Pregnancy-onset habitual snoring, gestational hypertension, and preeclampsia: prospective cohort study.
ABSTRACT: This study aimed to prospectively examine the impact of chronic vs pregnancy-onset habitual snoring on gestational hypertension, preeclampsia, and gestational diabetes.Third-trimester pregnant women were recruited from a large, tertiary medical center from March 2007 through December 2010 and screened for the presence and duration of habitual snoring, as a known marker for sleep-disordered breathing. Clinical diagnoses of gestational hypertension, preeclampsia, and gestational diabetes were obtained.Of 1719 pregnant women, 34% reported snoring, with 25% reporting pregnancy-onset snoring. After adjusting for confounders, pregnancy-onset, but not chronic, snoring was independently associated with gestational hypertension (odds ratio, 2.36; 95% confidence interval, 1.48-3.77; P < .001) and preeclampsia (odds ratio, 1.59; 95% confidence interval, 1.06-2.37; P = .024) but not gestational diabetes.New-onset snoring during pregnancy is a strong risk factor for gestational hypertension and preeclampsia. In view of the significant morbidity and health care costs associated with hypertensive diseases of pregnancy, simple screening of pregnant women may have clinical utility.
Project description:<h4>Objective</h4>To assess the frequency of obstructive sleep apnoea among women with and without hypertensive disorders of pregnancy.<h4>Design</h4>Cohort study.<h4>Setting</h4>Obstetric clinics at an academic medical centre.<h4>Population</h4>Pregnant women with hypertensive disorders (chronic hypertension, gestational hypertension, or pre-eclampsia) and women who were normotensive.<h4>Methods</h4>Women completed a questionnaire about habitual snoring and underwent overnight ambulatory polysomnography.<h4>Main outcome measures</h4>The presence and severity of obstructive sleep apnoea.<h4>Results</h4>Obstructive sleep apnoea was found among 21 of 51 women with hypertensive disorders (41%), but in only three of 16 women who were normotensive (19%, chi-square test, P=0.005). [Author correction added on 16 June 2014, after first online publication: Results mentioned in the abstract were amended.] Non-snoring women with hypertensive disorders typically had mild obstructive sleep apnoea, but >25% of snoring women with hypertensive disorders had moderate to severe obstructive sleep apnoea. Among women with hypertensive disorders, the mean apnoea/hypopnoea index was substantially higher in snorers than in non-snorers (19.9±34.1 versus 3.4±3.1, P=0.013), and the oxyhaemoglobin saturation nadir was significantly lower (86.4±6.6 versus 90.2±3.5, P=0.021). Among women with hypertensive disorders, after stratification by obesity, the pooled relative risk for obstructive sleep apnoea in snoring women with hypertension compared with non-snoring women with hypertension was 2.0 (95% CI 1.4-2.8).<h4>Conclusions</h4>Pregnant women with hypertension are at high risk for unrecognised obstructive sleep apnoea. Although longitudinal and intervention studies are urgently needed, given the known relationship between obstructive sleep apnoea and hypertension in the general population, it would seem pertinent that hypertensive pregnant women who snore should be tested for obstructive sleep apnoea, a condition believed to cause or promote hypertension.
Project description:Preeclampsia is a pregnancy-specific disorder of new-onset hypertension linked to placental ischemia. While obesity is a major risk factor for preeclampsia, not all obese pregnant women develop pregnancy-induced hypertension or preeclampsia. Previously, we reported that placental ischemia-induced hypertension is dependent upon intact signaling of the sympathetic nervous system. Moreover, in various models of obesity, blockade of MC4R (melanocortin-4 receptor) signaling protects against the development of hypertension via suppression of the sympathetic nervous system. Less is known about this pathway during obese pregnancy. Although blockade of MC4R may lead to increased body weight during pregnancy, we tested the hypothesis that placental ischemia-induced hypertension is attenuated in obese MC4R-deficient pregnant rats. On gestational day 14, MC4R wild-type or heterozygous-deficient (MC4R-def) rats were subjected to chronic placental ischemia via the reduced uterine perfusion pressure procedure or Sham surgery then examined on gestational day 19. In Sham MC4R-def versus Sham wild-type pregnant rats, there was increased body weight, fat mass, and circulating leptin levels but they had similar fetus weights. Reduced uterine perfusion pressure reduced fetus weights in both strains. Reduced uterine perfusion pressure increased blood pressure in wild-type rats but this response was significantly attenuated in MC4R-def rats, although blood pressure was elevated in Sham MC4R-def over Sham wild-type. These data indicate that while obese MC4R-def pregnant rats have higher blood pressure during pregnancy, placental ischemia-induced hypertension is attenuated in obese MC4R-def pregnant rats. Thus, obese women with abnormal MC4R signaling may be less susceptible to the development of placental ischemia-induced hypertension.
Project description:OBJECTIVE:We aimed to examine the ELABELA levels at different stages of pregnancy among normotensive controls and women with hypertensive disorders of pregnancy (HDP). STUDY DESIGN:A total of 336 blood samples of 169 women were collected from pre-pregnancy, the first, second, and third trimesters. Women were divided into the following six groups: 1) non-pregnant healthy women; 2) healthy pregnant controls; 3) chronic hypertension; 4) gestational hypertension; 5) preeclampsia; and 6) preeclampsia superimposed on chronic hypertension. ELABELA plasma concentrations were measured by human ELA Elisa Kit (Peninsula Laboratories International, Inc. USA). Kruskal-Wallis test was used to test whether ELABELA level in each type of HDP differed from that in gestational week-matched normotensive controls. MAIN OUTCOME MEASURES:Hypertensive disorders of pregnancy. RESULTS:In the first trimester, patients with gestational hypertension had higher ELABELA level than gestational week-matched normotensive controls [median (ng/ml): 31.9, (IQR (ng/ml): 16.3, 47.6) vs. 19.7 (13.7, 23.2), p?=?0.03]. In the second trimester, the levels were 49.2 (32.2, 69.1) vs 24.0 (13.0, 32.6) (p?=?0.002), respectively. The level for gestational hypertensive women in the third trimester did not differ significantly from that of normotensive women [43.8 (30.8, 62.7) vs 25.0 (12.3, 74.0), p?=?0.82]. The ELABELA levels were similar between preeclamptic women and normotensive controls throughout pregnancy. CONCLUSIONS:Maternal blood ELABELA levels in the first and second trimesters were elevated in women who developed gestational hypertension late in pregnancy, but the ELABELA level bears no significant relationship with preeclampsia during any stage of pregnancy.
Project description:Hypertensive disorders in pregnancy (HDPs) are leading perinatal diseases. Using a national cohort of 2,043,182 pregnant women in China, we evaluated the association between ambient temperatures and HDP subgroups, including preeclampsia or eclampsia, gestational hypertension, and superimposed preeclampsia. Under extreme temperatures, very cold exposure during preconception (12 weeks) increases odds of preeclampsia or eclampsia and gestational hypertension. Compared to preconception, in the first half of pregnancy, the impact of temperature on preeclampsia or eclampsia and gestational hypertension is opposite. Cold exposure decreases the odds, whereas hot exposure increases the odds. Under average temperatures, a temperature increase during preconception decreases the risk of preeclampsia or eclampsia and gestational hypertension. However, in the first half of pregnancy, temperature is positively associated with a higher risk. No significant association is observed between temperature and superimposed preeclampsia. Here we report a close relationship exists between ambient temperature and preeclampsia or eclampsia and gestational hypertension.
Project description:OBJECTIVES:Preeclampsia is divided into early-onset (delivery before 34 weeks of gestation) and late-onset (delivery at or after 34 weeks) subtypes, which may rise from different etiopathogenic backgrounds. Early-onset disease is associated with placental dysfunction. Late-onset disease develops predominantly due to metabolic disturbances, obesity, diabetes, lipid dysfunction, and inflammation, which affect endothelial function. Our aim was to use cluster analysis to investigate clinical factors predicting the onset and severity of preeclampsia in a cohort of women with known clinical risk factors. METHODS:We recruited 903 pregnant women with risk factors for preeclampsia at gestational weeks 12+0-13+6. Each individual outcome diagnosis was independently verified from medical records. We applied a Bayesian clustering algorithm to classify the study participants to clusters based on their particular risk factor combination. For each cluster, we computed the risk ratio of each disease outcome, relative to the risk in the general population. RESULTS:The risk of preeclampsia increased exponentially with respect to the number of risk factors. Our analysis revealed 25 number of clusters. Preeclampsia in a previous pregnancy (n = 138) increased the risk of preeclampsia 8.1 fold (95% confidence interval (CI) 5.7-11.2) compared to a general population of pregnant women. Having a small for gestational age infant (n = 57) in a previous pregnancy increased the risk of early-onset preeclampsia 17.5 fold (95%CI 2.1-60.5). Cluster of those two risk factors together (n = 21) increased the risk of severe preeclampsia to 23.8-fold (95%CI 5.1-60.6), intermediate onset (delivery between 34+0-36+6 weeks of gestation) to 25.1-fold (95%CI 3.1-79.9) and preterm preeclampsia (delivery before 37+0 weeks of gestation) to 16.4-fold (95%CI 2.0-52.4). Body mass index over 30 kg/m2 (n = 228) as a sole risk factor increased the risk of preeclampsia to 2.1-fold (95%CI 1.1-3.6). Together with preeclampsia in an earlier pregnancy the risk increased to 11.4 (95%CI 4.5-20.9). Chronic hypertension (n = 60) increased the risk of preeclampsia 5.3-fold (95%CI 2.4-9.8), of severe preeclampsia 22.2-fold (95%CI 9.9-41.0), and risk of early-onset preeclampsia 16.7-fold (95%CI 2.0-57.6). If a woman had chronic hypertension combined with obesity, gestational diabetes and earlier preeclampsia, the risk of term preeclampsia increased 4.8-fold (95%CI 0.1-21.7). Women with type 1 diabetes mellitus had a high risk of all subgroups of preeclampsia. CONCLUSION:The risk of preeclampsia increases exponentially with respect to the number of risk factors. Early-onset preeclampsia and severe preeclampsia have different risk profile from term preeclampsia.
Project description:BACKGROUND:Sleep-disordered breathing (SDB) is linked to adverse pregnancy outcomes. However, little is known about the association of SDB with timing of delivery. We examined the association of snoring frequency, a key SDB marker, and snoring intensity, a correlate of SDB severity, with time-to-delivery among a cohort of pregnant women. METHODS:In this prospective cohort study, 1483 third trimester pregnant women were recruited from the University of Michigan prenatal clinics. Women completed a questionnaire about their sleep, and demographic and pregnancy information was abstracted from medical charts. After exclusion of those with hypertension or diabetes, 954 women were classified into two groups by their snoring onset timing, chronic or pregnancy-onset. Within each of these groups, women were divided into four groups based on their snoring frequency and intensity: non-snorers; infrequent-quiet; frequent-quiet; or frequent-loud snorers. Cox proportional hazard regression models were used to investigate the association between snoring frequency and intensity and time-to-delivery, adjusting for maternal characteristics. RESULTS:Chronic snoring was reported by half of the pregnant women, and of those, 7% were frequent-loud snorers. Deliveries before 38 weeks' gestation are completed occurred among 25% of women with chronic, frequent-loud snoring. Compared with pre-pregnancy non-snorers, women with chronic frequent-loud snoring had an increased hazard ratio for delivery (adjusted hazard ratio 1.60, 95% confidence interval 1.04, 2.45). CONCLUSIONS:Snoring frequency and intensity is associated with time-to-delivery in women absent of hypertension or diabetes. Frequent-loud snoring may have a clinical utility to identify otherwise low-risk women who are likely to deliver earlier.
Project description:Background:Due to the high prevalence in pregnant women and potential association with pregnancy complications or perinatal outcomes, sleep-disordered breathing (SDB) has become an increasing concern. Methods:Pubmed and Embase were retrieved from inception until 2017 to conduct a meta-analysis to explore the association of SDB and several outcomes during gestation. A stratified analysis differentiated by the type of SDB [snoring alone/obstructive sleep apnea (OSA)] was also performed. Pooled odds ratios were produced for binary outcomes. Weighted mean differences were also produced for continuous outcomes. Sensitivity analysis was performed to identify the impact of individual studies on summary results and estimation of publication bias was performed by funnel plot. Results:35 studies with a total of 56,751,837 subjects were included. SDB during pregnancy was associated with a significantly increased risk of gestational diabetes mellitus (GDM), pregnancy-induced hypertension (PIH), and preeclampsia (PEC), but not significantly associated with fetal maternal outcomes, namely APGAR score and birth weight. Moreover, OSA was linked with an increasing risk of GDM, PIH, PEC and preterm birth while snoring appeared to increase the risk of GDM, PIH, and PEC. Conclusion:The finding provided potential evidence for association between SDB and adverse perinatal outcomes. SDB increased the risk of some pregnancy complications while its influence to fetal outcomes was not clear.
Project description:Copeptin, a surrogate biomarker of vasopressin, has been associated with renal function decline and may serve as a useful early biomarker for preeclampsia. We measured serum copeptin using samples collected longitudinally during pregnancy among unaffected controls (n=136) and cases of preeclampsia (n=169), gestational diabetes mellitus (n=92), gestational hypertension (n=101), and preterm birth (n=86) in the Calcium for Preeclampsia Prevention trial (1992-1995). Preeclampsia and gestational hypertension were defined as having a diastolic blood pressure?90 mm Hg on 2 occasions with and without proteinuria, respectively. The risk of pregnancy complications associated with copeptin was estimated by logistic regression adjusting for maternal age, race, body mass index, insurance status, marital status, current smoking, and clinical site. Baseline copeptin levels, at mean 16 weeks of gestation, were associated with increased preeclampsia risk (adjusted odds ratios and 95% confidence interval being 1.55 per log unit; 1.03-2.31) when compared with controls (P=0.03). The association was stronger among cases diagnosed before 37 weeks (1.86; 1.08-3.20) than those diagnosed later (1.45; 0.91-2.32). Copeptin levels rose with increasing gestational age in both cases and controls but remained significantly higher among those who were diagnosed with preeclampsia. Differences in levels of copeptin between cases and controls became more apparent closer to time of diagnosis. No significant associations were found for gestational hypertension without proteinuria, gestational diabetes mellitus, or preterm birth without preeclampsia. Copeptin levels are elevated in pregnant women before diagnosis of preeclampsia with elevation specific to this pregnancy complication rather than hypertension alone.
Project description:Preeclampsia is associated with oxidative stress, which is suspected to play a role in hypertension, placental ischemia, and fetal demise associated with the disease. Various cellular sources of oxidative stress, such as neutrophils, monocytes, and CD4(+) T cells have been suggested as culprits in the pathophysiology of preeclampsia. The objective of this study was to examine a role of circulating and placental CD4(+) T cells in oxidative stress in response to placental ischemia during pregnancy. CD4(+) T cells and oxidative stress were measured in preeclamptic and normal pregnant women, placental ischemic and normal pregnant rats, and normal pregnant recipient rats of placental ischemic CD4(+) T cells. Women with preeclampsia had significantly increased circulating (P=0.02) and placental CD4(+) T cells (P=0.0001); lymphocyte secretion of myeloperoxidase (P=0.004); and placental reactive oxygen species (P=0.0004) when compared with normal pregnant women. CD4(+) T cells from placental ischemic rats cause many facets of preeclampsia when injected into normal pregnant recipient rats on gestational day 13. On gestational day 19, blood pressure increased in normal pregnant recipients of placental ischemic CD4(+) T cells (P=0.002) compared with that in normal pregnant rats. Similar to preeclamptic patients, CD4(+) T cells from placental ischemic rats secreted significantly more myeloperoxidase (P=0.003) and induced oxidative stress in cultured vascular cells (P=0.003) than normal pregnant rat CD4(+)Tcells. Apocynin, a nicotinamide adenine dinucleotide phosphate inhibitor, attenuated hypertension and all oxidative stress markers in placental ischemic and normal pregnant recipient rats of placental ischemic CD4(+)Tcells (P=0.05). These data demonstrate an important role for CD4(+) T cells in mediating another factor, oxidative stress, to cause hypertension during preeclampsia.
Project description:Podocyturia, the shedding of live podocytes, is present at delivery in women with preeclampsia. The aim of this study was to test whether podocyturia is present earlier in pregnancy and predicts for preeclampsia. We also aimed to compare test characteristics of podocyturia with those of angiogenic factors previously implicated in the pathogenesis of this disorder. We prospectively enrolled 315 women who provided blood and urine samples at the end of the second trimesters of their pregnancies (median, 27 gestational weeks) and within 24 hours of their deliveries (median, 39.5 gestational weeks). Blood samples were analyzed for angiogenic markers, including placental growth factor, the soluble receptor fms-like tyrosine kinase receptor-1 for vascular endothelial growth factor, and endoglin. The urine sediments were analyzed for podocytes, identified by staining for podocin after culturing the urinary sediments for 24 hours. This analysis included all women who developed preeclampsia (n=15), gestational hypertension (n=15), and a subsample of women who remained normotensive throughout pregnancy (n=44), matched for maternal age and number of previous pregnancies to those who developed preeclampsia. At the second trimester collection, all women who developed preeclampsia had podocyturia, compared with none of those who remained normotensive or were diagnosed with gestational hypertension. Podocyturia in the second trimester had a significantly greater sensitivity and specificity for the subsequent diagnosis of preeclampsia than any single angiogenic marker or a combination thereof. Screening for podocyturia at the end of the second trimester may allow for accurate identification of pregnant women at risk for preeclampsia.