Genes candidatos de suscetibilidade a pré-eclampsia: estudo de associação

Preeclampsia is a multifactorial disease of unknown etiology that features with wide clinical symptoms, ranging from mild preeclampsia to severe forms, as eclampsia and HELLP syndrome. As a complex disease, preeclampsia is also influenced by genetic and environmental factors. Aiming to identify preeclampsia susceptibility genes, we genotyped a total of 22 genetic markers (single nucleotides polymorphisms SNPs) distributed in six candidates genes (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). By a case-control approach, the genotypic frequencies were compared between normotensive (control group) and preeclamptic women. The case s group was classified according to the disease clinical form in: preeclampsia, eclampsia and HELLP syndrome. As results we found the following genetic association: 1) ACVR2A and preeclampsia; 2) FLT1 and severe preeclampsia; 3) ERAP1 and eclampsia; 4) FLT1 and HELLP syndrome. When stratifying preeclampsia group according to symptoms severity (mild and severe preeclampsia) or according to the time of onset (early and late preeclampsia), it was detected that early preeclampsia is strongly associated to risk preeclampsia, eclampsia and HELLP syndrome have different genetic bases, although FLT1 gene seems to be involved in preeclampsia and HELLP syndrome pathophisiology

Genes candidatos de suscetibilidade a pré-eclampsia: estudo de associação

Preeclampsia is a multifactorial disease of unknown etiology that features with wide clinical symptoms, ranging from mild preeclampsia to severe forms, as eclampsia and HELLP syndrome. As a complex disease, preeclampsia is also influenced by genetic and environmental factors. Aiming to identify preeclampsia susceptibility genes, we genotyped a total of 22 genetic markers (single nucleotides polymorphisms SNPs) distributed in six candidates genes (ACVR2A, FLT1, ERAP1, ERAP2, LNPEP e CRHBP). By a case-control approach, the genotypic frequencies were compared between normotensive (control group) and preeclamptic women. The case s group was classified according to the disease clinical form in: preeclampsia, eclampsia and HELLP syndrome. As results we found the following genetic association: 1) ACVR2A and preeclampsia; 2) FLT1 and severe preeclampsia; 3) ERAP1 and eclampsia; 4) FLT1 and HELLP syndrome. When stratifying preeclampsia group according to symptoms severity (mild and severe preeclampsia) or according to the time of onset (early and late preeclampsia), it was detected that early preeclampsia is strongly associated to risk preeclampsia, eclampsia and HELLP syndrome have different genetic bases, although FLT1 gene seems to be involved in preeclampsia and HELLP syndrome pathophisiology

Agregação familiar e resultados maternos e perinatais da pré-eclâmpsia severa em população do Rio Grande do Norte

To determine whether there is familiar aggregation of severe preeclampsia in a Brazilian population from Rio Grande do Norte and to characterize the maternal and perinatal outcomes in the studied population. Methods: A case control study was performed with 412 participants who were admitted at Maternidade Escola Januário Cicco (MEJC) for medical care. Of these, 264 subjects presented normal blood pressure and 148 were cases. Cases were composed of eclampsia (n=47), HELLP Syndrome (n=85) and Eclampsia associated with HELLP syndrome (n=16). The diagnosis of these illness were based on the citeria developed by National High Blood Pressure Education Program Working (2000). An interview was performed with each subject and questions related to personal and familiar history of hypertension, preeclampsia, HELLP syndrome and eclampsia. Statistical analysis was performed and comparison of median and mean between cases and controls were performed, with the level of significance of 5%. The Odds-Ratio was determined to estimate the risk of preeclampsia within the families. Results: There were no difference in the demographic data between cases and controls. Previous history of chronic hypertension and preeclampsia was more frequent in the case group. Headaches were more frequent in eclampsia and epigastric pain in the HELLP syndrome cases. Bleeding and oliguria were more frequently found in the eclampsia associated with HELLP syndrome cases. Acute Renal insufficiency was a common complication in the case group, but these cases did not evolve to chronic renal insufficiency. The maternal mortality was 0.4% and the perinatal mortality was high, 223 per 1,000 live births. The 111 risk of a woman to develop preeclampsia whose mother has hypertension or had preeclampsia was respectively 2.5 and 3.5. This risk was increased 5 times, when a sibling has hypertension and 6 times when both sibling and mother had previous history of preeclampsia. Conclusions: This study confirms that there is familiar aggregation of preeclampsia in this Brazilian population. The potential for cardiovascular complications due to development of chronic hypertension indicates the need of closely follow up of women who develop preeclampsia

Perfil epidemiológico dos distúrbios hipertensivos na gravidez

The preeclampsia is a disease that evolves to high death rate for the mother and for the fetus. The incidence of this disease in the world is variable and there are no data of this disturb in the Brazilian population. This paper had the objective to determine the incidence and risk factors for development of hypertensive disorders of pregnancy in a neighborhood in Natal, RN, Brazil, taking place a prospective study, cohort type, with the objective of evaluating the entire pregnancy of 242 women that got pregnant between 2004-2007. The incidence of hypertensive disorders was of 17%, while the incidence of preeclampsia was of 13.8%. The age average of women that developed the hypertensive disorders was of 27.4 years (SD±.9), whilst those that developed preeclampsia was of 26.6 (SD ±7.8) years and the normotensive was of 23.9 (SD±5.8) (p=0.002). It is noted a significant increase of the hypertensive disorder with age (p=0.0265). The gestational age for those who developed preeclampsia was lower than the women that developed normotensive pregnancy (p=0.0002). The body mass index (BMI) of the group of women that developed the hypertensive disorder was of 25.8 (SD±3.9), significantly higher than the group of normotensive women with 23.5 (SD±3.7) (p=0.02). The levels of triglycerides and cholesterol tended to be higher on women with preeclampsia than on normotensive, p=0.0502 and p=0.0566, respectively. Six (6) women presented with severe preeclampsia and one (1) developed HELLP Syndrome. The resolution of the pregnancy was performed by cesarean section in 70% of women that developed hypertensive disorders, whilst the normotensive was of 23.6% (p<0.0001). A subgroup of the studied subjects was reassessed one year after labor, revealing that 50% of the patients were still hypertensive. There were no larger complications nor mother death during labor. The incidence of hypertensive disorders are above the levels noted in other studies and 30% of the women were within the poles of greater risk for the hypertensive disorders; the elevated BMI in the beginning of the pregnancy is a risk factor for hypertensive disorder. The risk of severe complication in preeclampsia is high, with imminence of eclampsia occurring in 20.1% of women who developed hypertensive disorder of pregnancy. The adequate prenatal care and the opportune labor assistance may minimize the complications of the pregnancy hypertension and avoid mother death, although the risk of women remaining hypertensive is elevated

Doença cardiovascular em mulheres com histórico de pré-eclâmpsia e seguimento no sistema único de saúde

The aim of the present study was to analyze cardiovascular risk of women with a history of preeclampsia, as well as its follow-upin the National Health System.This is a cross-sectional quantitative research conducted at the Januário Cicco Maternity School. The study population was composed of 573 women selected from a databank belonging to the Women s Health Research Group of the Gynecology Department at Universidade Federal do Rio Grande do Norte, with a history of preeclampsia, and normotensives who gave birth at this institution five years before. The final sample consisted of 147 women, 64 in the group with a history of PE and 83 normotensives. Data were collected on a questionnaire containing the following: sociodemographic aspects, anthropometric measures, life habits, personal and family history of pregnancy-induced hypertension, family history of cardiovascular diseases and frequency of measuring current blood pressure levels. In relation to the association between cardiovascular risk and altered blood pressure (≥130x85 mmHg), the likelihood of exhibiting the latter condition was significantly higher in women with a history of preeclampsia (CI 95% 4.12-38.92), the overweight and obese (CI 95% 1.70-20.75), and in those with a family historyof CVD and personal history of PIH (CI 95% 0.78-47.07 and CI 95% 3.20-25.39) respectively. Likewise, the probability of having altered blood pressure was higher in women with fasting glycemia ≥100mg/dL (CI 95% 2.09-24.73), as well as in those with triglycerides ≥150mg/dl (CI 95% 1.72-9.66). After fitting the logistic model, diagnosis previous preeclampsia and altered triglycerides remained as explanatory variables.The women with a history of preeclampsia five years before exhibited altered blood pressure levels, clinical and laboratory manifestations suggestive of elevated risk for cardiovascular disease, as well as family and personal history of hypertension. There is no differential treatment or adequate outpatient follow-up for this population in basic health care units

Interação entre a equipe de enfermagem e a gestante com diagnóstico de pré-eclâmpsia

The objective of this exploratory descriptive study with a qualitative approach was to analyze the perception of the nursing team and the pregnant women hospitalized with pre-eclampsia regarding the interactive process occurring in the care relationship. Data were collected by semi-structured interview with twenty nursing professionals that work in the high-risk ward and ten pregnant women with the diagnosis of pre-eclampsia. The discourses were analyzed using the content analysis method, in the modality of thematic identification. Three categories were identified that describe the perception of the interaction by the nursing professionals: recognizing the needs of the hospitalized pregnant woman, understanding the woman with pre-eclampsia, and presenting difficulties in the interactive process. With regards to the pregnant women, four categories emerged: recognizing the clinical care, feeling the lack of information, experiencing feelings during the hospitalization, and envisioning the interaction process. The meaning of the discourses was analyzed according to the principles of symbolic interactionism. The results indicate that both, the nursing professionals and the pregnant women, have a limited perception of their interaction, suggesting a need for further reflection about this reality in the health service units and in the nursing education environment

Prevalência e fatores associados à morbidade materna: inquérito populacional em Natal/RN

INTRODUCTION: Severe maternal morbidity , also known as maternal near miss , has been used as an alternative to the study of maternal mortality , since being more frequent shares the same determinants and enables the implementati on of epidem iological surveillance of cases . Since then, hospital audits ha ve been carried out to determine the rates of maternal near miss, its mai n causes and associated factors . More recently, population surveys based on self - reported morbidity have als o been presented as vi able in identifying these cases . OBJECTIVE: The aim of this study was to determine the prevalence and associated factors of maternal near miss and complications during pregnancy and puerperal period in Natal/RN. METHODS: A cross - secti onal population - based study was conducted in Natal /RN , Brazil, which has as its target population women aged 15 to 49 years who were pregnant in the last five years. It was carried out a probabilistic sam pling design based on a multi - stage complex sample , in which 60 census tracts were selected from three strata (north , south - east and west). Afterwards, domiciles were visited in order to obtain a sample of the 908 eligible women in whom a questionnaire was applied. The descriptive analyzes and bivariate ass ociations were performed using the Chi - square test and the estimate of the prevalence ratio (PR ) with 95% confidence interval (CI) and considering the weights and design effects . The Poisson regression analysis , also with 5% significance and 95% CI, was us ed for analyzes of associated factors. RESULTS: 848 women were identified and interviewed after visits in 8.227 households corresponding to a response rate of 93 . 4 %. The prevalence of maternal near miss was 41 . 1 /1 000NV, being the Intensive Care Unity stay i ng (19 . 1 /1 000 LB ) and eclampsia (13 . 5/1000LB) the most important marker s . The prevalence of complications in the puerperal peri od was 21 . 2 %, and hemorrhage (10 . 7%) and urinary tract infection (10 . 7%) the most frequently reported clinical conditions and rema in ing in the hospital for over a week after delivery the mo st frequent intervention (5.4%) . Regarding associated factors , the bivariate analysis showed an association between the increased number of complications in women of black/brown race ( PR= 1 . 23; CI95 % : 1 . 04 - 1 . 46) and lower socioeconomic status ( PR= 1 . 33; CI95%: 1 . 12 - 1 . 58) in women who had pre natal care in public service ( PR= 1 . 42; CI95%: 1 . 16 to 1 . 72 ) and that were not advised during prenatal about where they should do the d elivery (PR= 1 . 24; CI95%: 1 . 05 - 1 . 46), made the del ivery in the public service (PR= 1 . 63; CI95%: 1 . 30 - 2 . 03), had to search for more than one hospital for delivery (PR=1 . 22; CI95%: 1 . 03 - 1 . 45) and had no companion during childbirth ( PR =1 . 19; CI95%: 1 . 01 - 1 . 41) or at all times of childbirth c are - before, during and after childbirth - ( PR= 1 . 25, CI95%: 1 . 05 - 1 . 48) . Moreover, the number of days postpartum hospitalization was higher in women who had more complications (P R= 1 . 59 ; CI95%: 1 . 36 - 1 . 86). In the final regression model for both birth place (P R= 1 . 21 ; CI 95% : 1 . 02 to 1 . 44 ) and socioeconomic status (PR = 1.54 ; CI95%: 1 . 25 - 1 . 90 ) the association remained. CONCLUSION : Conducting population surveys using the pragmatic definition of near miss is feasible and may add importa nt information about this ev ent . It was possible to find the expression of health inequalities related to maternal health in the analysis of both socioeconomic conditions and on the utilization of health services.

Determinantes genéticos e ambientais das doenças hipertensivas da gravidez

The development of complex diseases such as preeclampsia are determined by both environmental and genetic factors, but there is also interaction among these factors. Preeclampsia is a pregnancy-specific disorder characterized by de-novo hypertension and proteinuria after 20th week of gestation. There is a broad spectrum of clinical presentations related to hypertensive disorders of pregnancy (HDP) that can range from mild preeclampsia to eclampsia (seizures) or HELLP syndrome (Hemolysis, Elevation of Liver enzymes, Low Platelets). Those clinical outcomes might be linked to different pathological mechanisms. Our work aims to identify factors (i.e. genes and environmental) associated with the HDP’s clinical spectrum. Using a case-control approach, we selected a total of 1498 pregnant women for epidemiological and genetic studies, encompassing 755 normotensive (control); 518 preeclampsia; 84 eclampsia; and 141 HELLP. Women were genotyped for 18 SNPs across 5 candidate genes (FLT1, ACVR2A, ERAP1, ERAP2 and LNPEP). For the environmental factors, we found maternal age, parity status and pre-gestational body mass index as important risk factors associated with disease. Genes were associated in a phenotype-specific manner: ACVR2A with early preeclampsia (rs1424954, p=0.002); FLT1 with HELLP syndrome (rs9513095, p=0.003); and ERAP1 with eclampsia (rs30187, p=0.03). Our results suggest that different genetic mechanisms along with specific environmental factors might determine the clinical spectrum of HDP. In addition, phenotype refinement seems to be an essential step in the search for complex disease genes

Prevalência e fatores associados ao Near Miss Materno: inquérito populacional em uma capital do Nordeste Brasileiro

The scope of this study was to determine the prevalence of near misses and complications during pregnancy and the puerperal period, identifying the main clinical and intervention markers and socioeconomic and demographic factors associated with near misses. It involved a cross-sectional, population-based and probabilistic study with multi-stage complex sampling design conducted in Natal, State of Rio Grande do Norte, Brazil. A validated questionnaire was given to 848 women aged 15 to 49 identified in 8,227 households in 60 census sectors. In theanalysis of associations, the Chi-square test applied and calculated the prevalence ratio (PR) with Confidence Interval (CI) of 95% and 5% significance. The prevalence of maternal near misses was 41.1/1000LB, with hospitalization in an Intensive Care Unit (19.1/1000LB) and eclampsia (13.5/1000LB) being the most important markers. The prevalence of complications during pregnancy and the puerperal period was 21.2%. The highest prevalence of near misses was observed in older women, of black/brown race and low socioeconomic status. Conducting population surveys is feasible and may add important information to the study of near misses and the markers highlight the need for enhancing maternal care to reduce health inequality.

Prevalência e fatores associados ao Near Miss Materno: inquérito populacional em uma capital do Nordeste Brasileiro

The scope of this study was to determine the prevalence of near misses and complications during pregnancy and the puerperal period, identifying the main clinical and intervention markers and socioeconomic and demographic factors associated with near misses. It involved a cross-sectional, population-based and probabilistic study with multi-stage complex sampling design conducted in Natal, State of Rio Grande do Norte, Brazil. A validated questionnaire was given to 848 women aged 15 to 49 identified in 8,227 households in 60 census sectors. In theanalysis of associations, the Chi-square test applied and calculated the prevalence ratio (PR) with Confidence Interval (CI) of 95% and 5% significance. The prevalence of maternal near misses was 41.1/1000LB, with hospitalization in an Intensive Care Unit (19.1/1000LB) and eclampsia (13.5/1000LB) being the most important markers. The prevalence of complications during pregnancy and the puerperal period was 21.2%. The highest prevalence of near misses was observed in older women, of black/brown race and low socioeconomic status. Conducting population surveys is feasible and may add important information to the study of near misses and the markers highlight the need for enhancing maternal care to reduce health inequality.

Receptores de citocinas proinflamatórias na pré-eclâmpsia

Preeclampsia is a disease specific of human pregnancy that affects 3-8% of pregnant women, and it is one of the three leading causes of maternal mortality and morbidity. The disease is characterized by hypertension and proteinuria after the 20th week of gestation. The risk factors for this disease are not completely understood but appear to include dysregulation of the immune response arising from defects in placentation, environmental and genetic factors. This study aimed to determine whether the variation in the amount of proinflammatory cytokine receptors IL-1R2, IL-6R and TNF-αR1 would be involved in preeclampsia. They were recruited women with preeclampsia (n=24) and women who evolved during pregnancy without changes in blood pressure (n=12) were recruited. Clinical and laboratory data were collected. The cytokine receptors (IL-1R2, TNF-αR1 and IL-6R) were assessed in mononuclear cells isolated from peripheral blood using flow cytometry (Control = 8; PE = 24). C-reactive protein (CRP) was determined by CRP ultrasensitive method (Control = 7; PE = 18) was performed using sera pregnant women. Women with preeclampsia had higher weight at the beginning of the pregnancy (p=0.0171) and lower gestational age at delivery (0.0008). Classical monocytes were decreased in preeclampsia but not intermediate or non-classical monocytes. The frequency of IL-1R2 pro inflammatory cytokine receptors is decreased in women with PE only in the subpopulation of non-classical monocytes (p = 0.0011). TNF-αR1 receptor and IL-6R, had a decreased frequency in the three subpopulations of monocyte (classic, intermediate and non-classical) when compared to women with normal pregnancy. An increase in IL-1R2 receptor in TCD4+ lymphocytes, but a decrease in TNF-receptor and IL-6R in women with preeclampsia were found. No differences in the frequency of those receptors in CD3+/CD8+ in preeclampsia. There was no difference in C-reactive protein in preeclampsia. The reduction in the amount of IL-1R2, TNF- αR1 and IL-6R monocytes and lymphocytes can be involved in the regulation of inflammation observed in preeclampsia, contributing to disease.