Microbial Metabolites and Outcomes of Pregnancy Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 201
- 试验地点
- 1
- 主要终点
- TMAO level
研究概览
简要总结
Emerging data connect diet, the gut microbiota and its metabolites in cardiometabolic disease. Hypertensive disorders of pregnancy (HDP) are common and are a leading cause of maternal and neonatal morbidity. HDP likely share similar pathophysiology as cardiometabolic disease in non-pregnant people with a yet unrevealed role of diet and the gut microbiota, including systemic inflammation and endothelial dysfunction.
Despite high biological plausibility that nutrition, the gut microbiota and its metabolites may play a role in health and disease in pregnancy, there is a paucity of data regarding these associations, thus limiting advancement of the field. Similar to the proposed pathogenesis for diet, gut microbiota and the microbial metabolite trimethylamine-N-oxide (TMAO) in cardiovascular disease, we hypothesize that the interplay between maternal diet, the gut microbiota and its associated microbial metabolites play a mechanistic role in HDP. We propose to test this hypothesis in a racially-diverse US cohort to determine association with adverse pregnancy outcomes, specifically future development of HDP. We propose to prospectively collect plasma and urine TMAO throughout pregnancy from a cohort of 200 pregnant participants.
Through 1) characterizing plasma and urine TMAO levels across each trimester of pregnancy, and 2) assessment of this microbial metabolite as a predictor of development of HDP, we have the potential to identify a biomarker that would allow us to identify people at risk of HDP early in pregnancy and provide new opportunities for therapeutic interventions to improve maternal and neonatal outcomes.
详细描述
Overall Plan:
To evaluate maternal markers of metabolism including the maternal microbial metabolite, Trimethylamine N-oxide (TMAO), across pregnancy, and its association with development of hypertensive disorders of pregnancy.
Research Design and Methods:
This prospective longitudinal cohort will enroll pregnant patients in their first trimester of pregnancy (10-14 weeks gestation). Plasma, serum, blood ribonucleic acid (RNA) and urine samples will be collected at the time of enrollment, along with dietary assessment, and self-reported demographic information. The total volume of blood for research lab purposes will be 22.5 cc (one 10 ml lavender top tube, one 10 ml serum separator tube, and one 2.5 ml PAXgene blood RNA tube). If research labs are drawn in coordination with other necessary prenatal labs, the anticipated maximum volume at blood draw would be 42-50 cc of blood, depending on combination of commonly ordered prenatal labs. The total amount of blood drawn from pregnant subjects (including clinical and research draws) will not exceed 50ml in a two-week period. Plasma, serum, blood RNA and urine samples will again be collected in the second trimester, at 24-28 weeks. In addition, maternal plasma, serum, blood RNA and urine will be collected at the time of delivery admission. A 10 cc sample of cord blood will be obtained after delivery and the placenta will be sent to pathology for evaluation. The investigators will measure TMAO levels and other markers of metabolism on all three maternal samples and that of the cord blood. Deoxyribonucleic acid (DNA) from the buffy coat of plasma collection and RNA from a PAXgene blood tube will be obtained for molecular testing of metabolic biomarkers. The placenta will be examined pathologically with attention to vascular pathology. In addition, a dietary history will be obtained at each time point using the interviewer-guided ASA24 (Automated self-administered 24-hour dietary assessment tool)-a web-based survey provided at no cost through the National Institutes of Health website under a researcher-only password protected account (https://epi.grants.cancer.gov/asa24/).
Data and Sample Collection:
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Able to speak and read English
- •Single, viable intrauterine pregnancy
- •No known fetal abnormalities
排除标准
- •Multiple gestation
- •Chromosomal abnormalities
- •Major birth defects
- •Congenital infections
研究组 & 干预措施
Pregnant persons
This prospective longitudinal cohort will enroll pregnant patients in their first trimester of pregnancy (10-14 weeks gestation).
结局指标
主要结局
TMAO level
时间窗: Delivery
TMAO level in maternal blood and urine
TMAO level
时间窗: 10-14 weeks gestation
TMAO level in maternal blood and urine
TMAO level
时间窗: 24-28 weeks gestation
TMAO level in maternal blood and urine
次要结局
未报告次要终点