Original Research
Obstetrics
Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia

https://doi.org/10.1016/j.ajog.2021.11.1366Get rights and content

Background

Impaired vascular function is a central feature of pathologic processes preceding the onset of preeclampsia. Arterial stiffness, a composite indicator of vascular health and an important vascular biomarker, has been found to be increased throughout pregnancy in those who develop preeclampsia and at the time of preeclampsia diagnosis. Although sleep-disordered breathing in pregnancy has been associated with increased risk for preeclampsia, it is unknown if sleep-disordered breathing is associated with elevated arterial stiffness in pregnancy.

Objective

This prospective observational cohort study aimed to evaluate arterial stiffness in pregnant women, with and without sleep-disordered breathing and assess the interaction between arterial stiffness, sleep-disordered breathing, and preeclampsia risk.

Study Design

Women with high-risk singleton pregnancies were enrolled at 10 to 13 weeks’ gestation and completed the Epworth Sleepiness Score, Pittsburgh Sleep Quality Index, and Restless Legs Syndrome questionnaires at each trimester. Sleep-disordered breathing was defined as loud snoring or witnessed apneas (≥3 times per week). Central arterial stiffness (carotid-femoral pulse wave velocity, the gold standard measure of arterial stiffness), peripheral arterial stiffness (carotid-radial pulse wave velocity), wave reflection (augmentation index, time to wave reflection), and hemodynamics (central blood pressures, pulse pressure amplification) were assessed noninvasively using applanation tonometry at recruitment and every 4 weeks from recruitment until delivery.

Results

High-risk pregnant women (n=181) were included in the study. Women with sleep-disordered breathing (n=41; 23%) had increased carotid-femoral pulse wave velocity throughout gestation independent of blood pressure and body mass index (P=.042). Differences observed in other vascular measures were not maintained after adjustment for confounders. Excessive daytime sleepiness, defined by Epworth Sleepiness Score >10, was associated with increased carotid-femoral pulse wave velocity only in women with sleep-disordered breathing (Pinteraction=.001). Midgestation (first or second trimester) sleep-disordered breathing was associated with an odds ratio of 3.4 (0.9–12.9) for preeclampsia, which increased to 5.7 (1.1–26.0) in women with sleep-disordered breathing and hypersomnolence, whereas late (third-trimester) sleep-disordered breathing was associated with an odds ratio of 8.2 (1.5–39.5) for preeclampsia.

Conclusion

High-risk pregnant women with midgestational sleep-disordered breathing had greater arterial stiffness throughout gestation than those without. Sleep-disordered breathing at any time during pregnancy was also associated with increased preeclampsia risk, and this effect was amplified by hypersomnolence.

Introduction

Sleep-disordered breathing (SDB) is characterized by a range of abnormalities from snoring with subtle airflow narrowing to complete airway obstruction (apneas).1,2 These perturbations result in disrupted sleep and intermittent hypoxia, which have been subsequently shown to increase sympathetic activity and oxidative stress and have been associated with cardiovascular disease and hypertension.3, 4, 5, 6

AJOG at a Glance

Sleep-disordered breathing (SDB) in pregnancy is associated with increased preeclampsia risk.

Arterial stiffness, a marker of vascular health, is increased in women who develop preeclampsia.

It is unknown if SDB in pregnancy is associated with elevated arterial stiffness.

SDB was independently associated with increased arterial stiffness throughout gestation.

Excessive daytime sleepiness was associated with increased arterial stiffness in women with SDB in the first or the second trimester (termed midgestation).

Midgestation SDB combined with excessive daytime sleepiness was associated with a 5.7 odds ratio for preeclampsia.

SDB in the third trimester (termed late-gestation) was associated with an 8.2 odds ratio for preeclampsia.

This study demonstrated an independent association between maternal SDB and arterial stiffness throughout pregnancy and established the role of excessive daytime sleepiness as an effect modifier of arterial stiffness and preeclampsia risk.

The physical and hormonal changes of pregnancy (ie, weight gain, reduced upper airway size, estrogen-related rhinitis) may predispose women to SDB, and accumulating evidence links SDB to adverse pregnancy outcomes.7,8 Snoring is a hallmark feature of SDB, and is more prevalent in pregnancy, particularly in the third trimester (35%), compared with nonpregnant women of similar age (4%–14%).9 Importantly, maternal snoring has been associated with adverse pregnancy outcomes, including fetal growth restriction, gestational hypertension, and diabetes.10,11 Polysomnography (overnight sleep recordings) is the reference standard for diagnosing SDB, and allows the measurement of complete (apneas) and partial (hypopneas) upper airway obstructions during sleep. However, polysomnography is not always feasible because it requires participants to sleep overnight in the laboratory, and is associated with greater cost and resource requirements. In previous studies using polysomnography in pregnancy, the prevalence of SDB (17%–45%) was similar to that obtained from snoring-based assessments.1 Importantly, SDB in pregnancy is most often characterized by snoring and associated subtle flow limitation rather than by apneas.12, 13, 14, 15

Women with SDB (defined either by snoring or polysomnography) were found to have a 2.3-fold greater odds for developing a hypertensive disorder of pregnancy, that is, gestational hypertension or preeclampsia, independent of major confounders, including obesity.8 Increased sympathetic activity, systemic inflammation, and oxidative stress may be the mediating mechanisms in the association between SDB and elevations in blood pressure.16, 17, 18 Similarly, a large prospective pregnancy cohort study using sleep assessments to diagnose SDB found an independent association between SDB and preeclampsia (odds ratio [OR], 1.95; 95% confidence interval [CI], 1.18–3.23) and hypertensive disorders of pregnancy (OR, 1.73; 95% CI, 1.19–2.52).7 However, studies examining mechanisms linking SDB with adverse outcomes and vascular health in pregnancy are lacking.

SDB is an independent risk factor for cardiovascular disease, and has been associated with increased arterial stiffness in the general population.19,20 Arterial stiffness is a composite indicator of vascular health and an independent predictor of cardiovascular morbidity and mortality.21 Arterial stiffness and hemodynamic parameters represent early noninvasive indicators of subclinical vascular dysfunction.21 Consequently, their early measurement and detection may enable timely intervention to improve vascular outcomes not only in the short term, but also in the long term, given that the history of preeclampsia is associated with increased cardiovascular risk later in life.22, 23, 24 Because vascular dysfunction is a central feature of pathologic processes preceding preeclampsia, arterial stiffness also represents a promising biomarker in pregnant women. Indeed, we have previously demonstrated that carotid-femoral pulse wave velocity (cfPWV), the reference standard for the measure of arterial stiffness, is predictive of preeclampsia,25 whereas we also found that cfPWV values measured throughout pregnancy diverged after 14 to 17 weeks’ gestation, which is known to be the most critical period for preeclampsia prophylaxis26; increasing arterial stiffness was noted among women who subsequently developed preeclampsia.27 However, it is unknown if SDB contributes to increased arterial stiffness in this population. Therefore, the aims of the present study were to: (1) characterize arterial stiffness and hemodynamic parameters in women, with and without SDB throughout gestation, and (2) investigate the association of SDB and sleep quality with preeclampsia.

Section snippets

Study design

This was a prospective observational cohort study of women with high-risk singleton pregnancies recruited at >14 weeks’ gestation from 2 tertiary obstetrical clinics in Montreal, Canada. High-risk pregnancy criteria included at least 1 of the following at the time of recruitment: age ≥35 years, body mass index (BMI) ≥25 kg/m2, chronic hypertension, preexisting diabetes mellitus or renal disease, conception via in vitro fertilization, or personal or first-degree relative family history of

Characterization of sleep-disordered breathing

Of the 235 recruited women, 191 women completed follow-up assessments and of these (Supplemental Table 1), 181 women (94.8%) completed the sleep questionnaires (“sleep cohort”) (Supplemental Table 2). Reasons for dropping out included abortion, arrhythmia, and loss to follow-up at the recruiting clinics (Figure 1). Compared with women who did not complete the sleep questionnaires, these women had a lower prepregnancy BMI but similar baseline arterial stiffness and hemodynamic measures (

Principal findings

This study prospectively investigated the association between maternal SDB and arterial stiffness in high-risk pregnant women, both of which are associated with increased risk of preeclampsia. We demonstrated that SDB was associated with increased stiffness, and that this effect was compounded by excessive daytime sleepiness.

Results

We found that among women with high-risk pregnancies, SDB in the first or second trimester was associated with greater central arterial stiffness starting at 10 to 13

Acknowledgments

We thank the Royal Victoria Hospital and Jewish General Hospital obstetrical clinical and administrative staff for their help in coordinating the study participants, the ultrasonographers for performing the uterine artery Doppler ultrasounds, and volunteers who aided in the data collection. Importantly, we are grateful to the pregnant women who participated in our study.

References (58)

  • K. Phan et al.

    A longitudinal analysis of arterial stiffness and wave reflection in preeclampsia: identification of changepoints

    Metabolism

    (2021)
  • S.S. Daskalopoulou et al.

    The 2015 Canadian Hypertension Education Program recommendations for blood pressure measurement, diagnosis, assessment of risk, prevention, and treatment of hypertension

    Can J Cardiol

    (2015)
  • D.J. Buysse et al.

    The Pittsburgh Sleep Quality Index: a new instrument for psychiatric practice and research

    Psychiatry Res

    (1989)
  • R.P. Allen et al.

    Restless legs syndrome: diagnostic criteria, special considerations, and epidemiology. A report from the restless legs syndrome diagnosis and epidemiology workshop at the National Institutes of Health

    Sleep Med

    (2003)
  • L.F. Drager et al.

    Obstructive sleep apnea, hypertension, and their interaction on arterial stiffness and heart remodeling

    Chest

    (2007)
  • I.T. Vlachantoni et al.

    Effects of continuous positive airway pressure (CPAP) treatment for obstructive sleep apnea in arterial stiffness: a meta-analysis

    Sleep Med Rev

    (2013)
  • N. Edwards et al.

    Hemodynamic responses to obstructive respiratory events during sleep are augmented in women with preeclampsia

    Am J Hypertens

    (2001)
  • L.M. O’Brien et al.

    Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia: prospective cohort study

    Am J Obstet Gynecol

    (2012)
  • M.F. O’Rourke et al.

    Mechanical factors in arterial aging: a clinical perspective

    J Am Coll Cardiol

    (2007)
  • R. Tauman et al.

    Maternal snoring during pregnancy is associated with enhanced fetal erythropoiesis--a preliminary study

    Sleep Med

    (2011)
  • Y.H. Chen et al.

    Obstructive sleep apnea and the risk of adverse pregnancy outcomes

    Am J Obstet Gynecol

    (2012)
  • J.M. Louis et al.

    Maternal and neonatal morbidities associated with obstructive sleep apnea complicating pregnancy

    Am J Obstet Gynecol

    (2010)
  • B.W.J. Mol et al.

    Pre-eclampsia

    Lancet

    (2016)
  • J.M. Louis et al.

    Predictors of sleep-disordered breathing in pregnancy

    Am J Obstet Gynecol

    (2018)
  • J. Hosselet et al.

    Classification of sleep-disordered breathing

    Am J Respir Crit Care Med

    (2001)
  • J.W. Weiss et al.

    Sympathoexcitation and arterial hypertension associated with obstructive sleep apnea and cyclic intermittent hypoxia

    J Appl Physiol (1985)

    (2015)
  • C.B. Ferreira et al.

    Increased sympathetic responses induced by chronic obstructive sleep apnea are caused by sleep fragmentation

    J Appl Physiol (1985)

    (2020)
  • S. Jelic et al.

    Inflammation, oxidative stress, and repair capacity of the vascular endothelium in obstructive sleep apnea

    Circulation

    (2008)
  • L. Lavie et al.

    Molecular mechanisms of cardiovascular disease in OSAHS: the oxidative stress link

    Eur Respir J

    (2009)
  • Cited by (0)

    The authors report no conflict of interest.

    This study was supported by funding from the Fonds de recherche du Québec – Santé (FRQS), Heart and Stroke Foundation of Canada, McGill University Department of Obstetrics and Gynecology Academic Enrichment Fund, and Canadian Foundation for Women’s Health. K. P. was supported by the FRQS, Société québécoise d’hypertension artérielle, and the Canadian Institutes of Health Research. S.S.D. holds a FRQS Clinician Scientist-Senior salary award. The funding sources had no involvement in study design, the collection, analysis, and interpretation of data, the writing of the report, or the decision to submit the article for publication.

    Cite this article as: Phan K, Pamidi S, Gomez YH, et al. Sleep-disordered breathing in high-risk pregnancies is associated with elevated arterial stiffness and increased risk for preeclampsia. Am J Obstet Gynecol 2022;226:833.e1-20.

    View full text