Obesity and Sleep Apnea in Pregnancy

怀孕期间的肥胖和睡眠呼吸暂停

• 批准号: 10213820
• 负责人: QI FU
• 金额: $ 68.76万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10213820
• 关键词: Adult; American College of Obstetricians and Gynecologists; Angiogenic Factor; Apnea; Atrial Natriuretic Factor; Biological Markers; Blood Pressure; Body mass index; Cardiac; Cardiovascular Diseases; Cardiovascular system; Development; Endoglin; Enrollment; Equilibrium; Exercise; Future; Gestational Diabetes; Guidelines; Heart; Home; Hormones; Hypertension; Individual; Institute of Medicine (U.S.); Knowledge; Lead; Measurement; Measures; Morbidity - disease rate; Mothers; Natriuretic Peptides; Non obese; Obesity; Obstructive Sleep Apnea; Organ; Outcome; PGF gene; Pathogenesis; Peptide Hydrolases; Physiological; Postpartum Period; Posture; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Pregnant Women; Premature Birth; Preventive; Psyche structure; Recommendation; Research; Research Project Grants; Rest; Risk; Risk Factors; Serum; Sleep; Sleep Apnea Syndromes; Sodium Chloride; Stress; Sympathetic Nervous System; System; Techniques; Testing; Update; Vascular Endothelial Growth Factor Receptor-1; Venous blood sampling; Water; Weight Gain; Weight maintenance regimen; Woman; adult obesity; adverse outcome; adverse pregnancy outcome; biomarker development; cardiovascular health; cardiovascular risk factor; early pregnancy; excessive weight gain; fetal; gestational weight gain; high risk; indexing; maternal obesity; mortality; neuromechanism; obese mothers; obese person; obesity biomarkers; pregnancy hypertension; pregnant; prepregnancy; primary endpoint; relating to nervous system; response

Maternal obesity is a major risk factor for adverse pregnancy outcomes (e.g., preeclampsia, gestational diabetes, preterm birth, etc.). This increased risk is attributed, at least in part, to obstructive sleep apnea (OSA), defined as an Apnea and Hypopnea Index (AHI) ≥5. Obese mothers with OSA are at a very high risk for complicated pregnancies. However, it is unknown if the increased risk of OSA is due to being obese at the onset of pregnancy or to excessive weight gain during pregnancy. In addition, the mechanism(s) by which obesity-related OSA creates increased pregnancy risk are also unknown. Obesity, OSA, and pregnancy per se are all associated with sympathetic activation. Whether maternal obesity and OSA increase the risk of adverse pregnancy outcomes through sympathetic neural mechanisms needs to be determined. In addition to the sympathetic nervous system, the natriuretic peptide system also contributes significantly to cardiovascular health and disease. Corin is a transmembrane protease discovered in the heart where it converts pro-atrial natriuretic peptide to active atrial natriuretic peptide, a cardiac hormone that regulates salt-water balance and blood pressure (BP). Corin has been suggested to be involved in the pathogenesis of preeclampsia. Conversely, obese adults were found to have an increased corin content. Whether corin can be used as a biomarker for obesity and/or OSA related pregnancy risk needs to be investigated. The overall objectives of this research are 1) to compare the impact of obesity versus excessive gestational weight gain on OSA in obese and nonobese women; 2) to investigate the mechanism(s) by which obesity and OSA increase cardiovascular risk during pregnancy; and 3) to identify biomarker(s) for obesity-related OSA in pregnant women. To accomplish these objectives, we will enroll early pregnant (≤8 wks. of gestation) obese (pre-pregnancy BMI ≥30 kg/m2) and nonobese (BMI 18.5-24.9 kg/m2) women and follow them throughout gestation. In-home sleep testing will be carried out during early pregnancy and will be repeated between weeks 30-32 of gestation. We will compare AHI, the development or worsening of OSA, and pregnancy outcomes in obese and nonobese women with and without weight gain above the Institute of Medicine recommended levels (Aim 1). We will also use the state-of-the-art technique of microneurography to measure resting sympathetic activity and sympathetic neural responses to physiological stimulations during early and late (32-34 wks.) pregnancy, and postpartum (6-10 wks. post) in obese women with and without OSA and nonobese women without OSA (Aim 2). Finally, venous blood samples will be taken in women enrolled in Aim 2 for measurements of serum corin content and pregnancy-specific angiogenic factors. The relationships between corin, pregnancy-specific angiogenic factors, sympathetic activity, and BP will be explored (Aim 3). Information gained will increase our understanding of the mechanisms by which obesity and OSA increase cardiovascular risk during pregnancy, which will lead to the development of biomarker(s) for early prediction of adverse outcomes, and set a primary target for future preventive options to be developed.

孕产妇肥胖是不良妊娠结局的主要危险因素（例如，先兆子痫， 妊娠糖尿病，早产等）。这种增加的风险至少部分归因于 阻塞性睡眠呼吸暂停（OSA），定义为呼吸暂停，呼吸呼吸呼吸呼吸暂停（AHI）≥5。肥胖的母亲 OSA患上复杂的怀孕风险很高。但是，未知是否增加 OSA的风险是由于怀孕发作时肥胖或在 怀孕。另外，与肥胖相关的OSA创建的机制增加了 怀孕风险也未知。肥胖，OSA和怀孕本身都与 交感激活。产妇肥胖和OSA是否增加了不良怀孕的风险 需要确定通过交感神经力学的结果。除了 同情神经系统，亚位钠肽系统也有显着贡献 心血管健康和疾病。科林是在心脏中发现的跨膜蛋白酶 它将亲原亚催化肽转化为主动性心动尿肽的位置，心脏 调节盐水平衡和血压（BP）的激素。建议科林是 参与先兆子痫的发病机理。相反，发现肥胖的成年人有一个 增加了科林含量。 Corin是否可以用作肥胖和/或OSA相关的生物标志物 需要研究怀孕风险。这项研究的总体目标是1）比较 肥胖与妊娠体重增加的影响对肥胖和非肥胖妇女的OSA的影响； 2）调查肥胖和OSA增加心血管风险的机制 怀孕; 3）鉴定孕妇肥胖相关OSA的生物标志物。完成 这些目标，我们将招募早期怀孕（妊娠≤8wks。）肥胖（怀孕前BMI≥30 kg/m2）和非肥胖症（BMI 18.5-24.9 kg/m2）妇女，并在妊娠期间跟随她们。在家睡觉 测试将在怀孕初期进行，并将在30-32周之间重复 妊娠。我们将比较AHI，OSA的发展或担忧以及怀孕结果 肥胖和非肥胖妇女，有和没有体重增加的医学研究所建议 级别（目标1）。我们还将使用微功能学的最新技术来测量 在静止 早期和晚期（32-34周）怀孕，以及产后（6-10wks。post） 没有OSA和无肥胖女性没有OSA（AIM 2）。最后，将采集静脉血液样本 参加AIM 2的妇女以测量血清核心含量和妊娠特异性血管生成 因素。科林，怀孕特异性血管生成因素，交感神经之间的关系 将探索活动和BP（AIM 3）。获得的信息将增加我们的理解 肥胖和OSA在怀孕期间增加心血管风险的机制 这将导致生物标志物的发展，以早期预测不良后果，并且 为未来的预防选择设定了一个主要目标。