Obesity and Sleep Apnea in Pregnancy

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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.