Publications by authors named "Denis Gallot"

71 Publications

Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial.

PLoS Med 2021 Feb 11;18(2):e1003448. Epub 2021 Feb 11.

Pôle de gynécologie obstétrique, médecine fœtale, médecine et biologie de la reproduction, centre Olympe de Gouges, CHRU de Tours, Tours, France.

Background: Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2).

Methods And Findings: This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section.

Conclusions: In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone.

Trial Registration: ClinicalTrials.gov NCT02907060.
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http://dx.doi.org/10.1371/journal.pmed.1003448DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877637PMC
February 2021

Predictors of Short Latency Period Exceeding 48 h after Preterm Premature Rupture of Membranes.

J Clin Med 2021 Jan 4;10(1). Epub 2021 Jan 4.

Obstetrics and Gynaecology Department, Clermont-Ferrand University Hospital, 63000 Clermont-Ferrand, France.

Background: Preterm premature rupture of membranes (PPROM) is a complication responsible for a third of preterm births. Clinical management is initially hospital based, but homecare management is possible if patients are clinically stable 48 h after PPROM. This study set out to determine factors that are predictive of short latency (delivery ≤ 7 days) exceeding 48 h after PPROM, enabling estimation of the prevalence of maternal and neonatal complications and comparison of maternal and fetal outcomes between inpatient and outpatient management.

Method: This was a monocentric retrospective study conducted between 1 January 2010 and 28 February 2017 on all patients experiencing PPROM at 24 to 34 weeks + 6 days and who gave birth after 48 h. Maternal, obstetric, fetal, and neonatal variables were included in the data collected. The primary endpoint was latency, defined as the number of days between rupture of membranes and delivery.

Results: 170 consecutive patients were analyzed. Short latency could be predicted by the need for tocolysis, a cervical length less than 25 mm at admission and the existence of anamnios. Outpatient follow-up was not found to lead to increased maternal morbidity or neonatal mortality.

Conclusion: Our study highlights predictive factors of short latency exceeding 48 h after PPROM. Knowledge of these factors may provide justification for outpatient monitoring of patients presenting with a long cervix, absence of need for tocolysis and persistence of amniotic fluid and, thus, no risk factors after 48 h of admission.
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http://dx.doi.org/10.3390/jcm10010150DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7796089PMC
January 2021

Rationale and design of ePPOP-ID: a multicenter randomized controlled trial using an electronic-personalized program for obesity in pregnancy to improve delivery.

BMC Pregnancy Childbirth 2020 Oct 7;20(1):602. Epub 2020 Oct 7.

Department of medicine, endocrinology division, Mc Master university, Hamilton, Canada.

Background: Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for adverse pregnancy, delivery and birth outcomes. Pregnancy is an ideal moment for nutritional interventions in order to establish healthier lifestyle behaviors in women at high risk of obstetric and neonatal complications.

Methods: Electronic-Personalized Program for Obesity during Pregnancy to Improve Delivery (ePPOP-ID) is an open multicenter randomized controlled trial which will assess the efficacy of an e-health web-based platform offering a personalized lifestyle program to obese pregnant women in order to reduce the rate of labor procedures and delivery interventions in comparison to standard care. A total of 860 eligible pregnant women will be recruited in 18 centers in France between 12 and 22 weeks of gestation, randomized into the intervention or the control arm and followed until 10 weeks of postpartum. The intervention is based on nutrition, eating behavior, physical activity, motivation and well-being advices in which personalization is central, as well as the use of a mobile/tablet application. Inputs includes data from the medical record of participants (medical history, anthropometric data), from the web platform (questionnaires on dietary habits, eating behavior, physical activity and motivation in both groups), and adherence to the program (time of connection for the intervention group only). Data are collected at inclusion, 32 weeks, delivery and 10 weeks postpartum. As primary outcome, we will use a composite endpoint score of obstetrical interventions during labor and delivery, defined as caesarean section and instrumental delivery (forceps and vacuum extractor). Secondary outcomes will consist of data routinely collected as part of usual antenatal and perinatal care, such as GWG, hypertension, preeclampsia, as well as fetal and neonatal outcomes including premature birth, gestational age at birth, birth weight, macrosomia, Apgar score, arterial umbilical cord pH, neonatal traumatism, hyperbilirubinemia, respiratory distress syndrome, transfer in neonatal intensive care unit, and neonatal adiposity. Post-natal outcomes will be duration of breastfeeding, maternal weight retention and child weight at postnatal visit.

Discussion: The findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy.

Trial Registration: ClinicalTrials.gov Identifier: NCT02924636 / October 5th 2016.
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http://dx.doi.org/10.1186/s12884-020-03288-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7542973PMC
October 2020

Human Amnion Epithelial Cells (AECs) Respond to the FSL-1 Lipopeptide by Engaging the NLRP7 Inflammasome.

Front Immunol 2020 7;11:1645. Epub 2020 Aug 7.

Genetics, Reproduction and Development (GReD) Laboratory, Clermont Auvergne University, CNRS UMR 6293, INSERM U1103, Translational Approach to Epithelial Injury and Repair Team, Clermont-Ferrand, France.

Inflammation is the leading mechanism involved in both physiological and pathological rupture of fetal membranes. Our aim was to obtain a better characterization of the inflammasome-dependent inflammation processes in these tissues, with a particular focus on the nucleotide-binding oligomerization domain (NOD)-like receptor, pyrin domain containing protein 7 (NLRP7) inflammasome. The presence of NLRP7 inflammasome actors [NLRP7, apoptosis-associated speck-like protein containing a CARD domain (ASC), and caspase-1] was confirmed by reverse transcriptase-polymerase chain reaction (RT-PCR) in human amnion and choriodecidua at the three trimesters and at term. The protein concentrations were then determined by enzyme-linked immunosorbent assay in term tissues, with or without labor. The presence of and in human fetal membranes was investigated using a PCR approach. Human amnion epithelial cells (AECs) were treated for 4 or 20 h with fibroblast-stimulating lipopeptide-1 (FSL-1), a -derived ligand. Transcripts and proteins quantity was then measured by RT-quantitative PCR and Western blotting, respectively. NLRP7 and ASC colocalization was confirmed by immunofluorescence. Western blots allowed analysis of pro-caspase-1 and gasdermin D cleavage. NLRP7, ASC, and caspase-1 transcripts were expressed in both sheets of human fetal membranes during all pregnancy stages, but only ASC protein expression was increased with labor. In addition, and were detected for the first time in human fetal membranes. NLRP7 and caspase-1 transcripts, as well as NLRP7, ASC, and pro-caspase-1 protein levels, were increased in FSL-1-treated AECs. The NLRP7 inflammasome assembled around the nucleus, and pro-caspase-1 and gasdermin D were cleaved into their mature forms after FSL-1 stimulation. Two new mycoplasmas, and , were identified in human fetal membranes, and a lipopeptide derived from was found to induce NLRP7 inflammasome formation in AECs.
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http://dx.doi.org/10.3389/fimmu.2020.01645DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7426397PMC
April 2021

Trajectories of antidepressant drugs during pregnancy: A cohort study from a community-based sample.

Br J Clin Pharmacol 2021 Mar 4;87(3):965-987. Epub 2020 Aug 4.

Département de Médecine Générale, UFR de Médicine, Université Clermont Auvergne, Clermont-Ferrand, France.

Aims: The aim of this study was to monitor the trajectories of antidepressant use during pregnancy and the postpartum period among women chronically treated with antidepressants before their pregnancy, and to assess characteristics associated with each trajectory.

Methods: This cohort study included all pregnant women whose data were included in the General Sample of Beneficiaries (EGB) database affiliated with the French Health Insurance System, from 2009 to 2014. Women were followed up until 6 months after childbirth. Chronic treatment was defined as exposure over the 6-month period preceding pregnancy. A group-based trajectory model (GBMT) was estimated to identify distinctive longitudinal profiles of antidepressant use.

Results: Among 760 women chronically treated with antidepressants before their pregnancy, 55.8% stopped their treatment permanently in the first trimester, 20.4% discontinued it for a minimum of 3 months and resumed it postpartum, and 23.8% maintained it throughout pregnancy and postpartum. No sociodemographic or medical characteristics were associated with any trajectory group. Women who maintained treatment presented more frequent obstetric complications and postpartum psychiatric disorders. Among women who interrupted treatment, prescription of benzodiazepines and anxiolytics decreased initially but rose postpartum to a higher level than before pregnancy.

Conclusions: Pregnant women treated with antidepressant require a re-evaluation of psychiatric treatment. It is necessary to pay attention to obstetric complications for severely depressed women. Additionally, as relapse was associated with increased benzodiazepine use, it is important to carefully monitor all women who stop antidepressant treatment during pregnancy.
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http://dx.doi.org/10.1111/bcp.14449DOI Listing
March 2021

Occurrence of a RAGE-Mediated Inflammatory Response in Human Fetal Membranes.

Front Physiol 2020 25;11:581. Epub 2020 Jun 25.

CNRS, INSERM, GReD, Université Clermont Auvergne, Clermont-Ferrand, France.

Context: Sterile inflammation has been shown to play a key role in the rupture of the fetal membranes (FMs). Moreover, an early and exacerbated runaway inflammation can evolve into a preterm premature rupture of membranes and lead to potential preterm birth. In this context, we investigated the receptor for advanced glycation end products (RAGE), an axis implied in physiological sterile inflammation, in conjunction with two major ligands: AGEs and High-Mobility Group Box 1 (HMGB1). Our first objective was to determine the spatiotemporal expression profiles of the different actors of the RAGE-signaling axis in human FMs, including its intracellular adaptors Diaphanous-1 and Myd88. Our second goal was to evaluate the functionality of RAGE signaling in terms of FMs inflammation.

Methods: The presence of the actors (RAGE, HMGB1, Myd88, and Diaphanous-1) at the mRNA level was investigated by reverse transcription quantitative polymerase chain reaction (RT-qPCR) in the human amnion and choriodecidua at the three trimesters and at term. Measurements were conducted at two distinct zones: the zone of intact morphology (ZIM) and the zone of altered morphology (ZAM). Then, proteins were quantified using Western blot analysis, and their localization was evaluated by immunofluorescence in term tissues. In addition, pro-inflammatory cytokine secretion was quantified using a Multiplex assay after the treatment of amnion and choriodecidua explants with two RAGE ligands (AGEs and HMGB1) in the absence or presence of a RAGE inhibitor (SAGEs).

Results: The FMs expressed the RAGE-signaling actors throughout pregnancy. At term, RNA and protein overexpression of the RAGE, HMGB1, and Diaphanous-1 were found in the amnion when compared to the choriodecidua, and the RAGE was overexpressed in the ZAM when compared to the ZIM. The two RAGE ligands (AGEs and HMGB1) induced differential cytokine production (IL1β and TNFα) in the amnion and choriodecidua.

Conclusion: Considered together, these results indicate that RAGE signaling is present and functional in human FMs. Our work opens the way to a better understanding of FMs weakening dependent on a RAGE-based sterile inflammation.
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http://dx.doi.org/10.3389/fphys.2020.00581DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330021PMC
June 2020

Study of sRAGE, HMGB1, AGE, and S100A8/A9 Concentrations in Plasma and in Serum-Extracted Extracellular Vesicles of Pregnant Women With Preterm Premature Rupture of Membranes.

Front Physiol 2020 23;11:609. Epub 2020 Jun 23.

Centre de Recherche du Centre Hospitalier Universitaire (CHU) de Québec-Université Laval, Québec City, QC, Canada.

Preterm premature rupture of membranes (PPROM), defined as rupture of fetal membranes prior to 37 weeks of gestation, complicates approximately 2-4% of pregnancies and is responsible for 40% of all spontaneous preterm births. PPROM arises from complex pathophysiological pathways with a key actor: inflammation. Sterile inflammation is a feature of senescence-associated fetal membrane maturity. During specific steps of sterile inflammation, cells also release highly inflammatory damage-associated molecular pattern markers (DAMPs), such as high-mobility group box 1 (HMGB1) or S100A8/A9, known to link and activate the receptor for advanced glycation end products (RAGE). The objective of this study was to measure longitudinally during pregnancy concentrations of the soluble form of RAGE (sRAGE) and its main ligands (AGE, HMGB1, S100A8/A9) in blood specimens. We studied 246 pregnant women (82 with PPROM and 164 matched control pregnant women without complications) from a cohort of 7,866 pregnant women recruited in the first trimester and followed during pregnancy until delivery. sRAGE, AGE, HMGB1, and S100A8/A9 concentrations were measured in plasma and in serum-extracted extracellular vesicles from first trimester (T1), second trimester (T2), and delivery (D). In plasma, we observed, in both PPROM and control groups, (i) a significant increase of HMGB1 concentrations between T1 vs. T2, T1 vs. D, but not between T2 vs. D; (ii) a significant decrease of sRAGE concentrations between T1 and T2 and a significant increase between T2 and D; (iii) a significant decrease of AGE from T1 to D; (iv) no significant variation of S100A8/A9 between trimesters. In intergroup comparisons (PPROM vs. control group), there were no significant differences in time variation taking into account the matching effects. There was a correlation between plasma and serum-extracted extracellular vesicle concentrations of sRAGE, AGE, HMGB1, and S100A8/A9. Our results suggest that the rupture of fetal membranes (physiological or premature) is accompanied by a variation in plasma concentrations of sRAGE, HMGB1, and AGE. The study of RAGE and its main ligands in extracellular vesicles did not give additional insight into the pathophysiological process conducting to PPROM.
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http://dx.doi.org/10.3389/fphys.2020.00609DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324632PMC
June 2020

A snapshot of the Covid-19 pandemic among pregnant women in France.

J Gynecol Obstet Hum Reprod 2020 Sep 4;49(7):101826. Epub 2020 Jun 4.

Assistance Publique-Hôpitaux de Paris, 75004, Paris, France.

Objective: To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes.

Methods: We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected.

Results: Active cases of COVID-19 increased exponentially during March 1-31, 2020; the numbers fell during April 1-14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3-18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0-7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0-0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01-2.9) in the critical group died from prematurity.

Conclusion: COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.
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http://dx.doi.org/10.1016/j.jogoh.2020.101826DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7270811PMC
September 2020

Is laterality of congenital diaphragmatic hernia a reliable prognostic factor? French national cohort study.

Prenat Diagn 2020 07 8;40(8):949-957. Epub 2020 May 8.

Department of Obstetrics and Gynecology, Hôpitaux universitaires de Strasbourg, Strasbourg, France.

Objectives: The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival.

Methods: This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes.

Results: A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26).

Conclusion: Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.
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http://dx.doi.org/10.1002/pd.5706DOI Listing
July 2020

Breech presentation: Clinical practice guidelines from the French College of Gynaecologists and Obstetricians (CNGOF).

Eur J Obstet Gynecol Reprod Biol 2020 Sep 25;252:599-604. Epub 2020 Mar 25.

Service de gynécologie-obstétrique, CHU de Rouen, Université de Rouen, France.

Objective: To determine the optimal management of singleton fetuses in breech presentation.

Materials And Methods: Consultation of the PubMed database, the Cochrane Library and guidelines issued by the French and foreign obstetrical societies or colleges.

Results: In France, 5% of women have breech deliveries (level of evidence [LE] 3). One third of them have a planned vaginal delivery (LE3), and 70% of these give birth vaginally (LE3). External cephalic version (ECV) is associated with lower rates of both breech presentation at birth (LE2) and of cesarean deliveries (LE3) without any increase in severe maternal (LE3) or perinatal morbidity (LE3). Women with a fetus in breech presentation at term should be informed that ECV can be attempted starting at 36 weeks of gestation (professional consensus). Planned vaginal delivery of breech presentation may be associated with a higher risk of composite perinatal mortality or serious neonatal morbidity than planned cesarean birth (LE2). These two modes do not differ for neurodevelopmental outcomes at two years (LE2), cognitive and psychomotor outcomes between 5 and 8 years (LE3), or adult intellectual performance (LE4). Short- and long-term maternal complications appear similar in the two groups, unless subsequent pregnancies are under consideration. Pregnancies after a cesarean delivery are at higher risk of uterine rupture, placenta accreta spectrum disorders, and hysterectomy (LE2). Women who want a planned vaginal delivery should be offered a pelvimetry at term (Grade C) and should have ultrasonography to verify that the fetal head is not hyperextended (professional consensus) to plan their mode of delivery. Complete breech presentation, a previous cesarean, nulliparity, and term prelabor rupture of membranes are not, each one by itself, per se contraindications to planned vaginal delivery (professional consensus). Term breech presentation is not a contraindication to labor induction when the criteria for planned vaginal delivery are met (Grade C).

Conclusion: In cases of breech presentation at term, the child and the mother are at low risk of severe morbidity after either planned vaginal or planned cesarean delivery. The French College of Obstetricians and Gynecologists (CNGOF) considers that planned vaginal delivery is a reasonable option in most cases (professional consensus). The decision about the planned route of delivery should be shared by the woman and her healthcare provider, who must respect her right to autonomy.
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http://dx.doi.org/10.1016/j.ejogrb.2020.03.033DOI Listing
September 2020

Risk Factors and Outcomes of Preterm Premature Rupture of Membranes in a Cohort of 6968 Pregnant Women Prospectively Recruited.

J Clin Med 2019 Nov 15;8(11). Epub 2019 Nov 15.

Department of Molecular Biology, Medical biochemistry and Pathology, Faculty of Medicine, Centre de recherche du CHU de Québec-Université Laval, Québec City, QC G1V 0A6, Canada.

We revisited risk factors and outcomes related to the preterm premature rupture of membranes (PPROM). A total of 7866 pregnant women were recruited during 5 years at their first prenatal visit to the perinatal clinic of the institution. We compared three groups (women without prematurity, women with spontaneous preterm labor with intact membranes (sPL with IM), women with PPROM) regarding 60 criteria about characteristics, lifestyle, medical, gynecological, obstetrical history of mothers, medication during pregnancy, events at delivery, and complications in neonates. Logistic regression analyses adjusting for potential confounding factors were used. Of the 6968 women selected, 189 (2.8%) presented a PPROM, and 225 (3.2%) an sPL with IM. The specific risk factors for PPROM were body mass index (BMI) <18.5 kg/m (adjusted odds ratio, aOR: 2.00 (1.09-3.67)), history of PPROM (aOR: 2.75 (1.19-6.36)), nulliparity (aOR: 2.52 (1.77-3.60)), gestational diabetes (aOR: 1.87 (1.16-2.99)), and low level of education (aOR: 2.39 (1.20-4.78)). The complications associated with PPROM were abruption placentae, cesarean, APGAR 5' <4, birth weight <2500 g, stillbirth, neonatal jaundice, and hospitalization of mother and neonates. All these complications were also associated with sPL with IM. Our study confirms some of the risk factors of PPROM and highlights a new one: gestational diabetes. Outcomes of PPROM are related to prematurity.
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http://dx.doi.org/10.3390/jcm8111987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912547PMC
November 2019

Induction of labour in case of premature rupture of membranes at term with an unfavourable cervix: protocol for a randomised controlled trial comparing double balloon catheter (+oxytocin) and vaginal prostaglandin (RUBAPRO) treatments.

BMJ Open 2019 06 20;9(6):e026090. Epub 2019 Jun 20.

Obstetrics and Gynaecology Department, Clermont-Ferrand University Hospital, Clermont-Ferrand, France.

Introduction: Premature rupture of membranes (PROM) occurs at term in 8% of pregnancies. Several studies have demonstrated that the risk of chorioamnionitis and neonatal sepsis increases with duration of PROM. Decreasing the time interval between PROM and delivery is associated with lower rates of maternal infections. In case of an unfavourable cervix, the use of prostaglandin for cervical maturation demonstrates some advantages over oxytocin. The use of double balloon catheter in reduction of PROM duration has not been evaluated in the literature.

Methods And Analysis: We are conducting a prospective, monocentric, randomised clinical trial on pregnant women with an unfavourable cervix showing PROM at term (RUBAPRO).After 12-24 hours of PROM, women are randomly assigned to one group treated with a double balloon catheter for 12 hours, with oxytocin administered after 6 hours or to the control group treated with 24 hours of vaginal prostaglandin followed by oxytocin infusion alone. Patients (n=80) are randomised at a 1:1 ratio with stratification on parity.The inclusion criteria are a Bishop score of <6, cephalic presentation at term and confirmed PROM. Women with suspected chorioamnionitis; group B streptococcus (GBS) carrier; a history of caesarean delivery or any contraindication for vaginal delivery are excluded.The time from induction to delivery is the primary outcome. Secondary outcomes were mode of delivery, maternofetal morbidity and the effect of parity on strategies for reduction of PROM duration.To sufficiently demonstrate a difference (10 hours) between groups-with a statistical power of 90% and a two-tailed α of 5%-40 patients per group will be required.

Ethics And Dissemination: Written informed consent is required from participants.National Ethics Committee approval was obtained in August 2017. The results will be published in a peer-reviewed journal and presented at relevant conferences. Access to raw data will be available only to members of the research team.

Trial Registration Number: NCT03310333.
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http://dx.doi.org/10.1136/bmjopen-2018-026090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6596956PMC
June 2019

Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF).

Eur J Obstet Gynecol Reprod Biol 2019 May 2;236:1-6. Epub 2019 Mar 2.

Inserm UMR 1153 Equipe de recherche en Epidémiologie Obstétricale, Périnatale et Pédiatrique (EPOPé), Centre de Recherche Epidémiologie et Statistique Sorbonne Paris Cité, Paris, France; Service de Gynécologie Obstétrique, Hôpital Trousseau, AP-HP, Paris, France; Université Pierre et Marie Curie, Paris, France.

In France, the frequency of premature rupture of the membranes (PROM) is 2%-3% before 37 weeks' gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing enterocolitis (LE2). The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1 are recommended in cases of uncertainty (professional consensus). Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1). Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days (Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is negative (professional consensus). The following are not recommended for antibiotic prophylaxis: amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-generation cephalosporins, clindamycin, or metronidazole (professional consensus). Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home (professional consensus). Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection (professional consensus). No guidelines can be issued about the frequency of this monitoring (professional consensus). Adequate evidence does not exist to support a recommendation for or against the routine initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional consensus). In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the standard obstetric indications (professional consensus). Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with PPROM (professional consensus).
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http://dx.doi.org/10.1016/j.ejogrb.2019.02.021DOI Listing
May 2019

Fetal fibronectin test for threatened preterm delivery 48h after admission: Cost-effectiveness study.

Eur J Obstet Gynecol Reprod Biol 2019 Mar 12;234:75-78. Epub 2019 Jan 12.

Pôle Femme Et Enfant, Centre Hospitalier Universitaire de Clermont-Ferrand, Clermont-Ferrand, France; Equipe « Translational Approach to Epithelial Injury and Repair », GReD, CNRS UMR 6293, INSERM U1103, Université Clermont Auvergne, Clermont-Ferrand, France. Electronic address:

Objective: The aim of this work was to assess the cost-effectiveness of the fetal fibronectin (fFN) test at 48 h after admission for threatened preterm delivery to promote early discharge.

Study Design: Before-and-after study to calculate the incremental cost-effectiveness ratio (ICER). Patients were enrolled 48 h after admission in a tertiary care centre for threatened preterm delivery between 24 and 34 weeks. fFN testing was performed. During the first period, physician was blinded to fFN test and discharge occurred after apparent reduced symptomatology at physician's discretion. During the second period, fFN test was revealed to physician and discharge was immediately proposed to negative test patients. The costs considered in this analysis were the direct medical costs from the hospital perspective: costs of hospitalisation, treatment, and imaging procedures. The efficacy criterion selected was the number of deliveries at 7 and at 14 days after admission for threatened preterm delivery.

Results: The study included 178 pregnant patient, 99 during the first period (July 2008-October 2009) and 79 during the second (March 2010-February 2012). The lengths of hospital stays were shorter during the second period, with more than 50% of women discharged home between 48 and 72 h (p < 0.0001) resulting in a cost-saving of 76 051 euros. The number of deliveries at 7 and at 14 days was similar between the two periods.

Conclusion: The fFN test at 48 h after admission supported early discharge and was safe and cost-effective.
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http://dx.doi.org/10.1016/j.ejogrb.2018.12.043DOI Listing
March 2019

Laryngotracheoesophageal cleft, a rare differential diagnosis of esophageal atresia.

J Gynecol Obstet Hum Reprod 2018 Dec 16;47(10):577-579. Epub 2018 Sep 16.

Pôle Femme Et Enfant, CHU Estaing, 1, place Lucie-et-Raymond-Aubrac, 63003 Clermont-Ferrand Cedex 1, France; Equipe "Translational approach to epithelial injury and repair", Université Clermont-Auvergne, CNRS, Inserm, GReD, 63000 Clermont-Ferrand, France. Electronic address:

A laryngotracheoesophageal cleft, commonly called laryngeal cleft (LC), is a congenital malformation of the posterior part of the larynx creating an abnormal communication between the laryngotracheal axis and the pharyngoesophageal axis. The prenatal ultrasonographic features associating absent stomach, polyhydramnios and mediastinal "pouch sign" are usually considered pathognomonic for esophageal atresia. This observation demonstrates that they can also correspond to a severe form of laryngotracheoesophageal cleft extending to the carina.
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http://dx.doi.org/10.1016/j.jogoh.2018.09.003DOI Listing
December 2018

Benefit of Risk Score-Guided Prophylaxis in Pregnant Women at Risk of Thrombotic Events: A Controlled Before-and-After Implementation Study.

Thromb Haemost 2018 Sep 13;118(9):1564-1571. Epub 2018 Aug 13.

INSERM U1059, Saint-Etienne, France.

Background:  Management of pregnant women at risk of venous thromboembolism (VTE) and placental vascular complications (PVCs) remains complex. Guidelines do not definitively specify optimal strategies.

Objective:  Our objective was to evaluate the impact of employing risk score-driven prophylaxis strategies on VTE and PVC rates in at-risk pregnant women.

Materials And Methods:  This study, conducted in 21 French maternity units, compared VTE and PVC rates before and after implementation of a risk scoring system to determine prophylactic strategies.

Results:  A total of 2,085 pregnant women at risk of VTE or PVC were enrolled. Vascular events occurred in 190 (19.2%) patients before and 140 (13.0%) after implementation of risk score-driven prophylaxis (relative risk [RR] = 0.68 [0.55; 0.83]). The incidence of deep vein thrombosis during pregnancy was reduced (RR = 0.30 [0.14; 0.67]). PVC comprised mainly pre-eclampsia, occurring in 79 patients before and 42 patients after risk score implementation (RR = 0.52 [0.36; 0.75]). Post-partum haemorrhage occurred in 32 patients (3.2%) before and 48 patients (4.5%) after risk score implementation (RR = 1.38 [0.89; 2.13],  = 0.15).

Conclusion:  Use of a simple risk scoring system, developed by experts in VTE and PVC research to guide prophylaxis, reduced the risk of thrombotic events during pregnancy without any significant increase in bleeding risk.
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http://dx.doi.org/10.1055/s-0038-1668524DOI Listing
September 2018

Laparoscopic cervico-isthmic cerclage: About 25 cases.

J Gynecol Obstet Hum Reprod 2018 Oct 7;47(8):385-389. Epub 2018 Jul 7.

CHU Clermont-Ferrand, 1, place Lucie et Raymond Aubrac, 63100 Clermont-Ferrand cedex 1, France.

Introduction: The purpose of this study is to report on our experience of laparoscopic cervico-isthmic cerclage.

Material And Method: A monocentric retrospective study covering a 13-year period during which 25 cases of laparoscopic cerclage outside of pregnancy were performed, using the technique described by Dubuisson, at the University Hospital of Clermont-Ferrand. Individual patient data included pregnancy outcomes before and after cerclage and the characteristics of surgery.

Results: The mean age of the patients was 33.9 (±4.6) years. A total of 68 pregnancies were recorded before cerclage, including 31 late miscarriages, 11 premature deliveries, with only 9 pregnancies attaining full-term. The average time of surgery was 54 (±17.5) minutes with a hospital stay of 24h. 3 minor intraoperative complications (12%) with hemorrhage <300cc were noted and managed intraoperatively. In some cases laparoscopy allowed treatment of associated pathologies (septum resection, adhesiolysis, endometriosis, ovarian drilling, tube assessment). 21 pregnancies (68% of patients) were recorded post cerclage including 5 early miscarriages and 16 cesarean deliveries with an average time taken to conceive of 11.8 months. The overall neonatal survival rate after cerclage was 76.2% versus 16.20% before surgery (p<0.0001), with a 100% neonatal survival rate beyond the 1st trimester as compared to 21.6% before cerclage (p<0.0001).
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http://dx.doi.org/10.1016/j.jogoh.2018.07.002DOI Listing
October 2018

Retinoic acid and tracheal occlusion for diaphragmatic hernia treatment in rabbit fetuses.

Prenat Diagn 2018 06;38(7):482-492

"Translational approach to epithelial injury and repair" team, Université Clermont Auvergne, CNRS, Inserm, GReD, 63000, Clermont-Ferrand, France.

Introduction: Lung hypoplasia and pulmonary arterial hypertension in congenital diaphragmatic hernia lead to a high perinatal mortality. Although sustained fetoscopic tracheal occlusion (TO) improves lung development, a major side effect is abnormal pneumocyte differentiation. This study evaluated the potential ability of intratracheal retinoic acid (RA) administration to reduce adverse effects of sustained TO in a rabbit model of diaphragmatic hernia.

Methods: A left diaphragmatic defect was created on day 23 in time-dated pregnant rabbits. On day 28, the same rabbits underwent sham surgery or TO, with an injection of empty or RA-loaded liposomes. On day 30, the fetuses were harvested, and the lungs were processed for histology, immunohistochemistry, and gene expression quantification.

Results: A tracheal RA injection at the time of TO had no effect on the lung-to-body-weight ratio, radial alveolar count or lung connective tissue composition. Retinoic acid plus TO had synergic effects on vascular measurements, proportional medial thickness, and endothelin-1 receptor type-A gene expression. The most noticeable effect was recovery of normal pneumocyte differentiation.

Conclusion: Retinoic acid plus TO prevented abnormal pneumocyte differentiation and seemed to have a beneficial effect on pulmonary vascularization.
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http://dx.doi.org/10.1002/pd.5256DOI Listing
June 2018

Cigarette smoke condensate affects the retinoid pathway in human amnion.

Placenta 2017 Oct 1;58:98-104. Epub 2017 Sep 1.

Team "Translational Approach to Epithelial Injury and Repair", Université Clermont Auvergne, CNRS, Inserm, GReD, F-63000 Clermont-Ferrand, France.

Introduction: The preterm premature rupture of membranes (PPROM) is a frequent pathology responsible of more than 30% of preterm births. Tobacco smoking is one of the most frequently described risk factors identified and contributes to the pre term weakening of fetal membranes. As previously demonstrated, all-trans retinoic acid (atRA) regulates several genes involved in the extracellular matrix dynamics, an essential actor in fetal membrane ruptures. We hypothesized that cigarette smoke may affect this pathway in human amnion.

Methods: Amnion was obtained from full-term fetal membranes collected from non-smoking women after cesarean births and used either as explants or for the isolation of derived epithelial cells. The pro-healing and transcriptomic effects of atRA were studied by a scratch assay experiment and quantitative RT-PCR, respectively, after treatment with dimethyl sulfoxyde (DMSO), atRA, DMSO + cigarette smoke condensate (CSC), or atRA + CSC.

Results: Our results show a strong alteration of the retinoid pathway after CSC treatment on amnion-derived epithelial cells and explants. We first demonstrated that CSC inhibits the activity of the RARE reporter gene in amnion-derived epithelial cells. Then, atRA's effects on both the transcription of its target genes and wound healing were demonstrated to be inhibited or at least decreased by the CSC in human amnion epithelial cells.

Discussion: Here, we demonstrated that CSC altered the retinoid signal, already known to have roles in fetal membrane physiopathology. These results highlight a potential negative action of maternal smoking on the retinoid pathway in human amnion and more generally on pregnancy.
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http://dx.doi.org/10.1016/j.placenta.2017.08.076DOI Listing
October 2017

Effects of tracheal occlusion with retinoic acid administration on normal lung development.

Prenat Diagn 2017 May 16;37(5):427-434. Epub 2017 Apr 16.

EA7281 - Retinoids, Reproduction Developmental Diseases, Auvergne University, Clermont-Ferrand, France.

Introduction: Tracheal occlusion (TO) is an investigational therapy for severe congenital diaphragmatic hernia that decreases pulmonary hypoplasia, but sustained TO also induces deficient surfactant synthesis. Intramuscular maternal administration of retinoic acid (RA) in a surgical rabbit model of congenital diaphragmatic hernia showed a beneficial effect on lung maturation. We evaluated the potential of RA delivery into the trachea and studied the combined effects of TO and RA on normal lung development.

Methods: Experiments were performed on normal rabbit fetuses. Liposomes and capric triglyceride (Miglyol ), alone and with RA, were administered in the trachea just before TO (d26). Lung morphology and surfactant production were studied at term (d30).

Results: Tracheal occlusion increased lung weight and enhanced alveolar development but increased apoptotic activity and decreased surfactant expression. Tracheal injection of RA improved surfactant production to levels of normal controls.

Conclusion: We established the potential of liposome and Miglyol as RA vehicle for delivering this bioactive molecule in the fetal airways. Tracheal RA injection seems to oppose the effects of TO in fetuses with normal lungs. © 2017 John Wiley & Sons, Ltd.
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http://dx.doi.org/10.1002/pd.5012DOI Listing
May 2017

All-trans retinoic acid promotes wound healing of primary amniocytes through the induction of LOXL4, a member of the lysyl oxidase family.

Int J Biochem Cell Biol 2016 12 18;81(Pt A):10-19. Epub 2016 Oct 18.

Clermont Université, Auvergne University, EA7281- Retinoids, Reproduction, Developmental Diseases, Medicine School, 63000 Clermont-Ferrand, France.

Thirty percent of preterm births directly result from preterm premature rupture of fetal membranes (PPROM). Clinical management currently proposes using a collagen plug to mechanically stop loss of amniotic fluid. Vitamin A and its active metabolite (retinoic acid) have well-known pro-healing properties and could thus make good candidates as a proposable adjuvant to this mechanical approach. Here we investigate the molecular mechanisms involved in the pro-healing properties of all-trans retinoic acid (atRA) in fetal membranes via an approach using an in vitro primary amniocyte wound model and transcriptomics. The results demonstrate that atRA promotes migration in primary amniocytes, improving wound healing in vitro by up to 90%. This effect is mediated by the induction of LOXL4, which plays a crucial role in the dynamics of the extracellular matrix by regulating collagen reticulation. This new insight into how atRA exerts its pro-healing properties prompts us to propose using atRA as a candidate strategy to help prevent future PPROM.
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http://dx.doi.org/10.1016/j.biocel.2016.10.007DOI Listing
December 2016

Nuclear retinoid receptors and pregnancy: placental transfer, functions, and pharmacological aspects.

Cell Mol Life Sci 2016 10 9;73(20):3823-37. Epub 2016 Aug 9.

EA7281, Retinoids, Reproduction Developmental Diseases, School of Medicine, Clermont Université, Université d'Auvergne, 63000, Clermont-Ferrand, France.

Animal models of vitamin A (retinol) deficiency have highlighted its crucial role in reproduction and placentation, whereas an excess of retinoids (structurally or functionally related entities) can cause toxic and teratogenic effects in the embryo and foetus, especially in the first trimester of human pregnancy. Knock-out experimental strategies-targeting retinoid nuclear receptors RARs and RXRs have confirmed that the effects of vitamin A are mediated by retinoic acid (especially all-trans retinoic acid) and that this vitamin is essential for the developmental process. All these data show that the vitamin A pathway and metabolism are as important for the well-being of the foetus, as they are for that of the adult. Accordingly, during this last decade, extensive research on retinoid metabolism has yielded detailed knowledge on all the actors in this pathway, spurring the development of antagonists and agonists for therapeutic and research applications. Natural and synthetic retinoids are currently used in clinical practice, most often on the skin for the treatment of acne, and as anti-oncogenic agents in acute promyelocytic leukaemia. However, because of the toxicity and teratogenicity of retinoids during pregnancy, their pharmacological use needs a sound knowledge of their metabolism, molecular aspects, placental transfer, and action.
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http://dx.doi.org/10.1007/s00018-016-2332-9DOI Listing
October 2016

Postpartum hemorrhage: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF): in collaboration with the French Society of Anesthesiology and Intensive Care (SFAR).

Eur J Obstet Gynecol Reprod Biol 2016 Mar 21;198:12-21. Epub 2015 Dec 21.

INSERM U1153, Equipe de recherche en Epidémiologie Obstétricale, Périnatale et Pédiatrique (EPOPé), Paris, France; DHU Risques et Grossesse, 53 avenue de l'observatoire, Paris, France; Maternité Port-Royal, Université Paris Descartes, Groupe hospitalier Cochin Broca Hôtel-Dieu, Assistance Publique-Hôpitaux de Paris, Paris, France.

Postpartum haemorrhage (PPH) is defined as blood loss ≥500mL after delivery and severe PPH as blood loss ≥1000mL, regardless of the route of delivery (professional consensus). The preventive administration of uterotonic agents just after delivery is effective in reducing the incidence of PPH and its systematic use is recommended, regardless of the route of delivery (Grade A). Oxytocin is the first-line prophylactic drug, regardless of the route of delivery (Grade A); a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM (professional consensus). After vaginal delivery, routine cord drainage (Grade B), controlled cord traction (Grade A), uterine massage (Grade A), and routine bladder voiding (professional consensus) are not systematically recommended for PPH prevention. After caesarean delivery, placental delivery by controlled cord traction is recommended (grade B). The routine use of a collector bag to assess postpartum blood loss at vaginal delivery is not systematically recommended (Grade B), since the incidence of severe PPH is not affected by this intervention. In cases of overt PPH after vaginal delivery, placement of a blood collection bag is recommended (professional consensus). The initial treatment of PPH consists in a manual uterine examination, together with antibiotic prophylaxis, careful visual assessment of the lower genital tract, a uterine massage, and the administration of 5-10 IU oxytocin injected slowly IV or IM, followed by a maintenance infusion not to exceed a cumulative dose of 40IU (professional consensus). If oxytocin fails to control the bleeding, the administration of sulprostone is recommended within 30minutes of the PPH diagnosis (Grade C). Intrauterine balloon tamponade can be performed if sulprostone fails and before recourse to either surgery or interventional radiology (professional consensus). Fluid resuscitation is recommended for PPH persistent after first line uterotonics, or if clinical signs of severity (Grade B). The objective of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8g/dL. During active haemorrhaging, it is desirable to maintain a fibrinogen level ≥2g/L (professional consensus). RBC, fibrinogen and fresh frozen plasma (FFP) may be administered without awaiting laboratory results (professional consensus). Tranexamic acid may be used at a dose of 1 g, renewable once if ineffective the first time in the treatment of PPH when bleeding persists after sulprostone administration (professional consensus), even though its clinical value has not yet been demonstrated in obstetric settings. It is recommended to prevent and treat hypothermia in women with PPH by warming infusion solutions and blood products and by active skin warming (Grade C). Oxygen administration is recommended in women with severe PPH (professional consensus). If PPH is not controlled by pharmacological treatments and possibly intra-uterine balloon, invasive treatments by arterial embolization or surgery are recommended (Grade C). No technique for conservative surgery is favoured over any other (professional consensus). Hospital-to-hospital transfer of a woman with a PPH for embolization is possible once hemoperitoneum is ruled out and if the patient's hemodynamic condition so allows (professional consensus).
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http://dx.doi.org/10.1016/j.ejogrb.2015.12.012DOI Listing
March 2016

Impact of prenatal diagnosis on the outcome of patients with a transposition of great arteries: A 24-year population-based study.

Birth Defects Res A Clin Mol Teratol 2016 Mar 21;106(3):178-84. Epub 2015 Dec 21.

EA 4681, PEPRADE, Clermont Université, Université d'Auvergne, Clermont-Ferrand, France.

Background: Transposition of great arteries (TGA) defined as the combination of concordant atrioventricular and discordant ventriculo-arterial connections is one of the most common congenital heart defects. Prenatal diagnosis of TGA remains difficult. To determine the impact of antenatal diagnosis we evaluated the sensitivity of antenatal detection and the neonatal mortality of TGA considering two study periods and two major types of TGA.

Methods: A cross-sectional study was performed. Data were collected from a French population-based birth defect registry. From 1988 to 2012, 94 fetuses with TGA were registered. The study period was subdivided into the 1988 to 1999 period and the 2000 to 2012 period. Two types of TGA were considered: isolated TGA (n = 66) and associated TGA (n = 28). A stratified analysis was performed considering the study periods and the types of TGA.

Results: Considering the study periods, the sensitivity of prenatal detection of TGA increased significantly (9.8% vs. 51.5%, p = 0.0001). The same trend was found for associated TGA (4.8% vs. 33.3%, p = 0.002) and isolated TGA (21.1% vs. 100%, p < 0.001). A late diagnosis of TGA (7 days after birth) was observed in 13.2% of cases. Neonatal mortality decreased significantly over time for isolated TGA (25.0% vs. 0 p = 0.01). Prenatal diagnosis of both types of TGA did not improve survival.

Conclusion: We demonstrated that prenatal diagnosis and neonatal mortality of TGA varied greatly according to the malformation type and the study period. This could be explained by an improvement in terms of medical management.
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http://dx.doi.org/10.1002/bdra.23474DOI Listing
March 2016

Comment and reply on: Guidelines for the management of spontaneous preterm labor: identification of spontaneous preterm labor, diagnosis of preterm premature rupture of membranes, and preventive tools for preterm birth.

J Matern Fetal Neonatal Med 2015 Jun 17:1-2. Epub 2015 Jun 17.

a CHU Estaing Pôle Gynécologie-Obstétrique-Reproduction Humaine Clermont-Ferrand, France Faculté de Médecine, Clermont Université Clermont-Ferrand, France.

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http://dx.doi.org/10.3109/14767058.2011.633671DOI Listing
June 2015

Aquaporins and Fetal Membranes From Diabetic Parturient Women: Expression Abnormalities and Regulation by Insulin.

J Clin Endocrinol Metab 2015 Oct 24;100(10):E1270-9. Epub 2015 Jul 24.

Retinoids, Reproduction Developmental Diseases (D.B., M.R., G.M., C.P., D.G., L.B., V.S.), School of Medicine, Clermont Université, Université d'Auvergne, F-63000 Clermont-Ferrand, France; Biochemistry and Molecular Biology Department (D.B., G.M., R.L. V.S.), CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France; Biostatistics Unit Department (B.P.), CHU Clermont-Ferrand, F-63000 Clermont-Ferrand, France; School of Medicine Henri-Warembourg (P.D., I.F.), Université Lille 2, PRES Lille Nord de France, F-59000 Lille, France; and Integrative Genomics and Modelization of Metabolic Diseases (A.V.), EGID, School of Medicine Henri-Warembourg, Université Lille 2, PRES Lille Nord de France, F-59000 Lille, France.

Context: During pregnancy, aquaporins (AQPs) expressed in fetal membranes are essential for controlling the homeostasis of the amniotic volume, but their regulation by insulin was never explored in diabetic women.

Objective: The aim of our study was to investigate the involvement of AQPs 1, 3, 8, and 9 expressed in fetal membranes in diabetic parturient women and the control of their expression by insulin.

Design And Participants: From 129 fetal membranes in four populations (controls, type 1, type 2 [T2D], and gestational diabetes [GD]), we established an expression AQP profile. In a second step, the amnion was used to study the control of the expression and functions of AQPs 3 and 9 by insulin.

Main Outcomes And Measures: The expression of transcripts and proteins of AQPs was studied by quantitative RT-PCR and ELISA. We analyzed the regulation by insulin of the expression of AQPs 3 and 9 in the amnion. A tritiated glycerol test enabled us to measure the impact of insulin on the functional characteristics. Using an inhibitor of phosphatidylinositol 3-kinase, we analyzed the insulin intracellular signaling pathway.

Results: The expression of AQP3 protein was significantly weaker in groups T2D and GD. In nondiabetic fetal membranes, we showed for the amnion (but not for the chorion) a significant repression by insulin of the transcriptional expression of AQPs 3 and 9, which was blocked by a phosphatidylinositol 3-kinase inhibitor.

Conclusion: In fetal membranes, the repression of AQP3 protein expression and functions observed in vivo is allowed by the hyperinsulinism described in pregnant women with T2D or GD.
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http://dx.doi.org/10.1210/jc.2015-2057DOI Listing
October 2015

[Management of preterm labor on cervical-uterine incompetence using a pessary cerclage obstetrical].

Pan Afr Med J 2015 24;20:284. Epub 2015 Mar 24.

Service de Gynécologie-Obstétrique et Biologie de la Reproduction, CHU Estaing, 1, Place Lucie Aubrac, 63001 Clermont-Ferrand.

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http://dx.doi.org/10.11604/pamj.2015.20.284.5847DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4483363PMC
April 2016

Prenatal diagnosis of the VACTERL association using routine ultrasound examination.

Birth Defects Res A Clin Mol Teratol 2015 Oct 2;103(10):880-6. Epub 2015 Jun 2.

Pôle Gynéco-Obstétrique-Reproduction Humaine, CHU Clermont-Ferrand, Clermont-Ferrand, France.

Background: The prognosis and early neonatal management of the VACTERL association depend mainly on the severity of malformations ascertained prenatally.

Methods: Here we reviewed the spectrum of clinical features observed in cases of VACTERL association ascertained prenatally through ultrasound examination but examined at birth and compared them with cases ascertained postnatally.

Results: From 1995 to 2011, a total of 19 cases of VACTERL association were observed in our center; 10 were ascertained prenatally and confirmed after birth whereas 9 were ascertained only after birth. The types and frequencies of malformations observed prenatally were as follows: renal malformations (45%), tracheoesophageal fistula (44%), cardiac malformations (20%), vertebral (13%), and limb (11%) defects. Anal atresia was never detected using routine prenatal ultrasound examination.

Conclusion: Further studies of fetuses with the VACTERL association are necessary to better delineate the malformations spectrum observed prenatally to improve the early recognition of the VACTERL association.
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http://dx.doi.org/10.1002/bdra.23346DOI Listing
October 2015

Congenital diaphragmatic hernia may be associated with 17q12 microdeletion syndrome.

Am J Med Genet A 2015 Jan 25;167A(1):250-3. Epub 2014 Nov 25.

Cytogénétique Médicale, Univ Clermont1, UFR Médecine, CHU Clermont-Ferrand, CHU Estaing, France; EA 4677, ERTICa, Université d'Auvergne, Clermont-Ferrand, France.

Microdeletions of 17q12 encompassing TCF2 are associated with maturity-onset of diabetes of the young type 5, cystic renal disease, pancreatic atrophy, Mullerian aplasia in females and variable cognitive impairment. We report on a patient with a de novo 17q12 microdeletion, 1.8 Mb in size, associated with congenital diaphragmatic hernia (CDH). The 5-year-old male patient presented multicystic renal dysplasia kidneys, minor facial dysmorphic features and skeletal anomalies, but neither developmental delay nor behavioral abnormalities. CDH has been previously associated with the 17q12 microdeletion syndrome only in one prenatal case. The present study reinforces the hypothesis that CDH is part of the phenotype for 17q12 microdeletion and that 17q12 encompasses candidate(s) gene(s) involved in diaphragm development. We suggest that PIGW, a gene involved in an early step of GPI biosynthesis, could be a strong candidate gene for CDH.
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http://dx.doi.org/10.1002/ajmg.a.36840DOI Listing
January 2015

Metabolic disturbances of the vitamin A pathway in human diaphragmatic hernia.

Am J Physiol Lung Cell Mol Physiol 2015 Jan;308(2):L147-57

Congenital diaphragmatic hernia (CDH) is a common life-threatening congenital anomaly resulting in high rates of perinatal death and neonatal respiratory distress. Some of the nonisolated forms are related to single-gene mutations or genomic rearrangements, but the genetics of the isolated forms (60% of cases) still remains a challenging issue. Retinoid signaling (RA) is critical for both diaphragm and lung development, and it has been hypothesized that subtle disruptions of this pathway could contribute to isolated CDH etiology. Here we used time series of normal and CDH lungs in humans, in nitrofen-exposed rats, and in surgically induced hernia in rabbits to perform a systematic transcriptional analysis of the RA pathway key components. The results point to CRPBP2, CY26B1, and ALDH1A2 as deregulated RA signaling genes in human CDH. Furthermore, the expression profile comparisons suggest that ALDH1A2 overexpression is not a primary event, but rather a consequence of the CDH-induced lung injury. Taken together, these data show that RA signaling disruption is part of CDH pathogenesis, and also that dysregulation of this pathway should be considered organ specifically.
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http://dx.doi.org/10.1152/ajplung.00108.2014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4338943PMC
January 2015