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

据估计，美国约12%的育龄妇女曾寻求过医疗服务 治疗不孕不育症。辅助生殖技术(ART)包括实现受孕的所有不孕症治疗； 体外受精(IVF)是通过体外精液使卵母细胞受精的过程；非体外受精技术 治疗方法包括诱导排卵、人工授精和宫内受精。2013年，在 在美国，有近6.8万名婴儿通过试管婴儿出生，占所有出生婴儿的1.7%，这一比例 这一数字在过去十年中翻了一番。到目前为止，还没有以人群为基础的艺术和 美国的试管受精将ART治疗、出生结局、登记确认的出生缺陷和 学校里的表演。通过这项拟议的研究，我们试图填补这一知识空白。本研究的目的是 评估儿童死亡、出生缺陷的风险及其对小学成绩的影响 通过试管受精和ART受孕，他们的兄弟姐妹，以及纽约、德克萨斯、马萨诸塞州和北部的对照 卡罗莱纳。这项拟议的研究将基于2004-18年出生的婴儿，估计将包括163,000名试管受精 儿童，41,000名试管婴儿兄弟姐妹和1,250,000名非试管婴儿对照儿童。总的具体目标：比较 试管婴儿的出生缺陷和死亡率以及对学习成绩的影响， 非体外受精技术，以及自发的，包括兄弟姐妹。假设1：通过试管婴儿出生的孩子风险更高 出生缺陷的风险比对照组高；风险因治疗方法和父母特征而异。主要 目的：1)测试试管婴儿和非试管婴儿的出生缺陷风险是否高于 自然受孕；2)确定每组中影响风险的父母因素；3)试管受精 小组，以确定影响风险的治疗因素。假设2：通过试管婴儿出生的孩子有更高的 死亡风险与他们的兄弟姐妹和非试管婴儿相比，主要是由于多胞胎状态 (更有可能被认为是双胞胎、三胞胎或四胞胎，但出生时是单胞胎；或有 出生为双胞胎、三胞胎或四胞胎)和相关的过度生长限制(小于胎龄) 和早产儿。这种更大的与围产期相关的死亡风险被假设为不显著的 年龄，并因不孕症治疗和父母因素(特别是高龄产妇减少)而异 分娩年龄和较高的母亲受教育程度)。假设3：通过试管婴儿出生的孩子有更多的 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试管受精控制的孩子，主要是因为他们的多元身份(更有可能是 双胞胎的受孕为双胞胎、三胞胎或四胞胎的，但出生时为单胞胎的；或出生为双胞胎、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 更大的围产期相关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大和产妇受教育程度的提高而降低)。

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).