Measuring Early Pregnancy Glycemia and Its Impact on Adverse Outcomes

妊娠期高血糖有许多公认的并发症，包括胎儿过度生长和 随之而来的风险有剖腹产、产伤、肩难产、新生儿低血糖和童年。 肥胖症等等。现有的证据表明，这些后遗症的发展始于早期 妊娠，在妊娠期糖尿病常规诊断前几个月。尽管如此，没有 被广泛接受的妊娠早期高血糖诊断标准。这在一定程度上是由于重大限制。 用于测量怀孕期间血糖的工具；孕妇尚未完全受益 从过去40年来使用连续血糖监测进行血糖评估方面的进展 (CGM)和糖化标志物(如血红蛋白A1c)。使用这些工具准确评估血糖 不仅可以调查怀孕早期血糖和不良反应之间的关系 结果，但也用于确定调节这些结果风险的血糖外因素 妊娠早期高血糖妇女。我们建议利用我们现有的基础设施招聘 对妊娠早期不同种族的孕妇进行一项纵向观察队列研究 马萨诸塞州波士顿两个地点怀孕期间的血糖(5000次/年总和)作为多项研究的一部分 与NIDDK合作的中心联盟。我们的研究团队，孕期血糖专家 代谢、糖化蛋白分析、CGM和围产期基因组学，带来了数十年的合作经验 在多中心研究中，招聘非常成功，并长期保留。在怀孕的参与者中 如果怀孕前三个月没有糖尿病患者，我们将使用口服进行一系列的血糖评估 妊娠期间的葡萄糖耐量试验、CGM和糖化标志物。我们将跟踪参与者完成 分娩以确定产妇和新生儿的结局。在目标1中，我们将使用CGM来定义 早孕与胎龄、出生体重和其他高血糖有关- 相关的不良后果。在目标2中，我们将确定最佳糖化标记物，可在非空腹情况下测量 血样，以评估怀孕早期和跨孕期的血糖。在目标3中，我们将测试Key Extra- 血糖因子(母体胰岛素抵抗和常见的胎儿遗传变异)作为影响 母体血糖与不良结局的关系。这些调查将建立一个新的 诊断早期妊娠高血糖的护理标准，简化临床血糖测量 怀孕，并为产科人口带来精准糖尿病护理方面的进展。

Hyperglycemia in pregnancy has numerous well-established complications including fetal overgrowth and its attendant risks of cesarean delivery, birth trauma, shoulder dystocia, neonatal hypoglycemia, and childhood obesity, among others. Available evidence suggests that the development of these sequelae begins in early pregnancy, months prior to conventional diagnosis of gestational diabetes mellitus. Despite this, there are no widely accepted diagnostic criteria for hyperglycemia in early pregnancy. This is due, in part, to major limitations of the tools employed for glycemic measurements in pregnancy; pregnant women have not yet fully benefitted from advances accrued over the past four decades in glycemic assessment using continuous glucose monitoring (CGM) and glycated markers (such as hemoglobin A1c). Accurate assessments of glycemia using these tools would allow not only for the investigation of the relationship between early pregnancy glycemia and adverse outcomes, but also for the identification of extra-glycemic factors that modulate the risk of these outcomes in women with early pregnancy hyperglycemia. We propose to use our established infrastructure for recruitment of ethnically-diverse pregnant women in the first trimester to conduct a longitudinal observational cohort study of glycemia in pregnancy at two sites in Boston, Massachusetts (5000 deliveries/year combined) as part of a multi- center Consortium in collaboration with the NIDDK. Our team of investigators, expert in gestational glucose metabolism, glycated protein assays, CGM, and perinatal genomics, brings decades of experience collaborating in multicenter studies with highly successful recruitment and long-term retention. Among pregnant participants without pre-existing diabetes enrolled in the first trimester, we will perform serial glycemic assessment using oral glucose tolerance tests, CGM, and glycated markers across gestation. We will follow participants through delivery to ascertain maternal and neonatal outcomes. In Aim 1 we will use CGM to define hyperglycemia in early pregnancy based on association with large for gestational age birth weight and other hyperglycemia- associated adverse outcomes. In Aim 2 we will identify an optimal glycated marker, measurable on a non-fasting blood sample, to assess glycemia in early pregnancy and across gestation. In Aim 3 we will test key extra- glycemic factors (maternal insulin resistance and common fetal genetic variation) as effect modifiers of the relationship between maternal glycemia and adverse outcomes. These investigations will establish a new standard of care for diagnosis of early pregnancy hyperglycemia, simplify clinical measurement of glycemia in pregnancy, and bring advances in precision diabetes care to the obstetric population.