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.

HELLP Syndrome a Severe Form of Preeclampsia: a Comparative Study of Clinical and Laboratorial Parameters

The objective of this study was to compare clinical, laboratorial, maternal and perinatal results between HELLP Syndrome and severe Preeclampsia. An observational study comparing women with HELLP Syndrome (n=71) to women with severe preeclampsia (n=253) was done. The authors analyzed the early course of the pathologies and the outcomes in both groups. HELLP syndrome occurred in 28% of all the cases and was more frequent at gestational age before 32 weeks (n=39 – 55%) than severe preeclampsia (n=108 - 42%), with more newborns weighting less than 1500g (27 – 38.6% vs 65 – 25.6%; p=0.036). Thrombocytopenia below 100 000/μL (aOR, 2.14; 95% CI, 1.49 – 3.06) and LDH>1 000 UI/L (aOR: 5.17; 95% CI 2.19 – 12.16) were risk factors for HELLP. Maternal morbidity (eclampsia, abruptio placentae, and acute renal failure) was similar in both cohorts; eight stillbirths (6 in severe preeclampsia and 2 in HELLP Syndrome) occurred. There were no maternal deaths. In conclusion, in this study the authors confirmed that HELLP Syndrome is a severe form of preeclampsia with an earlier presentation in pregnancy, worst laboratorial findings and more prematurity rates.

Dimethyl Acetals, an Indirect Marker of the Endogenous Antioxidant Plasmalogen Level, are Reduced in Blood Lipids of Sudanese Pre-eclamptic Subjects whose Background Diet is High in Carbohydrate

In Sudanese women with (n = 60) and without (n = 65) pre-eclampsia, circulating lipids, plasma and red cell saturated and monounsaturated fatty (MUFA) acids and dimethyl acetals (DMAs) were investigated. DMAs are an indirect marker of levels of plasmalogens, endogenous antioxidants, which play a critical role in oxidative protection, and cholesterol homeostasis. The pre-eclamptics had higher C18:1n-9 (p < 0.001) and ΣMUFA (p < 0.01) in plasma free fatty acids, C16:1n-7, C18:1n-9, ΣMUFA; 16:0/16:1n-7 (p < 0.01) in erythrocyte choline phosphoglycerides (ePC) and 16:1n-7, 18:1n-7 and 16:0/16:1n-7 (p < 0.01) in erythrocyte ethanolamine phosphoglycerides (ePE). In contrast, the DMAs 18:0, 18:1 and ΣDMAs in ePE, and 16:0, 18:0 and ΣDMAs in ePC were reduced (p < 0.001) in the pre-eclamptic women. This study of pregnant women with high carbohydrate and low fat background diet suggests pre-eclampsia is associated with oxidative stress and enhanced activity of the microsomal enzyme stearyl-CoA desaturase (delta 9 desaturase), as assessed by palmitic/palmitoleic (C16:0/C16:n-1) and stearic/oleic (C18/C18:1n-9) ratios.

Factores de riesgo maternos asociados con bajo peso al nacer en el Hospital Vicente Corral Moscoso, Cuenca febrero-junio 2004

El bajo peso al nacer se ha definido como un peso menor de 2.500 gr. en el momento del nacimiento. El objetivo fue conocer los factores de riesgo maternos asociados con bajo peso al nacer por lo que se hizo un estudio de casos y controles precesado en EPI INFO 2002 con una muestra calculdada de 100 pacientes con Power de 80y IC 95que cincluyó edad materna, estado civil, talla materna menos de 141 cm, peso materno, antecedentes de abortos previos, antecedentes de muerte fetal, hipertensión crónica, diabetes, enfermedad cardíaca, renal, epilepsia, primiparidad, intervalo intergenésico menor que 2 años, si han cursado en el embarazo actual con amenaza de aborto, preclampsia/eclampsia. ITU, placenta previa, anomalías congénitas fetales, niños pequeños a su cargo, controles prenatales, sexo fetal, trabajo materno, consumo de alcohol, tabaco y drogas. Los factores de riesgo que se encontró fueron edad materna menor de 19 años (OR 4.57), abortos previos (OR 3.92), antecedentes de muerte fetal (OR 3.13), primiparidad (OR 1.38), intervalo intergenésico menor que 2 años (OR 1.84), amenaza de aborto durante el embarazo actual (OR 3.91), Preclampsia/eclampsia (OR 6.77), menos de 6 controles prenatales (OR 2.24), los otros factores de riesgo estudiados no tuvieron una representación estadísticamente significativa

Fetal-maternal interface impedance parallels local NADPH oxidase related superoxide production

Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20-22 and 40-41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance.

Características del parto, puerperio inmediato y del recién nacido en madres adolescentes del Hospital Vicente Corral Moscoso de la ciudad de Cuenca, marzo-mayo del 2008

Estudio de cohorte prospectiva. Universo: embarazadas de 10 a 19 años y de 20 a 29 años del departamento de Obstetricia, Hospital Vicente Corral Moscoso - Cuenca, Marzo a Mayo del año 2008. Muestra: 391 parturientas. Unidad de análisis: ficha clínica y formulario CLAP. Se registró el nivel de instrucción, estado civil, y paridad, se valoró el tipo de parto, procedimientos durante el parto, patólogías, número de fetos. Se clasificó según peso, talla, edad gestacional, Apgar, perímetro cefálico, patología, necesidad de reanimación y destino del recién nacido. Resultados: la prevalencia del embarazo en adolescentes es de 34.53%. El 46.21% tiene nivel de instrucción primaria. Unión libre 42.42%. Primigestas 65.90%. Parto vaginal 71%. Cesárea 29%. La adolescencia constituye factor de riesgo para la prevalencia de episiotomía (RR: 2.123), así mismo para la eclampsia (RR: 11) y hemorragias del primer trimestre (RR 3.775), no así, es factor protector para amenaza de parto pretérmino (RR 0.95). El recién nacido el 71.21% es adecuado, 24.24% es pequeño, el 4.54% es grande para la edad gestacional. La adolescencia es factor de riesgo para la talla baja del recién nacido (RR 1.436), microcefalia (RR 1.304), Apgar al quinto minuto menor de 73.78%. La adolescencia se asocia a mayor incidencia enfermedad de membrana hialina (RR 4.50). El 10.60% de recién nacidos de madres adolescentes ingresó a neonatología

Predictors of maternal mortality among critically ill obstetric patients

Aim Evaluation of the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU). Methods A case control study to evaluate the predictors of maternal mortality among critically ill obstetric patients managed at the intensive care unit (ICU) of the University of Ilorin Teaching Hospital, Ilorin, Nigeria from 1st January 2010 to 30th June 2013. Participants were critically ill obstetric patients who were admitted and managed at the ICU during the study period. Subjects were those who died while controls were age and parity matched survivors. Statistical analysis was with SPSS-20 to determine chi square, Cox-regression and odds ratio; p value < 0.05 was significant. Results The mean age of subjects and controls were 28.92 ± 5.09 versus 29.44 ± 5.74 (p = 0.736), the level of education was higher among controls (p = 0.048) while more subjects were of low social class (p = 0.321), did not have antenatal care (p = 0.131) and had partners with lower level of education (p = 0.156) compared to controls. The two leading indications for admission among subjects and controls were massive postpartum haemorrhage and severe preeclampsia or eclampsia. The mean duration of admission was higher among controls (3.32 ± 2.46 versus 3.00 ± 2.58; p = 0.656) while the mean cost of ICU care was higher among the subjects (p = 0.472). The statistical significant predictors of maternal deaths were the patient’s level of education, Glasgow Coma Scale (GCS) score, oxygen saturation, multiple organ failure at ICU admission and the need for mechanical ventilation or inotrophic drugs after admission. Conclusion The clinical state at ICU admission of the critically ill obstetric patients is the major outcome determinant. Therefore, early recognition of the need for ICU care, adequate pre-ICU admission supportive care and prompt transfer will improve the outcome.

Perinatal complications associated with preterm deliveries at 24 to 33 weeks and 6 days gestation (2011- 2012): A hospital-based retrospective study

Background: Morbidity and mortality of preterm babies are important issues in perinatal medicine. In developed countries, preterm delivery is the cause of about 70% of mortality and 75% of morbidity in the neonatal period, respectively. Objective: The aim of this study was to determine the risk factors for preterm labor and the outcomes, in terms of perinatal mortality and morbidity at the time of discharge home, among preterm infants at less than 34 weeks gestation. Materials and Methods: A retrospective study was conducted and all infants with a gestational age of 24 to 33 weeks and 6 days who were born from November 1st , 2011 to March 31, 2012 were enrolled in this study. Results: From 1185 preterm infants were born during this period, 475 (40.08%) infants with less than 34 weeks gestational age were included in the study. Our study showed the major obstetrical risk factors for preterm labor were as follows: preeclampsia (21%), premature rupture of membranes (20.3%), abruption of placenta (10%), and idiopathic cases (48.7%). The neonatal mortality rate in less than 34 weeks was 9.05%. Significant perinatal morbidity causesd in less than 34 weeks were as follows: sepsis (46.94%), respiratory distress syndrome (41.47%), patent ductus arteriosus (21.47%), retinopathy of prematurity (3.57%), necrotizing entrocolitis (1.68%), intra-ventricular hemorrhage (9%), and broncho-pulmonary dysplasia (0.84%). Conclusion: Preterm birth is associated with adverse perinatal outcome. This situation needs to be improved by directing appropriately increased resources for improving prenatal health services and providing advanced neonatal care.

The relationship between 25-hydroxyvitamin D concentration in early pregnancy and pregnancy outcomes in a large, prospective cohort

Vitamin D insufficiency and deficiency have been associated with an increased risk of adverse pregnancy outcomes. Controversy remains as findings have been inconsistent between disparate populations. The aim of this study was to investigate the relationship between vitamin D status and pregnancy outcomes in a large, prospective pregnancy cohort. 25-Hydroxyvitamin D concentration was analysed in serum samples collected at 15 weeks of gestation from 1710 New Zealand women participating in a large, observational study. Associations between vitamin D status and pre-eclampsia, preterm birth, small for gestational age (SGA) and gestational diabetes were investigated. The mean 25-hydroxyvitamin D concentration was 72·9 nmol/l. In all, 23 % had 25-hydroxyvitamin D concentrations <50 nmol/l, and 5 % of participants had concentrations <25 nmol/l. Women with 25-hydroxyvitamin D concentrations <75 nmol/l at 15 weeks of gestation were more likely to develop gestational diabetes mellitus than those with concentrations >75 nmol/l (OR 2·3; 95 % CI 1·1, 5·1). However, this effect was not significant when adjustments were made for BMI and ethnicity (OR 1·8; 95 % CI 0·8, 4·2). 25-Hydroxyvitamin D concentration at 15 weeks was not associated with development of pre-eclampsia, spontaneous preterm birth or SGA infants. Pregnancy complications were low in this largely vitamin D-replete population.