Iodine Deficiency: Novel assessment methods and implications for reproductive health

项目摘要/摘要 近几十年来，美国缺碘情况急剧增加，导致20%以上的人缺碘 育龄妇女。此外，不孕不育和流产越来越常见，影响深远。 身体、社交和情感方面的后果。需要有针对性的低成本干预措施来解决这些问题 不利的生殖后果。碘是一种潜在的治疗方法，因为它是生物学上的 对生殖、胎盘形成和生长发育所涉及的关键荷尔蒙很重要 后代。严重缺乏对甲状腺功能减退症和不可逆脑损伤的影响是众所周知的 有缺陷的孕妇的后代。然而，人们对缺乏对女性的影响知之甚少 生育力、生育力、妊娠丢失等妊娠并发症。研究的含义是 缺乏症已被证明具有相当的挑战性，因为它并不总是出现在临床上，而且每天都有令人难以置信的变数- 今天。通常建议需要10个尿样才能准确地分类儿童的碘状况 一个个体。然而，许多研究没有遵循这一建议，而是依赖于单一的现场尿液，这种尿液可以 导致发现严重减弱，阻碍了碘研究的进展。准确的证据基础是 迫切需要为有关碘强化、补充和饮食的政策和个人决策提供信息 所有这些都提供了一种潜在的低成本解决方案，以促进妇女和 他们的后代。我们提出了一种新的应用生物样品池来分类个体的碘状况和 克服先前的测量挑战。我们 池化 开发了一种创新的混合设计，既使用了 和随机抽样，在怀孕前和整个怀孕期间测量碘。 这项研究的目的是调查碘对生殖和围产儿结局的作用，包括罕见的 研究了受精率、生育力、早孕丢失的结果。这项工作将利用勤奋的学习 (n=1228)，现有的明确的、先入为主的妇女队列，这些妇女有怀孕损失的高风险，每天 尿液收集先入为主，如果她们怀孕了，在怀孕的前四周 全程补充现场尿样，并在分娩时采集胎盘。使用新型生物杀虫剂 合并方法我们将对怀孕前、怀孕早期、怀孕中期和怀孕晚期的碘状况进行分类。使用试验 模拟的方法，我们将调查碘缺乏的影响，跨越关键的敏感期 对生殖和围产期结局的影响。我们还将测量胎盘样本中的碘；目前对此知之甚少 孕期母体碘如何与胎盘碘相关，以及这种相互关系如何与妊娠相关 结果。通过对碘状态的新表征，成功地实现了这些目标 通过使用生物素池和胎盘进行怀孕的先入为主的研究将使研究成为可能 碘在生殖和围产期健康中的作用。如果牵涉其中，碘是一种低成本的干预措施，这可能是 用于针对有不良后果风险的女性。

PROJECT SUMMARY/ABSTRACT Iodine deficiency has increased dramatically in the U.S. in recent decades leading to over 40% deficiency in reproductive age women. Moreover, infertility and pregnancy loss are increasingly common with far reaching physical, social, and emotional consequences. Targeted low-cost interventions are needed to address these adverse reproductive outcomes. Iodine is a potential therapeutic for these outcomes as it is biologically important for critical hormones involved in reproduction, placentation, and growth and development of offspring. Severe deficiency is well known for its effect on hypothyroidism and irreversible brain damage in offspring of deficient pregnant women. However, little is understood on the effects of deficiency on women's fertility, fecundity, pregnancy loss, and other pregnancy complications. Research into the implications of deficiency has proven quite challenging as it does not always present clinically and is incredibly variable day- to-day. It is commonly recommended that 10 urine samples are needed to accurately classify iodine status of an individual. Yet many studies fail to follow this recommendation and rely on a single spot urine which can lead to grossly attenuated findings, hampering progress in iodine research. An accurate evidence base is critically needed to inform policy and individual decisions on iodine fortification, supplementation, and dietary intake, all which of which offer a potential low-cost solution to promote the health and wellbeing of women and their offspring. We propose a novel application of biospecimen pooling to classify individual's iodine status and overcome prior measurement challenges. We pooling have developed an innovative hybrid design that uses both and random sampling to measure iodine in preconception and throughout pregnancy.The overarching goal of this study is to investigate the role of iodine on reproductive and perinatal outcomes including rarely studied outcomes of fecundability, fertility, very early pregnancy loss. This work will utilize the EAGeR study (n=1228), an existing well-defined, preconception cohort of women at high risk for pregnancy loss with daily urine collection preconception, and if they achieved pregnancy, during the first four weeks of pregnancy with additional spot urine samples throughout, and collection of the placenta at delivery. Using novel biospecimen pooling methods we will classify iodine status in preconception, early-, mid-, and late- pregnancy. Using a trial emulation approach, we will investigate the effects of iodine deficiency, across critical periods of susceptibility on reproductive and perinatal outcomes. We will also measure iodine in placenta samples; little is known about how maternal iodine in gestation relates to placental iodine and how this interrelationship relates to pregnancy outcomes. The successful completion of these aims with the novel characterization of iodine status from preconception through gestation using biospecimen pooling and in the placenta will enable investigations into iodine's role in reproductive and perinatal health. If implicated, iodine is a low-cost intervention, that could be used to target women at risk for adverse outcomes.