Orna Sever and Riva Tauman
Sleep is an essential biological function in humans. Sleep is governed by two major neural mechanisms: the sleep homeostatic process, which builds up as a function of time awake, and the daily circadian rhythm of sleep and wake propensity.
All adult humans sleep for approximately one-third of their lives; thus, the fetus is exposed to a mother who is asleep for one-third of their gestation (1). Alterations in sleep patterns are among a multitude of physiologic changes occurring during pregnancy in most women. Changes in sleep duration, sleep architecture, and sleep quality perceptions have all been reported, with clear differences between trimesters (2,3) (Figure 33.1).
Figure 33.1 Factors influencing sleep during pregnancy. (Source: Ref. 9, with permission.)
In a large sample of women across all months of pregnancy, women have been shown to experience poor sleep quality (76%), insufficient nighttime sleep (38%), and significant daytime sleepiness (49%). Frequent nighttime awakenings were reported in almost all women, and daytime naps were reported to be taken by almost 80% of women. Symptoms of insomnia (57%), sleep-disordered breathing (SDB) (19%), and restless legs syndrome (RLS) (24%) were all commonly endorsed (4).
In the general population, epidemiologic studies have shown an association between short sleep duration and increased risk of obesity, diabetes, hypertension, and mortality (5,6). Specific sleep disorders, such as SDB, insomnia, circadian rhythm disorders, and RLS, have been linked with a higher risk of developing depression and cardiovascular and metabolic diseases (7,8).
The relationship between sleep and pregnancy outcomes has become an area of intense research interest in recent years. The associations between SDB, short sleep duration, sleep disruption, and adverse maternal and fetal outcomes were investigated, and the significance of sleep disturbances to maternal and fetal health during the short course of pregnancy is becoming clearer.
In this chapter, we review the most common sleep disorders in pregnancy, i.e., SDB, RLS, insomnia, and short sleep duration, and their effect on pregnancy outcomes.
Sleep-disordered breathing in pregnancy
SDB is a spectrum of abnormal respiration during sleep that ranges from “primary/habitual” snoring to obstructive sleep apnea (OSA). SDB is characterized by some combination of repeated events of partial or complete upper airway obstruction during sleep, disruption of ventilation, intermittent hypoxia, sleep fragmentation, and intrathoracic pressure swings. The clinical manifestations of SDB include snoring, witnessed breathing interruptions/pauses, gasping or choking, frequent awakenings, dry mouth, unrefreshing sleep, and daytime sleepiness. The diagnosis is confirmed by an overnight sleep study that can be conducted in the sleep laboratory (polysomnography) or at home (10). If left untreated, SDB can lead to severe neurocognitive, metabolic, and cardiovascular consequences (11).
During pregnancy, physiological and hormonal changes render women susceptible to worsening or to developing SDB. Potential risk factors include reduction in upper airway size due to increased fluid retention and weight gain, nasal obstruction due to increased edema from high estrogen (also known as pregnancy rhinitis), and changes in lung mechanics (reduced functional residual capacity and residual volume) (12).
Similar to the general population, obesity and increased age have been shown to increase the risk of SDB during pregnancy (13). Since approximately 37% of women of reproductive age are considered obese (14), maternal SDB has become more common with a 24% annual increase in prevalence (15). High-risk women with chronic hypertension, gestational diabetes, a history of preeclampsia, and/or a twin gestation are also at increased risk for developing SDB (16). Similar to the general population, SDB may improve with lateral positioning due to the effect on lung dynamics and upper airway dimensions (17).
The prevalence of OSA in the nonpregnant population of reproductive age women is 0.7%–6.5% (18). In pregnancy, habitual snoring has been reported in up to 46% in the third trimester (19), and the prevalence of gestational OSA based on objective assessment of sleep was found to be 3.6% in early pregnancy and 8.3% in midpregnancy (20). The diagnosis of SDB in women is often not simple. In the general population, women are likely to be delayed in receiving a diagnosis of SDB due to their low self-reports of classic symptoms, different spectrum of symptoms including daytime fatigue, morning headaches, symptoms of depression, and sleepiness that are not very specific and can be even more confusing during pregnancy (21).
Data from recent years suggest that SDB during pregnancy increases the risk of gestational hypertensive disorders and gestational diabetes (15,22). In a large prospective cohort study including 3,306 nulliparous women who underwent home sleep apnea testing in early and mid-pregnancy, it has been demonstrated that women with OSA were at increased risk for developing preeclampsia and gestational diabetes, after adjusting for confounding variables (20). Interestingly, in women with preeclampsia, reversibility of symptoms was demonstrated following treatment of OSA and even improvement in fetal well-being in utero (23,24).
The effect of maternal SDB on the fetus is less clear. Reports on maternal SDB and adverse fetal outcomes have thus far revealed inconclusive findings most likely due to limitations such as the subjective assessment of sleep, lack of uniformity in study designs, heterogeneous populations, and inadequate adjustment for pregnancy complications such as maternal obesity, preeclampsia, and diabetes (Figure 33.2).
Figure 33.2 Potential pathways/mechanism linking sleep disordered breathing with adverse pregnancy outcome.
Preterm birth: Only a small number of studies utilizing subjective measures of SDB have investigated the effect of maternal SDB on preterm birth and revealed inconsistent findings; however, in four out of the five largest studies conducted (>1,000 women), an association between SDB symptoms and preterm birth has been reported (1). Data from larger population-based studies using objective assessment of sleep suggest that there is a relationship between maternal SDB and preterm birth (1).
Fetal growth: The effect of maternal SDB on fetal growth has been studied in recent years, but most of the studies used subjective assessment of sleep; the latter suggested that there is no clear association between birth weight and SDB. A small number of studies have thus far used objective assessment of sleep during pregnancy, and most of them were retrospective, using large epidemiological databases, and revealed inconsistent findings. Recently, we published a prospective study on the anthropometric outcomes of infants born to nonobese otherwise healthy pregnant women with SDB. We demonstrated that maternal SDB in pregnancy—even in a mild form—was associated with accelerated fetal growth, increased birth weight, birth length, and greater adiposity. The proportion of large for gestational age babies was significantly higher among those nonobese healthy women (25).
Stillbirth: Currently, there are only three studies that have reported stillbirth in women with and without SDB. In a retrospective review of 55 million hospital discharge records from a nationwide U.S. sample, no relationship was found between SDB and stillbirth (15).
Offspring’s neurodevelopment: The effect of maternal SDB on the offspring’s neurodevelopment has not been studied extensively. There is only one study, published by our group on 74 women with uncomplicated pregnancy using objective assessment of sleep. In that study, we performed a neurobehavioral test three times in the first 6 months of life to the infants, and in addition, the parents completed an infant development inventory at the age of 1 year. Our findings showed that maternal SDB during pregnancy has no adverse effect of neonatal and infant neuromotor development but may affect social development at 1 year (26).
The long-term effect of maternal SDB on the offspring’s growth and development as well as the effect of treatment for maternal SDB on fetal growth and development have not yet been studied.
SDB is most likely underdiagnosed in pregnant women. Habitual snoring, older age, chronic hypertension, and high pre-pregnancy body mass index (BMI) could be reliable indicators for preexisting SDB in early pregnancy. These risk factors should alert healthcare providers to have a high level of suspicion of SDB and to evaluate women’s sleep history with a plan for early referral to a sleep specialist to obtain evidence about abnormal respiratory events by undergoing an overnight sleep study (polysomnography) or home portable sleep monitors that may be a convenient and cost-effective alternative to laboratory polysomnography.
There are no specific guidelines for treatment of SDB in pregnancy. The treatment options and recommendations are similar to guidelines for the general population (10). The goal of therapy includes resolution of signs and symptoms, improving sleep length and quality, normalizing apneic events and oxygen saturation levels, and thus minimizing maternal and fetal complications.
Behavioral modification includes control of weight gain, avoiding smoking and alcohol use, treating nasal congestion, and following good sleep hygiene measures. Regarding sleeping position, there are data supporting minimizing supine sleep and favoring left lateral position (17).
In the general population with OSA, first-line treatment involves the use of a continuous positive airway pressure (CPAP) device. The use of CPAP decreases the number of apneic events and improves the recurrent hypoxia and sleep fragmentation. CPAP is associated with decreased hypertension, neurocognitive performance, overall cardiovascular morbidity, and stroke. CPAP is generally well tolerated in pregnancy (27).
Limited information exists on CPAP efficiency in pregnancy. Small studies have reported that CPAP improves maternal and fetal outcomes for women with OSA, preeclampsia, or risk factors such as chronic hypertension (28,29).
CPAP treatment has been shown to improve nocturnal oxygen saturation, blood pressure, and fetal movements (23,24). Autotitrating CPAP is better suited for pregnant women’s condition to adjust therapeutic CPAP pressure when the severity changes during pregnancy. CPAP may need to be readjusted around 24 weeks of pregnancy because of pregnancy-induced nasal congestion and increased BMI and again after delivery (30).
Restless leg syndrome in pregnancy
RLS, also known as Willis-Ekbom disease, is a common sensorimotor disorder characterized by a strong, nearly irresistible urge to move the limbs during rest, which improves with movement and worsens during the evening and night. About 70% of patients with RLS complain about sleep-onset insomnia (31) (Table 33.1).
Table 33.1 Restless leg syndrome criteria for diagnosis
An urge to move the legs that is usually, but not always, accompanied or caused by uncomfortable and unpleasant leg sensations
The symptoms begin or worsen during rest or inactivity
The symptoms are partially or totally relieved by movements such as walking or stretching
The symptoms only occur or are worse in the evening or night than during the day