类结果的置信区间较宽。由于这是一项观察性研究,无法调整所有潜在的混杂因素;我们已经使用分层来探索潜在的调节和中介因素,在有数据的情况下。
这是第一项调查接受供体 ART 后出生的儿童癌症风险的研究。尽管基于少数病例,但结果令人欣慰,为家庭和临床医生提供了信心。检测到的肝母细胞瘤风险略有增加,但意义重大,与低出生体重有关,低出生体重是这种肿瘤类型的已知风险因素。应该强调的是,绝对风险很小。然而,需要进行更长时间随访的进一步研究。
研究资金/利益冲突:这项工作得到了英国癌症研究中心(C36038/A12535)和国家健康研究所(405526)的资助,并得到了大奥蒙德街儿童医院 NHS 基金会信托基金和伦敦大学学院的国家健康研究所生物医学研究中心的支持。儿童癌症研究小组(CCRG)的工作得到了慈善机构 CHILDREN with CANCER UK、国家癌症情报网络、苏格兰政府和英格兰及威尔士卫生部的支持。没有利益冲突。
无。