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www.AJOG .org
OBSTETRICS
Implications of sleep-disordered breathing in pregnancy Q1 Q3 Francesca
L. Facco, MD; David W. Ouyang, MD; Phyllis C. Zee, MD, PhD; Anna E. Strohl, MD; Anna B. Gonzalez, MD; Courtney Lim, MD; William A. Grobman, MD, MBA OBJECTIVE: The objective of the study was to examine the relationship
RESULTS: Of the 188 women with a valid early pregnancy sleep study,
between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort.
182 had complete delivery records. There was no relationship demonstrated between SDB exposure in early or late pregnancy and preeclampsia, preterm birth less than 34 weeks, and small-forgestational-age (95%) neonates. Conversely, SDB severity in early pregnancy was associated with the risk of developing gestational diabetes (no SDB, 25%; mild SDB, 43%; moderate/ severe SDB, 63%; P ¼ .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8).
STUDY DESIGN: This was a planned analysis of a prospective
cohort designed to estimate the prevalence and trends of SDB in high-risk pregnant women. We recruited women with a body mass index of 30 kg/m2 or greater, chronic hypertension, pregestational diabetes, prior preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea hypopnea index of 5 or greater and further grouped into severity categories: mild SDB (5-14.9), moderate SDB (15-29.9), and severe SDB (30). Pregnancy outcomes (preeclampsia, gestational diabetes, preterm birth, infant weight) were abstracted by physicians blinded to the SDB results.
CONCLUSION: This study suggests a dose-dependent relationship
between SDB in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight were demonstrated. Key words: adverse pregnancy outcomes, gestational diabetes, pregnancy, sleep apnea, sleep-disordered breathing
Cite this article as: Facco FL, Ouyang DW, Zee PC, et al. Implications of sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014;210:xx-xx.
S
leep disordered breathing (SDB) refers to a group of disorders characterized by abnormal respiratory patterns (eg, apneas, hypopneas) or abnormal gas exchange (eg, hypoxia) during sleep.1,2 Obstructive sleep apnea, the most common type of SDB, is characterized by airway narrowing during sleep that leads to respiratory disruption, hypoxia, and sleep fragmentation.
Pregnancy has been associated with several alterations in sleep and a high frequency of sleep disturbances.3 Many studies have demonstrated that SDB symptoms (snoring, excessive daytime sleepiness) are common in pregnancy and that the prevalence of SDB symptoms increases as pregnancy progresses.3-6 This progression is at least partly related to the weight gain, edema,
From the Department of Obstetrics and Gynecology, Magee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA (Dr Facco); Department of Obstetrics and Gynecology, North Shore University Health System, Pritzker School of Medicine, University of Chicago, Evanston (Drs Ouyang and Gonzalez), and Departments of Neurology (Dr Zee) and Obstetrics and Gynecology (Drs Strohl, Lim, and Grobman), Feinberg School of Medicine, Northwestern University, Chicago, IL. Received Oct. 21, 2013; revised Dec. 18, 2013; accepted Dec. 23, 2013. This study was supported by National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grant K12HD050121 and Preeclampsia Foundation Vision grant K12HD043441, and Northwestern Memorial Foundation Dixon Translational Research Initiative. The authors report no conflict of interest. Presented at the 32nd annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 11-16, 2013. Reprints: Francesca Facco, MD, Department of Obstetrics and Gynecology, Magee-Womens Hospital, 300 Halket St., Room 2233, Pittsburgh, PA 15213. [email protected]. 0002-9378/$36.00 ª 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.12.035
and hyperemia of pregnancy that lead to upper airway narrowing and increased airway resistance. In nonpregnant populations, SDB has been linked not only to poor sleep and impaired daytime function but also to adverse health outcomes, such as cardiovascular and metabolic disease.7-13 Recent data also have suggested a potential link between SDB and adverse pregnancy outcomes such as hypertensive disorders of pregnancy, gestational diabetes, and preterm birth.14-20 In a retrospective study, Chen at al15 reported that SDB was associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 1.6, 95% confidence interval [CI], 2.16e11.26), gestational diabetes (aOR, 1.63; 95% CI, 1.07e2.48), and preterm birth (aOR, 2.31; 95% CI, 1.77e3.01). Such data underscore the potential association between SDB and adverse pregnancy outcomes and the importance of gaining a better understanding of this link. However, most of the research regarding the epidemiology of SDB in pregnancy is retrospective or cross-sectional, and the
MONTH 2014 American Journal of Obstetrics & Gynecology FLA 5.2.0 DTD YMOB9608_proof 25 January 2014 7:31 pm ce
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Obstetrics
majority of studies have relied on selfreported symptom assessments. The objective of this study was to examine the relationship between objectively assessed SDB during pregnancy and the risk of adverse pregnancy outcomes.
M ATERIALS
AND
M ETHODS
This was a planned secondary analysis of a study that was designed to evaluate the prevalence of and trends in SDB across pregnancy among women at high risk for developing preeclampsia.21,22 We recruited women with prepregnancy body mass index (BMI) of 30 kg/m2 or greater, chronic hypertension, pregestational diabetes (type 1 or type 2), a prior history of preeclampsia, and/or a twin gestation. The study subjects were recruited as a convenience sample from ambulatory care practices at 2 university centers serving women with both private and public insurance. After signing informed consent, women completed an at-home, overnight sleep evaluation with the WatchPAT100 (Itamar Medical Ltd, Caesarea, Israel) during early pregnancy (between 6 and 20 weeks of gestation) and were asked to repeat the study in late pregnancy (between 28 and 37 weeks of gestation). The Watch-PAT 100, which has a peripheral arterial tonometry (PAT) finger plethysmograph and standard oxygen saturation (SpO2) probe, allows the recording of the PAT signal, heart rate, and oxyhemoglobin saturation. Sleep time is estimated using an inbuilt actigraph.23 Analysis of these signals allows for the determination of an apnea hypopnea index (AHI), which is a sum of the number of apneas (breathing pauses) and hypopneas (shallow breathing) that occur per hour of sleep. In adults an AHI of 0-4.9 is considered normal and an AHI of 5 or greater defines SDB. An AHI of 5-14.9 is typically considered mild SDB, 15-29.9 moderate SDB, and 30 or greater severe SDB.1,2,24,25 The Watch-PAT proprietary software algorithm was used to analyze the PAT signal amplitude along with the heart rate and SpO2 to estimate the AHI. An AHI event was scored if either a PAT
www.AJOG.org amplitude reduction occurred with 3% or greater oxyhemoglobin desaturation or 4% or greater oxyhemoglobin desaturation occurred.26 Studies in nonpregnant populations have shown that respiratory indices, such as the AHI, derived from the Watch-PAT are strongly correlated (r ¼ 0.90) with those obtained from inlaboratory polysomnography (PSG) and also have demonstrated that the Watch-PAT is an accurate and reliable ambulatory method for the detection of SDB.23,26-28 O’Brien et al29 recently presented data comparing the WatchPAT to full PSG in third-trimester pregnant subjects. Their results indicate that among pregnant women, the WatchPAT AHI correlated very well with PSG AHI (r ¼ 0.76, P < .0001) and that the Watch-PAT demonstrated excellent sensitivity (88%) and specificity (86%) for the identification of SDB in pregnancy.29 All participants received obstetrical care by their physicians, who were unaware of the sleep study results. However, women were informed if their AHI was 10 or greater and given contact information for sleep specialists in the area if they were interested in further evaluation. Given that there are currently no sanctioned pregnancy-specific guidelines for SDB treatment or evidence that treatment in the short term has an impact on maternal, obstetric, or neonatal outcomes, no alteration of care was recommended or mandated for study participants, regardless of AHI. Pregnancy outcomes were abstracted from the medical record by physicians unaware of the SDB status of the study subjects. Outcomes of interest included preeclampsia, gestational diabetes, preterm birth (
www.AJOG .org
OBSTETRICS
Implications of sleep-disordered breathing in pregnancy Q1 Q3 Francesca
L. Facco, MD; David W. Ouyang, MD; Phyllis C. Zee, MD, PhD; Anna E. Strohl, MD; Anna B. Gonzalez, MD; Courtney Lim, MD; William A. Grobman, MD, MBA OBJECTIVE: The objective of the study was to examine the relationship
RESULTS: Of the 188 women with a valid early pregnancy sleep study,
between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort.
182 had complete delivery records. There was no relationship demonstrated between SDB exposure in early or late pregnancy and preeclampsia, preterm birth less than 34 weeks, and small-forgestational-age (95%) neonates. Conversely, SDB severity in early pregnancy was associated with the risk of developing gestational diabetes (no SDB, 25%; mild SDB, 43%; moderate/ severe SDB, 63%; P ¼ .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8).
STUDY DESIGN: This was a planned analysis of a prospective
cohort designed to estimate the prevalence and trends of SDB in high-risk pregnant women. We recruited women with a body mass index of 30 kg/m2 or greater, chronic hypertension, pregestational diabetes, prior preeclampsia, and/or a twin gestation. Objective assessment of SDB was completed between 6 and 20 weeks and again in the third trimester. SDB was defined as an apnea hypopnea index of 5 or greater and further grouped into severity categories: mild SDB (5-14.9), moderate SDB (15-29.9), and severe SDB (30). Pregnancy outcomes (preeclampsia, gestational diabetes, preterm birth, infant weight) were abstracted by physicians blinded to the SDB results.
CONCLUSION: This study suggests a dose-dependent relationship
between SDB in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight were demonstrated. Key words: adverse pregnancy outcomes, gestational diabetes, pregnancy, sleep apnea, sleep-disordered breathing
Cite this article as: Facco FL, Ouyang DW, Zee PC, et al. Implications of sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014;210:xx-xx.
S
leep disordered breathing (SDB) refers to a group of disorders characterized by abnormal respiratory patterns (eg, apneas, hypopneas) or abnormal gas exchange (eg, hypoxia) during sleep.1,2 Obstructive sleep apnea, the most common type of SDB, is characterized by airway narrowing during sleep that leads to respiratory disruption, hypoxia, and sleep fragmentation.
Pregnancy has been associated with several alterations in sleep and a high frequency of sleep disturbances.3 Many studies have demonstrated that SDB symptoms (snoring, excessive daytime sleepiness) are common in pregnancy and that the prevalence of SDB symptoms increases as pregnancy progresses.3-6 This progression is at least partly related to the weight gain, edema,
From the Department of Obstetrics and Gynecology, Magee-Womens Hospital, University of Pittsburgh, Pittsburgh, PA (Dr Facco); Department of Obstetrics and Gynecology, North Shore University Health System, Pritzker School of Medicine, University of Chicago, Evanston (Drs Ouyang and Gonzalez), and Departments of Neurology (Dr Zee) and Obstetrics and Gynecology (Drs Strohl, Lim, and Grobman), Feinberg School of Medicine, Northwestern University, Chicago, IL. Received Oct. 21, 2013; revised Dec. 18, 2013; accepted Dec. 23, 2013. This study was supported by National Institutes of Health/Eunice Kennedy Shriver National Institute of Child Health and Human Development grant K12HD050121 and Preeclampsia Foundation Vision grant K12HD043441, and Northwestern Memorial Foundation Dixon Translational Research Initiative. The authors report no conflict of interest. Presented at the 32nd annual meeting of the Society for Maternal-Fetal Medicine, San Francisco, CA, Feb. 11-16, 2013. Reprints: Francesca Facco, MD, Department of Obstetrics and Gynecology, Magee-Womens Hospital, 300 Halket St., Room 2233, Pittsburgh, PA 15213. [email protected]. 0002-9378/$36.00 ª 2014 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.ajog.2013.12.035
and hyperemia of pregnancy that lead to upper airway narrowing and increased airway resistance. In nonpregnant populations, SDB has been linked not only to poor sleep and impaired daytime function but also to adverse health outcomes, such as cardiovascular and metabolic disease.7-13 Recent data also have suggested a potential link between SDB and adverse pregnancy outcomes such as hypertensive disorders of pregnancy, gestational diabetes, and preterm birth.14-20 In a retrospective study, Chen at al15 reported that SDB was associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 1.6, 95% confidence interval [CI], 2.16e11.26), gestational diabetes (aOR, 1.63; 95% CI, 1.07e2.48), and preterm birth (aOR, 2.31; 95% CI, 1.77e3.01). Such data underscore the potential association between SDB and adverse pregnancy outcomes and the importance of gaining a better understanding of this link. However, most of the research regarding the epidemiology of SDB in pregnancy is retrospective or cross-sectional, and the
MONTH 2014 American Journal of Obstetrics & Gynecology FLA 5.2.0 DTD YMOB9608_proof 25 January 2014 7:31 pm ce
1.e1
56 57 58 59 60 61 62 63 64 65 66 67 68 69 70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 87 88 89 90 91 92 93 94 95 96 97 98 99 100 101 102 103 104 105 106 107 108 109 110
Research 111 112 113 114 115 116 117 118 119 120 121 122 123 124 125 126 127 128 129 130 131 132 133 134 135 136 137 138 139 140 141 142 143 144 145 146 147 148 149 150 151 152 153 154 155 156 157 158 159 160 161 162 163 164 165 166
Obstetrics
majority of studies have relied on selfreported symptom assessments. The objective of this study was to examine the relationship between objectively assessed SDB during pregnancy and the risk of adverse pregnancy outcomes.
M ATERIALS
AND
M ETHODS
This was a planned secondary analysis of a study that was designed to evaluate the prevalence of and trends in SDB across pregnancy among women at high risk for developing preeclampsia.21,22 We recruited women with prepregnancy body mass index (BMI) of 30 kg/m2 or greater, chronic hypertension, pregestational diabetes (type 1 or type 2), a prior history of preeclampsia, and/or a twin gestation. The study subjects were recruited as a convenience sample from ambulatory care practices at 2 university centers serving women with both private and public insurance. After signing informed consent, women completed an at-home, overnight sleep evaluation with the WatchPAT100 (Itamar Medical Ltd, Caesarea, Israel) during early pregnancy (between 6 and 20 weeks of gestation) and were asked to repeat the study in late pregnancy (between 28 and 37 weeks of gestation). The Watch-PAT 100, which has a peripheral arterial tonometry (PAT) finger plethysmograph and standard oxygen saturation (SpO2) probe, allows the recording of the PAT signal, heart rate, and oxyhemoglobin saturation. Sleep time is estimated using an inbuilt actigraph.23 Analysis of these signals allows for the determination of an apnea hypopnea index (AHI), which is a sum of the number of apneas (breathing pauses) and hypopneas (shallow breathing) that occur per hour of sleep. In adults an AHI of 0-4.9 is considered normal and an AHI of 5 or greater defines SDB. An AHI of 5-14.9 is typically considered mild SDB, 15-29.9 moderate SDB, and 30 or greater severe SDB.1,2,24,25 The Watch-PAT proprietary software algorithm was used to analyze the PAT signal amplitude along with the heart rate and SpO2 to estimate the AHI. An AHI event was scored if either a PAT
www.AJOG.org amplitude reduction occurred with 3% or greater oxyhemoglobin desaturation or 4% or greater oxyhemoglobin desaturation occurred.26 Studies in nonpregnant populations have shown that respiratory indices, such as the AHI, derived from the Watch-PAT are strongly correlated (r ¼ 0.90) with those obtained from inlaboratory polysomnography (PSG) and also have demonstrated that the Watch-PAT is an accurate and reliable ambulatory method for the detection of SDB.23,26-28 O’Brien et al29 recently presented data comparing the WatchPAT to full PSG in third-trimester pregnant subjects. Their results indicate that among pregnant women, the WatchPAT AHI correlated very well with PSG AHI (r ¼ 0.76, P < .0001) and that the Watch-PAT demonstrated excellent sensitivity (88%) and specificity (86%) for the identification of SDB in pregnancy.29 All participants received obstetrical care by their physicians, who were unaware of the sleep study results. However, women were informed if their AHI was 10 or greater and given contact information for sleep specialists in the area if they were interested in further evaluation. Given that there are currently no sanctioned pregnancy-specific guidelines for SDB treatment or evidence that treatment in the short term has an impact on maternal, obstetric, or neonatal outcomes, no alteration of care was recommended or mandated for study participants, regardless of AHI. Pregnancy outcomes were abstracted from the medical record by physicians unaware of the SDB status of the study subjects. Outcomes of interest included preeclampsia, gestational diabetes, preterm birth (
