Assisted Reproduction and Child Health: Risk of Birth Defects, Mortality, and Effect on Grade School Performance

据估计，美国约有12%的育龄妇女曾经求医 治疗不孕症辅助生殖技术（ART）包括所有不孕症治疗，以实现概念; 体外受精（IVF）是卵母细胞在体外通过精液受精的过程;非IVF ART 治疗方法包括诱导排卵、人工授精和子宫内授精。2013年在 在美国，有近68，000名婴儿通过试管婴儿出生，占所有出生人数的1.7%， 在过去的十年里翻了一番。到目前为止，还没有一项基于人群的ART研究， 美国的IVF将ART治疗数据、出生结果、登记确认的出生缺陷和 学校表现。通过这项研究，我们试图填补这一知识空白。本研究旨在 评估死亡率、出生缺陷的风险以及对儿童小学成绩的影响 通过IVF和ART受孕的人，他们的兄弟姐妹，以及纽约、德克萨斯州、马萨诸塞州和北 卡罗莱纳。这项拟议的研究将基于2004年至2018年的出生人数，估计将包括163，000例试管婴儿 41，000名IVF兄弟姐妹和1，250，000名非IVF对照儿童。总体具体目标：比较 出生缺陷率和死亡率，以及对试管婴儿儿童学习成绩的影响， 非IVF ART和自发，包括兄弟姐妹。假设1：试管婴儿出生的孩子风险更高 出生缺陷的风险高于对照组;风险因治疗和父母特征而异。初级 目的：1）测试IVF和非IVF ART出生的出生缺陷风险是否高于IVF ART出生的风险。 自然受孕的分娩; 2）确定影响各组风险的父母因素; 3）在IVF中 组，以确定影响风险的治疗因素。假设2：试管婴儿出生的孩子 与他们的兄弟姐妹和非IVF对照儿童相比，死亡风险，主要是由于多个状态 （更大的可能性被认为是双胞胎，三胞胎，或四胞胎，但作为一个单胞胎出生;或有 出生时为双胞胎、三胞胎或四胞胎）和相关的过度生长限制（小于胎龄儿） 和早产这一更大的围产期相关死亡风险被假设为不显著， 年龄，并因不孕治疗和父母因素而异（特别是年龄较大的产妇 分娩年龄和母亲教育程度较高）。假设3：试管婴儿出生的孩子 教育成绩较差的风险，更有可能需要特殊教育服务， 他们的兄弟姐妹和非IVF对照儿童，主要是由于他们的多元性状态（更大的可能性是 被认为是双胞胎，三胞胎或四胞胎，但出生时是单胞胎;或出生时是双胞胎，三胞胎，或 四胞胎）和相关的过度生长限制（小于胎龄）和早产。这 更大的围产期相关的教育风险因不孕症治疗和父母因素而异（特别是 随着产妇分娩年龄的增加和产妇教育程度的提高而减少）。

It is estimated that about 12% of reproductive age women in the United States have ever sought medical care for infertility. Assisted reproductive technology (ART) includes all infertility treatments to achieve conception; in vitro fertilization (IVF) is the process by which an oocyte is fertilized by semen outside the body; non-IVF ART treatments include ovulation induction, artificial insemination, and intrauterine insemination. In 2013 in the United States, there were nearly 68,000 babies born from IVF, accounting for 1.7% of all births, a proportion which has doubled over the past decade. To date, there has not been a population-based study of ART and IVF in the United States linking data on ART treatments, birth outcomes, registry-confirmed birth defects, and school performance. With this proposed study we seek to fill this knowledge gap. The purpose of this study is to evaluate the risk of mortality, birth defects, and effect on grade school performance among children conceived through IVF and ART, their siblings, and controls in New York, Texas, Massachusetts, and North Carolina. This proposed study will be based on births from 2004-18, and will include an estimated 163,000 IVF children, 41,000 IVF siblings, and 1,250,000 non-IVF control children. Overall Specific Aim: To compare the rates of birth defects and mortality, and effect on school performance among children conceived with IVF, non-IVF ART, and spontaneously, including siblings. Hypothesis 1: Children born from IVF have higher risks for birth defects than the control group; the risk varies by treatments and parental characteristics. Primary Aims:1) To test whether the risk of birth defects in IVF and non-IVF ART births are higher than in spontaneously-conceived births; 2) To identify parental factors affecting risk within each group; 3) In the IVF group, to identify treatment factors that affect the risk. Hypothesis 2: Children born from IVF have higher risks of death compared to their siblings and non-IVF Control children, primarily due to plurality status (greater likelihood of being conceived as a twin, triplet, or quadruplet, but born as a singleton; or of having been born a twin, triplet, or quadruplet) and associated excess of growth restriction (small-for-gestational age) and prematurity. This greater perinatally-related mortality risk is hypothesized to be nonsignificant by two years of age, and varies by infertility treatments and parental factors (particularly reduced with older maternal age at delivery and higher maternal educational status). Hypothesis 3: Children born from IVF have greater risks of poorer educational performance and are more likely to need special education services compared to their siblings and non-IVF Control children, primarily due to their plurality status (greater likelihood of being conceived as a twin, triplet, or quadruplet, but born as a singleton; or of having been born a twin, triplet, or quadruplet) and the associated excess of growth restriction (small-for-gestational age) and prematurity. This greater perinatally-related educational risk varies by infertility treatments and parental factors (particularly reduced with older maternal age at delivery and higher maternal educational status).