Sleep Breath DOI 10.1007/s11325-015-1188-9
ORIGINAL ARTICLE
Sleep disorders in pregnancy and their association with pregnancy outcomes: a prospective observational study S. K. Sharma 1 & A. Nehra 1 & S. Sinha 1 & M. Soneja 1 & K. Sunesh 2 & V. Sreenivas 3 & D. Vedita 4
Received: 13 November 2014 / Revised: 8 March 2015 / Accepted: 21 April 2015 # Springer-Verlag Berlin Heidelberg 2015
Abstract Purpose Sleep disturbances such as insomnia, nocturnal awakenings, restless legs syndrome, habitual snoring, and excessive daytime sleepiness are frequent during pregnancy, and these have been linked to adverse maternal and fetal outcomes. Methods A prospective observational study was performed in high-risk Indian pregnant women. We used modified Berlin questionnaire (MBQ), Pittsburgh sleep quality index (PSQI), International Restless Legs Syndrome Study Group 2011 criteria, and Epworth sleepiness scale to diagnose various sleep disorders, such as symptomatic OSA, poor sleep quality and insomnia, RLS, and excessive daytime sleepiness, respectively, in successive trimesters of pregnancy. Outcome variables of interest were development of gestational hypertension (GH), gestational diabetes mellitus (GDM), and cesarean delivery (CS); the Apgar scores; and low birth weight (LBW). The relationship between sleep disorders and outcomes was explored using logistic regression analysis. Results Outcome data were obtained in 209 deliveries. As compared to nonsnorers, women who reported snoring once, twice, and thrice or more had odds ratios for developing GH—
* S. K. Sharma
[email protected] 1
Department of Medicine, All India Institute of Medical Sciences, New Delhi 110029, India
2
Department of Obstetrics and Gynecology, All India Institute of Medical Sciences, New Delhi 110029, India
3
Department of Biostatistics, All India Institute of Medical Sciences, New Delhi 110029, India
4
Department of Radio-Diagnosis, PGIMS, Rohtak 124001, Haryana, India
4.0 (95 % CI 1.3–11.9), 1.5 (95 % CI 0.5–4.5), and 2.9 (95 % CI 1.0–8.2) and for undergoing CS—5.3 (95 % CI 1.7–16.3), 4.9 (95 % CI 1.8–13.1), and 5.1 (95 % CI 1.9–14.9), respectively. Pregnant women who were persistently positive on MBQ had increased odds for GH and CS. Conclusions Snoring and high-risk MBQ in pregnant women are strong risk factors for GH and CS. In view of the significant morbidity and health care costs, simple screening of pregnant women with questionnaires such as MBQ may have clinical utility. Keywords Obstructive sleep apnea . Cesarean delivery . Gestational hypertension . Restless legs syndrome . Modified Berlin questionnaire . Pittsburgh sleep quality index
Introduction Obstructive sleep apnea (OSA) is a common sleep disorder characterized by repeated episodes of complete or partial upper airway collapse resulting in hypoxemia with or without hypercarbia. These hypoxic episodes lead to fragmentation of sleep [1]. As compared to a nonpregnant woman, a gravid woman has profound physical, physiological, hormonal, and behavioral changes. Interplay of these factors decides whether a woman develops OSA or not during pregnancy. Weight gain during pregnancy [2], upward displacement of the diaphragm by fetus [3], and estrogen-induced mucosal edema and hyperemia predispose women [4] to habitual snoring and OSA. Decreased rapid eye movement sleep and increased minute ventilation [5] are counterbalancing forces that are protective against OSA. The hypoxic episodes due to OSA have been implicated as a cause of endothelial dysfunction, proinflammatory cytokine activation, placental dysfunction, and sympathetic activation, which predispose women to gestational
Sleep Breath
hypertension (GH), preeclampsia, low birth weight (LBW) in babies, intrauterine growth retardation, and gestational diabetes mellitus (GDM) [1, 6]. The prevalence of OSA and habitual snoring in the general population is 5 and 6.7 %, respectively. However, the true prevalence of OSA in pregnancy is unclear [7, 8]. There is a paucity of data on sleep disorders concerning Asian pregnant women and, in particular, Indian women [9, 10], but a limited number of published studies from Asia show very high prevalence of snoring and OSA in pregnant women [9–11]. Various studies have also shown conflicting results on the association between OSA and various pregnancy outcomes. A study by Loube et al. [12] reported no association between mothers with frequent snoring and LBW infants, whereas a large study by Chen et al. [9] reported that compared with women without OSA, adjusted odds ratios for LBW, preterm birth, small-forgestational-age infants, cesarean delivery, and preeclampsia in women with OSA were 1.76 (95 % CI 1.28–2.40), 2.31 (95 % CI 1.77–3.01), 1.34 (95 % CI 1.09–1.66), 1.74 (95 % CI 1.48– 2.04), and 1.60 (95 % CI 2.16–11.26), respectively. Therefore, whether there was an association between OSA and adverse pregnancy outcomes remains unanswered. Insomnia is also increasingly being recognized as a highly prevalent and underdiagnosed disorder in pregnancy with reported prevalence between 52 and 62 % [13, 14]. Factors that have been implicated in the high prevalence of insomnia in pregnancy are pelvic girdle pain, low back pain, and increased frequency of micturition. Adjustment problems, vomiting, and anxiety may also contribute to insomnia. Insomnia, poor sleep quality, and decreased sleep duration have been implicated in poor obstetric outcomes, including the development of GH and GDM [15], and placental abruption [16]. Restless legs syndrome (RLS) is also a commonly recognized disorder in pregnant women [17]. This study aimed to prospectively examine the impact of sleep disorders on GH, preeclampsia, LBW, low Apgar score, and GDM in Indian pregnant women.
Methods Patient selection The study was conducted at the All India Institute of Medical Sciences (AIIMS) hospital, a tertiary-level referral center in New Delhi, India. The study protocol was approved by the departmental research committee and institutional review board of the institute. Subjects were selected from the patients attending the outpatient department (OPD) of the AIIMS from July 2012 to July 2014. Pregnant patients with singleton pregnancy aged between 20 and 45 years attending AIIMS antenatal OPD in the first trimester of pregnancy were recruited and followed up in successive trimesters (see Fig. 1). All
subjects received obstetrical care by their physician, and no alteration of obstetrical care was recommended or mandated for the study participants. Consenting patients with singleton pregnancy aged between 20 and 45 years were included in the study, whereas those with gestational trophoblastic disease and multifetal gestation were excluded. At the time of enrollment in the first trimester, the patients were also asked to fill in separate set of questionnaires on memory basis to know quality of sleep and prevalence of sleep disorders before pregnancy. Questionnaire-based follow-up was done in the second and third trimesters. So, each patient who completed the study was screened with a questionnaire at four times, that is, before pregnancy (on memory basis at the time of enrollment in study in the first trimester) and during the first, second, and third trimester. Patients who were lost to follow-up, those who had abortions, or those with incomplete data about perinatal outcomes were excluded from the study. Modified Berlin questionnaire All the subjects were requested to fill in the modified Berlin questionnaire (MBQ) [18] themselves, preferably in the presence of their bed partners. Subjects who could not read and write were administered the questionnaire by the first author (SKS) with the help of their spouse. Locally translated version (Hindi) of the questionnaire was used for subjects who could not read and write English. The questionnaire was backtranslated into English with no difference in the meaning conveyed. Pittsburgh sleep quality index Pittsburgh sleep quality index (PSQI) [19] is an instrument used to measure the quality and patterns of sleep in adults. It has seven components: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last month. Scores range from 0 to 21 and global scores higher than 5 yield a sensitivity and specificity of 89.6 and 86.5, respectively, in the general population. RLS diagnosis [20, 21] was clinically made based on International Restless Legs Syndrome Study Group (IRLSSG) 2011 criteria. Epworth sleepiness scale (ESS) [22] was used to evaluate excessive daytime sleepiness. Maternal and neonatal outcome data The medical records of all enrolled women and their infants were reviewed, and information regarding antepartum course, delivery, and postdelivery complications (up to 6 weeks) was recorded. Chart abstraction was performed by an individual masked to sleep status of the study participants. Obtained
Sleep Breath Fig. 1 Flow diagram of the participants
329 patients screened in antenatal OPD, AIIMS 40 patients refused to participate 16 multifetal gestations 273 patients in the first trimester 273 prepregnancy sleep assessment on memory basis
18 patients lost to follow-up 22 abortions 233 patients in the second trimester 4 patients lost to follow-up 9 abortions 220 patients in the third trimester 11 patients lost to follow-up 209 maternal and fetal outcomes at delivery
maternal and neonatal data included obstetric history, parity, and comorbidities, which included hypertension, GDM, hypothyroidism, cesarean birth, LBW, and Apgar scores at 1 and 5 min. The American College of Obstetricians and Gynecologists clinical definitions used for the diagnosis of the comorbidities mentioned earlier included chronic hypertension (systolic blood pressure ≥140 mm Hg or diastolic blood pressure ≥90 mm Hg based on the average of two or more readings at each of two or more visits before 20 weeks or use of antihypertensive medication before pregnancy) and pre-GDM (any of the following at the initial prenatal visit: fasting plasma glucose ≥126 mg/dL, hemoglobin-A1c ≥6.5 %, or random plasma glucose ≥200 mg/dL) [23]. The diagnosis of preeclampsia required a systolic blood pressure >140 mm Hg or a diastolic blood pressure >90 mm Hg associated with significant proteinuria (>300 mg/dL) occurring on two occasions within 4 h to 14 days; GH was the former without evidence of significant proteinuria [24]. GDM was diagnosed per recommendations by the American Diabetes Association 2013 guidelines [25]. LBW was defined as birth weight 5)
15.1 (0.3–0.6)
10 (12.8) 6 (4.6)
Twice
1 (0.8)
1.6 (0.6–4.1)
12 (9.2)
Three times or more 7 (9)
52 (66.7) 112 (85.5) 1.0
9 (11.5)
Negative always
Once
MBQ
4.9 (1.8–13.1)
13 (16.7) 7 (5.3)
Twice
5.3 (1.7–16.3)
43 (55.1) 113 (86.3) 1.0
10 (12.8) 5 (3.82)
Negative always
P value
Yes (%)
OR (95 % CI)
Yes (%)
No (%)
LBW
Gestation hypertension
Cesarean delivery
GDM
Neonatal outcomes
Maternal outcomes
Maternal and neonatal outcomes associated with symptom-diagnosed OSA and other sleep disorders (n=209)
Once
Snoring
Disorders
Table 2
No (%)
OR (95 % CI)
2 (5.3)
1 (2.6)
3 (7.9)
32 (84.2)
5 (13.6)
9 (23.7)
89 (42.6)
54 (25.8)
4 (10.5)
1 (2.6)
4 (10.5)
29 (76.3)
4 (10.5)
2 (5.3)
3 (7.9)
1. 3 (0.4–4.1)
0.5 (0.1–2.2)
1.1 (0.3–4.1)
4.9 (1.2–20.2)
2.1 (0.6–6.8)
2.7 (0.9–7.6)
1.0
4.7 (1.1–19.7)
0.3 (0.0–2.4)
1.1 (0.3–3.5)
7 (4.1)
9 (5.3)
13 (7.6)
1.3 (0.3–6.4)
0.5 (0.1–4.0)
1.0 (0.3–3.8)
142 (83.0) 1.0
10 (5.8)
42 (24.6)
70 (40.9)
49 (28.7)
4 (2.3)
15 (8.8)
17 (9.9)
135 (79.0) 1.0
14 (8.2)
18 (10.5)
12 (7.0)
156 (74.6) 127 (74.3) 1
Yes (%)
Apgar 5 [18], it has not been validated for screening of OSA in pregnant women. As we know from previous studies that presenting complaints of OSA differ markedly in female patients from their male counterparts [36, 37], a validated questionnaire is required for OSA screening in pregnant women. This is particularly true in light of the present and past studies showing that OSA may be more common in pregnant women than previously thought and may partly be responsible for adverse perinatal outcomes. As hypertension is one of the major components in risk categorization in MBQ, we believe that it may overestimate the prevalence of OSA in preeclampsia patients and underestimate the prevalence of OSA in nonpreeclamptic pregnant women. This is because hypertension is less common in pregnant women in the 20–45-year age group as compared to other nonpregnant patients with OSA who are generally middle-aged or old men with obesity and metabolic syndrome [18, 38]. Also, complain of fatigue is more common in pregnant women as compared to the general population, and it is one of the criteria for risk categorization in MBQ, so MBQ may overestimate the prevalence of OSA in pregnant women. However, OSA in this population is likely to be underestimated given that the atypical symptoms may be mistaken as physical, mental, or emotional manifestations of changes occurring during pregnancy [36, 37, 39, 40]. The majority of studies to date in pregnant women have assessed the validity of screening questionnaires; prospective studies are necessary to ascertain the validity of symptombased diagnosis in this very important subgroup of population. However, the cost-effectiveness and efficiency of using the questionnaires to screen pregnant women in outpatient and research settings should be considered. Another limitation of this study was that large numbers of patients were lost to follow-up during the study, which is inherent in prospective studies. This study was performed in a tertiary-level referral center, so great caution must be exercised in extrapolating these findings to all pregnant women. As the diagnosis of sleep disorders before the onset of pregnancy was made retrospectively on the basis of patient recall, it involves recall bias. Also due to the small number of cases, we were not able to calculate odds ratio for preeclampsia and Apgar score at 5 min. The strength of this study was that our analysis was performed in a prospectively acquired study group of pregnant women and thus avoids bias inherent to case–control and
retrospective studies. Also, we collected data for the prevalence of sleep disorders in prepregnancy as well as for followed up patients in the postpartum period. The prospective nature of this study also allowed us to show that sleep disorders preceded the development of most perinatal outcomes such as cesarean birth and development of GH. This observation is vital as it is sine qua non to prove causality of association. To the best of our knowledge, this study is the first study from the Indian subcontinent on sleep problems in pregnancy and their relationship with pregnancy outcomes.
Conclusion &
Sleep disorders may predispose pregnant women to various adverse pregnancy outcomes such as GH and cesarean delivery, which increase morbidity. These findings assume greater importance as GH and cesarean delivery contribute to long-term morbidity for patients. Simple office-based screening tools may help in the identification of women who require further evaluation for sleep-disordered breathing in the future. The MBQ may prove a useful screening tool in pregnant women for the screening of sleep-disordered breathing. Further research is required in this field to increase awareness about sleep disorders in this subgroup of patients.
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Conflict of interest All authors declare that they have no conflict of interest. Funding None.
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