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

基本信息

批准号：
10701659
负责人：
Camille Elise Powe
金额：
$ 78.09万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-09-20 至 2025-07-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10701659
关键词：
Accounting Affect Albumins Biological Assay Birth Weight Birth trauma Blood Glucose Blood specimen Boston Caring Cesarean section Classification Clinical Collaborations Conceptions Continuous Glucose Monitor DNA Data Development Diabetes Mellitus Diagnosis Discipline of obstetrics Dystocia Early Diagnosis Enrollment Erythrocytes Fetal Macrosomia Fingers 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 diagnostic criteria early pregnancy ethnic diversity evidence base experience fetal genetic profiling glucose metabolism glycation improved in utero hyperglycemia inter-individual variation maternal outcome neonatal outcome novel obesity in children observational cohort study pregnant recruit response risk mitigation screening standard of care tool

项目摘要

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.

妊娠期高血糖有许多已知的并发症，包括胎儿过度生长及其剖腹产、产伤、肩难产、新生儿低血糖和儿童期的伴随风险肥胖等。现有证据表明这些后遗症的发展始于早期妊娠期，常规诊断妊娠期糖尿病前几个月。尽管如此，没有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限制用于妊娠期血糖测量的工具；孕妇尚未完全受益过去四十年在使用连续血糖监测进行血糖评估方面取得的进展 (CGM) 和糖化标记物（如血红蛋白 A1c）。使用这些工具准确评估血糖不仅可以研究妊娠早期血糖与不良反应之间的关系的结果，还可以识别调节这些结果风险的额外血糖因素妊娠早期有高血糖的妇女。我们建议利用我们现有的基础设施来招聘对妊娠前三个月的不同种族孕妇进行纵向观察队列研究马萨诸塞州波士顿两个地点的妊娠期血糖（每年总计 5000 次分娩）作为多方面研究的一部分中心联盟与 NIDDK 合作。我们的研究团队是妊娠血糖专家代谢、糖化蛋白检测、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，招募和长期保留非常成功。在怀孕的参与者中如果在妊娠前三个月没有预先存在糖尿病，我们将使用口服药物进行连续血糖评估整个妊娠期的葡萄糖耐量测试、CGM 和糖化标记物。我们将跟随参与者分娩以确定孕产妇和新生儿的结局。在目标 1 中，我们将使用 CGM 来定义高血糖：基于与大于胎龄出生体重和其他高血糖相关的早孕- 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，可在非禁食的情况下进行测量血液样本，以评估妊娠早期和整个妊娠期的血糖。在目标 3 中，我们将测试关键的额外功能 - 血糖因素（母体胰岛素抵抗和常见的胎儿遗传变异）作为影响调节剂母亲血糖与不良后果之间的关系。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，简化妊娠期血糖的临床测量怀孕，并为产科人群带来精准糖尿病护理的进步。