Sleep disordered Sleep disordered breathing and pregnancybreathing and pregnancy

Ghada Bourjeily, MDGhada Bourjeily, MDAssistant Professor of MedicineAssistant Professor of Medicine

Warren Alpert Medical School of Brown UniversityWarren Alpert Medical School of Brown UniversityWomen and Infants’ HospitalWomen and Infants’ Hospital

Financial disclosureFinancial disclosure

Received research funding awards from:Received research funding awards from:Rhode Island FoundationRhode Island FoundationACCP women’s health network / Chest ACCP women’s health network / Chest

FoundationFoundationPerkins Charitable FoundationPerkins Charitable Foundation

Normal sleep in pregnancyNormal sleep in pregnancyPhysiologic changes of pregnancy relating Physiologic changes of pregnancy relating

to sleep disordered breathingto sleep disordered breathingEpidemiology and clinical presentation of Epidemiology and clinical presentation of

SDB in pregnancySDB in pregnancyPregnancy and fetal outcomes Pregnancy and fetal outcomes CPAPCPAP

Sleep in pregnancySleep in pregnancy

Sleep is notoriously disturbed in Sleep is notoriously disturbed in pregnancypregnancy

Recently, AASM recognized a pregnancy-Recently, AASM recognized a pregnancy-associated sleep disorder as a separate associated sleep disorder as a separate entityentity

American Academy of Sleep Medicine 2000.American Academy of Sleep Medicine 2000.

Sleep in early pregnancySleep in early pregnancy

Fatigue and sleepiness are frequent Fatigue and sleepiness are frequent symptoms in the first trimestersymptoms in the first trimester

Total sleep time reported to be increased Total sleep time reported to be increased in the first trimester compared to in the first trimester compared to preconception preconception

Sleep efficiency is reduced compared to Sleep efficiency is reduced compared to before pregnancybefore pregnancy

Lee KA. Obstet Gynecol 2000; 95(1):14-8.Lee KA. Obstet Gynecol 2000; 95(1):14-8.

Sleep late in pregnancySleep late in pregnancyTotal Total nocturnalnocturnal sleep starts falling by end sleep starts falling by end

of 2nd trimester and continues to 3rd of 2nd trimester and continues to 3rd trimestertrimester

Total sleep time in 3Total sleep time in 3rdrd trimester may be trimester may be higher mainly because of daytime napshigher mainly because of daytime naps

Wake time after sleep onset increasedWake time after sleep onset increased

Sleep postpartumSleep postpartum

Why is sleep disrupted in a normal Why is sleep disrupted in a normal pregnancy?pregnancy?

Factors that influence sleep in healthy Factors that influence sleep in healthy pregnancy:pregnancy:MechanicalMechanicalHormonalHormonal

Mechanical factorsMechanical factorsGastroesophageal reflux (1)Gastroesophageal reflux (1)NocturiaNocturiaMusculoskeletal factorsMusculoskeletal factorsObstetric factorsObstetric factors

Habr F. DDW 2010Habr F. DDW 2010

Hormonal factorsHormonal factors

Levels in pregnancyLevels in pregnancy Effect on sleep architectureEffect on sleep architecture

EstrogenEstrogen IncreasedIncreased Decreases REM in ratsDecreases REM in ratsIncreases SWS in humansIncreases SWS in humans

ProgesteroneProgesterone IncreasedIncreased Increases REM in ratsIncreases REM in ratsIncreases NREM in humansIncreases NREM in humans

ProlactinProlactin IncreasedIncreased Increases REM in rabbits and ratsIncreases REM in rabbits and ratsIncreases SWS in humansIncreases SWS in humans

CRH / CortisolCRH / Cortisol IncreasedIncreased Decreases SWS in humansDecreases SWS in humans

GHRH / GHGHRH / GH IncreasedIncreased Increases SWS in rats, rabbits and humansIncreases SWS in rats, rabbits and humans

OxytocinOxytocin Increased, peaks at Increased, peaks at nightnight

Likely causes arousalsLikely causes arousals

Beta-HCGBeta-HCG IncreasedIncreased Longer sleep time and reduced activity in Longer sleep time and reduced activity in ratsrats

Bourjeily et al. Sleep physiology in pregnancy. Pulmonary Problems in Pregnancy; Humana/Springer. Eds Bourjeily and Rosene-Montella.

Are pregnant women at Are pregnant women at risk for sleep apnea?risk for sleep apnea?

Potential risk factors for SDB in pregnancyPotential risk factors for SDB in pregnancy

Nasal congestion and gestational rhinitis (1)Nasal congestion and gestational rhinitis (1) Increased Mallampati scores (2)Increased Mallampati scores (2) Reduction in size of upper airway (3,4)Reduction in size of upper airway (3,4) Weight gainWeight gain Reduction in FRC (5) and airway collapsibility (6)Reduction in FRC (5) and airway collapsibility (6) Vacuum effect related to increased ventilator drive (7)Vacuum effect related to increased ventilator drive (7)

1-Young T. J All Clin Immunol 1997; 99: S757-62.1-Young T. J All Clin Immunol 1997; 99: S757-62.2- Pilkington S. Br J Anesth 1995; 74:638-422- Pilkington S. Br J Anesth 1995; 74:638-423- Iczi B. ERJ 2006; 27:321-73- Iczi B. ERJ 2006; 27:321-74- Iczi B. AJRCCM 2003; 167:137-404- Iczi B. AJRCCM 2003; 167:137-405- Crapo R. Clin Obstet Gynecol 1995; 39:3-165- Crapo R. Clin Obstet Gynecol 1995; 39:3-166- White DP. AJRCCM 2005; 172:1363-706- White DP. AJRCCM 2005; 172:1363-707- Edwards N. Thorax 2002; 57:555-87- Edwards N. Thorax 2002; 57:555-8

Potential risk factors for SDB in pregnancyPotential risk factors for SDB in pregnancy

Nasal congestion and gestational rhinitis (1)Nasal congestion and gestational rhinitis (1) Increased Mallampati scores (2)Increased Mallampati scores (2) Reduction in size of upper airway (3,4)Reduction in size of upper airway (3,4) Weight gainWeight gain Reduction in FRC (5) and airway collapsibility (6)Reduction in FRC (5) and airway collapsibility (6) Vacuum effect related to increased ventilator drive (7)Vacuum effect related to increased ventilator drive (7)

1-Young T. J All Clin Immunol 1997; 99: S757-62.1-Young T. J All Clin Immunol 1997; 99: S757-62.2- Pilkington S. Br J Anesth 1995; 74:638-422- Pilkington S. Br J Anesth 1995; 74:638-423- Iczi B. ERJ 2006; 27:321-73- Iczi B. ERJ 2006; 27:321-74- Iczi B. AJRCCM 2003; 167:137-404- Iczi B. AJRCCM 2003; 167:137-405- Crapo R. Clin Obstet Gynecol 1995; 39:3-165- Crapo R. Clin Obstet Gynecol 1995; 39:3-166- White DP. AJRCCM 2005; 172:1363-706- White DP. AJRCCM 2005; 172:1363-707- Edwards N. Thorax 2002; 57:555-87- Edwards N. Thorax 2002; 57:555-8

Physiologic changes predisposing Physiologic changes predisposing to SDB in pregnancyto SDB in pregnancy

Diaphragmatic Diaphragmatic elevation and elevation and consequent consequent reduction in reduction in

FRCFRC

Physiologic changes predisposing Physiologic changes predisposing to SDB in pregnancyto SDB in pregnancy

Progesterone is a respiratory stimulantProgesterone is a respiratory stimulantPregnant women have lower PaCO2 and Pregnant women have lower PaCO2 and

respiratory alkalosisrespiratory alkalosisHypocapnia and respiratory alkalosis may Hypocapnia and respiratory alkalosis may

lead to central apneas in non-pregnant (1)lead to central apneas in non-pregnant (1)More predisposed to central apneas?More predisposed to central apneas?

Javaheri S. NEJM 1999; 341:949-54Javaheri S. NEJM 1999; 341:949-54

Central apneasCentral apneas 19 pregnant women (unpublished data) with 19 pregnant women (unpublished data) with

symptoms of OSA underwent PSG and symptoms of OSA underwent PSG and compared to age, AHI, BMI and gender matched compared to age, AHI, BMI and gender matched controlscontrols1 out of 19 pregnant subjects had 2 central apneas.1 out of 19 pregnant subjects had 2 central apneas.Pregnant women did not have a significantly higher Pregnant women did not have a significantly higher

number of central apneas than controlsnumber of central apneas than controls

Despite baseline respiratory alkalosis, CO2 does Despite baseline respiratory alkalosis, CO2 does not reach apnea threshold.not reach apnea threshold.

Factors protecting against SDB in pregnancyFactors protecting against SDB in pregnancy

Progesterone:Progesterone: Increases ventilatory driveIncreases ventilatory drive Increases the EMG activity of upper airway dilator muscles (1)Increases the EMG activity of upper airway dilator muscles (1)

Estrogen:Estrogen: HRT reduces AHI (2,3)HRT reduces AHI (2,3) Induction of menopause shows no effect (4)Induction of menopause shows no effect (4)

Preference for a lateral sleeping position(5)Preference for a lateral sleeping position(5) Decrease in REM sleep (6)Decrease in REM sleep (6)1- Popovic RM. J Appl Physiol 1998; 84: 1055-621- Popovic RM. J Appl Physiol 1998; 84: 1055-622- Bixter EO. Am J Resp Crit Care Med 2001; 163:607-6132- Bixter EO. Am J Resp Crit Care Med 2001; 163:607-6133- Manber R. Sleep 2003;26: 163-168.3- Manber R. Sleep 2003;26: 163-168.4- D’Ambrosio C. Gender Med 2005; 2:238-454- D’Ambrosio C. Gender Med 2005; 2:238-455- Mills GH. Anesthesia 2004; 49:249-505- Mills GH. Anesthesia 2004; 49:249-506- Driver H. Sleep 1992; 15:449-536- Driver H. Sleep 1992; 15:449-53

PrevalencePrevalencePrevalence of SDB in pregnant women Prevalence of SDB in pregnant women

has not yet been studiedhas not yet been studiedSymptoms of SDB much more common Symptoms of SDB much more common

than the non-pregnant populationthan the non-pregnant populationEstimates from European and North Estimates from European and North

American studies suggest loud snoring in American studies suggest loud snoring in 14-46% (1,2,3)14-46% (1,2,3)

1- Franklin K Chest 2000; 117:137-411- Franklin K Chest 2000; 117:137-412- Calaora –Tournadre. Rev Med Int 2006; 27:291-52- Calaora –Tournadre. Rev Med Int 2006; 27:291-53- Bourjeily G. Eur Resp J 2010; 36:1-8.3- Bourjeily G. Eur Resp J 2010; 36:1-8.

So, does that mean SDB is more prevalent?So, does that mean SDB is more prevalent?

Validated questionnaires for assessment Validated questionnaires for assessment of clinical pretest probability in non-of clinical pretest probability in non-pregnant populationpregnant population

Predictive power of these questionnaires Predictive power of these questionnaires not validated in the non-pregnant not validated in the non-pregnant populationpopulation

Berlin questionnaire (1,2) poor predictive Berlin questionnaire (1,2) poor predictive valuevalue

1- Sahin FK. Int J Gynecol Obstet 2008;100:141-61- Sahin FK. Int J Gynecol Obstet 2008;100:141-62- Olivarez SA. AJOG 2010; 202:552.e1-72- Olivarez SA. AJOG 2010; 202:552.e1-7

What’s so special about What’s so special about pregnancy and SDB and pregnancy and SDB and

why is this population worth why is this population worth studying separately?studying separately?

Consequences of apnea on Consequences of apnea on pregnant womanpregnant woman

Pregnancy associated with lower residual Pregnancy associated with lower residual volume and lower functional residual volume and lower functional residual capacity (FRC)capacity (FRC)

Lower oxygen reserve because of lower Lower oxygen reserve because of lower FRC and higher oxygen consumptionFRC and higher oxygen consumption

Response to apnea in pregnancyResponse to apnea in pregnancy

Cheun compared the response of term Cheun compared the response of term pregnant women and controls undergoing pregnant women and controls undergoing gynecologic surgery to investigator-gynecologic surgery to investigator-induced apneasinduced apneas

Cheun. J Korean Med Sci 1992; Cheun. J Korean Med Sci 1992; 7(1):6-107(1):6-10

Pregnancy outcomesPregnancy outcomes

PreeclampsiaPreeclampsia

Preeclampsia is a condition unique to Preeclampsia is a condition unique to human pregnancies.human pregnancies.

Preeclampsia is characterized by:Preeclampsia is characterized by:BP>140/100 mm Hg BP>140/100 mm Hg Proteinuria in excess of 300mg/24 hours.Proteinuria in excess of 300mg/24 hours.

Other associated symptoms include:Other associated symptoms include:Leg swelling / edemaLeg swelling / edemaMulti-organ dysfunction in severe casesMulti-organ dysfunction in severe cases

PreeclampsiaPreeclampsia

PEC is an important cause of:PEC is an important cause of:Infant prematurityInfant prematurityNeonatal morbidityNeonatal morbidityMaternal morbidity and mortalityMaternal morbidity and mortalityMaternal ICU admissionsMaternal ICU admissionsPrecursor of cardiovascular diseasePrecursor of cardiovascular disease

Gestational diabetesGestational diabetesDiabetes occurring during pregnancy and Diabetes occurring during pregnancy and

not predatingnot predating30-50% of women with GDM end up 30-50% of women with GDM end up

developing DM later in lifedeveloping DM later in lifeGDM is:GDM is:

Cause for infant morbidity including Cause for infant morbidity including macrosomiamacrosomia

Other complications Other complications Risk factor for PECRisk factor for PEC

Bourjeily G et al. Clin Chest Med 2011;32(1): 175-189

Gestational diabetesGestational diabetes

When all 3 symptoms were combined, the When all 3 symptoms were combined, the association with GDM was even stronger.association with GDM was even stronger.OR 6.14, 2.33-16.23 (95% CI)OR 6.14, 2.33-16.23 (95% CI)aOR 5.25, 2.95-14.09 (95% CI)aOR 5.25, 2.95-14.09 (95% CI)

There was no significant effect of Insulin There was no significant effect of Insulin versus diet on the associationversus diet on the association

The chicken or the egg?

The chicken or the eggThe chicken or the egg

SDB leading to PEC?SDB leading to PEC?SDB, metabolic syndrome, poor SDB, metabolic syndrome, poor

cardiovascular outcomescardiovascular outcomesCardiovascular disease with many similar risk Cardiovascular disease with many similar risk

factors as PECfactors as PECPEC leading to SDB?PEC leading to SDB?

Upper airway changes associated with PEC Upper airway changes associated with PEC may lead development of SDBmay lead development of SDB

Hemodynamic effects of PEC on Hemodynamic effects of PEC on obstructive events during sleepobstructive events during sleep

Edwards et al studied:Edwards et al studied:10 pregnant patients with OSA10 pregnant patients with OSA10 pregnant patients with OSA and severe 10 pregnant patients with OSA and severe

PEC (7/10 on antihypertensives)PEC (7/10 on antihypertensives)BP measured by beat to beat BP measured by beat to beat

photoplethysmographyphotoplethysmographySleep architecture similar in both groupsSleep architecture similar in both groups

Edwards N et al. AJH 2001;14:1090-5Edwards N et al. AJH 2001;14:1090-5

Effect of PEC on post-apnea hemodynamics

Edwards N AJH 2001; ;14:1090-5;14:1090-5

Delivery methodDelivery methodC section: C section:

Rate about 30% or less in general populationRate about 30% or less in general populationHigher morbidityHigher morbidityLonger hospital stayLonger hospital stayHigher rates of complications: bleeding, Higher rates of complications: bleeding,

venous thromboembolism, anesthesia etc…venous thromboembolism, anesthesia etc…Vaginal deliveryVaginal delivery

Most commonMost commonLess complicatedLess complicated

Fetal outcomesFetal outcomes

Consequences of apnea on fetusConsequences of apnea on fetus

Concern for fetal wellbeing with recurrent Concern for fetal wellbeing with recurrent desaturations and possible hypoventilationdesaturations and possible hypoventilation

Data from high altitude residents strongly Data from high altitude residents strongly suggests risk of growth restriction and suggests risk of growth restriction and PEC with chronic hypoxiaPEC with chronic hypoxia

Data on intermittent hypoxia less clearData on intermittent hypoxia less clear

Bourjeily G et al. Clin Chest Med 2011; 32(1): 175-189

Acute hemodynamic effects of CPAP in PEC

CPAP and BP in PECCPAP and BP in PECA study by Edwards et al recruited patients with A study by Edwards et al recruited patients with

severe PEC:severe PEC:Baseline PSG with continuous BP Baseline PSG with continuous BP

measurementsmeasurementsMean BP measurements were calculated in Mean BP measurements were calculated in

different stages of sleepdifferent stages of sleepRepeat PSG with same measurements but with Repeat PSG with same measurements but with

CPAPCPAP

Edwards N. AJRCCM 2000;162:619-25Edwards N. AJRCCM 2000;162:619-25

Edwards N. AJRCCM 2000

CPAP and cardiac output in CPAP and cardiac output in PECPEC

A study of 24 PEC and 15 controls around 34 A study of 24 PEC and 15 controls around 34 weeks gestation.weeks gestation.

Methods:Methods:PEC randomized to CPAP or no CPAPPEC randomized to CPAP or no CPAPPSG baseline night and intervention nightPSG baseline night and intervention nightBeat to beat BP measurement using Beat to beat BP measurement using

photoplethysmographyphotoplethysmographySV, HR, CO and SVR derived from SV, HR, CO and SVR derived from

photoplethysmographphotoplethysmographBlyton DM. Sleep 2004Blyton DM. Sleep 2004

Blyton DM. Sleep 2004

Blyton DM. Sleep 2004

Chronic effects of CPAP therapy in PEC

CPAP and PECCPAP and PECA study by Guilleminault et al:A study by Guilleminault et al:

12 patients with risk factors (7 CHTN, 3 12 patients with risk factors (7 CHTN, 3 obese, 2 prior PEC)obese, 2 prior PEC)

First PNVFirst PNVPSG baselinePSG baselineCPAP therapy for all pts with flow limitationCPAP therapy for all pts with flow limitationBaseline CPAP titration then titration between Baseline CPAP titration then titration between

20-22wks20-22wks

Guilleminault C. Sleep Medicine 2007Guilleminault C. Sleep Medicine 2007

CPAP and PECCPAP and PECFindings:Findings:

All patients had flow limitations at baselineAll patients had flow limitations at baselineIn the 7 patients with CHTN:In the 7 patients with CHTN:

No titration of BP meds needed No titration of BP meds needed Mean SBP 128mmHg and mean DBP 86mmHgMean SBP 128mmHg and mean DBP 86mmHgAll with normal nocturnal dip in BP on CPAPAll with normal nocturnal dip in BP on CPAPNo PEC and normal birth weightsNo PEC and normal birth weights

In 3 obese patients:In 3 obese patients:1 PEC1 PEC1 PTL1 PTL1 miscarriage1 miscarriage

Guilleminault C. Sleep Medicine Guilleminault C. Sleep Medicine 20072007

CPAP and BPCPAP and BP

Randomized, controlled trial of CPAP or Randomized, controlled trial of CPAP or no CPAP:no CPAP:CHTN and snorersCHTN and snorers““First weeks” of pregnancyFirst weeks” of pregnancyUsual care + CPAP compared to usual care.Usual care + CPAP compared to usual care.

Poyares et al. Sleep Med 2007Poyares et al. Sleep Med 2007

Poyares D. Sleep Medicine; 2007

Pregnancy and neonatal outcomesPregnancy and neonatal outcomes

In that study, the treatment group had:In that study, the treatment group had:Significant difference in APGAR scores at 1 minute Significant difference in APGAR scores at 1 minute

but not at 5 minutesbut not at 5 minutesSignificantly higher number of unscheduled Significantly higher number of unscheduled

postpartum visitspostpartum visitsHowever, there was no difference in birth weight However, there was no difference in birth weight

between the 2 groupsbetween the 2 groupsPEC occurred in 1/9 in controls and 0/7 PEC occurred in 1/9 in controls and 0/7

treatment groupstreatment groupsPoyares D. Sleep medicine 2007Poyares D. Sleep medicine 2007

How are we doing with screening How are we doing with screening for the disease in pregnancy?for the disease in pregnancy?

200 surveys mailed200 surveys mailed102 surveys 102 surveys

answered and mailed answered and mailed backback

750 patients agreed 750 patients agreed to fill the survey outto fill the survey out

Title Frequency PercentMD,

Attending49 48.04

MD, Resident 22 21.57

RNP 7 6.86

CNM 24 23.53

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Snoring

Almost never

Occasionally

Often

Very often

Almost always

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

Fetal movement

Almost never

Occasionally

Often

Very often

Almost always

SummarySummary Pregnancy physiology may predispose to Pregnancy physiology may predispose to

sleep disordered breathingsleep disordered breathingSymptoms of SDB associated with Symptoms of SDB associated with

adverse pregnancy outcomes and possibly adverse pregnancy outcomes and possibly some adverse fetal outcomessome adverse fetal outcomes

CPAP appears to have significant CPAP appears to have significant hemodynamic effects in patients with PEC hemodynamic effects in patients with PEC

Further studies are sorely needed in this Further studies are sorely needed in this areaarea

o Women’s Health Network/Chest Foundation AwardWomen’s Health Network/Chest Foundation Award

Collaborators and research teamoChristina Raker, ScDChristina Raker, ScDoSusan Martin, RASusan Martin, RAoCynthia Citino, RACynthia Citino, RAoRobin Moore, RPSGT, REEGT Robin Moore, RPSGT, REEGT oLaura O’Donnell, RPSGTLaura O’Donnell, RPSGToSandra Befera, RNSandra Befera, RNoNadia Aoun, MDNadia Aoun, MDoKatherine Sharkey, MD, PhDKatherine Sharkey, MD, PhDoRichard Millman, MDRichard Millman, MDoMargaret Miller, MDMargaret Miller, MDoMichel Chalhoub, MDMichel Chalhoub, MD

o Perkins Charitable FoundationPerkins Charitable Foundationo Rhode Island FoundationRhode Island Foundation