Mechanism of development of pre-eclampsia linking breathing disorders to endothelial dysfunction
Section snippets
Background
Despite being one of leading causes of maternal death and a major contributor of maternal and perinatal morbidity, the mechanism responsible for the pathogenesis of pre-eclampsia remains unclear [1], [2]. Evidence shows that inadequate oxygenation from various causes leads to the initiation of an abnormal autonomic response. Several studies show a strong association between obstructive sleep apnea (OSA) and hypertension in the non-pregnant state [3], [4]. Few studies in pregnancy corroborate
Incidence of snoring, hypoapnea and sleep apnea in the non-pregnant state, pregnancy and pre-eclampsia
The incidence of snoring, hypoapnea, and sleep apnea is 9% in non-pregnant females and 14% in pregnant women [9], [10], [11]. By the third trimester, 24% of women were reported to have a snoring problem (symptom of sleep apnea). Habitual snorers had a higher frequency of pregnancy-induced hypertension (14%) compared to 6% of non-habitual snorers. The intrauterine growth retardation incidence was 7% in habitual snorers compared to 2.6% in non-snorers [10]. In this study it was noted that all
Obstructive sleep apnea and abnormal renin–angiotensin system
Pre-eclamptic patients are observed to have an abnormal renin–angiotensin system [20]. There is a significant interaction between angiotensin-converting enzyme gene insertion/deletion polymorphism and OSA, suggesting another mechanism for the development of hypertension [21]. Chronic induced intermittent hypoxia (CIHO) in rats can cause levels of circulating renin activity and angiotensin II to increase, which suggests that an activated renin–angiotensin system may contribute to the
Obstructive sleep apnea associated with endothelial function index and vascular spasms
Pre-eclampsia is known to be associated with vasoconstriction. Mechanical properties of vessels are abnormal in pre-eclamptic patients. Flow-meditated dilation is decreased in pre-eclamptic women [23]. A study conducted in OSA patients revealed that CPAP treatment restored the compromised flow-mediated dilation [24]. In a study comparing normal pregnant with pre-eclamptic patients the latter had higher respiratory disturbance index during sleep and lower endothelial function index [6].
Relationship of autonomic nervous system to normal and abnormal respiration in the non-pregnant, normal pregnant and pre-eclampsia condition
The autonomic (sympatho-vagal) balance is strongly associated with respiration [25]. Increased vagal (parasympathetic) tone is associated with slow breathing and increased tidal volume, while irregular shallow fast breathing is associated with increased sympathetic tone [25], [26], [27]. Studies on both normotensive pregnant and pre-eclamptic women have shown that the vagal response (parasympathetic tone) is decreased in pre-eclampsia [28]. Other studies have concluded that both sympathetic and
Decrease in incidence of pre-eclampsia and improvement of hypertension, with restoration of normal breathing and relaxation exercises
Another line of evidence supporting this theory is the decrease in the incidence of pre-eclampsia following the restoration of normal breathing. In a study by DiPietro et al. induced maternal relaxation during 32nd week of pregnancy resulted in significant changes in maternal heart rate, skin conduction and increased respiratory sinus arrhythmia. Parallel significant alterations of fetal neural behavior were observed including decreased fetal heart rate, and increased fetal heart rate
Summary
There is strong evidence to support the notion that pre-eclampsia is initiated by dysarrhythmic respiration. Either orthostatic stress-induced respiratory changes or sleep apnea or combination of both elicit imbalance of autonomic nervous system towards sympathetic state. The resultant abnormal cardiopulmonary synchronization significantly diminishes vagal balance. The imbalance leads to vascular changes in the mother, fetus and placenta. The cycle of intermittent anoxia from sleep-associated
Conclusion
Based on various epidemiological, experimental animal studies and sleep studies we cited in this article it appears that there is strong evidence that disordered breathing is an important pathogenic mechanism for the development of pre-eclampsia. This is further supported by the evidence cited that the correction of disordered breathing results in the decreased incidence of pre-eclampsia. While these findings are supportive they cannot prove a causal relationship. Further controlled prospective
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Is sleep-disordered breathing associated with miscarriages? An emerging hypothesis
2014, Medical HypothesesCitation Excerpt :Additionally, OSA has been linked to decreased levels of adiponectin and alterations in leptin levels; both of these peptides have been linked to impaired glucose control. All of the above factors have been shown to be related to the development of gestational diabetes and preeclampsia, both of which are well-known to be associated with pregnancy loss [42–44]. Whether it is sleep fragmentation, sleep deprivation, chronic intermittent hypoxemia, or a combination of these factors that predisposes to the above adverse events is unknown.
Pseudo three-dimensional vision-based nail-fold morphological and hemodynamic analysis
2012, Computers in Biology and MedicineCitation Excerpt :As shown in Tables 5 and 6, the calibers of arteriolar limb, curved segment, and venular limb of capillary for normal subjects are all smaller than the patients with hypertension. It can be explained by that increased blood pressure tends to cause capillary dilation, which damages end-organ sites and leads to hypertension, proteinuria, and edema [12]. Contrast to the capillary, inward eutrophic remodeling of resistance vasculature of small arteries is manifested as reduced lumen, an increase of ratio of media width to lumen diameter, and constant media cross-sectional area for patients with essential hypertension (For review, see [38,20,24]).
Obstructive Sleep Apnea in Pregnancy
2022, Acta Academiae Medicinae Sinicae