Background This objective of this study was to diagnose Obstructive Sleep Apnoea (OSA) in pregnant women using Questionnaire-based methods and to determine any association of Sleep-Disordered Breathing (SDB) with Hypertensive Disorder of Pregnancy (HDP). Additionally, the study aimed to identify factors associated with OSA.
Methods This case–control study was conducted in department of Obstetrics in tertiary care hospital in Delhi. We Identified SDB using Berlin Questionnaire and Modified Stop-Bang Questionnaire in 100 pregnant women with Hypertension and 100 normotensive controls. We compared the groups using appropriate statistical analysis.
Results The mean age of women with HDP (25.46 ± 4.38) was found to be slightly higher than controls (24.13 ± 3.89) (p value-0.02). Sleep apnoea as depicted by the presence of either high-risk STOP Bang or Berlin score was seen more often in hypertensive women in 45% as compared to controls in 8% (p value < 0.001). Higher pre-pregnancy weight (58.58 ± 9.77 vs. 53.0 ± 6.59), higher BMI (24.03 ± 5.89 vs. 20.68 ± 1.49), higher mean neck circumference (14.97 vs. 14.27 inches) weight gain more than 11 kg during pregnancy (55.6% vs. 38.2%) were the high-risk factors more commonly associated with SDB as seen in women with OSA in hypertensive women. On logistic regression analysis, the presence of OSA was singularly responsible for development of Hypertension (Odds Ratio–13.014, 95% CI 5.237–32.337) (p value < 0.001).
Conclusion Gestational hypertension appears to be strongly associated with the presence of obstructive sleep apnoea. The recognition and treatment of OSA during pregnancy may lead to improved outcomes.
Keywords : Hypertensive disorders of pregnancy (HDP) · Preeclampsia · Sleep-disordered breathing (SDB) · Obstructive sleep Apnoea (OSA) · Stop-Bang Questionnaire · Berlin Questionnaire
Hypertensive Disorders of Pregnancy (HDP) are a leading
cause of maternal and perinatal morbidity and mortality.
These are common medical disorders which can result in
serious foeto-maternal consequences, affecting 7–10% of
pregnant women [1]. According to worldwide estimates,
they are responsible for > 500,000 foetal and neo-natal
deaths and > 70,000 maternal deaths every year [2]. Despite
years of research, the underlying cause and pathogenesis of
preeclampsia remains elusive. Recent studies suggest that Sleep-Disordered Breathing (SDB) such as Obstructive
Sleep Apnoea (OSA) is more prevalent in pregnant women
with Preeclampsia [3]. The increased prevalence of SDB
during pregnancy has been attributed to weight gain, narrowing
of the upper airway due to pharyngeal oedema and
increased upper airway resistance [4]. The HDP and sleep
disorders share many risk factors, including obesity/overweight,
hypertension, and advanced age. SDB is thought
to cause sympathetic activation, oxidative stress, endothelial
dysfunction due to persistent and repeated episodes of
hypoxia and arousal during sleep, potentially leading to
development of hypertension and other cardiovascular morbidities
[5, 6]. However, more research is needed to fully
understand the epidemiology of SDB in pregnancy, its relation
to development of hypertensive disorders of pregnancy,
and its effect on maternal and foetal health remains to be
explored.
The gold standard method for diagnosing SDB or OSA
is a full night polysomnography (PSG), but this technique
is time consuming, highly technically complex and resource
intensive, requiring skilled sleep professionals and may
not be practical in all clinical settings. Nonetheless, various
studies have proven that there are a few questionnaires
such as the ‘STOP BANG’ and ‘Berlin Questionnaire’ that
have predictive performance in diagnosing similar to polysomnography
[7]. Therefore, identifying SDB or OSA can
be done with fair degree of certainty using these validated,
globally accepted and published questionnaires.
This study aimed to diagnose OSA in pregnant women
using questionnaire-based methods and to investigate the
association of Sleep-Disordered Breathing with Hypertensive
Disorder of Pregnancy (HDP) (including Preeclampsia),
as well as to identify factors associated with SDB during
pregnancy.
This case–control study was conducted at a tertiary care hospital
in Delhi, following clearance from the departmental
ethics committee. The study group comprised 100 singleton
pregnancies in third trimesters, including both primigravida
and multigravida, with hypertension. The control group consisted
of 100 gestation period and age matched normotensive
pregnant women with no other medical conditions.
The identification of Sleep-disordered breathing was done
using Berlin questionnaire and modified STOP-BANG questionnaire
in both study and control groups, and the results
were compared using appropriate statistical analysis.
The STOP BANG questionnaire consists of eight questions,
related to the Snoring, Tiredness, Observed apnoea,
high blood Pressure (STOP) and Body mass index (BMI),
Age, Neck circumference and Gender (BANG), asked to both patient and her spouse. As Age older than 50 years
and male sex are not applicable to pregnant women, the
maximum STOP-BANG score in this population is six and
a STOP-BANG score greater than three indicates moderate
to severe OSA [8].
The Berlin Questionnaire is a validated patient survey that
assesses the risk of Obstructive Sleep Apnoea (OSA) based
on the presence and frequency of snoring, wake time, sleepiness
or fatigue and a history of obesity and/or hypertension
[9]. Patients are classified as high risk if they score positive
in two or more categories and low risk if they score positive
in only one or no category.
Both study and control subjects were well matched in
major confounding factors including mean gestational age
(p value = 0.22), pre-pregnancy BMI (p value = 0.26), prepregnancy
weight (p value = 0.35), parity (p value = 0.32),
religion (p value = 0.44) and socioeconomic status (p
value = 0.29) (Table 1). However, the mean age of women
with HDP (25.46 ± 4.38) was slightly higher than controls
(24.13 ± 3.89) (p value = 0.02) and the neck circumference
was significantly greater in cases (15.15 ± 1.24) as compared
to controls (14.24 ± 1.27) (p value < 0.001) (Table 2).
Sleep parameters were also compared in both the pregnant
groups (Table 2). Snoring, a surrogate marker of sleep
disorders, was observed in 57% of hypertensive women, compared to 22% of controls (p value < 0.001). Day time
sleepiness (hypersomnolence), an indirect indicator of poor
sleep quality, was higher in cases (55%) compared to controls
(25%) (p value < 0.001). The poor sleep quality marked
with sleep fragmentation and frequent arousals, likely due
to breathing pauses (apnoea’s), accompanying snoring
in these women, may be a risk factor for development of
hypertension.
High-risk STOP BANG score was seen in 40% of hypertensive women as compared to 7% of controls (p value < 0.001). Similarly, high-risk Berlin score was more commonly seen in cases (40%) as compared to controls (8%) (p value < 0.001). Sleep apnoea, as indicated by the presence of either high-risk STOP BANG or Berlin score, was observed in 45% of hypertensive women as compared to 8% of controls (p value < 0.001). These results suggest a strong association between gestational hypertension and obstructive sleep apnoea.
To identify any potential risk factors for the development of OSA amongst hypertensive pregnant women, various parameters were compared (Table 3). It was found that women with OSA had a higher pre-pregnancy weight (in Kg) (58.58 ± 9.77 vs. 53.0 ± 6.59) (p value < 0.001) and higher BMI (24.03 ± 5.89 vs. 20.68 ± 1.49) (p value < 0.001). Although the difference was not statistically significant, the weight gain (of more than 11 kg) during pregnancy was more commonly associated with OSA in women (55·6%) versus (38·2%) amongst those who did not have OSA (p value 0.08). There was a significant association between higher mean neck circumference (in inches) and the development of OSA (14.97 ± 1.75) versus (14.27 ± 1.42 inches) than those without OSA (p value = 0.02). However, there seemed to have no bearing of Obstructive Sleep Apnoea with regards to age of women or severity of hypertension in the candidates of this study group (Table 3).
In the multivariate logistic regression analysis, it was discovered that the presence of obstructive sleep apnoea was strongly linked to development of hypertension with Odds Ratio of 13.014, and 95% Confidence Interval of 5.237–32.337 (p value < 0.001) (Table 4). Furthermore, weight gain during pregnancy (> 11 kg in this group) was also identified as risk factor for development of hypertension with Odds ratio of 1.154 and 95% Confidence Interval of 1.053–1.265 (p value = 0.002). Pre-pregnancy weight, parity, maternal age, and religious ethnicity were not significant confounding factors and were not found to be associated with a high risk for development of HDP among the study participants (p value > 0.05). These findings underscore the importance of considering sleep-disordered breathing, particularly OSA, in the evaluation and management of hypertensive disorders during pregnancy.
The pathogenesis and development of hypertensive disorders
of pregnancy has been an enigma, with multiple factors
attributed to it. One of these factors is defective trophoblastic
invasion of spiral arterioles, which leads to cellular
ischaemia in the placenta. Consequently, an imbalance arises
between anti-angiogenic and pro-angiogenic factors. Similar
disturbances have also been observed in sleep disorders like
obstructive sleep apnoea [10].
The repetitive and dynamic upper airway obstruction during
sleep, which can be caused by alterations in biochemical
and hormonal environment, as well as inherent genetic predispositions
during pregnancy, may lead to the manifestation
of obstructive sleep disorders. This condition of sleepdisordered
breathing is characterized by recurring episodes
of apnoea/hypopnea, resulting in hypoxemia and repeated
arousals from sleep. Consequently, this disrupts the normal
angiogenic processes of Renin–angiotensin system, leading
to endothelial dysfunction [4].
These episodes of obstructive sleep apnoea (OSA) have been hypothesized and widely accepted as high-risk factors for development of hypertension and other cardiovascular Disorders in non-pregnant individuals. Therefore, it is logical to consider that they may also play a role for development of hypertensive disorders of pregnancy [5].
The sleep parameters of 100 hypertensive pregnant women and 100 non-hypertensive pregnant women were compared in this study. Confounding factors, such as prepregnancy weight, socioeconomic factors, parity, pre-pregnancy BMI, period of gestation on enrolment, were found to be similar in both the groups. However, age of hypertensive women was slightly higher (p value – 0·02). Therefore, based on the findings of this study, age can be considered as a risk factor for development of hypertension during pregnancy, as the hypertensive group consisted of older women compared to non-hypertensive group. Additionally, the main high-risk factors for the development of hypertensive disorders of pregnancy were similar in both the groups and include obesity, excess weight gain during pregnancy, high BMI, and advanced maternal age among others.
In the present study, it was observed that the mean neck circumference was higher in hypertensive women (15.15 inches) compared to control group (14.24 inches). This finding suggests a potential association between neck circumference and obstructive sleep apnoea with resultant hypertension in these women, and it might be one of the causative factors for development of Obstructive sleep Apnoea. Several studies, including the findings of John Reid, have reported a significant association between neck circumference and hypertension [11]. In this particular study, it was observed that pregnant women with pregnancyinduced hypertension had higher mean neck circumference (38.6 ± 3.4 cm), as compared to healthy pregnant women (34.2 ± 3.2 cm) (p value < 0.001) in their study. This also indicates that an increased neck circumference may serve as a potential marker or risk factor for development of OSA and resultant hypertension.
DeclarationsConflict of interest This material is the authors' own original work, which has not been previously published elsewhere. The research was ethically approved by Institutional Ethics committee, Kasturba Hospital, Delhi. There is no conflict of interest.