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.

产妇肥胖是不良妊娠结局的主要风险因素（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），定义为呼吸暂停低通气指数（AHI）≥5。肥胖母亲 阻塞性睡眠呼吸暂停综合症（OSA）导致复杂妊娠的风险非常高。然而，不知道是否增加了 OSA的风险是由于怀孕初期肥胖或怀孕期间体重过度增加。 怀孕此外，肥胖相关的OSA产生增加的机制 怀孕风险也是未知的。肥胖、阻塞性睡眠呼吸暂停综合征和怀孕本身都与 交感神经激活母亲肥胖和OSA是否增加不良妊娠的风险 需要确定通过交感神经机制的结果。除了有 交感神经系统，利钠肽系统也有助于显着 心血管健康和疾病。Corin是一种在心脏中发现的跨膜蛋白酶 在那里它将前心房利钠肽转化为活性心房利钠肽， 调节盐水平衡和血压（BP）的激素。科林被认为是 参与先兆子痫的发病机制。相反，肥胖的成年人被发现有一个 增加Corin含量。corin是否可用作肥胖和/或OSA相关的生物标志物 怀孕风险需要调查。本研究的总体目标是：1）比较 肥胖与妊娠期体重过度增加对肥胖和非肥胖妇女OSA的影响; 2)研究肥胖和OSA增加心血管风险的机制， 妊娠;和3）鉴定妊娠妇女中肥胖相关OSA的生物标志物。完成 这些目标，我们将入组早孕（妊娠≤8周）肥胖（孕前BMI ≥30 kg/m2）和非肥胖（BMI 18.5-24.9 kg/m2）妇女，并在整个妊娠期对其进行随访。居家睡眠 测试将在妊娠早期进行，并将在妊娠30-32周之间重复进行。 怀孕我们将比较AHI、OSA的发展或恶化以及妊娠结局， 肥胖和非肥胖妇女，体重增加和不增加超过医学研究所推荐的 水平（目标1）。我们还将使用最先进的显微神经成像技术来测量 静息交感神经活动和交感神经对生理刺激的反应 早期和晚期（32-34周）妊娠和产后（6-10周后）， 无阻塞性睡眠呼吸暂停综合症（OSA）的非肥胖女性和无阻塞性睡眠呼吸暂停综合症（OSA）的非肥胖女性（目标2）。最后，将采集静脉血样， 入组Aim 2的妇女，测量血清corin含量和妊娠特异性血管生成 因素corin与妊娠特异性血管生成因子、交感神经系统的关系 活动，并将探讨BP（目标3）。获得的信息将增加我们的理解 肥胖和阻塞性睡眠呼吸暂停综合征增加怀孕期间心血管风险的机制， 这将导致开发用于早期预测不良结局的生物标志物，以及 为今后制定的预防性备选办法设定一个主要目标。