Screening for pre-eclampsia using sFlt-1/PlGF ratio cut-off of 38 at 30-37 weeks' gestation

Objective: To evaluate the soluble fms-like tyrosine kinase 1 (sFLT-1) to placental growth factor (PLGF) ratio cut-off of 38 for prediction of preeclampsia (PE) in routine assessment in singleton pregnancies at 30-37 weeks’ gestation. Methods: This was a prospective observational study in women attending for a third-trimester ultrasound scan at 30-37 weeks as part of routine pregnancy care. Serum sFlt-1 and PlGF were measured and their ratio calculated. We estimated the detection rate (DR), false positive rate (FPR), positive predictive value (PPV) and negative predictive value (NPV) of sFLT-1/PLGF >38 for prediction of delivery with PE at 4 weeks after assessment. Results: The study population of 12,305 singleton pregnancies was examined at a median of 32.4 (range 30.0-36.9) weeks and included 14 (0.11%), 77 (0.63%) and 227 (1.84%) that subsequently delivered with PE at 4 weeks’ after assessment, respectively. The DR, FPR, PPV and NPV of sFLT-1/PLGF >38 in the prediction of delivery with PE at 4 weeks were 20.7%, 4.3%, 8.3% and 98.47%. Conclusion: In routine screening of singleton pregnancies, the performance of sFLT 1/PLGF >38 is modest for prediction of delivery with PE at 38 predicted 79% of cases with PE at <1 week at FPR of 4.5%; consequently, a policy of hospitalizing patients with this ratio would potentially lead to unnecessary hospitalization in 4.5% of pregnancies and a ratio of <38 would falsely reassure one fifth of the women that will deliver with PE at <1 week from assessment

Proposed clinical management of pregnancies after combined screening for pre-eclampsia at 30-34 weeks' gestation

Objective: To estimate the patient-specific risk of preeclampsia (PE) at 30-34 weeks’ gestation by a combination of maternal characteristics and medical history with multiple of the median (MoM) values of mean arterial pressure, uterine artery pulsatility index, serum the median (MoM) values of mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and serum soluble fmsm-like tyrosine kinase-1 and stratify women into high-, intermediate- and low-risk management groups. Methods: This was a prospective observational study in women attending for a third-trimester ultrasound scan at 30-34 weeks as part of routine pregnancy care. Patient-specific risks of delivery with PE at <4 weeks from assessment and at <40 weeks’ of delivery with PE at <4 weeks from assessment and at <40 weeks’ gestation were calculated using the competing risks model to combine the prior risk from maternal characteristics and medical history with MoM values of MAP, UTPI, PLGF and sFLT-1. On the basis of these risks the population was stratified into high-, intermediate- and low-risk groups. Different risk cut-offs were used to vary the proportion of the population stratified into each risk category and the performance of screening for delivery with PE at <4 weeks and delivery with PE from four weeks after assessment and up to 40 weeks’ gestation (PE 4w-40GW) was estimated. Results: The study population of 8,128 singleton pregnancies included 234 (2.9%) that subsequently developed PE. Using a risk cut-off for PE at <4 weeks of 1 in 50 and a risk cut-off of 1 in 150 for PE at <40 weeks’ gestation the proportion of the population stratified into high-, intermediate- and low-risk was about 3%, 26% and 71%, respectively. The high-risk group contained 90% of pregnancies with PE at at <4 weeks and 40% of those with PE at 4w-40GW. The intermediate-risk group contained a further 49% of women with PE at 4w-40GW. In the low-risk group, none of the women developed PE at <4 weeks and only 0.3% developed PE at 4w-40GW. Conclusion: The study presents risk stratification of PE by the combined test at 30-34 weeks aiming to identify a high-risk group in need of intensive monitoring from the time of the initial assessment and up to 40 weeks’ gestation and an intermediate-risk group, in need of monitoring starting from four weeks after the initial assessment and up to 40 weeks’ gestation. All pregnancies would need to be reassessed at 40 weeks’ gestation

Predicting delivery of a small‐for‐gestational‐age infant and adverse perinatal outcome in women with suspected pre‐eclampsia

Objective: To evaluate the test performance of 47 biomarkers and ultrasound parameters for the prediction of delivery of a small‐for‐gestational‐age (SGA) infant and adverse perinatal outcome in women presenting with suspected pre‐eclampsia. Methods: This was a prospective, multicenter observational study in which 47 biomarkers and ultrasound parameters were measured in 397 women with a singleton pregnancy presenting with suspected preterm pre‐eclampsia between 20 + 0 and 36 + 6 weeks' gestation, with the objective of evaluating them as predictors of subsequent delivery of a SGA infant and adverse perinatal outcome. Women with confirmed pre‐eclampsia at enrollment were excluded. Factor analysis and stepwise logistic regression were performed in two prespecified groups stratified according to gestational age at enrollment. The primary outcome was delivery of a SGA infant with a birth weight < 3rd customized centile (SGA‐3), and secondary outcomes were a SGA infant with a birth weight < 10th customized centile and adverse perinatal outcome. Results: In 274 women presenting at 20 + 0 to 34 + 6 weeks' gestation, 96 (35%) delivered a SGA‐3 infant. For prediction of SGA‐3, low maternal placental growth factor (PlGF) concentration had a sensitivity of 93% (95% CI, 84–98%) and negative predictive value (NPV) of 90% (95% CI, 76–97%) compared with a sensitivity of 71% (95% CI, 58–82%) and a NPV of 79% (95% CI, 68–87%) for ultrasound parameters (estimated fetal weight or abdominal circumference < 10th centile). No individual biomarker evaluated had a better performance than did PlGF, and marker combinations made only small improvements to the test performance. Similar results were found in 123 women presenting between 35 + 0 and 36 + 6 weeks' gestation. Conclusion: In women presenting with suspected preterm pre‐eclampsia, measurement of PlGF offers a useful adjunct for identifying those at high risk of delivering a SGA infant, allowing appropriate surveillance and timely intervention

Fabrication and evaluation of nanostructured thin layer catalysts for PEMFC

La technologie de piles à combustible PEM (Proton Exchange Membrane) voit encore sa commercialisation limitée du fait de son coût élevé. L'un des éléments les plus coûteux est le catalyseur, constitué de platine, métal noble, représentant 25 % du coût global. L'étude mise en place dans le cadre de cette thèse s'oriente vers l'amélioration de l'utilisation de cet élément. La voie de nanostructuration s'avère d'un intérêt majeur afin de maintenir des tailles de structure proposant des propriétés électrocatalytiques intéressantes. De plus, l'élaboration électrochimique de catalyseurs présente l'avantage majeur de remplir l'une des conditions nécessaires en pile à combustible : le contact électronique. La réunion des deux précédents points nous a permis de mettre en place un procédé d'élaboration électrochimique de nanostructures, ensuite charactérisées par méthodes électrochimiques et physiques afin d'évaluer et de comprendre leurs propriétés catalytiques.A key point for the Proton Exchange Membrane Fuel Cell (PEMFC) improvement and commercialization is the enhancement of mass specific electroactivity of platinum to reduce the cost (about 25% of the overall cost). The study set up as part of this thesis is directed towards improving the use of this element. Nanostructuration is of major interest to maintain the size structure offering interesting electrocatalytic properties. In addition, the development of electrochemical catalysts has the major advantage of satisfying the necessary conditions in fuel cell: the electronic contact. We propose an innovative process to elaborate a metal nanowires array on microporous substrate which allows gas diffusion by a simple electrodeposition method. As-made structures had been physically and electrochemically characterized to evaluate and understand their electrocatalytic activity

Maternal and Neonatal Tolerance of Antiretroviral Treatment During Pregnancy in the HAART Era

L’objectif de cette thèse était d’étudier les associations potentielles entre les traitements antirétroviraux reçus par les femmes enceintes infectées par le VIH et les complications pouvant survenir au cours de la grossesse ou être diagnostiquées dans la période néonatale. Ce travail est issu en majeure partie des données de l’Enquête Périnatale Française (ANRS-EPF), cohorte nationale multicentrique ayant inclus plus de 20 000 couples mères-enfants depuis 1986. Actuellement, presque toutes les femmes sont traitées par combinaisons antirétrovirales puissantes (cART ; 98% en 2013) et le taux de transmission est inférieur à 1% : 0.6% (IC95% : 0.4%-0.8% pour la période 2005-2013). La première partie portait sur le risque d’accouchement prématuré dont le taux a augmenté significativement entre la période 1990-1993 et 2005-2009, passant de 9.2% à 14.3%. Le risque d’accouchement prématuré était significativement associé au traitement par cART, par rapport aux monothérapies et bithérapies d’INTI, et au traitement débuté avant la conception par rapport aux traitements débutés en cours de grossesse. La survenue d’une cytolyse hépatique était fréquente (17%), et était liée à la fois à la prématurité, et au type de traitement, plus fréquentes avec les IP qu’avec les inhibiteurs non nucléosidiques de la transcriptase inverse. La perturbation du bilan hépatique pourrait être un facteur intermédiaire dans la relation entre traitements et accouchement prématuré. La seconde partie portait sur les malformations congénitales. D’une part, elle a permis de mettre en évidence une association entre exposition à l’efavirenz au premier trimestre de grossesse et les malformations neurologiques, bien que concernant peu de cas (n=4) et n’atteignant la significativité que dans une analyse de sensibilité. Cette association incite à maintenir une vigilance chez les enfants exposés in utero à cette molécule classée tératogène par la FDA mais prescrite de plus en plus largement. D’autre part, l’exposition au premier trimestre à la zidovudine était associée à la survenue de malformations cardiaques. La troisième partie a complété cette étude par une analyse de la fonction cardiaque, des modifications infracliniques de la contractilité et de l’épaisseur des parois du ventricule gauche ont été mises en évidence chez les enfants exposés in utero à une combinaison de traitement contenant la zidovudine et la lamivudine. Ces résultats ne remettent pas en question l’efficacité majeure des traitements antirétroviraux pour la prévention de la transmission de la mère à l’enfant du VIH, mais incitent à la poursuite d’une surveillance épidémiologique des effets indésirables potentiels, de manière à optimiser les prescriptions pour un meilleur rapport bénéfice/risque.Our objective was to study potential associations between antiretroviral treatment and obstetrical or neonatal complications in a population of HIV-positive pregnant women. Most of the analyses were conducted with data from the French Perinatal Cohort (ANRS-EPF), an ongoing multicenter national cohort with more than 20 000 mother-infant pairs included since 1986. In the recent years, most women receive combination antiretroviral therapies (cART ; 98% en 2013) and the trasnsmission rate is consistently under 1% : 0.6% (IC95% : 0.4%-0.8% for 2005-2013). Risk of preterm birth was significantly associated with cART, when compared to NRTI monotherapy or dual therapy, and with timing of treatment, higher for women treated at conception than for those initiating treatment during pregnancy. The occurrence of liver enzyme elevation was frequent (17%), and was associated both with preterm birth and with PI-based treatment, when compared to NNRTIs. LEE could be an intermediate factor between cART and preterm birth. The second part of this work was a study of congenital birth defect in the cohort, and showed an association between first trimester-exposure to efavirenz and neurological defects, but this concerned small numbers (n=4), and reached significance only in a sensitivity analysis. This association encourages us to maintain awareness concerning this molecule, considered teratogenic by the FDA but more and more largely prescribed. We also reported an association between first-trimester exposure to zidovudine and congenital heart defects. In a third part, we studied heart function, differences in contractility and septum thickness of the left ventricle was found, among girls exposed to a combination containing zidovudine and lamivudineThese results do not question the great progress of antiretroviral treatment in the prevention of mother-to-child transmission, but they encourage us to continue epidemiologic surveillance of potential side effects, in order to optimize prescriptions for an improved benefit/risk ratio

Nanostructuration de couches actives pour piles à combustible PEM

A key point for the Proton Exchange Membrane Fuel Cell (PEMFC) improvement and commercialization is the enhancement of mass specific electroactivity of platinum to reduce the cost (about 25% of the overall cost). The study set up as part of this thesis is directed towards improving the use of this element. Nanostructuration is of major interest to maintain the size structure offering interesting electrocatalytic properties. In addition, the development of electrochemical catalysts has the major advantage of satisfying the necessary conditions in fuel cell: the electronic contact. We propose an innovative process to elaborate a metal nanowires array on microporous substrate which allows gas diffusion by a simple electrodeposition method. As-made structures had been physically and electrochemically characterized to evaluate and understand their electrocatalytic activity.La technologie de piles à combustible PEM (Proton Exchange Membrane) voit encore sa commercialisation limitée du fait de son coût élevé. L'un des éléments les plus coûteux est le catalyseur, constitué de platine, métal noble, représentant 25 % du coût global. L'étude mise en place dans le cadre de cette thèse s'oriente vers l'amélioration de l'utilisation de cet élément. La voie de nanostructuration s'avère d'un intérêt majeur afin de maintenir des tailles de structure proposant des propriétés électrocatalytiques intéressantes. De plus, l'élaboration électrochimique de catalyseurs présente l'avantage majeur de remplir l'une des conditions nécessaires en pile à combustible : le contact électronique. La réunion des deux précédents points nous a permis de mettre en place un procédé d'élaboration électrochimique de nanostructures, ensuite charactérisées par méthodes électrochimiques et physiques afin d'évaluer et de comprendre leurs propriétés catalytiques

Préface

Sibiude Jean-Luc. Préface. In: Lieux de cultes : aires votives, temples, églises, mosquées. IXe Colloque international sur l’histoire et l’archéologie de l’Afrique du Nord antique et médiévale (Tripoli, 19-25 février 2005) Préface de Jean-Luc Sibiude, ambassadeur de France en Libye. Paris : Éditions du Centre National de la Recherche Scientifique, 2008. p. 5. (Études d'antiquités africaines