Sleep disordered
breathing and pregnancy
Ghada Bourjeily, MD
Assistant Professor of Medicine
Warren Alpert Medical School of Brown University
Women and Infants’ Hospital
Financial disclosure
Received research funding awards from:
Rhode Island Foundation
ACCP women’s health network / Chest
Foundation
Perkins Charitable Foundation
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
Sleep in pregnancy
Sleep is notoriously disturbed in
pregnancy
Recently, AASM recognized a pregnancyassociated sleep disorder as a separate
entity
American Academy of Sleep Medicine 2000.
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.
Sleep late in pregnancy
Total nocturnal sleep starts falling by end
of 2nd trimester and continues to 3rd
trimester
Total sleep time in 3rd trimester may be
higher mainly because of daytime naps
Wake time after sleep onset increased
Sleep postpartum
Why is sleep disrupted in a normal
pregnancy?
Factors that influence sleep in healthy
pregnancy:
Mechanical
Hormonal
Mechanical factors
Gastroesophageal reflux (1)
Nocturia
Musculoskeletal factors
Obstetric factors
Habr F. DDW 2010
Hormonal factors
Levels in pregnancy Effect on sleep architecture
Estrogen
Increased
Decreases REM in rats
Increases SWS in humans
Progesterone
Increased
Increases REM in rats
Increases NREM in humans
Prolactin
Increased
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-HCG
Increased
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.
Are pregnant women at
risk for sleep apnea?
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: S757-62.
2- Pilkington S. Br J Anesth 1995; 74:638-42
3- Iczi B. ERJ 2006; 27:321-7
4- Iczi B. AJRCCM 2003; 167:137-40
5- Crapo R. Clin Obstet Gynecol 1995; 39:3-16
6- White DP. AJRCCM 2005; 172:1363-70
7- Edwards N. Thorax 2002; 57:555-8
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: S757-62.
2- Pilkington S. Br J Anesth 1995; 74:638-42
3- Iczi B. ERJ 2006; 27:321-7
4- Iczi B. AJRCCM 2003; 167:137-40
5- Crapo R. Clin Obstet Gynecol 1995; 39:3-16
6- White DP. AJRCCM 2005; 172:1363-70
7- Edwards N. Thorax 2002; 57:555-8
Physiologic changes predisposing
to SDB in pregnancy
Diaphragmatic
elevation and
consequent
reduction in
FRC
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
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.
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: 1055-62
2- Bixter EO. Am J Resp Crit Care Med 2001; 163:607-613
3- Manber R. Sleep 2003;26: 163-168.
4- D’Ambrosio C. Gender Med 2005; 2:238-45
5- Mills GH. Anesthesia 2004; 49:249-50
6- Driver H. Sleep 1992; 15:449-53
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; 117:137-41
2- Calaora –Tournadre. Rev Med Int 2006; 27:291-5
3- Bourjeily G. Eur Resp J 2010; 36:1-8.
So, does that mean SDB is more prevalent?
Validated questionnaires for assessment
of clinical pretest probability in nonpregnant 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;100:141-6
2- Olivarez SA. AJOG 2010; 202:552.e1-7
What’s so special about
pregnancy and SDB and
why is this population worth
studying separately?
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
Response to apnea in pregnancy
Cheun compared the response of term
pregnant women and controls undergoing
gynecologic surgery to investigatorinduced apneas
Cheun. J Korean Med Sci 1992; 7(1):6-10
Pregnancy outcomes
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
Preeclampsia
PEC is an important cause of:
Infant prematurity
Neonatal morbidity
Maternal morbidity and mortality
Maternal ICU admissions
Precursor of cardiovascular disease
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
Bourjeily G et al. Clin Chest Med 2011;32(1): 175-189
Gestational diabetes
When all 3 symptoms were combined, the
association with GDM was even stronger.
OR 6.14, 2.33-16.23 (95% CI)
aOR 5.25, 2.95-14.09 (95% CI)
There was no significant effect of Insulin
versus diet on the association
The chicken or the egg?
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
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
Effect of PEC on post-apnea hemodynamics
Edwards N AJH 2001; ;14:1090-5
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
Fetal outcomes
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
Bourjeily G et al. Clin Chest Med 2011; 32(1): 175-189
Acute hemodynamic effects of CPAP in PEC
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
Edwards N. AJRCCM 2000
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
Blyton DM. Sleep 2004
Blyton DM. Sleep 2004
Chronic effects of CPAP therapy in PEC
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
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
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
Poyares D. Sleep Medicine; 2007
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
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
Title
Frequency Percent
MD,
Attending
49
48.04
MD, Resident
22
21.57
RNP
7
6.86
CNM
24
23.53
100%
90%
80%
70%
Almost never
60%
Occasionally
50%
Often
40%
Very often
Almost always
30%
20%
10%
0%
Snoring
100%
90%
80%
70%
Almost never
60%
Occasionally
50%
Often
40%
Very often
Almost always
30%
20%
10%
0%
Fetal movement
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
o Women’s Health Network/Chest Foundation Award
o Perkins Charitable Foundation
o Rhode Island Foundation
Collaborators and research team
oChristina Raker, ScD
oSusan Martin, RA
oCynthia Citino, RA
oRobin Moore, RPSGT, REEGT
oLaura O’Donnell, RPSGT
oSandra Befera, RN
oNadia Aoun, MD
oKatherine Sharkey, MD, PhD
oRichard Millman, MD
oMargaret Miller, MD
oMichel Chalhoub, MD