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Background About 1.3 million pregnant women lived with HIV and were eligible to receive antiretroviral therapy (ART) worldwide in 2021. The World Health Organization recommends protease inhibitors (PI)-based regimen as second or third-line during pregnancy. With remaining pregnant women exposed to PIs, there is still an interest to assess whether this treatment affects perinatal outcomes. Adverse perinatal outcomes after prenatal exposure to PI-based ART remain conflicting: some studies report an increased risk of preterm birth (PTB) and low-birth-weight (LBW), while others do not find these results. We assessed adverse perinatal outcomes associated with prenatal exposure to PI-based compared with non-nucleoside reverse transcriptase (NNRTI)-based ART. Methods We performed a systematic review searching PubMed, Reprotox, Clinical Trial Registry (clinicaltrials.gov) and abstracts of HIV conferences between 01/01/2002 and 29/10/2021. We used Oxford and Newcastle-Ottawa scales to assess the methodological quality. Studied perinatal outcomes were spontaneous abortion, stillbirth, congenital abnormalities, PTB ( Results Out of the 49,171 citations identified, our systematic review included 32 published studies, assessing 45,427 pregnant women. There was no significant association between prenatal exposure to PIs compared to NNRTIs for VPTB, LBW, SGA, stillbirth, and congenital abnormalities. However, it was inconclusive for PTB, and PI-based ART is significantly associated with an increased risk of VSGA (sRR 1.41 [1.08-1.84]; I2 = 0%) compared to NNRTIs. Conclusions We did not report any significant association between prenatal exposure to PIs vs NNRTIs-based regimens for most of the adverse perinatal outcomes, except for VSGA significantly increased (+ 41%). The evaluation of antiretroviral exposure on pregnancy outcomes remains crucial to fully assess the benefice-risk balance, when prescribing ART in women of reproductive potential with HIV. PROSPERO number CRD42022306896.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause severe placental lesions leading rapidly to intrauterine fetal death (IUFD). From August 2020 to September 2021, in the pathology department of Toulouse Oncopole, we analyzed 50 placentas from COVID-19-positive unvaccinated mothers. The purpose of our study is to describe the clinicopathological characteristics of these placental damages and to understand the pathophysiology. Ten of them (20%) showed placental lesions with positive immunohistochemistry for SARS-CoV-2 in villous trophoblasts. In five cases (10%), we observed massive placental damage associating trophoblastic necrosis, fibrinous deposits, intervillositis, as well as extensive hemorrhagic changes due to SARS-CoV-2 infection probably responsible of IUFD by functional placental insufficiency. In five other cases, we found similar placental lesions but with a focal distribution that did not lead to IUFD but live birth. These lesions are independent of maternal clinical severity of COVID-19 infection because they occur despite mild maternal symptoms and are therefore difficult to predict. In our cases, they occurred 1-3 weeks after positive SARS-CoV-2 maternal real-time polymerase chain reaction testing and were observed in the 2nd and 3rd trimesters of pregnancies. When these lesions are focal, they do not lead to IUFD and can be involved in intrauterine growth restriction. Our findings, together with recent observations, suggest that future pregnancy guidance should include stricter pandemic precautions such as screening for a wider array of COVID-19 symptoms, enhanced ultrasound monitoring, as well as newborn medical surveillance.

SUMMARY OF RECOMMENDATIONS: 1. Oxytocin for induction or augmentation of labor should not be started when there is a previous scar on the body of the uterus (such as previous classical cesarean section, uterine perforation or myomectomy when uterine cavity is reached) or in any other condition where labor or vaginal delivery are contraindicated. (Moderate quality evidence +++-; Strong recommendation). 2. Oxytocin should not be started before at least 1 h has elapsed since amniotomy, 6 h since the use of dinoprostone (30 min if vaginal insert) and 4 h since the use of misoprostol (Low quality evidence ++- -; Moderate recommendation). 3. Cardiotocography (CTG) should be performed and a normal pattern without tachysystole should be documented for at least 30 min before oxytocin is used. Continuous CTG, with adequate monitoring of both fetal heart rate and uterine contractions, should be maintained for as long as oxytocin is used, and thereafter until delivery (Low ++- - to moderate +++- quality evidence; Strong recommendation). 4. For labor induction, at least 1-h should be allowed after amniotomy before oxytocin infusion is started, to evaluate whether adequate uterine contractility has meanwhile ensued. For augmentation of labor, if the membranes are intact and there are conditions for a safe amniotomy, the latter should be considered before oxytocin is started (Very low quality evidence +- --; Weak recommendation). 5. Oxytocin should be administered intravenously using the following regimen: 5 IU oxytocin diluted in 500 mL of 0.9% normal saline (NaCl) (each mL contains 10 mIU of oxytocin), in an infusion pump at increasing rates, as shown in Table 1, until a frequency of 3-4 contractions per 10 min is reached, a non-reassuring CTG pattern ensues, or maximum rates are reached (Low quality evidence ++ - -; Strong recommendation). If the frequency of contractions exceeds 5 in 10 min, the infusion rate should be reduced, even if a normal CTG pattern is present. With a non-reassuring CTG pattern, urgent clinical assessment by an obstetrician is indicated, and strong consideration should be given to reducing or stopping the oxytocin infusion. The minimal effective dose of oxytocin should always be used. (Low ++- - to Moderate +++- - quality evidence; Strong recommendation). 6. Use of oxytocin for induction and augmentation of labor should be regularly audited (Low quality evidence ++--; Strong recommendation).

OBJECTIVE To assess the cost-effectiveness of vaginal misoprostol (PGE1; 25 μg) compared with a slow-release dinoprostone (PGE2) pessary (10 μg) for labor induction due to an unfavorable cervix at term. METHODS We used data from an open-label multicenter, randomized non-inferiority trial that recruited women for whom labor was induced for medical reasons. The incremental cost-effectiveness ratio was assessed from the payer's perspective, with the focus on inpatient care costs and using the cesarean deliveries avoided (CDA) rate as the primary analysis and the rate of vaginal delivery within 24 h (VD24) as the secondary analysis. RESULTS Analyses were based on 790 women in each group. Differences between treatment arms were the mean cost per patient of €4410 and €4399, a CDA rate of 80.1% and 77.9% and a VD24 rate of 46.1% and 59.4% for dinoprostone and misoprostol, respectively. Dinoprostone is not cost-effective according to the CDA rate and misoprostol was either a cost-effective or a dominant strategy according to the VD24. CONCLUSION Misoprostol and dinoprostone have equal cost management with mixed efficacy according to the clinical outcome used. Finally, misoprostol may be an attractive option for hospitals as the price is lower and it is easier to use. TRIAL REGISTRATION ClinicalTrials.gov: NCT01765881. URL: https://clinicaltrials.gov/ct2/show/NCT01765881. ClinicalTrialRegistrer.eu: 2011-000933-35. URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-000933-35/FR.

Background: About 1.3 million pregnant women lived with HIV and were eligible to receive antiretroviral therapy (ART) worldwide in 2021. The World Health Organization recommends protease inhibitors (PI)-based regimen as second or third-line during pregnancy. With remaining pregnant women exposed to PIs, there is still an interest to assess whether this treatment affects perinatal outcomes. Adverse perinatal outcomes after prenatal exposure to PI-based ART remain conflicting: some studies report an increased risk of preterm birth (PTB) and low-birth-weight (LBW), while others do not find these results. We assessed adverse perinatal outcomes associated with prenatal exposure to PI-based compared with non-nucleoside reverse transcriptase (NNRTI)-based ART. Methods: We performed a systematic review searching PubMed, Reprotox, Clinical Trial Registry (clinicaltrials.gov) and abstracts of HIV conferences between 01/01/2002 and 29/10/2021. We used Oxford and Newcastle-Ottawa scales to assess the methodological quality. Studied perinatal outcomes were spontaneous abortion, stillbirth, congenital abnormalities, PTB (Results: Out of the 49,171 citations identified, our systematic review included 32 published studies, assessing 45,427 pregnant women. There was no significant association between prenatal exposure to PIs compared to NNRTIs for VPTB, LBW, SGA, stillbirth, and congenital abnormalities. However, it was inconclusive for PTB, and PI-based ART is significantly associated with an increased risk of VSGA (sRR 1.41 [1.08-1.84]; I2=0%) compared to NNRTIs. Conclusions: We did not report any significant association between prenatal exposure to PIs vs NNRTIs-based regimens for most of the adverse perinatal outcomes, except for VSGA significantly increased (+41%). The evaluation of antiretroviral exposure on pregnancy outcomes remains crucial to fully assess the benefice-risk balance, when prescribing ART in women of reproductive potential with HIV. PROSPERO number: CRD42022306896.

Premature placental senescence is a hallmark of pregnancy-related disorders such as intrauterine growth restriction (IUGR) and preeclampsia (PE), two major cause of maternal and neonatal morbidity and mortality. Oxidative stress and lipid peroxidation are involved in the pathogenesis of PE and IUGR, and may play a role in placental aging. In this study, we investigated whether 4-hydroxy-2-nonenal (HNE), a lipid peroxidation-derived aldehyde present in preeclamptic placentas, may contribute to premature senescence in placenta-related complications. Placentas from PE-affected women, exhibited several senescence patterns, such as an increased expression of phosphorylated (serine-139) histone γH2AX, a sensitive marker of double-stranded DNA breaks, the presence of lipofuscin granules, and an accumulation of high molecular weight cross-linked and ubiquitinated proteins. PE placentas showed an accumulation of acetylated proteins consistent with the presence of HNE-adducts on sirtuin 1 (SIRT1). Likewise, oxidative stress and senescence markers together with SIRT1 modification by HNE, were observed in murine placentas from mice treated with lipopolysaccharide during gestation and used as models of IUGR. The addition of HNE and ONE (4-oxo-2-nonenal), to cultured HTR-8/SVneo human trophoblasts activated the senescence-associated- β-galactosidase, and generated an accumulation of acetylated proteins, consistent with a modification of SIRT1 by HNE. Altogether, these data emphasize the role of HNE and lipid peroxidation-derived aldehydes in premature placental senescence in PE and IUGR, and more generally in pathological pregnancies.

Traditional obstetric units are inadequate for the level of monitoring required in pre-eclamptic patients. It remains to be determined which facility and tools should be implemented. The aim of this work was to identify predictive factors of admission to Intensive Care Unit (ICU) admissions for pregnancy-related hypertensive complications.We conducted an observational, retrospective multicenter study (Toulouse, Nantes). Both have a level III maternity unit and an ICU. The selected patients had one or more of the following diagnoses on admission in the ICU or during hospitalization: pre-eclampsia, eclampsia, HELLP syndrome, Acute Fatty Liver of Pregnancy (AFLP), Hemolytic Uremic Syndrome (HUS). SAPS II, SOFA and APACHE II on admission, and a validated nursing workload assessment score: TISS 28, were collected.211 parturient women were included. According to the multivariate analysis: APACHE II and SAPS 2 severity scores15 were significantly higher in the TISS 28 ≥ 20 group. There were also higher rates of uricemia360 mmol/l.To date, there are no reliable and validated predictive factors of severity to guide the transfer of pre-eclamptic patients to an ICU. The combination of an increased APACHE II score and uricemia, as well as a high care workload score that could help with the transfer of high-risk pre-eclamptic patients to a specific care facility. This hypothesis should be tested prospectively. This work could incite reflection on the value of creating obstetric intensive care units, according to the size of the maternity unit.

Résumé Un nouveau coronavirus (SARS-CoV-2) mis en évidence en fin d’année 2019 en Chine se diffuse à travers tous les continents. Le plus souvent à l’origine d’un syndrome infectieux sans gravité, associant à différents degrés des symptômes bénins (fièvre, toux, myalgies, céphalées et éventuels troubles digestifs) le SARS-Covid-2 peut être à l’origine de pathologies pulmonaires graves et parfois de décès. Les données sur les conséquences pendant la grossesse sont limitées. Les premières données chinoises publiées semblent montrer que les symptômes chez la femme enceinte sont les mêmes que ceux de la population générale. mais il y a un risque qu'il y ai plus de formes graves. Il n’y a pas de cas de transmission maternofœtale intra utérine mais des cas de nouveau-nés infectés précocement font penser qu’il pourrait y avoir transmission verticale per-partum ou néonatale. Une prématurité induite et des cas de détresses respiratoires chez les nouveau-nés de mères infectées ont été décrits. La grossesse est connue comme une période plus à risque pour les conséquences des infections respiratoires, comme pour la grippe, il parait donc important de dépister le Covid-19 en présence de symptômes et de surveiller de façon rapprochée les femmes enceintes infectées. Dans ce contexte d’épidémie de SARS-Covid-2, les sociétés savantes de gynécologie-obstétrique, d’infectiologie et de néonatalogie ont proposé un protocole français de prise en charge des cas possibles et avérés de SARS-Covid-2 chez la femme enceinte. Ces propositions peuvent évoluer de façon quotidienne avec l’avancée de l’épidémie et des connaissances chez la femme enceinte.

HELLP syndrome is a rare and severe pregnancy complication which exposes to severe maternal and fetal morbidity. Management of HELLP syndrome occurring before 34 weeks of gestation (WG) is still controversial but conservative management may be beneficial in patients with stable HELLP syndrome. The aim of the study was thus to identify which maternal and fetal prognostic factors could be predictive of HELLP syndrome evolution.From 2003 to 2016, all patients with HELLP syndrome occurring between 26 and 34 WG were retrospectively enrolled. Study population was stratified according to obstetrical management. Patients in whom delivery was initiated within 48 h following diagnosis constituted the active management group. In the expectant management group, pregnancy was prolonged until maternal or fetal follow up indicated delivery.Ninety-nine patients were included in our study. Among them, 61 were managed expectantly. At baseline, the active management group was more likely to suffer from persistent hyperreflexia (While expectant management in HELLP syndrome might be beneficial through its reduction of prematurity, it cannot be conducted in all patients. Identification of baseline parameters predictive of disease evolution is thus of tremendous importance to define which obstetrical approach should be prioritized.

INTRODUCTION Our aim was to identify risk factors for failed induction in morbidly obese patients undergoing the induction of labor at term. MATERIAL AND METHODS This was a retrospective multicenter study on a cohort of 235 patients with a body mass index greater than 40 kg/m2 and giving birth to a singleton in cephalic presentation, who had an induction of labor from 38 weeks of amenorrhea. Scheduled cesareans and spontaneous vaginal deliveries were excluded. Maternal, peri-partum and neonatal characteristics were analyzed according to the delivery route. RESULTS In all, 235 patients were included. Of these, 62.5% patients delivered vaginally and 37.5% by cesarean section. The frequency of nulliparity was greater in patients who had a cesarean section (56 [interquartile range, IQR, 38.1] vs 56 [IQR 63.6], P

Objective: The magnitude and direction of effects on pregnancy outcomes of the lockdown imposed during COVID-19 have been uncertain and debated. Therefore, we aimed to quantify delivery and perinatal outcomes during the first nationwide lockdown due to the COVID-19 pandemic compared with the same durations of time for the pre- and post-lockdown periods. Study design: This was a retrospective cohort study of six university hospital maternity units distributed across France, each of which serves as the obstetric care referral unit within its respective perinatal network. Maternal and perinatal outcomes were compared between the lockdown period and same-duration (i.e., 55-day) periods before and after the 2020 lockdown (pre-lockdown: 22 January–16 March; lockdown: 17 March–10 May; post-lockdown: 11 May–4 July). We compared the overall rates of Caesarean delivery (CD), pre-labor CD, labor induction, operative vaginal delivery, severe postpartum hemorrhage (≥1 L), severe perineal tear, maternal transfusion, and neonatal mortality and morbidity (1- and 5-min Apgar scores < 7), hypoxia and anoxia (umbilical arterial pH < 7.20 or

International audience; Background: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial.Objective: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix.Study design: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of

Objective: To evaluate women’s choice in the method of labour induction between oral misoprostol, PGE2 pessary and the Foley catheter. To compare women’s satisfaction according to their choice and to identify factors associated with patient satisfaction. Design: Prospective cohort study. Setting: Tertiary hospital in Toulouse, France, from July 2019 to October 2020. Population: All women admitted for labour induction at term, by either oral misoprostol, PGE2 pessary or Foley catheter. Methods: Women chose their preferred method. Before and after the delivery, they were asked to argument their choice and to evaluate their satisfaction through the use of questionnaires. Main outcome measures: Global level of satisfaction. Results: Of the 520 women included, 67,5% of women chose oral Misoprostol compared to 21% PGE2 pessary and 11.5% the Foley catheter. Regarding global satisfaction, we found no significant difference between the three groups: 78,4%, 68,8% and 71,2% (p=0,091) for respectively oral misoprostol, PGE2 pessary and Foley catheter. Factors that seem to improve women’s satisfaction were nulliparity (OR = 2.03, 95%CI [1.19 - 3.53]), delivery within 24 hours after the start of induction (OR = 3.46, 95%CI. [2.02 - 6.14]) and adequate information (OR = 4.21,95%CI [1.86 - 9.64]). Factors associated with lower satisfaction rates were postpartum hemorrhage (OR = 0.51, 95%CI [0.30 - 0.88]) and caesarean section (OR = 0.31, 95%CI [0.17 - 0.54]). Conclusion: Women satisfaction rates were not different between the three methods, when chosen by the patients themselves. These finding should encourage caregivers to promote shared decision making when possible.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. On June 2008 and February 2009, Dear Doctor Letters (DDLs) were sent by the French Health Authorities (AFSSAPS) to remind practitioners of risks with NSAIDs after the fifth month of pregnancy. The aim of this study was to evaluate the impact of these letters on NSAID prescriptions during late pregnancy. EFEMERIS is a French database that registers drugs prescribed and reimbursed during pregnancy and outcomes between 2004 and 2015. We performed a descriptive study and a 'before-and-after' comparison of NSAID prescriptions between 3 June 2006 and 3 June 2008 ('before group'), and between 1 March 2010 and 1 March 2012 ('after group'). We carried out a Cochran Armitage trend test to check whether the rate of women exposed to NSAIDs varies linearly over time. We identified 948 (4.38%) pregnant women in the 'before group' and 678 (2.73%) in the 'after group' receiving at least one NSAID prescription in late pregnancy (P < 0.0001). Between 2006 and 2012, mainly prescriptions for morniflumate/niflumic acid (1.7% vs. 0.9%; P < 0.0001), ibuprofen (0.8% vs. 0.6%; P = 0.01) and ketoprofen (0.7% vs. 0.3%; P < 0.0001) fell significantly after DDLs. The Cochran Armitage trend test shows that the percentage of women exposed to NSAIDs in late pregnancy decreased significantly during the study period (P < 0.0001). This study highlighted a significant decrease in the percentage of women receiving NSAID prescriptions during late pregnancy after DDLs. This decrease is not linked to a specific women's profile or prescriber's medical discipline.

OBJECTIVE To assess, according to chorionicity, the perinatal outcome of twin pregnancy in which vaginal delivery is planned. METHODS JUMODA (JUmeaux MODe d'Accouchement) was a national prospective population-based cohort study of twin pregnancies, delivered in 176 maternity units in France, from February 2014 to March 2015. In this planned secondary analysis, we assessed, according to chorionicity, the perinatal outcome of twin pregnancies, in which vaginal delivery was planned, that delivered at or after 32 weeks of gestation with the first twin in cephalic presentation. In order to select a population with well-recognized indications for planned vaginal delivery, we applied the same exclusion criteria as those in the Twin Birth Study, an international randomized trial. Monochorionic twin pregnancies with twin-to-twin transfusion syndrome or twin anemia-polycythemia sequence were defined as complicated and were excluded. The primary outcome was a composite of intrapartum mortality and neonatal morbidity and mortality. Multivariable logistic regression models were used to control for potential confounders. Subgroup analyses were conducted according to birth order (first or second twin) and gestational age at delivery (

International audience; Background: Induction of labor is among the most common procedures for pregnant women. Only a few randomized clinical trials with relatively small samples have compared misoprostol with dinoprostone. Although their efficacy seems similar, their safety profiles have not been adequately evaluated, and economic data are sparse. Objective: This study aimed to test the noninferiority of vaginal misoprostol (prostaglandin E1) (25 μg) to a slow-release dinoprostone (prostaglandin E2) pessary (10 μg) for induction of labor with an unfavorable cervix at term. Study Design: This was an open-label multicenter randomized noninferiority trial at 4 university hospitals of the Research Group in Obstetrics and Gynecology between 2012 and 2015. We recruited women who underwent induction of labor for medical reasons, those with a Bishop score of ≤5 at ≥36 weeks’ gestation, and those with a cephalic-presenting singleton pregnancy with no previous cesarean delivery. Women were randomly allocated to receive either vaginal misoprostol at 4-hour intervals (25 μg) or a 10-mg slow-release dinoprostone pessary. The primary outcome was the total cesarean delivery rate. Noninferiority was defined as a difference in the cesarean delivery rates between the groups of no more than 5%. Secondary outcomes included neonatal and maternal morbidity, vaginal delivery at

Preeclampsia (PE) is a multifactorial pregnancy disease, characterized by new-onset gestational hypertension with (or without) proteinuria or end-organ failure, exclusively observed in humans. It is a leading cause of maternal morbidity affecting 3–7% of pregnant women worldwide. PE pathophysiology could result from abnormal placentation due to a defective trophoblastic invasion and an impaired remodeling of uterine spiral arteries, leading to a poor adaptation of utero-placental circulation. This would be associated with hypoxia/reoxygenation phenomena, oxygen gradient fluctuations, altered antioxidant capacity, oxidative stress, and reduced nitric oxide (NO) bioavailability. This results in part from the reaction of NO with the radical anion superoxide (O2•−), which produces peroxynitrite ONOO-, a powerful pro-oxidant and inflammatory agent. Another mechanism is the progressive inhibition of the placental endothelial nitric oxide synthase (eNOS) by oxidative stress, which results in eNOS uncoupling via several events such as a depletion of the eNOS substrate L-arginine due to increased arginase activity, an oxidation of the eNOS cofactor tetrahydrobiopterin (BH4), or eNOS post-translational modifications (for instance by S-glutathionylation). The uncoupling of eNOS triggers a switch of its activity from a NO-producing enzyme to a NADPH oxidase-like system generating O2•−, thereby potentiating ROS production and oxidative stress. Moreover, in PE placentas, eNOS could be post-translationally modified by lipid peroxidation-derived aldehydes such as 4-oxononenal (ONE) a highly bioreactive agent, able to inhibit eNOS activity and NO production. This review summarizes the dysfunction of placental eNOS evoked by oxidative stress and lipid peroxidation products, and the potential consequences on PE pathogenesis., Graphical abstract Image 1, Highlights • Physiological ROS production is enhanced during pregnancy. • eNOS is one of the main target of oxidative stress in PE placenta. • eNOS is S-glutathionylated in PE placentas. • eNOS is modified by lipid oxidation products in PE placentas.

Objective: The effect of lockdowns during the coronavirus (COVID-19) pandemic on pregnancy outcomes remains uncertain. We aimed to evaluate the association between the COVID-19-related lockdown and pregnancy outcomes in maternity hospitals in France. Study design: This was a retrospective cohort study from six tertiary referral hospitals in different regions of France. Three 55-day periods were compared: pre-lockdown from 22 January 2020, lockdown from 17 March 2020, and post-lockdown from 11 May 2020 to 4 July 2020. We included all women who delivered singleton or multiple pregnancies, who delivered at ≥24 weeks of gestation and with birthweights ≥500 g. We documented gestational ages at the delivery of liveborn and stillborn infants (‘stillbirths’). These were categorized as having a very low birthweight (VLBW, +6 weeks, between weeks 28+0 and 31+6, and between 32+0 and weeks 36+6 were 1.0%, 1.9%, and 4.4%, respectively. After adjustment, these rates were stable between periods 1 and 2 (adjusted odds ratio, aOR 0.90; 95% confidence interval, CI 0.69–1.19) and between periods 2 and 3 (aOR 1.04; 95% CI 0.80–1.36). Although more VLBW neonates were born during lockdown (3.5% vs. 2.6%, p = 0.03), this difference did not persist after adjustment (aOR 0.84, CI 95% 0.64–1.10). The LBW rates were similar during the three periods at 12.5% overall. The stillbirth rate was unaffected by the lockdown. Conclusion: The pregnancy outcomes (preterm birth, LBW, VLBW, and stillbirth rates) were not modified by the COVID-19 lockdown in our cohort study in France. Considering the discrepancies in results and methodological issues in previous published studies, there is not sufficient evidence to conclude that such lockdowns have any impact on perinatal outcomes.

Resume Objectifs Le coronavirus SARS-CoV-2 mis en evidence en fin d’annee 2019 en Chine a atteint tous les continents, avec plus de 28 millions de cas declares dont plus de 920 000 deces au 17/9/2020. Le plus souvent a l’origine d’un syndrome infectieux benin, associant a differents degres des symptomes (fievre, toux, myalgies, cephalees et eventuels troubles digestifs), voire totalement asymptomatique, le SARS-CoV-2 peut etre a l’origine de pathologies pulmonaires graves et parfois de deces. Methode Au vu de l’evolution de l’epidemie, le College national des gynecologues obstetriciens francais a decide de mettre a jours les avis emis precedemment. Pour cela, le meme groupe d’experts, a ete sollicite avec realisation d’une revue de la litterature et prise en compte des avis de la Direction Generale de la Sante, la Haute Autorite de Sante, du Haut Conseil de Sante Publique. Resultats Les donnees pendant la grossesse sont plus nombreuses et plus precises. Les donnees publiees semblent montrer que les symptomes chez les femmes enceintes sont les memes que ceux de la population generale et qu’un sur risque existe chez la femme enceinte particulierement au troisieme trimestre. Un cas de transmission materno-fœtale intra uterine a ete formellement identifie. Une prematurite induite et des cas de detresses respiratoires chez les nouveau-nes de meres infectees ont ete decrits. Conclusion A la lumiere des nouvelles donnees, nous proposons une actualisation des recommandations de prise en charge. Ces propositions peuvent encore evoluer avec l’avancee de la pandemie et de potentielles nouvelles connaissances chez la femme enceinte.

BackgroundPre-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.MethodsElectronic-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.DiscussionThe findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy.Trial registrationClinicalTrials.govIdentifier:NCT02924636/ October 5th 2016.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-β4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-β4 abundance was confirmed with ELISA. Knockout of thymosin-β4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin β4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable. ispartof: KIDNEY INTERNATIONAL vol:99 issue:3 pages:737-749 ispartof: location:United States status: published

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.

International audience; OBJECTIVE: To assess neonatal morbidity and mortality according to whether cephalic second twins were born after internal version followed by total breech extraction or after instructions to push. We hypothesized that interval version would result in shorter intertwin delivery intervals and lower cesarean delivery rates for the second twin and therefore better neonatal outcomes. METHODS: These planned analyses of the JUMODA (JUmeaux MODe d'Accouchement) cohort, a national prospective population-based study of twin deliveries, examined births of cephalic second twins after vaginal birth of the first twin at or after 32 weeks of gestation. The internal version group of second twins born in breech presentation after obstetric maneuvers was compared with the pushing group, comprising those born in cephalic presentation. The primary outcome was a composite of neonatal morbidity and mortality. Multivariate modified Poisson regression models were used to control for potential confounders. RESULTS: Of 2,256 cephalic second twins, 487 (21.6%) were born in breech presentation after internal version and total breech extraction and 1,769 (78.4%) in cephalic presentation after pushing. Composite neonatal morbidity and mortality was not lower in the internal version (17/487 [3.5%]) compared with the pushing group (38/1,769 [2.1%]; adjusted relative risk [aRR] 1.73 [95% CI 0.98-3.05]), although median [quartile 1-quartile 3] intertwin delivery intervals were shorter (5 [4-8] vs 8 [5-12] minutes, P

Objective Increased expression of soluble fms-like tyrosine kinase 1 (sFlt-1), associated with a decrease in placental growth factor (PlGF), plays a key role in the pathogenesis of preeclampsia (PE). We evaluated the prognostic value of the sFlt-1/PlGF ratio for the onset of adverse maternofetal outcomes (AMFO) in case of early-onset PE with attempted expectant management. Study Design From October 2016 through November 2018, all singleton pregnancies complicated by early-onset PE (before 34 weeks of gestation) were included in a cohort study. The plasma levels of sFlt-1 and PlGF were blindly measured on admission. For the statistical analysis, we performed a bivariate analysis, a comparison of the receiving operating characteristic curves and a survival analysis estimated by the Kaplan–Meier method. Results Among 109 early PE, AMFO occurred in 87 pregnancies (79.8%), mainly hemolysis, elevated liver enzymes, and low platelet count syndrome and severe fetal heart rate abnormalities requiring urgent delivery. The area under the curve (AUC) of sFlt-1/PlGF ratio was 0.82 (95% confidence interval [CI]: 0.73–0.88) for the risk of AMFO and the difference between the AUCs was significant for each separate standard parameter (p = 0.018 for initial diastolic blood pressure, p = 0.013 for alanine aminotransferase, p Conclusion The sFlt-1/PlGF ratio is an additional tool in the prediction of AMFO in proven early-onset PE, which is likely to improve care by anticipating severe complications. Key Points

Objective To assess whether chorioamnionitis is associated with cerebral palsy (CP) or death at 2 years' corrected age in infants born before 32 weeks of gestation after spontaneous birth. Study design EPIPAGE-2 is a national, prospective, population-based cohort study of children born preterm in France in 2011; recruitment periods varied by gestational age. This analysis includes infants born alive after preterm labor or preterm premature rupture of membranes from 240/7 to 316/7 weeks of gestation. We compared the outcomes of CP, death at 2 years' corrected age, and “CP or death at age 2” according to the presence of either clinical chorioamnionitis or histologic chorioamnionitis. All percentages were weighted by the duration of the recruitment period. Results Among 2252 infants born alive spontaneously before 32 weeks of gestation, 116 (5.2%) were exposed to clinical chorioamnionitis. Among 1470 with placental examination data available, 639 (43.5%) had histologic chorioamnionitis. In total, 346 infants died before 2 years and 1586 (83.2% of the survivors) were evaluated for CP at age 2 years. CP rates were 11.1% with and 5.0% without clinical chorioamnionitis (P = .03) and 6.1% with and 5.3% without histologic chorioamnionitis (P = .49). After adjustment for confounding factors, CP risk rose with clinical chorioamnionitis (aOR 2.13, 95% CI 1.12-4.05) but not histologic chorioamnionitis (aOR 1.21, 95% 0.75-1.93). Neither form was associated with the composite outcome “CP or death at age 2.” Conclusions Among infants very preterm born spontaneously, the risk of CP at a corrected age of 2 years was associated with exposure to clinical chorioamnionitis but not histologic chorioamnionitis.

Objective To investigate the association between absent or reversed end-diastolic flow (ARED) on umbilical artery Doppler ultrasound and poor neurological outcome at 2 years of age after very preterm birth associated with suspected fetal growth restriction (FGR) or maternal hypertensive disorders. Methods The study population comprised all very preterm (22–31 completed weeks) singleton pregnancies delivered because of suspected FGR and/or maternal hypertensive disorders that had umbilical artery Doppler and 2-year follow-up available included in EPIPAGE-2, a prospective, nationwide, population-based cohort of preterm births in France in 2011. Univariate and two-level multivariable logistic regression analyses were used to assess the association of ARED in the umbilical artery, as compared with normal or reduced end-diastolic flow, with severe or moderate neuromotor and/or sensory disability and with an Ages and Stages Questionnaire (ASQ) score below a threshold. This was defined as a score more than 2 SD below the mean in any of the five domains, at age 2, adjusting for gestational age at delivery. ASQ is used to identify children at risk of developmental delay requiring reinforced follow-up and further evaluation. Descriptive statistics and bivariate tests were weighted according to the duration of the inclusion periods. Results The analysis included 484 children followed up at 2 years of age, for whom prenatal umbilical artery Doppler ultrasound was available. Among them, 8/484 (1.6%) had severe or moderate neuromotor and/or sensory disability, and 156/342 (45.4%) had an ASQ score below the threshold. Compared with normal or reduced end-diastolic flow in the umbilical artery (n = 305), ARED (n = 179) was associated with severe or moderate neuromotor and/or sensory disability (adjusted odds ratio (OR), 11.3; 95% CI, 1.4–93.2) but not with an ASQ score below the threshold (adjusted OR, 1.2; 95% CI, 0.8–1.9). Conclusion Among children delivered before 32 weeks of gestation due to suspected FGR and/or maternal hypertensive disorder who survived until 2 years of age, prenatal ARED in the umbilical artery was associated with a higher incidence of severe or moderate neuromotor and/or sensory disability. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd. EPIPAGE-2 was funded by the French Institute of Public Health Research/Institute of Public Health and its partners: the French Health Ministry, the National Institute of Health and Medical Research (INSERM), the National Institute of Cancer, and the National Solidarity Fund for Autonomy (CNSA); the National Research Agency through the French EQUIPEX program for investments in the future (reference ANR-11-EQXP-0038); and the PREMUP Foundation.

International audience; Regulatory measures and public concerns regarding bisphenol A (BPA) have led to its replacement by a variety of alternatives in consumer products. Due to their structural similarity to BPA, these alternatives are under surveillance, however, for potential endocrine disruption. Understanding the materno-fetal transfer of these BPA-related alternatives across the placenta is therefore crucial to assess prenatal exposure risks. The objective of the study was to assess and compare the placental transfer of a set of 15 selected bisphenols (BPs) (BP 4-4, BPA, BPAF, BPAP, 3-3 BPA, BPB, BPBP, BPC, BPE, BPF, BPFL, BPM, BPP, BPS and BPZ) using the ex vivo human placental perfusion model. The UHPLC–MS/MS method for simultaneous quantification of these BPs in perfusion media, within a concentration range of 0.003–5 μM, was able to measure placenta transfer rates as low as 0.6%–4%. Despite their structural similarities, these BPs differed greatly in placental transport efficiency. The placental transfer rates of BP4-4, BPAP, BPE, BPF, 3-3BPA, BPB, BPA were similar to that of antipyrine, indicating that their main transport mechanism was passive diffusion. By contrast, the placental transfer rates of BPFL and BPS were very limited, and intermediate for BPBP, BPZ, BPC, BPM, BPP and BPAF, suggesting weak diffusional permeability and/or that their passage might involve efflux transport. These placental transfer data will be particularly useful for predicting the fetal exposure of this important class of emerging contaminants.

Resume Objectif Elaborer des recommandations pour la pratique des IVG. Materiel et methodes Consultation de la base de donnees Medline, de la Cochrane Library et des recommandations des societes savantes francaises et etrangeres. Resultats Le nombre d’IVG est stable depuis plusieurs decennies. Il existe plusieurs elements expliquant le choix de l’IVG lorsqu’il existe une grossesse non prevue (GNP). L’initiation precoce de la contraception et le choix de la contraception en rapport avec la vie de la femme sont associes a une diminution des GNP. Les contraceptions reversibles de longue duree d’action apparaissent comme une contraception a positionner en premiere ligne pour l’adolescente du fait de son efficacite (grade C). L’echographie avant une IVG doit etre encouragee mais n’est pas indispensable pour realiser une IVG (accord professionnel). Des l’apparition echographique de l’embryon, l’estimation de la datation de la grossesse se fait par la mesure de la longueur cranio-caudale (LCC) ou par la mesure du diametre biparietal (BIP) a partir de 11 SA (grade B). Les mesures etant fiables a ± 5 jours, l’IVG peut etre realisee lorsque les mesures de LCC et/ou de BIP sont respectivement inferieures a 90 mm et 30 mm (accord professionnel). L’IVG medicamenteuse realisee avec la dose de 200 mg de mifepristone associe au misoprostol est efficace a tout âge gestationnel (NP1). Avant 7 SA, la prise de mifepristone sera suivie entre 24 et 48 heures de la prise de misoprostol par voie orale, buccale, sublinguale voire vaginale a la dose de 400 μg eventuellement renouvele apres 3 heures (NP1, grade A). Au-dela de 7 SA, les modes d’administration du misoprostol, par voie vaginale, sublinguale ou buccale, sont plus efficaces et mieux toleres que la voie orale (NP1). Il est recommande d’utiliser systematiquement une preparation cervicale lors d’une IVG instrumentale (accord professionnel). Le misoprostol est un agent de premiere intention pour la preparation cervicale a la dose de 400 μg (grade A). L’aspiration evacuatrice est preferable au curetage (grade B). Un uterus perfore lors d’une aspiration instrumentale ne doit pas etre considere en routine comme un uterus cicatriciel (accord professionnel). L’IVG instrumentale n’est pas associee a une augmentation du risque d’infertilite ulterieure ou de GEU (NP2). Les consultations medicales pre-IVG n’influent pas sur la decision d’interrompre ou non la grossesse et une majorite de femmes est assez sure de son choix lors de ces consultations. L’acceptabilite de la methode et la satisfaction des femmes semblent plus grandes lorsque celles-ci sont en mesure de choisir la methode d’IVG (grade B). Il n’y a pas de relation entre une augmentation des troubles psychiatriques et le recours a l’IVG (NP2). Les femmes ayant des antecedents psychiatriques sont a risque accru de troubles psychiques apres la survenue d’une grossesse non prevue (NP2). En cas d’IVG instrumentale, la contraception estro-progestative orale et le patch devraient etre debutes des le jour de l’IVG, l’anneau vaginal insere dans les 5 jours suivant l’IVG (grade B). En cas d’IVG medicamenteuse, l’anneau vaginal devrait etre insere dans la semaine suivant la prise de mifepristone, la contraception estro-progestative orale et le patch devraient etre debutes le jour meme ou le lendemain de la prise des prostaglandines (grade C). En cas d’IVG instrumentale, l’implant devrait etre insere le jour de l’IVG (grade B). En cas d’IVG medicamenteuse, l’implant peut etre insere a partir du jour de la prise de mifepristone (grade C). Le DIU au cuivre et au levonorgestrel doit etre insere preferentiellement le jour de l’IVG instrumentale (grade A). En cas d’IVG medicamenteuse, un DIU peut etre insere dans les 10 jours suivant la prise de mifepristone apres s’etre assure par echographie de l’absence de grossesse intra-uterine (grade C). Conclusion L’application de ces recommandations devrait favoriser une prise en charge plus homogene et amelioree des femmes desirant une IVG.

Journal de Gynecologie Obstetrique et Biologie de la Reproduction - Vol. 45 - N° 8 - p. 827-834

Preeclampsia (PE) is a leading cause of pregnancy complications, affecting 3-7% of pregnant women worldwide. The pathophysiology of preeclampsia involves a redox imbalance, oxidative stress and a reduced nitric oxide (NO) bioavailability. The molecular and cellular mechanisms leading to the dysfunction of the placental endothelial NO synthase (eNOS) are not clarified. This study was designed to investigate whether aldehydes generated by lipid peroxidation products (LPP), may contribute to placental eNOS dysfunction in PE. The analysis of placentas from PE-affected patients and normal pregnancies, showed a significant increase in protein carbonyl content, indicative of oxidative stress-induced protein modification, as shown by the accumulation of acrolein, 4-hydroxynonenal (HNE), and 4-oxo-2(E)-nonenal (ONE) adducts in PE placentas. In contrast, the levels of these LPP-adducts were low in placentas from normal pregnancies. Immunofluorescence and confocal experiments pointed out a colocalization of eNOS with ONE-Lys adducts, whereas eNOS was not modified in normal placentas. LC-MS/MS analysis of recombinant eNOS preincubated with ONE, allowed to identify several ONE-modified Lys-containing peptides, confirming that eNOS may undergo post-translational modification by LPP. The preincubation of HTR-8/SVneo human trophoblasts (HTR8) with ONE, resulted in ONE-Lys modification of eNOS and a reduced generation of NO. ONE inhibited the migration of HTR8 trophoblasts in the wound closure model, and this was partly restored by the NO donor, NOC-18, which confirmed the important role of NO in the invasive potential of trophoblasts. In conclusion, placental eNOS is modified by ONE in PE placentas, which emphasizes the sensitivity of this protein to oxidative stress in the disturbed redox environment of preeclamptic pregnancies.

International audience

Cesarean delivery rates at extreme prematurity have regularly increased over the past years, and few previous studies have investigated severe maternal morbidity associated with extreme preterm cesarean delivery.The aim of this study was to evaluate whether gestational age26 weeks of gestation (weeks) was associated with severe maternal morbidity and mortality (SMMM) of preterm cesarean deliveries in comparison with cesarean deliveries between 26 and 34 weeks.The Etude Epidémiologique sur les petits âges gestationnels (EPIPAGE) 2 is a national prospective population-based cohort study of preterm births in 2011. We included mothers with cesarean deliveries between 22 and 34 weeks, excluding those who had a cesarean delivery for the second twin only and those with pregnancy terminations. SMMM was analyzed as a composite endpoint defined as the occurrence of at least 1 of the following complications: severe postpartum hemorrhage defined by the use of a blood transfusion, intensive care unit admission, or death. To assess the association of gestational age26 weeks and SMMM, we used multivariate logistic regression and a propensity score-matching approach.Among 2525 women having preterm cesarean deliveries, 116 before 26 weeks and 2409 between 26 and 34 weeks, 407 (14.4%) presented with SMMM. The SMMM occurred in 31 mothers (26.7%) who were at gestational age26 weeks vs 376 (14.2%) between 26 and 34 weeks (P .001). Cluster multivariate logistic regression showed significant association of gestational age26 weeks and SMMM (adjusted odds ratio [aOR], 2.50; 95% confidence interval [CI], 1.42-4.40) and propensity score-matching analysis was consistent with these results (aOR, 2.27; 95% CI, 1.31-3.93).Obstetricians should know about the higher SMMM associated with cesarean deliveries before 26 weeks, integrate this knowledge into decisions regarding cesarean delivery, and be prepared to manage the associated complications.

Decreased nitric oxide (NO) bioavailability plays a critical role in the pathophysiology of preeclampsia (PE). Recent evidence indicates that S-glutathionylation may occur on the endothelial nitric oxide synthase (eNOS), leading to eNOS uncoupling, characterized by a decreased NO production and an increased generation of superoxide anion (O2•–). We hypothesized that eNOS glutathionylation may occur in PE placentas and participate in eNOS dysfunction. The glutathionylation of eNOS was investigated in thirteen PE-affected patients and in nine normal pregnancies. Immunofluorescence, confocal microscopy and western-blot experiments carried out on eNOS immunoprecipitates, revealed a high level of eNOS glutathionylation in PE placentas, mostly reversed by dithiotreitol (DTT), thus indicative of S-glutathionylation. In order to investigate whether eNOS glutathionylation may alter trophoblast migration, an important event occurring during early placentation, cultured HTR-8/SVneo human trophoblasts (HTR8) were exposed either to low pO2 (O2 1%) or to pO2 changes (O2 1–20%), in order to generate oxidative stress. Trophoblasts exposed to low pO2, did not undergo oxidative stress nor eNOS S-glutathionylation, and were able to generate NO and migrate in a wound closure model. In contrast, trophoblasts submitted to low/high pO2 changes, exhibited oxidative stress and a (DTT reversible) S-glutathionylation of eNOS, associated with reduced NO production and migration. The autonomous production of NO seemed necessary for the migratory potential of HTR8, as suggested by the inhibitory effect of eNOS silencing by small interfering RNAs, and the eNOS inhibitor L-NAME, in low pO2 conditions. Finally, the addition of the NO donor, NOC-18 (5 µM), restored in part the migration of HTR8, thereby emphasizing the role of NO in trophoblast homeostasis. In conclusion, the high level of eNOS S-glutathionylation in PE placentas provides new insights in the mechanism of eNOS dysfunction in this disease., Graphical abstract fx1, Highlights • eNOS is S-glutathionylated in preeclamptic placentas. • Oxidative stress evoked by pO2 changes, triggers eNOS S-glutathionylation in HTR8. • pO2 changes alter the invasive potential of HTR8 in the wound closure model. • The NO donor NOC-18 restores the invasive potential of HTR8.

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most widely used drugs. On June 2008 and February 2009, Dear Doctor Letters (DDLs) were sent by the French Health Authorities (AFSSAPS) to remind practitioners of risks with NSAIDs after the fifth month of pregnancy. The aim of this study was to evaluate the impact of these letters on NSAID prescriptions during late pregnancy. EFEMERIS is a French database that registers drugs prescribed and reimbursed during pregnancy and outcomes between 2004 and 2015. We performed a descriptive study and a 'before-and-after' comparison of NSAID prescriptions between 3 June 2006 and 3 June 2008 ('before group'), and between 1 March 2010 and 1 March 2012 ('after group'). We carried out a Cochran Armitage trend test to check whether the rate of women exposed to NSAIDs varies linearly over time. We identified 948 (4.38%) pregnant women in the 'before group' and 678 (2.73%) in the 'after group' receiving at least one NSAID prescription in late pregnancy (P 0.0001). Between 2006 and 2012, mainly prescriptions for morniflumate/niflumic acid (1.7% vs. 0.9%; P 0.0001), ibuprofen (0.8% vs. 0.6%; P = 0.01) and ketoprofen (0.7% vs. 0.3%; P 0.0001) fell significantly after DDLs. The Cochran Armitage trend test shows that the percentage of women exposed to NSAIDs in late pregnancy decreased significantly during the study period (P 0.0001). This study highlighted a significant decrease in the percentage of women receiving NSAID prescriptions during late pregnancy after DDLs. This decrease is not linked to a specific women's profile or prescriber's medical discipline.

ObjectiveTo estimate the magnitude of the correlation between neonatal outcomes of twins and demonstrate how this information can be used in the design of randomised controlled trials (RCTs) in women with twin pregnancies.DesignSecondary analysis of data from 12 RCTs.SettingObstetric care in multiple countries, 2004-2012.Population or sample4504 twin pairs born to women who participated in RCTs to assess treatments given during pregnancy.MethodsIntraclass correlation coefficients (ICCs) were estimated using log-binomial and linear models.Main outcome measuresPerinatal death, respiratory distress syndrome, bronchopulmonary dysplasia, intraventricular haemorrhage, necrotising enterocolitis, sepsis, neonatal intensive care unit admission, birthweight, low birthweight and two composite measures of adverse neonatal outcome.ResultsICCs for the composite measures of adverse neonatal outcome were all above 0.5, indicating moderate to strong correlation between adverse outcomes of twins. For individual neonatal outcomes, median ICCs across trials ranged from 0.13 to 0.79 depending on the outcome. An example illustrates how ICCs can be used in sample size calculations for RCTs in women with twin pregnancies.ConclusionsThe correlation between neonatal outcomes of twins varies considerably between outcomes and may be lower than expected. Our ICC estimates can be used for designing and analysing RCTs that recruit women with twin pregnancies and for performing meta-analyses that include such RCTs. Researchers are encouraged to report ICCs for neonatal outcomes in twins in their own RCTs.Tweetable abstractCorrelation between neonatal outcomes of twins depends on the outcome and may be lower than expected.Tweetable abstract Correlation between neonatal outcomes of twins depends on the outcome and may be lower than expected.

Little is known about neurodevelopment of children exposed to psychotropic drugs during pregnancy. The purpose of this study was to evaluate the effects of prenatal exposure to psychotropic drugs on psychomotor development in children. This observational study used the EFEMERIS database. The database records the drugs prescribed and delivered during pregnancy and the resulting outcomes. Neurodevelopment at nine and 24 months of children born to women exposed to psychotropic drugs (anxiolytics, antidepressants, neuroleptics and anti-epileptics) during the second and/or third trimesters of pregnancy was compared to children who were not exposed to these drugs. Psychomotor development of 493 children (1.5%) exposed to psychotropic drugs during pregnancy was compared to 32 303 unexposed children. Exposure to psychotropic drugs during pregnancy was associated with an increased risk of abnormal motor development at 9 months (OR = 1.3 [1.1-2.2]) and abnormal motor and mental development at 24 months (OR = 4.8 [2.1-11.0] and OR = 2.3 [1.05-4.9]). Increased risk was observed in children born to women exposed to anti-epileptic drugs, neuroleptics or antidepressants during pregnancy. This study found a higher rate of deviation from the normal developmental milestones in children born to women exposed to psychotropic drugs during pregnancy and more particularly antidepressants, neuroleptics and anti-epileptics.

Postpartum haemorrhage (PPH) is defined as blood loss >= 500 mL after a delivery and severe PPH as blood loss >= 1000 mL, regardless of the a route of delivery (professional consensus). The preventive a administration of uterotonic agents just after delivery is effective in a reducing the incidence of PPH and its systematic use is recommended, a regardless of the route of delivery (Grade A). Oxytocin is the first a line prophylactic drug, regardless of the route of delivery (Grade A); a a slowly dose of 5 or 10 IU can be administered (Grade A) either IV or IM a (professional consensus).After vaginal delivery, routine cord drainage a (Grade B), controlled cord traction (Grade A), uterine massage (Grade a A), and routine bladder voiding (professional consensus) are not a systematically recommended for PPH prevention. After caesarean delivery, a placental delivery by controlled cord traction is recommended (grade B). a The routine use of a collector bag to assess postpartum blood loss at a vaginal delivery is not systematically recommended (Grade B), since the a incidence of severe PPH is not affected by this intervention. In cases a of overt PPH after vaginal delivery, placement of a blood collection bag a is recommended (professional consensus). The initial treatment of PPH a consists in a manual uterine examination, together with antibiotic a prophylaxis, careful visual assessment of the lower genital tract, a a uterine massage, and the administration of 5-10 IU oxytocin injected a slowly IV or IM, followed by a maintenance infusion not to exceed a a cumulative dose of 40 IU (professional consensus). If oxytocin fails to a control the bleeding, the administration of sulprostone is recommended a within 30 minutes of the PPH diagnosis (Grade C). Intrauterine balloon a tamponade can be performed if sulprostone fails and before recourse to a either surgery or interventional radiology (professional consensus). a Fluid resuscitation is recommended for PPH persistent after first line a uterotonics, or if clinical signs of severity (Grade B). The objective a of RBC transfusion is to maintain a haemoglobin concentration (Hb) >8 a g/dL. During active haemorrhaging, it is desirable to maintain a a fibrinogen level >= 2 g/L (professional consensus). RBC, fibrinogen and a fresh frozen plasma (FFP) may be administered without awaiting a laboratory results (professional consensus). Tranexamic acid may be used a at a dose of 1 g, renewable once if ineffective the first time in the a treatment of PPH when bleeding persists after sulprostone administration a (professional consensus), even though its clinical value has not yet a been demonstrated in obstetric settings. It is recommended to prevent a and treat hypothermia in women with PPH by warming infusion solutions a and blood products and by active skin warming (Grade C). Oxygen a administration is recommended in women with severe PPH (professional a consensus). If PPH is not controlled by pharmacological treatments and a possibly intra-uterine balloon, invasive treatments by arterial a embolization or surgery are recommended (Grade C). No technique for a conservative surgery is favoured over any other (professional a consensus). Hospital-to-hospital transfer of a woman with a PPH for a embolization is possible once hemoperitoneum is ruled out and if the a patient's hemodynamic condition so allows (professional consensus). (C) a 2015 Elsevier Ireland Ltd. All rights reserved.

Resume Ce travail s’appuie sur une revue exhaustive de la litterature. Bases de donnees consultees ( Pubmed , Medline , Cochrane library , Cochrane database of systematic reviews , EMBASE, RCOG, ACOG) concernant les meta-analyses, essais randomises, registres, revue de la litterature, etudes controlees et grandes etudes non controlees, publies sur le sujet jusqu’en 2016 en langue francaise ou anglo-saxonne.

International audience; The aim of our study was to evaluate the bidirectional transfer of Bisphenol S (BPS) and its main metabolite, BPS Glucuronide (BPSG), using the model of perfused human placenta and to compare the obtained values with those of Bisphenol A (BPA) and BPA Glucuronide. Fourteen placentas at term were perfused in an open dual circuit with deuterated BPS (1 and 5 μM) and non-labelled BPSG (2.5 μM) and a freely diffusing marker antipyrine (800 ng/ml) in the presence of albumin (25 mg/ml). In a second experiment, the potential role of P-glycoprotein in the active efflux of BPS across the placental barrier was studied using the well-established P-glycoprotein inhibitor, PSC833 (2 and 4 μM). Placental transfer of BPS was much lower than that of BPA in both directions. The placental clearance index of BPS in the materno-fetal direction was three times lower than in the opposite direction, strongly suggesting some active efflux transport. However, our results show that P-glycoprotein is not involved in limiting the materno-fetal transfer of BPS. Placental transfer of BPSG in the fetal compartment was almost non-existent indicating that, in the fetal compartment, BPSG originates mainly from feto-placental metabolism. The feto-maternal clearance index for BPSG was 20-fold higher than the materno-fetal index. We conclude that the blood-placental barrier is much more efficient in limiting fetal exposure to BPS than to BPA, indicating that the placenta has a crucial role in protecting the human fetus from BPS exposure.

INTRODUCTION The objective was to evaluate the quality of life of pregnant women with a full-term birth from the first trimester to the 9th month using the EQ5D-3L questionnaire, comparing physiological, simple pathological, or complex pathological pregnancies. MATERIAL AND METHODS A prospective cohort of 500 pregnant women over the age of 18 was monitored between 2015 and 2017 at the Toulouse University Hospital (France). The data were collected monthly with an online report. Given that the decrease in quality of life was not linear during pregnancy, unadjusted and adjusted piecewise linear regression models were performed, considering 3 periods of time during pregnancy: 3-4, 4-8, and 8-9 months. The 5 dimensions of the EQ5D-Index and perceived health status were also analyzed. RESULTS In total, 1847 questionnaires were collected. Between the 4th and 8th months, the quality of life was lower for pathological pregnancies (P

To compare the short- and long-term perineal consequences (at 6 months postpartum) and short-term neonatal consequences of instrumental rotation (IR) to those induced by assisted delivery (AD) in the occiput posterior (OP) position, in case of manual rotation failure. A prospective observational cohort study; tertiary referral hospital including all women presenting with persistent OP position who delivered vaginally after manual rotation failure with attempted IR or AD in OP position from September 2015 to October 2016. Maternal and neonatal outcomes of all attempted IR deliveries were compared with OP operative vaginal deliveries. Main outcomes measured were pelvic floor function at 6 months postpartum including Wexner score for anal incontinence and ICIQ-FLUTS for urinary symptoms. Perineal morbidity comprised severe perineal tears, corresponding to third and fourth degree lacerations. Fetal morbidity parameters comprised low neonatal Apgar scores, acidaemia, major and minor fetal injuries and neonatal intensive care unit admissions. Among 5265 women, 495 presented with persistent OP positions (9.4%) and 111 delivered after manual rotation failure followed by AD delivery: 58 in the IR group and 53 in the AD in OP group. The incidence of anal sphincter injuries was significantly reduced after IR attempt (1.7% vs. 24.5%; p

Objectives To investigate the efficacy of antenatal corticosteroid (ACS) therapy on short-term neonatal outcomes in preterm twins, and further document the influence of the ACS-to-delivery interval. Design EPIPAGE-2 is a nationwide observational multicentre prospective cohort study of neonates born between 22 and 34 completed weeks of gestation. Setting All French maternity units, except in a single administrative region, between March and December 2011. Population A total of 750 twin neonates born between 24 and 31 weeks of gestation. Methods Exposure to ACSs was examined in four groups: single complete course, with an ACS administration-to-delivery interval of ≤7 days; single complete course, with an ACS-to-delivery interval of >7 days; repeated courses; or no ACS treatment. Main outcome measures Neonatal outcomes analysed were severe bronchopulmonary dysplasia, periventricular leukomalacia or intraventricular haemorrhage grade III/IV, in-hospital mortality, and a composite indicator of severe outcomes. Results Compared with no ACSs, in multivariable analysis, a single course of ACSs with an administration-to-delivery interval of ≤7 days was significantly associated with a reduced rate of periventricular leukomalacia or intraventricular haemorrhage grade III/IV (aOR 0.2; CI 95% 0.1–0.5), in-hospital mortality (0.3; 0.1–0.6), and the composite indicator (0.1; 0.1–0.3), whereas a single course of ACDs with an administration-to-delivery interval of >7 days did not significantly reduce the frequency of in-hospital mortality (0.7; 0.3–1.8). No significant differences in terms of benefit or risk were found when comparing repeated courses with a single complete course. Conclusion In preterm twins, a single complete course of antenatal corticosteroids was associated with an improvement of severe neurological outcome, whereas reduced in-hospital mortality was seen only when the ACS-to-delivery interval was ≤7 days. Tweetable abstract A single complete course of antenatal steroids reduced severe neurological morbidity in preterm twins (24–31 weeks).