Obstructive sleep apnoea in pregnant women with obesity : prevalence, mechanisms and screening tools

• Main Author: Johns, Emma Christine
• Format: Dissertation
• Language: English
• Published: University of Edinburgh 2021
• Subjects: diagnostic tools; maternal obesity; obstructive sleep apnoea; OSA; pregnancy-related health complications; sleep questionnaires
• DOI: 10.7488/era/1810

Obesity is an excessive accumulation of fat which is associated with an increased risk of adverse health outcomes. More than 1 in 5 pregnant women in the United Kingdom are currently classified as obese. Women with obesity are at a higher risk of a range of adverse pregnancy outcomes during the antenatal and peripartum periods. Compared to offspring of lean women, the offspring of women with obesity are more likely to be born large for gestational age and to develop cardiometabolic disease across their lifespan. Obesity is the major modifiable risk factor for obstructive sleep apnoea (OSA). An accumulating body of observational evidence suggests that women with OSA during pregnancy have a higher risk of adverse pregnancy outcomes, in particular gestational diabetes and hypertensive disorders of pregnancy. The biological mechanisms underpinning these associations are poorly understood. As in the non-pregnant population, obesity is a key risk factor for OSA during pregnancy. The optimal method of screening for OSA in pregnant women is uncertain. This thesis describes a prospective cohort study performed between 2018 and 2020. It investigates the prevalence of OSA in women with class III obesity (body mass index [BMI] ≥40 kg/m2 ), explores potential mechanisms contributing to adverse pregnancy outcomes through analysis of placental gene expression profiles of women with obesity and OSA, and assesses the utility of OSA screening tools in pregnant women. Chapter 1 contains an overview of the literature in the field of maternal obesity, maternal OSA and mechanistic investigation into the relationship between OSA and cardiometabolic disease as it may relate to pregnancy. Chapter 2 outlines the study methods and scientific techniques which were utilised to undertake the work described thereafter. In Chapter 3, the prevalence of OSA in a cohort of women with class III obesity, and in a comparator lean group, was assessed using home-based sleep studies. OSA was identified in 37.5% of women with obesity in the second trimester, and 50.0% of women with obesity in the third trimester. In comparison, 2.6% of lean women in the second trimester and 9.1% of lean women in the third trimester had OSA. This is the first longitudinal account of OSA prevalence in pregnant women with class III obesity specifically. Exploratory analyses of inflammatory and metabolic markers quantified in maternal serum obtained in the second and third trimesters are also presented. In Chapter 4, results of gene expression profiling of placentae from women with obesity and OSA, and from controls with obesity and no OSA, are presented. Using mRNA sequencing, no significant differences in the expression of genes relevant to the development of adverse pregnancy outcomes were identified. The complexities of identifying potentially relevant findings using this technique in the present cohort, and the need to consider alternative sites contributing to the development of adverse pregnancy outcomes, are discussed. In Chapter 5, the predictive capacity of several OSA screening tools, including tools designed for use in pregnancy and non-pregnancy, were assessed in the study cohort. A pregnancy-specific model published in 2018 by Louis et al. was the most effective tool to screen for OSA in lean and obese pregnant women, including in those with characteristics (e.g., parity and gestation) different to the cohort in whom the tool was developed. The potential application of this model as a screening tool with categorical outcomes relating to the risk of OSA is considered. Chapter 6 summarises the main findings of this thesis and considers future directions of research which may be beneficial. In summary, the work presented in this thesis highlights the high prevalence of OSA in women with class III obesity, a group whose prevalence is set to increase in coming decades. The findings of placental gene expression profiling do not provide clarity regarding the biological mechanisms underlying adverse pregnancy outcomes in maternal OSA, but are, nonetheless, an important contribution to the literature. The utility of a recently published pregnancy-specific screening tool in obese and lean pregnant women is demonstrated, and potential future applications of this tool are considered.