Sleep-disordered breathing (SDB) or sleep-related breathing disorders are characterized by abnormalities of respiration during sleep. SDB can be further grouped into obstructive sleep apnea (OSA), central sleep apnea disorders, sleep-related hypoventilation disorders, and sleep-related hypoxemia disorder (1). A published study indicated that SDB was highly prevalent in pregnant women for substantial physiological and hormonal changes during the gravid stage (2). Meanwhile, it has been confirmed that pregnant women are more vulnerable to OSA than non-pregnant women (3). A study conducted on 500 females suggested that the prevalence of snoring increased from 7.9 to 21.2% through the first to the third trimester of pregnancy (4).

The considerable prevalence of SDB in pregnant women has drawn increasing attention. As suggested by recent studies, SDB has potentially increased the risk of advanced pregnancy complications such as gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC) (5–7). These pregnancy complications can be strongly related to several adverse maternal outcomes. For instance, GDM has been recognized as a risk factor for neonatal hypoglycemia, premature delivery and fetal macrosomia (8–10). Besides, SDB may be associated with preterm birth (PTB) and low birth weight (BW). It was suggested by several studies that both snoring and OSA were linked with an increased risk of PTB, a major cause of infant mortality (6, 11–13). Low BW impacted neonatal mortality in a similar way (14). Also, it was indicated that gestational SDB was likely to affect the neurobehavioral development in infants (15).

In recent years, researchers attempted to clarify the association between SDB and maternal–fetal outcomes. However, the corresponding results were not conclusive and some contradictions have been found in the current literature. For instance, a recent meta-analysis indicated a significant impact of SDB on GDM, PIH, and BW (16) while another study denied such an impact (17). Besides that, SDB was reported to induce the elevation of circulating inflammatory markers and this trend can be used to predict PTB (18), but this conclusion was challenged by a study which revealed no significant association between SDB and PTB (17). Apart from these controversies, the power of some studies was limited by other factors such as the small sample size (19). For this sake, we designed and conducted this meta-analysis to examine whether SDB was associated with adverse pregnancy complications and maternal–fetal outcomes.

Pregnancy is a unique physiological stage in which women experience remarkable changes in hormone secretion, respiration physiology, cardiovascular function and sleep. Several studies have suggested that the incidence of SDB increased with the progression of pregnancy. Thus, we speculated that the above changes were likely to have some impact on the pathology of SDB. For instance, a high estradiol levels during pregnant may cause a narrowing of the upper airways and this could lead to snoring. It was also reported in a previous survey that weight gain might be another conceivable mechanism to explain why women with SDB during pregnancy experienced significant increase (24). As suggested by the famous Developmental Origins of Health and Disease, adverse maternal events during the early course of pregnancy may produce permanent and structural changes in infants through the process of Early Life Programming and Imprinting (51). As a result, identifying key adverse maternal events plays a critical role in maternal and infant care. In our study, the exploration of the association between SDB during pregnancy and perinatal outcomes is essential.

The present study conducted a meta-analysis to detect the association between SDB during pregnancy and perinatal outcomes. Unlike previous studies, both pregnancy complications and fetal–maternal outcomes were investigated in our study: GDM, PIH, PEC, BW, APGAR score, and PTB (4, 31). We discovered that gestational SDB appeared to be associated with some pregnancy complications, specifically with an increased risk of GDM, PIH, PEC, and PTB. As suggested by our study, there was no association between gestational SDB and fetal outcomes (APGAR scores, BW). A stratified analysis by the type of SDB (snoring/OSA) further suggested that pregnant women with snoring alone were associated with an increased risk of GDM, PIH, and PEC, the similar association existed in OSA. Our meta-analysis updated the included studies and supported the conclusions from Ding 2014 (16) article. Besides, our meta-analysis made a distinction between snoring and OSA while Ding 2014 article did not. In addition, we also updated data when it comes to comparison with prior studies. However, our study did not show significant association between snoring and the risk of PTB, but we confirmed that pregnant women with OSA exhibited a higher risk of PTB.

The majority of current studies investigated the epidemiological features of SDB and their potential association with maternal health. However, studies rarely explained the corresponding mechanism underpinned the potential association. For example, a large scale studies conducted in the USA revealed that gestational OSA accompanied with obesity may increase its association with GDM, PIH, PEC, and PTB (38), but in this typical cross-sectional study the possible causal relationship between OSA and pregnancy complications was not particularly explained. To our knowledge, SDB can induce intermittent hypoxia and sleep fragmentation which may cause sympathetic activation, oxidative stress and inflammation (52). Sympathetic activation may further trigger blood pressure changes, alter glucose homeostasis and induce insulin resistance, eventually causing hypertension and diabetes (53). Similarly, both oxidative stress and inflammation were also thought to be responsible for insulin resistance and gestational diabetes (54). Furthermore, SDB during pregnancy experiences significant increase in the chest load when they begin inhalation. This can decrease the cardiac output by 33% on average and further cause a reduction in the placental blood supply (55). Deficiency in placental blood supply may be associated with an increased risk of adverse maternal outcomes (12, 16, 56–58). Also, as we knew, snoring was a typical mild symptom of OSA. Patients with OSA were supposed to encounter a similar or even greater risk of adverse maternal–fetal outcomes than those with snoring alone. However, this trend was not distinctly observed in our result except for PTB. The influence of small size studies might be the cause or our assumption was not accurate.

Several limitations needed to be noted in this meta-analysis. To begin with, the results were possibly impacted by potential confounding factors. We extracted aORs from included study when they were available and calculated rORs when only raw data was accessible. The aORs provided by the previous studies were results after adjustments of confounding factors, while the rORs that we obtained were exposed to the influence of confounding factors. Since the risk factors may interact with SDB, thereby they may influence the risk of pregnancy complications or adverse maternal outcome in a different way. The most noteworthy confounding factor was obesity. As admitted by ICSD-3, snoring is linked to obesity and the major predisposing factor for OSA is excess body weight. However, OSA and obesity commonly coexist and even have similar clinical consequences such as insulin resistance and oxidative stress. Thus, it was a huge challenge to separate the effects of OSA from obesity. Moreover, trials in this field were not sufficient enough to get a convincing result. In addition, some other factors which may also have great impact such as chemo sensitivity and ethnicity are not fully considered. Sleep apnea prevalence is known to be different among various ethnicities. For instance, OSA mechanisms might vary across ethnicities according to a prior study (59). Yet only one trial of 35 included studies pointed out that the ethnic difference has been adjusted, which renders our research lack consideration of ethnic difference. In summary, our meta-analysis provided a comprehensive review for the association of SDB and adverse pregnancy complications or maternal–fetal outcomes. SDB during pregnancy was significantly associated with an increased risk of GDM, PIH, PEC, and PTB, but not with fetal maternal outcomes (APGAR and BW). Respectively, OSA was linked with an increased risk of GDM, PIH, PEC, and PTB, snoring alone appeared to increase the risk of GDM, PIH, and PEC. The result from our study provided new insights into maternal–fetal health care and leaded us to carry out ongoing research in this area.

LL, KZ, and JH: substantial contribution to the conception and design of the work; acquisition, analysis, and interpretation of the data; drafting the manuscript and revising it critically for important intellectual content; final approval of the version to be published; agreement to be accountable for the work. SL: interpretation of the data; critical revision of the manuscript; final approval of the version to be published; agreement to be accountable for the work.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.