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Sleep disordered breathing and pregnancy Ghada Bourjeily, MD Assistant Professor of Medicine Warren Alpert Medical School of Brown University Women and.

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Presentation on theme: "Sleep disordered breathing and pregnancy Ghada Bourjeily, MD Assistant Professor of Medicine Warren Alpert Medical School of Brown University Women and."— Presentation transcript:

1 Sleep disordered breathing and pregnancy Ghada Bourjeily, MD Assistant Professor of Medicine Warren Alpert Medical School of Brown University Women and Infants’ Hospital

2 Financial disclosure Received research funding awards from:  Rhode Island Foundation  ACCP women’s health network / Chest Foundation  Perkins Charitable Foundation

3  Normal sleep in pregnancy  Physiologic changes of pregnancy relating to sleep disordered breathing  Epidemiology and clinical presentation of SDB in pregnancy  Pregnancy and fetal outcomes  CPAP

4 Sleep in pregnancy  Sleep is notoriously disturbed in pregnancy  Recently, AASM recognized a pregnancy- associated sleep disorder as a separate entity American Academy of Sleep Medicine 2000.

5 Sleep in early pregnancy  Fatigue and sleepiness are frequent symptoms in the first trimester  Total sleep time reported to be increased in the first trimester compared to preconception  Sleep efficiency is reduced compared to before pregnancy Lee KA. Obstet Gynecol 2000; 95(1):14-8.

6 Sleep late in pregnancy  Total nocturnal sleep starts falling by end of 2nd trimester and continues to 3rd trimester  Total sleep time in 3 rd trimester may be higher mainly because of daytime naps  Wake time after sleep onset increased

7 Sleep postpartum

8 Why is sleep disrupted in a normal pregnancy?  Factors that influence sleep in healthy pregnancy:  Mechanical  Hormonal

9 Mechanical factors  Gastroesophageal reflux (1)  Nocturia  Musculoskeletal factors  Obstetric factors Habr F. DDW 2010

10 Hormonal factors

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12 Levels in pregnancy Effect on sleep architecture EstrogenIncreased Decreases REM in rats Increases SWS in humans ProgesteroneIncreased Increases REM in rats Increases NREM in humans ProlactinIncreased Increases REM in rabbits and rats Increases SWS in humans CRH / Cortisol Increased Decreases SWS in humans GHRH / GH Increased Increases SWS in rats, rabbits and humans Oxytocin Increased, peaks at night Likely causes arousals Beta-HCGIncreased Longer sleep time and reduced activity in rats Bourjeily et al. Sleep physiology in pregnancy. Pulmonary Problems in Pregnancy; Humana/Springer. Eds Bourjeily and Rosene-Montella.

13 Are pregnant women at risk for sleep apnea?

14 Potential risk factors for SDB in pregnancy  Nasal congestion and gestational rhinitis (1)  Increased Mallampati scores (2)  Reduction in size of upper airway (3,4)  Weight gain  Reduction in FRC (5) and airway collapsibility (6)  Vacuum effect related to increased ventilator drive (7) 1-Young T. J All Clin Immunol 1997; 99: S Pilkington S. Br J Anesth 1995; 74: Iczi B. ERJ 2006; 27: Iczi B. AJRCCM 2003; 167: Crapo R. Clin Obstet Gynecol 1995; 39: White DP. AJRCCM 2005; 172: Edwards N. Thorax 2002; 57:555-8

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16 Potential risk factors for SDB in pregnancy  Nasal congestion and gestational rhinitis (1)  Increased Mallampati scores (2)  Reduction in size of upper airway (3,4)  Weight gain  Reduction in FRC (5) and airway collapsibility (6)  Vacuum effect related to increased ventilator drive (7) 1-Young T. J All Clin Immunol 1997; 99: S Pilkington S. Br J Anesth 1995; 74: Iczi B. ERJ 2006; 27: Iczi B. AJRCCM 2003; 167: Crapo R. Clin Obstet Gynecol 1995; 39: White DP. AJRCCM 2005; 172: Edwards N. Thorax 2002; 57:555-8

17 Physiologic changes predisposing to SDB in pregnancy  Diaphragmatic elevation and consequent reduction in FRC FRC

18 Physiologic changes predisposing to SDB in pregnancy  Progesterone is a respiratory stimulant  Pregnant women have lower PaCO2 and respiratory alkalosis  Hypocapnia and respiratory alkalosis may lead to central apneas in non-pregnant (1)  More predisposed to central apneas? Javaheri S. NEJM 1999; 341:949-54

19 Central apneas  19 pregnant women (unpublished data) with symptoms of OSA underwent PSG and compared to age, AHI, BMI and gender matched controls  1 out of 19 pregnant subjects had 2 central apneas.  Pregnant women did not have a significantly higher number of central apneas than controls  Despite baseline respiratory alkalosis, CO2 does not reach apnea threshold.

20 Factors protecting against SDB in pregnancy  Progesterone:  Increases ventilatory drive  Increases the EMG activity of upper airway dilator muscles (1)  Estrogen:  HRT reduces AHI (2,3)  Induction of menopause shows no effect (4)  Preference for a lateral sleeping position(5)  Decrease in REM sleep (6) 1- Popovic RM. J Appl Physiol 1998; 84: Bixter EO. Am J Resp Crit Care Med 2001; 163: Manber R. Sleep 2003;26: D’Ambrosio C. Gender Med 2005; 2: Mills GH. Anesthesia 2004; 49: Driver H. Sleep 1992; 15:449-53

21 Prevalence  Prevalence of SDB in pregnant women has not yet been studied  Symptoms of SDB much more common than the non-pregnant population  Estimates from European and North American studies suggest loud snoring in 14-46% (1,2,3) 1- Franklin K Chest 2000; 117: Calaora –Tournadre. Rev Med Int 2006; 27: Bourjeily G. Eur Resp J 2010; 36:1-8.

22 So, does that mean SDB is more prevalent?  Validated questionnaires for assessment of clinical pretest probability in non- pregnant population  Predictive power of these questionnaires not validated in the non-pregnant population  Berlin questionnaire (1,2) poor predictive value 1- Sahin FK. Int J Gynecol Obstet 2008;100: Olivarez SA. AJOG 2010; 202:552.e1-7

23 What’s so special about pregnancy and SDB and why is this population worth studying separately?

24 Consequences of apnea on pregnant woman  Pregnancy associated with lower residual volume and lower functional residual capacity (FRC)  Lower oxygen reserve because of lower FRC and higher oxygen consumption

25 Response to apnea in pregnancy  Cheun compared the response of term pregnant women and controls undergoing gynecologic surgery to investigator- induced apneas Cheun. J Korean Med Sci 1992; 7(1):6-10

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29 Pregnancy outcomes

30 Preeclampsia  Preeclampsia is a condition unique to human pregnancies.  Preeclampsia is characterized by:  BP>140/100 mm Hg  Proteinuria in excess of 300mg/24 hours.  Other associated symptoms include:  Leg swelling / edema  Multi-organ dysfunction in severe cases

31 Preeclampsia  PEC is an important cause of:  Infant prematurity  Neonatal morbidity  Maternal morbidity and mortality  Maternal ICU admissions  Precursor of cardiovascular disease

32 Gestational diabetes  Diabetes occurring during pregnancy and not predating  30-50% of women with GDM end up developing DM later in life  GDM is:  Cause for infant morbidity including macrosomia  Other complications  Risk factor for PEC

33 Bourjeily G et al. Clin Chest Med 2011;32(1):

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36 Gestational diabetes  When all 3 symptoms were combined, the association with GDM was even stronger.  OR 6.14, (95% CI)  aOR 5.25, (95% CI)  There was no significant effect of Insulin versus diet on the association

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38 The chicken or the egg?

39 The chicken or the egg  SDB leading to PEC?  SDB, metabolic syndrome, poor cardiovascular outcomes  Cardiovascular disease with many similar risk factors as PEC  PEC leading to SDB?  Upper airway changes associated with PEC may lead development of SDB

40 Hemodynamic effects of PEC on obstructive events during sleep  Edwards et al studied:  10 pregnant patients with OSA  10 pregnant patients with OSA and severe PEC (7/10 on antihypertensives)  BP measured by beat to beat photoplethysmography  Sleep architecture similar in both groups Edwards N et al. AJH 2001;14:1090-5

41 Effect of PEC on post-apnea hemodynamics ;14: Edwards N AJH 2001; ;14:1090-5

42 Delivery method  C section:  Rate about 30% or less in general population  Higher morbidity  Longer hospital stay  Higher rates of complications: bleeding, venous thromboembolism, anesthesia etc…  Vaginal delivery  Most common  Less complicated

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45 Fetal outcomes

46 Consequences of apnea on fetus  Concern for fetal wellbeing with recurrent desaturations and possible hypoventilation  Data from high altitude residents strongly suggests risk of growth restriction and PEC with chronic hypoxia  Data on intermittent hypoxia less clear

47 Bourjeily G et al. Clin Chest Med 2011; 32(1):

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49 Acute hemodynamic effects of CPAP in PEC

50 CPAP and BP in PEC  A study by Edwards et al recruited patients with severe PEC:  Baseline PSG with continuous BP measurements  Mean BP measurements were calculated in different stages of sleep  Repeat PSG with same measurements but with CPAP Edwards N. AJRCCM 2000;162:619-25

51 Edwards N. AJRCCM 2000

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53 CPAP and cardiac output in PEC  A study of 24 PEC and 15 controls around 34 weeks gestation.  Methods:  PEC randomized to CPAP or no CPAP  PSG baseline night and intervention night  Beat to beat BP measurement using photoplethysmography  SV, HR, CO and SVR derived from photoplethysmograph Blyton DM. Sleep 2004

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56 Chronic effects of CPAP therapy in PEC

57 CPAP and PEC  A study by Guilleminault et al:  12 patients with risk factors (7 CHTN, 3 obese, 2 prior PEC)  First PNV  PSG baseline  CPAP therapy for all pts with flow limitation  Baseline CPAP titration then titration between 20-22wks Guilleminault C. Sleep Medicine 2007

58 CPAP and PEC  Findings:  All patients had flow limitations at baseline  In the 7 patients with CHTN:  No titration of BP meds needed  Mean SBP 128mmHg and mean DBP 86mmHg  All with normal nocturnal dip in BP on CPAP  No PEC and normal birth weights  In 3 obese patients:  1 PEC  1 PTL  1 miscarriage Guilleminault C. Sleep Medicine 2007

59 CPAP and BP  Randomized, controlled trial of CPAP or no CPAP:  CHTN and snorers  “First weeks” of pregnancy  Usual care + CPAP compared to usual care. Poyares et al. Sleep Med 2007

60 Poyares D. Sleep Medicine; 2007

61 Pregnancy and neonatal outcomes  In that study, the treatment group had:  Significant difference in APGAR scores at 1 minute but not at 5 minutes  Significantly higher number of unscheduled postpartum visits  However, there was no difference in birth weight between the 2 groups  PEC occurred in 1/9 in controls and 0/7 treatment groups Poyares D. Sleep medicine 2007

62 How are we doing with screening for the disease in pregnancy?  200 surveys mailed  102 surveys answered and mailed back  750 patients agreed to fill the survey out TitleFrequencyPercent MD, Attending MD, Resident RNP76.86 CNM

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65 Summary  Pregnancy physiology may predispose to sleep disordered breathing  Symptoms of SDB associated with adverse pregnancy outcomes and possibly some adverse fetal outcomes  CPAP appears to have significant hemodynamic effects in patients with PEC  Further studies are sorely needed in this area

66 o Women’s Health Network/Chest Foundation Award Collaborators and research team o Christina Raker, ScD o Susan Martin, RA o Cynthia Citino, RA o Robin Moore, RPSGT, REEGT o Laura O’Donnell, RPSGT o Sandra Befera, RN o Nadia Aoun, MD o Katherine Sharkey, MD, PhD o Richard Millman, MD o Margaret Miller, MD o Michel Chalhoub, MD o Perkins Charitable Foundation o Rhode Island Foundation


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