Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia.
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ABSTRACT: Background and purpose
Preeclampsia affects 3% to 8% of pregnancies and increases risk of pregnancy-associated stroke (PAS). Data are limited on which women with preeclampsia are at highest risk for PAS.Methods
Using billing data from the 2003 to 2012 New York State Department of Health inpatient database, we matched women with preeclampsia and PAS 1:3 to preeclamptic controls based on age and race/ethnicity. Pre-defined PAS risk factors included pregnancy complications, infection present on admission, vascular risk factors, prothrombotic states, and coagulopathies. We constructed multivariable conditional logistic regression models to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) for independent risk factors for PAS.Results
Among women aged 12 to 55 years admitted to New York State hospitals for any reason during the study period (n=3 373 114), 88 857 had preeclampsia, and 197 of whom (0.2%) had PAS. In multivariable analysis, women with preeclampsia and stroke were more likely than controls to have severe preeclampsia or eclampsia (OR, 7.2; 95% confidence interval [CI], 4.6-11.3), infections present on admission (OR, 3.0; 95% CI, 1.6-5.8), prothrombotic states (OR, 3.5; 95% CI, 1.3-9.2), coagulopathies (OR, 3.1; 95% CI, 1.3-7.1), or chronic hypertension (OR, 3.2; 95% CI, 1.8-5.5). Additional analyses matched and stratified by severity of preeclampsia confirmed these results.Conclusions
Infections, chronic hypertension, coagulopathies, and underlying prothrombotic conditions increase PAS risk in women with preeclampsia. These women may warrant closer monitoring.
SUBMITTER: Miller EC
PROVIDER: S-EPMC5539968 | biostudies-literature | 2017 Jul
REPOSITORIES: biostudies-literature
Publications
Risk Factors for Pregnancy-Associated Stroke in Women With Preeclampsia.
Miller Eliza C EC Gatollari Hajere J HJ Too Gloria G Boehme Amelia K AK Leffert Lisa L Marshall Randolph S RS Elkind Mitchell S V MSV Willey Joshua Z JZ
Stroke 20170525 7
<h4>Background and purpose</h4>Preeclampsia affects 3% to 8% of pregnancies and increases risk of pregnancy-associated stroke (PAS). Data are limited on which women with preeclampsia are at highest risk for PAS.<h4>Methods</h4>Using billing data from the 2003 to 2012 New York State Department of Health inpatient database, we matched women with preeclampsia and PAS 1:3 to preeclamptic controls based on age and race/ethnicity. Pre-defined PAS risk factors included pregnancy complications, infectio ...[more]
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Project description:ImportanceA genetic contribution to preeclampsia susceptibility has been established but is still incompletely understood.ObjectiveTo disentangle the underlying genetic architecture of preeclampsia and preeclampsia or other maternal hypertension during pregnancy with a genome-wide association study (GWAS) of hypertensive disorders of pregnancy.Design, setting, and participantsThis GWAS included meta-analyses in maternal preeclampsia and a combination phenotype encompassing maternal preeclampsia and preeclampsia or other maternal hypertensive disorders. Two overlapping phenotype groups were selected for examination, namely, preeclampsia and preeclampsia or other maternal hypertension during pregnancy. Data from the Finnish Genetics of Pre-eclampsia Consortium (FINNPEC, 1990-2011), Finnish FinnGen project (1964-2019), Estonian Biobank (1997-2019), and the previously published InterPregGen consortium GWAS were combined. Individuals with preeclampsia or other maternal hypertension during pregnancy and control individuals were selected from the cohorts based on relevant International Classification of Diseases codes. Data were analyzed from July 2020 to February 2023.ExposuresThe association of a genome-wide set of genetic variants and clinical risk factors was analyzed for the 2 phenotypes.ResultsA total of 16 743 women with prior preeclampsia and 15 200 with preeclampsia or other maternal hypertension during pregnancy were obtained from FINNPEC, FinnGen, Estonian Biobank, and the InterPregGen consortium study (respective mean [SD] ages at diagnosis: 30.3 [5.5], 28.7 [5.6], 29.7 [7.0], and 28 [not available] years). The analysis found 19 genome-wide significant associations, 13 of which were novel. Seven of the novel loci harbor genes previously associated with blood pressure traits (NPPA, NPR3, PLCE1, TNS2, FURIN, RGL3, and PREX1). In line with this, the 2 study phenotypes showed genetic correlation with blood pressure traits. In addition, novel risk loci were identified in the proximity of genes involved in the development of placenta (PGR, TRPC6, ACTN4, and PZP), remodeling of uterine spiral arteries (NPPA, NPPB, NPR3, and ACTN4), kidney function (PLCE1, TNS2, ACTN4, and TRPC6), and maintenance of proteostasis in pregnancy serum (PZP).Conclusions and relevanceThe findings indicate that genes related to blood pressure traits are associated with preeclampsia, but many of these genes have additional pleiotropic effects on cardiometabolic, endothelial, and placental function. Furthermore, several of the associated loci have no known connection with cardiovascular disease but instead harbor genes contributing to maintenance of successful pregnancy, with dysfunctions leading to preeclampsialike symptoms.
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Project description:BACKGROUND: Preeclampsia (PE) is a multi-causal disease characterized by the development of hypertension and proteinuria in the second half of pregnancy. Multiple risk factors have been associated with the development of PE. Moreover, it is known that these risk factors vary between populations from developed and developing countries. The aim of this study is to identify which risk factors are associated with the development of preeclampsia (PE) among Colombian women. METHODS: A multi-centre case-control study was conducted between September 2006 and July 2009 in six Colombian cities. Cases included women with PE (n = 201); controls were aged-matched pregnant women (n = 201) without cardiovascular or endocrine diseases for a case-control ratio of 1:1. A complete medical chart, physical examination and biochemical analysis were completed before delivery. Multivariable logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) of potential risk factors associated with PE. RESULTS: The presence of factors present in the metabolic syndrome cluster such as body mass index >31 Kg/m2 (OR = 2.18; 1.14-4.14 95% CI), high-density lipoprotein <1.24 mmol/L (OR = 2.42; 1.53-3.84 95% CI), triglycerides >3.24 mmol/L (OR = 1.60; 1.04-2.48 95% CI) and glycemia >4.9 mmol/L (OR = 2.66; 1.47-4.81 95%CI) as well as being primigravidae (OR = 1.71; 1.07-2.73 95% CI) were associated with the development of PE, after adjusting for other variables. CONCLUSION: Factors present in the cluster of metabolic syndrome and primigravidity were associated with a greater risk of PE among Colombian women. Understanding the role of this cluster of risk factors in the development of PE is of crucial importance to prevent PE and remains to be determined.
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Project description:ImportancePreeclampsia is a leading cause of maternal and perinatal morbidity and mortality worldwide. Within-country studies have reported racial differences in the presentation and outcome, but little is known about differences between countries.ObjectiveTo compare preeclampsia prevalence, risk factors, and pregnancy outcomes between the Swedish and Chinese populations.Design, setting, and participantsThis cross-sectional study compared deliveries from the Swedish national Medical Birth Register (2007-2012) and the China Labor and Delivery Survey (2015-2016). The Swedish Medical Birth Register records maternal, pregnancy, and neonatal information for nearly all deliveries in Sweden. The China Labor and Delivery Survey was conducted throughout China, and these data were reweighted to enable national comparisons. Participants included 555 446 deliveries from Sweden and 79 243 deliveries from China. Data management and analysis was conducted from November 2018 to August 2020 and revised in February to March 2021.ExposuresMaternal characteristics, parity, multiple gestation, chronic and gestational diabetes, cesarean delivery.Main outcomes and measuresPreeclampsia prevalence and risk factors, overall and for mild and severe forms and rates of adverse neonatal outcomes compared with pregnancies with no gestational hypertension.ResultsThe 555 446 Swedish pregnancies and 79 243 Chinese pregnancies had mean (SD) maternal age of 30.9 (5.3) years and 28.6 (4.6) years, respectively. The overall prevalence of preeclampsia was similar in Sweden and China, 16 068 (2.9%) and 1803 (2.3%), respectively, but with 5222 cases (32.5%) considered severe in Sweden and 1228 cases (68.1%) considered severe in China. Obesity (defined as BMI ≥28 in China and BMI ≥30 in Sweden) was a stronger risk factor in China compared with Sweden (China: odds ratio [OR], 5.12; 95% CI, 3.82-6.86; Sweden: OR, 3.49; 95% CI, 3.31-3.67). Nulliparity had a much stronger association with severe preeclampsia in Sweden compared with China (Sweden: OR, 3.91; 95% CI, 3.65-4.18; China: OR, 1.65; 95% CI, 1.20-2.25). The overall stillbirth rate for singleton in China was more than 3-fold higher than in Sweden (846/77 512[1.1%] vs 1753/547 219 [0.3%], P < .001), and 10-fold higher among women with preeclampsia (66/1652 [4.6%] vs 60/14 499[0.4%], P < .001).Conclusions and relevanceIn this study, the prevalence rates of preeclampsia in Sweden and China were similar, but women in China had more severe disease and worse pregnancy outcomes than women in Sweden. The associations of obesity and nulliparity with preeclampsia suggest a role for lifestyle and health care factors but may reflect some differences in pathophysiology. These findings have relevance for current efforts to identify high-risk pregnancies and early serum markers because the value of risk prediction models and biomarkers may be population specific.
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Project description:ObjectiveIt remains unclear what roles placenta-originated angiogenic factors play in the pathogenesis of preeclampsia among hypertensive women. We compared maternal soluble fms-like tyrosine kinase 1 (sFlt-1) and placental growth factor (PlGF) levels throughout pregnancy in women with normal blood pressure (BP), elevated BP and hypertension in early pregnancy and their risks of developing preeclampsia.DesignA prospective cohort study.SettingKK Women's and Children's Hospital, Singapore.Participants923 women with singleton pregnancy <14 weeks of gestation were included in the prospective Neonatal and Obstetrics Risks Assessment cohort between September 2010 and October 2014. Systolic, diastolic, mean arterial blood pressure (MAP) were measured at 11-14 weeks.Primary and secondary outcomesMaternal serum sFlt-1, PlGF and sFlt-1/PlGF ratio were tested at 11-14, 18-22, 28-32 and 34 weeks onwards of gestation. Preeclampsia was main pregnancy outcome.ResultsWomen were divided based on their BP in early pregnancy: normal (n=750), elevated BP (n=98) and hypertension (n=75). Maternal sFlt-1 levels and sFlt-1/PlGF ratios were higher in hypertensive women throughout pregnancy, but maternal PlGF levels were not significantly lower. Rise in maternal systolic, diastolic BP and MAP at 11-14 weeks were significantly associated with higher sFlt-1/PlGF ratios during pregnancy. A 10 mm Hg increase in MAP was associated with a 5.6-fold increase in risk of preterm preeclampsia and a 3.3-fold increase in risk of term preeclampsia, respectively.ConclusionWomen with elevated BP in early pregnancy already had a higher sFlt-1/PlGF ratio in early gestation and throughout pregnancy, and an increased risk of preeclampsia. In contrast, PlGF levels in these women remained normal.
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Project description:Background and Purpose- In the United States, black Americans exhibit a greater risk of stroke and burden of stroke risk factors than whites; however, it is unclear whether these stroke risk factors influence stroke risk differently across racial groups. Methods- In total, 126 018 participants of the Women's Health Initiative (11 389 black and 114 629 white women), free of stroke and coronary heart disease at baseline (1994-1998), were followed through 2010. Participants completed baseline clinical exams with standardized measurements of blood pressure and anthropometrics, medication inventory and self-reported questionnaires on sociodemographics, behaviors/lifestyle, and medical history. Incident total, ischemic and hemorrhagic strokes were updated annually through questionnaires with medical record confirmation. Rate differences (per 100 000 person-years) and hazard ratios (HR) based on multivariable Cox models and were estimated. Results- Over a median of 13 years, 4344 stroke events were observed. Absolute incidence rates were higher in black than white women in each age group. In age-adjusted analyses, the risk of stroke was significantly higher among black compared with white women (HR=1.47, 95% CI, 1.33-1.63); adjustment for stroke risk factors, which may be on the causal pathway, attenuated the estimate. Racial disparities were greatest among women 50 to <60 years (HR=3.48; 95% CI, 2.31-5.26; rate difference =99) and diminished with increasing age (60 to <70 HR=1.80; 95% CI, 1.50-2.16; rate difference =107; ≥70 years: HR=1.26; 95% CI, 1.10-1.43; rate difference =87; Pinteraction <0.001). Black women 50 to <60 years remained at significantly higher risk than white women after adjustment for stroke risk factors (HR=1.76; 95% CI, 1.09-2.83). Conclusions- There was a moderately greater risk of total stroke among black compared with white women; however, racial disparities were greatest among women aged 50 to <60 years. Interventions targeted at younger black women may provide the greatest benefit in reducing disparities.
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Project description:Preeclampsia is a major cause of maternal and fetal morbidity. Emerging research shows an association with environmental exposures. The present aim was to investigate associations between early pregnancy serum levels of perfluoroalkyl substances (PFAS) and preeclampsia. Within the Swedish SELMA study, eight PFAS were measured at median 10 gestational weeks and cases of preeclampsia were postnatally identified from registers. Associations between individual PFAS and preeclampsia were assessed, adjusting for parity, age, weight and smoking. Out of 1,773 women in the study group, 64 (3.6%), developed preeclampsia. A doubling of PFOS and PFNA exposure, corresponding to an inter-quartile increase, was associated with an increased risk for preeclampsia of about 38-53% respectively. Serum PFOS within the highest quartile was associated with an odds ratio of 2.68 (CI 95%: 1.17-6.12), equal to the increased risk associated with nulliparity, when compared to exposure in the first quartile. The same associations were identified, although with higher risk estimates, in analyses restricted to nulliparous women. For other PFAS, there were no associations. In conclusion and consistent with limited previous research only on PFOS, increasing serum levels of PFOS and PFNA during early pregnancy were associated with a clinically relevant risk of preeclampsia, adjusting for established confounders.
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Project description:An episode of clinically recovered acute kidney injury (r-AKI) has been identified as a risk factor for future hypertension and cardiovascular disease. Our objective was to assess whether r-AKI was associated with future preeclampsia and other adverse pregnancy outcomes and to identify whether severity of AKI or time interval between AKI and pregnancy was associated with pregnancy complications. We conducted a retrospective cohort study of women who delivered infants between 1998 and 2016 at Massachusetts General Hospital. AKI was defined using the 2012 Kidney Disease Improving Global Outcomes laboratory criteria with subsequent clinical recovery (estimate glomerular filtration rate, >90 mL/min per 1.73 m2 before conception). AKI was further classified by severity (Kidney Disease Improving Global Outcomes stages 1-3) and time interval between AKI episode and the start of pregnancy. Women with r-AKI had an increased rate of preeclampsia compared with women without previous r-AKI (22% versus 9%; P<0.001). Infants of women with r-AKI were born earlier (gestational age, 38.2±3.0 versus 39.0±2.2 weeks; P<0.001) and were more likely to be small for gestational age (9% versus 5%; P=0.002). Increasing severity of r-AKI was associated with increased risk of preeclampsia for stages 2 and 3 AKI (adjusted odds ratio, 3.5; 95% confidence interval, 2.1-5.7 and adjusted odds ratio, 6.5; 95% confidence interval, 3.5-12.0, respectively), but not for stage 1 (adjusted odds ratio, 1.7; 95% confidence interval, 0.9-3.2). A history of AKI before pregnancy, despite apparent full recovery, was associated with increased risk of pregnancy complications. Severity and timing of the AKI episode modified the risk.
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Project description:(1) Background: To investigate whether women suffering from recurrent pregnancy loss (RPL) have a higher prevalence of self-reported depression than healthy controls and to assess the associated risk factors for RPL women self-reporting the symptom of depression. (2) Methods: A cross-sectional study investigating 247 women with histories of RPL and 193 healthy women was performed in Southwest China. The Zung Self-Rating Depression Scale (SDS) was used to measure self-reported depression, and the prevalence of self-reported depression was compared between the two groups. Sociodemographic data for the two groups and clinical information for the RPL group were collected by questionnaires. (3) Results: The prevalence of self-reported depression was higher in the RPL group than in the control group (45.3% vs. 30.1%, p < 0.01). Subgroup analyses indicated that the statistical difference in the prevalence of self-reported depression was significant in the subgroups of women in the first trimester of gestation, age ≥ 36 years, BMI ≥ 18.5 kg/m2, working hours ≤ 8 h/day, university and higher education, and urban residence. Multivariable logistic analysis indicated that age ≥ 36 years, >2 times of spontaneous miscarriages, and no history of live birth were independent risk factors for RPL women self-reporting depression. (4) Conclusions: A higher prevalence of self-reported depression was observed in RPL patients than in healthy women. The psychological status for RPL patients with age ≥ 36 years, >2 times of spontaneous miscarriages, or without a history of a live birth needs to be further addressed.
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Project description:An imbalance in circulating angiogenic factors plays a central role in the pathogenesis of preeclampsia.We prospectively studied 616 women who were evaluated for suspected preeclampsia. We measured plasma levels of antiangiogenic soluble fms-like tyrosine kinase 1 (sFlt1) and proangiogenic placental growth factor (PlGF) at presentation and examined for an association between the sFlt1/PlGF ratio and subsequent adverse maternal and perinatal outcomes within 2 weeks. The median sFlt1/PlGF ratio at presentation was elevated in participants who experienced any adverse outcome compared with those who did not (47.0 [25th-75th percentile, 15.5-112.2] versus 10.8 [25th-75th percentile, 4.1-28.6]; P<0.0001). Among those presenting at <34 weeks (n=167), the results were more striking (226.6 [25th-75th percentile, 50.4-547.3] versus 4.5 [25th-75th percentile, 2.0-13.5]; P<0.0001), and the risk was markedly elevated when the highest sFlt1/PlGF ratio tertile was compared with the lowest (odds ratio, 47.8; 95% confidence interval, 14.6-156.6). Among participants presenting at <34 weeks, the addition of sFlt1/PlGF ratio to hypertension and proteinuria significantly improved the prediction for subsequent adverse outcomes (area under the curve, 0.93 for hypertension, proteinuria, and sFlt1/PlGF versus 0.84 for hypertension and proteinuria alone; P=0.001). Delivery occurred within 2 weeks of presentation in 86.0% of women with an sFlt1/PlGF ratio ?85 compared with 15.8% of women with an sFlt1/PlGF ratio <85 (hazard ratio, 15.2; 95% confidence interval, 8.0-28.7).In women with suspected preeclampsia presenting at <34 weeks, circulating sFlt1/PlGF ratio predicts adverse outcomes occurring within 2 weeks. The accuracy of this test is substantially better than that of current approaches and may be useful in risk stratification and management. Additional studies are warranted to validate these findings.
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