[Impact of the mode of follow-up of preterm premature rupture of membranes before 36 weeks of gestation on the latency period.] / Impact du mode de suivi des ruptures prématurées des membranes avant 36 SA sur la durée de latence.

INTRODUCTION: Preterm premature rupture of membranes (PPROM) is the main cause of premature delivery, complicating 1-3% of all pregnancies. Conventional hospitalization (CH) is the most frequent mode of follow-up, but homecare (HC) seems to be an alternative. OBJECTIVES: Study of the impact of the monitoring mode on the duration of the latency period and on the latency ratio after PPROM, and analysis of the risk factors modifying this ratio. METHODS: This was a bicentric retrospective cohort study here-abouts including patients who presented a PPROM between 24 and 36 weeks of gestation from 2016 to 2018. Patients had a follow-up in HC at Lille University Hospital center (UHC) and in CH at Nantes UHC according to two different follow-up protocols. The latency ratio corresponded to the real latency period divided by the latency period to theoretical term. RESULTS: We included 154 patients : 102 in HC and 52 in CH. The mean latency period was significantly higher in HC : 36.9±21.8 days, corresponding to an 85.5±23.7% latency ratio versus 20.2±12 days, corresponding to an 66.9±29.8% latency ratio in CH (p< 0.001). The latency ratio in CH was correlated with term at PPROM (p = 0.001). CONCLUSIONS: The duration of the latency period seems prolonged for PPROM followed by HC management versus CH in selected populations. This study suggests a benefit to HC in stable patients.

Perinatal outcomes between immediate vs deferred selective termination in dichorionic twin pregnancies with fetal congenital anomalies: a French multicenter study.

BACKGROUND: Because selective termination for discordant dichorionic twin anomalies carries a risk of pregnancy loss, deferring the procedure until the third trimester can be considered in settings where it is legal. OBJECTIVE: To determine whether perinatal outcomes were more favorable following deferred rather than immediate selective termination. STUDY DESIGN: A French multicenter retrospective study from 2012 to 2023 on dichorionic twin pregnancies with selective termination for fetal conditions, which were diagnosed before 24 weeks gestation. Pregnancies with additional risk factors for late miscarriage were excluded. We defined 2 groups according to the intention to perform selective termination within 2 weeks after the diagnosis of the severe fetal anomaly was established (immediate selective termination) or to wait until the third trimester (deferred selective termination). The primary outcome was perinatal survival at 28 days of life. Secondary outcomes were pregnancy losses before 24 weeks gestation and preterm delivery. RESULTS: Of 390 pregnancies, 258 were in the immediate selective termination group and 132 in the deferred selective termination group. Baseline characteristics were similar in both groups. Overall survival of the healthy co-twin was 93.8% (242/258) in the immediate selective termination group vs 100% (132/132) in the deferred selective termination group (P<.01). Preterm birth <37 weeks gestation was lower in the immediate than in the deferred selective termination group (66.7% vs 20.2%; P<.01); preterm birth <28 weeks gestation and <32 weeks gestation did not differ significantly (respectively 1.7% vs 0.8%; P=.66 and 8.26% vs 11.4%; P=.36). In the deferred selective termination group, an emergency procedure was performed in 11.3% (15/132) because of threatened preterm labor, of which 3.7% (5/132) for imminent delivery. CONCLUSION: Overall survival after selective termination was high regardless of the gestational age at which the procedure was performed. Postponing selective termination until the third trimester seems to improve survival, whereas immediate selective termination reduces the risk of preterm delivery. Furthermore, deferred selective termination requires an expert center capable of performing the selective termination procedure on an emergency basis if required.

Risk factors for placenta accreta spectrum disorders in women with any prior cesarean and a placenta previa or low lying: a prospective population-based study.

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.

Prevention of Rhesus-D Alloimmunization in the First Trimester of Pregnancy: Economic Analysis of Three Management Strategies.

Anti-D alloimmunization in the first trimester of pregnancy has long been the subject of prevention with anti-D immunoglobulins during events at risk of fetomaternal hemorrhage. Although the efficacy of preventing anti-D alloimmunization by an injection of immunoglobulin at 28 weeks of gestation (WG) is obvious, the literature provides little evidence of the effectiveness before 12+6 WG and several countries have modified their recommendations. In the presumed absence of a difference in alloimmunization risk between early and late prevention, our objective was to evaluate and compare the cost of treatment for 3 alloimmunization prevention strategies in France, the United Kingdom, and the Netherlands. This was a single-center retrospective study. Our target population included all women who received anti-D immunoglobulins (Rhophylac) in the first trimester of pregnancy before 12+6 WG at Nantes University Hospital in 2018 (N = 356). Within the target population, 2 other populations were constituted based on British (N = 145) and Dutch (N = 142) clinical practice guidelines (CPG). These 3 populations were analyzed for the comparative cost of treatment for prevention from a health system perspective. The average cost of Rhophylac alloimmunization prevention for 1 episode was €117.8 from a health system perspective. The total cost attributed to prevention in 2018 at Nantes University Hospital (N = 356) was €41,931.4 according to this perspective. If the UK CPG or Dutch CPG had been applied to the Nantes target population, a saving of around 60% would have been achieved. At the national level, the cost according to the health system perspective specifically attributable to induced abortion (N estimated = 26,916) could represent a total cost of €3,170,704. This study highlighted the high cost of the French prevention strategy in the first trimester of pregnancy compared with British or Dutch strategies. The modification of our practices would allow substantial financial savings to the French health system but would also avoid the nonrecommended exposure to a blood product at this term, would allow a faster medical management and a relief of the care system.

Evaluation Tools for Assessing Autonomy of Surgical Residents in the Operating Room and Factors Influencing Access to Autonomy: A Systematic Literature Review.

BACKGROUND: Surgical residents in France lack a clear pedagogical framework for achieving autonomy in the operating room. The progressive acquisition of surgical autonomy is a determining factor in the confidence of operators for their future independent practice. Currently, there is no autonomy scale commonly used in Europe. The objective of this study is to identify existing tools for quantifying the autonomy of residents and the factors that influence it. MATERIALS AND METHODS: We conducted a qualitative systematic review following the recommendations of the Systematic Review Without Meta-Analysis (SWiM) guidelines. Publications were extracted from the MEDLINE (PubMed), EMBASE, and PSYCINFO databases. All publications without date restrictions up to July 2022 were identified. RESULTS: Among the 231 identified publications, 21 met the inclusion criteria. Seventeen publications used a graded autonomy assessment tool by the student and/or the teacher, while 4 used evaluations by an observing third party. We found 8 different autonomy scales, with the Zwisch Scale representing 57.1% of the cases. Factors influencing autonomy were diverse, including the work context, experience, and gender of the resident and their teacher. DISCUSSION: We found heterogeneity in the tools used to "measure" the autonomy of a resident in the operating room. The SIMPL tool or the Zwisch Scale appear to be the most frequently used tools. The relationship between autonomy, performance, confidence, and knowledge may require multidimensional tools that encompass various areas of competence, but this could make their daily application more challenging. The factors influencing autonomy are numerous; and understanding them would improve teaching in the operating room. There is a significant lack of data on surgical autonomy in France, as well as a lack of evaluation in the field of gynecology-obstetrics worldwide.

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.

Knowledge and Practice Behaviours of Obstetricians/Gynecologists and Midwives Concerning Periodontal Health and Pregnancy.

PURPOSE: The purpose of the present study was to evaluate the level of knowledge of prenatal health professionals concerning the relationship between periodontal diseases and pregnancy complications, as well as their professional implications in the oral health field. MATERIALS AND METHODS: A questionnaire was distributed to obstetricians/gynecologists, interns specialised in obstetrics/gynecology, midwives, and student midwives at Loire Atlantique and Vendée hospitals (France). The questionnaire included 5 sociodemographic questions and 14 questions regarding the level of knowledge about the relationship between periodontal diseases and pregnancy complications as well as the professionals' level of involvement in oral health care. RESULTS: Twenty-three obstetricians/gynecologists and 55 midwives responded to the questionnaire. Preterm delivery and chorioamnionitis were the most frequently mentioned complications of pregnancy, whereas the risk of pre-eclampsia was rarely mentioned. Half of the professionals said they were aware of the oral manifestations of pregnancy. Gingivitis and an increased risk of caries were the most frequently mentioned items, whereas epulis was the least frequently mentioned item. The level of involvement of prenatal care practitioners in oral health care was limited due to a lack of competence and time. Nevertheless, 64% of the participants discussed the risks of poor oral hygiene with their patients. CONCLUSION: There is good knowledge among French gynecologists/obstetricians and midwives regarding the oral manifestations of pregnancy. However, there is still a lack of knowledge concerning the links between periodontal diseases and pregnancy complications. The involvement and behaviour of pregnancy professionals in the oral health field is inadequate. The present survey highlights the need to improve the initial and continuing education of obstetricians and midwives on this topic.

Adrenal Gland Necrosis in Pregnancy: How to Manage? Case Series at Nantes University Hospital and Literature Review.

Adrenal necrosis is a rare but serious cause of abdominal pain of thrombotic origin during pregnancy. There is often a delay in diagnosis and treatment. The objective was to specify the clinical and paraclinical signs suggestive of adrenal necrosis, making it possible to improve the delay in diagnostic. The secondary objective was to establish a multidisciplinary protocol regarding management. This is a case report of pregnant women with a radiological diagnosis of adrenal gland necrosis. In parallel, we carried out a systematic review in the same period. We studied these patients' clinical, biological and radiological data. We included eight patients with a computed tomography scan diagnosis of adrenal necrosis and fifteen articles in the literature describing twenty-four cases. All the patients presented with the same symptoms. The treatment was based on curative anticoagulation. The diagnosis of adrenal gland necrosis is worth suggesting in view of the array of sudden morphine-resistant abdominal pain associated with a biological inflammatory syndrome. The diagnosis is based on the computed tomography scan. Three to six months of curative anticoagulation is recommended as well as a thrombophilia and endocrinological assessment to rule out adrenal insufficiency.

Neurodevelopmental Outcome at Corrected Age of 2 Years among Children Born Preterm with Operative Vaginal Delivery: A Population-Based Study (LIFT Cohort).

The aim of the study was to determine whether operative vaginal delivery (OVD) was associated with non-optimal neurocognitive development at the corrected age of 2 years for preterm singletons using the Loire Infant Follow-up Team (LIFT) longitudinal cohort, a French regional perinatal network and prospective, population-based cohort of preterm infants. For this study, we included women with cephalic singletons and planned vaginal delivery from 24 to 34 weeks' gestation between 2006 and 2016. The main exposure was the mode of delivery (spontaneous vaginal delivery (SVD), OVD, and cesarean delivery (CS) during labor). The primary outcome was non-optimal neurodevelopmental outcome at the corrected age of 2 years assessed by a physical examination, a neuropsychological test, and/or a parental questionnaire. Secondary outcomes were survival at discharge and survival at discharge without morbidity. We used the multivariate logistic regression and propensity score methods to compare outcomes associated with OVD. The study included 1934 infants born preterm: 1384 (71.6%) with SVD, 87 (4.5%) with OVD, and 463 (23.9%) with CS. Neonates with SVD, OVD, and CS did not differ in survival (97.0%, 97.7%, and 97.8%, respectively; p = 0.79) or in survival without morbidity (82.8%, 86.2%, and 82.7%, respectively; p = 0.71). In survived infants, 1578 (81.6%) were evaluated at age two: 279 (17.7%) were considered to have a non-optimal neurodevelopmental outcome (18.3% after SVD, 18.0% after OVD, and 15.9% after CS; p = 0.57). Propensity score analysis showed that OVD was not associated with non-optimal neurocognitive development at age two, with an adjusted odds ratio (aOR) of 0.86 and a 95% confidence interval (95% CI) of 0.47-1.69, compared with SVD; and an aOR of 0.76 and a 95% CI of 0.31-1.8, compared with CS. Operative vaginal delivery was not associated with non-optimal neurocognitive development at 2 years of corrected age for preterm singletons.

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.

Oxytocin versus prostaglandins for labour Induction of women with an unfavourable cervix after 24 hours of cervical ripening (OPIC): protocol for an open multicentre randomised non-inferiority trial.

INTRODUCTION: It remains uncertain whether the most appropriate management for women with an unfavourable cervix after 24 hours of cervical ripening is repeating the ripening procedure or proceeding directly to induction by oxytocin. No adequately powered trial has compared these strategies. We hypothesise that induction of labour with oxytocin among women who have just undergone an ineffective first ripening procedure is not associated with a higher risk of caesarean delivery than a repeated cervical ripening with prostaglandins. METHODS AND ANALYSIS: We will conduct a multicentre, non-inferiority, open-label, randomised controlled trial aimed at comparing labour induction by oxytocin with a second cervical ripening that uses prostaglandins (slow-release vaginal dinoprostone; oral misoprostol 25 µg; dinoprostone vaginal gel 2 mg). Women (n=1494) randomised in a 1:1 ratio in 10 French maternity units must be ≥18 years with a singleton fetus in vertex presentation, at a term from ≥37+0 weeks of gestation, and have just completed a 24-hour cervical ripening procedure by any method (pharmacological or mechanical) with a Bishop score ≤6. Exclusion criteria comprise being in labour, having more than 3 contractions per 10 min, or a prior caesarean delivery or a history of uterine surgery, or a fetus with antenatally suspected severe congenital abnormalities or a non-reassuring fetal heart rate. The primary endpoint will be the caesarean delivery rate, regardless of indication. Secondary outcomes concern delivery, perinatal morbidity, maternal satisfaction and health economic evaluations. The nature of the assessed procedures prevents masking the study investigators and patients to group assignment. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The ethics committee 'Comité de Protection des Personnes Ile de France VII' approved this study on 2 April 2021 (No 2021-000989-15). Study findings will be submitted for publication and presented at relevant conferences. TRIAL REGISTRATION NUMBER: NCT04949633.

Chorionicity and neurodevelopmental outcomes at 5½ years among twins born preterm: the EPIPAGE2 cohort study.

OBJECTIVE: To compare the neurodevelopmental outcomes of preterm twins at 5½ years by chorionicity of pregnancy. DESIGN: Prospective nationwide population-based EPIPAGE2 (Etude Epidémiologique sur les Petits Âges Gestationnels) cohort study. SETTING: A total of 546 maternity units in France, between March and December 2011. POPULATION: A total of 1126 twins eligible for follow-up at 5½ years. METHODS: The association of chorionicity with outcomes was analysed using multivariate regression models. MAIN OUTCOME MEASURES: Survival at 5½ years with or without neurodevelopmental disabilities (comprising cerebral palsy, visual, hearing, cognitive deficiency, behavioural difficulties or developmental coordination disorders) were described and compared by chorionicity. RESULTS: Among the 1126 twins eligible for follow-up at 5½ years, 926 (82.2%) could be evaluated: 228 monochorionic (MC) and 698 dichorionic (DC). Based on chronicity and gestational age of birth, we found no significant differences for severe neonatal morbidity. The rates of moderate/severe neurobehavioral disabilities were similar in infants from DC pregnancies versus infants from MC pregnancies (OR 1.22, 95% CI 0.65-2.28). By gestational age and without twin-twin transfusion syndrome (TTTS), no difference according to chorionicity was found for all neurodevelopmental outcome measures. CONCLUSIONS: The neurodevelopmental outcomes among preterm twins at 5½ years is similar, irrespective of chorionicity.

Postpartum Depression after Maternal Isolation during the COVID-19 Pandemic: The MUMI-19 Study (Mothers Undergoing Mental Impact of COVID-19 Pandemic).

Background: The COVID-19 pandemic has shaken the world by imposing unprecedented health measures, including in the postpartum period. Objectives: We aim to assess the impact of maternal isolation in the immediate postpartum period on the rate of postpartum depression (PPD) in a tertiary center. Study Design: We conducted a prospective cohort study, between 22 April and 29 October 2020, using anonymous questionnaires on 265 participants (129 during lockdown and 135 outside). The Edinburgh Postnatal Depression Scale (EPDS) was used as screening for PPD. We used a univariate logistic regression model to analyze the association between risk factors and PPD. Results: There was no difference between the two groups for PPD assessed by an EPDS score >10.5 on day 30 and/or day 60 (23.1% vs. 29.3%, p = 0.661) but on day 3 it was higher (31% vs. 17.8%, p = 0.015) during the lockdown period and partners were more impacted psychologically (48.3% vs. 10.5%, p < 0.001). Parity ≥1 was a protective factor for PPD (OR = 0.2, 95% CI [0.1−0.6], p = 0.003). Risk factors of PPD were: history of psychological abuses (OR = 6.4, CI 95% [1.1−37.6], p = 0.04), stressful life event (OR = 4.5, CI 95% [1.6−12.6], p = 0.004), and bad birth experience (OR = 5.1, CI 95% [1.4−17.8], p = 0.012). Conclusion: Maternal isolation in the immediate postpartum period is associated with an increased rate of moderate to severe symptoms of postpartum blues. The well-known long-term consequences of PPD must be balanced against the expected benefits of partner's restrictive access to maternity ward.

Difference in Pap test uptake between women who have sex with women and other women in France: A comparative survey of 2032 women.

The elimination of cervical cancer has been a priority of the World Health Organization since 2018. The number of these cancers induced by the human papillomavirus (HPV) could be drastically reduced through vaccination and regularly screening by Pap tests. Guidelines for cervical cancer screening apply to all women, including those who have sexual relations with women (WSW), as HPV can be transmitted during sex between two women. As far as we know, our study is the first that compare the Pap test rate between WSW and other women in France. We developed an 18-item questionnaire available on the internet for 15 days and finally analyzed the responses of 2032 women. Based on their responses about their self-definition of their sexual orientation and their sexual behavior, we classified them into three groups of women: exclusive WSW, mixed WSW, and non-WSW. For each question, we tested the statistical differences in responses between these three groups. Our study shows in a large sample representative of the French population that exclusive WSW undergo Pap tests significantly less often than either mixed WSW or non-WSW. Among the exclusive WSW, 28.9 % had never had a Pap test, compared with 9 % of the mixed WSW and 3.1 % of non-WSW (p < 0,001). The responses to our questionnaire contribute to an understanding of this disparity and thus help to envision solutions for better care of all women, regardless of their sexual orientation; this point is crucial for prevention of cervical cancer.

Low-dose aspirin to prevent preeclampsia and growth restriction in nulliparous women identified by uterine artery Doppler as at high risk of preeclampsia: A double blinded randomized placebo-controlled trial.

INTRODUCTION: This trial evaluates whether daily low-dose aspirin initiated before 16 weeks of gestation can reduce preeclampsia and fetal growth restriction in nulliparous women identified by first-trimester uterine artery Dopplers as at high risk of preeclampsia. METHODS: This randomized, blinded, placebo-controlled, parallel-group trial took place in 17 French obstetric departments providing antenatal care. Pregnant nulliparous women aged ≥ 18 years with a singleton pregnancy at a gestational age < 16 weeks of gestation with a lowest pulsatility index ≥ 1.7 or a bilateral protodiastolic notching for both uterine arteries on an ultrasound performed between 11+0 and 13+6 weeks by a certified sonographer were randomized at a 1:1 ratio to 160 mg of low-dose aspirin or to placebo to be taken daily from inclusion to their 34th week of gestation. The main outcome was preeclampsia or a birthweight ≤ 5th percentile. Other outcomes included preeclampsia, severe preeclampsia, preterm preeclampsia, preterm delivery before 34 weeks, mode of delivery, type of anesthesia, birthweight ≤ 5th percentile and perinatal death. RESULTS: The trial was interrupted due to recruiting difficulties. Between June 2012 and June 2016, 1104 women were randomized, two withdrew consent, and two had terminations of pregnancies. Preeclampsia or a birthweight ≤ 5th percentile occurred in 88 (16.0%) women in the low-dose aspirin group and in 79 (14.4%) in the placebo group (proportion difference 1.6 [-2.6; 5.9] p = 0.45). The two groups did not differ significantly for the secondary outcomes. CONCLUSION: Low-dose aspirin was not associated with a lower rate of either preeclampsia or birthweight ≤ 5th percentile in women identified by their first-trimester uterine artery Doppler as at high risk of preeclampsia. TRIAL REGISTRATION: (NCT0172946).

Neonatal outcomes for women at risk of preterm delivery given half dose versus full dose of antenatal betamethasone: a randomised, multicentre, double-blind, placebo-controlled, non-inferiority trial.

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.

Trial of Labor Compared With Elective Cesarean Delivery for Low-Lying Placenta.

OBJECTIVE: To compare outcomes of women with low-lying placenta by planned mode of delivery and distance from the internal os distance. METHODS: Six tertiary maternity hospitals in France participated in this retrospective multicenter study of births from 2007-2012. Women with low-lying placenta , defined as an internal os distance of 20 mm or less, who gave birth after 35 weeks of gestation were included and classified in the planned trial-of-labor or elective cesarean delivery groups. The primary endpoint was severe postpartum hemorrhage (PPH) defined as blood loss exceeding 1,000 mL. Secondary outcomes were composite variables of severe maternal and neonatal morbidity. We used multivariable logistic regression and propensity scores to compare outcomes by planned mode of delivery. RESULTS: Among 128,233 births during the study period, 171 (0.13%) women had low-lying placenta: 70 (40.9%) in the trial-of-labor group and 101 (59.1%) who underwent elective cesarean delivery. The rate of severe PPH was 22.9% (16/70, 95% CI 13.7-34.4) for the trial-of-labor group and 23.0% (23/101, 95% CI 15.2-32.5) for the cesarean delivery group ( P =.9); severe maternal and neonatal morbidity rates were likewise similar (2.9% vs 2.0% [ P =.7] and 12.9% vs 9.9% [ P =.5], respectively). Trial-of-labor was not significantly associated with a higher rate of severe PPH after multivariable logistic regression and propensity score-weighted analysis (adjusted odds ratio [aOR] 1.42, 95% CI 0.62-3.24 [ P =.4]; and aOR 1.34, 95% CI 0.53-3.38 [ P =.5], respectively). The vaginal delivery rate in the trial-of-labor group was 50.0% (19/38) in those with an internal os distance of 11-20 mm and 18.5% (5/27) in those with a distance of 1-10 mm. CONCLUSION: Our results support a policy of offering a trial of labor to women with low-lying placenta after 35 weeks of gestation and an internal os distance of 11-20 mm. An internal os distance of 1-10 mm reduces the likelihood of vaginal birth considerably, compared with 11-20 mm, but without increasing the incidence of severe PPH or severe maternal morbidity.

Cervical Dilators Used Concurrently With Misoprostol to Shorten Labor in Second-Trimester Termination of Pregnancy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate the use of cervical dilators concurrently with misoprostol to shorten labor in second-trimester medical termination of pregnancy. METHODS: This multicenter randomized controlled trial compared the efficacy of cervical dilators inserted concurrently with misoprostol with that of misoprostol, alone, to shorten labor for women undergoing termination of pregnancy between 15 0/7 and 27 6/7 weeks of gestation. The primary outcome was the proportion of women with a duration of labor exceeding 12 hours. Secondary outcomes included median duration of labor, time to amniotomy, side effects, complications, NPRS (Numeric Pain Rating Scale) score, and women's distress as measured by the IES-R (Impact of Event Scale-Revised). These outcomes also were studied separately in the nulliparous subgroup. To demonstrate a reduction of 50% of the proportion of women with a duration of labor exceeding 12 hours in the dilator group, with a power of 80% and a 2-sided 0.05 significance level, a sample of 268 women (134 in each group) was required. RESULTS: Between December 2017 and September 2019, this study enrolled and analyzed 347 women: 174 in the dilator group and 173 in the control group, including 87 and 93 nulliparous patients, respectively. Sociodemographic and obstetric characteristics were similar between groups. The proportion of women with labor exceeding 12 hours was not different between groups (49/174 [28.2%] in the dilator group vs 53/173 [30.6%] in the control group [ P =.61] for the whole population, and 37/87 [42.5%] vs 42/93 [45.2%] [ P =.72], respectively, among nulliparous patients). Median duration of labor was 8.5 hours in the dilator group compared with 9.2 hours in the control group ( P =.65) for the whole population, and 10.5 hours compared with 11.8 hours, respectively, among nulliparous patients ( P =.33). Median time to amniotomy was 3.6 hours in the dilator group compared with 5.0 hours in the control group ( P =.08) for the whole population, and 3.5 hours compared with 6.7 hours, respectively, among nulliparous patients ( P =.003). Side effects, complications, NPRS score, and IES-R score were similar between groups. CONCLUSION: Cervical dilators inserted concurrently with misoprostol did not reduce the proportion of women whose labor exceeded 12 hours compared with misoprostol alone. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT03194230.

Efficacy and Safety of Transcranial Electric Stimulation during the Perinatal Period: A Systematic Literature Review and Three Case Reports.

Introduction: The perinatal period is an at-risk period for the emergence or decompensation of psychiatric disorders. Transcranial electrical stimulation (tES) is an effective and safe treatment for many psychiatric disorders. Given the reluctance to use pharmacological treatments during pregnancy or breastfeeding, tES may be an interesting treatment to consider. Our study aims to evaluate the efficacy and safety of tES in the perinatal period through a systematic literature review followed by three original case reports. Method: Following PRISMA guidelines, a systematic review of MEDLINE and ScienceDirect was undertaken to identify studies on tES on women during the perinatal period. The initial research was conducted until 31 December 2021 and search terms included: tDCS, transcranial direct current stimulation, tACS, transcranial alternating current stimulation, tRNS, transcranial random noise stimulation, pregnancy, perinatal, postnatal, and postpartum. Results: Seven studies reporting on 33 women during the perinatal period met the eligibility criteria. No serious adverse effects for the mother or child were reported. Data were limited to the use of tES during pregnancy in patients with schizophrenia or unipolar depression. In addition, we reported three original case reports illustrating the efficacy and safety of tDCS: in a pregnant woman with bipolar depression, in a pregnant woman with post-traumatic stress disorder (sham tDCS), and in a breastfeeding woman with postpartum depression. Conclusions: The results are encouraging, making tES a potentially safe and effective treatment in the perinatal period. Larger studies are needed to confirm these initial results, and any adverse effects on the mother or child should be reported. In addition, research perspectives on the medico-economic benefits of tES, and its realization at home, are to be investigated in the future.