Redução da morbi-mortalidade na síndrome de hellp completa com o uso de altas doses de dexametasona

Objective: To determine the clinical maternal and neonatal outcomes in HELLP syndrome patients treated with dexamethasone who either developed renal injury or renal insufficiency and to identify predictive values of urea and creatinine for the identification of subjects with HELLP syndrome at risk of developing renal insufficiency. Methods: Non-radomized intervention study of dexamethasone use in HELLP syndrome. A total of 62 patients were enrolled at Maternidade Escola Januário Cicco (MEJC). Patients received a total of 30 mg of dexamethasone IV, in three doses of 10 mg every 12 hours. A clinical and laboratory follow up were performed at 24, 48 and 72 hours. Patients were followed up to 6 months after delivery. Patients were grouped in accordance to renal function, i.e, normal and some type of renal lesion. Renal lesion was considered when creatinine was equal or greater than 1.3 mg/dl and diuresis less than 100 ml in 4 hours period and renal insufficiency was defined when dialysis was needed. Results: A total of 1230 patients with preeclampsia were admitted at MEJC. Of those 62 (5%) developed HELLP syndrome. There was no statistical difference in the groups with renal involvement or normal renal function with respect to the demographics, type of anesthesia used and delivery, and weight of the newborn. An improvement in the AST, ALT, LDH, haptoglobine, antithrombine, fibrinogenen and platelets was observed within 72 hours after dexamethosone use. There was a significant increase in the diuresis within the interval of 6 hours before the delivery and 24 hours after it. Of the 62 patients, 46 (74. 2%) had normal renal function and 16 (25.8%) evolved with renal lesion, with 5 (8.1%) needing dialysis. These 5 patients who received dialysis recovered the xi renal function. The delay in administering dexamethasone increased in 4.6% the risk of development of renal insufficiency. Patients with renal insufficiency had received significantly more blood products than subjects without renal lesion (p=0.03). Diuresis, leukocytes, uric acid, urea, creatinine were significantly different between the groups with normal renal function, renal lesion and renal insufficiency. The levels of creatinine 1.2mg/dl and uric acid 51mg/dl, at admission are predictive of subjects who will evolve with renal lesion (p<0.001). Maternal mortality was 3.2%. None of the subjects with renal insufficiency evolved with chronic renal disease. Conclusions: Dexamethasone in patients with HELLP syndrome seems to reduce significantly the hepatic microthrombosis and normalize hemostasis as seen by improvement of liver function. Renal injury can be considered, in HELLP syndrome, when creatinine levels are greater than 1.3 mg/dl and diuresis less than 100 ml/h in interval of 4 hours. The level of creatinine greater than 1.2 mg/dl and urea greater than 51mg/dl are predictive of subjects with HELLP syndrome who will develop renal injury. Patients who receive more red cell packs develop renal insufficiency. Finally, the delay in administering dexamethasone increases the risk of developing renal insufficiency

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

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

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