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International audience; BackgroundAntenatal 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.MethodsWe 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.FindingsBetween 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.InterpretationBecause 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.

AIM Birth asphyxia can lead to organ dysfunction, varying from isolated biological acidosis to hypoxic-ischemic encephalopathy (HIE). Pathophysiology of moderate or severe HIE is now well known and guidelines exist regarding the care required in this situation. However, for newborns without moderate or severe HIE, no consensus is available. Our objective was to describe the immediate neonatal consequences and need for care of asphyxiated newborns without moderate or severe HIE. METHODS Multicentre retrospective study from January 2015 to December 2017 in two academic centres, including neonates ≥37 gestational weeks with pathological foetal acidemia (umbilical arterial pH

Prelabour rupture of membranes (PROM) exposes both foetuses and mothers to the risk of infection. Induction of labour has been proposed to reduce this risk, but its neonatal and maternal risks and benefits must be balanced against those of expectant management (EM). Recent randomized studies of preterm PROM show that EM until 37 weeks of gestation is associated with lower overall neonatal morbidity. In term PROM, active management is associated with a shorter birth interval but not with lower rates of neonatal infection. Similar maternal and neonatal outcomes are reported regardless of whether induction uses oxytocin, PGE2, or oral misoprostol.

To re-visit short-term outcomes and associated risk factors of newborns with hypoxic-ischemic encephalopathy (HIE) in an era where hypothermia treatment (HT) is widespread.This is a prospective population-based cohort in French neonatal intensive care units (NICU). Neonates born at or after 34 weeks of gestational age with HIE were included; main outcomes were in-hospital death and discharge with abnormal or normal MRI. Associations of early perinatal risk factors, present at birth or at admission to NICU, with these outcomes were studied.A total of 794 newborns were included and HT was administered to 670 (84.4%); 18.3% died and 28.5% and 53.2% survived with abnormal and normal MRI, respectively. Severe neurological status, Apgar score at 5 mn ≤5, lactate at birth ≥11 mMoles/l, and glycemia ≥100 mg/dL at admission were associated with an increased risk of death (relative risk ratios (aRRR) (95% CI) 19.93 (10.00-39.70), 2.89 (1.22-1.62), 3.06 (1.60-5.83), and 2.55 (1.38-4.71), respectively). Neurological status only was associated with survival with abnormal MRI (aRRR (95% CI) 1.76 (1.15-2.68)).Despite high use of HT in this cohort, 46.8% died or presented brain lesions. Early neurological and biological examinations were associated with unfavorable outcomes and these criteria could be used to target children who warrant further neuroprotective treatment.Clinical trial registry, NCT02676063, ClinicalTrials.gov.In this population-based cohort of newborns with HIE where 84% received hypothermia, 46.8% still had an unfavorable evolution (death or survival with abnormal MRI). Risk factors for death were high lactate, low Apgar score, severe early neurological examination, and high glycaemia. While studies have established risk factors for HIE, few have focused on early perinatal factors associated with short-term prognosis. This French population-based cohort updates knowledge about early risk factors for adverse outcomes in the era of widespread cooling. In the future, criteria associated with an unfavorable evolution could be used to target children who would benefit from another neuroprotective strategy with hypothermia.

We investigated whether nonsurgical termination of pregnancy after 14 weeks of gestation increases the risk of preterm delivery in a subsequent pregnancy. We conducted a two-centre retrospective case-control study. Patients who underwent non-surgical termination of pregnancy after 14 weeks of gestation between 2012 and 2015 and who gave birth after 14 weeks of gestation to a live-born singleton infant were included. Control patients were those who gave birth after 37 weeks of gestation (the same month as a case patient) and had a second delivery of a singleton foetus after 14 weeks of gestation. The primary outcome was preterm delivery during the second pregnancy period. We included 151 cases and 302 controls and observed 13 (8.6%) preterm births during the second pregnancy in the case group versus 8 (2.6%) (odds ratio: 3.62; 95% confidence interval: 1.40-8.65

International audience; Background: The pathogenesis of late-onset sepsis (LOS) in preterm infants is poorly understood and knowledge about risk factors, especially prenatal risk factors, is limited. This study aimed to assess the association between the cause of preterm birth and LOS in very preterm infants.Methods: 2052 very preterm singletons from a national population-based cohort study alive at 72 h of life were included. Survival without LOS was compared by cause of preterm birth using survival analysis and Cox regression models.Results: 437 (20.1%) had at least one episode of LOS. The frequency of LOS varied by cause of preterm birth: 17.1% for infants born after preterm labor, 17.9% after preterm premature rupture of membranes, 20.3% after a placental abruption, 20.3% after isolated hypertensive disorders, 27.5% after hypertensive disorders with fetal growth restriction (FGR), and 29.4% after isolated FGR. In multivariate analysis, when compared to infants born after preterm labor, the risk remained higher for infants born after hypertensive disorders (hazard ratio HR = 1.7, 95% CI = 1.2-2.5), hypertensive disorders with FGR (HR = 2.6, 95% CI = 1.9-3.6) and isolated FGR (HR = 2.9, 95% CI = 1.9-4.4).Conclusion: Very preterm infants born after hypertensive disorders or born after FGR had an increased risk of LOS compared to those born after preterm labor.Impact: Late-onset sepsis risk differs according to the cause of preterm birth. Compared with those born after preterm labor, infants born very preterm because of hypertensive disorders of pregnancy and/or fetal growth restriction display an increased risk for late-onset sepsis. Antenatal factors, in particular the full spectrum of causes leading to preterm birth, should be taken into consideration to better prevent and manage neonatal infectious morbidity and inform the parents.

International audience; Despite antenatal corticosteroids therapy, respiratory distress syndrome (RDS) is still a leading cause of neonatal morbidity and mortality in premature newborns. To date, the relationship between in utero fetal drug exposure and occurrence of RDS remains poorly evaluated. This study aims to describe the pharmacokinetics of betamethasone in pregnant women and to evaluate the transplacental drug transfer and administration scheme for the prevention of RDS. Pregnant women > 27 weeks' gestation and who received at least a single dose of betamethasone for prevention of RDS were enrolled. Maternal, cord blood, and amniotic fluid betamethasone time-courses were analyzed using the Monolix software. A total of 220 maternal blood, 56 cord blood, and 26 amniotic fluid samples were described by a two-compartment model with two effect compartments linked by rate transfer constants. Apparent clearances and volumes of distribution parameters were allometrically scaled for a 70 kg third trimester pregnant woman. The impact of a twin pregnancy was found to increase maternal clearance by 28%. Using a fetal-to-mother exposure ratio, the median (95% confidence interval (CI)) transplacental transfer of betamethasone was estimated to 35% (95% CI 0.11-0.67). After adjustment for gestational age and twin pregnancy, RDS was found to be associated to the time spent in utero below quantifiable concentrations (i.e., < 1 ng/mL): odds ratio of 1.10 (95% CI 1.01-1.19) per day increase (P < 0.05). Trying to take into account both efficacy and safety, we simulated different dosing schemes in order to maintain a maximum of fetuses above 1 ng/mL without exceeding the total standard dose.

In this study, we aimed to analyze the value of annexin-A5 anticoagulant ratio (A5R) and non-criteria antibodies for the diagnosis of APS in patients with clinical seronegative APS. Three groups were defined, including 21 seronegative APS patients with unexplained obstetrical adverse events or thrombosis history, 15 confirmed APS patients with triple aPL positivity, and a control group of 20 healthy patients without any history of thrombosis or pregnancy complications. Seronegative APS patients have similar levels of A5R in comparison to healthy controls (202% [171%-238%] versus 191% [178%-221%]; p = 0.65), whereas triple-positive APS patients have significantly more reduced A5R in comparison to both seronegative and healthy patients (149% [138%-158%] versus 202% [171%-238%] and 191% [178%-221%], respectively, p 0.001). The non-criteria aPL were found in 24% of seronegative APS: anti-PE IgM in 3 cases (14%) and anti-PS/PT IgG and anti-PS/PT IgM in 1 (5%) case each. The frequency of non-criteria APL was significantly more frequent in comparison to healthy controls (p = 0.048). All triple-positive APS patients have at least one non-criteria aPL, and the non-criteria aPL were significantly more frequent in these patients compared to seronegative APS and healthy controls (p 0.001). Whereas A5R levels do not allow to discriminate seronegative APS from healthy controls, our results demonstrate that non-criteria aPL can help to APS diagnosis in clinical seronegative APS.Key points• Annexin-A5 resistance testing does not help for the diagnosis of seronegative APS.• The non-criteria antiphospholipid antibodies can contribute to APS diagnosis in patients without conventional antibodies.

Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of1000 mL or red cell transfusion by day 2, its failure to reduce the incidence of hemorrhage-related secondary clinical outcomes (TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial) makes its use questionable. The magnitude of its effect may differ in women at higher risk of blood loss, including those with multiple pregnancies.This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies.This was a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery trial data, a double-blind, randomized controlled trial from March 2018 to January 2020 in 27 French maternity hospitals, that included 319 women with multiple pregnancies. Women with a cesarean delivery before or during labor at ≥34 weeks of gestation were randomized to receive intravenously 1 g of tranexamic acid (n=160) or placebo (n=159), both with prophylactic uterotonics. The primary outcome was a calculated estimated blood loss of1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements.Of the 4551 women randomized in this trial, 319 had a multiple pregnancy and cesarean delivery, and 298 (93.4%) had primary outcome data available. This outcome occurred in 62 of 147 women (42.2%) in the tranexamic acid group and 67 of 152 (44.1%) receiving placebo (adjusted risk ratio, 0.97; 95% confidence interval, 0.68-1.38; P=.86). No significant between-group differences occurred for any hemorrhage-related clinical outcomes: gravimetrically estimated blood loss, provider-assessed clinically significant hemorrhage, additional uterotonics, postpartum blood transfusion, arterial embolization, and emergency surgery (P.05 for all comparisons).Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

There is no consensus on an optimal strategy for managing the active phase of the second stage of labor. Intensive pushing could not only reduce pushing duration, but also increase abnormal fetal heart rate because of cord compression and reduced placental perfusion and oxygenation resulting from the combination of uterine contractions and maternal expulsive forces. Therefore, it may increase the risk of neonatal acidosis and the need for operative vaginal delivery.This study aimed to assess the effect of the management encouraging "moderate" pushing vs "intensive" pushing on neonatal morbidity.This study was a multicenter randomized controlled trial, including nulliparas in the second stage of labor with an epidural and a singleton cephalic fetus at term and with a normal fetal heart rate. Of note, 2 groups were defined: (1) the moderate pushing group, in which women had no time limit on pushing, pushed only twice during each contraction, and observed regular periods without pushing, and (2) the intensive pushing group, in which women pushed 3 times during each contraction and the midwife called an obstetrician after 30 minutes of pushing to discuss operative delivery (standard care). The primary outcome was a composite neonatal morbidity criterion, including umbilical arterial pH of7.15, base excess of10 mmol/L, lactate levels of6 mmol/L, 5-minute Apgar score of7, and severe neonatal trauma. The secondary outcomes were mode of delivery, episiotomy, obstetrical anal sphincter injuries, postpartum hemorrhage, and maternal satisfaction.The study included 1710 nulliparous women. The neonatal morbidity rate was 18.9% in the moderate pushing group and 20.6% in the intensive pushing group (P=.38). Pushing duration was longer in the moderate group than in the intensive group (38.8±26.4 vs 28.6±17.0 minutes; P.001), and its rate of operative delivery was 21.1% in the moderate group compared with 24.8% in the intensive group (P=.08). The episiotomy rate was significantly lower in the moderate pushing group than in the intensive pushing group (13.5% vs 17.8%; P=.02). We found no significant difference for obstetrical anal sphincter injuries, postpartum hemorrhage, or maternal satisfaction.Moderate pushing has no effect on neonatal morbidity, but it may nonetheless have benefits, as it was associated with a lower episiotomy rate.

The aim of the study was to identify the obstetric risk factors for hypoxic-ischemic encephalopathy (HIE) in infants with asphyxia at birth.This multicenter case-control study covered the 5-year period from 2014 through 2018 and included newborns ≥36 weeks of gestation with an umbilical pH at birth ≤7.0. Cases were newborns who developed moderate or severe HIE; they were matched with controls with pH ≤7.0 at birth over the same period without moderate or severe HIE. The factors studied were maternal, gestational, intrapartum, delivery-related, and neonatal characteristics. A multivariable analysis was performed to study the maternal, obstetric, and neonatal factors independently associated with moderate or severe HIE.Our review of the records identified 41 cases and 98 controls. Compared with controls, children with moderate or severe HIE had a lower 5-min Apgar score, lower umbilical artery pH, and higher cord lactate levels at birth and at 1 h of life. Obstetric factors associated with moderate or severe HIE were the occurrence of an acute event (adjusted odds ratio [aOR] 6.4; 95% confidence interval [CI] 1.8-22.5), maternal fever (aOR 3.5; 95% CI 1.0-11.9), and thick meconium during labor (aOR 2.9; 95% CI 1.0-8.6).HIE is associated with a lower 5-min Apgar score and with the severity of acidosis at birth and at 1 h of life. In newborns with a pH7.0 at birth, the occurrence of an acute obstetric event, maternal fever, and thick meconium are independent factors associated with moderate or severe HIE.

International audience; Background: The main reason to avoid trial of labor after cesarean delivery is the possibility of uterine rupture. Identifying women at risk is thus an important aim, for it would enable women at low risk to proceed with a secure planned vaginal birth. bjective: To evaluate the impact of proposing mode of delivery based on the ultrasound measurement of the lower uterine segment thickness on a composite outcome of maternal-fetal mortality and morbidity, compared with usual management, among pregnant women with a previous cesarean delivery.Study Design: This multicenter, randomized, controlled, parallel-group, unmasked trial was conducted at 8 referral university hospitals with a neonatal intensive care unit and enrolled 2948 women at 36 weeks 0 days to 38 weeks 6 days of gestation with 1 previous low transverse cesarean delivery and no contraindication to trial of labor. Women in the study group had their lower uterine segment thickness measured by ultrasound. Those with measurements >3.5 mm, were encouraged to choose a planned vaginal delivery, and those with measurements ≤3.5 mm, were encouraged to choose a planned repeat cesarean delivery. This measurement was not taken in the control group; their mode of delivery was decided according to standard management. The primary outcome was a composite criterion comprising maternal mortality, uterine rupture, uterine dehiscence, hysterectomy, thromboembolic disease, transfusion, endometritis, perinatal death, or neonatal encephalopathy. Prespecified secondary outcomes were repeat cesarean deliveries, elective or after trial of labor.Results: The study group included 1472 women, and the control group included 1476 women. These groups were similar at baseline. The primary outcome occurred in 3.4% of the study group and 4.3% of the control group (relative risk, 0.78; 95% confidence interval, 0.54–1.13: risk difference, −1.0%; 95% confidence interval, −2.4 to 0.5). The uterine rupture rate in the study group was 0.4% and in the control group 0.9% (relative risk, 0.43; 95% confidence interval, 0.15–1.19). The planned cesarean delivery rate was 16.4% in the study group and 13.7% in the control group (relative risk, 1.21; 95% confidence interval, 1.00–1.47), whereas the rates of cesarean delivery during labor were 25.1% and 25.0% (relative risk, 1.01; 95% confidence interval, 0.89–1.14) in the study and control groups, respectively.Conclusion: Ultrasound measurements of lower uterine segment thickness did not result in a statistically significant lower frequency of maternal and perinatal adverse outcomes than standard management. However, because this study was underpowered, further research should be encouraged.

International audience; Objective: To assess the association between early empirical antibiotics and neonatal adverse outcomes in very preterm infants without risk factors of early-onset sepsis.Study design: This is a secondary analysis of the EPIPAGE-2 study, a prospective national population-based cohort that included all liveborn infants at 22-31 completed weeks of gestation in France in 2011. Infants at high risk of early-onset sepsis (born after preterm labor or preterm premature rupture of membranes, or from mother who had clinical chorioamnionitis or received antibiotics during the last 72 hours) were excluded. Early antibiotic exposure was defined as antibiotics started at Day 0 or Day 1 of life, regardless of the duration and type of antibiotics. We compared treated and untreated patients by using inverse probability of treatment weighting based on estimated propensity score. Results: Among 648 very preterm infants at low risk of early-onset sepsis, 173 (26.2%) had early antibiotics treatment. Early antibiotic exposure was not associated with death or late-onset sepsis or necrotizing enterocolitis (OR=1.04 [95%CI=0.72-1.50]). However, it was associated with higher odds of severe cerebral lesions (OR=2.71 [95%CI=1.25-5.86]) and moderate-to-severe bronchopulmonary dysplasia (OR=2.30 [95%CI=1.21-4.38]). Conclusion: Early empirical antibiotics administrated in very preterm infants at low risk of early-onset sepsis were associated with a higher risk of severe cerebral lesions and moderate-to-severe bronchopulmonary dysplasia.

International audience; 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.

To assess survival to discharge without severe neonatal morbidity by planned mode of delivery for twins born before 32 weeks of gestation.The JUMODA (JUmeaux MODe d'Accouchement) study was a French national prospective, population-based, cohort study of twin deliveries conducted from February 2014 to March 2015. This planned secondary analysis included diamniotic twin pregnancies from 26 0/7 through 31 6/7 weeks of gestation. Exclusion criteria included contraindications to vaginal delivery and situations for which planned cesarean delivery is favored, and neonatal prognosis depends largely on the underlying pathology rather than the planned mode of delivery. The primary outcome was survival to discharge without severe neonatal morbidity (bronchopulmonary dysplasia, grade 3 or grade 4 intraventricular hemorrhage, periventricular leukomalacia, stage 2 or stage 3 necrotizing enterocolitis). The association between planned mode of delivery and primary outcome was assessed by multivariate Poisson regression model. A propensity-score approach with inverse probability of treatment weighting also was performed to control for indication bias. Subgroup analyses according to birth order and sensitivity analyses limited to spontaneous preterm births only were performed.Among 424 very preterm twin pregnancies, 192 (45.3%) had a planned cesarean delivery and 232 (54.7%) had a planned vaginal delivery. Survival to discharge without severe morbidity did not differ in the two groups: 308 of 384 (80.2%) after planned cesarean and 375 of 464 (80.8%) after planned vaginal delivery (crude relative risk 0.99; 95% CI 0.91-1.15; adjusted relative risk 1.02; 95% CI 0.93-1.11). After applying inverse probability of treatment weighting, planned cesarean delivery still was not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal birth (relative risk 1.11; 95% CI 0.84-1.46). Subgroup and sensitivity analyses showed similar results.Planned cesarean delivery for very preterm twins is not associated with higher survival to discharge without severe neonatal morbidity than planned vaginal delivery. These results suggest that very preterm delivery should not be considered a per se indication for planned cesarean in twin pregnancies.

Resume Objectifs Les calcifications intra-abdominales (iA) retrouvees lors d’une echographie obstetricale peuvent etre isolees ou associees a d’autres anomalies. Notre objectif etait d’etudier tous les cas de calcifications iA isolees echographiquement pris en charge dans notre centre, en decrivant leur localisation precise, leur bilan etiologique et l’issue neonatale associee. Methodes Nous avons realise une etude monocentrique retrospective descriptive sur les nouveau-nes ayant eu un diagnostic de calcification iA isolee en echographie de reference antenatale ainsi qu’un avis au centre pluridisciplinaire de diagnostic prenatal a l’hopital Trousseau et nes entre le 1er janvier 2008 et le 30 juin 2018. Les criteres d’exclusion etaient : les calcifications retro-peritoneales, les calcifications iA associees a des anomalies digestives ou autres malformations congenitales. Resultats Les 32 cas de calcifications iA isolees representaient 46 % de toutes les calcifications iA. Apres exclusion de 9 dossiers pour donnees neonatales manquantes, parmi les 23 cas de calcifications isolees, 15 concernaient des calcifications hepatiques, 5 des peri-hepatiques et 2 des peritoneales. Un fœtus etait porteur a la fois de calcifications intra- et peri-hepatiques. La majorite des calcifications sont restees stables tout au long de la grossesse. Aucun cas d’aneuploidie, de fœtopathie infectieuse, ni de mucoviscidose n’a ete retrouve. L’issue neonatale de tous ces enfants a ete favorable. Conclusions En cas de calcification iA paraissant isolee apres echographie de reference et stable sur plusieurs echographies, apres avoir elimine une fœtopathie infectieuse et recherche les mutations les plus frequentes de la mucoviscidose chez les parents, le pronostic est favorable.

Resume Objectif Determiner la prise en charge des patientes avec une rupture prematuree des membranes avant 37 semaines d’amenorrhee (SA). Methodes Synthese de la litterature a partir des bases de donnees PubMed et Cochrane et des recommandations des societes et colleges francais et etrangers. Resultats En France, la frequence de la rupture prematuree des membranes (RPM) est de 2 a 3 % avant 37 SA (Niveau de preuve [NP] 2) et de moins de 1 % avant 34 SA (NP2). La prematurite et l’infection intra-uterine sont les complications majeures de la RPM avant terme (NP2). La prolongation de la duree de latence est benefique (NP2). Par rapport aux autres causes de prematurite, la RPM avant terme n’est pas associee a un sur-risque evident de morbi-mortalite neonatale, sauf en cas d’infection intra-uterine, qui est associee a une augmentation des morts fœtales in utero (NP3), des infections neonatales precoces (NP2) et des enterocolites ulceronecrosantes (NP2). Le diagnostic de la RPM avant terme est principalement clinique (accord professionnel). En cas de doute diagnostique, il est recommande d’utiliser les tests de detection d’IGFBP-1 ou de PAMG-1 (accord professionnel). Il est recommande d’hospitaliser les patientes lors du diagnostic de RPM avant terme (accord professionnel). Il n’existe pas d’argument suffisant pour recommander ou ne pas recommander une tocolyse initiale (grade C). Si une tocolyse etait prescrite, il est recommande de ne pas la prolonger plus de 48 heures (grade C). Il est recommande d’administrer une cure antenatale de corticoides si l’âge gestationnel est inferieur a 34 SA (grade A) et du sulfate de magnesium en cas d’accouchement imminent avant 32 SA (grade A). Il est recommande de prescrire une antibioprophylaxie a l’admission (grade A) pour reduire la morbidite neonatale et maternelle (NP1). L’amoxicilline, les cephalosporines de 3eme generation et l’erythromycine (accord professionnel) peuvent etre utilisees en monotherapie, ou l’association erythromycine–amoxicilline (accord professionnel), pour une duree de 7 jours (grade C). Toutefois, un arret precoce de l’antibioprophylaxie semble acceptable en cas de prelevement vaginal initial negatif (accord professionnel). Il n’est pas recommande de prescrire comme antibioprophylaxie l’association amoxicilline-acide clavulanique (accord professionnel), des aminosides, des glycopeptides, des cephalosporines de premiere ou deuxieme generation, de la clindamycine ou du metronidazole (accord professionnel). La prise en charge a domicile des patientes cliniquement stables apres au moins 48 heures de surveillance hospitaliere est possible (accord professionnel). Au cours de la surveillance, il est recommande d’identifier les elements cliniques et biologiques evocateurs d’une infection intra-uterine (accord professionnel). Il n’est pas possible d’emettre de recommandations sur la frequence de cette surveillance (accord professionnel). En cas d’examen de surveillance isolement positif chez une patiente asymptomatique (CRP augmentee, hyperleucocytose, prelevement vaginal positif), il n’est pas recommande d’initier systematiquement une antibiotherapie (accord professionnel). En cas d’infection intra-uterine, il est recommande d’administrer immediatement une antibiotherapie associant une betalactamine a un aminoside (grade B), par voie intraveineuse (grade B) et de faire naitre l’enfant (grade A). La cesarienne en cas d’infection intra-uterine est reservee aux indications obstetricales habituelles (accord professionnel). Il est recommande d’avoir une attitude expectative en cas de RPM non compliquee avant 37 SA (grade A), meme en cas de prelevement positif pour le streptocoque B, sous couvert d’une antibioprophylaxie a l’admission (accord professionnel). L’ocytocine et les prostaglandines sont deux options envisageables pour le declenchement du travail en cas de RPM avant terme (accord professionnel). Conclusion La prise en charge de la rupture prematuree des membranes avant terme non compliquee repose sur l’expectative jusqu’a 37 SA (grade A).

Preterm premature rupture of membranes (PPROM) is associated with an increased risk of serious maternal, fetal, and neonatal morbidities. We compared neonatal outcomes of women with PPROM before 34+0 weeks of gestation according to inpatient or outpatient management policy. 587 women with PPROM >48 hours, 246 (41.9%) in the group with an inpatient care policy (ICP) and 341 (58.1%) in the group with an outpatient care policy (OCP), were identified in France, from 2009 to 2012. Neonatal outcomes were compared between the two groups using logistic regression. A second analysis was performed to compare inpatient care and effective outpatient care (discharge from hospital) through propensity score matching. The outcome was a neonatal composite variable including one or more of the neonatal morbidity complications. The perinatal composite outcome was 14.6% with the ICP and 15.5% with the OCP (p = 0.76). After using the 1:1 ratio propensity score matching, effective outpatient care was not associated with a significantly higher risk of the perinatal composite outcome (OR 0.88, CI 0.35 to 2.25; p = 0.80) compared with inpatient care. Outpatient care is not associated with an increased rate of obstetric or neonatal complications and can be an alternative to hospital care for women with uncomplicated PPROM.

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

Villitis of unknown etiology (VUE) is characterized by lympho-histiocytic infiltrates, which are predominant within the villous stroma. VUE can be of low grade i.e. affecting less than 10 contiguous villi or high grade with either patchy or diffuse subgroups (the later concerning more than 30 % of distal villi). Several other placental lesions could be associated with VUE, in particular in diffuse subgroups, such as diffuse perivillous fibrin deposition and chronic intervillositis. One of the most characteristic features of VUE is the late onset of fetal growth restriction after 32 weeks of gestation, and earlier detection of villitis should first raise an infectious origin. High grade VUE has been associated with fetal growth restriction, prematurity, fetal deaths, recurrent pregnancy loss, central nervous system injury and is characterized by relatively high risk of recurrence (25-50 %). Prospective and well-designed studies are necessary to determine the real prevalence of these adverse pregnancy events associated with VUE. Data about the management of VUE are extremely scarce and thus no recommendation based on the literature review could be actually done.

Introduction Recurrent miscarriages are defined as three or more early miscarriages before 12 weeks of gestation. The aim of this study was to describe a cohort of women with unexplained recurrent miscarriages, evaluate several potential biomarkers of immune origin and describe the outcome of pregnancies under immunomodulatory therapies METHODS: Women having a history of at least 3 early miscarriages without any etiology were recruited from 3 university hospitals. Results Among 101 women with recurrent miscarriages, overall, 652 pregnancies have been included in the analysis. Women which experienced miscarriages were older (33.3 ± 5.4 versus 31.9 ± 6.7; p = 0.03), with history of more pregnancies (4 (2-6) versus 3.5 (1-5.75); p 0.0008), and less frequently the same partner (406 (74%) versus 79 (86%); p=0.01). There was no difference in the level and frequencies of biomarkers of immune origin (NK, lymphocyte, gammaglobulins and blood cytokine levels and endometrial uNK activation status), except the higher rates of positive antinuclear antibodies in women with live birth (12 (13%) versus 36 (7%); p=0.03). Among the 652 pregnancies, 215 (33%) have been treated and received either aspirin/low weighted molecular heparin (LMWH) and/or combined to different lines of immunomodulatory treatment. Patients with pregnancy under treatment had a significantly higher rate of cumulative live birth rate that those with untreated ones (43.0% vs 34.8%; p = 0.04). When compared to patients with untreated pregnancies, patients with steroids during the pregnancy had twice more chances to obtain live birth (OR 2.0, CI95% 1.1 - 3.7, p = 0.02). Conclusions Unexplained recurrent miscarriages could have improved obstetrical outcome under immunomodulatory therapies and in particular steroids.

International audience

International audience; 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 4 units of packed red blood cells within 6 months than cesarean hysterectomy.

Recurrent implantation failure is defined as the absence of pregnancy after at least three transfers of good-quality embryos after in vitro fecundation/intracytoplasic sperm injection.The aim of this study was to describe a multicentre cohort of women with unexplained RIF, to analyse the factors associated with clinical pregnancy and to evaluate the immunomodulatory therapies efficacy.Women were consecutively recruited from university departments with unexplained RIF.Sixty-four women were enrolled with mean age 36 ± 3 years. The rates of clinical pregnancy in 64 women were compared in untreated and treated cycles and according to therapies used during the last prospectively followed embryo transfer. A clinical pregnancy after the transfer was noted in 56 % pregnancies on intralipids and in 50 % on prednisone, versus 5 % in untreated ones (p0.001). The 340 embryo transfers of these 64 women resulted in 68 clinical pregnancies and 18 live births. Clinical pregnancies were significantly more frequent in treated versus untreated embryo transfers (44 % vs 9 %; p0.001) with odds ratio at 8.13 (95 % CI 4.49-14.72, p0.0001). Cumulative pregnancy rates were higher for steroid-treated transfers than for untreated transfers when considering overall transfers before and after using steroids and also only those under steroids. Cumulative pregnancy rates were not different from steroid- and intralipid-treated embryo transfers CONCLUSIONS: In this multicentre study of women with unexplained RIF, use of immunomodulatory treatments before embryo transfer resulted in higher clinical pregnancy. Randomised, well-designed studies in well-defined population of RIF women are necessary to confirm our preliminary data.

Background Intrahepatic cholestasis of pregnancy (ICP) is characterised by otherwise unexplained maternal pruritus, increased serum bile acid concentration over 10 μmol/L and spontaneous relief of symptoms and liver abnormalities after delivery. It occurs most frequently during the third trimester and is usually not induced by medication. Besides, azathioprine is recommended as first-line immunosuppressant in patients with steroid-dependent inflammatory bowel disease and is allowed during pregnancy, in order to stabilize maternal disease. Methods We reviewed all cases of ICP between 2010 and 2018 in two French perinatal centers. Results We encountered eight pregnancies complicated by atypical ICP among patients treated with azathioprine. ICP associated with azathioprine appears to be biologically more severe and to occur earlier than "standard" ICP. Furthermore, clinical and biochemical abnormalities related to ICP disappear when azathioprine is discontinued. Azathioprine safety should be reconsidered and practitioners advised to discuss discontinuing this drug as soon as ICP diagnosis is established.