A US-UK Collaborative Study of the Health of Children Born From In Vitro Fertilization: From Conception Through Young Adulthood

美英合作研究体外受精出生的儿童的健康状况：从受孕到成年

• 批准号: 10749238
• 负责人: BARBARA Joan LUKE
• 金额: $ 63.46万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10749238
• 关键词: Accounting; Acute; Adult; Age; Assisted Reproductive Technology; Authorization documentation; Autologous; Birth; Birth Order; Birth Weight; Cerebral Palsy; Child; Child Health; Childbirth; Childhood; Chronic Disease; Clinic; Collaborations; Conceptions; Congenital Abnormality; Country; Data; Databases; Defect; Development; Dropout; Embryo; Embryo Loss; Embryo Transfer; Embryology; Environmental Risk Factor; Epigenetic Process; Ethnic Origin; Fertilization; Fertilization in Vitro; First Births; Follow-Up Studies; Growth; Health; Heart Abnormalities; Height; Human; Individual; Infant; Intracytoplasmic Sperm Injections; Knowledge; Left; Life; Life Cycle Stages; Link; Lymphocyte Activation; Malignant Neoplasms; Malignant neoplasm of liver; Methodology; Morbidity - disease rate; Neonatal; Neonatal Mortality; Neurologic; Oocytes; Outcome; Parents; Pattern; Perinatal; Persons; Pregnancy; Premature Mortality; Procedures; Process; Race; Registries; Reporting; Research; Research Personnel; Risk; Role; Sample Size; Siblings; Societies; Socioeconomic Factors; Source; Survivors; Syndrome; System; Technology; Time; Twin Multiple Birth; Weight; adverse outcome; authority; early childhood; embryo cryopreservation; ethnic diversity; experience; fetal loss; follow-up; high risk; methylome; middle childhood; mortality; neonatal morbidity; obesity in children; oocyte cryopreservation; perinatal outcomes; racial diversity; respiratory; sex; young adult

PROJECT SUMMARY Since the birth of the first child from in vitro fertilization (IVF) in the UK in 1978 and in the US in 1981, more than ten million babies have been born from this technology, including more than 1.37 million babies annually worldwide. In 2018, IVF births accounted for 2.24% of all US births and 3.1% of all UK births. Consistent research findings indicate that IVF-conceived pregnancies and IVF-conceived children are at greater risk for a spectrum of adverse perinatal outcomes. A persistent, unresolved issue remains what proportion of the adverse perinatal and child health outcomes after IVF is due to parental factors and what proportion is due to the IVF procedures. In the US, the national IVF database, the Society for Assisted Reproductive Technology Clinic Outcome Reporting System is left-censored at 2004; it is not feasible to obtain data on earlier cycles. In addition, the US has few national databases to facilitate tracking children’s health over time. To overcome these limitations, we are partnering with researchers in the UK in this proposed study. The UK system, under the Human Fertilisation and Embryology Authority, can track individuals treated as early as 1991, linking all adults treated and all children conceived with IVF to a number of national databases. Through this collaboration, we seek to draw upon the strengths of each country: in the UK, longer follow-up and more linked health databases; in the US, more annual IVF cycles and births; and more racial and ethnic diversity. The long-term health of children conceived with IVF is still not clearly understood. Follow-up studies of the growth and health of IVF-conceived children have been limited by small sample sizes, high drop-out rates, and methodological issues, with many knowledge gaps remaining. In this proposed renewal, we are seeking to overcome these limitations using an early life-course approach to evaluate the growth and health of children born from IVF, from conception through childhood, and for the UK component, through adulthood. The two primary aims of this proposed renewal are (1) comprehensively evaluate the role of IVF conception on birth defects, cancer, and the co-occurrence of these conditions through large-scale registry linkages and analysis of the neonatal methylome and (2) to evaluate the effect of IVF treatment parameters, specifically the use of ICSI, number of embryos transferred (embryonic and/or fetal loss as plurality at conception versus at birth), oocyte source/state-embryo state combinations, on child growth (size at birth, and height and weight at ages 4-5 and 10-11) and health (birth defects, cancer, acute and chronic illness, and premature mortality), accounting for parental, socioeconomic, and environmental factors. This proposed study will include a total of more than 4.75 million children, including more than 458,000 IVF- conceived children born 1991-2018, 88,000 naturally-conceived siblings, and 4.2 million naturally-conceived control children, with 80.6 million person-years of follow-up, averaging 14.4 years in the US (ranging from birth to age 22) and 18.3 years in the UK (ranging from birth to age 36), and will provide a comprehensive contemporary picture of child health after conception by in vitro fertilization.

项目摘要 自1978年英国和1981年美国第一个试管婴儿诞生以来， 已有1000万婴儿通过这项技术出生，其中每年有超过137万婴儿 国际吧2018年，试管婴儿出生占美国所有出生人数的2.24%，占英国所有出生人数的3.1%。一致的研究 研究结果表明，体外受精怀孕和体外受精怀孕的孩子有更大的风险， 围产期的不良后果。一个持续存在的未解决的问题仍然是， 试管婴儿后的儿童健康结果是由于父母因素，而试管婴儿程序占多大比例。 在美国，国家试管婴儿数据库、辅助生殖技术临床结果协会 报告系统在2004年进行左删失;无法获得更早周期的数据。此外美国 几乎没有全国性的数据库来帮助跟踪儿童的健康状况。为了克服这些限制，我们 正在与英国的研究人员合作进行这项研究。英国的人工授精系统 和胚胎学管理局，可以跟踪早在1991年接受治疗的个人，将所有接受治疗的成年人和所有儿童联系起来 通过试管婴儿受孕的数据库通过这种合作，我们寻求利用 每个国家的优势：在英国，随访时间更长，健康数据库链接更多;在美国，每年更多 IVF周期和生育;以及更多的种族和民族多样性。IVF受孕儿童的长期健康 仍然没有被清楚地理解。对试管婴儿的生长和健康的后续研究已经 受样本量小、辍学率高和方法问题的限制，存在许多知识空白 剩下的在这个提议的更新中，我们正在寻求利用早期生命历程来克服这些限制 评估试管婴儿出生的儿童从受孕到童年的生长和健康的方法， 在英国，直到成年。这项建议的两个主要目的是：（1） 全面评估IVF概念对出生缺陷，癌症以及这些并发症的作用 通过大规模登记联系和新生儿甲基化组分析来评估条件，以及（2）评估 IVF治疗参数的影响，特别是ICSI的使用，移植的胚胎数量（胚胎和/或 妊娠时与出生时的胎儿丢失数），卵母细胞来源/状态-胚胎状态组合，对儿童 生长（出生时的大小，4-5岁和10-11岁的身高和体重）和健康（出生缺陷，癌症，急性和 慢性疾病和过早死亡），考虑到父母、社会经济和环境因素。 这项拟议的研究将包括总共超过475万名儿童，其中包括超过458，000名试管婴儿。 1991年至2018年出生的怀孕儿童，88，000名自然怀孕的兄弟姐妹，420万名自然怀孕的 对照组儿童，随访8060万人年，在美国平均随访14.4年（从出生 到22岁）和18.3年在英国（从出生到36岁），并将提供全面的 通过体外受精受孕后儿童健康的当代情况。