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Implications of sleep-disordered breathing in pregnancy

Published:December 26, 2013DOI:https://doi.org/10.1016/j.ajog.2013.12.035

      Objective

      The objective of the study was to examine the relationship between sleep-disordered breathing (SDB) and adverse pregnancy outcomes in a high-risk cohort.

      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.

      Results

      Of the 188 women with a valid early pregnancy sleep study, 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-for-gestational-age (<5%), or large-for-gestational-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 = .03). The adjusted odds ratio for developing gestational diabetes for moderate/severe SDB was 3.6 (0.6, 21.8).

      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

      Sleep 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.
      • Iber C.
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      The American Academy of Sleep Medicine manual for the scoring of sleep and associated events: rules, terminology and technical specifications.
      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.
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      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.
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      This progression is at least partly related to the weight gain, edema, 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.
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      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.
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      Interactions between pregnancy, obstructive sleep apnea, and gestational diabetes mellitus.
      In a retrospective study, Chen at al
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      • Lin H.C.
      Obstructive sleep apnea and the risk of adverse pregnancy outcomes.
      reported that SDB was associated with an increased risk of preeclampsia (adjusted odds ratio [aOR], 1.6, 95% confidence interval [CI], 2.16–11.26), gestational diabetes (aOR, 1.63; 95% CI, 1.07–2.48), and preterm birth (aOR, 2.31; 95% CI, 1.77–3.01). 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 majority of studies have relied on self-reported 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.

      Materials and Methods

      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.
      • Facco F.L.
      • Ouyang D.W.
      • Zee P.C.
      • Grobman W.A.
      Development of a pregnancy-specific screening tool for sleep apnea.

      Facco FL, Ouyang DW, Zee PC, Grobman WA. Sleep disordered breathing in a high risk cohort-prevalence and severity across pregnancy. Am J Perinatol, in press.

      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 Watch-PAT100 (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.
      • Hedner J.
      • Pillar G.
      • Pittman S.D.
      • Zou D.
      • Grote L.
      • White D.P.
      A novel adaptive wrist actigraphy algorithm for sleep-wake assessment in sleep apnea patients.
      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.
      • Iber C.
      • Ancoli-Israel S.
      • Chesson A.
      • Quan S.
      The American Academy of Sleep Medicine manual for the scoring of sleep and associated events: rules, terminology and technical specifications.
      • Berry R.B.
      • Budhiraja R.
      • Gottlieb D.J.
      • et al.
      Rules for scoring respiratory events in sleep: update of the 2007 AASM manual for the scoring of sleep and associated events. Deliberations of the Sleep Apnea Definitions Task Force of the American Academy of Sleep Medicine.
      • Park J.G.
      • Ramar K.
      • Olson E.J.
      Updates on definition, consequences, and management of obstructive sleep apnea. Mayo Clinic proceedings.
      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 amplitude reduction occurred with 3% or greater oxyhemoglobin desaturation or 4% or greater oxyhemoglobin desaturation occurred.
      • Pittman S.D.
      • Ayas N.T.
      • MacDonald M.M.
      • Malhotra A.
      • Fogel R.B.
      • White D.P.
      Using a wrist-worn device based on peripheral arterial tonometry to diagnose obstructive sleep apnea: in-laboratory and ambulatory validation.
      Studies in nonpregnant populations have shown that respiratory indices, such as the AHI, derived from the Watch-PAT are strongly correlated (r = 0.90) with those obtained from in-laboratory polysomnography (PSG) and also have demonstrated that the Watch-PAT is an accurate and reliable ambulatory method for the detection of SDB.
      • Hedner J.
      • Pillar G.
      • Pittman S.D.
      • Zou D.
      • Grote L.
      • White D.P.
      A novel adaptive wrist actigraphy algorithm for sleep-wake assessment in sleep apnea patients.
      • Pittman S.D.
      • Ayas N.T.
      • MacDonald M.M.
      • Malhotra A.
      • Fogel R.B.
      • White D.P.
      Using a wrist-worn device based on peripheral arterial tonometry to diagnose obstructive sleep apnea: in-laboratory and ambulatory validation.
      • Zou D.
      • Grote L.
      • Peker Y.
      • Lindblad U.
      • Hedner J.
      Validation a portable monitoring device for sleep apnea diagnosis in a population based cohort using synchronized home polysomnography.
      • Ayas N.T.
      • Pittman S.
      • MacDonald M.
      • White D.P.
      Assessment of a wrist-worn device in the detection of obstructive sleep apnea.
      O'Brien et al
      • O'Brien L.M.
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      • Shelgikar A.V.
      • Chames M.C.
      • Armitage R.
      • Chervin R.D.
      Validation of Watch-PAT-200 against polysomnography during pregnancy.
      recently presented data comparing the Watch-PAT to full PSG in third-trimester pregnant subjects. Their results indicate that among pregnant women, the Watch-PAT AHI correlated very well with PSG AHI (r = 0.76, P < .0001) and that the Watch-PAT demonstrated excellent sensitivity (88%) and specificity (86%) for the identification of SDB in pregnancy.
      • O'Brien L.M.
      • Bullough A.S.
      • Shelgikar A.V.
      • Chames M.C.
      • Armitage R.
      • Chervin R.D.
      Validation of Watch-PAT-200 against polysomnography during pregnancy.
      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 (<34 weeks' gestation), and birthweight. Preeclampsia was divided into the following categories in concordance with American College of Obstetricians and Gynecologists guidelines: (1) mild preeclampsia, which was new-onset systolic blood pressure of 140 mm Hg or greater or a diastolic blood pressure of 90 mm Hg or greater on 2 occasions 6 hours apart on or after 20 weeks 0/7 days of gestation and within 72 hours of a diagnosis of proteinuria (≥300 mg in a 24-hour urine collection, a spot protein creatinine (PC) ratio of 0.2, or the finding of ≥2+ on dipstick if a 24-hour urine or PC ratio was not available)
      American College of Obstetrics and Gynecology
      ACOG practice bulletin no. 33, January 2002. Diagnosis and management of preeclampsia and eclampsia.
      • Caritis S.
      • Sibai B.
      • Hauth J.
      • et al.
      Low-dose aspirin to prevent preeclampsia in women at high risk. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units.
      ; (2) severe preeclampsia in which criteria for mild preeclampsia are met plus 1 or more of the following: blood pressure of ≥160 mm Hg systolic or ≥110 mm Hg diastolic on 2 occasions at least 6 hours apart, proteinuria of ≥5 g, cerebral or visual disturbances, pulmonary edema or cyanosis, epigastric or right upper-quadrant pain, impaired liver function, thrombocytopenia, and/or fetal growth restriction; or (3) superimposed preeclampsia, which in a woman with hypertension before 20 weeks of gestation is a sudden increase in proteinuria if already present in early gestation, a sudden increase in hypertension, or the development of HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome.
      All diagnoses of preeclampsia were confirmed by a second physician.
      • Zou D.
      • Grote L.
      • Peker Y.
      • Lindblad U.
      • Hedner J.
      Validation a portable monitoring device for sleep apnea diagnosis in a population based cohort using synchronized home polysomnography.
      • Ayas N.T.
      • Pittman S.
      • MacDonald M.
      • White D.P.
      Assessment of a wrist-worn device in the detection of obstructive sleep apnea.
      Gestational diabetes was diagnosed according to glucose tolerance test standards (either a 100 g, 3-hour glucose tolerance test or a 75-g, 2-hour glucose tolerance test). Women with pregestational diabetes were excluded from the gestational diabetes analyses.
      Associations were explored between SDB presence/severity and our outcomes of interest through the use of the χ2, Fisher exact, and χ2 test for trend for categorical variables. Multivariable logistic regression was used to adjust for potential confounders. All tests were 2 tailed and a P < .05 was considered statistically significant. Statistical analysis was performed using SPSS 19.0 statistical software (SPSS Inc, Chicago, IL).
      For the primary study, designed to detected changes in SDB across pregnancy, we established that a sample size of 180 women would be required to complete the baseline study.

      Facco FL, Ouyang DW, Zee PC, Grobman WA. Sleep disordered breathing in a high risk cohort-prevalence and severity across pregnancy. Am J Perinatol, in press.

      We enrolled 233 women; 182 had valid sleep study data and delivered at the study sites. The incidence of early pregnancy SDB in this high-risk population was 30%. Assuming a 15% risk of preeclampsia in our non-SDB subjects and an α of 0.05, we had 80% power to detect an increase to 34% (crude odds ratio, 2.9) among women with SDB. This magnitude of association is consistent with that that has been observed between SDB and cardiovascular and metabolic diseases in nonpregnant individuals.
      • Peppard P.E.
      • Young T.
      • Palta M.
      • Skatrud J.
      Prospective study of the association between sleep-disordered breathing and hypertension.
      • Bradley T.D.
      • Floras J.S.
      Obstructive sleep apnoea and its cardiovascular consequences.
      This study was approved by the Institutional Review Board of Northwestern University and North Shore University Health System.

      Results

      Two hundred thirty-three women consented to participate in the primary study. One hundred eighty-eight and 128 of these women had a valid early and late pregnancy sleep study, respectively. The reasons for incomplete sleep data are presented in the Figure. The mean gestational age (±SD) was 16.7 ± 3.5 and 32.6 ± 2.4 weeks at the first and second sleep study, respectively.
      Figure thumbnail gr1
      FigureStudy recruitment
      Facco. Sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014.
      Demographic characteristics of the study population are provided in Table 1. Sixty-two percent of subjects were obese, 30% had chronic hypertension, 57% had pregestational diabetes, 15% had prior preeclampsia, and 6% had a twin gestation. Fifty-four percent of women had more than 1 qualifying risk factor. In early pregnancy 21%, 6%, and 3% of women had mild, moderate, or severe SDB, respectively. These frequencies increased to 35%, 7%, and 5% in the third trimester. Twenty-seven percent of participants (n = 34) experienced a worsening of SDB during pregnancy; 26 were cases of new-onset SDB, whereas the other 8 had SDB in early pregnancy that worsened in severity.

      Facco FL, Ouyang DW, Zee PC, Grobman WA. Sleep disordered breathing in a high risk cohort-prevalence and severity across pregnancy. Am J Perinatol, in press.

      Because of the small number of cases of moderate and severe SDB, we combined these 2 groups for further analysis.
      Table 1Characteristics of study participants
      CharacteristicEntire cohort

      (n = 188)
      Participants with an AHI ≤5 in early pregnancy

      (n = 132)
      Participants with an AHI ≥5 in early pregnancy

      (n = 56)
      P value
      Age, y33.0 ± 5.932.4 ± 6.134.4 ± 5.2.04
      Ethnoracial status
       White39.2%40.2%37.5%.8
       Black25.5%26.5%23.2%
       Hispanic20.2%18.2%25.0%
       Other14.9%15.1%14.3%
      Prepregnancy BMI, kg/m232.8 ± 8.730.8 ± 8.237.2 ± 8.3< .001
      Maternal history
       Chronic hypertension29.8%23.5%44.6%.004
       Pregestational diabetes57.4%62.1%46.4%.05
       Twins5.9%7.6%1.8%.2
       Nulliparous29.3%28.8%30.4%.8
       Prior preeclampsia16.5%14.4%21.4%.2
      AHI, apnea hypopnea index; BMI, body mass index.
      Facco. Sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014.
      Pregnancy outcomes were available for 182 of the 188 women with a valid early pregnancy sleep study. Two women had first trimester miscarriages, and 4 women were lost to follow-up.
      The rates of adverse pregnancy outcomes stratified by SDB status are presented in Tables 2 and 3. Preeclampsia occurred in 17.6% of women (14 cases of mild preeclampsia, 6 cases of severe preeclampsia, and 12 cases of superimposed preeclampsia). There was no relationship demonstrated between SDB in early or late pregnancy and preeclampsia. The rate of preterm birth less than 34 weeks was 9%, of which half were iatrogenic. There was no relationship demonstrated between SDB exposure in early or late pregnancy and either preterm birth less than 34 weeks or iatrogenic preterm birth less than 34 weeks. Similarly, there was no association between SDB and extremes of birthweight (less than 5% or greater than 95% for gestational age).
      • Alexander G.R.
      • Himes J.H.
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      A United States national reference for fetal growth.
      Table 2SDB in early pregnancy and adverse pregnancy outcomes
      VariableNo SDBMild SDB

      (AHI 5-14.9)
      Moderate/severe SDB (AHI ≥15)P value
      χ2 for trend
      Any preeclampsia24/127 (18.9)5/40 (12.5)3/15 (20).7
      Preeclampsia among women without CHTN17/99 (17.2)1/23 (4.3)2/8 (25).7
      Superimposed preeclampsia among women with CHTN7/28 (25)4/17 (23.5)1/7 (14.3).6
      Gestational diabetes13/49 (26.5)9/21 (42.9)5/8 (62.5).03
      Preterm birth <34 wks12/127 (9.4)3/40 (7.5)2/15 (13.3).8
      Iatrogenic preterm birth <34 wks6/127 (4.7)2/40 (5)1/15 (6.7).7
      Birthweight
      Birthweight was not available for 2 subjects.
       <5%1/125 (0.8)1/40 (2.5)0/15 (0).8
       >95%27/125 (21.6)7/40 (17.5)1/15 (6.7).2
      Data are n/N (%).
      AHI, apnea hypopnea index; CHTN, chronic hypertension; SDB, sleep-disordered breathing.
      Facco. Sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014.
      a χ2 for trend
      b Birthweight was not available for 2 subjects.
      Table 3SDB in late pregnancy and adverse pregnancy outcomes
      VariableNo SDBMild SDB

      AHI 5-14.9
      Moderate/severe SDB AHI ≥15P value
      χ2 for trend.
      Any preeclampsia13/67 (19.4)4/45 (8.9)2/16 (12.5).2
      Preeclampsia among women without CHTN10/50 (20)3/33 (9.1)1/7 (14.3).3
      Superimposed preeclampsia among women with CHTN3/17 (17.6)1/12 (8.3)1/9 (11.1).6
      Gestational diabetes4/25 (16)5/14 (35.7)5/11 (45.5).05
      Preterm birth <34 wks5/67 (7.5)1/45 (2.2)0/16 (0).1
      Iatrogenic preterm birth <34 wks4/67 (6)1/45 (2.2)0/16 (0).2
      Birthweight
       <5%1/67 (1.5)0/44 (0)0/16 (0).4
       >95%13/67 (19.4)1/44 (25)2/16 (12.5).9
      Data are n/N (%).
      AHI, apnea hypopnea index; CHTN, chronic hypertension; SDB, sleep-disordered breathing.
      Facco. Sleep-disordered breathing in pregnancy. Am J Obstet Gynecol 2014.
      a χ2 for trend.
      In contrast, increasing SDB severity in early pregnancy was associated with an increased risk of developing gestational diabetes (P = .03). This trend also was observed for SDB in late pregnancy, although the difference did not reach statistical significance. The unadjusted odds ratio for developing gestational diabetes was 2.1 (95% CI, 0.7–6.1) for women with mild SDB in early pregnancy and 4.6 (95% CI, 1.0–22.1) for women with moderate/severe SDB.
      Controlling for age, prepregnancy BMI, race/ethnicity, parity, chronic hypertension, and twin gestation, the aOR for developing gestational diabetes for mild SDB in early pregnancy was 1.5 (95% CI, 0.4–6.0) and 3.6 (95% CI, 0.6–21.8) for moderate/severe SDB. Although the aOR estimates derived from this modest sample size did not achieve statistical significance, they demonstrated the potential independent impact of SDB on glucose control during pregnancy.

      Conclusion

      This study suggests a dose-dependent relationship between SDB exposure in early pregnancy and the subsequent development of gestational diabetes. In contrast, no relationships were demonstrated between SDB during pregnancy and preeclampsia, preterm birth, and extremes of birthweight.
      Data from symptom-based studies and retrospective chart reviews have demonstrated a link between SDB and gestational diabetes. In a recent metaanalysis, Pamidi et al
      • Pamidi S.
      • Pinto L.M.
      • Marc I.
      • Benedetti A.
      • Schwartzman K.
      • Kimoff R.J.
      Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis.
      demonstrated a pooled, aOR of 1.86 (95% CI, 1.30–2.42) for gestational diabetes when SDB is suspected during pregnancy. A second, contemporaneous metaanalysis corroborates these data.
      • Luque-Fernandez M.A.
      • Bain P.A.
      • Gelaye B.
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      • Williams M.A.
      Sleep-disordered breathing and gestational diabetes mellitus: a meta-analysis of 9,795 participants enrolled in epidemiological observational studies.
      Our findings confirmed this relationship and in addition demonstrated a dose-response relationship between the severity of SDB in early pregnancy and the subsequent development of gestational diabetes.
      In contrast to prior reports, our study did not demonstrate a relationship between SDB and preeclampsia. Louis et al
      • Louis J.
      • Auckley D.
      • Miladinovic B.
      • et al.
      Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women.
      recently published a study similar in design and size (n = 175) to this study. They demonstrated that women with SDB (AHI of ≥5) were more likely to develop preeclampsia (aOR, 3.5; 95% CI, 1.3–9.9).
      • Louis J.
      • Auckley D.
      • Miladinovic B.
      • et al.
      Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women.
      It is important to note that the cohort in the study by Louis et al
      • Louis J.
      • Auckley D.
      • Miladinovic B.
      • et al.
      Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women.
      had a higher mean prepregnancy BMI and a higher percentage of black participants than the population in our study. Subjects in their study also suffered from more severe SDB compared with our cohort (ie, a median AHI in early pregnancy of 12.9 vs 9.8, respectively). Furthermore, prior studies may not have adequately distinguished between chronic hypertension and superimposed preeclampsia. Given the association between chronic hypertension and SDB, the misclassification of the former as superimposed preeclampsia would bias the results toward a positive association.
      In the present study, we attempted to lessen the chance of this bias by having any case of preeclampsia confirmed by a second abstractor. Although our sample size was modest, we had 80% power to detect an increase to 34% (crude odds ratio of 2.9) in the rate of preeclampsia in subjects with SDB. This magnitude of association is in the range of what has been reported by Pamidi et al,
      • Pamidi S.
      • Pinto L.M.
      • Marc I.
      • Benedetti A.
      • Schwartzman K.
      • Kimoff R.J.
      Maternal sleep-disordered breathing and adverse pregnancy outcomes: a systematic review and metaanalysis.
      in their meta-analysis (crude odds ratio, 2.86; 95% CI, 2.17–3.78) and by Louis et al
      • Louis J.
      • Auckley D.
      • Miladinovic B.
      • et al.
      Perinatal outcomes associated with obstructive sleep apnea in obese pregnant women.
      in their cohort study.
      Our study had several strengths. We used objective assessments of SDB in pregnancy, and our SDB data were ascertained prior to the adverse pregnancy outcomes. All chart abstraction was conducted by obstetricians who were unaware of the SDB exposure. Moreover, all preeclampsia cases were reviewed by a second abstractor, and all gestational diabetes cases were confirmed by review of glucose tolerance testing results.
      Our study has several limitations that require consideration as well. First, our study population was a high-risk, heterogeneous cohort, and we recognize that the results of our study may not be generalizable to all pregnant women. Healthier women may have greater consequences from SDB exposure; however, their likelihood of having SDB would be significantly less.
      Second, although all chart abstractors were blinded to the SDB exposure, participants with an AHI of 10 or greater were notified of their sleep study findings (14.9% and 30.5% of participants in early and late pregnancy, respectively). As part of our medical records review, we asked chart abstractors to search the record of all subjects for evidence that a clinical sleep study was performed, that a formal diagnosis of SDB was made, or that a subject was on continuous positive airway pressure (CPAP). To our knowledge, no participant received care for SDB during pregnancy.
      Lastly, the majority of our SDB cases, as expected in a young female cohort, were mild. Larger sample sizes are needed to more precisely ascertain how more severe SDB may impact pregnancy.
      Our study findings underscore the importance of systematically gathering further evidence on the impact of SDB on pregnancy. Studies addressing SDB's impact on pregnancy are heterogeneous in regard to study design and SDB definition. Furthermore, as we have illustrated, findings in these studies are inconsistent. Consequently, it is premature to suggest that obstetrical care providers should systematically screen for SDB in pregnancy. Such a change in care would require a massive education effort because most obstetrical providers have not been trained to screen for sleep disorders and would lead to increased health care costs.
      Moreover, at this time there is no evidence that treatment of SDB in the short term improves maternal or neonatal outcomes. CPAP has been used to improve pathophysiological derangements related to SDB. For example, CPAP improves biomarkers of inflammation and oxidative stress.
      • Bayram N.A.
      • Ciftci B.
      • Keles T.
      • et al.
      Endothelial function in normotensive men with obstructive sleep apnea before and 6 months after CPAP treatment.
      • Ciccone M.M.
      • Favale S.
      • Scicchitano P.
      • et al.
      Reversibility of the endothelial dysfunction after CPAP therapy in OSAS patients.
      • Kohler M.
      • Stoewhas A.C.
      • Ayers L.
      • et al.
      Effects of continuous positive airway pressure therapy withdrawal in patients with obstructive sleep apnea: a randomized controlled trial.
      • Ohike Y.
      • Kozaki K.
      • Iijima K.
      • et al.
      Amelioration of vascular endothelial dysfunction in obstructive sleep apnea syndrome by nasal continuous positive airway pressure—possible involvement of nitric oxide and asymmetric NG, NG-dimethylarginine.
      • Sharma S.K.
      • Agrawal S.
      • Damodaran D.
      • et al.
      CPAP for the metabolic syndrome in patients with obstructive sleep apnea.
      • Zamarron C.
      • Riveiro A.
      • Gude F.
      Circulating levels of vascular endothelial markers in obstructive sleep apnoea syndrome. Effects of nasal continuous positive airway pressure.
      It improves nocturnal respiratory indices, and in patients with significant symptoms of SDB, it can improve sleep and daytime function.
      • Tregear S.
      • Reston J.
      • Schoelles K.
      • Phillips B.
      Continuous positive airway pressure reduces risk of motor vehicle crash among drivers with obstructive sleep apnea: systematic review and meta-analysis.
      A recent study of middle aged, predominately male adults demonstrated that 3 months of CPAP therapy in individuals with at least moderate SDB was associated with a decrease in blood pressure, lipid levels, glycated hemoglobin levels, BMI, and abdominal fat content.
      • Sharma S.K.
      • Agrawal S.
      • Damodaran D.
      • et al.
      CPAP for the metabolic syndrome in patients with obstructive sleep apnea.
      Yet in nonpregnant adults, the role of CPAP in reversing or preventing long-term cardiovascular and metabolic morbidity remains unanswered, especially for patients with only mild SDB.
      • Barbe F.
      • Duran-Cantolla J.
      • Capote F.
      • et al.
      Long-term effect of continuous positive airway pressure in hypertensive patients with sleep apnea.
      • Duran-Cantolla J.
      • Aizpuru F.
      • Montserrat J.M.
      • et al.
      Continuous positive airway pressure as treatment for systemic hypertension in people with obstructive sleep apnoea: randomised controlled trial.
      • Haentjens P.
      • Van Meerhaeghe A.
      • Moscariello A.
      • et al.
      The impact of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea syndrome: evidence from a meta-analysis of placebo-controlled randomized trials.
      • Marin J.M.
      • Carrizo S.J.
      • Vicente E.
      • Agusti A.G.
      Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study.
      Similarly, the role of CPAP in preventing maternal/fetal morbidity during pregnancy has yet to be determined. Large, prospective cohorts that use objective SDB assessments across pregnancy are needed to accurately define the impact of SDB on pregnancy outcomes. Second, clinical trials of CPAP use in pregnancy are needed to determine whether short-term treatment of SDB in pregnancy can improve maternal and neonatal health.
      In summary, our study suggests a relationship between SDB and gestational diabetes but not with preeclampsia, preterm birth, or fetal growth. Future studies are needed to further and precisely determine the implications of SDB on pregnancy and to evaluate the impact of treatment of this sleep disorder during pregnancy on maternal and perinatal health.

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