Metabolic consequences of sleep and circadian disruption during pregnancy and postpartum

Abstract

Physiological changes during pregnancy may predict future cardiovascular and metabolic diseases; thus, identifying mechanisms driving cardiometabolic impairments, as well as potential interventions to improve health during pregnancy, is critical. Here we discuss how sleep and circadian disruption during pregnancy and postpartum affect cardiometabolic risk and identify future research directions.

Sleep and circadian homeostasis contribute to cardiometabolic health

Sleep is crucial for overall health and wellbeing [1]. This essential function is intricately linked to circadian rhythms, which are endogenous near 24-hour oscillations that regulate physiological and behavioral patterns. Both sleep and circadian rhythms are increasingly recognized as important determinants of cardiometabolic health, since disruption of either results in profound impairments in metabolic function, increased risk of obesity, type 2 diabetes, and cardiovascular disease [2]. For example, sleep and circadian disruption (circadian disruption defined as a mismatch between internal circadian rhythms and external behaviors) impair glucose tolerance and insulin sensitivity, as well as negatively impact blood pressure control, appetite regulation and systemic inflammation [2]. In addition, sleep disorders, such as obstructive sleep apnea (OSA), are common in the general population and also increase the risk for cardiometabolic diseases. Finally, short and disrupted sleep can induce circadian disruption, and the reverse is also true—circadian misalignment impairs sleep quality; thus, insufficient sleep and circadian disruption are inherently linked. The phrase “sleep and circadian disruption” is therefore used here to describe the combined effects of insufficient sleep (in duration or quality) and circadian disruption induced by several behaviors that result in an altered relationship between sleep-wake and associated behaviors.

Although controlled inpatient studies have demonstrated a consistent link between sleep and circadian disruption and impaired cardiometabolic outcomes, results have been primarily derived from male volunteers, or from studies underpowered to detect sex differences. Moreover, the increase in sleep and circadian disruption that commonly occurs during pregnancy and postpartum periods can acutely impair health outcomes as well as have important implications for long-term maternal disease risk. Figure 1 is a conceptual model depicting the risks associated with sleep and circadian disruption during pregnancy including both acute and long-term impacts.

Figure 1.

Sleep and circadian disruption during pregnancy and postpartum is associated with an increased risk for sleep disorders, such as obstructive sleep apnea and restless leg syndrome, gestational diabetes, and postpartum weight retention. This increases future risk of sleep disorders, type 2 diabetes, and obesity. It is critical to identify possible countermeasures to improve sleep during the pregnancy and postpartum periods. Figure created using BioRender.

The goal of this article, therefore, is to highlight the growing body of work supporting the negative impact of sleep and circadian disruption specifically during pregnancy and postpartum, as well as highlight possible future directions to improve sleep and circadian rhythms and thus long term cardiometabolic health.

Sleep and circadian disruption during pregnancy

Sleep duration is known to decrease over the course of pregnancy [1], and it is common for pregnant individuals to sleep less than the recommended 7 hours per night [1]. Pregnant individuals also experience variability in sleep timing (a form of circadian disruption), increased daytime sleepiness, and increased napping [1]. Additional forms of sleep disruption (e.g. increased number of awakenings, increased amount of time spent awake after sleep onset, and increased time spent in lighter stages of sleep) as well as insomnia symptoms are also common complaints during pregnancy likely due to hormonal and physical changes that occur. For example, increases in estrogen and progesterone, higher collapsibility of the upper respiratory pathway, fetal movement, urination during the night, and weight gain can all negatively impact sleep duration and quality during pregnancy [3]. Sleep disruption is reported to begin in the first trimester, may improve or plateau in the second trimester, and is reported to worsen in the third trimester [3].

Aside from variability in sleep timing during pregnancy, there are limited data on the existence of circadian disruption during, or as a consequence, of pregnancy in humans. Circadian rhythms of cortisol, body temperature and melatonin, all of which are regulated by the central circadian clock, appear to remain intact over the course of pregnancy, although absolute levels are suggested to change [4].

Furthermore, the prevalence of sleep disorders, such as sleep disordered breathing, including obstructive sleep apnea (OSA), and restless leg syndrome (RLS), increase during pregnancy. The increase in OSA is possibly due to increased upper airway collapsibility and decreased pharyngeal and nasal pathway diameters and increased adipose stores. OSA prevalence during pregnancy has been reported to be anywhere between 3% and 27% depending on gestational age and assessment method, whereas OSA in a nonpregnant population of reproductive-age females is between 0.7 and 6.5% [5]. The prevalence of RLS has been reported to be 21% across all trimesters, which is suggested to be due in part by changes in iron levels and/or estrogen and progesterone [6].

Metabolic consequences of sleep and circadian disruption during pregnancy and postpartum

During pregnancy, sleep and circadian disturbances are particularly concerning because of their association with increased risk for pre-eclampsia, gestational hypertension, preterm delivery, and gestational diabetes mellitus (GDM) [3]. GDM is one of the most common medical complications of pregnancy and increases the risk of future development of type 2 diabetes, obesity, and cardiovascular disease in pregnant individuals [6]. Consistent with epidemiologic studies in nonpregnant individuals, a U-shaped associated exists between sleep duration and health outcomes. Specifically, both short (<7 hours a night) and long (>9 hours a night) sleep duration are associated with an increased risk of GDM and pre-eclampsia, though likely through different mechanisms [3]. Additionally, pregnant individuals who sleep less than 6.25 hours per night have higher glucose levels during a glucose tolerance test and have an almost 3-fold higher odds of developing GDM as compared to those who sleep more than 6.25 hours [6]. Likewise, sleep disturbances (defined as poor sleep quality, extreme sleep duration, insomnia, RLS, sleep-disordered breathing and diagnosed OSA) increase the risk of GDM, pre-eclampsia, and adverse fetal outcomes [3]. Finally, sleep disorders during pregnancy also increase the risk for GDM with results from a meta-analysis of 7 studies reporting that pregnant individuals with OSA had a 1.55 higher odds of having GDM compared to no OSA [6].

There is limited research on the effects of circadian disruption on cardiometabolic outcomes during pregnancy, since experimental circadian disruption is not advisable given the potential risks and ethical concerns. Instead, findings from observational studies in shift workers have provided insights regarding circadian disruption during pregnancy. For example, shift work during pregnancy is associated with preeclampsia, preterm birth, and GDM [7]. Furthermore, a later midpoint of sleep (a surrogate marker of circadian phase) is associated with an increased risk for GDM as compared to an earlier midpoint of sleep [7]. Additionally there is a 75% increased odds of developing GDM in pregnant shift workers compared to day shift workers [7], as well as greater sleep timing variability, which explained 25% of the association between shift work and GDM, suggesting that circadian disruption associated with an altered timing of sleep may play a role in GDM risk associated with shift work.

Sleep disruption that begins during pregnancy typically continues into the postpartum period, during which individuals continue to report <7 hours of sleep per night and frequent nocturnal awakenings, likely due to residual hormonal changes as well as caring for a newborn [8]. There is also an increased risk of weight retention if insufficient sleep persists during the first year postpartum [9], which can further increase the risk of obesity and metabolic disease.

Additionally, sleep disorders such as OSA that develop during pregnancy increase the risk of developing future metabolic diseases [10, 11]. Although it may resolve in some individuals—particularly those with mild OSA that developed during pregnancy—many individuals will continue to display OSA symptoms into the postpartum period and may go on to be chronically affected [12].

Improving sleep during pregnancy and postpartum

Given the aforementioned risks associated with sleep and circadian disruption during pregnancy, it is critical to develop and test strategies to improve sleep during pregnancy and postpartum to improve health outcomes and disease risk [13]. Strategies such as pharmacotherapy, acupuncture, mindfulness, yoga, relaxation, and herbal medication have demonstrated some potential to improve sleep quality during pregnancy [13]; however, rigorously controlled clinical studies on these interventions have not been conducted. Massage and exercise are also suggested to improve sleep quality during postpartum [14], as is cognitive behavioral therapy for insomnia during pregnancy [15], although cardiometabolic outcomes were not assessed. Therefore, a significant gap remains for which rigorously controlled clinical trials are needed to assess the impact of improving sleep, as well as treating sleep disorders, during pregnancy on cardiometabolic outcomes.

Concluding remarks and future perspectives

The pregnancy and postpartum periods may hold predictive value for the development of future metabolic. Therefore, there is a critical need to mitigate the negative effects of sleep and circadian disruption on the health of pregnant individuals. High quality intervention studies are needed that focus on improving sleep during these periods in large and diverse populations. Improving sleep in pregnancy and postpartum may be particularly powerful in preventing or delaying the onset of metabolic disease in a substantial portion of the population.