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1.
Am J Obstet Gynecol ; 2020 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-32147290

RESUMO

BACKGROUND: Early spontaneous preterm delivery is often associated with microbial invasion of the amniotic cavity and/or intra-amniotic inflammation. OBJECTIVE: To develop and validate clinically feasible multivariable prediction models of spontaneous delivery within 7 days and microbial invasion of the amniotic cavity in women admitted with diagnose of preterm labor and intact membranes below 34 weeks. STUDY DESIGN: We used data from a cohort of women admitted from 2012 to 2018 with diagnosis of preterm labor below 34 weeks who had undergone amniocentesis to rule out microbial invasion of the amniotic cavity. Main outcome was spontaneous delivery within 7 days from admission. Secondary outcome was microbial invasion of the amniotic cavity, defined by a positive culture and/or 16S ribosomal RNA gene in amniotic fluid. The sample (n= 358) was divided into derivation (2012-2016) and validation cohorts (2017-2018). Logistic regression models using a stepwise selection of variables were developed for the outcomes evaluated. We explored as predictive variables ultrasound cervical length measurement at admission, maternal C-reactive protein (CRP), gestational age, amniotic fluid glucose and interleukin (IL)-6 (expressed as log unit). Models were developed in the derivation cohort and applied to the validation cohort and diagnostic performance was calculated. RESULTS: The derivation cohort included 263 women and the validation cohort 95 women. One hundred and five (39%, 105/268) of women spontaneously delivered in the following 7 days and 68 (19%, 68/358) had microbial invasion of the amniotic cavity. For spontaneous delivery within 7 days after admission, four predictors were identified: cervical length at admission, gestational age, amniotic fluid glucose and IL-6. The diagnostic performance of the model was assessed in the validation cohort using the receiver operating characteristic curve and showed an area under curve (AUROC) of 0.86 (95% confidence interval (CI) 0.77-0.95) with a detection rate of spontaneous delivery within 7 days of 87% , a false-positive rate of 33%, negative predictive value of 80% and negative Likelihood ratio of 0.1908. For microbial invasion of the amniotic cavity, two independent predictors of the amniotic cavity were identified: amniotic fluid glucose and maternal CRP. The AUROC in the validation cohort was 0.83 (95% confidence interval (CI) 0.70-0.96) with a detection rate of 76%, a false positive rate of 8%, negative predictive value of 93% and negative Likelihood ratio of 0.2591. CONCLUSIONS: In women with preterm labor, we propose two clinically feasible prediction models to classify as low versus high-risk of spontaneous delivery within 7 days and of microbial invasion of the amniotic cavity. The models showed a high diagnostic performance and could be of value to optimize clinical management.

2.
J Matern Fetal Neonatal Med ; : 1-4, 2020 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-32164477

RESUMO

Objectives: To evaluate the reproducibility of ultrasound cervical length (CL) measurement at the second trimester.Methods: A set of 565 cervical ultrasound images were collected at 19 + 0-24 + 6 weeks' gestation. Two senior maternal-fetal specialists measured CL in each image on three occasions 2 weeks apart. In the interval between the first and following two measures, the clinicians reviewed 20 images together to agree on the criteria for measurement. Measurements were analyzed for intra- and inter-observer disagreement. The robustness of patient classification when CL measure was used with different cutoff thresholds was analyzed.Results: Average intra-observer deviation was 2.8 mm for clinician 1 and 3.7 mm for clinician 2. Inter-observer deviation among the two clinicians was 5.2 and 3.2 mm before and after reviewing measurement criteria together. When cutoffs were used to classify as "short" cervix, disagreement ranged from 22 to 70% depending on operator and threshold used.Conclusion: Ultrasound CL measurements by experts showed moderate intra- and inter-observer reproducibility. The use of specific cutoffs to classify patients as high or low risk resulted in wide disagreements. The results stress the importance of training and quality assessments on considering universal screening application of CL measurement.

3.
Biosens Bioelectron ; 153: 112028, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31989937

RESUMO

Oxygen is vital for energy metabolism in mammals and the variability of the concentration is considered a clinical alert for a wide range of metabolic malfunctions in medicine. In this article, we describe the development and application of a micro-needle implantable platinum-based electrochemical sensor for measuring partial pressure of oxygen in intramuscular tissue (in-vivo) and vascular blood (ex-vivo). The Pt-Nafion® sensor was characterized morphological and electrochemically showing a higher sensitivity of -2.496 nA/mmHg (-1.495 nA/µM) when comparing with its bare counterpart. Our sensor was able to discriminate states with different oxygen partial pressures (pO2) for ex-vivo (blood) following the same trend of the commercial gas analyzer used as standard. For in-vivo (intramuscular) experiments, since there is not a gold standard for measuring pO2 in tissue, it was not possible to correlate the obtained currents with the pO2 in tissue. However, our sensor was able to detect clear statistical differences of O2 between hyperoxia and hypoxia states in tissue.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31909552

RESUMO

OBJECTIVE: Coarctation of the aorta (CoA) is associated with left ventricular (LV) dysfunction in neonates and adults; however cardiac structure and function in fetal CoA and the neonatal cardiac adaptation has not been described. We aimed to investigate the presence of cardiovascular structural remodeling and dysfunction in fetuses with CoA and their early postnatal cardiac adaptation. METHODS: A prospective observational case-control study was conducted in 30 fetuses with CoA and 60 gestational-age matched normal controls. A comprehensive echocardiographic evaluation was performed at third trimester of pregnancy and after birth (20 CoA and 44 controls). Additionally, myocardial microstructure was assessed in one fetus and one neonatal CoA, using synchrotron-based phase-contrast X-ray tomography and histology, respectively. RESULTS: Fetuses with CoA showed significant left-to-right volume redistribution with right ventricular (RV) size and output dominance and significant geometry alterations with an abnormally elongated left ventricle (LV) (LV sphericity: CoA median 2.4 (IQR 0.7) vs. controls 1.8 (0.4), p<0.001). Biventricular function was preserved, and no ventricular hypertrophy was observed. Synchrotron tomography and histological assessment revealed normal myocyte organization. Postnatally, the LV showed prompt remodeling becoming more globular (LV sphericity: CoA 1.5 (0.4) vs. controls 1.8 (0.3), p<0.001) with preserved systolic and normalized output, but altered diastolic parameters (LV E-wave velocity 97.0 (55.0) vs. 57.0 (16.0) cm/s; A-wave velocity 70.5 (24.8) vs. 47.0 (12.0) cm/s; A' 4.8 (5.1) vs. 6.0 (3.0) cm/s; p<0.05). The neonatal RV showed increased longitudinal function in the presence of a patent arterial duct. CONCLUSIONS: Our results suggest a unique fetal cardiac remodeling in which the LV stays smaller from the decreased growth stimulus of reduced volume load. Postnatally, the LV is acutely volume loaded resulting in an overall geometry change with higher filling velocities and preserved systolic function. These findings improve our understanding of CoA from fetal to neonatal life. This article is protected by copyright. All rights reserved.

5.
J Steroid Biochem Mol Biol ; 197: 105520, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31698034

RESUMO

The simultaneous determination of a broad panel of steroids provides more accurate information about the hormonal status than the detection of a single hormone. For that reason, the determination of the steroid profile, i.e. the endogenous steroid hormones and their main metabolites, has become the most powerful tool for the study of hormonal imbalances. The usefulness of the evaluation of the steroid profile in urine and plasma is widely accepted. However, despite its broad potential applicability, the evaluation of the whole steroid profile in alternative matrices such as amniotic fluid, saliva and breast milk remains almost unexplored. In this research we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of several steroids and their metabolites in amniotic fluid (28 analytes), saliva (15) and breast milk (12). Sample preparation, chromatographic conditions and mass spectrometric conditions (e.g. ionization species or ion source parameters) were optimized. The method was shown to be linear in the range of endogenous concentrations for all studied metabolites. Intra- and inter-assay accuracies were between 80% and 120% while intra- and inter-precisions were below 20% for all analytes in all matrices. The applicability of the method was evaluated by the comparison between the concentration ranges obtained in healthy volunteers (n = 30 per matrix) and the scarce data previously reported in literature. The concentration ranges for several analytes are reported for the first time. The present methodology represents a useful tool for the comprehensive evaluation of the steroid profile in alternative matrices and can be applicable for different clinical purposes.

6.
Am J Obstet Gynecol ; 222(1): 79.e1-79.e9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31336074

RESUMO

BACKGROUND: Preeclampsia and fetal growth restriction share some pathophysiologic features and are both associated with placental insufficiency. Fetal cardiac remodeling has been described extensively in fetal growth restriction, whereas little is known about preeclampsia with a normally grown fetus. OBJECTIVE: To describe fetal cardiac structure and function in pregnancies complicated by preeclampsia and/or fetal growth restriction as compared with uncomplicated pregnancies. STUDY DESIGN: This was a prospective, observational study including pregnancies complicated by normotensive fetal growth restriction (n=36), preeclampsia with a normally grown fetus (n=35), preeclampsia with fetal growth restriction (preeclampsia with a normally grown fetus-fetal growth restriction, n=42), and 111 uncomplicated pregnancies matched by gestational age at ultrasound. Fetal echocardiography was performed at diagnosis for cases and recruitment for uncomplicated pregnancies. Cord blood concentrations of B-type natriuretic peptide and troponin I were measured at delivery. Univariate and multiple regression analysis were conducted. RESULTS: Pregnancies complicated by preeclampsia and/or fetal growth restriction showed similar patterns of fetal cardiac remodeling with larger hearts (cardiothoracic ratio, median [interquartile range]: uncomplicated pregnancies 0.27 [0.23-0.29], fetal growth restriction 0.31 [0.26-0.34], preeclampsia with a normally grown fetus 0.31 [0.29-0.33), and preeclampsia with fetal growth restriction 0.28 [0.26-0.33]; P<.001) and more spherical right ventricles (right ventricular sphericity index: uncomplicated pregnancies 1.42 [1.25-1.72], fetal growth restriction 1.29 [1.22-1.72], preeclampsia with a normally grown fetus 1.30 [1.33-1.51], and preeclampsia with fetal growth restriction 1.35 [1.27-1.46]; P=.04) and hypertrophic ventricles (relative wall thickness: uncomplicated pregnancies 0.55 [0.48-0.61], fetal growth restriction 0.67 [0.58-0.8], preeclampsia with a normally grown fetus 0.68 [0.61-0.76], and preeclampsia with fetal growth restriction 0.66 [0.58-0.77]; P<.001). Signs of myocardial dysfunction also were observed, with increased myocardial performance index (uncomplicated pregnancies 0.78 z scores [0.32-1.41], fetal growth restriction 1.48 [0.97-2.08], preeclampsia with a normally grown fetus 1.15 [0.75-2.17], and preeclampsia with fetal growth restriction 0.45 [0.54-1.94]; P<.001) and greater cord blood B-type natriuretic peptide (uncomplicated pregnancies 14.2 [8.4-30.9] pg/mL, fetal growth restriction 20.8 [13.1-33.5] pg/mL, preeclampsia with a normally grown fetus 31.8 [16.4-45.8] pg/mL and preeclampsia with fetal growth restriction 37.9 [15.7-105.4] pg/mL; P<.001) and troponin I as compared with uncomplicated pregnancies. CONCLUSION: Fetuses of preeclamptic mothers, independently of their growth patterns, presented cardiovascular remodeling and dysfunction in a similar fashion to what has been previously described for fetal growth restriction. Future research is warranted to better elucidate the mechanism(s) underlying fetal cardiac adaptation in these conditions.

7.
Sci Rep ; 9(1): 18963, 2019 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-31831820

RESUMO

This study aims to investigate the relation between vaginal microbiota and exposition to intra-amniotic inflammation (IAI). We conducted a prospective cohort study in women with preterm labor <34 weeks who had undergone amniocentesis to rule out IAI. Vaginal samples were collected after amniocentesis. Women with IAI included those with positive amniotic fluid (AF) for a microorganism identified by specific culture media and Sanger sequencing 16S ribosomal RNA gene and/or high AF interleukin (IL)-6 levels. Vaginal microbiota was characterized by 16S ribosomal RNA gene amplicon sequencing. Specific quantitative PCR targeted to Lactobacillus spp. was also performed. Regression models were used to evaluate associations between vaginal microbiota and exposition to IAI. Concerning our results, 64 women were included. We observed an inverse association between AF IL-6 levels and load of Lactobacillus spp. Depletion in Lactobacillus spp. load was significantly associated with an early gestational age at delivery and a short latency to delivery. Microbial-diversity was found to be a risk factor for the subsequent occurrence of clinical chorioamnionitis. To the contrary, higher Lactobacillus spp. load had a protective role. In conclusion, the study identifies reduced bacterial load of Lactobacillus spp. in women exposed to IAI and found microbial-diversity and Lactobacillus spp. depletion to be associated with a worse perinatal outcome.

8.
Fetal Diagn Ther ; : 1-12, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31822009

RESUMO

OBJECTIVES: Fetal right ventricular (RV) function assessment is challenging due to the RV geometry and limitations of in utero assessment. Postnatally, 2D echocardiographic RV fractional area change (FAC) is used to assess RV global systolic function by calculating the percentage of change in RV area from systole to diastole. Reports on FAC are scarce in prenatal life, and nomograms throughout pregnancy are not available. Our aims were (1) to study prenatal RV FAC feasibility and reproducibility and (2) to construct nomograms for RV FAC and end-diastolic (ED) and end-systolic (ES) RV areas from 18 to 41 weeks of gestation. METHODS: Prospective cohort study including 602 low-risk singleton pregnancies undergoing a fetal echocardiography from 18 to 41 weeks of gestation. RV ED and ES areas were measured following standard recommendations for ventricular dimensions and establishing strict landmarks to identify the different phases of the cardiac cycle. RV FAC was calculated as: ([ED area - ES area]/ED area) × 100. RV FAC intra- and inter-observer reproducibility was evaluated in 45 fetuses by calculating the intraclass correlation coefficient (ICC). Parametric regressions were tested to model each parameter against gestational age (GA) and estimated fetal weight (EFW). RESULTS: RV areas and FAC were successfully obtained in ∼99% of fetuses with acceptable reproducibility throughout gestation (RV ED area inter-observer ICC [95% CI] 0.96 [0.93-0.98], RV ES area 0.97 [0.94-0.98], and FAC 0.69 [0.44-0.83]). Nomograms were constructed for RV ED and ES areas and FAC. RV areas showed a quadratic and logarithmic increase with GA and EFW, respectively. In contrast, RV FAC showed a slight quadratic decrease throughout gestation (mean RV FAC ranged from 36% at 18 weeks of gestation [10-90th centiles: 25-47%, respectively] to 29% at 41 weeks [10-90th centiles: 18-40%, respectively]). The best models for RV areas and FAC were a second-degree polynomial. CONCLUSIONS: RV FAC is a feasible and reproducible parameter to assess RV global systolic function in fetal life. We provide reference ranges adjusted by GA and EFW that can be used as normal references for the assessment of RV function in prenatal conditions.

9.
Acad Radiol ; 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31879159

RESUMO

Recent advances in fetal imaging open the door to enhanced detection of fetal disorders and computer-assisted surgical planning. However, precise segmentation of womb's tissues is challenging due to motion artifacts caused by fetal movements and maternal respiration during acquisition. This work aims to efficiently segment different intrauterine tissues in fetal magnetic resonance imaging (MRI) and 3D ultrasound (US). First, a large set of ninety-four radiomic features are extracted to characterize the mother uterus, placenta, umbilical cord, fetal lungs, and brain. The optimal features for each anatomy are identified using both K-best and Sequential Forward Feature Selection techniques. These features are then fed to a Support Vector Machine with instance balancing to accurately segment the intrauterine anatomies. To the best of our knowledge, this is the first time that "Radiomics" is expanded from classification tasks to segmentation purposes to deal with challenging fetal images. In addition, we evaluate several state-of-the-art deep learning-based segmentation approaches. Validation is extensively performed on a set of 60 axial MRI and 3D US images from pathological and clinical cases. Our results suggest that combining the selected 10 radiomic features per anatomy along with DeepLabV3+ or BiSeNet architectures for MRI, and PSPNet or Tiramisu for 3D US, can lead to the highest fetal / maternal tissue segmentation performance, robustness, informativeness, and heterogeneity. Therefore, this work opens new avenues for advancement of segmentation techniques and, in particular, for improved fetal surgical planning.

10.
Clin J Am Soc Nephrol ; 14(12): 1719-1732, 2019 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-31694864

RESUMO

BACKGROUND AND OBJECTIVES: Atypical hemolytic uremic syndrome is a form of thrombotic microangiopathy caused by dysregulation of the alternative complement pathway. There is evidence showing complement activation in other thrombotic microangiopathies. The aim of this study was to evaluate complement activation in different thrombotic microangiopathies and to monitor treatment response. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Complement activation was assessed by exposing endothelial cells to sera or activated-patient plasma-citrated plasma mixed with a control sera pool (1:1)-to analyze C5b-9 deposits by immunofluorescence. Patients with atypical hemolytic uremic syndrome (n=34) at different stages of the disease, HELLP syndrome (a pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count) or severe preeclampsia (n=10), and malignant hypertension (n=5) were included. RESULTS: Acute phase atypical hemolytic uremic syndrome-activated plasma induced an increased C5b-9 deposition on endothelial cells. Standard and lower doses of eculizumab inhibited C5b-9 deposition in all patients with atypical hemolytic uremic syndrome, except in two who showed partial remission and clinical relapse. Significant fibrin formation was observed together with C5b-9 deposition. Results obtained using activated-plasma samples were more marked and reproducible than those obtained with sera. C5b-9 deposition was also increased with samples from patients with HELLP (all cases) and preeclampsia (90%) at disease onset. This increase was sustained in those with HELLP after 40 days, and levels normalized in patients with both HELLP and preeclampsia after 6-9 months. Complement activation in those with malignant hypertension was at control levels. CONCLUSIONS: The proposed methodology identifies complement overactivation in patients with atypical hemolytic uremic syndrome at acute phase and in other diseases such as HELLP syndrome and preeclampsia. Moreover, it is sensitive enough to individually assess the efficiency of the C5 inhibition treatment.

11.
Eur J Endocrinol ; 181(5): 565-577, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539877

RESUMO

Design: Gestational diabetes mellitus (GDM) is one of the most common pregnancy complications and its prevalence is constantly rising worldwide. Diagnosis is commonly in the late second or early third trimester of pregnancy, though the development of GDM starts early; hence, first-trimester diagnosis is feasible. Objective: Our objective was to identify microRNAs that best distinguish GDM samples from those of healthy pregnant women and to evaluate the predictive value of microRNAs for GDM detection in the first trimester. Methods: We investigated the abundance of circulating microRNAs in the plasma of pregnant women in their first trimester. Two populations were included in the study to enable population-specific as well as cross-population inspection of expression profiles. Each microRNA was tested for differential expression in GDM vs control samples, and their efficiency for GDM detection was evaluated using machine-learning models. Results: Two upregulated microRNAs (miR-223 and miR-23a) were identified in GDM vs the control set, and validated on a new cohort of women. Using both microRNAs in a logistic-regression model, we achieved an AUC value of 0.91. We further demonstrated the overall predictive value of microRNAs using several types of multivariable machine-learning models that included the entire set of expressed microRNAs. All models achieved high accuracy when applied on the dataset (mean AUC = 0.77). The significance of the classification results was established via permutation tests. Conclusions: Our findings suggest that circulating microRNAs are potential biomarkers for GDM in the first trimester. This warrants further examination and lays the foundation for producing a novel early non-invasive diagnostic tool for GDM.


Assuntos
MicroRNA Circulante/sangue , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Tecido Adiposo/química , Adulto , Estudos de Casos e Controles , Diagnóstico Precoce , Feminino , Humanos , Aprendizado de Máquina , MicroRNAs/sangue , Placenta/química , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez , Reprodutibilidade dos Testes
12.
Comput Methods Programs Biomed ; 179: 104993, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443866

RESUMO

Twin-to-twin transfusion syndrome (TTTS) is a serious condition that may occur in pregnancies when two or more fetuses share the same placenta. It is characterized by abnormal vascular connections in the placenta that cause blood to flow unevenly between the babies. If left untreated, perinatal mortality occurs in 90% of cases, whilst neurological injuries are still present in TTTS survivors. Minimally invasive fetoscopic laser surgery is the standard and optimal treatment for this condition, but is technically challenging and can lead to complications. Acquiring and maintaining the required surgical skills need consistent practice, and a steep learning curve. An accurate preoperative planning is thus vital for complex TTTS cases. To this end, we propose the first TTTS fetal surgery planning and simulation platform. The soft tissue of the mother, the uterus, the umbilical cords, the placenta and its vascular tree are segmented and registered automatically from magnetic resonance imaging and 3D ultrasound using computer vision and deep learning techniques. The proposed state-of-the-art technology is integrated into a flexible C++ and MITK-based application to provide a full exploration of the intrauterine environment by simulating the fetoscope camera as well as the laser ablation, determining the correct entry point, training doctors' movements and trajectory ahead of operation, which allows improving upon current practice. A comprehensive usability study is reported. Experienced surgeons rated highly our TTTS planner and simulator, thus being a potential tool to be implemented in real and complex TTTS surgeries.


Assuntos
Transfusão Feto-Fetal/cirurgia , Fetoscopia/métodos , Modelos Anatômicos , Algoritmos , Gráficos por Computador , Simulação por Computador , Feminino , Transfusão Feto-Fetal/diagnóstico por imagem , Fetoscopia/estatística & dados numéricos , Humanos , Imagem Tridimensional , Recém-Nascido , Terapia a Laser/métodos , Terapia a Laser/estatística & dados numéricos , Imagem por Ressonância Magnética/estatística & dados numéricos , Modelagem Computacional Específica para o Paciente/estatística & dados numéricos , Placenta/diagnóstico por imagem , Gravidez , Interface Usuário-Computador , Útero/diagnóstico por imagem
13.
PLoS One ; 14(6): e0218192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31226127

RESUMO

Intrauterine growth restriction (IUGR) is a fetal condition that affects up to 10% of all pregnancies and is associated with cardiovascular structural and functional remodelling that persists postnatally. Some studies have reported an increase in myocardial coronary blood flow in severe IUGR fetuses which has been directly associated to the dilatation of the coronary arteries. However, a direct measurement of the coronaries' lumen diameter in IUGR has not been reported before. The aim of this paper is to perform, for the first time, a quantitative analysis of the effects of IUGR in cardiac geometry and coronary vessel size in a well-known rabbit model of IUGR using synchrotron-based X-ray Phase Contrast Tomography Imaging (X-PCI). Eight rabbit fetal hearts were imaged non-destructively with X-PCI. 3D reconstructions of the coronary arterial tree were obtained after semi-automatic image segmentation. Different morphometric features including vessel lumen diameter of the three main coronaries were automatically quantified. IUGR fetuses had more globular hearts and dilated coronary arteries as compared to controls. We have quantitatively shown that IUGR leads to structural coronary vascular tree remodelling and enlargement as an adaptation mechanism in response to an adverse environment of restricted oxygen and nutrients and increased perfusion pressure.


Assuntos
Vasos Coronários/diagnóstico por imagem , Retardo do Crescimento Fetal/diagnóstico por imagem , Feto/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Remodelação Vascular , Animais , Vasos Coronários/embriologia , Vasos Coronários/fisiopatologia , Modelos Animais de Doenças , Feminino , Retardo do Crescimento Fetal/fisiopatologia , Feto/fisiopatologia , Gravidez , Coelhos
14.
Med Image Anal ; 54: 263-279, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30954853

RESUMO

Recent advances in fetal magnetic resonance imaging (MRI) open the door to improved detection and characterization of fetal and placental abnormalities. Since interpreting MRI data can be complex and ambiguous, there is a need for robust computational methods able to quantify placental anatomy (including its vasculature) and function. In this work, we propose a novel fully-automated method to segment the placenta and its peripheral blood vessels from fetal MRI. First, a super-resolution reconstruction of the uterus is generated by combining axial, sagittal and coronal views. The placenta is then segmented using 3D Gabor filters, texture features and Support Vector Machines. A uterus edge-based instance selection is proposed to identify the support vectors defining the placenta boundary. Subsequently, peripheral blood vessels are extracted through a curvature-based corner detector. Our approach is validated on a rich set of 44 control and pathological cases: singleton and (normal / monochorionic) twin pregnancies between 25-37 weeks of gestation. Dice coefficients of 0.82 â€¯±â€¯ 0.02 and 0.81 â€¯±â€¯ 0.08 are achieved for placenta and its vasculature segmentation, respectively. A comparative analysis with state of the art convolutional neural networks (CNN), namely, 3D U-Net, V-Net, DeepMedic, Holistic3D Net, HighRes3D Net and Dense V-Net is also conducted for placenta localization, with our method outperforming all CNN approaches. Results suggest that our methodology can aid the diagnosis and surgical planning of severe fetal disorders.

15.
J Cell Mol Med ; 23(6): 3962-3973, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30941904

RESUMO

Intrauterine growth restriction (IUGR) is an obstetric complication characterised by placental insufficiency and secondary cardiovascular remodelling that can lead to cardiomyopathy in adulthood. Despite its aetiology and potential therapeutics are poorly understood, bioenergetic deficits have been demonstrated in adverse foetal and cardiac development. We aimed to evaluate the role of mitochondria in human pregnancies with IUGR. In a single-site, cross-sectional and observational study, we included placenta and maternal peripheral and neonatal cord blood mononuclear cells (PBMC and CBMC) from 14 IUGR and 22 control pregnancies. The following mitochondrial measurements were assessed: enzymatic activities of mitochondrial respiratory chain (MRC) complexes I, II, IV, I + III and II + III, oxygen consumption (cell and complex I-stimulated respiration), mitochondrial content (citrate synthase [CS] activity and mitochondrial DNA copy number), total ATP levels and lipid peroxidation. Sirtuin3 expression was evaluated as a potential regulator of bioenergetic imbalance. Intrauterine growth restriction placental tissue showed a significant decrease of MRC CI enzymatic activity (P < 0.05) and CI-stimulated oxygen consumption (P < 0.05) accompanied by a significant increase of Sirtuin3/ß-actin protein levels (P < 0.05). Maternal PBMC and neonatal CBMC from IUGR patients presented a not significant decrease in oxygen consumption (cell and CI-stimulated respiration) and MRC enzymatic activities (CII and CIV). Moreover, CS activity was significantly reduced in IUGR new-borns (P < 0.05). Total ATP levels and lipid peroxidation were preserved in all the studied tissues. Altered mitochondrial function of IUGR is especially present at placental and neonatal level, conveying potential targets to modulate obstetric outcome through dietary interventions aimed to regulate Sirtuin3 function.

16.
PLoS One ; 14(3): e0213279, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30830946

RESUMO

BACKGROUND: Mitochondrial toxicity related to maternal combined antiretroviral treatment (cART) may have an impact on the heart of HIV-exposed uninfected (HEU) fetuses. Our objective was to evaluate fetal cardiovascular and mitochondrial biomarkers in HIV pregnancies. METHODS: Prospective cohort including 47 HIV-infected and 47 non HIV-infected pregnancies. Fetal echocardiography was performed at 26-32 weeks of pregnancy. Umbilical cord blood and placental tissue were collected to study mitochondrial DNA content (mtDNA) (ratio 12SrRNA/RNAseP) and mitochondrial function (cytochrome c oxidase, COX, enzymatic activity) normalized by mitochondrial content (citrate synthase, CS). RESULTS: HEU fetuses showed hypertrophic hearts (left myocardial wall thickness: HIV mean 3.21 mm (SD 0.81) vs. non-HIV 2.72 (0.42), p = 0.012), with signs of systolic and diastolic dysfunction (isovolumic relaxation time: HIV 52.2 ms (8.85) vs. non-HIV 42.5 ms (7.30); p<0.001). Cord blood mitochondrial content was significantly increased in HIV-exposed fetuses (CS activity: HIV 82.9 nmol/min.mg of protein (SD 40.5) vs. non-HIV 56.7 nmol/min.mg of protein (28.4); p = 0.007), with no differences in mtDNA content and COX activity. Both myocardial and mitochondrial mass parameters were significantly associated with zidovudine exposure. CONCLUSIONS: HEU fetuses showed signs of increased myocardial and mitochondrial mass associated with maternal zidovudine treatment, suggesting a fetal adaptive response to cART toxicity.


Assuntos
Terapia Antirretroviral de Alta Atividade , Feto/patologia , Infecções por HIV/complicações , HIV/efeitos dos fármacos , Coração/fisiopatologia , Mitocôndrias/patologia , Complicações Infecciosas na Gravidez/epidemiologia , Efeitos Tardios da Exposição Pré-Natal/epidemiologia , Adulto , Estudos de Casos e Controles , Ecocardiografia , Feminino , Sangue Fetal , Feto/efeitos dos fármacos , Feto/virologia , Idade Gestacional , HIV/isolamento & purificação , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Coração/efeitos dos fármacos , Coração/virologia , Humanos , Troca Materno-Fetal , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/virologia , Gravidez , Complicações Infecciosas na Gravidez/virologia , Efeitos Tardios da Exposição Pré-Natal/virologia , Estudos Prospectivos
17.
Clin Epigenetics ; 11(1): 35, 2019 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-30808399

RESUMO

BACKGROUND: Genome-wide studies have begun to link subtle variations in both allelic DNA methylation and parent-of-origin genetic effects with early development. Numerous reports have highlighted that the placenta plays a critical role in coordinating fetal growth, with many key functions regulated by genomic imprinting. With the recent description of wide-spread polymorphic placenta-specific imprinting, the molecular mechanisms leading to this curious polymorphic epigenetic phenomenon is unknown, as is their involvement in pregnancies complications. RESULTS: Profiling of 35 ubiquitous and 112 placenta-specific imprinted differentially methylated regions (DMRs) using high-density methylation arrays and pyrosequencing revealed isolated aberrant methylation at ubiquitous DMRs as well as abundant hypomethylation at placenta-specific DMRs. Analysis of the underlying chromatin state revealed that the polymorphic nature is not only evident at the level of allelic methylation, but DMRs can also adopt an unusual epigenetic signature where the underlying histones are biallelically enrichment of H3K4 methylation, a modification normally mutually exclusive with DNA methylation. Quantitative expression analysis in placenta identified two genes, GPR1-AS1 and ZDBF2, that were differentially expressed between IUGRs and control samples after adjusting for clinical factors, revealing coordinated deregulation at the chromosome 2q33 imprinted locus. CONCLUSIONS: DNA methylation is less stable at placenta-specific imprinted DMRs compared to ubiquitous DMRs and contributes to privileged state of the placenta epigenome. IUGR-associated expression differences were identified for several imprinted transcripts independent of allelic methylation. Further work is required to determine if these differences are the cause IUGR or reflect unique adaption by the placenta to developmental stresses.


Assuntos
Metilação de DNA , Retardo do Crescimento Fetal/genética , Perfilação da Expressão Gênica/métodos , Placenta/química , Cromossomos Humanos Par 2/genética , Ilhas de CpG , Proteínas de Ligação a DNA/genética , Feminino , Retardo do Crescimento Fetal/metabolismo , Regulação da Expressão Gênica , Impressão Genômica , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Histonas/metabolismo , Humanos , Linhagem , Gravidez
18.
Sci Rep ; 9(1): 1950, 2019 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-30760806

RESUMO

The objective of this study was to evaluate the performance of a new version of quantusFLM®, a software tool for prediction of neonatal respiratory morbidity (NRM) by ultrasound, which incorporates a fully automated fetal lung delineation based on Deep Learning techniques. A set of 790 fetal lung ultrasound images obtained at 24 + 0-38 + 6 weeks' gestation was evaluated. Perinatal outcomes and the occurrence of NRM were recorded. quantusFLM® version 3.0 was applied to all images to automatically delineate the fetal lung and predict NRM risk. The test was compared with the same technology but using a manual delineation of the fetal lung, and with a scenario where only gestational age was available. The software predicted NRM with a sensitivity, specificity, and positive and negative predictive value of 71.0%, 94.7%, 67.9%, and 95.4%, respectively, with an accuracy of 91.5%. The accuracy for predicting NRM obtained with the same texture analysis but using a manual delineation of the lung was 90.3%, and using only gestational age was 75.6%. To sum up, automated and non-invasive software predicted NRM with a performance similar to that reported for tests based on amniotic fluid analysis and much greater than that of gestational age alone.

19.
Fetal Diagn Ther ; : 1-12, 2019 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-30612128

RESUMO

OBJECTIVE: There is a need for standardized reference values for cardiac dimensions in prenatal life. The objective of the present study was to construct nomograms for fetal cardiac dimensions using a well-defined echocardiographic methodology in a low-risk population. METHODS: This is a prospective cohort study including 602 low-risk singleton pregnancies undergoing a standardized fetal echocardiography to accurately assess fetal cardiac, ventricular, and atrial dimensions. Parametric regressions were tested to model each measurement against gestational age from 18 to 41 weeks of gestation. RESULTS: Nomograms were constructed for fetal cardiac dimensions (transverse and longitudinal diameters and areas) of the whole heart, atria, and ventricles, as well as myocardial wall thicknesses. All dimensions showed a progressive increase with gestational age. The best model for most parameters was a second-degree linear polynomial. Fetal cardiac, ventricular, and atrial diameters and areas were successfully obtained in 98.6% of the fetuses, while myocardial wall thicknesses could be obtained in 96.5% of the population. The results showed excellent interobserver and intraobserver reproducibility (intraclass correlation coefficient, ICC > 0.811 and ICC > 0.957, respectively). CONCLUSIONS: We provide standardized and comprehensively evaluated reference values for fetal cardiac morphometric parameters across gestation in a low-risk population. These no mograms would enable the early identification of different patterns of fetal cardiac remodeling.

20.
Fetal Diagn Ther ; 45(1): 50-56, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-29207386

RESUMO

BACKGROUND: A midtrimester cervical length (CL) <25 mm is associated with spontaneous preterm birth (sPTB). However, as CL ≥25 mm is not enough to exclude recurrence in high-risk patients, follow-up CL measurement later in pregnancy has been proposed. OBJECTIVES: To evaluate whether CL measurement at 26±1 weeks in asymptomatic high-risk patients improves the prediction of sPTB recurrence. METHODS: A retrospective cohort of high-risk women because of previous sPTB was analyzed. Patients with a CL ≥25 mm at 20±1 weeks and subsequent CL measurement at 26±1 weeks were included. The exclusion criteria were incomplete follow-up, any treatment before CL assessments, and medically indicated preterm birth. The association and predictive performance of CL at 26±1 weeks for sPTB was studied. RESULTS: Of 131 patients with a CL measurement at 26±1 weeks, 19 and 4.6% presented sPTB before 37 and 34 weeks, respectively. The rate of sPTB before 37 weeks was higher in women with a CL <25 mm (37.5 vs. 16.5%, RR 2.3 [1.07-4.8], p = 0.045), although the detection rate of CL at 26±1 weeks to predict sPTB before 37 weeks was 24% (95% CI 10-46%). The performance did not improve regardless of the selected cutoff. CONCLUSIONS: In asymptomatic high-risk patients, CL <25 mm at 26±1 weeks is associated with higher risk of sPTB. However, the prediction of recurrence by CL was low and did not improve, regardless of the selected cutoff.


Assuntos
Medida do Comprimento Cervical , Colo do Útero/diagnóstico por imagem , Nascimento Prematuro/etiologia , Adulto , Feminino , Idade Gestacional , Humanos , Valor Preditivo dos Testes , Gravidez , Nascimento Prematuro/fisiopatologia , Recidiva , Estudos Retrospectivos , Medição de Risco , Fatores de Risco
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