In total, 2,038 pregnant women were invited to participate; 1,719 (84%) agreed to complete the surveys, 98% of whom consented to medical record access. There were no differences in maternal age, gestational age, parity, or BMI between women who did or did not participate or who did/did not consent to medical record access (data not shown). Five women were subsequently excluded because they were <28 weeks’ gestation and two women were excluded because they were <18 years. In addition, 9 women moved out of the area before delivery. Thus, the total sample was 1,712 for prevalence data and 1,673 for pregnancy outcomes (). In total, 202 non-pregnant women were enrolled. Overall, 94% of women had bed partners; only 2% of partners complained about snoring when women classified themselves as non-snorers. This did not alter the association with outcomes and thus the analyses were performed with maternal self-report only.
shows population demographics. Pregnant women were more than twice as likely as controls to snore: 34.1% vs. 14·9%, p<0.0001.
Demographics of Participants
Overall, 34.1% of third-trimester women reported snoring; 66% were non-snorers at both pre-pregnancy and in the 3rd trimester, 25% started snoring during pregnancy, and 9% reported chronic snoring (). Snorers in general, as well as those with pregnancy-onset snoring specifically, were more likely to have chronic hypertension, gestational hypertension, and pre-eclampsia, than non-snorers. In contrast, although snorers were more likely to have gestational diabetes compared to non-snorers, further analysis revealed that it was the chronic, not pregnancy-onset, snorers who appeared to drive this relationship.
Comparison between pregnant women with and without snoring
In unadjusted analyses, pregnancy-onset, but not chronic, snoring was independently associated with gestational hypertension; OR 2.57, 95%CI 1.69–3.53, p<0.001, and pre-eclampsia; OR 1.71, 95%CI 1.20–2.44, p=0.003. There was no relationship with pregnancy-onset snoring and gestational diabetes; OR 1.29, 95%CI 0.96–1.74, p=0.09. However, chronic snoring was associated with gestational diabetes; OR 1.67, 95%CI 1.10–2.52, p=0.015.
A logistic regression model that controlled for potential covariates (maternal age, race, pre-pregnancy BMI, weight gain in excess of IOM recommendations, gravidity, smoking, education level, previous or family history of gestational hypertension or pre-eclampsia) showed that pregnancy-onset, but not chronic, snoring was independently associated with gestational hypertension, OR 2.36, 95%CI 1.48–3.77, p<0.001. In this model exceeding the IOM weight gain guidelines, but not pre-pregnancy BMI, was also independently associated with gestational hypertension; OR 2.68, 95%CI 1.72–4.18, p<0.001. .
Regression of gestational hypertension against snoring and other covariates
Similarly, in a logistic regression model controlling for the same covariates and including chronic hypertension and gestational diabetes, pregnancy-onset – but not chronic - snoring was independently associated with pre-eclampsia; OR 1.59, 95%CI 1.06–2.37; p=0.024; . No interactions were found between snoring and pre-pregnancy BMI for gestational hypertension or pre-eclampsia. Similarly, no interactions were found between snoring and weight gain in excess of IOM recommendations.
Regression of pre-eclampsia against snoring and other covariates
Blood glucose levels at the 24–26 week gestation 1-hour oral glucose tolerance test using a 50gram load were higher in snorers compared to non-snorers;124.0mg/dl vs. 117.2mg/dl, p<0.001, as was the proportion of women with abnormal glucose levels, defined as ≥140mg/dl; 30.2% vs. 22.1%, p=0.003. Glucose levels were not compared between women with and without pregnancy-onset snoring, as glucose was assessed in the second trimester. Neither pregnancy-onset nor chronic snoring was found to be associated with gestational diabetes in a multivariate model; however pre-pregnancy BMI and maternal age were associated ().
Regression of gestational diabetes against snoring and other covariates
graphically depicts the OR of pre-pregnancy obesity (BMI ≥ 30) and/or snoring in separate models for gestational hypertension, pre-eclampsia, and gestational diabetes after adjusting for covariates that were shown in to be associated with the outcome of interest. For illustrative purposes data are shown as snorers (pregnancy-onset and chronic snoring) vs. non-snorers. Four groups are represented: lean, non-snorer (BMI<25kg/m2, the reference group, n=689); lean snorer (n=195); obese, non-snorer, (n=189); and obese snorer (n=217). Compared to lean, non-snorers, both lean and obese snorers had significantly increased ORs for gestational hypertension: lean snorers OR 2.82, 95%CI 1.42–5.59, p=0.003, and obese snorers OR 2.39, 95%CI 1.22–4.71, p=0.012. Obese non-snorers were not at increased risk of gestational hypertension, OR 1.74, 95%CI 0.81–3.5, p=0.15. .
Adjusted odds ratio, and 95%CI of maternal morbidity by obesity and snoring status
Compared to lean non-snorers, only obese snorers had increased risk for pre-eclampsia; OR 1.58, 95%CI 1.01–2.78 p=0.05; . Conversely, only obese women, regardless of snoring status, had increased risk for gestational diabetes; OR 2.31, 95%CI 1.01–5.36, p=0.05 for obese non-snorers and OR 4.12, 95%CI 1.78–9.52, p=0.001 for obese snorers; .
If snoring plays a causative role in hypertension, then the PAR% suggests that 15.0% of gestational hypertension and 14.4% of pre-eclampsia in this population could be ameliorated by elimination of snoring. Similarly, 18.7% of gestational hypertension and 11.6% of pre-eclampsia could be ameliorated by elimination of pregnancy-onset snoring.
A total of 1.2% of women reported witnessed apneas. Snorers (chronic or pregnancy-onset) were more likely than non-snorers to endorse this; 3.0% vs. 0.4% respectively; p<0.001. Women with gestational hypertension, pre-eclampsia, or gestational diabetes were no more likely to report apnea than women without these conditions. However, the total number of women who reported apnea was small, precluding use of regression models.
This is the first large, prospective study to demonstrate that pregnancy-onset snoring confers significant risk to maternal cardiovascular health. These novel findings strongly implicate a role not only for snoring in general but, more specifically, for pregnancy-onset snoring in both gestational hypertension and pre-eclampsia. Furthermore, the PAR% suggests that if snoring plays a causal role in maternal hypertension, approximately 12–19% of hypertensive disorders during pregnancy might be ameliorated through treatment of snoring and any associated SDB. In contrast, the data did not suggest any independent role for snoring in gestational diabetes.
Notably, weight gain in excess of IOM recommendations, but not pre-pregnancy BMI, was found to play an independent role in gestational hypertension. Both pre-pregnancy BMI and excessive weight gain were independent predictors of pre-eclampsia. Although excessive weight gain is a known risk factor for post-partum weight retention,25
this is the first study to show its independent relationship to cardiovascular outcomes. This novel finding could have important implications for clinical care.
Our findings support and extend earlier observations that the frequency of snoring increases throughout pregnancy, peaks in the third trimester,4
and is a risk for hypertension.14, 15, 23, 26, 27
However, none of the previous studies investigated the impact of incident habitual snoring on maternal outcomes. Previous studies suggest that 14–23% of pregnant women habitually snore, compared to 4% of non-pregnant women,5, 23
although more recent estimates suggest a considerably higher proportion6,15
particularly in pre-eclampsia.6
Potential explanations of the lower frequencies in earlier studies are that only women attending low risk clinics who had vaginal deliveries were included5
and obesity was relatively infrequent in some populations.5, 23
Intriguing preliminary data suggest that new snoring during pregnancy is associated with increased erythropoesis and consequently increased levels of nucleated red blood cells in the umbilical cord.28
Erythropoesis occurs during periods of hypoxia, and conditions such as uterine growth restriction and maternal hypertension are associated with elevated counts.29
These findings in combination with our own implicate pregnancy-onset snoring as a particular concern.
Contrary to recent reports15, 30, 31
we did not find that snoring is associated with gestational diabetes. This discrepancy may be explained in part by different methodologies including recruitment of postpartum women,15
few women with the variable of interest,30, 31
and the lack of information about pre-pregnancy BMI.15
Nonetheless, the role of sleep in glucose control during pregnancy merits further investigation.
Although the pathogenesis of pre-eclampsia is not completely understood, the biological pathways include endothelial dysfunction, oxidative stress, and inflammation, with obesity being a major risk factor. The pathogenic process likely originates in the placenta during early pregnancy with abnormal implantation and vasculature development, leading to oxidative stress and inflammation with subsequent release of anti-angiogenic factors and widespread endothelial dysfunction.32
Of note, the mechanisms of sleep disruption that affect cardiovascular morbidity in non-pregnant individuals are remarkably similar to the biological pathways for pre-eclampsia, with strong evidence for oxidative stress, inflammation, sympathetic nervous systemic activation, endothelial dysfunction, dyslipidemia, and obesity as major factors in the pathophysiology of cardiovascular morbidity in SDB.33
These shared mechanistic pathways have been reviewed recently.34
Considering these overlapping risk factors, the finding that pregnancy-onset, but not chronic, snoring was associated with gestational hypertension and pre-eclampsia may be surprising. Sleep disruption and the consequent inflammatory cascade in early pregnancy may interfere with normal placental implantation,35
although this may not completely explain our findings since the majority of women with pregnancy-onset snoring started in their second or third trimesters. The possibility remains, however, that pregnancy-onset snoring could exacerbate underlying inflammatory processes and enhance underlying cardiovascular dysfunction. Another possibility is that fluid shifts36
or inflammation promotes the appearance of SDB. However, preliminary data show that treatment of SDB during pregnancy may improve blood pressure,37, 38
suggesting that SDB is more likely to contribute to hypertensive disease, rather than result from it or from a third process that causes both hypertension and SDB.
Key strengths of the present study include the largest sample size to date, prospective design, high response rate, adjustment for other known risk factors for gestational hypertension/pre-eclampsia (particularly a previous and family history of these conditions), and a population pool representative of other major medical centers. The University of Michigan Health System is the largest of only two in Washtenaw County that provide maternity services. Therefore, selection bias of a tertiary referral center should be minimal.
Use of symptom-based screening not yet validated against PSG in pregnant women could be a limitation. However, the major goal was to validate the utility of snoring directly as a predictor of maternal outcomes. Self-report of snoring is strongly and reliably associated with the PSG-derived AHI8, 20
and our own data confirm this in pregnancy.39
The present large-sample focus on snoring is also a strength of the study design as queries about snoring can be readily adopted in clinical practice for little expense. However, elucidation of mechanisms that underlie any association between SDB and pregnancy outcomes require investigation in PSG-studies that allow assessment of whether respiratory effort, airflow limitation, sleep fragmentation, or gas exchange abnormalities best predict adverse outcomes and treatment response.
It is possible that some recall bias occurred with regards to snoring duration. Although information was obtained prospectively, women may have been less aware of their pre-pregnancy snoring. A further limitation is the temporal relationship between snoring onset and time of a diagnosis of gestational hypertension, pre-eclampsia, or gestational diabetes. This study cannot prove the direction of this relationship but clearly suggests an independent association.
In conclusion, pregnancy-onset rather than chronic snoring is independently associated with gestational hypertension and pre-eclampsia but not gestational diabetes. Rather than a multi-item composite SDB screen, two simple questions about snoring and the timing of its appearance could be an effective strategy in busy clinical settings to assist in identification of pregnant women at high risk for hypertensive disorders. These findings reinforce the need for a randomized controlled trial to investigate the impact of treatment interventions on maternal hypertension.