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21 Sleep inPregnancy
https://t.me/medicina_free
factor in the pathogenesis of cardiovascular morbidity [128]. In pregnancy, sympa­thetic overactivity is one of the hallmarks of preeclampsia [129]. Furthermore, epi­sodes of intermittent hypoxia and reoxygenation are involved in the generation of reactive oxygen species and reduction in the levels of circulating antioxidants. The subsequent imbalance leads to oxidative stress which plays a central role in endo­thelial damage and ultimately hypertension [130]. It has been postulated that condi­tions of chronic sleep loss in pregnancy, such as insufcient sleep, insomnia, and poor sleep quality, could lead to sustained overload of the stress system, which may in turn impair the HPA axis and the proinammatory system, leading to poor preg­nancy outcomes [9, 127].
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Treatment Interventions
Treatment intervention trials for sleep disturbance in pregnancy are limited. For pregnant women with SDB, small studies and case reports show that use of positive airway pressure is safe and appears to improve maternal blood pressure and insulin secretion, extend time in utero, and improve markers of maternal and fetal well­being [131–136]. For insomnia, cognitive behavioral therapy (CBTI) is efcacious during pregnancy [137, 138]. A 5-week CBTI program for pregnant women demon- strated signicant reductions in insomnia symptoms and increases in subjective sleep quality as well as less time in bed, shorter sleep-onset latency, increased sleep efciency, and increased subjective total sleep time. Importantly, symptoms of depression, pregnancy-specic anxiety, and fatigue all decreased over the course of treatment [138]. Moreover, since access to trained clinicians can be challenging to many women, delivery of digital CBTI online has also been shown to improve sleep onset and maintenance symptoms as well as sleep duration [139]. Importantly, CBTI during pregnancy appears to protect against sleep loss after childbirth. Support for other therapies to improve sleep quality such as yoga/mindfulness, relaxation, herbal therapies, and acupuncture has also been reported (see Bacaro [140] for a review). However, whether these interventions translate to improvements in fetal outcomes is yet to be tested. Effective treatments, either via therapies such as posi­tive airway pressure for SDB or behavioral strategies to promote good hygiene, should be aggressively pursued in order to reduce the short- and long-term burden of the consequences of sleep deciency during pregnancy.
Circadian Rhythm Disruption
The majority of studies of circadian rhythms focus on nonpregnant individuals with shift work and nd associations with poor health outcomes, especially obesity and type 2 diabetes mellitus [141, 142]. Although an emerging area of investigation in pregnant women, circadian rhythm disruption has been associated with poorer
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fertility and early pregnancy loss via alterations in circadian rhythm-regulating gene expression [143]. Indeed, shift work has been reported to increase the risk of mis­carriage [144–146]. However, data on circadian disruption and its relationship with pregnancy outcomes is scarce. Recently, a large multicenter study of over 7000 women found that those who self-reported a late sleep midpoint (>5am) in early pregnancy– as a marker of circadian misalignment– had an aOR of 1.67 (95% CI
1.17–2.38) for GDM [147] and an aOR of 1.39 (95%CI 1.08–1.80) for preterm birth [148]. Similar ndings were reported by the same group using a sub-cohort of women with actigraphic measures, with a later sleep midpoint being associated with an increased odds for GDM (aOR 2.58, 95%CI 1.24–5.36) [16] although the asso­ciations between later sleep midpoint and preterm birth were not quite signicant in this smaller sample (aOR 1.68, 95%CI 0.88–3.20) [148].
Analysis of 24-hour rest-activity and saliva cortisol rhythms across the second and third trimester of gestation has shown that more robust activity rhythms are associated with more robust cortisol rhythms and suggest that more irregular sleep­activity rhythms may be associated with earlier gestational age [149]. Furthermore, women diagnosed with gestational-related disease (hypertension, gestational diabe­tes mellitus, and/or preeclampsia) showed a trend for higher cortisol levels [149], which is consistent with the relationship of hypercortisolism with gestational diabe­tes [150]. In light of these emerging ndings, there is an urgent need to explore the impact of disrupted circadian rhythms among the pregnant women and their off­spring. To that end, a large study in Malaysia is underway to investigate the role of circadian rhythms, activity, and nutrition during pregnancy on birth outcomes and infant growth [151].
L. M. O’Brien
Maternal Sleep Position
In recent years, data from several countries have shown that self-reported maternal supine going-to-sleep position is a signicant risk factor for late-gestation stillbirth (stillbirth at 28weeks’ gestation or more). Report of supine sleep position is three­to eightfold higher in women who experience a late stillbirth [101, 152–155] with an individual patient data analysis showing a 2.6-fold increased odds [156]. While it has long been recognized that posture in pregnancy– particularly during labor– has a profound impact on maternal hemodynamics, few people have extrapolated these practices to how a pregnant woman sleeps. In the supine position, the inferior vena cava is compressed, with subsequent reduced blood ow and a reduction in cardiac output [157]. Even in healthy late-gestation pregnancies, maternal position results in an approximate 6% reduction in oxygen delivery to the fetus and 11% reduction in fetal umbilical venous blood ow [158]. Maternal supine position has been demonstrated to induce fetal quiescence [159], an oxygen conserving state observed during periods of fetal hypoxia, and a small cross-sectional study has sug­gested that maternal supine sleep was linked to a vefold increase in low birth weight [101], a nding that was conrmed in a large individual patient data analysis
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of 1760 women and which found a threefold increase in small for gestational age [160]. Taken together, these ndings provide evidence of biological plausibility in the relationship of supine sleep to late-gestation stillbirth. Unlike the studies that have used self-report of going-to-sleep position mentioned above, a study of home sleep testing found no association between sleep position prior to 30weeks’ gesta­tion and stillbirth [161]. However, the latter study was conducted at a much earlier gestational age than other studies [101, 152–156], and this suggests that the heavier gravid uterus later in the third trimester likely conveys the risk. Other sleep behav­iors such as long sleep duration, non-restless sleep, and not waking in the night have also been associated with late stillbirth [162], which raises the question of whether long periods of undisturbed sleep increase the risk of late fetal demise. Data are lacking on how the neuroendocrine and autonomic system pathways are regulated in pregnant women during sleep, and this is a fertile area for investigation.
Since most pregnant women spend at least some time in the supine position [163], supine sleep is a potentially modiable risk factor which could prevent up to 10% of late stillbirths [154, 164]. While there is no intervention study adequately powered to investigate whether reduction in supine sleep translates to fewer still­births, several recent studies have shown promise in the ability to reduce time spent in the supine position without impacting sleep quality or duration [165–167] and even suggest that fetal heart rate decelerations can be reduced and infant birth weight may be increased [165, 167]. Work is ongoing in this area.
Summary
In summary, pregnancy is a vulnerable period for sleep disturbance and confers signicant impact to both maternal and fetal health. Clinicians caring for pregnant women should be mindful of the accumulating evidence, and identication of sleep disturbance and clinical sleep disorders should be prioritized. Effective therapies to reduce the public health burden of sleep deciencies are urgently needed since preg­nancy offers a window of opportunity to improve long-term health outcomes for both mothers and their babies.
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