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1.
PLoS One ; 16(10): e0258127, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34618852

RESUMEN

Population risks for neonatal hyperbilirubinaemia (NH) vary. Knowledge of local risks permits interventions that may reduce the proportion becoming severe. Between January 2015 and May 2016, in a resource-limited setting on the Thailand-Myanmar border, neonates from 28 weeks' gestation were enrolled into a prospective birth cohort. Each neonate had total serum bilirubin measurements: scheduled (24, 48, 72 and 144 hours of life) and clinically indicated; and weekly follow up until 1 month of age. Risk factors for developing NH were evaluated using Cox proportional hazard mixed model. Of 1710 neonates, 22% (376) developed NH (83% preterm, 19% term). All neonates born <35 weeks, four in five born 35-37 weeks, and three in twenty born ≥38 weeks had NH, giving an overall incidence of 249 per 1000 livebirths [95%CI 225, 403]. Mortality from acute bilirubin encephalopathy was 10% (2/20) amongst the 5.3% (20/376) who reached the severe NH threshold. One-quarter (26.3%) of NH occurred within 24 hours. NH onset varied with gestational age: at a median [IQR] 24 hours [24, 30] for neonates born 37 weeks or prematurely vs 59 hours [48, 84] for neonates born ≥38 weeks. Risk factors for NH in the first week of life independent of gestational age were: neonatal G6PD deficiency, birth bruising, Sgaw Karen ethnicity, primigravidae, pre-eclampsia, and prolonged rupture of membranes. The genetic impact of G6PD deficiency on NH was partially interpreted by using the florescent spot test and further genotyping work is in progress. The risk of NH in Sgaw Karen refugees may be overlooked internationally as they are most likely regarded as Burmese in countries of resettlement. Given high levels of pathological jaundice in the first 24 hours and overall high NH burden, guidelines changes were implemented including preventive PT for all neonates <35 weeks and for those 35-37 weeks with risk factors.


Asunto(s)
Bilirrubina/sangre , Deficiencia de Glucosafosfato Deshidrogenasa/sangre , Hiperbilirrubinemia Neonatal/sangre , Kernicterus/sangre , Estudios de Cohortes , Estudios Epidemiológicos , Grupos Étnicos/genética , Femenino , Genotipo , Deficiencia de Glucosafosfato Deshidrogenasa/complicaciones , Deficiencia de Glucosafosfato Deshidrogenasa/genética , Deficiencia de Glucosafosfato Deshidrogenasa/mortalidad , Humanos , Hiperbilirrubinemia Neonatal/genética , Hiperbilirrubinemia Neonatal/mortalidad , Hiperbilirrubinemia Neonatal/patología , Recién Nacido , Kernicterus/complicaciones , Kernicterus/genética , Kernicterus/mortalidad , Masculino , Mianmar/epidemiología , Preeclampsia/sangre , Preeclampsia/genética , Preeclampsia/mortalidad , Embarazo , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Tailandia/epidemiología
2.
Int J Mol Sci ; 22(19)2021 Sep 30.
Artículo en Inglés | MEDLINE | ID: mdl-34638993

RESUMEN

Preeclampsia (PE) is a leading cause of maternal and neonatal morbidity and mortality worldwide. Defects in trophoblast invasion, differentiation of extravillous trophoblasts and spiral artery remodeling are key factors in PE development. Currently there are no predictive biomarkers clinically available for PE. Recent technological advancements empowered transcriptome exploration and led to the discovery of numerous non-coding RNA species of which microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are the most investigated. They are implicated in the regulation of numerous cellular functions, and as such are being extensively explored as potential biomarkers for various diseases. Altered expression of numerous lncRNAs and miRNAs in placenta has been related to pathophysiological processes that occur in preeclampsia. In the following text we offer summary of the latest knowledge of the molecular mechanism by which lnRNAs and miRNAs (focusing on the chromosome 19 miRNA cluster (C19MC)) contribute to pathophysiology of PE development and their potential utility as biomarkers of PE, with special focus on sample selection and techniques for the quantification of lncRNAs and miRNAs in maternal circulation.


Asunto(s)
MicroARN Circulante/sangre , Preeclampsia/sangre , Preeclampsia/diagnóstico , ARN Largo no Codificante/sangre , Biomarcadores/sangre , Diferenciación Celular/genética , Movimiento Celular/genética , Proliferación Celular/genética , Cromosomas Humanos Par 19/genética , Cromosomas Humanos Par 19/metabolismo , MicroARN Circulante/genética , Femenino , Regulación del Desarrollo de la Expresión Génica , Humanos , Embarazo , ARN Largo no Codificante/genética , Transcriptoma , Trofoblastos/metabolismo
3.
Pan Afr Med J ; 39: 14, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34394805

RESUMEN

Preeclampsia is one of the most common complications of pregnancy and occurs in approximately 3-8% of all pregnancies worldwide. Although the aetiology of preeclampsia still largely remains unclear, it is thought to be related to endothelial dysfunction and can lead to serum lipid abnormalities. Therefore, this case-control study was conceived and designed with the aim to compare maternal lipid profile parameters and cardiovascular risk factors, between preeclamptic and healthy pregnancies. Blood samples were collected after overnight fasting from 48 preeclamptics and 96 healthy pregnant controls matched for age and gestational weeks and serum lipid profile concentrations were estimated and used them to calculate cardiac risk ratio I and II. There was a significant rise in serum lipid levels in pregnancies complicated by preeclampsia. These lipids turn out to be risk factor for cardiovascular diseases. Positive correlation of maternal serum lipids to high blood pressure suggests a causal relationship.


Asunto(s)
Lípidos/sangre , Preeclampsia/sangre , Adulto , Camerún , Estudios de Casos y Controles , Femenino , Edad Gestacional , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Embarazo , Adulto Joven
4.
BMJ ; 374: n1857, 2021 08 13.
Artículo en Inglés | MEDLINE | ID: mdl-34389547

RESUMEN

OBJECTIVE: To determine whether the addition of placental growth factor (PlGF) measurement to current clinical assessment of women with suspected pre-eclampsia before 37 weeks' gestation would reduce maternal morbidity without increasing neonatal morbidity. DESIGN: Stepped wedge cluster randomised control trial from 29 June 2017 to 26 April 2019. SETTING: National multisite trial in seven maternity hospitals throughout the island of Ireland PARTICIPANTS: Women with a singleton pregnancy between 20+0 to 36+6 weeks' gestation, with signs or symptoms suggestive of evolving pre-eclampsia. Of the 5718 women screened, 2583 were eligible and 2313 elected to participate. INTERVENTION: Participants were assigned randomly to either usual care or to usual care plus the addition of point-of-care PlGF testing based on the randomisation status of their maternity hospital at the time point of enrolment. MAIN OUTCOMES MEASURES: Co-primary outcomes of composite maternal morbidity and composite neonatal morbidity. Analysis was on an individual participant level using mixed-effects Poisson regression adjusted for time effects (with robust standard errors) by intention-to-treat. RESULTS: Of the 4000 anticipated recruitment target, 2313 eligible participants (57%) were enrolled, of whom 2219 (96%) were included in the primary analysis. Of these, 1202 (54%) participants were assigned to the usual care group, and 1017 (46%) were assigned the intervention of additional point-of-care PlGF testing. The results demonstrate that the integration of point-of-care PlGF testing resulted in no evidence of a difference in maternal morbidity-457/1202 (38%) of women in the control group versus 330/1017 (32%) of women in the intervention group (adjusted risk ratio (RR) 1.01 (95% CI 0.76 to 1.36), P=0.92)-or in neonatal morbidity-527/1202 (43%) of neonates in the control group versus 484/1017 (47%) in the intervention group (adjusted RR 1.03 (0.89 to 1.21), P=0.67). CONCLUSIONS: This was a pragmatic evaluation of an interventional diagnostic test, conducted nationally across multiple sites. These results do not support the incorporation of PlGF testing into routine clinical investigations for women presenting with suspected preterm pre-eclampsia, but nor do they exclude its potential benefit. TRIAL REGISTRATION: ClinicalTrials.gov NCT02881073.


Asunto(s)
Mortalidad Materna/tendencias , Factor de Crecimiento Placentario/metabolismo , Pruebas en el Punto de Atención/normas , Preeclampsia/diagnóstico , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Análisis por Conglomerados , Femenino , Edad Gestacional , Humanos , Lactante , Mortalidad Infantil/tendencias , Recién Nacido , Irlanda , Evaluación de Resultado en la Atención de Salud , Factor de Crecimiento Placentario/sangre , Pruebas en el Punto de Atención/estadística & datos numéricos , Preeclampsia/sangre , Preeclampsia/etnología , Embarazo
5.
J Am Heart Assoc ; 10(16): e020302, 2021 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-34387117

RESUMEN

Background We investigated the biomarker potential of growth differentiation factor 15 (GDF-15), a stress response protein highly expressed in placenta, to predict preeclampsia. Methods and Results In 2 prospective cohorts (cohort 1: 960 controls, 39 women who developed preeclampsia; cohort 2: 950 controls, 41 developed preeclampsia), plasma concentrations of GDF-15 at 36 weeks' gestation were significantly increased among those who developed preeclampsia (P<0.001), area under the receiver operating characteristic curves (AUC) of 0.66 and 0.71, respectively. In cohort 2 a ratio of sFlt-1/PlGF (a clinical biomarker for preeclampsia) had a sensitivity of 61.0% at 83.2% specificity to predict those who will develop preeclampsia (AUC of 0.79). A ratio of GDF-15×sFlt-1/PlGF yielded a sensitivity of 68.3% at 83.2% specificity (AUC of 0.82). GDF-15 was consistently elevated across a number of international cohorts: levels were higher in placenta and blood from women delivering <34 weeks' gestation due to preterm preeclampsia in Melbourne, Australia; and in the blood at 26 to 32 weeks' gestation among 57 women attending the Manchester Antenatal Vascular Service (MAViS, UK) who developed preeclampsia (P=0.0002), compared with 176 controls. In the Preeclampsia Obstetric adVerse Events biobank (PROVE, South Africa), plasma GDF-15 was significantly increased in women with preeclampsia with severe features (P=0.02; n=14) compared to controls (n=14). Conclusions We conclude circulating GDF-15 is elevated among women more likely to develop preeclampsia or diagnosed with the condition. It may have value as a clinical biomarker, including the potential to improve the sensitivity of sFlt-1/PlGF ratio.


Asunto(s)
Factor 15 de Diferenciación de Crecimiento/sangre , Placenta/metabolismo , Preeclampsia/sangre , Australia , Biomarcadores/sangre , Presión Sanguínea , Estudios de Casos y Controles , Inglaterra , Femenino , Factor 15 de Diferenciación de Crecimiento/genética , Humanos , Proteínas de la Membrana/sangre , Preeclampsia/diagnóstico , Preeclampsia/fisiopatología , Valor Predictivo de las Pruebas , Embarazo , Reproducibilidad de los Resultados , Sudáfrica , Regulación hacia Arriba , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre
6.
Sci Rep ; 11(1): 15934, 2021 08 05.
Artículo en Inglés | MEDLINE | ID: mdl-34354200

RESUMEN

A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer's disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates. Here, we describe a novel, sensitive assay that detects serum protein aggregates from patients with PE (n = 33 early onset and 33 late onset) and gestational age-matched controls (n = 77) as well as AD in both dementia and prodromal mild cognitive impairment (MCI, n = 24) stages with age-matched controls (n = 19). The assay employs exposure of genetically engineered, autophagy-deficient human trophoblasts (ADTs) to serum from patients. The aggregated protein complexes and their individual components, including transthyretin, amyloid ß-42, α-synuclein, and phosphorylated tau231, can be detected and quantified by co-staining with ProteoStat, a rotor dye with affinity to aggregated proteins, and respective antibodies. Detection of protein aggregates in ADTs was not dependent on transcriptional upregulation of these biomarkers. The ROC curve analysis validated the robustness of the assay for its specificity and sensitivity (PE; AUC: 1, CI: 0.949-1.00; AD; AUC: 0.986, CI: 0.832-1.00). In conclusion, we have developed a novel, noninvasive diagnostic and predictive assay for AD, MCI and PE.


Asunto(s)
Enfermedad de Alzheimer/sangre , Análisis Químico de la Sangre/métodos , Preeclampsia/sangre , Adulto , Enfermedad de Alzheimer/diagnóstico , Péptidos beta-Amiloides , Biomarcadores/sangre , Proteínas Sanguíneas/análisis , Disfunción Cognitiva/diagnóstico , Femenino , Pruebas Hematológicas/métodos , Humanos , Inmunohistoquímica , Fragmentos de Péptidos , Preeclampsia/diagnóstico , Embarazo , Agregado de Proteínas/fisiología , Curva ROC , Trofoblastos/efectos de los fármacos , alfa-Sinucleína , Proteínas tau
7.
Sci Rep ; 11(1): 16595, 2021 08 16.
Artículo en Inglés | MEDLINE | ID: mdl-34400721

RESUMEN

Fetal growth restriction is a leading cause of stillbirth that often remains undetected during pregnancy. Identifying novel biomarkers may improve detection of pregnancies at risk. This study aimed to assess syndecan-1 as a biomarker for small for gestational age (SGA) or fetal growth restricted (FGR) pregnancies and determine its molecular regulation. Circulating maternal syndecan-1 was measured in several cohorts; a large prospective cohort collected around 36 weeks' gestation (n = 1206), a case control study from the Manchester Antenatal Vascular service (285 women sampled at 24-34 weeks' gestation); two prospective cohorts collected on the day of delivery (36 + 3-41 + 3 weeks' gestation, n = 562 and n = 405 respectively) and a cohort who delivered for preterm FGR (< 34 weeks). Circulating syndecan-1 was consistently reduced in women destined to deliver growth restricted infants and those delivering for preterm disease. Syndecan-1 secretion was reduced by hypoxia, and its loss impaired proliferation. Matrix metalloproteinases and mitochondrial electron transport chain inhibitors significantly reduced syndecan-1 secretion, an effect that was rescued by coadministration of succinate, a mitochondrial electron transport chain activator. In conclusion, circulating syndecan-1 is reduced among cases of term and preterm growth restriction and has potential for inclusion in multi-marker algorithms to improve detection of poorly grown fetuses.


Asunto(s)
Retardo del Crecimiento Fetal/sangre , Metaloproteinasas de la Matriz/fisiología , Mitocondrias/fisiología , Placenta/metabolismo , Complicaciones del Embarazo/sangre , Sindecano-1/sangre , Adulto , Área Bajo la Curva , Peso al Nacer , Hipoxia de la Célula , Parto Obstétrico , Diabetes Gestacional/sangre , Transporte de Electrón/efectos de los fármacos , Femenino , Edad Gestacional , Humanos , Hipertensión/sangre , Recién Nacido , Recién Nacido Pequeño para la Edad Gestacional , Metformina/farmacología , Mitocondrias/efectos de los fármacos , Tamaño de los Órganos , Sobrepeso/sangre , Preeclampsia/sangre , Embarazo , Curva ROC , Fumar/sangre , Trofoblastos/enzimología
8.
Curr Opin Hematol ; 28(5): 323-330, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34267080

RESUMEN

PURPOSE OF REVIEW: Preeclampsia is a common complication of pregnancy and contributes significantly to maternal and fetal morbidity and mortality. A protective hypercoagulable state is often developed during late pregnancy and can evolve into a prothrombotic state in patients with preeclampsia. The underlying mechanism of this prothrombotic transition remains poorly understood. We discuss recent progress in understanding the pathophysiology of preeclampsia and associated prothrombotic state. RECENT FINDINGS: The hypercoagulable state developed during pregnancy is initiated by placental factors and progresses into the prothrombotic state in preeclampsia when the placenta is subjected ischemic and oxidative injuries. The cause of the preeclampsia-induced prothrombotic state is multifactorial, involving not only placental factors but also maternal conditions, which include genetic predisposition, preexisting medical conditions, and conditions acquired during pregnancy. Endotheliopathy is the primary pathology of preeclampsia and contributes to the prothrombotic state by inducing the dysregulation of coagulation, platelets, and adhesive ligands. SUMMARY: Patients with preeclampsia often develop a severe prothrombotic state that predisposes them to life-threatening thrombosis and thromboembolism during and after pregnancy. Early recognition and treatment of this prothrombotic state can improve maternal and infant outcomes of preeclampsia patients.


Asunto(s)
Predisposición Genética a la Enfermedad , Preeclampsia , Trombosis , Plaquetas/metabolismo , Femenino , Humanos , Placenta/metabolismo , Adhesividad Plaquetaria , Preeclampsia/sangre , Preeclampsia/genética , Embarazo , Proteínas Gestacionales/sangre , Proteínas Gestacionales/genética , Trombosis/sangre , Trombosis/genética
9.
BMC Pregnancy Childbirth ; 21(1): 532, 2021 Jul 27.
Artículo en Inglés | MEDLINE | ID: mdl-34315426

RESUMEN

BACKGROUND: Preeclampsia is a well-known cause of maternal mortality and morbidity in Ethiopia. The exact pathophysiology has not been fully understood. Calcium and magnesium deficiencies have been given emphasis to play roles in the pathophysiology. Although evidence is abundant, they are equivocal. The study aimed to see the association of dietary calcium intake, serum total calcium level and ionized calcium level with preeclampsia. It also evaluated the association between dietary calcium intake and serum calcium levels. MATERIALS AND METHODS: An unmatched case-control study was conducted in Gandhi Memorial, Tikur Anbessa, and Zewditu Memorial Hospitals, all in Addis Ababa, between October to December, 2019. Cases were 42 women with preeclampsia and controls were 42 normotensive women. The medical and obstetric history was gathered using a structured questionnaire and the dietary calcium intake information using a 24-h dietary recall. The serum levels of total serum calcium and ionized (free) calcium were measured using an inductively coupled mass spectrophotometer. Bivariate and multivariate logistic regression and Pearson correlation test were utilized during data analysis. RESULTS: In comparison with controls, women with preeclampsia had lower mean (± 1SD) levels of ionized calcium level (1.1 mmol/l ± 0.11), total serum calcium level (1.99 mmol/l ± 0.35) and lower median (IQR) dietary calcium intake (704 mg/24 h,458-1183). The odds of having preeclampsia was almost eight times greater in those participants with low serum ionized calcium level (OR 7.5, 95% CI 2.388-23.608) and three times higher in those with low total serum calcium level (OR 3.0, 95% CI 1.024-9.370). Low dietary calcium intake also showed statistically significant association with preeclampsia (OR 3.4, 95% CI 1.092 -10.723). Serum ionized calcium level and total serum calcium level showed positive correlation of moderate strength (p = 0.004, r = 0.307), but no correlation was found between dietary calcium intake with both forms of serum calcium levels. CONCLUSION: This study showed significant association between low dietary calcium intake and low serum calcium levels with preeclampsia, hence this can be used as a supportive local evidence for the current context-specific recommendation of calcium supplementation in societies with low-dietary calcium consumption in an attempt to prevent preeclampsia, therefore implementation study should be considered in Ethiopia to look for the feasibility of routine supplementation.


Asunto(s)
Calcio en la Dieta/administración & dosificación , Calcio/sangre , Calcio/deficiencia , Preeclampsia/sangre , Adulto , Estudios de Casos y Controles , Etiopía/epidemiología , Femenino , Humanos , Embarazo , Fenómenos Fisiologicos de la Nutrición Prenatal , Ingesta Diaria Recomendada
10.
J Am Heart Assoc ; 10(15): e021477, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34310191

RESUMEN

Background Placental derived cell-free DNA (cfDNA), widely utilized for prenatal screening, may serve as a biomarker for preeclampsia. To determine whether cfDNA parameters are altered in preeclampsia, we conducted a case-control study using prospectively collected maternal plasma (n=20 preeclampsia, n=22 normal) using our in-house validated prenatal screening assay. Methods and Results Isolated cfDNA was quantified, sequenced using Illumina NextSeq 500, and the placental-derived fraction was determined. Clinical and test characteristics were compared between preeclampsia and controls, followed by comparisons within the preeclampsia cohort dichotomized by cfDNA concentration. Lastly, cfDNA parameters in preeclampsia were correlated with markers of disease severity. Maternal age, body mass index, gestational age at delivery, cesarean rate, and neonatal birthweight were expectedly different between groups (P≤0.05). The placental-derived cfDNA fraction did not differ between groups (21.4% versus 16.9%, P=0.06); however, total cfDNA was more than 10 times higher in preeclampsia (1235 versus 106.5 pg/µL, P<0.001). This relationship persisted when controlling for important confounders (OR 1.22, 95% CI 1.04-1.43, P=0.01). The dichotomized preeclampsia group with the highest cfDNA concentration delivered earlier (33.2 versus 36.6 weeks, P=0.02) and had lower placental-derived fractions (9.1% versus 21.4%, P=0.04). Among preeclampsia cases, higher total cfDNA correlated with earlier gestational age at delivery (P=0.01) and higher maximum systolic blood pressure (P=0.04). Conclusions At diagnosis, total cfDNA is notably higher in preeclampsia, whereas the placental derived fraction remains similar to healthy pregnancies. In preeclampsia, higher total cfDNA correlates with earlier gestational age at delivery and higher systolic blood pressure. These findings may indicate increased release of cfDNA from maternal tissue injury.


Asunto(s)
Ácidos Nucleicos Libres de Células/sangre , Edad Gestacional , Preeclampsia , Diagnóstico Prenatal , Adulto , Biomarcadores/sangre , Presión Sanguínea , Índice de Masa Corporal , Estudios de Casos y Controles , Correlación de Datos , Femenino , Humanos , Edad Materna , Placenta/metabolismo , Preeclampsia/sangre , Preeclampsia/diagnóstico , Preeclampsia/fisiopatología , Embarazo , Diagnóstico Prenatal/métodos , Diagnóstico Prenatal/estadística & datos numéricos , Historia Reproductiva , Índice de Severidad de la Enfermedad
11.
Taiwan J Obstet Gynecol ; 60(4): 615-620, 2021 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-34247797

RESUMEN

OBJECTIVE: We aimed to compare the diagnostic efficiency of cystatin C with traditional kidney markers in preeclampsia and to evaluate the relationship of these markers with neutrophil-lymphocyte and thrombocyte-lymphocyte ratios. MATERIALS AND METHODS: 14 severe preeclampsia, 48 mild preeclampsia and 79 patients with healthy pregnancy who presented to our obstetrics and gynecology clinic within one year were compared. These three groups were compared in terms of demographic characteristics, physical findings, serum urea, creatinine, cystatin C levels, and neutrophil-lymphocyte and platelet-lymphocyte ratios. RESULTS: The mean serum cystatin C, creatinine and uric acid levels were higher in the severe preeclampsia group compared with the mild preeclamptic and healthy pregnancies (p < 0.001). While cystatin C values increased as the week of gestation increased in the mild preeclampsia group, there was no relation with the gestational week in the control group and the severe preeclampsia group. However, the highest cystatin C values were in the severe preeclampsia group, regardless of the week (p < 0.05). The area under the ROC curve was statistically significant for cystatin C, uric acid and creatinine, but of these three values, cystatin C had the highest sensitivity and specificity. Neutrophil-lymphocyte ratio (NLR) was significantly higher in the severe preeclampsia group than healthy pregnancies, but the level was not significant compared to mild preeclampsia. There was no difference between the groups in terms of platelet-lymphocyte ratio. CONCLUSION: It can be suggested that cystatin C level reflects renal functions better than uric acid and creatinine in preeclampsia. Cystatin C can be used as a prognostic marker in preeclamptic pregnancies, and rising levels may be valuable for predicting severe preeclampsia. Especially with advancing gestational week, the increase in cystatin C level may indicate an association with the development of preeclampsia. NLR levels may be a parameter correlating with severity in severe preeclampsia.


Asunto(s)
Recuento de Células Sanguíneas/estadística & datos numéricos , Cistatina C/sangre , Pruebas de Función Renal/estadística & datos numéricos , Preeclampsia/sangre , Preeclampsia/diagnóstico , Adulto , Biomarcadores/sangre , Plaquetas/metabolismo , Estudios de Casos y Controles , Creatinina/sangre , Femenino , Humanos , Riñón/fisiopatología , Linfocitos/metabolismo , Neutrófilos/metabolismo , Preeclampsia/fisiopatología , Embarazo , Pronóstico , Curva ROC , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Ácido Úrico/sangre
12.
Front Immunol ; 12: 667841, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34248946

RESUMEN

The hallmark of preeclampsia (PE) is a shift toward persistent inflammatory response, accompanied by endothelial dysfunction. The driving forces in PE are proinflammatory cytokine and growth factors, in parallel with reduced functionality of anti-inflammatory effectors, like regulatory T cells are observed. Unfortunately, no conclusive mechanism underlying preeclampsia has been identified. For this reason, research on preeclampsia is needed to provide a state of the art understanding of the pathophysiology, identification of new diagnostics tools and the development of targeted therapies. The 68 patients were divided into three groups: gestational hypertension (GH) group (n = 19) and PE group (n = 28) and a control group (n = 21). We have tested a set of 53 cytokines, chemokines and growth factors in preeclampsia and gestational hypertension, and then compared them with normal pregnancies. Using a diagnostic test assessment characteristic parameters (IL-22, MDC/CCL22, IL-2/IL-4 ratio) have been identified and cut-off values have been proposed to diagnose preeclampsia. All parameters had high negative or positive predictive values, above 80%. In conclusion, we have proposed a potential set of immune parameters to diagnose preeclampsia.


Asunto(s)
Citocinas/sangre , Hipertensión Inducida en el Embarazo/inmunología , Mediadores de Inflamación/sangre , Preeclampsia/inmunología , Proteínas ADAM/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Humanos , Hipertensión Inducida en el Embarazo/sangre , Hipertensión Inducida en el Embarazo/diagnóstico , Interleucina-2/sangre , Interleucina-4/sangre , Interleucinas/sangre , Preeclampsia/sangre , Preeclampsia/diagnóstico , Valor Predictivo de las Pruebas , Embarazo , Proteínas Supresoras de Tumor/sangre , Adulto Joven
13.
Am J Physiol Regul Integr Comp Physiol ; 321(2): R125-R138, 2021 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-34105357

RESUMEN

The pregnant Dahl salt-sensitive (S) rat is an established preclinical model of superimposed spontaneous preeclampsia characterized by exacerbated hypertension, increased urinary protein excretion, and increased fetal demise. Because of the underlying immune system dysfunction present in preeclamptic pregnancies in humans, we hypothesized that the pregnant Dahl S rat would also have an altered immune status. Immune system activation was assessed during late pregnancy in the Dahl S model and compared with healthy pregnant Sprague-Dawley (SD) rats subjected to either a sham procedure or a procedure to reduce uterine perfusion pressure (RUPP). Circulating immunoglobulin and cytokine levels were measured by enzyme-linked immunosorbent assay (ELISA) and Milliplex bead assay, respectively, and percentages of circulating, splenic, and placental immune cells were determined using flow cytometry. The pregnant Dahl S rat exhibited an increase in CD4+ T cells, and specifically TNFα+CD4+ T cells, in the spleen compared with virgin Dahl S rats. The Dahl also had increased neutrophils and decreased B cells in the peripheral blood as compared with Dahl virgin rats. SD rats that received the RUPP procedure had increases in circulating monocytes and increased IFN-É£+CD4+ splenic T cells. Together these findings suggest that dysregulated T cell activity is an important factor in both the pregnant Dahl S rats and SD rats after the RUPP procedure.


Asunto(s)
Linfocitos T CD4-Positivos/inmunología , Citocinas/sangre , Inmunoglobulinas/sangre , Placenta/inmunología , Preeclampsia/inmunología , Bazo/inmunología , Animales , Linfocitos B/inmunología , Linfocitos B/metabolismo , Linfocitos T CD4-Positivos/metabolismo , Modelos Animales de Enfermedad , Femenino , Edad Gestacional , Neutrófilos/inmunología , Neutrófilos/metabolismo , Fenotipo , Placenta/metabolismo , Preeclampsia/sangre , Embarazo , Ratas Endogámicas Dahl , Ratas Sprague-Dawley , Bazo/metabolismo
14.
Int J Mol Sci ; 22(10)2021 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-34070163

RESUMEN

Preeclampsia is associated with an increased cardiovascular morbidity of mother and offspring, thus contributing to a substantial burden in women and children's health. It has been proven that endothelial progenitor cell (EPC) numbers and functional characteristics are impaired in cardiovascular disease and preeclampsia, although causative factors for the latter have remained elusive. MicroRNA (miRNA) modifications are a potential mechanism through which exposure to an altered environment translates into the development of chronic disease. In this study, we examined whether development of preeclampsia corresponds to alterations of miRNAs in maternal- and cord-blood-derived EPC. To test this end, we analyzed maternal and neonatal miRNAs via RNA sequencing from endothelial cells of preeclamptic and healthy controls in different cell culture passages. We were able to demonstrate differentially represented miRNAs in all groups. Hsa-miR-1270 showed significantly different levels in cord blood EPC from preeclampsia versus control and was negatively correlated with mRNA levels of its predicted targets ANGPTL7 and TFRC. Transfection with an hsa-miR-1270 inhibitor decreased the tube formation capacity and chemotactic motility but did not change proliferation in vitro. Target predictions and gene set enrichment analyses identified alternative splicing as a significantly enriched pathway for hsa-miR-1270. The top miRNAs in three other groups were predicted to target transcriptional and developmental pathways. Here, we showed for the first time significantly different levels of miRNAs and differently represented mRNA levels of predicted target genes in EPC derived from preeclampsia. Understanding the effects of preeclampsia on the epigenetic mechanisms of EPC will be crucial and may provide initial insights for further evaluation of the benefits of therapies targeting this cell population.


Asunto(s)
Células Progenitoras Endoteliales/metabolismo , MicroARNs/genética , Preeclampsia/genética , Adulto , Proteínas Similares a la Angiopoyetina/genética , Antígenos CD/genética , Estudios de Casos y Controles , Proliferación Celular , Células Cultivadas , Quimiotaxis , Femenino , Sangre Fetal/citología , Sangre Fetal/metabolismo , Perfilación de la Expresión Génica , Humanos , Recién Nacido , Masculino , MicroARNs/sangre , MicroARNs/metabolismo , Neovascularización Patológica/genética , Preeclampsia/sangre , Preeclampsia/metabolismo , Embarazo , ARN Mensajero/sangre , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores de Transferrina/genética , Adulto Joven
15.
Medicine (Baltimore) ; 100(26): e26482, 2021 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-34190173

RESUMEN

ABSTRACT: To study the dynamic changes in perinatal coagulation function in patients with preeclampsia (PE).The general data and coagulation indexes of 290 PE patients during the perinatal period (prenatal and 1 and 3 days postpartum) and 256 healthy pregnant women in the third trimester of pregnancy were investigated, and the data were analyzed.Compared with healthy pregnant women, prothrombin time (PT), fibrinogen (FIB), platelet count (PLT), mean platelet volume (MPV), thrombocytocrit (PCT), maximum amplitude (MA), and coagulation index (CI) of PE patients decreased, and activated partial thrombin time (APTT), thrombin time (TT), D-dimer (DD), platelet distribution width (PDW) and K values increased before delivery (P < .05). APTT and FIB in PE patients were lower in the day 1 postpartum group than in the prenatal and postpartum day 3 groups, and TT, DD, and fibrin degradation products (FDP) were higher (P < .05). PCT and MPV were highest in the prenatal group (P < .05).Compared with that of healthy pregnant women, the coagulation function of PE patients is in a relatively low-coagulation and high-fibrinolysis state on postpartum day 1, which increases the risk of postpartum hemorrhage and other adverse outcomes.


Asunto(s)
Pruebas de Coagulación Sanguínea/métodos , Atención Perinatal , Pruebas de Función Plaquetaria/métodos , Hemorragia Posparto , Preeclampsia , Adulto , Coagulación Sanguínea/fisiología , China/epidemiología , Femenino , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Fibrinólisis/fisiología , Humanos , Atención Perinatal/métodos , Atención Perinatal/estadística & datos numéricos , Recuento de Plaquetas/métodos , Hemorragia Posparto/sangre , Hemorragia Posparto/etiología , Hemorragia Posparto/terapia , Preeclampsia/sangre , Preeclampsia/diagnóstico , Preeclampsia/fisiopatología , Embarazo , Resultado del Embarazo/epidemiología
16.
J Am Soc Nephrol ; 32(8): 1853-1863, 2021 08.
Artículo en Inglés | MEDLINE | ID: mdl-34155060

RESUMEN

Soluble Fms-like tyrosine kinase (sFlt-1/sVEGFR1) is a naturally occurring antagonist of vascular endothelial growth factor (VEGF). Despite being a secreted, soluble protein lacking cytoplasmic and transmembrane domains, sFlt-1 can act locally and be protective against excessive microenvironmental VEGF concentration or exert autocrine functions independently of VEGF. Circulating sFlt-1 may indiscriminately affect endothelial function and the microvasculature of distant target organs. The clinical significance of excess sFlt-1 in kidney disease was first shown in preeclampsia, a major renal complication of pregnancy. However, circulating sFlt-1 levels appear to be increased in various diseases with varying degrees of renal impairment. Relevant clinical associations between circulating sFlt-1 and severe outcomes (e.g., endothelial dysfunction, renal impairment, cardiovascular disease, and all-cause mortality) have been observed in patients with CKD and after kidney transplantation. However, sFlt-1 appears to be protective against renal dysfunction-associated aggravation of atherosclerosis and diabetic nephropathy. Therefore, in this study, we provide an update on sFlt-1 in several kidney diseases other than preeclampsia, discuss clinical findings and experimental studies, and briefly consider its use in clinical practice.


Asunto(s)
Lesión Renal Aguda/sangre , Microvasos/patología , Insuficiencia Renal Crónica/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Lesión Renal Aguda/cirugía , Biomarcadores/sangre , Vasos Coronarios/patología , Endotelio/fisiopatología , Femenino , Humanos , Riñón/irrigación sanguínea , Riñón/patología , Trasplante de Riñón , Preeclampsia/sangre , Embarazo , Diálisis Renal , Insuficiencia Renal Crónica/terapia
17.
Obstet Gynecol ; 137(6): 1023-1031, 2021 06 01.
Artículo en Inglés | MEDLINE | ID: mdl-33957644

RESUMEN

OBJECTIVE: To evaluate the clinical and laboratory characteristics in pregnancy that differentiate preeclampsia from acute renal allograft rejection and to investigate the maternal, neonatal, and graft sequelae of these diagnoses. METHODS: We conducted a retrospective case-controlled registry study of data abstracted from Transplant Pregnancy Registry International deliveries between 1968 and 2019. All adult kidney transplant recipients with singleton pregnancies of at least 20 weeks of gestation were included. Acute rejection was biopsy proven and preeclampsia was diagnosed based on contemporary criteria. Variables were compared using χ2, Fisher exact, and Wilcoxon rank sum tests as appropriate. Multivariable linear regression was used to analyze preterm birth. Kaplan-Meier curves with log-rank test and Cox proportional hazards model were used to compare graft loss over time. RESULTS: There were 26 pregnant women with biopsy-confirmed acute rejection who were matched by the year they conceived to 78 pregnant women with preeclampsia. Recipients with acute rejection had elevated peripartum serum creatinine levels (73% vs 14%, P<.001), with median intrapartum creatinine of 3.90 compared with 1.15 mg/dL (P<.001). Conversely, only patients with preeclampsia had a significant increase in proteinuria from baseline. Although there were no significant differences in maternal outcomes, graft loss within 2 years postpartum (42% vs 10%) and long-term graft loss (73% vs 35%) were significantly increased in recipients who experienced acute rejection (P<.001 for both). The frequency of delivery before 32 weeks of gestation was 53% with acute rejection and 20% with preeclampsia. After controlling for hypertension and immunosuppressant use, acute rejection was associated with higher frequency of delivery at less than 32 weeks of gestation (adjusted odds ratio 4.04, 95% CI 1.10-15.2). CONCLUSION: In pregnancy, acute rejection is associated with higher creatinine levels, and preeclampsia is associated with increased proteinuria. Acute rejection in pregnancy carries a risk of prematurity and graft loss beyond that of preeclampsia for kidney transplant recipients. FUNDING SOURCE: The Transplant Pregnancy Registry International is supported in part by an educational grant from Veloxis Pharmaceuticals.


Asunto(s)
Creatinina/sangre , Rechazo de Injerto/diagnóstico , Trasplante de Riñón/efectos adversos , Preeclampsia/diagnóstico , Proteinuria/orina , Enfermedad Aguda , Adulto , Estudios de Casos y Controles , Diagnóstico Diferencial , Femenino , Edad Gestacional , Rechazo de Injerto/sangre , Rechazo de Injerto/patología , Rechazo de Injerto/orina , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Preeclampsia/sangre , Preeclampsia/orina , Embarazo , Nacimiento Prematuro/etiología , Modelos de Riesgos Proporcionales , Sistema de Registros , Estudios Retrospectivos , Adulto Joven
18.
PLoS One ; 16(5): e0251227, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34010327

RESUMEN

Preeclampsia (PE) is a major cause of maternal and new-born morbidity and mortality. Angiogenic factors contribute a major role in the vascular dysfunction associated with PE. We investigated the circulating levels of vascular endothelial growth factor (VEGF), placental growth factor (PlGF) and soluble Feline McDonough Sarcoma (fms)-like tyrosine kinase-1 (sFlt1), their association with PE and diagnostic performance of disease among pregnant women in Uganda. Using a case-control study design, 106 women with PE and 106 with normal pregnancy were enrolled. Demographic and clinical characteristics, and anticoagulated blood samples were collected from participants. Plasma VEGF, PlGF and sFlt1 levels were measured using Luminex and enzyme linked immunosorbent assays (ELISA). Conditional logistic regression was used to explore association of angiogenic factors with PE and receiver operating characteristic analysis was performed to investigate PE diagnostic performance. Levels of VEGF and PIGF were significantly lower in cases compared to controls (VEGF: median = 0.71 pg/ml (IQR = 0.38-1.11) Vs 1.20 pg/ml (0.64-1.91), p-value<0.001 and PlGF: 2.20 pg/ml (1.08-5.86) Vs 84.62 pg/ml (34.00-154.45), p-value<0.001). Plasma levels of sFlt1 were significantly higher in cases than controls (median = 141.13 (71.76-227.10) x103 pg/ml Vs 19.86 (14.20-29.37) x103 pg/ml). Increasing sFlt1 levels were associated with increased likelihood of PE (aOR = 4.73; 95% CI, 1.18-19.01; p-value = 0.0287). The sFlt1/PlGF ratio and sFlt1 had a better performance for diagnosis of PE, with AUC = 0.95 (95% CI, 0.93-0.98) followed by PlGF with AUC = 0.94 (95% CI, 0.91-0.97). Therefore, sFlt1, sFlt1/PlGF ratio and PlGF are potential candidates for incorporation into algorithms for PE diagnosis in the Ugandan population.


Asunto(s)
Factor de Crecimiento Placentario/sangre , Preeclampsia/sangre , Factor A de Crecimiento Endotelial Vascular/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Modelos Logísticos , Preeclampsia/diagnóstico , Embarazo , Trimestres del Embarazo/sangre , Curva ROC , Uganda , Adulto Joven
19.
Hypertens Pregnancy ; 40(2): 144-151, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-34014801

RESUMEN

Objective: To evaluate the serum survivin level in preeclampsia.Methods: Eighty-eight pregnancies complicated with preeclampsia and 88 gestational-age (GA)-matched uncomplicated pregnancies were evaluated.Results: Mean serum survivin was detected to be significantly decreased in the early- (EOPE) and late-onset (LOPE) preeclampsia subgroups than the GA-matched control-groups; and were comparable in EOPE- and LOPE-groups after correction for GA. Serum survivin had weak negative correlations with systolic and diastolic arterial blood pressure.Conclusion: The serum survivin level was decreased in preeclamptic patients than the GA-matched controls. More comprehensive studies are needed to clarify the timing and extent of placental apoptosis in preeclampsia.


Asunto(s)
Preeclampsia/diagnóstico , Survivin/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Edad Gestacional , Humanos , Preeclampsia/sangre , Embarazo
20.
Hypertens Pregnancy ; 40(2): 162-170, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33941012

RESUMEN

OBJECTIVE: The aim of the study was to assess the potential role of oxidative stress and lipid status in the onset of preeclampsia.METHODS: 138 high-risk pregnant women were prospectively followed. Assessment of oxidative stress (TAS, TOS, AOPP and SH groups) and lipid status (t-C, LDL-C, HDL-C, TGC, APO-A1, APO-B) was carried out during the pregnancy.RESULTS: 30 women developed preeclampsia. TGC, atherogenic index of plasma, TAS and SH levels were higher in women who subsequently developed preeclampsia (p<0.05).CONCLUSION: Oxidative stress and lipid status disturbance have a potential role in the onset of preeclampsia in high risk pregnancies.


Asunto(s)
Antioxidantes/metabolismo , Lípidos/sangre , Estrés Oxidativo/fisiología , Preeclampsia/diagnóstico , Adulto , Apolipoproteína A-I/sangre , Apolipoproteínas B/sangre , Biomarcadores/sangre , Colesterol/sangre , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Femenino , Humanos , Preeclampsia/sangre , Preeclampsia/metabolismo , Embarazo , Embarazo de Alto Riesgo , Estudios Prospectivos , Triglicéridos/sangre
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