Pregnancy and sleep related disorders

1. Pregnancy and sleep related disorders Turan Acıcan Prof. MD Pulmonary Dept. Of Medical School of Ankara Univercity

2. SLEEP DURING PREGNANCY • Karacan and colleagues conducted one of the first clinical studies of sleep during pregnancy and compared seven women during the last month of pregnancy to age-matched nonpregnant women. The two groups spent about the same amount of time in bed trying to sleep, but the pregnant women had less total sleep. • Karacan I, Heine W, Agnew HW, et al: Characteristics of sleep patterns during late pregnancy and the postpartum periods. Am J Obstet Gynecol 1968;101:579-585.

3. First Trimester • Women report that sleep is interrupted during the first trimester by nausea, vomiting, backaches, and the increased need to urinate • Sleep begins to change as early as the tenth week of gestation. • Progesterone's soporific and sedating effect occured • Its thermogenic effect results in increased body temperature, and its inhibitory effect on smooth muscle acts on the urinary tract to cause frequent urination.

4. Second Trimester • Many women report that their sleep improves at night and they report more daytime energy into the second trimester. • As women transition into the second trimester, progesterone levels continue to rise, but more slowly. • Both subjective and objective sleep parameters are better during this trimester, but about 30% report onset of snoring that did not exist prior to pregnancy. • Pregnant women who snore may be at risk of preeclampsia (pregnancy-induced hypertension) and sleep apnea syndrome.

5. Third Trimester • The quality of sleep in the last trimester is worse than during the first two trimesters. During the third trimester, sleep is disrupted because of urinary frequency, backaches, shortness of breath, and leg cramps. • Many women also describe longer sleep onset latencies, more awakenings, less total sleep, and increasing levels of morning sleepiness over the course of the third trimester.

6. Overall, studies conclude that pregnant women have more awake time during the night as a result of the many symptoms and physical changes that occur over the 9 months of gestation. • In contrast, changes in sleep architecture seem to be minimal. REM sleep, however, either remains unchanged or diminishes slightly from the first trimester to the third trimester. • More studies, however, document less SWS over the course of pregnancy. It appears that more frequent or longer wake episodes during the sleep period have little effect on REM sleep but result in less SWS and total sleep time. Amy R. WolfsonKathryn A. Lee. Pregnancy and the Postpartum Period.. Printed from: Principles and Practice of Sleep Medicine 1278-86 (on 06 April 2009)

7. Hormones in pregnancy • Several hormones have a circadian rhythm that may change over the course of pregnancy and affect sleep architecture. • The hormones include growth hormone, prolactin, melatonin, cortisol, thyroid-stimulating hormone, and placental hormones (progesterone, estriol). • Estrogen and progesterone progressively increase during pregnancy • Prolactin levels increase between 25 weeks gestation and term.

8. Estrogen is known to decrease REM sleep, but the placental form of estrogen (estriol) is much weaker than the ovarian source. • Progesterone, on the other hand, has a sedating effect in both men and women when exogenously administered, and it appears to increase non-REM sleep.

9. Cortisol concentrations continue to peak in the early morning hours, but the half-life of cortisol is prolonged during pregnancy and levels increase twofold in late pregnancy and fourfold during labor. • Pregnant women who report sleeping poorly in the third trimester may have lower cortisol-to-melatonin ratios than good sleepers because of a lower early morning cortisol peak and a higher concentration of melatonin. • Uterine activity peaks at night along with peaks in oxytocin secretion and may explain the increased incidence of labor and delivery during the evening and night.

10. SLEEP DURING POSTPARTUM RECOVERY • Postpartum recovery is generally defined as the first 6 months after delivery. Most women would say that the postpartum period continues from birth until the infant is sleeping through the night. • Nearly 30% of mothers have disturbed sleep after the birth of their baby and that they experience more nighttime awakenings because of disruptions during the initial postpartum weeks (2 to 4 weeks) in comparison to the end of pregnancy and later postpartum months. • A mother's sleep is far more disrupted and less efficient during these early postpartum weeks than at other points in her life.

11. PREGNANCY AND POSTPARTUM HEALTH PROBLEMS ASSOCIATED WITH DISTURBED SLEEP • Several sleep disorders, such as sleep-disordered breathing, periodic limb movements, esophageal reflux, or restless legs syndrome, can be triggered or worsened by pregnancy. • These sleep disorders are most prevalent during the third trimester.

12. Pregnancy-Induced Hypertension (Preeclampsia) • Pregnancy-induced hypertension (PIH), also known as preeclampsia or toxemia of pregnancy, is a disorder that occurs in about 5% to 10% of pregnancies. • PIH is characterized by high blood pressure that has a flat circadian rhythm, without the nocturnal dip associated with sleep, and proteinuria. • Symptoms include excessive edema, severe headaches, nausea, blurred or double vision, and sleepiness. • Preeclampsia can progress to a life-threatening condition called eclampsia, which includes seizures and risk of coma and death of the mother and infant. The only definitive treatment is the delivery of the fetus and placenta.

13. Pre-eclampsia is a leading cause of maternal-fetal morbidity and mortality. Snoring and upper airway narroving is frequent in PIH. Significant overlap exists between the risk factors for pre-eclampsia and sleep-disordered breathing. Nasal continuous positive airway pressure (CPAP) has been proposed as therapy for pre-eclampsia. • Guilleminault C, Palombini L, Poyares D, Takaoka S, Huynh NT, El-Sayed Y Pre-eclampsia and nasal CPAP: part 1. Early intervention with nasal CPAP in pregnant women with risk-factors for pre-eclampsia: preliminary findings. sleep Med 2007:9(1):1-2

14. Snoring and Sleep-Disordered Breathing • It is also during pregnancy when about 15% to 20% of women report a new onset of snoring, whereas fewer than 5% report snoring prior to pregnancy. • Snoring results from a blocked airway as a result of narrowed passages, and most likely is caused by the increased fluid volume during pregnancy and the effects of estrogen on vascular tissue, which result in congested nasal passages. • Guilleminault C, Querra-Salva M, Chowdhuri S, Poyares D: Normal pregnancy, daytime sleeping, snoring and blood pressure. Sleep Med 2000;1:289-297

15. Loube and colleagues , in an investigation of self-reported snoring during pregnancy, showed that 14% of 350 pregnant women at the second and third trimester reported habitual snoring in comparison with 4% of 110 nonpregnant controls. • Shutte and colleagues showed that 27% of normal women reported snoring at the last trimester of pregnancy.

16. A retrospective study with data obtained the day of delivery found that 23% of 502 pregnant women reported loud snoring in the last week of the third trimester, whereas only 4% reported loud snoring before pregnancy. Franklin KA, Holmgren PA, Jonsson F, et al. Snoring, pregnancy-induced hypertension and growth retardation of the fetus. Chest 2000; 117:137–41.

17. In one retrospective survey, snoring was associated with higher blood pressure, and 10% of the pregnant snorers developed PIH compared with only 4% of nonsnoring women. • Infants born to the snoring mothers also had lower Apgar scores as well as higher risk of intrauterine growth retardation (7.1% versus 2.6%). Guilleminault C, Querra-Salva M, Chowdhuri S, Poyares D: Normal pregnancy, daytime sleeping, snoring and blood pressure. Sleep Med 2000;1:289-297

18. The presence of high levels of progesterone may be protective against sleep-disordered breathing in pregnancy,. • Obese women who become pregnant, however, are at greater risk of sleep apnea. When obese women were compared with nonobese women at about 12 weeks and 30 weeks of gestation, the obese group had a lower level of progesterone level and more snoring.

19. During pregnancy, increased initial body mass index and greater changes in neck circumference have been associated with higher prevalence of SDB symptoms Pien GW, Fife D, Pack AI, et al. Changes in symptoms of sleep disordered breathing during pregnancy. Sleep 2005;28(10): 1299–305.

20. Recently, Izci and colleagues demonstrated that upper airways are significantly narrower in pregnant women during late pregnancy in comparison with nonpregnant women or measurement in postpartum period Izci B, Vennelle M, Liston WA, et al. Sleep disordered breathing and upper airway size in pregnancy and postpartum. Eur Respir J 2006;27: 321–7.

21. The relationship between pregnancy and SDB is complex. Paradoxically, pregnancy leads to physical and biochemical changes that may both reduce and increase the risk for the development of sleep apnea .The presence of OSA in pregnancy may have adverse effects on maternal and fetal outcom Fotis Kapsimalis, Meir Kryger. Obstructive Sleep Apneain Pregnancy Sleep Med Clin Sci (2007) 603–613

22. Detrimental Weight gain Elevation of the diaphragm Reduction of functional reserve capacity Nasal congestion and rhinitis Hyperventilation Increased stage 1 of non-REM sleep Sleep fragmentation Protective Avoidance of supine position Increased minute ventilation Increased dilating actions of pharyngeal muscles Reduction of REM sleep Physiologic changes related to sleep-disordered breathing during pregnancy

23. Prevalence of obstructive sleep apneain pregnancy • The prevalence of OSA during pregnancy is not known because there are no prospective large population-based epidemiologic studies addressing this issue. Over the last three decades, the association of OSA with pregnancy has been based on published case reports with only some of them having polysomnographic documentation of the sleep apnea syndrome .

24. The first report was published by Joel-Cohen and Schoenfeld in 1978 and included three cases of pregnant women with clinically diagnosed OSA. They reported no maternal complication and intrauterine infant growth retardation in one case. • Joel-Cohen SJ, Schoenfeld A. Fetal response to periodic sleep apnea: a new syndrome in obstetrics. Eur J Obstet Gynecol Reprod Biol 1978;8(2):77–81.

25. The largest cohort was reported by Schoenfeld and colleagues with eight cases of clinically diagnosed OSA, which all resulted in delivery of babies with low birth weight. PSG was not performed. All these women were obese with snoring and witnessed apneas. Schoenfeld A, Ovadia Y, Neri A, et al. Obstructive sleep apnea (OSA)-implications in maternal-fetal medicine: a hypothesis. Med Hypotheses 1989; 30(1):51–4.

26. In five of eight cases with documented OSA the mother had PIH and one case reported severe pulmonary hypertension . • Intrauterine infant growth retardation was reported in three cases, whereas in two other cases infants had normal birth weight.

27. Edwards and colleagues investigated 11 women who were referred for suspected SDB, at late pregnancy and 3 months following delivery, and found that AHI (63 + 15 versus 18 + 4 events per hour; P < .03) and minimum nocturnal hemoglobin saturation (86% + 2% versus 91% + 1%; P < .01) were significantly improved after parturition. • They also found that during pregnancy arterial blood pressure peaked at 180 mm in comparison with 140 mm Hg postnatally. • This study indicates that late pregnancy may worsen the severity of SDB and lead to increased blood pressure. Edwards N, Blyton DM, Hennesy A, et al. Severity of sleep disordered breathing improves following parturition. Sleep 2005;28(6):737–41.

28. OSA was diagnosed in 4 (11.4%) of the 35 pregnant women who underwent PSG. Three (75%) had fetal heart decelerations accompanying maternal desaturation. The neonates of women diagnosed with OSA had lower mean Apgar scores and birth weights compared with neonates of women without OSA. Three neonates from the women diagnosed with OSA were admitted to the newborn healthcare unit. CONCLUSION: OSA in pregnancy has important maternal and fetal outcomes. Pregnant women should be assessed for symptoms of OSA and suspected cases should be offered PSG • Sahin FK, Koken G, Cosar E, Saylan F, Fidan F, Yilmazer M, Unlu M. obstructive sleep apnea in pregnancy and fetal outcome. Int J Gynaecol Obstet. 2008 Feb;100(2):141-6. Epub 2007 Oct 31.

29. 465 women in pregnancy were studied by random. The snoring rate, the relation with hyper blood pressure and preeclamptism, and the influence on infant were observed. • RESULT: The magnificent statistics shows total snoring rate is 24.7%(115/465). Of them, 28.7% meet the standard of OSAS, 12.17% with hyper blood pressure, 7.8% with preeclamptism, 5.2% infant with aplasia. Zhu W, Shu C. Obstructive sleep apnea of gestational period Lin Chuang Er Bi Yan Hou Ke Za Zhi. 2002 Jun;16(6):295-6.

30. These reports suggest that OSA may develop in women with risk factors for SDB or may worsen the severity of pre-existing OSA with several adverse outcomes, such as the development of maternal PIH or fetal intrauterine growth retardation.

31. Mechanisms that explain narrowing of upper airways in pregnancy • Several physiologic changes during pregnancy may predispose to upper airway increased resistance and reduced cross-sectional area. • The weight gain in pregnancy , the abdominal mass loading, and elevation of the diaphragm result in reduced lung volumes and functional residual capacity leading to upper airway narrowing • The pharyngeal edema of pregnancy and fat or soft tissue deposition around upper airways can also lead to narrowing.

32. In a recent study, physical examination showed that snoring pregnant women had abnormal oropharyngeal anatomy and nasal mucosa engorgement. • Sleep deprivation and fragmentation in pregnancy may also lead to loss of dilating muscle activity , and increased upper airway collapsibility results in this further upper airway narrowing Guilleminault C, Kreutzer M, Chang JL. Pregnancy, sleep disordered breathing and treatment with nasal continuous positive airway pressure. Sleep Med 2004;5:43–51.

33. Studies have shown that overweight women who become pregnant, women who gain excessive weight, and women who report snoring during pregnancy should be evaluated for sleep-disordered breathing, because the hypoxic events associated with apnea may result in intrauterine growth retardation or other neonatal complications. • External nasal dilation may be effective in women who snore without apneic events, • Guilleminault C, Kreutzer M, Chang JL: Pregnancy, sleep disordered breathing and treatment with nasal continuous positive airway pressure. Sleep Med 2004;5:43-51

34. Treatment of sleep-disordered breathingduring pregnancy • Treatment includes conservative measures and the application of CPAP by nasal mask . • Oral appliances have not been investigated in pregnancy-related SDB and they are not suggested because they could be impractical . • Surgical therapies like uvulopalatopharyngoplasty are not recommended during pregnancy because they are less effective and they have increased risk for complications during pregnancy. • Similarly, tracheostomy has been reported in one case but it is rarely necessary

35. Conservative measures • Include control of body weight gain, • avoidance of sleep time spent in the supine position, • elevation of the head during sleep, and • restriction of alcohol and sedatives consumption • These general measures are useful even in non-OSA syndrome pregnant women who report increases of simple snoring or daytime sleepiness without the documentation of sleep apneas .

36. Prevention of sleep-disordered breathingduring pregnancy • Every pregnant woman should be questioned about the symptoms suggesting OSA (obesity, snoring, observed apnea, daytime sleepiness) and if apnea is likely should be evaluated with full overnight PSG • Pregnant women who develop PIH or preeclampsia (particularly if they are obese) should be candidates for comprehensive PSG • In addition, those with a history of previous babies with intrauterine growth retardation should be further evaluated • Women with sleep apnea during pregnancy should be closely monitored for recurrence in subsequent pregnancies

37. Leg Cramps and Restless Legs Syndrome • Over the course of pregnancy, about one in three women consistently reports episodes of jerkiness of the extremities while falling asleep. • However, those who experience awakenings during the night from leg cramps increase from a low of 8% to 10% before and after pregnancy to a rate of 12% to 21% during the first trimester, 49% to 57% during the second trimester, and 73% to 75% in the third trimester. • Amy R. WolfsonKathryn A. Lee. Pregnancy and the Postpartum Period.. Printed from: Principles and Practice of Sleep Medicine 1278-86 (on 06 April 2009). www.sleepmedtext.com

38. Restless Legs Syndrome (RLS) is rare in healthy young adult women. Because of its association with iron deficiency anemia, however, between 15% and 25% of women develop RLS during pregnancy. • Although the RLS symptoms typically reverse after delivery, it can be "torture" when added to all of the other discomforts and difficulty sleeping in the third trimester. • The standard medications for RLS that include dopaminergics or opioids, with potential risk to the fetus (table), should be avoided, and preventative measures should begin with encouraging folate-enriched breads and cereals at the first prenatal visit

39. Postpartum Depression • Up to 50% to 60% of all new mothers experience a postpartum blues during the first 2 postpartum weeks. At some point during the first 3 to 6 months after delivery, between 10% and 15% of new mothers experience diagnosable postpartum depression. • Sleep deprivation and disrupted sleep-wake cycles are important. Sleep deprivation is likely to contribute to postpartum mood changes. A prior history of sleep disruption at the end of pregnancy may result in a higher incidence of postpartum blues. • Postpartum mothers' increased time awake during the night and poor sleep quality were strongly associated with increased negative daytime mood, or blues, particularly in the first 4 weeks after birth • Wisner KL, Parry BL, Piontek CM: Postpartum depression. N Engl J Med 2002;347:194-199

40. Because of the risks of antidepressant drug therapy to the fetus and to the newborn during breast-feeding, health care providers are hesitant to prescribe medications, • For postpartum women, it is recommended that any drug therapy should start with half of the lowest recommended level and be increased slowly in small increments. • If drug therapy is not a reasonable option, REM sleep deprivation or light therapy may be useful to consider. Amy R. WolfsonKathryn A. Lee. : Principles and Practice of Sleep Medicine 1278-86 ( 06 April 2009).

41. Clinical Results • The cause of excessive sleepiness and fatigue in a pregnant woman should be determined because of potential harm to the fetus or newborn. Some pregnant women develop specific sleep disorders such as RLS, sleep apnea, or insomnia, and others may develop postpartum depression. • Occurrence of sleep apnea or RLS has been associated with adverse pregnancy outcomes; therefore, particular attention should be given to complaints of leg movements, to • overweight women who become obese during pregnancy, and to those who develop complications of pregnancy such as preeclampsia. Amy R. WolfsonKathryn A. Lee. Pregnancy and the Postpartum Period.. Printed from: Principles and Practice of Sleep Medicine 1278-86 (on 06 April 2009) www.sleepmedtext.com