Assisted Reproductive Technology & Risk of Childhood Cancer

描述(由申请人提供)：在过去的二十年里，美国辅助生殖技术(ART)的使用稳步上升，原因有几个，包括高龄产妇生育和保险覆盖范围的扩大。研究报告称，辅助妊娠与自然妊娠相比，不良围产期结局的风险显著增加，包括早产过多、低出生体重和出生缺陷。抗逆转录病毒治疗和/或不孕不育可能会影响其他产前疾病的发病率，如儿童期癌症。此外，像Beckwith-Wiedemann和Angelman综合征这样的印记疾病在ART受孕的儿童中的患病率也很高；其中一些疾病反过来又极大地增加了儿童早期发生几种胚胎癌症的风险。几项关于辅助生殖和儿童癌症的队列、病例对照和病例系列研究都报告了无效的结果，尽管这些研究都受到样本量小的限制，无法区分特定的癌症类型。一项专门针对肝母细胞瘤的研究发现，使用不孕不育治疗或辅助生殖与疾病风险增加九倍相关。利用辅助生殖技术协会(SART)的资源以及20个州和纽约市的出生和癌症登记处，我们提议进行迄今为止规模最大的抗逆转录病毒治疗和儿童癌症风险研究。SART维护着一个持续的国家数据库，其中包括根据1992年联邦生育成功率和认证法案[PL 102-493]的要求在美国提供ART服务的项目。截至2006年，也就是可获得的最新数据年，这包括483个诊所的138,198个抗逆转录病毒治疗周期的综合数据(包括足以联系的识别符)，导致41,343例怀孕和54,656名婴儿在一年中怀孕。我们建议将2004年至2013年SART数据库中的数据与20个州和纽约市的出生和癌症登记处联系起来，其中包括ART出生人数最多的五个州(加利福尼亚州、纽约州、伊利诺伊州、新泽西州和马萨诸塞州)，以创建一个约3000万儿童的队列，其中包括超过46.7万名ART受孕儿童，以评估辅助生殖与儿童癌症风险之间的关联。这项研究的具体目的是比较辅助受孕儿童和普通人群中儿童癌症的发病率。

DESCRIPTION (provided by applicant): Use of assisted reproductive technology (ART) has risen steadily in the United States during the past two decades due to several reasons, including childbearing at older maternal ages and increasing insurance coverage. Studies have reported significantly higher risks of adverse perinatal outcomes in assisted- versus spontaneous-conception pregnancies, including an excess of prematurity, low birthweight, and birth defects. ART and/or infertility may influence the incidence of other conditions with prenatal origins, such as childhood cancer. In addition, the prevalence of imprinting disorders such as Beckwith-Wiedemann and Angelman syndromes is elevated among children conceived by ART; some of these disorders, in turn, drastically raise the risk of several embryonal cancers that occur in early childhood. Several cohort, case-control, and case- series studies of assisted reproduction and childhood cancer have reported null results, although all were limited by small sample size and could not differentiate specific cancer types. One study that focused specifically on hepatoblastoma found that use of infertility treatment or assisted reproduction was associated with a nine-fold increased risk of disease. Using the resources of the Society for Assisted Reproductive Technology (SART) and the birth and cancer registries in 20 States and New York City, we propose to conduct the largest study to date of ART and childhood cancer risk. SART maintains an ongoing national database of programs that provide ART services in the United States as mandated by the federal Fertility Success Rate and Certification Act of 1992 [PL 102-493]. As of 2006, the latest year of data available, this included comprehensive data (including identifiers sufficient for linkage) on 138,198 ART cycles from 483 clinics resulting in 41,343 pregnancies and 54,656 infants for a single year. We propose to link the data from the SART database from 2004-2013 to the birth and cancer registries of 20 states and New York City, including the five states with the highest numbers of ART births (California, New York, Illinois, New Jersey, and Massachusetts), to create a cohort of approximately 30 million children, including over 467,000 conceived by ART to evaluate the association between assisted reproduction and the risk for childhood cancer. The specific aim of this study is to compare the incidence of childhood cancer in children with assisted conception to that in the general population.