[Maternal mortality due to obstetric haemorrhage in France 2016-2018]. / Mortalité maternelle par hémorragie obstétricale en France 2016­2018.

Between 2016 and 2018, 20 maternal deaths were related to obstetric haemorrhage, excluding haemorrhage in the first trimester of pregnancy, representing a mortality ratio of 0.87 per 100,000 live births (95% CI 0.5 -1.3). Obstetric haemorrhage is the cause of 7.4% of all maternal deaths up to 1 year, 10% of maternal deaths within 42days, and 21% of deaths directly related to pregnancy (direct causes). Between 2001 and 2018, maternal mortality from obstetric haemorrhage has been considerably reduced, from 2.2deaths per 100,000 live births in 2001-2003 to 0.87 in the period presented here. Nevertheless, obstetric haemorrhage is still one of the main direct causes of maternal death, and remains the cause with the highest proportion of deaths considered probably (53%) or possibly (42%) preventable according to the CNEMM's collegial assessment (see chapter 3). The preventable factors reported are related to inadequate content of care in 94% of cases and/or organisation of care in 44% of cases. In this triennium, maternal death due to haemorrhage occurred mainly in the context of caesarean delivery (65% of cases, i.e. 13/20), and mostly in the context of emergency care (12/13). The main causes of obstetric haemorrhage were uterine rupture (6/20) in unscarred uterus or in association with placenta accreta, and surgical injury during the caesarean delivery (5/20). Every maternity hospital, whatever its resources and/or technical facilities, must be able to plan any obstetric haemorrhage situation that threatens the mother's vital prognosis. Intraperitoneal occult haemorrhage following caesarean section and uterine rupture require immediate surgery with the help of skilled surgeon resources with early and appropriate administration of blood products.

[Maternal mortality due to cardiovascular diseases in France 2016-2018]. / Mortalité maternelle par pathologies cardiovasculaires en France 2016­2018.

Between 2016 and 2018, cardiovascular diseases were responsible for 41 deaths, making it the leading cause of maternal death within 42 days postpartum in France. The maternal mortality ratio (MMR) for cardiovascular disease is 1.8 per 100,000 NV, a non-significant increase compared with the 2013-2015 triennium (MMR of 1.5 per 100,000 NV). Deaths from cardiac causes accounted for the majority (n=28), with 26 deaths secondary to cardiac disease aggravated by pregnancy (indirect deaths) and 2 deaths related to peripartum cardiomyopathy (direct deaths). Deaths from vascular causes (n=13) corresponded to 9 aortic dissections and 4 ruptures of large vessels, including 3 ruptures of the splenic artery. Preventability of death (possible or probable) was found in 56% of cases compared with 66% in the previous triennium. Care was considered sub-optimal in 57% of cases, down from 72% in the 2013-2015 triennium. In women with known cardiovascular disease, the areas for improvement concern multidisciplinary follow-up, repeated assessment of the cardiovascular risk (WHO grade) and early referral to an expert centre (expert cardiologists, obstetricians, anaesthetists and intensive care). In all pregnant women or women who have recently given birth, a cardiovascular etiology should be considered in the presence of suggestive symptoms (dyspnea, chest or abdominal pain). Ultrasound "point of care" examination (fluid effusions, cardiac dysfunction) and cardiac enzymes assay can help in the diagnosis. Finally, the woman must be involved in her own care.

[Maternal deaths and management by emergency departments in France 2016-2018]. / Mortalité maternelle et prise en charge par les services d'urgence en France 2016­2018.

In France, 272 maternal deaths occurred during the period 2016-2018, of which 131 were initially treated by healthcare professionals not specialized in obstetric. Fifty-six files were excluded because they did not concern emergency services or because there was insufficient data to allow analysis. Seventy-five cases of maternal deaths initially treated by emergency services (in-hospital emergency department [ED] or emergency medical ambulance [SAMU]) were analyzed. Fifty-six cases were treated by the SAMU and 22 by an ED (both in 3 cases). The causes of death were 20 cardiovascular events, 18 pulmonary embolisms, 9 neurological failures and 8 hemorrhagic shocks. The event occurred during pregnancy in 48 cases (64%) and during per or postpartum period in 27 cases (36%). The motivations for consultation at the ED were mainly pain (n=9), respiratory distress (n=6) or faintness (n=3). The reasons for calling emergency dispatching service (SAMU) were cardiorespiratory arrest in 32 cases (57%) and neurological failure (coma or status epilepticus) in 6 cases (11%). Among the 56 patients treated outside the hospital, 17 died on scene and 39 were transported to a resuscitation room (n=13), a specialized department (n=13), an obstetrics department (n=8) and less often in the ED (n=2). This was considered appropriate in 35 out of 39 cases (90%). Concerning the 75 files analyzed (ED and SAMU), death was considered unavoidable in 37 cases (49%) and potentially avoidable in 29 cases (38%) (maybe=23, probably=6). Avoidability could not be established in 9 cases. Among the 29 potentially avoidable deaths (38%), one of the criteria of avoidability concerned emergency services in 14 cases (ED=9, SAMU/SMUR=5, 18% of the files studied). ED's cares were considered optimal in 11 cases (50%) and non-optimal in 11 cases (50%). SAMU's cares were considered optimal in 45 cases (80%).

[Evolution of the rate of episiotomies and obstetric anal sphincter injuries since the last recommendations of 2018]. / Évolution du taux d'épisiotomies et des lésions obstétricales du sphincter de l'anus depuis les recommandations de 2018.

OBJECTIVES: There is a progressive reduction in the rate of episiotomies since the recommendations of the French college of gynaecologists. Our objective was to study the evolution of the rate of episiotomies and Obstetric Anus Sphincter Injury (OASI) since the restriction of episiotomies in our department. METHODS: Observational monocentric retrospective study performed at the Rouen University Hospital. The inclusion criteria were monofetal pregnancies, delivery at a term greater than or equal to 37 weeks of amenorrhea of a living, viable child and by cephalic presentation. We compared two periods corresponding to before and after the 2018 recommendations. We used logistic regression modelling to identify factors associated with the risk of episiotomies and of obstetrical anal injuries, overall and in case of instrumental delivery. RESULTS: We included 3329 patients for the 1st period and 3492 for the 2nd period, and the rate of instrumental deliveries were respectively of 16.4% (n=547) and 17.9% (n=626). Multivariate analysis showed a significant decrease in the rate of episiotomies in the 2nd period (OR 0.14, CI 95% [0.12; 0.16], P<0.0001). Main factors associated with the risk of OASI were primiparity (OR 6.21, CI 95% [3.19; 12.11]) and the use of forceps (OR 4.23, CI 95% [2.17; 8.27]) overall; and instrumental delivery using forceps (OR 3.25, CI 95% [1.69; 6.22]) and delivery during the 2nd period (OR 1.98, CI 95% [1.01; 3.88]) in case of instrumental delivery. CONCLUSIONS: Our study confirms that the voluntary reduction in the episiotomy rate does not seem to be associated with an increased risk of OASI, overall and in case of instrumental delivery. However, we show an increase in the rate of OASI in case of instrumental delivery since the latest recommendations.

Which fetal growth charts should be used in France? Position of the French College of Obstetricians and Gynecologists (CNGOF).

OBJECTIVE: To assess which fetal growth charts best describe intrauterine growth in France defined as the ability to classify 10% of fetuses below the 10th percentile (small for gestational age [SGA]) and above the 90th percentile (large for gestational age [LGA]) in the second and third trimesters. METHODS: We analyzed five studies on fetal ultrasound measurements using three French data sources. Two studies used second and third trimester ultrasound data from a nationwide birth cohort in 2011 (the ELFE study, N = 13 197 and N = 7747); one study used third trimester ultrasound data from on a nationwide cross-sectional study (the 2016 French National Perinatal Survey, N = 9940); and the last two studies were from the "Flash study" 2014 which prospectively collected ultrasound data from routine visits in the second and third trimesters (N = 4858 and N = 3522). For each study, we reported the percentage of measurements below the 10th percentile or above the 90th percentile, using French, Hadlock's, WHO and Intergrowth (IG) charts. RESULTS: WHO classified 4.7% and 16.3% of fetuses as having an estimated fetal weight (EFW) <10th and >90th percentiles in the second trimester compared to 3.3% and 34.7% with IG. The percentage of fetuses in the third trimester with an EFW <10th and >90th percentiles, ranged from 9.1% to 9.4% and from 8.0% to 11.1%, respectively, for WHO, and from 3.9% to 4.1% and from 17.3% to 21.6%, respectively, for IG. The WHO and IG charts for head circumference were very similar and performed well. Compared to the WHO charts, the French and Hadlock's charts deviated more frequently from the target percentiles values for EFW and biometric measures. CONCLUSION: It is recommended to use the WHO charts for the assessment of EFW and ultrasound biometric measurements in France (strong recommendation; low quality of evidence).

Low-Dose Remifentanil in Preterm Cesarean Section with General Anesthesia: A Randomized Controlled Trial.

BACKGROUND AND OBJECTIVE: The conventional technique of general anesthesia induction during a Cesarean section involves the use of opioids only after cord clamping. We hypothesized that the use of remifentanil before cord clamping might reduce the use of maternal supplemental anesthetic agents and improve the maternal hemodynamics status and neonatal adaptation of the preterm neonate. METHODS: A phase III, double-blind, randomized, placebo-controlled, hospital-based trial enrolled parturients undergoing a Cesarean section under general anesthesia before 37 weeks of gestation. Block randomization allocated pregnant women to remifentanil or placebo. The primary outcome was the rate of newborns with Apgar scores < 7 at 5 min. Secondary outcomes were maternal hemodynamic parameters, complications of anesthetic induction, use of adjuvant anesthetic agents, neonatal respiratory distress, umbilical cord pH, and lactate levels. RESULTS: A total of 52/55 participants were analyzed, comprising 27 women in the remifentanil group and 25 in the placebo group. Nine of 27 (33.3%) neonates had an Apgar score < 7 at 5 min in the remifentanil group versus 11/25 (44.0%) in the placebo group (p = 0.45, odds ratio = 0.66, 95 confidence interval 0.20-2.18). The blood cord gases, cognitive, behavior, sensory, sleeping, and feeding scores at 1 and 2 years of corrected age were not different. For the mothers, hemodynamic parameters, anesthesia duration, and the cumulative treatment dose until cord clamping did not differ between the groups. CONCLUSIONS: The use of a low dose of remifentanil before cord clamping for a Cesarean section appears to be safe both for the mother and the preterm newborn, but it does not improve maternal or neonatal outcomes. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov: NCT02029898.

Impact of discontinuing oxytocin in active labour on neonatal morbidity: an open-label, multicentre, randomised trial.

BACKGROUND: Oxytocin is effective in reducing labour duration but can be associated with fetal and maternal complications that could potentially be reduced by discontinuing the treatment during labour. We aimed to assess the impact of discontinuing oxytocin during active labour on neonatal morbidity. METHODS: STOPOXY was a multicentre, randomised, open-label, controlled, superiority trial conducted in 21 maternity units in France. Participants who received oxytocin before 4 cm dilation were randomly assigned 1:1 to either discontinuous oxytocin (oxytocin infusion stopped beyond a cervical dilation equal to or greater than 6 cm) or continuous oxytocin (administration of oxytocin continued until delivery). Randomisation was stratified by centre and parity. The primary outcome, neonatal morbidity, was assessed at birth using a composite variable defined by an umbilical arterial pH at birth less than 7·10, a base excess greater than 10 mmol/L, umbilical arterial lactates greater than 7 mmol/L, a 5-min Apgar score less than 7, or admission to the neonatal intensive care unit. Efficacy and safety was assessed in participants who were randomly assigned (excluding those who withdrew consent or were deemed ineligible after randomisation) and had reached a cervical dilation of at least 6 cm. This trial is registered with ClinicalTrials.gov, NCT03991091. FINDINGS: Of 2459 participants randomly assigned between Jan 13, 2020, and Jan 24, 2022, 2170 were eligible to receive the intervention and were included in the final modified intention-to-treat analysis. The primary outcome occurred for 102 (9·6%) of 1067 participants (95% CI 7·9 to 11·5) in the discontinuous oxytocin group and for 101 (9·2%) of 1103 participants (7·6 to 11·0) in the continuous oxytocin group; absolute difference 0·4% (95% CI -2·1 to 2·9); relative risk 1·0 (95% CI 0·8 to 1·4). There were no clinically significant differences in adverse events between the two groups of the safety population. INTERPRETATION: Among participants receiving oxytocin in early labour, discontinuing oxytocin when the active phase is reached does not clinically or statistically significantly reduce neonatal morbidity compared with continuous oxytocin. FUNDING: French Ministry of Health and the Département de la Recherche Clinique et du Développement de l'Assistance Publique-Hôpitaux de Paris.

Screening for small for gestational age infants in early vs late third-trimester ultrasonography: a randomized trial.

BACKGROUND: Recent studies have demonstrated that a routine third-trimester ultrasound scan may improve the detection of small for gestational age infants when compared with clinically indicated ultrasound scans but with no reported reduction in severe perinatal morbidity. Establishing the optimal gestational age for the third-trimester examination necessitates evaluation of the ability to detect small for gestational age infants and to predict maternal and perinatal outcomes. Intrauterine growth restriction most often corresponds with small for gestational age infants associated with pathologic growth patterns. OBJECTIVE: This study aimed to assess the performance of routine early ultrasound scans vs late ultrasound scans during the third trimester of pregnancy to identify small for gestational age infants and fetuses with intrauterine growth restriction. STUDY DESIGN: This was an open-label, randomized, parallel trial conducted in Upper Normandy, France, from 2012 to 2015. The study eligibility criteria were heathy, nulliparous women older than 18 years with gestational age determined using the crown-rump length at the first trimester routine scan and with no fetal malformation or suspected small for gestational age fetus at the routine second trimester scan. Pregnant women were randomly assigned to a third-trimester scan group at 31 weeks gestational age ±6 days (early ultrasound scan) or at 35 weeks gestational age ±6 days (late ultrasound scan). The primary outcome of this trial was the ability of a third trimester scan to predict small for gestational age infants (customized birth weight <10th percentile) and intrauterine growth restriction (customized birth weight

Timing and Preventability of Cardiovascular-Related Maternal Death.

OBJECTIVE: To describe the clinical profile, management, and potential preventability of maternal cardiovascular deaths. METHODS: We conducted a retrospective, descriptive study of all maternal deaths resulting from a cardiovascular disease during pregnancy or up to 1 year after the end of pregnancy in France from 2007 to 2015. Deaths were identified through the nationwide permanent enhanced maternal mortality surveillance system (ENCMM [Enquête Nationale Confidentielle sur les Morts Maternelles]). Women were classified into four groups based on the assessment of the national experts committee: those who died of a cardiac condition and those who died of a vascular condition and, within these two groups, whether the condition was known before the acute event. Maternal characteristics, clinical features and components of suboptimal care, and preventability factors, which were assessed with a standard evaluation form, were described among those four groups. RESULTS: During the 9-year period, 103 women died of cardiac or vascular disease, which corresponds to a maternal mortality ratio from these conditions of 1.4 per 100,000 live births (95% CI 1.1-1.7). Analyses were conducted on 93 maternal deaths resulting from cardiac (n=70) and vascular (n=23) disease with available data from confidential inquiry. More than two thirds of these deaths occurred in women with no known pre-existing cardiac or vascular condition. Among the 70 deaths resulting from a cardiac condition, 60.7% were preventable, and the main preventability factor was a lack of multidisciplinary prepregnancy and prenatal care for women with a known cardiac disease. For those with no known pre-existing cardiac condition, preventability factors were related mostly to inadequate prehospital care of the acute event, in particular an underestimation of the severity and inadequate investigation of the dyspnea. Among the 23 women who died of a vascular disease, three had previously known conditions. For women with no previously known vascular condition, 47.4% of deaths were preventable, and preventability factors were related mostly to wrong or delayed diagnosis and management of acute intense chest or abdominal pain in a pregnant woman. CONCLUSION: Most maternal deaths attributable to cardiac or vascular diseases were potentially preventable. The preventability factors varied according to the cardiac or vascular site and whether the condition was known before pregnancy. A more granular understanding of the cause and related risk factors for maternal mortality is crucial to identify relevant opportunities for improving care and training health care professionals.

Long-term risk of repeated surgeries in women managed for endometriosis: a 1,092 patient-series.

OBJECTIVE: To assess the long-term risk of repeated surgery in women undergoing complete excision of endometriosis by an experienced surgeon and to identify circumstances leading up to repeat surgery. DESIGN: Retrospective study based on data recorded in a large prospective database. SETTING: University Hospital. PATIENT(S): A total of 1,092 patients managed for endometriosis, from June 2009 to June 2018, by one surgeon. INTERVENTION(S): Complete excision of endometriosis lesions. MAIN OUTCOME MEASURE(S): The recording of a repeated surgery linked to endometriosis performed during follow-up. RESULT(S): Endometriosis was exclusively superficial in 122 patients (11.2%) and 54 women (5%) had endometriomas without associated deep endometriosis nodules. Deep endometriosis was managed in 916 women (83.9%), leading to infiltration or not of the bowel in 688 (63%) and 228 (20.9%) patients, respectively. A majority of patients were managed for severe endometriosis infiltrating the rectum (58.4%). Mean and median follow-up was 60 months. A total of 155 patients underwent a repeated surgery relating to endometriosis; 108 procedures were required because of recurrences (9.9%), 39 surgeries were related to the management of infertility by assisted reproductive techniques (3.6%), and in 8 surgeries, a direct relationship between surgery and endometriosis was probable but not certain (0.8%). The majority of procedures involved hysterectomy for adenomyosis (n=45, 4.1%). The probability of requiring repeated surgery at 1, 3, 5, 7, and 10 years was 3%, 11%, 18%, 23%, and 28%, respectively. Cox's multivariate model identified postoperative pregnancy and hysterectomy as being statistically significant independent predictors for a reduction in the probability of having a repeated surgery, after adjustment on continuous postoperative amenorrhea, the main localization of the disease, and management for endometriosis infiltrating the rectum during the first surgery. CONCLUSION(S): Up to 28% of patients may require a repeated surgical procedure during the 10 years after complete excision of endometriosis. Conservation of the uterus is followed by an increased risk of repeated surgery. The study is based on outcomes resulting from a single surgeon, which limits the generalizability of results.

Efficacy of early intrauterine balloon tamponade for immediate postpartum hemorrhage after vaginal delivery: a randomized clinical trial.

BACKGROUND: Many questions remain about the appropriate use of intrauterine balloon devices in postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. Available data suggest that early use of intrauterine balloon tamponade might be beneficial. OBJECTIVE: This study aimed to compare the effect of intrauterine balloon tamponade used in combination with second-line uterotonics vs intrauterine balloon tamponade used after the failure of second-line uterotonic treatment on the rate of severe postpartum hemorrhage in women with postpartum hemorrhage after vaginal delivery refractory to first-line uterotonics. STUDY DESIGN: This multicenter, randomized, controlled, parallel-group, nonblinded trial was conducted at 18 hospitals and enrolled 403 women who had just given birth vaginally at 35 to 42 weeks of gestation. The inclusion criteria were a postpartum hemorrhage refractory to first-line uterotonics (oxytocin) and requiring a second-line uterotonic treatment with sulprostone (E1 prostaglandin). In the study group, the sulprostone infusion was combined with intrauterine tamponade by an ebb balloon performed within 15 minutes of randomization. In the control group, the sulprostone infusion was started alone within 15 minutes of randomization, and if bleeding persisted 30 minutes after the start of sulprostone infusion, intrauterine tamponade using the ebb balloon was performed. In both groups, if the bleeding persisted 30 minutes after the insertion of the balloon, an emergency radiological or surgical invasive procedure was performed. The primary outcome was the proportion of women who either received ≥3 units of packed red blood cells or had a calculated peripartum blood loss of >1000 mL. The prespecified secondary outcomes were the proportions of women who had a calculated blood loss of ≥1500 mL, any transfusion, an invasive procedure and women who were transferred to the intensive care unit. The analysis of the primary outcome with the triangular test was performed sequentially throughout the trial period. RESULTS: At the eighth interim analysis, the independent data monitoring committee concluded that the incidence of the primary outcome did not differ between the 2 groups and stopped inclusions. After 11 women were excluded because they met an exclusion criterion or withdrew their consent, 199 and 193 women remained in the study and control groups, respectively, for the intention-to-treat analysis. The women's baseline characteristics were similar in both groups. Peripartum hematocrit level change, which was needed for the calculation of the primary outcome, was missing for 4 women in the study group and 2 women in the control group. The primary outcome occurred in 131 of 195 women (67.2%) in the study group and 142 of 191 women (74.3%) in the control group (risk ratio, 0.90; 95% confidence interval, 0.79-1.03). The groups did not differ substantially for rates of calculated peripartum blood loss pf ≥1500 mL, any transfusion, invasive procedure, and admission to an intensive care unit. Endometritis occurred in 5 women (2.7%) in the study group and none in the control group (P=.06). CONCLUSION: The early use of intrauterine balloon tamponade did not reduce the incidence of severe postpartum hemorrhage compared with its use after the failure of second-line uterotonic treatment and before recourse to invasive procedures.

Serial plotting of symphysis-fundal height and estimated fetal weight to improve the antenatal detection of infants small for gestational age: A cluster randomised trial.

OBJECTIVE: To assess whether standardised longitudinal reporting of growth monitoring information improves antenatal detection of infants who are small for gestational age (SGA), compared with usual care. DESIGN: Cluster-randomised controlled trial. SETTING: Sixteen French level-3 units in 2018-2019. POPULATION: Singleton pregnancies. METHODS: The intervention consisted of the serial plotting of symphysis-fundal height (SFH) and estimated fetal weight (EFW) measurements on customised growth charts using a software program, compared with standard antenatal care. We estimated relative risks (RR) adjusted for known risk factors for fetal growth restriction (FGR). MAIN OUTCOME MEASURES: The primary outcome was antenatal detection of FGR among SGA births (with birthweights below the tenth centile of French customised curves), defined as the mention of suspected FGR in medical records and either referral ultrasounds for growth monitoring or indicated delivery for FGR. Secondary outcomes were false-positive rates, mode of delivery, perinatal morbidity and mortality, and number of antenatal visits and ultrasounds. RESULTS: In total, seven intervention clusters (n = 4349) and eight control clusters (n = 4943) were analysed, after the exclusion of one intervention centre for a major deviation in protocol. SGA births represented 613 (14.1%) and 626 (12.7%) of all births, respectively. The rates of antenatal detection of FGR among SGA births were 40.0% in the intervention arm versus 37.1% in the control arm (crude RR 1.08, 95% CI 0.87-1.34; adj RR 1.09, 95% CI 0.88-1.35). No benefits of the intervention were detected in the analyses of secondary outcomes. CONCLUSIONS: Serial plotting of SFH and EFW measurements on customised growth charts did not improve the antenatal detection of FGR among SGA births.

Maternal sudden death: A nationwide retrospective study.

OBJECTIVE: To determine the prevalence of maternal sudden death (MSD) and to compare the characteristics of death between women with explained and unexplained sudden death. DESIGN: A national retrospective study in France. POPULATION: Maternal deaths related to an unexpected sudden cardiac arrest were extracted from the French National Confidential Enquiry into Maternal Deaths database for 2007-2012. METHODS: Maternal, pregnancy, sudden death characteristics and maternal investigations were compared between women with explained and unexplained cause of death. RESULTS: A total of 83 maternal sudden deaths and 4 949 890 live births occurred over the period studied, thus accounting for 16% of all maternal deaths (n = 510). Death was explained in 51 (61%) women and unexplained in 32 women (39%). Compared with women with unexplained death, women with explained death were more often found to have in-hospital cardiac arrest (47% versus 12%, P < 0.01), witnessed cardiac arrest (86% versus 62%, P = 0.03) and in-hospital death (82% versus 47%, P < 0.01). Postmortem investigations such as autopsy and/or CT scan (65% versus 31%, P < 0.01) were also more often carried out in women with explained death. The proportion of deaths for which the preventability factors could not be assessed was 58% among unexplained MSD and 7% among explained MSD. CONCLUSION: Maternal sudden death is a rare event but accounts for a high proportion of all maternal deaths. This highlights the importance of providing training in diagnostic and management strategy for care providers. Systematic postmortem investigations are required to help understand causes and improve practices.

Tranexamic acid for the prevention of blood loss after cesarean among women with twins: a secondary analysis of the TRAnexamic Acid for Preventing Postpartum Hemorrhage Following a Cesarean Delivery randomized clinical trial.

BACKGROUND: Although prophylactic tranexamic acid administration after cesarean delivery resulted in a lower incidence of calculated estimated blood loss of >1000 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. OBJECTIVE: This study aimed to compare the effect of tranexamic acid vs placebo to prevent blood loss after cesarean delivery among women with multiple pregnancies. STUDY DESIGN: 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 of >1000 mL or a red blood cell transfusion by 2 days after delivery. The secondary outcomes included clinical and laboratory blood loss measurements. RESULTS: 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). CONCLUSION: Among women with a multiple pregnancy and cesarean delivery, prophylactic tranexamic acid did not reduce the incidence of any blood loss-related outcomes.

Association Between Endometriosis Phenotype and Preterm Birth in France.

Importance: Endometriosis is an inflammatory disease with a heterogeneous presentation that affects women of childbearing age. Given the limitations of previous retrospective studies, it is still unclear whether endometriosis has adverse implications for pregnancy outcomes. Objective: To evaluate the association between the presence of endometriosis and preterm birth and whether the risk varied according to the disease phenotype. Design, Setting, and Participants: This cohort study with exposed and unexposed groups was conducted in 7 maternity units in France from February 4, 2016, to June 28, 2018. Participants included women with singleton pregnancies who were followed up before 22 weeks' gestation along with their newborns delivered at or after 22 weeks' gestation. The final follow-up occurred in July 2019. Data were analyzed from October 7, 2020, to February 7, 2021. Exposures: Women in the endometriosis group had a documented history of endometriosis and were classified according to 3 endometriosis phenotypes: isolated superficial peritoneal endometriosis (SUP), ovarian endometrioma (OMA; potentially associated with SUP), and deep endometriosis (DE; potentially associated with SUP and OMA). Women in the control group did not have a history of clinical symptoms of endometriosis before their current pregnancy. Main Outcomes and Measures: The primary outcome was preterm birth between 22 weeks and 36 weeks 6 days of gestation. Association between endometriosis and the primary outcome was assessed through univariate and multivariate logistic regression analyses and was adjusted for the following risk factors associated with preterm birth: maternal age, body mass index (calculated as weight in kilograms divided by height in meters squared) before pregnancy, country of birth, parity, previous cesarean delivery, history of myomectomy and hysteroscopy, and preterm birth. The same analysis was performed according to the 3 endometriosis phenotypes (SUP, OMA, and DE). Results: Of the 1351 study participants (mean [SD] age, 32.9 [5.0] years) who had a singleton delivery after 22 weeks of gestation, 470 were assigned to the endometriosis group (48 had SUP [10.2%], 83 had OMA [17.7%], and 339 had DE [72.1%]) and 881 were assigned to the control group. No difference was observed in the rate of preterm deliveries before 37 weeks 0 days of gestation between the endometriosis and control groups (34 of 470 [7.2%] vs 53 of 881 [6.0%]; P = .38). After adjusting for confounding factors, endometriosis was not associated with preterm birth before 37 weeks' gestation (adjusted odds ratio, 1.07; 95% CI, 0.64-1.77). The results were comparable for the different disease phenotypes (SUP: 6.2% [3 of 48]; OMA: 7.2% [6 of 83]; and DE: 7.4% [25 of 339]; P = .84). Conclusions and Relevance: This cohort study found no association between endometriosis and preterm birth, and the disease phenotype did not appear to alter the result. Monitoring the pregnancy beyond the normal protocols or changing management strategies for women with endometriosis may not be warranted to prevent preterm birth.

European guidelines on perinatal care- Peripartum care Episiotomy.

OF RECOMMENDATIONS1. Episiotomy should be performed by indication only, and not routinely (Moderate quality evidence +++-; Strong recommendation). Accepted indications for episiotomy are to shorten the second stage of labor when there is suspected fetal hypoxia (Low quality evidence ++-; Weak recommendation); to prevent obstetric anal sphincter injury in vaginal operative deliveries, or when obstetric sphincter injury occurred in previous deliveries (Moderate quality evidence +++-; Strong recommendation)2. Mediolateral or lateral episiotomy technique should be used (Moderate quality evidence +++-; Strong recommendation). Labor ward staff should be offered regular training in correct episiotomy techniques (Moderate quality evidence +++-; Strong recommendation).3. Pain relief needs to be considered before episiotomy is performed, and epidural analgesia may be insufficient. The perineal skin needs to be tested for pain before an episiotomy is performed, even when an epidural is in place. Local anesthetics or pudendal block need to be considered as isolated or additional pain relief methods (Low quality evidence ++-; Strong recommendation).4. After childbirth the perineum should be carefully inspected, and the anal sphincter palpated to identify possible injury (Moderate quality evidence +++-; Strong recommendation). Primary suturing immediately after childbirth should be offered and a continuous suturing technique should be used when repairing an uncomplicated episiotomy (High quality evidence ++++; Strong recommendation).

Tranexamic Acid for the Prevention of Blood Loss after Cesarean Delivery.

BACKGROUND: Prophylactic administration of tranexamic acid has been associated with reduced postpartum blood loss after cesarean delivery in several small trials, but evidence of its benefit in this clinical context remains inconclusive. METHODS: In a multicenter, double-blind, randomized, controlled trial, we assigned women undergoing cesarean delivery before or during labor at 34 or more gestational weeks to receive an intravenously administered prophylactic uterotonic agent and either tranexamic acid (1 g) or placebo. The primary outcome was postpartum hemorrhage, defined as a calculated estimated blood loss greater than 1000 ml or receipt of a red-cell transfusion within 2 days after delivery. Secondary outcomes included gravimetrically estimated blood loss, provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, and postpartum blood transfusion. RESULTS: Of the 4551 women who underwent randomization, 4431 underwent cesarean delivery, 4153 (93.7%) of whom had primary outcome data available. The primary outcome occurred in 556 of 2086 women (26.7%) in the tranexamic acid group and in 653 of 2067 (31.6%) in the placebo group (adjusted risk ratio, 0.84; 95% confidence interval [CI], 0.75 to 0.94; P = 0.003). There were no significant between-group differences in mean gravimetrically estimated blood loss or in the percentage of women with provider-assessed clinically significant postpartum hemorrhage, use of additional uterotonic agents, or postpartum blood transfusion. Thromboembolic events in the 3 months after delivery occurred in 0.4% of women (8 of 2049) who received tranexamic acid and in 0.1% of women (2 of 2056) who received placebo (adjusted risk ratio, 4.01; 95% CI, 0.85 to 18.92; P = 0.08). CONCLUSIONS: Among women who underwent cesarean delivery and received prophylactic uterotonic agents, tranexamic acid treatment resulted in a significantly lower incidence of calculated estimated blood loss greater than 1000 ml or red-cell transfusion by day 2 than placebo, but it did not result in a lower incidence of hemorrhage-related secondary clinical outcomes. (Funded by the French Ministry of Health; TRAAP2 ClinicalTrials.gov number, NCT03431805.).

Large ovarian endometriomas are associated with high pre-operative anti-Müllerian hormone concentrations.

RESEARCH QUESTION: Are large ovarian endometriomas associated with high pre-operative anti-Müllerian hormone (AMH) concentrations? DESIGN: Data from 332 women who underwent AMH measurement before surgery for endometriosis were prospectively recorded in a large database. Univariate analysis compared AMH concentrations in terms of the patients' baseline characteristics. A multivariate model was used to identify variables having an independent relationship with AMH concentration. RESULTS: Among 332 women included in the study, 47.6% were aged 18-30 years, 67.8% were infertile and 85.5% were nulliparous. A total of 66.3% had ovarian endometriomas, and 10.8% had cysts measuring over 6 cm. Bilateral cysts over 3 cm were recorded in 24.7% of the women. Univariate analysis identified two variables that had a statistically significant relationship with AMH concentration: the woman's age (P = 0.01) and cyst size (P < 0.001). Multivariate analysis revealed that ages of 36-40 years and over 40 years showed a significant association with lower AMH concentrations (P = 0.02 and P = 0.009, respectively), while a cyst size of over 6 cm was statistically associated with high AMH concentrations (P < 0.001), after adjustment for smoking, parity, rectosigmoid endometriotic nodules and a bilateral location of endometriomas. CONCLUSIONS: Pre-operative AMH concentration was significantly increased in women with large endometriomas of over 6 cm, independent of their age or the presence of bilateral endometriomas. This is relevant for both surgeons and patients when planning surgery in women with an intention to conceive post-operatively.

Fetal megacystis-microcolon: Genetic mutational spectrum and identification of PDCL3 as a novel candidate gene.

Megacystis-microcolon-intestinal-hypoperistalsis syndrome (MMIHS) is a severe congenital visceral myopathy characterized by an abdominal distension due to a large non-obstructed urinary bladder, a microcolon and intestinal hypo- or aperistalsis. Most of the patients described to date carry a sporadic heterozygous variant in ACTG2. More recently, recessive forms have been reported and mutations in MYH11, LMOD1, MYLK and MYL9 have been described at the molecular level. In the present report, we describe five patients carrying a recurrent heterozygous variant in ACTG2. Exome sequencing performed in four families allowed us to identify the genetic cause in three. In two families, we identified variants in MMIHS causal genes, respectively a nonsense homozygous variant in MYH11 and a previously described homozygous deletion in MYL9. Finally, we identified compound heterozygous variants in a novel candidate gene, PDCL3, c.[143_144del];[380G>A], p.[(Tyr48Ter)];[(Cys127Tyr)]. After cDNA analysis, a complete absence of PDLC3 expression was observed in affected individuals, indicating that both mutated transcripts were unstable and prone to mediated mRNA decay. PDCL3 encodes a protein involved in the folding of actin, a key step in thin filament formation. Presumably, loss-of-function of this protein affects the contractility of smooth muscle tissues, making PDCL3 an excellent candidate gene for autosomal recessive forms of MMIHS.

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

OBJECTIVE: To describe the course over time of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in French women from the beginning of the pandemic until mid-April, the risk profile of women with respiratory complications, and short-term pregnancy outcomes. METHODS: We collected a case series of pregnant women with COVID-19 in a research network of 33 French maternity units between March 1 and April 14, 2020. All cases of SARS-CoV-2 infection confirmed by a positive result on real-time reverse transcriptase polymerase chain reaction tests of a nasal sample and/or diagnosed by a computed tomography chest scan were included and analyzed. The primary outcome measures were COVID-19 requiring oxygen (oxygen therapy or noninvasive ventilation) and critical COVID-19 (requiring invasive mechanical ventilation or extracorporeal membrane oxygenation, ECMO). Demographic data, baseline comorbidities, and pregnancy outcomes were also collected. RESULTS: Active cases of COVID-19 increased exponentially during March 1-31, 2020; the numbers fell during April 1-14, after lockdown was imposed on March 17. The shape of the curve of active critical COVID-19 mirrored that of all active cases. By April 14, among the 617 pregnant women with COVID-19, 93 women (15.1 %; 95 %CI 12.3-18.1) had required oxygen therapy and 35 others (5.7 %; 95 %CI 4.0-7.8) had had a critical form of COVID-19. The severity of the disease was associated with age older than 35 years and obesity, as well as preexisting diabetes, previous preeclampsia, and gestational hypertension or preeclampsia. One woman with critical COVID-19 died (0.2 %; 95 %CI 0-0.9). Among the women who gave birth, rates of preterm birth in women with non-severe, oxygen-requiring, and critical COVID-19 were 13/123 (10.6 %), 14/29 (48.3 %), and 23/29 (79.3 %) before 37 weeks and 3/123 (2.4 %), 4/29 (13.8 %), and 14/29 (48.3 %) before 32 weeks, respectively. One neonate (0.5 %; 95 %CI 0.01-2.9) in the critical group died from prematurity. CONCLUSION: COVID-19 can be responsible for significant rates of severe acute, potentially deadly, respiratory distress syndromes. The most vulnerable pregnant women, those with comorbidities, may benefit particularly from prevention measures such as a lockdown.