The association between sleep-disordered breathing and maternal endothelial and metabolic markers in pregnancies complicated by obesity.

Mitchell L Onslow, Jennifer Wolsk, Stephen Wisniewski, Sanjay Patel, Marcia Gallaher, Carl Hubel, David J Cashmere, Francesca L Facco
Author Information
  1. Mitchell L Onslow: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
  2. Jennifer Wolsk: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
  3. Stephen Wisniewski: Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania.
  4. Sanjay Patel: Center for Sleep and Cardiovascular Outcomes Research, Division of Pulmonary Allergy and Critical Care Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
  5. Marcia Gallaher: Magee-Womens Research Institute, Pittsburgh, Pennsylvania.
  6. Carl Hubel: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.
  7. David J Cashmere: University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
  8. Francesca L Facco: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pittsburgh, Pennsylvania.

Abstract

STUDY OBJECTIVES: To evaluate the impact of sleep-disordered breathing (SDB) on vascular, angiogenic and metabolic analytes in pregnancy.
METHODS: Participants with a body mass index ≥30 kg/m underwent polysomnography at 14-20 weeks gestation (visit 1). Participants with SDB (defined as an apnea-hypopnea index ≥5 events/h) were then enrolled in a separate trial. SDB-negative participants returned for a polysomnogram at 28-31 weeks (visit 2) and were recategorized as persistent-negative SDB or new-onset SDB. Mean arterial blood pressure, mean uterine artery Doppler pulsatility index, endoglin, soluble Feline McDonough Sarcoma-like tyrosine kinase 1, placental growth factor, and the homeostatic model assessment for insulin resistance were measured after each visit. Our primary outcome was a composite of uterine artery Doppler pulsatility index, soluble FMS-like tyrosine kinase 1/placental growth factor ratio, and homeostatic model assessment for insulin resistance. For secondary analyses, each outcome variable was analyzed independently.
RESULTS: A total of 242 and 130 participants completed visit 1 and visit 2, respectively. Newly diagnosed SDB was present in 37% of individuals at visit 1 and 31% of individuals at visit 2. No significant differences in our composite outcome vector were observed in individuals with and without SDB at either visit. In our secondary analysis, mean arterial blood pressure (88.7 ± 7.3 mm Hg vs 85.4 ± 7.1 mm Hg, = .04) and fasting glucose (92.4 ± 15.2 mg/dL vs 86.6 ± 11.5 mg/dL, = .05) were higher in participants with early pregnancy SDB. These associations were not observed for new-onset SDB. No associations were observed between uterine artery Doppler pulsatility index and angiogenic markers and SDB in pregnancy.
CONCLUSIONS: SDB in early pregnancy was not associated with our composite primary outcome but was associated with higher mean arterial blood pressure and fasting glucose. The pathophysiologic changes that occur in pregnant individuals with SDB and how they lead to an increased risk of preeclampsia and gestational diabetes remain poorly understood.
CLINICAL TRIAL REGISTRATION: Registry: ClinicalTrials.gov; Name: Sleep Disordered Breathing, Obesity and Pregnancy Study (SOAP); URL: https://clinicaltrials.gov/ct2/show/NCT02086448; Identifier: NCT02086448.
CITATION: 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. . 2023;19(1):97-109.

Keywords

Associated Data

ClinicalTrials.gov | NCT02086448

References

  1. Eur Respir J. 2010 Oct;36(4):849-55 [PMID: 20525714]
  2. N Engl J Med. 2004 Feb 12;350(7):672-83 [PMID: 14764923]
  3. Am J Obstet Gynecol. 2012 Dec;207(6):487.e1-9 [PMID: 22999158]
  4. Obstet Gynecol. 2017 Jan;129(1):31-41 [PMID: 27926645]
  5. J Clin Sleep Med. 2012 Oct 15;8(5):597-619 [PMID: 23066376]
  6. Am J Pathol. 2001 May;158(5):1713-21 [PMID: 11337369]
  7. Am J Epidemiol. 2013 May 1;177(9):1006-14 [PMID: 23589584]
  8. Hypertension. 2008 Apr;51(4):1027-33 [PMID: 18259003]
  9. BMJ. 2008 May 17;336(7653):1117-20 [PMID: 18480117]
  10. PLoS One. 2010 Oct 12;5(10):e13270 [PMID: 20967275]
  11. Chest. 2014 Oct;146(4):982-990 [PMID: 24831859]
  12. Diabet Med. 2005 Oct;22(10):1434-9 [PMID: 16176208]
  13. Pulm Med. 2013;2013:521087 [PMID: 23936649]
  14. Am J Obstet Gynecol. 2005 Aug;193(2):429-36 [PMID: 16098866]
  15. Ultrasound Obstet Gynecol. 2016 May;47(5):573-9 [PMID: 26582336]
  16. Int J Obes (Lond). 2019 May;43(5):1070-1081 [PMID: 30254363]
  17. J Physiol. 2019 May;597(10):2639-2650 [PMID: 31002746]
  18. Exp Mol Med. 2012 Jan 31;44(1):1-9 [PMID: 22228176]
  19. Obstet Gynecol Int. 2009;2009:275613 [PMID: 19936122]
  20. Nat Med. 2006 Jun;12(6):642-9 [PMID: 16751767]
  21. Ultrasound Obstet Gynecol. 2011 May;37(5):534-7 [PMID: 20878683]
  22. Am J Obstet Gynecol. 1998 Oct;179(4):946-51 [PMID: 9790376]
  23. J Clin Endocrinol Metab. 2019 Jul 1;104(7):2569-2579 [PMID: 30794722]
  24. N Engl J Med. 2000 May 11;342(19):1378-84 [PMID: 10805822]
  25. Thorax. 2014 Apr;69(4):371-7 [PMID: 24262432]
  26. Chest. 2021 Jan;159(1):356-365 [PMID: 32687908]
  27. Am J Respir Crit Care Med. 2014 Jul 15;190(2):218-25 [PMID: 24897551]
  28. Ultrasound Obstet Gynecol. 2014 May;43(5):500-7 [PMID: 24339044]
  29. Am J Obstet Gynecol. 2016 May;214(5):651.e1-5 [PMID: 26640073]
  30. Obstet Gynecol. 2020 Jun;135(6):e237-e260 [PMID: 32443079]
  31. Sleep. 2004 Nov 1;27(7):1405-17 [PMID: 15586794]
  32. J Matern Fetal Neonatal Med. 2009 Nov;22(11):1021-38 [PMID: 19900040]
  33. Am J Obstet Gynecol. 2007 Sep;197(3):244.e1-8 [PMID: 17826405]
  34. Sleep Med. 2016 Sep;25:156-161 [PMID: 27810258]
  35. Ultrasound Obstet Gynecol. 2008 Aug;32(2):138-46 [PMID: 18634131]
  36. Asian Biomed (Res Rev News). 2009 Oct 1;3(5):477-486 [PMID: 21625410]
  37. Am J Respir Crit Care Med. 2003 May 1;167(9):1181-5 [PMID: 12615621]
  38. Diabetologia. 2010 Mar;53(3):481-8 [PMID: 19946661]
  39. Circulation. 2014 Sep 16;130(12):1003-8 [PMID: 25223771]
  40. Am J Obstet Gynecol. 2011 Apr;204(4):327.e1-6 [PMID: 21458622]
  41. J Perinat Med. 2015 Jan;43(1):81-7 [PMID: 24846956]
  42. JAMA. 2012 May 23;307(20):2169-76 [PMID: 22618924]
  43. N Engl J Med. 2006 Sep 7;355(10):992-1005 [PMID: 16957146]
  44. J Clin Invest. 2003 Mar;111(5):649-58 [PMID: 12618519]
  45. Diabetologia. 1985 Jul;28(7):412-9 [PMID: 3899825]
  46. Am J Hypertens. 2007 Apr;20(4):437-42 [PMID: 17386353]
  47. Obstet Gynecol. 2018 Feb;131(2):e49-e64 [PMID: 29370047]
  48. Obstet Gynecol. 2020 Jul;136(1):118-127 [PMID: 32541276]

Grants

  1. R01 HL120354/NHLBI NIH HHS

MeSH Term

Animals
Cats
Female
Humans
Pregnancy
Arterial Pressure
Insulin Resistance
Obesity
Placenta Growth Factor
Sleep Apnea Syndromes

Chemicals

Placenta Growth Factor

Word Cloud

Created with Highcharts 10.0.0SDBvisit1pregnancyindexsleep-disorderedbreathingmetabolic2outcomeindividuals±participantsarterialbloodpressuremeanuterinearteryDopplerpulsatilitycompositeobserved7markersendothelialangiogenicParticipantsweeksnew-onsetsolubletyrosinekinasegrowthfactorhomeostaticmodelassessmentinsulinresistanceprimarysecondarymmHgvs4=fastingglucosemg/dLhigherearlyassociationsassociatedassociationmaternalpregnanciescomplicatedobesitySTUDYOBJECTIVES:evaluateimpactvascularanalytesMETHODS:bodymass≥30kg/munderwentpolysomnography14-20gestationdefinedapnea-hypopnea≥5events/henrolledseparatetrialSDB-negativereturnedpolysomnogram28-31recategorizedpersistent-negativeMeanendoglinFelineMcDonoughSarcoma-likeplacentalmeasuredFMS-like1/placentalratioanalysesvariableanalyzedindependentlyRESULTS:total242130completedrespectivelyNewlydiagnosedpresent37%31%significantdifferencesvectorwithouteitheranalysis8838504921586611505CONCLUSIONS:pathophysiologicchangesoccurpregnantleadincreasedriskpreeclampsiagestationaldiabetesremainpoorlyunderstoodCLINICALTRIALREGISTRATION:Registry:ClinicalTrialsgovName:SleepDisorderedBreathingObesityPregnancyStudySOAPURL:https://clinicaltrialsgov/ct2/show/NCT02086448Identifier:NCT02086448CITATION:OnslowMLWolskJWisniewskiSet al202319:97-109

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