Logo of nihpaAbout Author manuscriptsSubmit a manuscriptNIH Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Obstet Gynecol Surv. Author manuscript; available in PMC Jun 3, 2010.
Published in final edited form as:
Obstet Gynecol Surv. Apr 2009; 64(4): 273–280.
doi:  10.1097/OGX.0b013e318195160e
PMCID: PMC2880322
NIHMSID: NIHMS206266

How Disturbed Sleep May Be a Risk Factor for Adverse Pregnancy Outcomes A Hypothesis

Michele L. Okun, PhD,* James M. Roberts, MD,§ Anna L. Marsland, PhD, and Martica Hall, PhD||

Abstract

Adverse pregnancy outcomes associated with significant maternal and infant morbidity are on the rise in Western society despite advances of medical technology. Current risk factors are insufficient to identify women at greatest risk of developing an adverse outcome. An attempt to identify novel contributors to increased risk is warranted. Sleep disturbances are frequent during pregnancy, yet are often dismissed as irrelevant. Emerging evidence indicates that sleep disturbances are associated with poor health outcomes, including cardiovascular disease. Disturbed sleep is also linked with an increased inflammatory response. Increased inflammation is proposed as a key biological pathway through which chronic disease and adverse pregnancy outcomes develop. In this paper, we propose a model and a testable hypothesis of how disturbed sleep in the first 20 weeks of pregnancy could contribute to adverse pregnancy outcomes such as preeclampsia, intrauterine growth restriction, and preterm birth via increased inflammation.

Target Audience

Obstetricians & Gynecologists, Family Physicians

Leaning Objectives

After completion of this article, the reader should be able to outline data linking sleep disturbances with an increased risk of some systemic disorders, recall characteristics of pregnancy complications which support the hypothesis that sleep disturbances may be related to these pregnancy outcomes, and summarize the likelihood and types of sleep disturbances that are common in pregnant women.

In the United States over 1 million pregnancies each year result in adverse outcomes that increase maternal and infant morbidity (1, 2). The most frequent adverse outcomes include preeclampsia, intrauterine growth restriction (IUGR), and preterm birth. Despite extensive research and the identification of multiple risk factors little progress has been made in understanding or preventing these disorders. The need to explore novel contributors to these disorders is highlighted by the fact that established risk factors identify only about 50% of women at risk for adverse outcomes (2-5). Sleep disturbances, a frequent complaint of pregnant women (6, 7), are now recognized as important contributors to several disease states and we propose that sleep disturbances may be a novel contributor to adverse pregnancy outcomes.

Sleep is not merely the absence of waking. On the contrary, it is a state during which specialized physiological activities occur in the brain and throughout the body. It is an active process in which metabolism, tissue restoration, memory consolidation, and general homeostatic balance is maintained (8, 9). Homeostatic and circadian influences dictate that we spend approximately one-third of our lives asleep (10). Yet, to date, the primary focus in the pathogenesis of disease has been on the role of waking factors with little attention to sleep.

Sleep disturbances are implicated in both increased morbidity and mortality. Poor sleep quality is associated with increased risk for depression (11-13) (Okun et al, in press), whereas short sleep duration is associated with increased incidence of diabetes (14, 15), obesity (16, 17), as well as increased all-cause mortality (18-20). Of the many disease outcomes associated with poor sleep, cardiovascular disease is of particular relevance to several pregnancy complications, such as preeclampsia, IUGR, and preterm birth. These adverse pregnancy outcomes share risk factors with cardiovascular disease and are associated with a greater risk of developing cardiovascular disease later in life (21, 22). Therefore, for purposes of illustration we emphasize the consistent association of poor sleep quality and short sleep duration with increased risk of cardiovascular disease (23-27), an association that is stronger in women than men (23, 26).

Disturbed sleep affects several biological pathways associated with cardiovascular morbidity, including neuroendocrine, metabolic, and inflammatory systems. One way that disturbed sleep may increase cardiovascular disease is by exacerbating well recognized cardiovascular risk factors. Importantly, many of these are also risk factors for adverse pregnancy outcomes. Two major risk factors for cardiovascular disease are obesity (16, 17, 28-30) and independently, increased insulin resistance (31, 32). Short sleep duration and sleep disturbances are associated with increased BMI (16, 17, 29, 33), whereas experimental sleep deprivation and poor sleep quality can increase insulin resistance (31, 34).

Several risk factors for cardiovascular disease also increase adverse pregnancy outcomes. Preeclampsia and spontaneous preterm birth are increased in women with BMIs >30 (35-37), and increased insulin resistance is associated with higher rates of preeclampsia and growth restricted babies (38-40). Furthermore, these adverse pregnancy outcomes share pathophysiological features with cardiovascular disease. Increased oxidative stress, endothelial dysfunction and inflammation are implicated in the pathogenesis of cardiovascular disease and adverse pregnancy outcomes (21, 22, 41, 42). We propose that through these common mechanisms disturbed sleep may contribute to the risk of adverse pregnancy outcomes.

We review the relevant published literature to support the hypothesis that disturbed sleep may increase adverse pregnancy outcomes. Information specifically addressing sleep disturbances and pregnancy outcomes is limited. Therefore, our goal is to use existing information on the relationship of sleep to disease, and particularly cardiovascular disease, to inform a rationale and a testable hypothesis for how disturbed sleep may increase preeclampsia, IUGR, and preterm birth.

Sleep and Pregnancy

A common perception is that sleep is markedly disturbed in pregnancy (6, 7, 43). Sleep disturbances are typically classified as: disturbed sleep quality, poor sleep continuity, short/long sleep duration, restless legs syndrome, and sleep disordered breathing. Sparse data are available that indicate what to expect with regards to the timing, degree, frequency, and/or severity of a specific pregnancy-related sleep disturbance. Although up to 75% of pregnant women experience some form of sleep disruption during pregnancy, the number of women who report significant sleep complaints in the first trimester is only about 25% (7).

Common Pregnancy-Related Sleep Disturbances

The subjective perception of poor sleep quality is the most commonly assessed sleep disturbance during pregnancy (7, 44-46), with sleep quality typically declining as pregnancy progresses (7, 47). Sleep continuity, another measure of sleep, is the degree of fragmentation in a sleep period. Several indices describe sleep continuity, including sleep latency, number of awakenings, and total minutes spent awake. Pregnancy is characterized by poor sleep continuity (7, 44, 45, 48-50). Sleep is also assessed by evaluating the amount of sleep achieved during the night. Sleep duration varies throughout pregnancy typically decreasing by term (7, 45, 47, 51). Restless leg syndrome is a neurosensory disorder that typically begins in the evening and often prevents a person from falling asleep. It can contribute to poor sleep continuity and quality. It is common during pregnancy with rates reaching 27% by the third trimester (52, 53). Finally, sleep disordered breathing includes abnormalities of respiratory pattern (pauses in breathing) or the quantity of ventilation during sleep. It can greatly disturb sleep quality, continuity and duration. Sleep disordered breathing is thought to increase during pregnancy by as much as 20% (54).

Sleep and Adverse Outcomes

Data linking sleep disturbances and adverse pregnancy outcomes are limited (48, 55-59). Women with preeclampsia have poorer sleep quality and continuity than women without preeclampsia (55, 56), whereas shorter sleep duration in late pregnancy is associated with longer labor times and increased cesarean section rates (58). Sleep disordered breathing, and snoring, a common symptom of sleep disordered breathing, are linked with increased risk for preeclampsia, gestational hypertension, and small-for-gestational-age infants (60-62). Although these studies suggest that certain sleep disturbances are related to adverse outcomes, small sample sizes and cross-sectional designs preclude clear conclusions.

Additional Considerations

It is likely that sleep disturbances may not all have the same impact to increase adverse outcomes. Sleep quality (63-66) and sleep disordered breathing (67, 68), for example, have a greater effect on the inflammatory response than sleep duration or sleep continuity. Sleep disordered breathing leads to hypoxia followed by restitution of normoxia. This well recognized pathogenic cascade leads to oxidative stress and a subsequent increase in inflammatory activation (69). It is also prudent to assert that we do not believe that sleep disturbances are an independent causal link to adverse outcomes. We propose that in conjunction with other risk factors, the risk for adverse outcomes may be increased among the 25% of pregnant women with significant sleep disturbances during the first trimester.

Inflammation as a Relevant Biological Pathway

Of the several mechanisms by which sleep alters normal physiology, augmented inflammatory activation could provide a link between disturbed sleep and adverse pregnancy outcomes. Poor sleep quality and continuity, reduced sleep duration, and sleep disordered breathing, are all associated with augmentation of the inflammatory response as indicated by increased circulating concentrations of the proinflammatory cytokines, interleukin (IL)-6 and tumor necrosis factor (TNF)-α (70-73), and the acute phase protein, C-reactive protein (CRP) (74-76).

Inflammation is considered a component of the pathogenesis of adverse pregnancy outcomes (77-80). IL-6, TNF-α and CRP are increased with preeclampsia, (81-84), IUGR, (77, 79, 85), and preterm labor/birth (86-89). One mechanism by which inflammation may increase adverse pregnancy outcomes is by interfering with normal trophoblast invasion. In experimental studies, increased inflammatory cytokines, such as TNF-α, interfere with trophoblast implantation (90, 91). Remodeling of the spiral arteries to increase placental perfusion requires normal trophoblast invasion (38, 92, 93). Failed remodeling of these vessels with associated reduced trophoblast invasion is present with preeclampsia, pregnancies complicated by IUGR and one third of the cases of preterm birth (94).

The Hypothesis

In Figure 1, we propose a model of the possible role of sleep and inflammation in the pathogenesis of adverse pregnancy outcomes. We propose that sleep disturbances during the first 20 weeks of pregnancy contribute to increased systemic inflammation. Despite the necessity of a dominant proinflammatory profile for early pregnancy success (95), based on in vitro experiments in which cytokines inhibit trophoblast invasion, it is postulated that an exacerbated inflammatory response interferes with normal trophoblast invasion. This would result in subsequent disruption of the remodeling of the maternal vessels of the maternal vascular bed, an abnormality present in preeclampsia, preterm birth, and pregnancies with IUGR (96).

Fig. 1
We propose that the major effects of disturbed sleep occur in the first 20 weeks of pregnancy. During this time many important physiological events take place. One of these, the profound remodeling of maternal vessels perfusing the placenta to increase ...

We propose that “positive feedback” plays a role in the association of sleep disturbance with increased inflammation. In this regard, it is well documented that disturbed sleep (naturally occurring or induced experimentally) is associated with increased markers of inflammation (70, 72, 73, 75, 97). It is also well recognized that systemic inflammation results in a disruption of sleep (98, 99). The bi-directional relationships linking disturbed sleep and inflammation may amplify their association and consequences in pregnancy.

The model also proposes that health behaviors can contribute independently to increased sleep disturbance and inflammation, and thus increase risk of adverse pregnancy outcomes. Again, relationships are bi-directional, with lifestyle choices impacting sleep parameters and vice versa. Smoking, for instance, is associated with poor sleep continuity and shorter sleep duration (100). This sleep disruption can result in anxiety, which, in turn, leads to increased smoking due to the anxiolytic properties of cigarettes (101). Alcohol use similarly disturbs sleep continuity (102) and sleep duration (103). Despite this, alcohol is frequently used as a self-remedy for sleep problems, resulting in further sleep disruption (104). In support of the proposed model, consistent evidence shows that both smoking and excessive alcohol intake are associated with increased inflammation (105, 106). Similarly, obesity and its metabolic correlates, including insulin resistance, are associated with short sleep duration, often resulting from sleep disordered breathing (107). Short sleep duration can also result in weight gain, via reductions in the anorexogenic hormone, leptin, and increases in the appetite-promoting hormone, ghrelin (108, 109). Furthermore, adipose tissue is a prominent producer of proinflammatory cytokines; hence, obese individuals have higher circulating levels of inflammatory markers than individuals of more normal weight (110).

A further pathway that may link sleep and inflammation is the neuroendocrine system. Several positive and negative feedback processes play a role in closely regulating hormonal and neuronal factors that modulate inflammatory processes. The release of adrenal hormones (catecholamines) and activation of sympathetic nerves increases the production of inflammatory cytokines from activated immune organs and cells (111). In turn, catecholamines disturb sleep (112). The bi-directionality of these systems is auto-amplifying as disturbed sleep increases nocturnal sympathetic activity (113, 114). Hormones from the hypothalamic-pituitary-adrenal (HPA) axis are also linked with inflammatory responses. The HPA axis regulates inflammatory responses via cortisol secretion. Cortisol ordinarily suppresses the production of proinflammatory cytokines (115, 116). As part of a negative feed back loop, proinflammatory cytokines can stimulate the HPA axis to produce more cortisol (111) that shuts off the inflammatory response. However, chronic cortisol secretion results in a down-regulation of glucocorticoid receptor sensitivity that blunts cortisol’s suppressive effects (115). Of interest here is that the hormones of the HPA axis are secreted in a diurnal manner paralleling the sleep-wake cycle (117). Disrupted sleep, however, can produce mild elevations in HPA axis hormones (114). Thus, sleep disturbances that accompany pregnancy may begin a cascade of effects to dysregulate this homeostatic process. Specifically, both disrupted sleep and inflammation result in chronic HPA activation, which in turn, results in decreased glucocorticoid sensitivity and prolonged/exaggerated inflammatory responses. As depicted in Figure 1, this auto-amplifying process may increase the risk of adverse pregnancy outcomes, particularly when it occurs early in gestation.

The capacity of sleep to engender these feed forward loops is because of the fact that sleep, despite its necessity for healthy survival (118, 119), can be modified both by endogenous and exogenous factors. Pregnancy initiates physiological changes that affect sleep. Volume redistribution leads to nocturia and nocturnal awakenings (120). Furthermore, humans are able to voluntarily override the biological drive to sleep. The amount and quality of sleep a woman achieves is often influenced by demands of life, work, and family (121). Therefore, we suggest that altering sleep patterns, whether from pregnancy changes or “voluntarily,” results in disturbed sleep that can initiate the cascade of processes outlined in Figure 1.

Beginning early in the first trimester, pregnant women report an increase in the number of awakenings and time spent awake at night (7). Although a high percentage of women report disturbed sleep, few actually experience complications. Why do some women develop adverse outcomes, whereas others do not? This raises a consideration important to most biological systems and also an important component of this or any hypothesis proposing risk factors for adverse pregnancy outcomes. Obesity, for example, is a major risk factor for preeclampsia with a 3-fold increased frequency of preeclampsia in women with a BMI >30 (35, 122). However, since the usual incidence of preeclampsia is 3% to 4%, almost 90% of obese women will not develop preeclampsia. Sleep disturbances do not exist in isolation. As with obesity, if sleep disturbances are identified as a risk for adverse outcomes they may be operative only in pregnancies in which they interact with maternal or fetal factors that converge with disturbed sleep, perhaps at the level of increased inflammation, to adversely affect a particular pregnancy.

Testing the Hypothesis

The hypothesis presented is testable. There are several ways to collect sleep data. The gold standard in measuring sleep is polysomnography because it provides an objective, physiological assessment of sleep-wake patterns for an entire sleep period (123). However, this method is often cost-prohibitive as the recording time and data are restricted by expense and high participant burden. A more practical and less costly alternative is to use actigraphy and sleep diaries concurrently. An actigraph is a wrist-watch like device that is activated by movement and allows objective evaluation of behavioral sleep variables including awakenings, wake time during the night and total sleep time that may not be perceivable by the participant (124). The combination with subjective assessments of sleep (e.g., sleep diaries) allows for the collection of data over long periods of time and at multiple time points. Other strategies can evaluate sleep disordered breathing, such as questionnaires for the woman or her bed partner asking about specific symptoms of sleep disordered breathing. Sleep disordered breathing can also be assessed objectively, but more invasively, by devices that measure ventilatory flow limitation during sleep.

To relate disturbed sleep to an exaggerated inflammatory response, ideally multiple blood samples would be obtained to determine diurnal rhythmicity of the inflammatory markers. Subject burden, particularly among pregnant women, is a concern and reduced sampling frequency may be a more realistic approach.

Our hypothesis suggests that the gestational period during which the sleep-inflammation relationship is evaluated is important. Among the few prior studies that have considered sleep as a risk factor in pregnancy outcomes, sleep was assessed after 22-weeks gestation (48, 57, 58). Also as yet, no interaction between sleep disturbances and inflammatory activation on adverse outcomes has been tested. We propose that the interaction between disturbed sleep and inflammation needs to be examined before 20-weeks gestation during the stage of vascular remodeling of the vessels perfusing the placenta.

Ideally, we suggest examining this relationship in a cohort of at least 400 nulliparous women without a diagnosed psychiatric or sleep disorder. We suggest this sample size given a conservative prevalence rate of 15% in the development of either preeclampsia, IUGR, or preterm delivery. Collection of sleep data would be for three 2-week periods so that consistent sleep patterns and variability can be determined. At the conclusion of each 2-week period, blood samples, self-reported data on confounding variables, such as depression, stress, and health behaviors, and anthropomorphic data would be collected. Finally, pregnancy and delivery outcomes would be retrieved from patient medical records. The final sample of women used to test the relationship would be ascertained using a nested case-control design matching women with a complication to those with normal outcomes on various sociodemographic variables.

Summary and Conclusion

Disturbed sleep, although very common in pregnancy, has not been examined as a factor contributing to risk for adverse pregnancy outcomes. We propose a model linking sleep disturbances in early gestation to adverse pregnancy outcomes via increased inflammation. Specifically, we propose a feed forward loop between sleep disruption and inflammation during a critical period of early pregnancy when inflammation can act to inhibit the trophoblast invasion and associated remodeling of maternal blood vessels that perfuse the placenta. Assessing sleep disturbances as a risk factor for adverse outcomes could provide a target for intervention especially since sleep problems are amenable to treatment.

Acknowledgments

Supported by K99R00 grant NR010813 (to M.L.O.).

Footnotes

The authors have disclosed that they have no financial relationships with or interests in any commercial companies pertaining to this educational activity.

The Faculty and Staff in a position to control the content of this CME activity have disclosed that they have no financial relationships with, or financial interests in, any commercial companies pertaining to this educational activity.

Lippincott Continuing Medical Education Institute, Inc. has identified and resolved all faculty conflicts of interest regarding this educational activity.

REFERENCES

1. Lumley J. Defining the problem: the epidemiology of preterm birth. BJOG. 2003;110(suppl 20):3–7. [PubMed]
2. Pregnancy complications. Internet Communication; 2006. March of Dimes.
3. Hollander MH, Paarlberg KM, Huisjes AJ. Gestational diabetes: a review of the current literature and guidelines. Obstet Gynecol Surv. 2007;62:125–136. [PubMed]
4. Ness RB, Roberts JM. Epidemiology of hypertension. In: Lindheimer MD, Roberts JM, Cunningham FG, editors. Chesley’s Hypertensive Disorders in Pregnancy. Appleton & Lange; Stamford, CT: 1999. pp. 43–65.
5. Peacock JL, Bland JM, Anderson HR. Preterm delivery: effects of socioeconomic factors, psychological stress, smoking, alcohol, and caffeine. BMJ. 1995;311:531–535. [PMC free article] [PubMed]
6. Lee KA. Sleep during pregnancy and postpartum. In: Lee-Chiong T, editor. Encyclopedia of Sleep Medicine. John Wiley & Sons, Inc.; New Jersey, NJ: 2006. pp. 629–635.
7. Okun ML, Coussons-Read ME. Sleep disruption during pregnancy: how does it influence serum cytokines? J Reprod Immunol. 2007;73:158–165. [PubMed]
8. Fuller PM, Gooley JJ, Saper CB. Neurobiology of the sleep-wake cycle: sleep architecture, circadian regulation, and regulatory feedback. J Biol Rhythms. 2006;21:482–493. [PubMed]
9. Markov D, Goldman M. Normal sleep and circadian rhythms: neurobiologic mechanisms underlying sleep and wakefulness. Psychiatr Clin North Am. 2006;29:841–853. [PubMed]
10. Saper CB, Cano G, Scammell TE. Homeostatic, circadian, and emotional regulation of sleep. J Comp Neurol. 2005;493:92–98. [PubMed]
11. Breslau N, Roth T, Rosenthal L, et al. Sleep disturbance and psychiatric disorders: a longitudinal epidemiological study of young adults. Biol Psychiatry. 1996;39:411–418. [PubMed]
12. Ford DE, Kamerow DB. Epidemiologic study of sleep disturbances and psychiatric disorders. An opportunity for prevention? JAMA. 1989;262:1479–1484. [PubMed]
13. Perlis ML, Giles DE, Buysse DJ, et al. Self-reported sleep disturbance as a prodromal symptom in recurrent depression. J Affect Disord. 1997;42:209–12. [PubMed]
14. Ayas NT, White DP, Al Delaimy WK, et al. A prospective study of self-reported sleep duration and incident diabetes in women. Diabetes Care. 2003;26:380–384. [PubMed]
15. Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Sleep duration as a risk factor for diabetes incidence in a large US sample. Sleep. 2007;30:1667–1673. [PMC free article] [PubMed]
16. Bjorvatn B, Sagen IM, Oyane N, et al. The association between sleep duration, body mass index and metabolic measures in the Hordaland Health Study. J Sleep Res. 2007;16:66–76. [PubMed]
17. Kohatsu ND, Tsai R, Young T, et al. Sleep duration and body mass index in a rural population. Arch Intern Med. 2006;166:1701–1705. [PubMed]
18. Heslop P, Smith GD, Metcalfe C, et al. Sleep duration and mortality: the effect of short or long sleep duration on cardiovascular and all-cause mortality in working men and women. Sleep Med. 2002;3:305–314. [PubMed]
19. Kripke DF, Garfinkel L, Wingard DL, et al. Mortality associated with sleep duration and insomnia. Arch Gen Psychiatry. 2002;59:131–136. [PubMed]
20. Nilsson PM, Nilsson JA, Hedblad B, et al. Sleep disturbance in association with elevated pulse rate for prediction of mortality–consequences of mental strain? J Intern Med. 2001;250:521–529. [PubMed]
21. Agatisa PK, Ness RB, Roberts JM, et al. Impairment of endothelial function in women with a history of preeclampsia: an indicator of cardiovascular risk. AmJ Physiol Heart Circ Physiol. 2004;286:H1389–H1393. [PubMed]
22. Manten GT, Sikkema MJ, Voorbij HA, et al. Risk factors for cardiovascular disease in women with a history of pregnancy complicated by preeclampsia or intrauterine growth restriction. Hypertens Pregnancy. 2007;26:39–50. [PubMed]
23. Cappuccio FP, Stranges S, Kandala NB, et al. Gender-specific associations of short sleep duration with prevalent and incident hypertension: the Whitehall II Study. Hypertension. 2007;50:693–700. [PMC free article] [PubMed]
24. Leineweber C, Kecklund G, Janszky I, et al. Poor sleep increases the prospective risk for recurrent events in middle-aged women with coronary disease. The Stockholm Female Coronary Risk Study. J Sychosom Res. 2003;54:121–127. [PubMed]
25. Leineweber C, Kecklund G, Orth-Gomer K. Prediction of cardiocerebrovascular and other significant disease from disturbed sleep and work strain. Scand J Work Environ Health. 2007;33:215–222. [PubMed]
26. Meisinger C, Heier M, Lowel H, et al. Sleep duration and sleep complaints and risk of myocardial infarction in middle-aged men and women from the general population: the MONICA/KORA Augsburg cohort study. Sleep. 2007;30:1121–27. [PMC free article] [PubMed]
27. Newman AB, Enright PL, Manolio TA, et al. Sleep disturbance, psychosocial correlates, and cardiovascular disease in 5201 older adults: the Cardiovascular Health Study. J Am Geriatr Soc. 1997;45:1–7. [PubMed]
28. Gangwisch JE, Malaspina D, Boden-Albala B, et al. Inadequate sleep as a risk factor for obesity: analyses of the NHANES I. Sleep. 2005;28:1289–1296. [PubMed]
29. Hasler G, Buysse DJ, Klaghofer R, et al. The association between short sleep duration and obesity in young adults: a 13-year prospective study. Sleep. 2004;27:661–666. [PubMed]
30. Patel SR, Malhotra A, White DP, et al. Association between reduced sleep and weight gain in women. Am J Epidemiol. 2006;164:947–954. [PMC free article] [PubMed]
31. Suarez EC. Self-reported symptoms of sleep disturbance and inflammation, coagulation, insulin resistance and psychosocial distress: evidence for gender disparity. Brain Behav Immun. 2008;22:960–968. [PMC free article] [PubMed]
32. Tasali E, Leproult R, Ehrmann DA, et al. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci USA. 2008;105:1044–1049. [PMC free article] [PubMed]
33. Vgontzas AN, Lin HM, Papaliaga M, et al. Short sleep duration and obesity: the role of emotional stress and sleep disturbances. Int J Obes. 2008;32:801–809. [PubMed]
34. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354:1435–1439. [PubMed]
35. Bodnar LM, Catov JM, Klebanoff MA, et al. Prepregnancy body mass index and the occurrence of severe hypertensive disorders of pregnancy. Epidemiology. 2007;18:234–239. [PubMed]
36. Doherty DA, Magann EF, Francis J, et al. Pre-pregnancy body mass index and pregnancy outcomes. Int J Gynaecol Obstet. 2006;95:242–247. [PubMed]
37. Siega-Riz AM, Siega-Riz AM, Laraia B. The implications of maternal overweight and obesity on the course of pregnancy and birth outcomes. Matern Child Health J. 2006;10:S153–S156. [PMC free article] [PubMed]
38. Ness RB, Sibai BM. Shared and disparate components of the pathophysiologies of fetal growth restriction and preeclampsia. Am J Obstet Gynecol. 2006;195:40–49. [PubMed]
39. Solomon CG, Carroll JS, Okamura K, et al. Higher cholesterol and insulin levels in pregnancy are associated with increased risk for pregnancy-induced hypertension. Am J Hypertens. 1999;12:276–282. [PubMed]
40. Versen-Hoeynck FM, Powers RW. Maternal-fetal metabolism in normal pregnancy and preeclampsia. Front Biosci. 2007;12:2457–2470. [PubMed]
41. Kuiper J, van Puijvelde GH, van Wanrooij EJ, et al. Immunomodulation of the inflammatory response in atherosclerosis. Curr Opin Lipidol. 2007;18:521–526. [PubMed]
42. Roberts JM, Lain KY. Recent Insights into the pathogenesis of pre-eclampsia. Placenta. 2002;23:359–372. [PubMed]
43. Pien GW, Schwab RJ. Sleep disorders during pregnancy. Sleep. 2004;27:1405–1417. [PubMed]
44. Hertz G, Fast A, Feinsilver SH, et al. Sleep in normal late pregnancy. Sleep. 1992;15:246–251. [PubMed]
45. Lee KA, Zaffke ME, McEnany G. Parity and sleep patterns during and after pregnancy. Obstet Gynecol. 2000;95:14–18. [PubMed]
46. Mindell JA, Jacobson BJ. Sleep disturbances during pregnancy. J Obstet Gynecol Neonatal Nurs. 2000;29:590–597. [PubMed]
47. Signal TL, Gander PH, Sangalli MR, et al. Sleep duration and quality in healthy nulliparous and multiparous women across pregnancy and post-partum. Aust N Z J Obstet Gynaecol. 2007;47:16–22. [PubMed]
48. Beebe KR, Lee KA. Sleep disturbance in late pregnancy and early labor. J Perinat Neonatal Nurs. 2007;21:103–108. [PubMed]
49. Brunner DP, Munch M, Biedermann K, et al. Changes in sleep and sleep electroencephalogram during pregnancy. Sleep. 1994;17:576–582. [PubMed]
50. Driver HS, Shapiro CM. A longitudinal study of sleep stages in young women during pregnancy and postpartum. Sleep. 1992;15:449–453. [PubMed]
51. Hedman C, Pohjasvaara T, Tolonen U, et al. Effects of pregnancy on mothers’ sleep. Sleep Med. 2002;3:37–42. [PubMed]
52. Lee KA, Zaffke ME, Baratte-Beebe K. Restless legs syndrome and sleep disturbance during pregnancy: the role of folate and iron. J Womens Health Gend Based Med. 2001;10:335–341. [PubMed]
53. Manconi M, Govoni V, De Vito A, et al. Pregnancy as a risk factor for restless legs syndrome. Sleep Med. 2004;5:305–308. [PubMed]
54. Pien GW, Fife D, Pack AI, et al. Changes in symptoms of sleep-disordered breathing during pregnancy. Sleep. 2005;28:1299–1305. [PubMed]
55. Edwards N, Blyton CM, Kesby GJ, et al. Pre-eclampsia is associated with marked alterations in sleep architecture. Sleep. 2000;23:619–625. [PubMed]
56. Ekholm EM, Polo O, Rauhala ER, et al. Sleep quality in preeclampsia. Am J Obstet Gynecol. 1992;167:1262–1266. [PubMed]
57. Evans ML, Dick MJ, Clark AS. Sleep during the week before labor: relationships to labor outcomes. Clin Nurs Res. 1995;4:238–249. [PubMed]
58. Lee KA, Gay CL. Sleep in late pregnancy predicts length of labor and type of delivery. Am J Obstet Gynecol. 2004;191:2041–2046. [PubMed]
59. Stinson JC, Lee KA. Premature labor and birth: influence of rank and perception of fatigue in active duty military women. Mil Med. 2003;168:385–390. [PubMed]
60. Franklin KA, Holmgren PA, Jonsson F, et al. Snoring, pregnancy-induced hypertension, and growth retardation of the fetus. Chest. 2000;117:137–141. [PubMed]
61. Izci B, Martin SE, Dundas KC, et al. Sleep complaints: snoring and daytime sleepiness in pregnant and pre-eclamptic women. Sleep Med. 2005;6:163–169. [PubMed]
62. Perez-Chada D, Videla AJ, O’Flaherty ME, et al. Snoring, witnessed sleep apnoeas and pregnancy-induced hypertension. Acta Obstet Gynecol Scand. 2007;86:788–792. [PubMed]
63. Burgos I, Richter L, Klein T, et al. Increased nocturnal interleukin-6 excretion in patients with primary insomnia: a pilot study. Brain Behav Immun. 2006;20:246–253. [PubMed]
64. Cakirbay H, Bilici M, Kavakci O, et al. Sleep quality and immune functions in rheumatoid arthritis patients with and without major depression. Int J Neurosci. 2004;114:245–256. [PubMed]
65. Friedman EM, Hayney MS, Love GD, et al. Social relationships, sleep quality, and interleukin-6 in aging women. Proc Natl Acad Sci USA. 2005;102:18757–18762. [PMC free article] [PubMed]
66. Okun ML, Hall M, Coussons-Read ME. Sleep disturbances increase interleukin-6 production during pregnancy: implications for pregnancy complications. Reprod Sci. 2007;14:560–567. [PubMed]
67. Guilleminault C, Kirisoglu C, Ohayon MM. C-reactive protein and sleep-disordered breathing. Sleep. 2004;27:1507–1511. [PubMed]
68. Yao M, Tachibana N, Okura M, et al. The relationship between sleep-disordered breathing and high-sensitivity Creactive protein in Japanese men. Sleep. 2006;29:661–665. [PubMed]
69. Ciftci TU, Kokturk O, Bukan N, et al. The relationship between serum cytokine levels with obesity and obstructive sleep apnea syndrome. Cytokine. 2004;28:87–91. [PubMed]
70. Irwin MR, Wang M, Campomayor CO, et al. Sleep deprivation and activation of morning levels of cellular and genomic markers of inflammation. Arch Intern Med. 2006;166:1756–1762. [PubMed]
71. Redwine L, Dang J, Hall M, et al. Disordered sleep, nocturnal cytokines, and immunity in alcoholics. Psychosom Med. 2003;65:75–85. [PubMed]
72. Vgontzas AN, Zoumakis E, Bixler EO, et al. Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines. J Clin Endocrinol Metab. 2004;89:2119–2126. [PubMed]
73. von Kanel R, Dimsdale JE, Ancoli-Israel S, et al. Poor sleep is associated with higher plasma proinflammatory cytokine interleukin-6 and procoagulant marker fibrin D-dimer in older caregivers of people with Alzheimer’s disease. J Am Geriatr Soc. 2006;54:431–437. [PubMed]
74. McDade TW, Hawkley LC, Cacioppo JT. Psychosocial and behavioral predictors of inflammation in middle-aged and older adults: the Chicago health, aging, and social relations study. Psychosom Med. 2006;68:376–381. [PubMed]
75. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43:678–683. [PubMed]
76. Shamsuzzaman AS, Winnicki M, Lanfranchi P, et al. Elevated C-reactive protein in patients with obstructive sleep apnea. Circulation. 2002;105:2462–2464. [PubMed]
77. Bartha JL, Romero-Carmona R, Comino-Delgado R. Inflammatory cytokines in intrauterine growth retardation. Acta Obstet Gynecol Scand. 2003;82:1099–1102. [PubMed]
78. Freeman DJ, McManus F, Brown EA, et al. Short and long-term changes in plasma inflammatory markers associated with preeclampsia. Hypertension. 2004;44:708–714. [PubMed]
79. Holcberg G, Huleihel M, Sapir O, et al. Increased production of tumor necrosis factor-alpha TNF-alpha by IUGR human placentae. Eur J Obstet Gynecol Reprod Biol. 2001;94:69–72. [PubMed]
80. Romero R, Espinoza J, Goncalves LF, et al. Inflammation in preterm and term labour and delivery. Seminin Fetal Neonatal Med. 2006;11:317–326. [PubMed]
81. Afshari JT, Ghomian N, Shameli A, et al. Determination of interleukin-6 and tumor necrosis factor-alpha concentrations in Iranian-Khorasanian patients with preeclampsia. BMC Pregnancy Childbirth. 2005;5:14. [PMC free article] [PubMed]
82. Dekker GA, Sibai BM. The immunology of preeclampsia. Seminin Perinatol. 1999;23:24–33. [PubMed]
83. Hayashi M, Ueda Y, Ohkura T, et al. Interleukin-6 concentrations in the placenta and blood in normal pregnancies and preeclampsia. Horm Metab Res. 2005;37:419–424. [PubMed]
84. Hayashi M, Ueda Y, Yamaguchi T, et al. Tumor necrosis factor-alpha in the placenta is not elevated in pre-eclamptic patients despite its elevation in peripheral blood. Am J Reprod Immunol. 2005;53:113–119. [PubMed]
85. Laskowska M, Leszczynska-Gorzelak B, Laskowska K, et al. Evaluation of maternal and umbilical serum TNFalpha levels in preeclamptic pregnancies in the intrauterine normal and growth-restricted fetus. J Matern Fetal Neonatal Med. 2006;19:347–351. [PubMed]
86. Dudley DJ. Cytokines in preterm and term parturition. In: Hill JA, editor. Cytokines in Human Reproduction. John Wiley & Sons, Inc.; New York, NY: 2000. pp. 171–202.
87. Holst RM, Mattsby-Baltzer I, Wennerholm UB, et al. Interleukin-6 and interleukin-8 in cervical fluid in a population of Swedish women in preterm labor: relationship to microbial invasion of the amniotic fluid, intra-amniotic inflammation, and preterm delivery. Acta Obstet Gynecol Scand. 2005;84:551–557. [PubMed]
88. Menon R, Merialdi M, Lombardi SJ, et al. Differences in the placental membrane cytokine response: a possible explanation for the racial disparity in preterm birth. Am J Reprod Immunol. 2006;56:112–118. [PubMed]
89. Vogel I, Thorsen P, Curry A, et al. Biomarkers for the prediction of preterm delivery. Acta Obstet Gynecol Scand. 2005;84:516–525. [PubMed]
90. Fluhr H, Krenzer S, Stein GM, et al. Interferon-gamma and tumor necrosis factor-alpha sensitize primarily resistant human endometrial stromal cells to Fas-mediated apoptosis. J Cell Sci. 2007;120:4126–4133. [PubMed]
91. Salamonsen LA, Hannan NJ, Dimitriadis E. Cytokines and chemokines during human embryo implantation: roles in implantation and early placentation. Seminin Reprod Med. 2007;25:437–444. [PubMed]
92. Khong TY, De Wolf F, Robertson WB, et al. Inadequate maternal vascular response to placentation in pregnancies complicated by pre-eclampsia and by small-for-gestational age infants. Br J Obstet Gynaecol. 1986;93:1049–1059. [PubMed]
93. Roberts JM, Taylor RN, Musci TJ, et al. Preeclampsia: an endothelial cell disorder. Am J Obstet Gynecol. 1989;161:1200–1204. [PubMed]
94. Arias F, Rodriquez L, Rayne SC, et al. Maternal placental vasculopathy and infection: two distinct subgroups among patients with preterm labor and preterm ruptured membranes. Am J Obstet Gynecol. 1993;168:585–591. [PubMed]
95. Mor G. Inflammation and pregnancy: The role of toll-like receptors in trophoblast-immune interaction. Ann.NY Acad Sci. 2008;1127:121–128. [PubMed]
96. Roberts JM, Gammill HS. Preeclampsia: recent insights. Hypertension. 2005;46:1243–1249. [PubMed]
97. Frey DJ, Fleshner M, Wright KP., Jr. The effects of 40 hours of total sleep deprivation on inflammatory markers in healthy young adults. Brain Behav Immun. 2007;21:1050–1057. [PubMed]
98. Mills P, von Kanel R, Norman D, et al. Inflammation and sleep in healthy individuals. Sleep. 2007;30:729–735. [PMC free article] [PubMed]
99. Motivala SJ, Sarfatti A, Olmos L, et al. Inflammatory markers and sleep disturbance in major depression. Psychosom Med. 2005;67:187–194. [PubMed]
100. Phillips BA, Danner FJ. Cigarette smoking and sleep disturbance. Arch Intern Med. 1995;155:734–737. [PubMed]
101. Colrain IM, Trinder J, Swan GE. The impact of smoking cessation on objective and subjective markers of sleep: review, synthesis, and recommendations. Nicotine Tob Res. 2004;6:913–925. [PubMed]
102. Roehrs T, Roth T. Sleep, sleepiness, and alcohol use. Alcohol Res Health. 2001;25:101–109. [PubMed]
103. Palmer CD, Harrison GA, Hiorns RW. Association between smoking and drinking and sleep duration. Ann Hum Biol. 1980;7:103–107. [PubMed]
104. Roehrs T, Hollebeek E, Drake C, et al. Substance use for insomnia in Metropolitan Detroit. J Psychosom Res. 2002;53:571–576. [PubMed]
105. Crews FT, Bechara R, Brown LA, et al. Cytokines and alcohol. Alcohol Clin Exp Res. 2006;30:720–730. [PubMed]
106. Helmersson J, Larsson A, Vessby B, et al. Active smoking and a history of smoking are associated with enhanced prostaglandin F(2alpha), interleukin-6 and F2-isoprostane formation in elderly men. Atherosclerosis. 2005;181:201–207. [PubMed]
107. Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002;165:1217–1239. [PubMed]
108. Bass J, Turek FW. Sleepless in America: a pathway to obesity and the metabolic syndrome? Arch Intern Med. 2005;165:15–16. [PubMed]
109. Spiegel K, Knutson K, Leproult R, et al. Sleep loss: a novel risk factor for insulin resistance and Type 2 diabetes. J Appl Physiol. 2005;99:2008–2019. [PubMed]
110. Vgontzas AN, Bixler EO, Papanicolaou DA, et al. Chronic systemic inflammation in overweight and obese adults. JAMA. 2000;283:2235. [PubMed]
111. Szelenyi J, Vizi ES. The catecholamine cytokine balance: interaction between the brain and the immune system. Ann NY Acad Sci. 2007;1113:311–324. [PubMed]
112. Guggisberg AG, Hess CW, Mathis J. The significance of the sympathetic nervous system in the pathophysiology of periodic leg movements in sleep. Sleep. 2007;30:755–766. [PMC free article] [PubMed]
113. Irwin M, Clark C, Kennedy B, et al. Nocturnal catecholamines and immune function in insomniacs, depressed patients, and control subjects. Brain Behav Immun. 2003;17:365–372. [PubMed]
114. Meerlo P, Sgoifo A, Suchecki D. Restricted and disrupted sleep: effects on autonomic function, neuroendocrine stress systems and stress responsivity. Sleep Med Rev. 2008;12:197–210. [PubMed]
115. Sapolsky RM, Romero LM, Munck AU. How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev. 2000;21:55–89. [PubMed]
116. Sorrells SF, Sapolsky RM. An inflammatory review of glucocorticoid actions in the CNS. Brain Behav Immun. 2007;21:259–272. [PMC free article] [PubMed]
117. Born J, Fehm HL. The neuroendocrine recovery function of sleep. Noise Health. 2000;2:25–38. [PubMed]
118. Adam K. Sleep as a restorative process and a theory to explain why. Prog Brain Res. 1980;53:289–305. [PubMed]
119. Everson CA. Clinical assessment of blood leukocytes, serum cytokines, and serum immunoglobulins as responses to sleep deprivation in laboratory rats. Am J Physiol Regul Integr Comp Physiol. 2005;289:R1054–R1063. [PubMed]
120. Baratte-Beebe KR, Lee K. Sources of midsleep awakenings in childbearing women. Clin Nurs Res. 1999;8:386–397. [PubMed]
121. Wolfson AR, Lee KA. Pregnancy and the post partum. In: Kryger MH, Roth T, Dement WC, editors. Principles and Practices of Sleep Medicine. Elsevier Saunders; Philadelphia, PA: 2005. pp. 1278–1286.
122. Dixit A, Girling JC. Obesity and pregnancy. J Obstet Gynaecol. 2008;28:14–23. [PubMed]
123. Baker FC, Maloney S, Driver HS. A comparison of subjective estimates of sleep with objective polysomnographic data in healthy men and women. J Psychosom Res. 1999;47:335–341. [PubMed]
124. Lockley SW, Skene DJ, Arendt J. Comparison between subjective and actigraphic measurement of sleep and sleep rhythms. J Sleep Res. 1999;8:175–183. [PubMed]
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