Longitudinal metabolic profiling throughout gestation in the plasma and urine of women who develop early-onset preeclampsia
早发性先兆子痫女性整个妊娠期血浆和尿液的纵向代谢分析
基本信息
- 批准号:9397970
- 负责人:
- 金额:$ 0.93万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2016
- 资助国家:美国
- 起止时间:2016-08-05 至 2017-09-05
- 项目状态:已结题
- 来源:
- 关键词:AddressAffectAmino AcidsAngiogenic FactorBiochemistryBiologicalBiologyBirth WeightBloodBlood CirculationBlood PressureCessation of lifeClinicalClinical TreatmentComplexDevelopmentDiabetes MellitusDiscipline of obstetricsDiseaseDoctor of PhilosophyEtiologyFailureFetusFunctional disorderFutureGeneral HospitalsGenomicsGestational AgeGray unit of radiation doseHospitalsHypertensionInfantInstitutesInvestigationKidneyKnowledgeLaboratory StudyLate-Onset DisorderLeadLeftLipidsLiquid ChromatographyMass Spectrum AnalysisMassachusettsMeasuresMetabolicMothersNeonatal MortalityNon-Insulin-Dependent Diabetes MellitusNucleotidesOutputPathogenesisPathway interactionsPatientsPhenotypePhysiologyPlacentaPlasmaPositioning AttributePre-EclampsiaPregnancyPregnancy TrimestersPregnant WomenPremature BirthProteinsProteinuriaPublic HealthReportingResearch DesignResearch PersonnelSamplingSeizuresSubgroupTechniquesTestingTimeUnited StatesUrineWomanWorkbaseclinical careclinical phenotypeclinical predictorscohortcollaborative environmentdisease phenotypeearly onsetexperienceexperimental studyfetalimprovedinsightlaboratory experiencematernal morbiditymedical schoolsmetabolic phenotypemetabolic profilemetabolomemetabolomicsneonatal morbidityorganic acidpathophysiology of preeclampsiapregnancy disorderpublic health relevancesmall moleculesugartraining opportunityurinary
项目摘要
DESCRIPTION (provided by applicant): Preeclampsia is a severe disorder that affects 3-7% of all pregnancies. It is a leading cause of maternal and neonatal morbidity and mortality worldwide. Preeclampsia is characterized by new-onset hypertension and proteinuria after 20 weeks gestation. Left untreated, it can lead to maternal seizures, multi-organ failure, and death. Delivery is the only cure, which often necessitates preterm birth. Despite extensive investigation, the etiology of preeclampsia is poorly understood. Improved understanding of the disease could significantly improve clinical care for pregnant women. Recently metabolomics (i.e., metabolic profiling, meaning the examination of cellular metabolites such as sugars, amino acids, organic acids, nucleotides, and lipids) has emerged as a promising technique for understanding complex diseases, such as hypertension and type 2 diabetes. This approach is also useful for understanding disorders of pregnancy, since maternal metabolites represent the output of a network of interactions between maternal, fetal, and placental compartments. Initial metabolic profiling experiments in women with preeclampsia have demonstrated altered metabolites; however, these studies have significant limitations. Specifically, (1) the metabolic signatures reported in women with preeclampsia have been unique in each study; (2) subgroups of women with preeclampsia have been analyzed together (i.e., those with early- and late-onset disease); (3) only one time point in gestation has been analyzed in each study; (4) urine analysis is lacking from most studies. We propose here the first longitudinal, global metabolic profiling of both maternal plasma and urine in each trimester of pregnancy in women who developed early-onset preeclampsia (requiring delivery prior to 37 weeks). The samples for this analysis are already banked and ready for use. The cohort includes 2105 total women, 56 of whom developed early-onset preeclampsia. We will characterize the global metabolic profile in maternal blood and urine in women with early-onset preeclampsia and matched controls using well-established liquid chromatography tandem mass spectroscopy platforms. Changes in metabolites will be analyzed between trimesters for each patient. Additionally, differences in metabolites between preeclamptics and matched controls will be analyzed by trimester. We will then assess if the metabolic phenotype can identify subgroups of patients based on their clinical phenotypes with a focus on gestational age at delivery, infant birth weight, and abnormal laboratory studies. These experiments will define the metabolic profile throughout pregnancy in women who develop early-onset preeclampsia and will enhance our understanding of pathways involved in disease pathogenesis. Ultimately, this knowledge has the potential to lead to new predictive tests and treatments for preeclampsia.
描述(由申请人提供):先兆子痫是一种严重疾病,影响 3-7% 的妊娠,是全球孕产妇和新生儿发病和死亡的主要原因。先兆子痫的特点是妊娠 20 周后新发高血压和蛋白尿。如果不及时治疗,可能会导致产妇癫痫发作、多器官衰竭和死亡,而分娩是唯一的治疗方法,尽管发生率很高,但通常需要早产。调查显示,对先兆子痫的病因知之甚少,提高对这种疾病的了解可以显着改善最近的代谢组学(即代谢分析,即糖、氨基酸、有机酸、核苷酸、和脂质)已成为了解高血压和 2 型糖尿病等复杂疾病的一种有前途的技术,这种方法对于了解妊娠疾病也很有用,因为母体代谢物代表了相互作用网络的输出。先兆子痫女性的初始代谢分析实验表明,这些研究具有显着的局限性,具体而言,(1)每项研究中报告的先兆子痫女性的代谢特征都是独特的。 2) 对患有先兆子痫的女性亚组进行了分析(即患有早发型和晚发型疾病的女性);(3) 仅对妊娠期的一个时间点进行了分析; (4) 大多数研究都缺乏尿液分析,我们在此建议对患有早发性先兆子痫的女性(需要在 37 岁之前分娩)进行妊娠每个三个月的母体血浆和尿液的首次纵向、全面代谢分析。该分析的样本已储存并可供使用,其中 56 名女性患有早发性先兆子痫,我们将描述母体血液和尿液的总体代谢特征。在患有早发性先兆子痫的女性和匹配对照中,使用完善的液相色谱串联质谱平台分析每位患者在妊娠期间的代谢物变化,此外,我们还将分析妊娠期先兆子痫和匹配对照之间代谢物的差异。然后评估代谢表型是否可以根据临床表型识别患者亚组,重点关注分娩胎龄、婴儿出生体重和异常实验室研究。这些实验将定义。患有早发性先兆子痫的女性在整个怀孕期间的代谢特征将增强我们对疾病发病机制的了解,最终,这些知识有可能导致先兆子痫的新预测测试和治疗。
项目成果
期刊论文数量(0)
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Kathryn Johnson Gray其他文献
Kathryn Johnson Gray的其他文献
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{{ truncateString('Kathryn Johnson Gray', 18)}}的其他基金
Clinical and functional follow-up of maternal and fetal preeclampsia genetic risk loci
母婴子痫前期遗传风险位点的临床和功能随访
- 批准号:
10660975 - 财政年份:2022
- 资助金额:
$ 0.93万 - 项目类别:
Clinical and functional follow-up of maternal and fetal preeclampsia genetic risk loci
母婴子痫前期遗传风险位点的临床和功能随访
- 批准号:
10424668 - 财政年份:2022
- 资助金额:
$ 0.93万 - 项目类别:
Signatures of dysfunctional mitochondrial fatty acid oxidation that predispose to early-onset preeclampsia
线粒体脂肪酸氧化功能失调的特征易患早发性先兆子痫
- 批准号:
10395937 - 财政年份:2019
- 资助金额:
$ 0.93万 - 项目类别:
Signatures of dysfunctional mitochondrial fatty acid oxidation that predispose to early-onset preeclampsia
线粒体脂肪酸氧化功能失调的特征易患早发性先兆子痫
- 批准号:
9906266 - 财政年份:2019
- 资助金额:
$ 0.93万 - 项目类别:
Signatures of dysfunctional mitochondrial fatty acid oxidation that predispose to early-onset preeclampsia
线粒体脂肪酸氧化功能失调的特征易患早发性先兆子痫
- 批准号:
10253476 - 财政年份:2019
- 资助金额:
$ 0.93万 - 项目类别:
Signatures of dysfunctional mitochondrial fatty acid oxidation that predispose to early-onset preeclampsia
线粒体脂肪酸氧化功能失调的特征易患早发性先兆子痫
- 批准号:
10604296 - 财政年份:2019
- 资助金额:
$ 0.93万 - 项目类别:
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