Obstructive Sleep Apnoea (OSA)

• Pregnant women with obstructive sleep apnoea (OSA) may be at increased risk of adverse maternal and perinatal outcomes.
• Increasing evidence suggests that asthma and OSA are associated, and one can influence the severity of the other.
• Risk factors include obesity and increasing maternal age.
• The risk of OSA is highest in the 3rd trimester, but in most cases, the OSA is classed as mild.
• In women where symptoms are suggestive of OSA, a sleep study may be warranted with trial CPAP treatment where the apnoea-hypopnea index (AHI) >=5.

Sleep disordered breathing is an umbrella term encompassing a number of conditions that include simple snoring, increased upper airway resistance and obstructive sleep apnoea (OSA). In OSA the upper airway partially or completely obstructs during sleep repeatedly causing microarousals and resulting poor sleep quality and hypoxaemia (Izci-Balserak & Pien 2010). In non-pregnant individuals OSA is associated with a 2-3 fold increased risk of cardiac and metabolic abnormalities, particularly hypertension (Gottlieb & Punjabi 2020). In pregnancy OSA is independently associated with hypertension, preeclampsia and gestational diabetes (Facco et al. 2016, Luque-Fernandez et al. 2013)

Generally OSA occurs predominantly in older, obese patients, particularly males, and is uncommon in women of childbearing age. However OSA is seen more frequently in pregnant women compared to their non-pregnant age-matched counterparts. The prevalence of OSA increases with increasing gestational age (Pien et al., 2014). In the first trimester prevalence estimates of OSA vary between 3.6 and 10.5%, mid-pregnancy 8.3% and in the third trimester up to 27% of high risk women are affected (Pien et al. 2014, Facco et al. 2016). Even in third trimester severe disease is uncommon and greater than 80% of OSA is mild . Independent risk factors for the development of third trimester OSA are elevated body mass index and increasing maternal age (Pien et al. 2014).

Symptoms of sleep disordered breathing in pregnancy can include snoring, witnessed apnoeas, gasping, choking and increased daytime sleepiness (Pien et al. 2005).

In pregnancy a number of physiologic, physical and hormonal changes increase the risk of developing obstructive sleep apnoea, a condition that is otherwise relatively uncommon in women of reproductive age (Izci-Balserak & Pien 2010, Pien et al. 2014). Definite evidence of causality is lacking but the mechanisms of this may include; increased upper airway mucosal blood flow causing oedema, obstruction and increased Mallampati score secondary to the effects of increased circulating sex hormones; increased prevalence of non-allergic rhinitis; increased maternal blood volume leading to upper airway congestion and reduced airway calibre; physical elevation of the diaphragm by the enlarging uterus causing reductions in respiratory volumes, small airway closure and ventilation-perfusion mismatch, exacerbated in the supine position; and increased arousals leading to greater respiratory instability (Izci-Balserak & Pien 2010, Izci-Balserak 2015).

OSA diagnosis is based on polysomnography (sleep study) with an apnoea-hypopnea index (AHI) of greater than or equal to 5 (Malhotra and White 2002). Traditionally OSA severity is graded based on the degree of elevation of the AHI although it has been suggested that other markers of severity such as degree and duration of hypoxia may be more closely associated with clinical status and outcomes (Cao et al. 2020). If OSA is suspected the STOP BANG questionnaire can be used as a screening tool, which has been used in research studies of pregnancy (Sag et al. 2021).

The main risk factors for the development of OSA in pregnancy are obesity and increasing maternal age, but any condition that reduces the calibre of the upper airway, such as tonsillar enlargement and macroglossia, increases the risk of OSA (Izci-Balserak 2015). Systematic reviews have found that pregnant women with OSA are at increased risk of a number of adverse outcomes including intrauterine growth restriction, gestational hypertension, preeclampsia and gestational diabetes mellitus, however these analyses are limited by study heterogeneity and lack of adjustment for confounders (Pamidi et al. 2014, Luque-Fernandez et al. 2013).

Both OSA and asthma are common conditions and they frequently co-exist, more often than can be explained by the high prevalence of both conditions or shared risk factors, particularly obesity, gastroesophageal reflux disease and allergic rhinitis (Alharbi et al. 2009, Prasad et al. 2019). The prevalence of OSA in asthma patients is 8-52.6%, and may be even higher (up to 95%) in those with severe asthma (Davies et al. 2019). There is increasing evidence that OSA and asthma are associated and that each condition may influence the severity of the other (Prasad et al. 2019). There is emerging evidence that OSA increases airway inflammation, sputum neutrophils and airway remodelling and that asthma increases the likelihood of upper airway collapse, important in the pathogenesis for OSA (Taillé et al. 2016). The presence of OSA has been associated with poor asthma control (Davies et al. 2019). Treatment of OSA with CPAP in asthma patients has been shown to improve asthma control and health-related quality of life but not lung function or bronchial hyperresponsiveness (Lafond et al. 2007, Kauppi et al. 2016). Furthermore OSA and asthma may have overlapping nocturnal symptoms, complicating the diagnosis of each condition.

There are no data specifically examining the effect of the presence of OSA on asthma status or asthma outcomes in pregnancy.

In non-pregnant women with moderate to severe OSA treatment with continuous positive airway pressure (CPAP) has been shown to improve daytime sleepiness and quality of life, and lower blood pressure (Giles et al. 2006). Other treatments such as oral appliances and positional modifications have been shown to have less impact on the AHI than CPAP but do improve daytime sleepiness (Giles et al. 2006, Srijithesh et al. 2019, Lim et al. 2006). These interventions may be better tolerated and have better adherence than CPAP and are particularly useful for patients who have mild OSA and do not tolerate CPAP (Srijithesh et al. 2019, Lim et al. 2006).

There is limited data available on the effects of treatment of OSA during pregnancy. One study randomised pregnant women into a polysomnography screening group or usual case group, the screening group undertook two sleep studies, one in early pregnancy and one in late pregnancy and those with AHI >=5 were prescribed autoregulated positive airway pressure (APAP) (Kalkhoff et al. 2022). The study was limited by small sample size, low APAP prescription rates and low compliance with APAP, and found that treatment with APAP did not result in a reduction in the primary endpoint, a composite of hypertension, preterm birth, low birthweight, stillbirth and gestational diabetes mellitus (Kalkhoff et al. 2022). Larger studies are needed to further examine whether treatment of OSA with CPAP in pregnancy improves maternal and neonatal outcomes.

There have been no randomised studies examining the effect of treatment of OSA on asthma outcomes during pregnancy.

Given the lack of robust data to inform decisions regarding treatment of OSA in pregnant women with asthma, a pragmatic approach is to perform a sleep study in those with symptoms suggestive of OSA, particularly in the presence of risk factors such as obesity or increased maternal age. Those with an AHI >=5 who are symptomatic may warrant a trial of treatment with CPAP.