Measuring Early Pregnancy Glycemia and Its Impact on Adverse Outcomes

测量早期妊娠血糖及其对不良后果的影响

• 批准号: 9901046
• 负责人: Camille Elise Powe
• 金额: $ 76.13万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-20 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9901046
• 关键词: Accounting; Affect; Albumins; Biological Assay; Birth Weight; Birth trauma; Blood Glucose; Blood specimen; Boston; Caring; Cesarean section; Classification; Clinical; Cohort Studies; Collaborations; Conceptions; DNA; Data; Development; Diabetes Mellitus; Diagnosis; Diagnostic; Discipline of obstetrics; Dystocia; Early Diagnosis; Enrollment; Erythrocytes; Fetal Macrosomia; First Pregnancy Trimester; Genetic; Genetic Determinism; Genetic Variation; Genomics; Genotype; Gestational Age; Gestational Diabetes; Glucose; Glycosylated hemoglobin A; Goals; Guidelines; Hematology; High Risk Woman; Hyperglycemia; Infant; Infrastructure; Insulin; Insulin Resistance; Investigation; Late pregnancy; Longitudinal Studies; Masks; Massachusetts; Maternal Physiology; Measurable; Measurement; Measures; Modification; Monitor; Mothers; Multicenter Studies; National Institute of Diabetes and Digestive and Kidney Diseases; Neonatal; Neonatal Hypoglycemia; OGTT; Outcome; Participant; Patients; Perinatal; Physiological; Physiology; Population; Pregnancy; Pregnancy Complications; Pregnant Women; Proteins; Research Personnel; Risk; Risk Factors; Second Pregnancy Trimester; Shoulder; Site; Testing; Third Pregnancy Trimester; Time; Umbilical Cord Blood; Woman; Work; adverse outcome; adverse pregnancy outcome; base; early pregnancy; ethnic diversity; evidence base; experience; fetal; genetic profiling; glucose metabolism; glucose monitor; improved; in utero; inter-individual variation; neonatal outcome; novel; obesity in children; pregnant; recruit; response; screening; standard of care; tool

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.

妊娠期高血压有许多公认的并发症，包括胎儿过度生长及其 伴随的风险包括剖宫产、产伤、肩难产、新生儿低血糖和儿童期 肥胖症，等等。现有的证据表明，这些后遗症的发展开始于早期 妊娠，常规诊断妊娠期糖尿病前数月。尽管如此，没有 被广泛接受的妊娠早期高血糖诊断标准。这部分是由于主要的局限性 用于妊娠期血糖测量的工具;孕妇尚未完全受益 在过去四十年中，使用连续葡萄糖监测进行血糖评估取得了进展， (CGM)和糖化标记物（如血红蛋白A1 c）。使用这些工具准确评估风险 不仅可以调查早期妊娠流产和不良反应之间的关系， 结果，但也用于识别调节这些结果风险的血糖外因素， 妊娠早期高血糖的女性。我们建议利用现有的基础设施， 在妊娠早期对不同种族的孕妇进行纵向观察性队列研究， 在马萨诸塞州波士顿的两个研究中心进行妊娠试验（合计5000例分娩/年），作为多项研究的一部分， 中心联盟与NIDDK合作。我们的研究团队，妊娠期血糖专家 代谢，糖化蛋白测定，CGM和围产期基因组学，带来了数十年的经验合作 在多中心研究中，招募和长期保留非常成功。在妊娠受试者中 如果在妊娠早期没有预先存在的糖尿病，我们将使用口服胰岛素进行连续血糖评估。 葡萄糖耐量试验、CGM和整个妊娠期的糖化标记物。我们将跟踪参与者， 分娩，以确定产妇和新生儿的结果。在目标1中，我们将使用CGM来定义高血糖症， 早期妊娠与大于胎龄儿出生体重和其他高血糖症的相关性， 相关的不良后果。在目标2中，我们将确定一个最佳的糖化标记物，可在非禁食状态下测量。 血液样本，以评估妊娠早期和整个妊娠期的妊娠率。在目标3中，我们将测试关键额外- 血糖因子（母体胰岛素抵抗和常见的胎儿遗传变异）作为 产妇流产与不良结局的关系。这些调查将建立一个新的 妊娠早期高血糖诊断护理标准，简化妊娠早期高血糖临床测量 怀孕，并为产科人口带来精确糖尿病护理的进步。