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Objective: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section. Design: Prospective population‐based study. Setting: All 176 maternity hospitals of eight French regions. Population: Two hundred and forty‐nine women with PAS, from a source population of 520 114 deliveries. Methods: Women with PAS were classified into two risk‐profile groups, with or without the high‐risk combination of placenta praevia (or an anterior low‐lying placenta) and at least one prior caesarean. These two groups were described and compared. Main outcome measures: Population‐based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes. Results: The PAS population‐based incidence was 4.8/10 000 (95% CI 4.2–5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally. Conclusion: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean. Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes. Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes. [ABSTRACT FROM AUTHOR]

The objective of this study was to evaluate the obstetrical and neonatal consequences of a new protocol for the management of spontaneous labour in low-risk patients. This new algorithm was significantly associated with a longer period of complete dilatation in the nulliparous (P = 0.004), a decrease in the rate of amniotomy (P = 0.04), and a decrease in oxytocin consumption (P = 0.03). Increase in oxytocin use was also observed (P = 0.03). [ABSTRACT FROM AUTHOR]

Résumé L’objectif de cette revue était d’évaluer les bénéfices et risques des méthodes d’induction du travail et d’évacuation utérine en cas de mort fœtale in utero au-delà de 14 semaines d’aménorrhée. Au deuxième trimestre, les données sont nombreuses mais de qualité méthodologique faible. En termes d’efficacité (délais induction-expulsion et taux d’expulsion dans les 24 heures) et de tolérance en l’absence d’antécédent de césarienne, le meilleur protocole d’induction du travail au deuxième trimestre de la grossesse semble être l’association mifépristone 200 mg par voie orale suivie 24–48 heures plus tard de l’administration vaginale de misoprotol 200 à 400 mg toutes les 4 à 6 heures. Au troisième trimestre, il existe très peu de données. Les circonstances sont semblables au déclenchement du travail sur fœtus viable. À terme ou à proximité du terme, l’oxytocine et la dinoprostone possèdent une AMM dans cette indication mais le misoprostol peut être une alternative selon le score de Bishop et aux posologies du déclenchement. En cas d’utérus cicatriciel, le risque de rupture utérine est augmenté lors d’une induction médicale du travail par les prostaglandines. Les doses minimales efficaces de misoprostol doivent être utilisées (100 à 200 μg toutes les 4 à 6 heures). La préparation cervicale préalable par l’administration de mifépristone et éventuellement par l’utilisation de laminaires semble essentielle dans cette situation. The objective of this review was to assess benefits and harms of different management options for induction of labor and obtaining of uterine vacuity in case of fetal death beyond of 14 weeks of gestation. In second-trimester, the data are numerous but low methodological quality. In terms of efficiency (induction-expulsion time and uterine evacuation within 24 hours rate) and tolerance in the absence of antecedent of caesarean section, the best protocol for induction of labor in the second-trimester of pregnancy appears to be mifepristone 200 mg orally followed 24–48 hours later by vaginal administration of misoprostol 200 to 400 μg every 4 to 6 hours. In third-trimester, there is very little data. The circumstances are similar to induction of labor with living fetus. A term or near term, oxytocin and dinoprostone have a marketing authorization in this indication but misoprostol may be an alternative as the Bishop score and dose of induction of labor with living fetus. In case of previous caesarean section, the risk of uterine rupture is increased in case of a medical induction of labor with prostaglandins. The lowest effective doses should be used (100 to 200 μg every 4 to 6 hours). Prior cervical preparation by the administration of mifepristone and possibly the use of laminar seems essential in this situation. [ABSTRACT FROM AUTHOR]

Résumé L’objectif de cette revue était d’évaluer les bénéfices et les risques précoces et tardifs des traitements des fausses couches (FC) du premier trimestre de la grossesse. L’évacuation chirurgicale du produit de conception est le traitement le plus efficace et le plus rapide. Suivant la situation clinique, le traitement médical par le misoprostol (grossesse arrêtée) et la simple expectative (FC incomplète) peuvent être envisagés sans majorer les risques de complications hémorragiques et infectieuses. Ces alternatives obligent cependant à un suivi ambulatoire en général plus long avec des risques accrus de saignements prolongés et de chirurgie non programmée. The objective of this review was to assess early and late benefits and harms of different management options for first-trimester miscarriage. Surgical uterine evacuation remains the most effective and the quickest method of treatment. Depending on the clinical situation, medical treatment using misoprostol (missed miscarriage) or expectative attitude (incomplete miscarriage) does not increase the risk of complications, neither haemorrhagic nor infectious. However, these alternatives generally require longer outpatient follow-up, which leads to more prolonged bleeding and not planned surgical procedures. [ABSTRACT FROM AUTHOR]

Abstract: The delivery of the foetus and placenta remains the curative treatment for PE, usually allowing a spontaneous, quick and complete regression of all clinical signs and biological anomalies within the first days. However, the risk of developing complications associated with the condition persists mainly during the first 48 to 72hours and up to one week post partum. Post partum haemodynamic upset and the administered therapeutic measures are predisposing factors to these complications. This critical period therefore requires intensive monitoring and the delivery of appropriate treatments. [Copyright &y& Elsevier]

In intrauterine pregnancies of uncertain viability with a gestational sac without a yolk sac (with a mean of three orthogonal transvaginal ultrasound measurements <25mm), the suspected pregnancy loss should only be confirmed after a follow-up scan at least 14 days later shows no embryo with cardiac activity (Grade C). In intrauterine pregnancies of uncertain viability with an embryo <7mm on transvaginal ultrasound, the suspected pregnancy loss should only be confirmed after a follow-up scan at least 7 days later (Grade C). In pregnancies of unknown location after transvaginal ultrasound (i.e. not visible in the uterus), a threshold of at least 3510IU/l for the serum human chorionic gonadotrophin assay is recommended; above that level, a viable intrauterine pregnancy can be ruled out (Grade C). Postponing conception after an early miscarriage in women who want a new pregnancy is not recommended (Grade A). A work-up for women with recurrent pregnancy loss should include the following: diabetes (Grade A), antiphospholipid syndrome (Grade A), hypothyroidism with anti-thyroid peroxidase (anti-TPO) and anti-thyroglobulin (anti-Tg) antibodies (Grade A), vitamin deficiencies (B9, B12) (Grade C), hyperhomocysteinaemia (Grade C), hyperprolactinaemia (Grade B), diminished ovarian reserve (Grade C), and a uterine malformation or an acquired uterine abnormality amenable to surgical treatment (Grade C). The treatment options recommended for women with a missed early miscarriage are vacuum aspiration (Grade A) or misoprostol (Grade B); and the treatment options recommended for women with an incomplete early miscarriage are vacuum aspiration (Grade A) or expectant management (Grade A). In the absence of both chorioamnionitis and rupture of the membranes, women with a threatened late miscarriage and an open cervix, with or without protrusion of the amniotic sac into the vagina, should receive McDonald cerclage, tocolysis with indomethacin, and antibiotics (Grade C). Among women with a threatened late miscarriage and an isolated undilated shortened cervix (<25mm on ultrasound), cerclage is only indicated for those with a history of either late miscarriage or preterm delivery (Grade A). Among women with a threatened late miscarriage, an isolated undilated shortened cervix (<25mm on ultrasound) and no uterine contractions, daily treatment with vaginal progesterone up to 34 weeks of gestation is recommended (Grade A). Hysteroscopic section of the septum is recommended for women with a uterine septum and a history of late miscarriage (Grade C). Correction of acquired abnormalities of the uterine cavity (e.g. polyps, myomas, synechiae) is recommended after three early or late miscarriages (Grade C). Prophylactic cerclage is recommended for women with a history of three late miscarriages or preterm deliveries (Grade B). Low-dose aspirin and low-molecular-weight heparin at a preventive dose are recommended for women with obstetric antiphospholipid syndrome (Grade A). Glycaemic levels should be controlled before conception in women with diabetes (Grade A). [ABSTRACT FROM AUTHOR]

The literature suggests that misoprostol can be offered to patients for off-label use as it has reasonable efficacy, risk/benefit ratio, tolerance and patient satisfaction, according to the criteria for evidence-based medicine. Both the vaginal and sublingual routes are more effective than the oral route for first-trimester cervical dilatation. Vaginal misoprostol 800 μg, repeated if necessary after 24 or 48 h, is a possible alternative for management after early pregnancy failure. However, misoprostol has not been demonstrated to be useful for the evacuation of an incomplete miscarriage, except for cervical dilatation before vacuum aspiration. Oral mifepristone 200 mg, followed 24–48 h later by vaginal, sublingual or buccal misoprostol 800 μg (followed 3–4 h later, if necessary, by misoprostol 400 μg) is a less efficacious but less aggressive alternative to vacuum aspiration for elective or medically-indicated first-trimester terminations; this alternative becomes increasingly less effective as gestational age increases. In the second trimester, vaginal misoprostol 800–2400 μg in 24 h, 24–48 h after at least 200 mg of mifepristone, is an alternative to surgery, sulprostone and gemeprost. Data for the third trimester are sparse. For women with an unripe cervix and an unscarred uterus, vaginal misoprostol 25 μg every 3–6 h is an alternative to prostaglandin E2 for cervical ripening at term for a live fetus. When oxytocin is unavailable, misoprostol can be used after delivery for prevention (sublingual misoprostol 600 μg) and treatment (sublingual misoprostol 800 μg) of postpartum haemorrhage. The use of misoprostol to promote cervical dilatation before diagnostic hysteroscopy or surgical procedures is beneficial for premenopausal women but not for postmenopausal women. Nonetheless, in view of the side effects of misoprostol, its use as a first-line treatment is not indicated, and it should be reserved for difficult cases. Misoprostol is not useful for placing or removing the types of intra-uterine devices used in Europe, regardless of parity. [ABSTRACT FROM AUTHOR]

The movement of potyviruses, the largest genus of single-stranded, positive-sense RNA viruses responsible for serious diseases in crops, is very complex. As potyviruses developed strategies to hijack the host secretory pathway and plasmodesmata (PD) for their transport, the goal of this study was to identify membrane and/or PD-proteins that interact with the 6K2 protein, a potyviral protein involved in replication and cell-to-cell movement of turnip mosaic virus (TuMV). Using split-ubiquitin membrane yeast two-hybrid assays, we screened an Arabidopsis cDNA library for interactors of TuMV 6K2. We isolated AtHVA22a (Hordeum vulgare abscisic acid responsive gene 22), which belongs to a multigenic family of transmembrane proteins, homologous to Receptor expression-enhancing protein (Reep)/Deleted in polyposis (DP1)/Yop1 family proteins in animal and yeast. HVA22/DP1/Yop1 family genes are widely distributed in eukaryotes, but the role of HVA22 proteins in plants is still not well known, although proteomics analysis of PD fractions purified from Arabidopsis suspension cells showed that AtHVA22a is highly enriched in a PD proteome. We confirmed the interaction between TuMV 6K2 and AtHVA22a in yeast, as well as in planta by using bimolecular fluorescence complementation and showed that TuMV 6K2/AtHVA22a interaction occurs at the level of the viral replication compartment during TuMV infection. Finally, we showed that the propagation of TuMV is increased when AtHVA22a is overexpressed in planta but slowed down upon mutagenesis of AtHVA22a by CRISPR-Cas9. Altogether, our results indicate that AtHVA22a plays an agonistic effect on TuMV propagation and that the C-terminal tail of the protein is important in this process., (© 2024 The Authors. Molecular Plant Pathology published by British Society for Plant Pathology and John Wiley & Sons Ltd.)

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population., (© 2024. The Author(s).)

Background: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, reports of growth and neurodevelopmental dose-related side-effects suggest that the current dose (12 mg plus 12 mg, 24 h apart) might be too high. We therefore investigated whether a half dose would be non-inferior to the current full dose for preventing respiratory distress syndrome., Methods: We designed a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial in 37 level 3 referral perinatal centres in France. Eligible participants were pregnant women aged 18 years or older with a singleton fetus at risk of preterm delivery and already treated with the first injection of antenatal betamethasone (11·4 mg) before 32 weeks' gestation. We used a computer-generated code producing permuted blocks of varying sizes to randomly assign (1:1) women to receive either a placebo (half-dose group) or a second 11·4 mg betamethasone injection (full-dose group) 24 h later. Randomisation was stratified by gestational age (before or after 28 weeks). Participants, clinicians, and study staff were masked to the treatment allocation. The primary outcome was the need for exogenous intratracheal surfactant within 48 h after birth. Non-inferiority would be shown if the higher limit of the 95% CI for the between-group difference between the half-dose and full-dose groups in the primary endpoint was less than 4 percentage points (corresponding to a maximum relative risk of 1·20). Four interim analyses monitoring the primary and the secondary safety outcomes were done during the study period, using a sequential data analysis method that provided futility and non-inferiority stopping rules and checked for type I and II errors. Interim analyses were done in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, NCT02897076., Findings: Between Jan 2, 2017, and Oct 9, 2019, 3244 women were randomly assigned to the half-dose (n=1620 [49·9%]) or the full-dose group (n=1624 [50·1%]); 48 women withdrew consent, 30 fetuses were stillborn, 16 neonates were lost to follow-up, and 9 neonates died before evaluation, so that 3141 neonates remained for analysis. In the intention-to-treat analysis, the primary outcome occurred in 313 (20·0%) of 1567 neonates in the half-dose group and 276 (17·5%) of 1574 neonates in the full-dose group (risk difference 2·4%, 95% CI -0·3 to 5·2); thus non-inferiority was not shown. The per-protocol analysis also did not show non-inferiority (risk difference 2·2%, 95% CI -0·6 to 5·1). No between-group differences appeared in the rates of neonatal death, grade 3-4 intraventricular haemorrhage, stage ≥2 necrotising enterocolitis, severe retinopathy of prematurity, or bronchopulmonary dysplasia., Interpretation: Because non-inferiority of the half-dose compared with the full-dose regimen was not shown, our results do not support practice changes towards antenatal betamethasone dose reduction., Funding: French Ministry of Health., Competing Interests: Declaration of interests TS reports receiving consulting fees from Dilafor. LS reports receiving consulting fees from Dilafor; lecture fees from Bayer, GlaxoSmithKline, and Sigvaris; and lecture and consulting fees from Ferring Pharmaceuticals. AJV reprts receiving consulting fees from Norgine. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections initiate in the bronchi of the upper respiratory tract and are able to disseminate to the lower respiratory tract, where infections can cause an acute respiratory distress syndrome with a high degree of mortality in elderly patients. We used reconstituted primary bronchial epithelia from adult and child donors to follow the SARS-CoV-2 infection dynamics. We show that, in epithelia from adult donors, infections initiate in multiciliated cells and spread within 24 to 48 h throughout the whole epithelia. Syncytia formed of ciliated and basal cells appeared at the apical side of the epithelia within 3 to 4 d and were released into the apical lumen, where they contributed to the transmittable virus dose. A small number of reconstituted epithelia were intrinsically more resistant to virus infection, limiting virus spread to different degrees. This phenotype was more frequent in epithelia derived from children versus adults and correlated with an accelerated release of type III interferon. Treatment of permissive adult epithelia with exogenous type III interferon restricted infection, while type III interferon gene knockout promoted infection. Furthermore, a transcript analysis revealed that the inflammatory response was specifically attenuated in children. Taken together, our findings suggest that apical syncytia formation is an underappreciated source of virus propagation for tissue or environmental dissemination, whereas a robust type III interferon response such as commonly seen in young donors restricted SARS-CoV-2 infection. Thus, the combination of interferon restriction and attenuated inflammatory response in children might explain the epidemiological observation of age-related susceptibility to COVID-19.

Background: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management., Objective: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ)., Study Design: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias., Results: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy., Conclusion: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective: To describe and compare the characteristics of women with placenta accreta spectrum (PAS) and their pregnancy outcomes according to the presence of placenta praevia and a prior caesarean section., Design: Prospective population-based study., Setting: All 176 maternity hospitals of eight French regions., Population: Two hundred and forty-nine women with PAS, from a source population of 520 114 deliveries., Methods: Women with PAS were classified into two risk-profile groups, with or without the high-risk combination of placenta praevia (or an anterior low-lying placenta) and at least one prior caesarean. These two groups were described and compared., Main Outcome Measures: Population-based incidence of PAS, characteristics of women, pregnancies, deliveries and pregnancy outcomes., Results: The PAS population-based incidence was 4.8/10 000 (95% CI 4.2-5.4/10 000). After exclusion of women lost to follow up from the analysis, the group with placenta praevia and a prior caesarean included 115 (48%) women and the group without this combination included 127 (52%). In the group with both factors, PAS was more often suspected antenatally (77% versus 17%; P < 0.001) and more often percreta (38% versus 5%; P < 0.001). This group also had more hysterectomies (53% versus 21%, P < 0.001) and higher rates of blood product transfusions, maternal complications, preterm births and neonatal intensive care unit admissions. Sensitivity analysis showed similar results after exclusion of women who delivered vaginally., Conclusion: More than half the cases of PAS occurred in women without the combination of placenta praevia and a prior caesarean delivery, and these women had better maternal and neonatal outcomes. We cannot completely rule out that some of the women who delivered vaginally had placental retention rather than PAS; however, we found similar results among women who delivered by caesarean., Tweetable Abstract: Half the women with PAS do not have both placenta praevia and a prior caesarean delivery, and they have better maternal outcomes., (© 2021 John Wiley & Sons Ltd.)

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., Competing Interests: The authors have declared that no competing interests exist.

Anaemia is frequently diagnosed during pregnancy. However, there are few data regarding its incidence, and the association with severe maternal morbidity remains uncertain and potentially biased in high-resource countries. The purpose of this study was to explore the association between gestational anaemia and severe acute maternal morbidity during and after delivery. We performed a cohort-nested case-control analysis from the epidemiology of severe maternal mortality (EPIMOMS) prospective study conducted in six French regions (2012-2013, n = 182,309 deliveries). There were 1669 women with severe acute maternal morbidity during or after delivery, according to a standardised definition obtained by expert consensus. The control group were randomly selected among women without severe morbidity who delivered in the same health centres (n = 3234). We studied the association between gestational anaemia and severe acute maternal morbidity during or after delivery overall, by cause, and by mode of delivery, using multivariable logistic regression and multiple imputation. Gestational anaemia was significantly more frequent in women with severe acute maternal morbidity (25.3%) than in controls (16.3%), p < 0.001, and mostly mild in both groups. After adjustment for confounders, women with gestational anaemia were at increased risk of overall severe acute maternal morbidity during and after delivery (adjusted OR (95%CI) 1.8 (1.5-2.1)). This association was also found for severe postpartum haemorrhage (adjusted OR (95%CI) 1.7 (1.5-2.0)), even after omitting the transfusion criterion (adjusted OR (95%CI) 1.9 (1.6-2.3)), and for severe acute maternal morbidity secondary to causes other than haemorrhage or pregnancy-related hypertensive disorders (adjusted OR (95%CI) 2.7 (1.9-4.0)). These results highlight the importance of optimising the diagnosis and management of anaemia during pregnancy., (© 2020 Association of Anaesthetists.)

Background: Carbohydrate intake during physical exercise improves muscle performance and decreases fatigue. We hypothesized that carbohydrate intake during labor, which is a period of significant physical activity, can decrease the instrumental vaginal delivery rate., Methods: In a multicenter, prospective, randomized, controlled trial, healthy adult pregnant women presenting with spontaneous labor were assigned to a "Carbohydrate" group (advised to drink 200 mL of apple or grape juice without pulp every 3 hours) or a "Fasting" group (water only). The primary outcome was the instrumental vaginal delivery rate. Secondary outcomes included duration of labor, rate of cesarean delivery, evaluation of maternal hunger, thirst, stress, fatigue, and overall feeling during labor by numeric rating scale (0 worst rating to 10 best rating), rate of vomiting, and hospital length of stay. Statistical analysis was performed on an intention-to-treat basis. The primary outcome was tested with the "Fasting" group as the reference group. The P values for secondary outcomes were adjusted for multiple comparisons. The differences between groups are reported with 99% confidence interval (CI)., Results: A total of 3984 women were analyzed (2014 in the Carbohydrate group and 1970 in the Fasting group). There was no difference in the rate of instrumental delivery between the Carbohydrate (21.0%) and the Fasting (22.4%) groups (difference, -1.4%; 99% CI, -4.9 to 2.2). No differences were found between the Carbohydrate and the Fasting groups for the duration of labor (difference, -7 minutes; 99% CI, -25 to 11), the rate of cesarean delivery (difference, -0.3%; 99% CI, -2.4 to 3.0), the rate of vomiting (difference, 2.8%; 99% CI, 0.2-5.7), the degree of self-reported fatigue (difference, 1; 99% CI, 0-2), self-reported hunger (difference, 0; 99% CI, -1 to 1), thirst (difference, 0; 99% CI, -1 to 1), stress (difference, 0; 99% CI, -1 to 1), overall feeling (difference, 0; 99% CI, 0-0), and the length of hospitalization (difference, 0; 99% CI, -1 to 0)., Conclusions: Carbohydrate intake during labor did not modify the rate of instrumental vaginal delivery.

Objective: To describe induction of labor practices in France and to identify factors associated with the use of different methods., Methods: The data came from the French prospective population-based cohort MEDIP (MEthodes de Déclenchement et Issues Périnatales), including consecutively during one month in 2015 all women with induction of labor and a live fetus in 7 perinatal networks. The characteristics of women, maternity units, gestational age, Bishop's score, decision mode, indication and methods of labor induction were described. Factors associated with the use of different methods were sought in univariate analyzes., Results: The rate of induction of labor during the study was 21% and 3042 women were included (95.9% participation rate). The two main indications were prolonged pregnancy (28.7%) and premature rupture of the membranes (25.4%). More than one-third of women received intravenous oxytocin in first method, 57.3% prostaglandins, 4.5% balloon catheter and 1.4% another method. Among the prostaglandins, the vaginal device of dinoprostone was the most used (71.6%) then the gel (20.7%) and the vaginal misoprostol (6.7%). Women with a balloon were more often of higher body mass index and multiparous with scarred uterus. The balloon and misoprostol were mainly used in university public hospitals., Conclusions: The evolution of induction of labor methods, due to new data from the literature and the development of new drugs or devices, invites to regularly repeat population-based studies on induction of labor., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

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)., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: To determine management of women with preterm premature rupture of membranes (PPROM)., Methods: Bibliographic search from the Medline and Cochrane Library databases and review of international clinical practice guidelines., Results: In France, PPROM rate is 2 to 3% before 37 weeks of gestation (level of evidence [LE] 2) and less than 1% before 34 weeks of gestation (LE2). Prematurity and intra-uterine infection are the two major complications of PPROM (LE2). Compared to other causes of prematurity, PPROM is not associated with an increased risk of neonatal mortality and morbidity, except in case of intra-uterine infection, which is associated with an augmentation of early-onset neonatal sepsis (LE2) and of necrotizing enterocolitis (LE2). PPROM diagnosis is mainly clinical (professional consensus). In doubtful cases, detection of IGFBP-1 or PAMG-1 is recommended (professional consensus). Hospitalization of women with PPROM is recommended (professional consensus). There is no sufficient evidence to recommend or not recommend tocolysis (grade C). If a tocolysis should be prescribed, it should not last more than 48hours (grade C). Antenatal corticosteroids before 34 weeks of gestation (grade A) and magnesium sulfate before 32 weeks of gestation (grade A) are recommended. Antibiotic prophylaxis is recommended (grade A) because it is associated with a reduction of neonatal mortality and morbidity (LE1). Amoxicillin, 3rd generation cephalosporins, and erythromycin in monotherapy or the association erythromycin-amoxicillin can be used (professional consensus), for 7 days (grade C). However, in case of negative vaginal culture, early cessation of antibiotic prophylaxis might be acceptable (professional consensus). Co-amoxiclav, aminosides, glycopetides, first and second generation cephalosporins, clindamycin, and metronidazole are not recommended for antibiotic prophylaxis (professional consensus). Outpatient management of women with clinically stable PPROM after 48hours of hospitalization is a possible (professional consensus). During monitoring, it is recommended to identify the clinical and biological elements suggesting intra-uterine infection (professional consensus). However, it not possible to make recommendation regarding the frequency of this monitoring. In case of isolated elevated C-reactive protein, leukocytosis, or positive vaginal culture in an asymptomatic patient, it is not recommended to systematically prescribe antibiotics (professional consensus). In case of intra-uterine infection, it is recommended to immediately administer an antibiotic therapy associating beta-lactamine and aminoside (grade B), intravenously (grade B), and to deliver the baby (grade A). Cesarean delivery should be performed according to the usual obstetrical indications (professional consensus). Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A), even in case of positive vaginal culture for B Streptococcus, provided that an antibiotic prophylaxis has been prescribed (professional consensus). Oxytocin and prostaglandins are two possible options to induce labor in case of PPROM (professional consensus)., Conclusion: Expectative management is recommended before 37 weeks of gestation in case of uncomplicated PPROM (grade A)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: To determine the diagnosis criteria and management of intra-uterine inflammation or infection (Triple I, III)., Methods: PubMed and Cochrane Central databases search., Results: III is defined as an infection of the fetal membranes, and/or other components like the decidua, fetus, amniotic fluid or placenta. This word should be preferred to the word chorioamnionitis that is less precise (Professional consensus). III clinical signs exhibit poor limited sensibility and specificity (EL3). The diagnosis of III is retained in case of maternal fever (defined by a body temperature≥38°C) with no alternative cause identified and at least 2 signs among the following: fetal tachycardia>160 bpm for 10min or longer, uterine pain of labor, purulent fluid from the cervical canal (Professional consensus). Maternal hyperleukocytosis>20 giga/L in the absence of corticosteroids treatment or increased plasmatic C-reactive protein also argue for III, despite their limited sensibility and specificity (EL3). III requires prompt delivery (Grade A). III is not by itself an indication for cesarean delivery (Professional consensus). Antibiotic treatment should cover Streptococcus agalactiae and Escherichia coli. Antibiotics should be started immediately and maintained all over delivery, to reduce neonatal and maternal morbidity (Grade B). Treatment should rely on a combination of betalactamin and aminoglycoside (Grade B). After vaginal delivery, one single dose of antibiotic is required. Antibiotic duration should be longer in case of bacteremia. Longer duration could be considered in case of persistent fever or of cesarean delivery (Professional consensus)., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Objective: Gestational diabetes and obesity are independent risk factors for obstetric and neonatal complications. The purpose of our study was to evaluate the impact of their association on pregnancy outcomes., Material and Methods: Monocentric retrospective cohort study including patients with obesity and gestational diabetes (GDM), those with GD without obesity, and those with obesity without GDM, who gave birth between 01 January 2012 and 31 December 2014, and whose GDM was exclusively monitored at our centre. The diagnostic criteria and management modalities of GDM were based on the 2010 CNGOF (Collège National des Gynécologues et Obstétriciens Français [French national college of obstetricians and gynaecologists]) Clinical Practice Recommendations. Obesity was defined as having a body mass index ≥30 Kg/m 2 ., Results: A total of 1,484 patients were included, 259 with GDM and obesity, 549 with GDM without obesity, 676 with obesity without GDM. In the GDM + obesity group, GDM was treated earlier and was more uncontrolled and more often treated with insulin in relation to non-obese women with GDM. These patients also presented a higher risk of caesarean section (OR 2.92, CI 95% 2.04-4.16, P<0.001), preeclampsia (OR 4.62, CI 95% 1.31-16.32, P=0.017), maternal morbidity (OR 2.05, CI 95% 1.37-3.04, P<0.001) and large foetus for gestational age (OR 1.91, CI 95% 1.26-2.88, P=0.002). Obesity alone was a risk factor in its own right for preeclampsia (OR 7.32, CI 95% 2.50-21.45, P<0.001) and macrosomia (OR 3.55, IC 95% 2.24-5.62, P<0.001), compared to non-obese patients with GDM. Uncontrolled GDM was associated independently of obesity with the risk of induced labour and large foetus for gestational age., Conclusion: Obesity on its own is a risk factor for obstetric complications and its association with GDM strongly impacts on pregnancy outcomes., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Importance: Randomized trials have not focused on neonatal complications of glyburide for women with gestational diabetes., Objective: To compare oral glyburide vs subcutaneous insulin in prevention of perinatal complications in newborns of women with gestational diabetes., Design, Settings, and Participants: The Insulin Daonil trial (INDAO), a multicenter noninferiority randomized trial conducted between May 2012 and November 2016 (end of participant follow-up) in 13 tertiary care university hospitals in France including 914 women with singleton pregnancies and gestational diabetes diagnosed between 24 and 34 weeks of gestation., Interventions: Women who required pharmacologic treatment after 10 days of dietary intervention were randomly assigned to receive glyburide (n=460) or insulin (n=454). The starting dosage for glyburide was 2.5 mg orally once per day and could be increased if necessary 4 days later by 2.5 mg and thereafter by 5 mg every 4 days in 2 morning and evening doses, up to a maximum of 20 mg/d. The starting dosage for insulin was 4 IU to 20 IU given subcutaneously 1 to 4 times per day as necessary and increased according to self-measured blood glucose concentrations., Main Outcomes and Measures: The primary outcome was a composite criterion including macrosomia, neonatal hypoglycemia, and hyperbilirubinemia. The noninferiority margin was set at 7% based on a 1-sided 97.5% confidence interval., Results: Among the 914 patients who were randomized (mean age, 32.8 [SD, 5.2] years), 98% completed the trial. In a per-protocol analysis, 367 and 442 women and their neonates were analyzed in the glyburide and insulin groups, respectively. The frequency of the primary outcome was 27.6% in the glyburide group and 23.4% in the insulin group, a difference of 4.2% (1-sided 97.5% CI, -∞ to 10.5%; P=.19)., Conclusion and Relevance: This study of women with gestational diabetes failed to show that use of glyburide compared with subcutaneous insulin does not result in a greater frequency of perinatal complications. These findings do not justify the use of glyburide as a first-line treatment., Trial Registration: clinicaltrials.gov Identifier: NCT01731431.

Objectives: Caesarean section is associated with increased maternal morbidity compared to a vaginal delivery, especially if it occurs during labour. Little data on caesarean section performed at full dilatation is available., Methods: This was a retrospective study done in University Hospital of type 3 over a period of ten years, including future primiparous patients who had a caesarean section performed at full dilatation, compared to a control group of patients whose caesarean section was conducted in first part of the labour. We collected different maternal data per- and postoperative and neonatal., Results: In total, 824 patients were enrolled including 412 in each group. For caesarean section at full dilatation, foetal extraction required more manoeuvres (RR=3.05; 95% CI: 2.1; 4.39; P<0.001); we noted more extension of hysterotomy (RR=1.79; 95% CI: 1.30; 2.46; P<0.001). Postoperative and neonatal maternal morbidity was not different, except more frequent neonatal trauma for caesarean section at full dilatation., Conclusion: A caesarean section at full dilatation has an excess intraoperative risk and requires great caution. Nevertheless, no significant increase of postoperative and neonatal complications can be proved., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Background: Macrosomic fetuses are at increased risk of shoulder dystocia. We aimed to compare induction of labour with expectant management for large-for-date fetuses for prevention of shoulder dystocia and other neonatal and maternal morbidity associated with macrosomia., Methods: We did this pragmatic, randomised controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care centres in France, Switzerland, and Belgium. Women with singleton fetuses whose estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via computer-generated permuted-block randomisation (block size of four to eight) to receive induction of labour within 3 days between 37(+0) weeks and 38(+6) weeks of gestation, or expectant management. Randomisation was stratified by centre. Participants and caregivers were not masked to group assignment. Our primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00190320., Findings: We randomly assigned 409 women to the induction group and 413 women to the expectant management group, of whom 407 women and 411 women, respectively, were included in the final analysis. Mean birthweight was 3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group. Induction of labour significantly reduced the risk of shoulder dystocia or associated morbidity (n=8) compared with expectant management (n=25; relative risk [RR] 0·32, 95% CI 0·15-0·71; p=0·004). We recorded no brachial plexus injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of spontaneous vaginal delivery was higher in women in the induction group than in those in the expectant management group (RR 1·14, 95% CI 1·01-1·29). Caesarean delivery and neonatal morbidity did not differ significantly between the groups., Interpretation: Induction of labour for suspected large-for-date fetuses is associated with a reduced risk of shoulder dystocia and associated morbidity compared with expectant management. Induction of labour does not increase the risk of caesarean delivery and improves the likelihood of spontaneous vaginal delivery. These benefits should be balanced with the effects of early-term induction of labour., Funding: Assistance Publique-Hôpitaux de Paris and the University of Geneva., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Uterine artery pseudoaneurysm is a rare complication of cesarean section. It can lead to severe postpartum hemorrhage. We report three cases of pseudoaneurysm diagnosed late after cesarean delivery, one followed by hemorrhagic shock. Ultrasound may point to the diagnosis, but arteriography of uterine arteries is decisive for the diagnosis. Selective artery embolization is recommended for treatment. Main advantages are complete occlusion of the pseudoaneurysm and fertility preservation., (Copyright © 2014 Elsevier Masson SAS. All rights reserved.)

The objective of this review was to assess benefits and harms of different management options for induction of labor and obtaining of uterine vacuity in case of fetal death beyond of 14 weeks of gestation. In second-trimester, the data are numerous but low methodological quality. In terms of efficiency (induction-expulsion time and uterine evacuation within 24 hours rate) and tolerance in the absence of antecedent of caesarean section, the best protocol for induction of labor in the second-trimester of pregnancy appears to be mifepristone 200mg orally followed 24-48 hours later by vaginal administration of misoprostol 200 to 400 μg every 4 to 6 hours. In third-trimester, there is very little data. The circumstances are similar to induction of labor with living fetus. A term or near term, oxytocin and dinoprostone have a marketing authorization in this indication but misoprostol may be an alternative as the Bishop score and dose of induction of labor with living fetus. In case of previous caesarean section, the risk of uterine rupture is increased in case of a medical induction of labor with prostaglandins. The lowest effective doses should be used (100 to 200 μg every 4 to 6 hours). Prior cervical preparation by the administration of mifepristone and possibly the use of laminar seems essential in this situation., (Copyright © 2014. Published by Elsevier SAS.)