Child Health After Assisted Reproductive Technology: A Population-Based Study

辅助生殖技术后的儿童健康：基于人群的研究

• 批准号: 8146206
• 负责人: EUGENE R DECLERCQ
• 金额: $ 62.86万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-09-20 至 2015-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8146206
• 关键词: 3 year old; Accident and Emergency department; Address; Admission activity; Affect; Age; Age-Years; Area; Assisted Reproductive Technology; Autologous; Bioethics; Birth; Birth Certificates; Boston; Caring; Centers for Disease Control and Prevention (U.S.); Cessation of life; Child; Child Development; Child health care; Childhood; Clinic; Clinical; Clinical Data; Collaborations; Conceptions; Congenital Abnormality; Data; Data Linkages; Data Sources; Databases; Death Certificates; Diagnosis; Early treatment; Embryo; Embryo Transfer; Enrollment; Epidemiology; Female; Fertility; Fetal Death; Fetal Development; Fetal Mortality Statistics; Foundations; Freezing; Germ Cells; Goals; Government; Growth; Health; Health Insurance; Hospitals; Individual; Infant; Infant Health; Infant Mortality; Infertility; Information Systems; Inpatients; Institution; Insurance Coverage; Intracytoplasmic Sperm Injections; Length of Stay; Life; Link; Live Birth; Longitudinal Studies; Low Birth Weight Infant; Massachusetts; Measures; Medicaid; Micromanipulation; Morbidity - disease rate; Mothers; Multiple Birth Offspring; Multivariate Analysis; Neonatal; Neonatal Mortality; Newborn Infant; Oocytes; Outcome; Outcome Measure; Outcome Study; Ovarian; Perinatal; Population; Pregnancy; Pregnancy Outcome; Procedures; Public Health; Public Health Schools; Records; Registries; Reporting; Reproductive Health; Research; Research Personnel; Research Proposals; Residual state; Risk; Role; Sample Size; Sampling; Services; Small for Gestational Age Infant; Societies; Source; Staging; Subgroup; System; Testing; Time; Treatment outcome; United States; Universities; Visit; Woman; Women' s Group; Work; base; blastocyst; cohort; comparison group; data management; disorder prevention; early childhood; endometriosis; fetal; hatching; hearing impairment; high risk; hospital utilization; implantation; innovation; intervention program; male; mortality; novel; ovulation disorders; perinatal health; population based; premature; programs; public health relevance; reproductive; sperm cell

DESCRIPTION (provided by investigator): Infertility affects an estimated 12 percent-15 percent of women of reproductive age. The use of fertility enhancing therapies, including Assisted Reproductive Technologies (ART), has risen steadily in the United States, with an estimated 1 percent-3 percent of births involving ART. Numerous studies have reported significantly higher risks of adverse perinatal outcomes in assisted-versus spontaneous-conception pregnancies. Infertility and sub fertility diagnoses, independent of ART, can also result in higher rates of adverse pregnancy outcomes. Documenting the added effect of ART, beyond underlying sub fertility, on child health outcomes remains a challenge. This applications describes an innovative collaboration between Boston University's School of Public Health, the Massachusetts Department of Public Health, the Society for Assisted Reproductive Technology, and the Centers for Disease Control and Prevention. The collaboration creates a unique longitudinal, population-based, source of data that combines detailed clinical information on ART treatment and infertility diagnoses for the resultant live births and fetal deaths from 2004 through 2011, with the Massachusetts Pregnancy to Early Life Longitudinal (PELL) Data System. PELL contains longitudinal data on pregnancy, births, deaths, hospital utilization, birth defects and public program participation including Early Intervention. The resulting database will track reproductive and child health outcomes to 3 years of age among three groups: babies conceived through ART (~18,000), and those not conceived through ART to subfertile women (~5,000) and those conceived to fertile women (~354,000). This project addresses key limitations of prior ART research (limited subfertility comparison groups, and lack of population-based data and longitudinal child health measures). Two broad hypotheses will be tested: (1) children born from ART treatments are at significantly higher risk of compromised fetal, perinatal, infant, and early childhood health outcomes compared to the two comparison groups, and (2) risk of adverse infant and child health outcomes will vary by ART treatment parameters, infertility diagnoses, and their interaction. The treatment parameters will include source of gametes; state of oocytes or embryos; stage of the embryo; micromanipulation; number of embryos transferred; early fetal loss; and number and outcome of prior treatment cycles. In both cases we will test these hypotheses at three age periods: 1) fetal/perinatal; 2) infant health to one year; and 3) child health to three years. The analyses will proceed in five stages: 1) univariate analyses; 2) unadjusted bivariate analyses; 3) multivariate analyses adjusted for known confounders; 4) subgroup analyses; and 5) path analysis to assess the differential effect of ART treatment parameters and infertility diagnoses, as well as the magnitude of the overall effect of ART, and the direct and indirect effects of plurality on perinatal and child health outcomes in an eight-year, population-based sample. The result will be the largest, most refined analysis ever completed of child health outcomes associated with ART. PUBLIC HEALTH RELEVANCE: Research has shown that children born after infertility and assisted reproductive technology (ART) treatments are at greater risk for adverse health outcomes, although the generalizability of prior studies has been hampered by small sample sizes and the lack of a subfertility comparison group. As the use of infertility treatments continue to rise, it is important to determine how much of this increased risk is related to the ART treatment rather than the underlying infertility, and if there are residual effects extending into early childhood. The proposed project will link ART clinical data from 2004 to 2011 to the Massachusetts Pregnancy to Early Life Longitudinal birth and fetal death file (resulting in approximately 18,000 ART assisted births, 5,000 births with no ART but other subfertility indicators, and 380,000 other births), facilitating the largest and most comprehensive U.S. study to date on infertility, ART and child health from birth to age three.

描述（由研究者提供）：估计 12%-15% 的育龄妇女患有不孕症。在美国，包括辅助生殖技术 (ART) 在内的生育增强疗法的使用量稳步上升，估计有 1%-3% 的新生儿涉及 ART。许多研究报告称，与自然受孕相比，辅助妊娠出现不良围产期结局的风险明显更高。独立于抗逆转录病毒治疗的不孕症和不育症诊断也可能导致不良妊娠结局发生率更高。除了潜在的低生育能力之外，记录 ART 对儿童健康结果的额外影响仍然是一个挑战。该应用程序描述了波士顿大学公共卫生学院、马萨诸塞州公共卫生部、辅助生殖技术协会以及疾病控制和预防中心之间的创新合作。此次合作创建了一个独特的、基于人群的纵向数据源，将 2004 年至 2011 年期间 ART 治疗和不孕不育诊断的详细临床信息与马萨诸塞州妊娠至早期生命纵向 (PELL) 数据系统相结合，包括 2004 年至 2011 年的活产和胎儿死亡。 PELL 包含有关怀孕、出生、死亡、医院利用率、出生缺陷和公共项目参与（包括早期干预）的纵向数据。由此产生的数据库将跟踪三组人至 3 岁的生殖和儿童健康结果：通过 ART 受孕的婴儿（约 18,000 名）、未通过 ART 受孕的生育力低下的妇女（约 5,000 名）和生育能力强的妇女受孕的婴儿（约 354,000 名）。该项目解决了先前 ART 研究的主要局限性（生育力低下比较组有限，以及缺乏基于人群的数据和纵向儿童健康措施）。将测试两个广泛的假设：(1) 与两个对照组相比，接受 ART 治疗出生的儿童胎儿、围产期、婴儿和幼儿健康结果受损的风险显着更高；(2) 婴儿和儿童健康结果不良的风险将因 ART 治疗参数、不孕症诊断及其相互作用而异。处理参数将包括配子来源；卵母细胞或胚胎的状态；胚胎阶段；显微操作；移植胚胎的数量；胎儿早期流产；先前治疗周期的数量和结果。在这两种情况下，我们将在三个年龄阶段检验这些假设：1）胎儿/围产期； 2）婴儿健康至一周岁； 3) 儿童健康至三岁。分析将分五个阶段进行：1）单变量分析； 2）未经调整的双变量分析； 3）针对已知混杂因素进行调整的多变量分析； 4）亚组分析； 5) 路径分析，以评估 ART 治疗参数和不孕不育诊断的差异效应，以及 ART 总体效应的大小，以及基于八年人口的样本中多种因素对围产期和儿童健康结果的直接和间接影响。结果将是迄今为止对与 ART 相关的儿童健康结果进行的最大规模、最精细的分析。 公共健康相关性：研究表明，不孕症和辅助生殖技术 (ART) 治疗后出生的儿童出现不良健康结果的风险更大，尽管先前研究的普遍性因样本量小和缺乏生育力低下对照组而受到阻碍。随着不孕不育治疗的使用不断增加，重要的是要确定这种增加的风险有多少与 ART 治疗有关，而不是与潜在的不孕不育有关，以及是否有残留影响延伸到幼儿期。拟议的项目将把 2004 年至 2011 年 ART 临床数据与马萨诸塞州妊娠至早期出生和胎儿死亡纵向档案联系起来（导致大约 18,000 例 ART 辅助分娩、5,000 例未接受 ART 但有其他生育能力低下指标的新生儿，以及 380,000 例其他出生），促进迄今为止最大、最全面的美国关于不孕症、ART 和儿童健康的研究从出生到三岁。