Obesity and Sleep Apnea in Pregnancy

母亲肥胖是不良妊娠结局的主要危险因素(例如，先兆子痫、 妊娠期糖尿病、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(阻塞性睡眠呼吸暂停)，定义为呼吸暂停和低通气指数(≥)5.肥胖母亲 阻塞性睡眠呼吸暂停综合征是复杂妊娠的高危人群。然而，目前还不清楚是否会增加 患阻塞性睡眠呼吸暂停综合征的风险是由于怀孕初期肥胖或在怀孕期间体重增加过多。 怀孕了。此外，肥胖相关的阻塞性睡眠呼吸暂停综合征产生的机制(S)增加 怀孕风险也是未知的。肥胖、阻塞性睡眠呼吸暂停综合症和怀孕本身都与 交感神经激活。母亲肥胖和阻塞性睡眠呼吸暂停是否会增加不良妊娠风险 通过交感神经机制的结果需要确定。除 交感神经系统，利钠肽系统也对 心血管健康和疾病。Corin是在心脏中发现的一种跨膜蛋白酶。 在那里它将前心钠素转化为活性心钠素，一种心脏 调节盐水平衡和血压的荷尔蒙。科林被建议成为 参与了子痫前期的发病机制。相反，肥胖的成年人被发现有一个 增加了Corin的含量。Corin是否可以作为肥胖和/或OSA相关的生物标志物 需要对怀孕风险进行调查。本研究的总体目标是：1)比较 肥胖和过度妊娠体重增加对肥胖和非肥胖女性OSA的影响； 2)研究肥胖和阻塞性睡眠呼吸暂停综合征增加心血管疾病风险的机制(S) 3)寻找孕妇肥胖相关阻塞性睡眠呼吸暂停的生物标志物(S)。要完成 这些目标，我们将招收早孕(≤)8周。孕期)肥胖(孕前体重指数≥30 体重指数(BMI)为18.5-24.9公斤/平方米的非肥胖妇女，并在整个妊娠期间对她们进行跟踪。居家睡眠 检测将在怀孕早期进行，并将在30-32周之间重复 怀孕了。我们将比较AHI、OSA的发展或恶化以及妊娠结局 肥胖和非肥胖女性体重增加或不增加超过医学研究所推荐 级别(目标1)。我们还将使用最先进的显微神经学技术来测量 静息交感神经活动和交感神经对生理刺激的反应 早和晚(32-34周)怀孕和产后(6-10周。帖子)在肥胖女性中 没有OSA的女性和没有OSA的非肥胖女性(目标2)。最后，将采集静脉血样 在AIM 2中登记的妇女测量血清Corin含量和妊娠特异性血管生成 各种因素。Corin与妊娠特异性血管生成因子、交感神经的关系 活动，将探索BP(目标3)。所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症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果的生物标记物(S)，以及 为未来要制定的预防方案设定一个主要目标。

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.