Original Research| Volume 5, ISSUE 3, 100840, March 2023

A trial of positive airway pressure for the treatment of sleep apnea in pregnancy

Published:December 20, 2022DOI:


      The pathophysiology of obstructive sleep apnea in pregnancy remains poorly understood and studies examining the effect of treatment with positive airway pressure on pregnancy have been limited.


      This study aimed to perform a randomized controlled trial of positive airway pressure treatment for obstructive sleep apnea in pregnancy.


      Participants with a body mass index ≥30 kg/m2 underwent polysomnography at 14 to 20 weeks’ gestation (visit 1) and those with obstructive sleep apnea (apnea-hypopnea index ≥5 but <50) were enrolled. In phase 1, participants were randomized to autotitrating positive airway pressure vs sham positive airway pressure; in phase 2, the sham arm was replaced with a sleep hygiene control. Participants returned at 28 to 31 weeks’ gestation (visit 2). The mean arterial blood pressure, uterine artery Doppler pulsatility index, endoglin, soluble FMS-like tyrosine kinase 1 levels, and placental growth factor levels were measured, as well as fasting glucose and insulin to calculate insulin resistance (homeostatic model assessment for insulin resistance). The primary outcome was a composite of the uterine artery Doppler pulsatility index, soluble FMS-like tyrosine kinase 1 to placental growth factor ratio, and the homeostatic model assessment for insulin resistance. For secondary analyses, each outcome variable was analyzed independently. Adherence to treatment was examined.


      A total of 241 participants completed visit 1, and 89 (37%) had an apnea-hypopnea index between 5 and 50. Of the those, 51 participants were randomized in phase 1 and 38 in phase 2. There was no significant difference in our primary outcome by treatment group. In secondary analyses, the uterine artery Doppler pulsatility index was lower in participants on autotitrating positive airway pressure when compared with sleep hygiene controls. Otherwise, there were no differences in the mean arterial blood pressure, angiogenic markers, or metabolic markers in phase 1, phase 2, or across the entire study. The overall adherence to autotitrating positive airway pressure therapy was low, but the mean use was greater in phase 2 (0.3±0.6 hours/night vs 1.3±2.3 hours/night; P=.10). For those on active therapy, fasting glucose values decreased as adherence increased.


      This randomized controlled trial of autotitrating positive airway pressure in pregnancy did not find any differences in a composite primary cardiometabolic risk profile between the treatment groups. Higher autotitrating positive airway pressure adherence was associated with lower fasting glucose levels. The use of a sham positive airway pressure control arm in phase1 may have negatively impacted adherence to active treatment.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to American Journal of Obstetrics & Gynecology MFM
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Young T
        • Finn L
        • Austin D
        • Peterson A.
        Menopausal status and sleep-disordered breathing in the Wisconsin Sleep Cohort Study.
        Am J Respir Crit Care Med. 2003; 167: 1181-1185
        • Peppard PE
        • Young T
        • Barnet JH
        • Palta M
        • Hagen EW
        • Hla KM.
        Increased prevalence of sleep-disordered breathing in adults.
        Am J Epidemiol. 2013; 177: 1006-1014
        • Zamarrón C
        • Valdés Cuadrado L
        • Alvarez-Sala R
        Pathophysiologic mechanisms of cardiovascular disease in obstructive sleep apnea syndrome.
        Pulm Med. 2013; 2013521087
        • Pien GW
        • Schwab RJ.
        Sleep disorders during pregnancy.
        Sleep. 2004; 27: 1405-1417
        • Hedman C
        • Pohjasvaara T
        • Tolonen U
        • Suhonen-Malm AS
        • Myllylä VV.
        Effects of pregnancy on mothers’ sleep.
        Sleep Med. 2002; 3: 37-42
        • Pien GW
        • Fife D
        • Pack AI
        • Nkwuo JE
        • Schwab RJ.
        Changes in symptoms of sleep-disordered breathing during pregnancy.
        Sleep. 2005; 28: 1299-1305
        • Facco FL
        • Kramer J
        • Ho KH
        • Zee PC
        • Grobman WA.
        Sleep disturbances in pregnancy.
        Obstet Gynecol. 2010; 115: 77-83
        • Peppard PE
        • Young T
        • Palta M
        • Skatrud J.
        Prospective study of the association between sleep-disordered breathing and hypertension.
        N Engl J Med. 2000; 342: 1378-1384
        • Punjabi NM
        • Shahar E
        • Redline S
        • et al.
        Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study.
        Am J Epidemiol. 2004; 160: 521-530
        • Reichmuth KJ
        • Austin D
        • Skatrud JB
        • Young T.
        Association of sleep apnea and type II diabetes: a population-based study.
        Am J Respir Crit Care Med. 2005; 172: 1590-1595
        • Pien GW
        • Pack AI
        • Jackson N
        • Maislin G
        • Macones GA
        • Schwab RJ.
        Risk factors for sleep-disordered breathing in pregnancy.
        Thorax. 2014; 69: 371-377
        • Facco FL
        • Parker CB
        • Reddy UM
        • et al.
        Association between sleep-disordered breathing and hypertensive disorders of pregnancy and gestational diabetes mellitus.
        Obstet Gynecol. 2017; 129: 31-41
        • Onslow ML
        • Wolsk J
        • Wisniewski S
        • et al.
        The association between sleep disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity.
        J Clin Sleep Med. 2022; ([Epub ahead of print])
        • Farabi SS
        • Barbour LA
        • Heiss K
        • Hirsch NM
        • Dunn E
        • Hernandez TL.
        Obstructive sleep apnea is associated with altered glycemic patterns in pregnant women with obesity.
        J Clin Endocrinol Metab. 2019; 104: 2569-2579
        • Bourjeily G
        • Curran P
        • Butterfield K
        • Maredia H
        • Carpenter M
        • Lambert-Messerlian G.
        Placenta-secreted circulating markers in pregnant women with obstructive sleep apnea.
        J Perinat Med. 2015; 43: 81-87
        • Blyton DM
        • Sullivan CE
        • Edwards N.
        Reduced nocturnal cardiac output associated with preeclampsia is minimized with the use of nocturnal nasal CPAP.
        Sleep. 2004; 27: 79-84
        • Blyton DM
        • Skilton MR
        • Edwards N
        • Hennessy A
        • Celermajer DS
        • Sullivan CE.
        Treatment of sleep disordered breathing reverses low fetal activity levels in preeclampsia.
        Sleep. 2013; 36: 15-21
        • Guilleminault C
        • Kreutzer M
        • Chang JL.
        Pregnancy, sleep disordered breathing and treatment with nasal continuous positive airway pressure.
        Sleep Med. 2004; 5: 43-51
        • Guilleminault C
        • Palombini L
        • Poyares D
        • Takaoka S
        • Huynh NT
        • El-Sayed Y.
        Pre-eclampsia and nasal CPAP: part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: preliminary findings.
        Sleep Med. 2007; 9: 9-14
        • Poyares D
        • Guilleminault C
        • Hachul H
        • et al.
        Pre-eclampsia and nasal CPAP: part 2. Hypertension during pregnancy, chronic snoring, and early nasal CPAP intervention.
        Sleep Med. 2007; 9: 15-21
        • Berry RB
        • Budhiraja R
        • Gottlieb DJ
        • et al.
        Rules for scoring respiratory events in sleep: update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events. Deliberations of the sleep apnea definitions task force of the American Academy of Sleep Medicine.
        J Clin Sleep Med. 2012; 8: 597-619
        • Rodway GW
        • Weaver TE
        • Mancini C
        • et al.
        Evaluation of sham-CPAP as a placebo in CPAP intervention studies.
        Sleep. 2010; 33: 260-266
        • Budhiraja R
        • Kushida CA
        • Nichols DA
        • et al.
        Impact of randomization, clinic visits, and medical and psychiatric Cormorbidities on continuous positive airway pressure adherence in obstructive sleep apnea.
        J Clin Sleep Med. 2016; 12: 333-341
        • Llurba E
        • Carreras E
        • Gratacós E
        • et al.
        Maternal history and uterine artery Doppler in the assessment of risk for development of early- and late-onset preeclampsia and intrauterine growth restriction.
        Obstet Gynecol Int. 2009; 2009275613
        • Plasencia W
        • Maiz N
        • Poon L
        • Yu C
        • Nicolaides KH.
        Uterine artery Doppler at 11 + 0 to 13 + 6 weeks and 21 + 0 to 24 + 6 weeks in the prediction of pre-eclampsia.
        Ultrasound Obstet Gynecol. 2008; 32: 138-146
        • Venkatesha S
        • Toporsian M
        • Lam C
        • et al.
        Soluble endoglin contributes to the pathogenesis of preeclampsia.
        Nat Med. 2006; 12: 642-649
        • Levine RJ
        • Lam C
        • Qian C
        • et al.
        Soluble endoglin and other circulating antiangiogenic factors in preeclampsia.
        N Engl J Med. 2006; 355: 992-1005
        • Maynard SE
        • Min JY
        • Merchan J
        • et al.
        Excess placental soluble fms-like tyrosine kinase 1 (sFlt1) may contribute to endothelial dysfunction, hypertension, and proteinuria in preeclampsia.
        J Clin Invest. 2003; 111: 649-658
        • Levine RJ
        • Maynard SE
        • Qian C
        • et al.
        Circulating angiogenic factors and the risk of preeclampsia.
        N Engl J Med. 2004; 350: 672-683
        • De Falco S.
        The discovery of placenta growth factor and its biological activity.
        Exp Mol Med. 2012; 44: 1-9
        • Bitó T
        • Földesi I
        • Nyári T
        • Pál A.
        Prediction of gestational diabetes mellitus in a high-risk group by insulin measurement in early pregnancy.
        Diabet Med. 2005; 22: 1434-1439
        • Matthews DR
        • Hosker JP
        • Rudenski AS
        • Naylor BA
        • Treacher DF
        • Turner RC.
        Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man.
        Diabetologia. 1985; 28: 412-419
        • Hauth JC
        • Clifton RG
        • Roberts JM
        • et al.
        Maternal insulin resistance and preeclampsia.
        Am J Obstet Gynecol. 2011; 204 (327.e1–6)
      1. Gestational hypertension and preeclampsia: ACOG Practice Bulletin, Number 222.
        Obstet Gynecol. 2020; 135: e237-e260
      2. ACOG Practice Bulletin No. 190: gestational diabetes mellitus.
        Obstet Gynecol. 2018; 131: e49-e64
        • Bayram NA
        • Ciftci B
        • Keles T
        • et al.
        Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment.
        Sleep. 2009; 32: 1257-1263
        • Ciccone MM
        • Favale S
        • Scicchitano P
        • et al.
        Reversibility of the endothelial dysfunction after CPAP therapy in OSAS patients.
        Int J Cardiol. 2012; 158: 383-386
        • Stajić D
        • Ilić D
        • Vuković J
        • Baturan B
        • Ilić A
        • Milovančev A.
        The effect of continuous positive airway pressure treatment on hypertensive disorder in pregnant women with obstructive sleep apnea.
        Sleep Breath. 2022; 26: 297-305
        • Chirakalwasan N
        • Amnakkittikul S
        • Wanitcharoenkul E
        • et al.
        Continuous positive airway pressure therapy in gestational diabetes with obstructive sleep apnea: a randomized controlled trial.
        J Clin Sleep Med. 2018; 14: 327-336
        • Watach AJ
        • Hwang D
        • Sawyer AM.
        Personalized and patient-centered strategies to improve positive airway pressure adherence in patients with obstructive sleep apnea.
        Patient Prefer Adherence. 2021; 15: 1557-1570
        • Askland K
        • Wright L
        • Wozniak DR
        • Emmanuel T
        • Caston J
        • Smith I.
        Educational, supportive and behavioural interventions to improve usage of continuous positive airway pressure machines in adults with obstructive sleep apnoea.
        Cochrane Database Syst Rev. 2020; 4CD007736
        • Patil SP
        • Ayappa IA
        • Caples SM
        • Kimoff RJ
        • Patel SR
        • Harrod CG.
        Treatment of adult obstructive sleep apnea with positive airway pressure: an American Academy of Sleep Medicine systematic review, meta-analysis, and GRADE assessment.
        J Clin Sleep Med. 2019; 15: 301-334
        • Pamidi S
        • Meltzer SJ
        • Garfield N
        • et al.
        A pilot randomized-controlled trial on the effect of CPAP treatment on glycemic control in gestational diabetes: study design and methods.
        Front Endocrinol (Lausanne). 2018; 9: 659
        • US National Library of Medicine
        Continuous positive airway pressure (CPAP) for sleep apnea in pregnancy (SLEEP).
        2018 (Available at) (Accessed December 7, 2022)
        • US National Library of Medicine
        Positive airway pressure, sleep apnea, and the placenta (PAP-SAP) (PAP-SAP).
        2015 (Available at) (Accessed December 7, 2022)