Aims: Obstructive sleep apnea (OSA) is associated with placenta-mediated adverse clinical outcomes. We aimed at comparing placenta-secreted proteins, such as first and second trimester Down syndrome screening markers which have been linked to preeclampsia, and markers of angiogenesis in pregnant women with OSA, and pregnant controls at low risk for OSA.
Methods: A case-control study of pregnant women with OSA and controls at low risk for OSA was performed. Levels of first and second trimester markers were reported as multiple of median (MoM), and adjusted for body mass index (BMI). Stored samples were tested for markers of angiogenesis and adjusted for gestational age, BMI, and chronic hypertension.
Results: A total of 24 women with OSA and 166 controls had screening markers. BMI was higher in cases compared to controls, P=0.01. MoM levels of placenta associated plasma protein-A (PAPP-A) were significantly lower in cases versus controls, even after adjusting for BMI (0.52 IQR 0.48 vs. 1.01 IQR 0.63, P=0.009). The ratio of soluble vascular endothelial growth factor receptor 1 to placental growth factor was significantly higher in cases than controls, even after adjusting for confounders (4.42 IQR 2.52 vs. 2.93 IQR 2.01, P=0.009).
Conclusion: Circulating placenta-secreted glycoproteins and markers of angiogenesis are altered in pregnant women with OSA.
The authors would like to thank Elizabeth Eklund and Cheryl Felber for their contributions to this research. (Both are employed by Women and Infants Hospital of Rhode Island and have nothing to disclose.)
Conflict of interest statement
Authors’ conflict of interest disclosure: The authors report no conflict of interest.
Financial support: Dr. Bourjeily’s work was supported by the Perkins Charitable Foundation. The foundation did not have a role in the design, the data analysis, or manuscript preparation.
 Anderson UD, Olsson MG, Kristensen KH, Akerstrom B, Hansson SR. Review: Biochemical markers to predict preeclampsia. Placenta. 2012;33 Suppl:S42–7.10.1016/j.placenta.2011.11.021Search in Google Scholar
 Aquilina J, Barnett A, Thompson O, Harrington K. Second-trimester maternal serum inhibin A concentration as an early marker for preeclampsia. Am J Obstet Gynecol. 1999;181:131–6.10.1016/S0002-9378(99)70448-5Search in Google Scholar
 Audibert F, Boucoiran I, An N, Aleksandrov N, Delvin E, Bujold E, et al. Screening for preeclampsia using first-trimester serum markers and uterine artery Doppler in nulliparous women. Am J Obstet Gynecol. 2010;203:383 e1–8.10.1016/j.ajog.2010.06.014Search in Google Scholar PubMed
 Berger S, Aronson D, Lavie P, Lavie L. Endothelial progenitor cells in acute myocardial infarction and sleep-disordered breathing. Am J Respir Crit Care Med. 2013;187:90–8.10.1164/rccm.201206-1144OCSearch in Google Scholar PubMed
 Blumenstein M, Mitchell MD, Groome NP, Keelan JA. Hypoxia inhibits activin A production by term villous trophoblast in vitro. Placenta. 2002;23:735–41.10.1053/plac.2002.0868Search in Google Scholar
 Bourjeily G, Mazer J, Paglia M. Outcomes of sleep disordered breathing in pregnancy. Open Sleep J. 2013;6:28–36.10.2174/1874620901306010028Search in Google Scholar
 Bourjeily G, Raker CA, Chalhoub M, Miller MA. Pregnancy and fetal outcomes of symptoms of sleep-disordered breathing. Eur Respir J. 2010;36:849–55.10.1183/09031936.00021810Search in Google Scholar PubMed
 Bourjeily G, Raker C, Chalhoub M, Miller M. Excessive daytime sleepiness in late pregnancy may not always be normal: results from a cross-sectional study. Sleep Breath. 2013;17:735–40.10.1007/s11325-012-0753-8Search in Google Scholar PubMed
 Bourjeily G, Raker C, Paglia MJ, Ankner G, O’Connor K. Patient and provider perceptions of sleep disordered breathing assessment during prenatal care: a survey-based observational study. Ther Adv Respir Dis. 2012;6:211–9.10.1177/1753465812444958Search in Google Scholar PubMed
 Chen YH, Kang JH, Lin CC, Wang IT, Keller JJ, Lin HC. Obstructive sleep apnea and the risk of adverse pregnancy outcomes. Am J Obstet Gynecol. 2012;206:136 e1–5.10.1016/j.ajog.2011.09.006Search in Google Scholar PubMed
 Depoix C, Barret LA, Hubinont C, Debieve F. Viability of primary term cytotrophoblast cell culture in normoxia and hypoxia. Mol Hum Reprod. 2013;19:29–34.10.1093/molehr/gas042Search in Google Scholar PubMed
 Eddib A, Solimani N, Rodgers B, Yeh J. Decreased maternal serum inhibin-A in pregestational diabetic women: implication for adjustment. J Reprod Med. 2008;53:785–8.Search in Google Scholar
 Faupel-Badger JM, Wang Y, Staff AC, Karumanchi SA, Stanczyk FZ, Pollak M, et al. Maternal and cord steroid sex hormones, angiogenic factors, and insulin-like growth factor axis in African-American preeclamptic and uncomplicated pregnancies. Cancer Causes Control. 2012;23:779–84.10.1007/s10552-012-9934-9Search in Google Scholar PubMed PubMed Central
 Foidart JM, Munaut C, Chantraine F, Akolekar R, Nicolaides KH. Maternal plasma soluble endoglin at 11–13 weeks’ gestation in pre-eclampsia. Ultrasound Obstet Gynecol. 2010;35:680–7.10.1002/uog.7621Search in Google Scholar PubMed
 Foster GD, Sanders MH, Millman R, Zammit G, Borradaile KE, Newman AB, et al. Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Care. 2009;32:1017–9.10.2337/dc08-1776Search in Google Scholar PubMed PubMed Central
 Hegewald MJ, Crapo RO. Respiratory physiology in pregnancy. Clin Chest Med. 2011;32:1–13.10.1016/j.ccm.2010.11.001Search in Google Scholar PubMed
 Izci B, Riha RL, Martin SE, Vennelle M, Liston WA, Dundas KC, et al. The upper airway in pregnancy and pre-eclampsia. Am J Respir Crit Care Med. 2003;167:137–40.10.1164/rccm.200206-590OCSearch in Google Scholar PubMed
 Lambert-Messerlian GM, Palomaki GE, Neveux LM, Chien E, Friedman A, Rosene-Montella K, et al. Early onset preeclampsia and second trimester serum markers. Prenat Diagn. 2009;29:1109–17.10.1002/pd.2387Search in Google Scholar PubMed
 Lavie L, Kraiczi H, Hefetz A, Ghandour H, Perelman A, Hedner J, et al. Plasma vascular endothelial growth factor in sleep apnea syndrome: effects of nasal continuous positive air pressure treatment. Am J Respir Crit Care Med. 2002;165:1624–8.10.1164/rccm.20110-040OCSearch in Google Scholar PubMed
 Lim JH, Kim SY, Park SY, Yang JH, Kim MY, Ryu HM. Effective prediction of preeclampsia by a combined ratio of angiogenesis-related factors. Obstet Gynecol. 2008;111:1403–9.10.1097/AOG.0b013e3181719b7aSearch in Google Scholar PubMed
 Louis JM, Auckley D, Sokol RJ, Mercer BM. Maternal and neonatal morbidities associated with obstructive sleep apnea complicating pregnancy. Am J Obstet Gynecol. 2010;202:261 e1–5.10.1016/j.ajog.2009.10.867Search in Google Scholar PubMed
 Maislin G, Pack AI, Kribbs NB, Smith PL, Schwartz AR, Kline LR, et al. A survey screen for prediction of apnea. Sleep. 1995;18:158–66.10.1093/sleep/18.3.158Search in Google Scholar
 Maynard SE, Crawford SL, Bathgate S, Yan J, Robidoux L, Moore M, et al. Gestational angiogenic biomarker patterns in high risk preeclampsia groups. Am J Obstet Gynecol. 2013;209:53 e1–9.10.1016/j.ajog.2013.03.017Search in Google Scholar
 Muttukrishna S, Knight PG, Groome NP, Redman CW, Ledger WL. Activin A and inhibin A as possible endocrine markers for pre-eclampsia. Lancet. 1997;349:1285–8.10.1016/S0140-6736(96)09264-1Search in Google Scholar
 National Health and Nutrition Examination Survey (NHANES): Healthy weight, overweight, and obesity among U.S. adults. 2003. Available from: http://www.cdc.gov/nchs/data/nhanes/databriefs/adultweight.pdf.Search in Google Scholar
 O’Brien LM, Bullough AS, Owusu JT, Tremblay KA, Brincat CA, Chames MC, et al. Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia: prospective cohort study. Am J Obstet Gynecol. 2012;207:487.e1–9.10.1016/j.ajog.2012.08.034Search in Google Scholar PubMed PubMed Central
 Olivarez SA, Ferres M, Antony K, Mattewal A, Maheshwari B, Sangi-Haghpeykar H, et al. Obstructive sleep apnea screening in pregnancy, perinatal outcomes, and impact of maternal obesity. Am J Perinatol. 2011;28:651–8.10.1055/s-0031-1276740Search in Google Scholar PubMed PubMed Central
 Olsen RN, Woelkers D, Dunsmoor-Su R, Lacoursiere DY. Abnormal second-trimester serum analytes are more predictive of preterm preeclampsia. Am J Obstet Gynecol. 2012;207:228 e1–7.10.1016/j.ajog.2012.06.006Search in Google Scholar PubMed
 Pilkington S, Carli F, Dakin MJ, Romney M, De Witt KA, Dore CJ, et al. Increase in Mallampati score during pregnancy. Br J Anaesth. 1995;74:638–42.10.1093/bja/74.6.638Search in Google Scholar PubMed
 Polliotti BM, Fry AG, Saller DN, Mooney RA, Cox C, Miller RK. Second-trimester maternal serum placental growth factor and vascular endothelial growth factor for predicting severe, early-onset preeclampsia. Obstet Gynecol. 2003;101: 1266–74.Search in Google Scholar
 Rana S, Powe CE, Salahuddin S, Verlohren S, Perschel FH, Levine RJ, et al. Angiogenic factors and the risk of adverse outcomes in women with suspected preeclampsia. Circulation. 2012;125:911–9.10.1161/CIRCULATIONAHA.111.054361Search in Google Scholar PubMed PubMed Central
 Reimer T, Rohrmann H, Stubert J, Pecks U, Glocker MO, Richter DU, et al. Angiogenic factors and acute-phase proteins in serum samples of preeclampsia and HELLP patients: a matched-pair analysis. J Matern Fetal Neonatal Med. 2013;26:263–9.10.3109/14767058.2012.733747Search in Google Scholar PubMed
 Volna J, Kemlink D, Kalousova M, Vavrova J, Majerova V, Mestek O, et al. Biochemical oxidative stress-related markers in patients with obstructive sleep apnea. Med Sci Monit. 2011;17:CR491–7.10.12659/MSM.881935Search in Google Scholar PubMed PubMed Central
Data from this study were presented at the 26th and 27th Annual Meetings of the Associated Professional Sleep Societies’, June 9–13, 2012, in Boston, MA, and June 1–5, 2013, in Baltimore, MD.
The authors stated that there are no conflicts of interest regarding the publication of this article.
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