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

描述(由调查人员提供)：据估计，育龄妇女中有12%-15%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一直在稳步上升，估计有1%-3%的分娩涉及ART。许多研究报告称，辅助妊娠与自然妊娠相比，不良围产期结局的风险要高得多。与抗逆转录病毒治疗无关的不孕症和亚生育诊断也可能导致更高的不良妊娠结局发生率。记录抗逆转录病毒疗法对儿童健康结果的额外影响，而不仅仅是潜在的亚生育率，仍然是一个挑战。这份申请书描述了波士顿大学公共卫生学院、马萨诸塞州公共卫生部、辅助生殖技术学会和疾病控制和预防中心之间的创新合作。这项合作创建了一个独特的、以人群为基础的纵向数据来源，该数据来源将2004年至2011年期间活产和胎儿死亡的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)数据系统结合在一起。Pell包含关于怀孕、出生、死亡、医院利用、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3岁以下的生殖和儿童健康结果：通过抗逆转录病毒疗法怀孕的婴儿(约18,000人)，通过辅助生殖技术怀孕的婴儿(约5,000人)，以及由生育妇女怀孕的婴儿(约354,000人)。该项目解决了现有技术研究的主要局限性(亚生育比较组有限，缺乏以人口为基础的数据和纵向儿童健康衡量标准)。将检验两个广泛的假设：(1)与两个对照组相比，接受抗逆转录病毒治疗的儿童出生的胎儿、围产期、婴儿和儿童早期健康结果受损的风险显著更高，(2)不良婴幼儿健康结果的风险将因抗逆转录病毒治疗参数、不孕症诊断及其相互作用而不同。治疗参数将包括配子的来源；卵母细胞或胚胎的状态；胚胎的阶段；显微操作；移植的胚胎数量；早期胎儿丧失；以及先前治疗周期的数量和结果。在这两种情况下，我们将在三个年龄段检验这些假设：1)胎儿/围产期；2)婴儿健康到一岁；以及3)儿童健康到三岁。分析将分五个阶段进行：1)单变量分析；2)未调整的双变量分析；3)对已知混杂因素进行调整的多变量分析；4)亚组分析；5)通径分析，以评估抗逆转录病毒治疗参数和不孕症诊断的不同影响，以及抗逆转录病毒治疗的总体影响的大小，以及多元对围产期和儿童健康结果的直接和间接影响。结果将是有史以来完成的对与抗逆转录病毒治疗相关的儿童健康结果的最大、最精细的分析。 公共卫生相关性：研究表明，不孕不育和辅助生殖技术(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亚生育比较组而受到阻碍。随着不孕症治疗的使用持续增加，重要的是要确定这种增加的风险在多大程度上与抗逆转录病毒治疗有关，而不是与潜在的不孕症有关，以及是否存在延续到儿童早期的后遗症影响。拟议的项目将把2004年至2011年的抗逆转录病毒治疗临床数据与马萨诸塞州的妊娠与早期生命纵向出生和胎儿死亡档案联系起来(结果是大约18,000例辅助生育技术助产，5,000例没有抗逆转录病毒治疗但有其他亚生育指标的出生，以及380,000例其他出生)，从而推动了迄今为止规模最大、最全面的美国关于不孕症、抗逆转录病毒治疗和从出生到三岁儿童健康的研究。

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.