Survival without severe neonatal morbidity after antenatal betamethasone dose reduction: a post hoc analysis of a randomized non-inferiority trial.

BACKGROUND: Antenatal betamethasone is recommended before preterm delivery to accelerate fetal lung maturation. However, its optimal dose remains unknown. A 50% dose reduction was proposed to decrease the potential dose-related long-term neurodevelopmental side effects, including psychological development, sleep, and emotional disorders. Because noninferiority of the half dose in terms of the need for exogenous surfactant was not shown in the primary analysis, its impact on survival without major neonatal morbidity needs to be investigated. OBJECTIVE: This study aimed to investigate the impact of antenatal betamethasone dose reduction on survival of very preterm infants without severe neonatal morbidity, a factor known to have a strong correlation with long-term outcomes. STUDY DESIGN: We performed a post hoc secondary analysis of a randomized, multicenter, double-blind, placebo-controlled, noninferiority trial, testing half (11.4 mg once; n=1620) vs full (11.4 mg twice, 24 hours apart; n=1624) antenatal betamethasone doses in women at risk of preterm delivery. To measure survival without severe neonatal morbidity at hospital discharge among neonates born before 32 weeks of gestation, we used the definition of the French national prospective study on preterm children, EPIPAGE 2, comprising 1 of the following morbidities: grade 3 to 4 intraventricular hemorrhage, cystic periventricular leukomalacia, necrotizing enterocolitis stage ≥2, retinopathy of prematurity requiring anti-vascular endothelial growth factor therapy or laser, and moderate-to-severe bronchopulmonary dysplasia. RESULTS: After exclusion of women who withdrew consent or had pregnancy termination and of participants lost to follow-up (8 in the half-dose and 10 in the full-dose group), the rate of survival without severe neonatal morbidity among neonates born before 32 weeks of gestation was 300 of 451 (66.5%) and 304 of 462 (65.8%) in the half-dose and full-dose group, respectively (risk difference, +0.7%; 95% confidence interval, -5.6 to +7.1). There were no significant between-group differences in the cumulative number of neonatal morbidities. Results were similar when using 2 other internationally recognized definitions of severe neonatal morbidity and when considering the overall population recruited in the trial. CONCLUSION: In the BETADOSE trial, severe morbidity at discharge of newborns delivered before 32 weeks of gestation was found to be similar among those exposed to 11.4-mg and 22.8-mg antenatal betamethasone. Additional studies are needed to confirm these findings.

Tailoring a specific medical leadership development program for faculty members: the Lyon-Ottawa experience.

The development of leadership skills has been the topic of several position statements over recent decades, and the need of medical leaders for a specific training was emphasized during the COVID-19 crisis, to enable them to adequately collaborate with governments, populations, civic society, organizations, and universities. However, differences persist as to the way such skills are taught, at which step of training, and to whom. From these observations and building on previous experience at the University of Ottawa, a team of medical professors from Lyon (France), Ottawa, and Montreal (Canada) universities decided to develop a specific medical leadership training program dedicated to faculty members taking on leadership responsibilities. This pilot training program was based on a holistic vision of a transformation model for leadership development, the underlying principle of which is that leaders are trained by leaders. All contributors were eminent French and Canadian stakeholders. The model was adapted to French faculty members, following an inner and outer analysis of their specific needs, both contextual and related to their time constraints. This pilot program, which included 10 faculty members from Lyon, was selected to favor interactivity and confidence in older to favor long-term collaborations between them and contribute to institutional changes from the inner; it combined several educational methods mixing interactive plenary sessions and simulation exercises during onescholar year. All the participants completed the program and expressed global satisfaction with it, validating its acceptability by the target. Future work will aim to develop the program, integrate evaluation criteria, and transform it into a graduating training.

Live birth rate after cervicoisthmic cerclage in patients with previous late miscarriage and/or premature delivery.

OBJECTIVE: This study assesses the effectiveness of cervicoisthmic cerclage on the live birth rate, measured before and after performing this cerclage in a series of 62 patients with a history of late miscarriage and/or premature delivery. STUDY DESIGN: All patients who underwent cervicoisthmic cerclage in one of the 3 university hospitals of the Hospices Civils de Lyon, between January 1, 2010, and April 1, 2019, and with a history of at least one late miscarriage or spontaneous premature birth, were included. Obstetrical and neonatal data for all pregnancies before and after cervicoisthmic cerclage were collected from medical records, completed by a phone call to patients in case of missing data. RESULTS: We included 62 patients with a total of 224 pregnancies before and 95 pregnancies after cervicoisthmic cerclage. Forty-one (66%) cerclages were performed vaginally, 12 (19%) by laparotomy and 9 (15%) by laparoscopy. The live birth rate among all pregnancies evolving beyond 14 weeks was 23% before and 86% after cerclage (p < 0.01). The rate of delivery beyond 32 weeks was 13% before and 81% after cerclage, with a median term of delivery of 21 weeks and 37 weeks respectively. Twenty-two (35%) patients had at least one live birth before cerclage and 43 (69%) patients after cerclage. Five (8%) postoperative complications occurred (2 grade I, 2 grade II and 1 grade III). CONCLUSION: The markedly high live birth rate when compared to before the cerclage strongly suggests a major role for the technique of cervicoisthmic cerclage in patients with a heavy obstetrical history.

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.

Minimum evidence-based care in intrauterine growth-restricted fetuses and neonatal prognosis.

BACKGROUND: Introduction: There is clear evidence that fetuses with intrauterine growth restriction (IUGR) do not receive the minimum evidence-based care during their antenatal management. OBJECTIVE: Considering that optimal management of IUGR may reduce neonatal morbi-mortality in IUGR, the objective of the present study was to evaluate the impact of antenatal management of IUGR according to the recommendations of the French college of gynecologists and obstetricians (CNGOF) on the neonatal prognosis of IUGR fetuses. STUDY DESIGN: From a historical cohort of 31,052 children, born at the Femme Mère Enfant hospital (Lyon, France) between January 1, 2011 and December 31, 2017, we selected the population of IUGR fetuses. The minimum evidence-based care (MEC) in the antenatal management of fetuses with IUGR was defined according to the CNGOF recommendations and neonatal prognosis of early and late IUGR fetuses were assessed based on the whether or not they received MEC. The neonatal prognosis was defined according to a composite criterion that included neonatal morbidity and mortality. RESULTS: A total of 1020 fetuses with IUGR were studied. The application of MEC showed an improvement in the neonatal prognosis of early-onset IUGR (p = 0.003), and an improvement in the neonatal prognosis of IUGR born before 32 weeks (p = 0.030). Multivariate analysis confirmed the results showing an increase in neonatal morbi-mortality in early-onset IUGR in the absence of MEC with OR 1.79 (95% CI 1.01-3.19). CONCLUSION: Diagnosed IUGR with MEC had a better neonatal prognosis when born before 32 weeks. Regardless of the birth term, MEC improved the neonatal prognosis of fetuses with early IUGR. Improvement in the rate of MEC during antenatal management has a significant impact on neonatal prognosis.

Fetal growth restriction: underdiagnosed condition with non-optimal screening.

BACKGROUND: Fetal Growth restriction (FGR) is the pathological failure of a fetus to reach its biologically determined growth potential. Detection of FGR fetuses is a universally agreed key objective of antenatal care. Antenatal detection of FGR has undeniable benefits, juggling between intensive fetal surveillance and optimized timing of delivery; it reduces adverse perinatal outcomes by up to four-fold. However, FGR is still widely underdiagnosed. We aimed to identify the prevalence of FGR diagnosis in our wards and study the impact of the 2013 published French guidelines on the detection rate of FGR. The secondary objective aimed to highlight the factors of suboptimal screening in the population of non-diagnosed FGR fetuses and emphasize the screening method that led to antenatal diagnosis of FGR. MATERIALS AND METHODS: We conducted a retrospective study at a single tertiary maternity center in Lyon-France, the Femme Mère Enfant Hospital, including the exhaustive population of FGR born after 24 + 0 weeks of gestation from 1 January 2011 to 31 December 2017. FGR was defined combining the neonatal and antenatal consensus-based definitions for early and late FGR in absence of congenital anomalies, excluding small for gestational age fetuses. For all FGR fetuses, we compared the antenatal detection rate of FGR during 2011-2013 to 2015-2017, since the French guidelines were published in December 2013. When FGR fetuses underwent an antenatal diagnosis of FGR, we retrospectively collected the characteristics that led to the diagnosis. When fetuses were not diagnosed as FGR, we retrospectively reviewed the implementation of the recommended screening method, enabling to evaluate whether screening was optimal or not. Statistical analysis was performed in July 2018, and statistical significance was regarded as a p-value <.05. RESULTS: Over the seven-year period, and among 31,052 newborns, 1020 (3.3%) infants were identified as FGR and met the inclusion criteria. The detection rate of FGR was similar before and after publication of the French Guidelines related to FGR in 2013. Indeed, 50.8% (201/395) FGR were diagnosed between 2011 and 2013 versus 52.6% (245/465) between 2015 and 2017 (p = .59). In the population of non-diagnosed FGR infants, screening was suboptimal in 80%. Symphysis-fundal height (SFH) was not measured in 10.7%, with no difference before and after 2014 (7.3 versus 11.8% p = .11). Ultrasound examination for fetal biometry had not been prescribed in spite of abnormal SFH in 47.7% of undiagnosed FGR infants. Diagnosis has been missed in 11.5% of infants because of misinterpretation of the estimated fetal weight's centile. CONCLUSION: FGR is widely underdiagnosed. However, the limited performances can partially be explained by the regular misuse of screening method in clinical practice. Despite the systematic third trimester ultrasound screening, the detection rate of FGR was similar to the one reported in the medical literature. The timing of routine third trimester ultrasound in low-risk women may be rethought.

Characteristics of the delayed respiratory syncytial virus epidemic, 2020/2021, Rhône Loire, France.

The Rhône-Loire metropolitan areas' 2020/21 respiratory syncytial virus (RSV) epidemic was delayed following the implementation of non-pharmaceutical interventions (NPI), compared with previous seasons. Very severe lower respiratory tract infection incidence among infants ≤ 3 months decreased twofold, the proportion of cases among children aged > 3 months to 5 years increased, and cases among adults > 65 years were markedly reduced. NPI appeared to reduce the RSV burden among at-risk groups, and should be promoted to minimise impact of future RSV outbreaks.

Standardized healthcare pathway in intrauterine growth restriction and minimum evidence-based care.

INTRODUCTION: Fetal growth restricted fetuses are less likely to receive evidence-based care; a previous work demonstrated an improvement in neonatal prognosis when fetuses with intrauterine growth restriction (IUGR) received minimum evidence based-care. OBJECTIVE: The objective of the study was to evaluate the impact of a standardized healthcare pathway on the implementation of the recommended clinical practice in the antenatal management of IUGR fetuses, in comparison to a traditional pathway. The quality of the implementation of practice has been defined whether or not minimum evidence-based care (MEC), defined according to the recommendations of the French college of gynecologists and obstetricians (CNGOF), has been implemented. STUDY DESIGN: From a historical cohort of 31,052 children, born at the Femme Mère Enfant Hospital (Lyon, France) between January 1st, 2011 and December 31st, 2017, we selected the population of IUGR fetuses. We compared the rate of MEC between the IUGR fetuses followed-up in the traditional healthcare pathway versus the IUGR fetuses followed-up in a standardized healthcare pathway between 2015 and 2017. RESULTS: A total of 245 IUGR were tracked between 2015 and 2017. Over this period, 120 fetuses were followed within the traditional pathway and 125 within the IUGR pathway. The standardized pathway resulted in a higher rate of MEC (86,4%) when compared to IUGR fetuses followed-up in the traditional pathway (27,5% (OR* 20 (95 % CI 10.0-39.7). Among early-onset IUGR: 31 % received MEC in the traditional pathway versus 83 % in the standardized pathway (p<0.001). Among late-onset IUGR: 22 % received MEC in the traditional pathway versus 92 % in the standardized pathway (p<0.001). The provided care in the standardized pathway resulted in an increase of complete antenatal corticosteroid therapy (92,8 %) when compared to the traditional pathway (50.0 %; p<0.001) and a reduction of the rate of caesarean sections before labor for non-reassuring fetal heart rate (15 %) when compared to the traditional pathway (41.3 % p=0.007). CONCLUSION: The standardized pathway improves the implementation of the local recommendations in the management of early- and late-onset IUGR. This study is the first to suggest a standardized care pathway in prenatal medicine. A medico-economic study could estimate the health care savings that such a pathway would provide by allowing a medical management in accordance with the recommendations.

A Framework Proposal for Quality and Safety Measurement in Gynecologic Emergency Care.

OBJECTIVE: To define and assess the prevalence of potentially life-threatening gynecologic emergencies among women presenting for acute pelvic pain for the purpose of developing measures to audit quality of care in emergency departments. METHODS: We conducted a mixed-methods multicenter study at gynecologic emergency departments in France and Belgium. A modified Delphi procedure was first conducted in 2014 among health care professionals to define relevant combinations of potentially life-threatening conditions and near misses in the field of gynecologic emergency care. A prospective case-cohort study in the spring of 2015 then assessed the prevalence of these potentially life-threatening emergencies and near misses among women of reproductive age presenting for acute pelvic pain. Women in the case group were identified at 21 participating centers. The control group consisted of a sample of women hospitalized for acute pelvic pain not caused by a potentially life-threatening condition and a 10% random sample of outpatients. RESULTS: Eight gynecologic emergencies and 17 criteria for near misses were identified using the Delphi procedure. Among the 3,825 women who presented for acute pelvic pain, 130 (3%) were considered to have a potentially life-threatening condition. The most common diagnoses were ectopic pregnancies with severe bleeding (n=54; 42%), complex pelvic inflammatory disease (n=30; 23%), adnexal torsion (n=20; 15%), hemorrhagic miscarriage (n=15; 12%), and severe appendicitis (n=6; 5%). The control group comprised 225 hospitalized women and 381 outpatients. Diagnostic errors occurred more frequently among women with potentially life-threatening emergencies than among either hospitalized (odds ratio [OR] 1.7, 95% CI 1.1-2.7) or outpatient (OR 14.7, 95% CI 8.1-26.8) women in the control group. Of the women with potentially life-threatening conditions, 26 met near-miss criteria compared with six with not potentially life-threatening conditions (OR 25.6, 95% CI 10.9-70.7). CONCLUSIONS: Potentially life-threatening gynecologic emergencies are high-risk conditions that may serve as a useful framework to improve quality and safety in emergency care.

Rationale and design of ePPOP-ID: a multicenter randomized controlled trial using an electronic-personalized program for obesity in pregnancy to improve delivery.

BACKGROUND: Pre-pregnancy obesity and excessive gestational weight gain (GWG) are established risk factors for adverse pregnancy, delivery and birth outcomes. Pregnancy is an ideal moment for nutritional interventions in order to establish healthier lifestyle behaviors in women at high risk of obstetric and neonatal complications. METHODS: Electronic-Personalized Program for Obesity during Pregnancy to Improve Delivery (ePPOP-ID) is an open multicenter randomized controlled trial which will assess the efficacy of an e-health web-based platform offering a personalized lifestyle program to obese pregnant women in order to reduce the rate of labor procedures and delivery interventions in comparison to standard care. A total of 860 eligible pregnant women will be recruited in 18 centers in France between 12 and 22 weeks of gestation, randomized into the intervention or the control arm and followed until 10 weeks of postpartum. The intervention is based on nutrition, eating behavior, physical activity, motivation and well-being advices in which personalization is central, as well as the use of a mobile/tablet application. Inputs includes data from the medical record of participants (medical history, anthropometric data), from the web platform (questionnaires on dietary habits, eating behavior, physical activity and motivation in both groups), and adherence to the program (time of connection for the intervention group only). Data are collected at inclusion, 32 weeks, delivery and 10 weeks postpartum. As primary outcome, we will use a composite endpoint score of obstetrical interventions during labor and delivery, defined as caesarean section and instrumental delivery (forceps and vacuum extractor). Secondary outcomes will consist of data routinely collected as part of usual antenatal and perinatal care, such as GWG, hypertension, preeclampsia, as well as fetal and neonatal outcomes including premature birth, gestational age at birth, birth weight, macrosomia, Apgar score, arterial umbilical cord pH, neonatal traumatism, hyperbilirubinemia, respiratory distress syndrome, transfer in neonatal intensive care unit, and neonatal adiposity. Post-natal outcomes will be duration of breastfeeding, maternal weight retention and child weight at postnatal visit. DISCUSSION: The findings of the ePPOP-ID trial will help design e-health intervention program for obese women in pregnancy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02924636 / October 5th 2016.

Pregnancy-related thrombosis risk in patients with protein C deficiency and comparison with pregnant women with heterozygous factor V Leiden mutation.

: The risk of pregnancy-related venous thromboembolism is high in patients with inherited thrombophilia. The aim of this study was to compare the risk of pregnancy related-venous thromboembolism of women with protein C (PC) deficiency to patients with heterozygous factor V Leiden mutation. 145 consecutive pregnant women with confirmed PC deficiency or heterozygous factor V Leiden mutation were prospectively enrolled in the study. Lyon venous thromboembolism-risk score was used to individually tailor antithrombotic prophylaxis. The use of a validated clinical score presents the advantage to have a homogenous management of the venous thromboembolism risk in patients having similar risk factors. 53 pregnancies with PC deficiency were compared with 190 pregnancies in heterozygous factor V Leiden mutation carriers. 50% of the patients with PC deficiency and 64% of the heterozygous factor V Leiden mutation carriers were asymptomatic. According to the Lyon-venous thromboembolism risk score, 50% of patients with PC deficiency and 51% of heterozygous factor V Leiden carriers did not received any antepartum heparin prophylaxis. 34 and 37% of patients respectively received heparin prophylaxis during the third trimester only. No venous thromboembolism was observed in patients with PC deficiency and one postpartum venous thromboembolism occurred in a patient with heterozygous factor V Leiden. In the absence of randomized controlled clinical studies, we report here a large prospective series of pregnant women with PC deficiency. In our cohort, no difference of outcome, in terms of venous thromboembolism, was observed between pregnant women with PC deficiency and those with heterozygous factor V Leiden. Based on our results, low-molecular-weight heparin prophylaxis should not be mandatory in all pregnant women with PC deficiency. Similar prophylaxis strategies may be applied to women with factor V Leiden mutation or PC deficiency.

Identification of risk factors for postpartum urinary retention following vaginal deliveries: A retrospective case-control study.

OBJECTIVE: Postpartum urinary retention (PUR) is an uncommon complication of vaginal delivery, defined as a failure to void spontaneously in the six hours following vaginal birth. The objective of this study was to identify risk factors for PUR in order to provide prompt management. STUDY DESIGN: A retrospective, comparative, case-control study, including two groups of 96 patients who delivered vaginally, was conducted at the Women and Children's University Hospital in Lyon, France. Patients were selected based on data extraction from the medical records of the obstetrics and gynecology department. The first group included patients with postpartum urinary retention and the second group, without PUR, was selected randomly, respecting 1:1 matching criteria, paired according to the year of delivery and patient's age at delivery. RESULTS: Logistic regression analysis found that instrumental delivery (OR 13.42, 95%CI [3.34;53.86], p = 0.0002), absence of spontaneous voiding before leaving the delivery room (OR 6.14, 95%CI [2.56;14.73], p < 0.0001), no intact perineum (OR 3.29, 95%CI [1.10;9.90], p = 0.03) and vulvar edema or perineal hematoma (OR 8.05, 95%CI [1.59;40.67], p = 0.01) were independent risk factors associated with PUR. CONCLUSION: The present study identified risk factors for PUR that should be taken into consideration as soon as delivery is over in order to implement appropriate management. Future studies are needed to assess the contribution of early systematic bladder scanning in patients with risk factors for early diagnosis of PUR.

Preterm premature rupture of the membranes: Guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF).

In France, the frequency of premature rupture of the membranes (PROM) is 2%-3% before 37 weeks' gestation (level of evidence [LE] 2) and less than 1% before 34 weeks (LE2). Preterm delivery and intrauterine infection are the major complications of preterm PROM (PPROM) (LE2). Prolongation of the latency period is beneficial (LE2). Compared with other causes of preterm delivery, PPROM is associated with a clear excess risk of neonatal morbidity and mortality only in cases of intrauterine infection, which is linked to higher rates of in utero fetal death (LE3), early neonatal infection (LE2), and necrotizing enterocolitis (LE2). The diagnosis of PPROM is principally clinical (professional consensus). Tests to detect IGFBP-1 or PAMG-1 are recommended in cases of uncertainty (professional consensus). Hospitalization is recommended for women diagnosed with PPROM (professional consensus). Adequate evidence does not exist to support recommendations for or against initial tocolysis (Grade C). If tocolysis is prescribed, it should not continue longer than 48 h (Grade C). The administration of antenatal corticosteroids is recommended for fetuses with a gestational age less than 34 weeks (Grade A) and magnesium sulfate if delivery is imminent before 32 weeks (Grade A). The prescription of antibiotic prophylaxis at admission is recommended (Grade A) to reduce neonatal and maternal morbidity (LE1). Amoxicillin, third-generation cephalosporins, and erythromycin (professional consensus) can each be used individually or eythromycin and amoxicillin can be combined (professional consensus) for a period of 7 days (Grade C). Nonetheless, it is acceptable to stop antibiotic prophylaxis when the initial vaginal sample is negative (professional consensus). The following are not recommended for antibiotic prophylaxis: amoxicillin-clavulanic acid (professional consensus), aminoglycosides, glycopeptides, first- or second-generation cephalosporins, clindamycin, or metronidazole (professional consensus). Women who are clinically stable after at least 48 h of hospital monitoring can be managed at home (professional consensus). Monitoring should include checking for clinical and laboratory factors suggestive of intrauterine infection (professional consensus). No guidelines can be issued about the frequency of this monitoring (professional consensus). Adequate evidence does not exist to support a recommendation for or against the routine initiation of antibiotic therapy when the monitoring of an asymptomatic woman produces a single isolated positive result (e.g., elevated CRP, or hyperleukocytosis, or a positive vaginal sample) (professional consensus). In cases of intrauterine infection, the immediate intravenous administration (Grade B) of antibiotic therapy combining a beta-lactam with an aminoglycoside (Grade B) and early delivery of the child are both recommended (Grade A). Cesarean delivery of women with intrauterine infections is reserved for the standard obstetric indications (professional consensus). Expectant management is recommended for uncomplicated PROM before 37 weeks (Grade A), even when a sample is positive for Streptococcus B, as long as antibiotic prophylaxis begins at admission (professional consensus). Oxytocin and prostaglandins are two possible options for the induction of labor in women with PPROM (professional consensus).

Reference percentiles for paired arterial and venous umbilical cord blood gases: An indirect nonparametric approach.

BACKGROUND: Reference intervals for arterial and venous umbilical cord blood gas (UCBG) parameters are scarce, are mainly focused on pH, pO2, pCO2 and base deficit, and are usually assessed using parametric tests, despite a generally skewed data distribution. Here, the purpose is to determine reference percentiles for nine parameters of concomitant arterial and venous UCBG (CAV-UCBG) from neonates at birth, using nonparametric tests. METHODS: Results of CAV-UCBG, assayed over a 4.5-year period, were extracted from a hospital laboratory database for pH, pCO2, pO2, oxygen saturation, concentration of total oxygen, total carbon dioxide, hydrogen carbonate, total haemoglobin, and acid-base excess. Exclusion criteria were: a venous-arterial pH difference <0.02, an arterial-venous pCO2 <0.7 kPa, and a venous pCO2 <2.9 kPa. Nonparametric bivariate kernel density estimations were used for the selection of plots within the 95% percentile surface of the pCO2-to-pH relationship (NBKDE-95P). Outliers from skewed data were removed using an adjusted-Tukey method, and percentiles were calculated according to the CLSI EP28-A3 nonparametric method. RESULTS: Overall, 31% (5033/16164) of CAV-UCBG were discarded using the three exclusion criteria. Then, 6% (670/11131) of CAV-UCBG were excluded from the NBKDE-95P, and 0.1 to 3.5% outliers were subsequently removed. Depending on the parameter, the 2.5th and 97.5th percentiles from the whole group were similar or slightly narrower compared to reference intervals from other studies, while those from female and male neonates did not differ substantially. CONCLUSIONS: Using an indirect nonparametric approach, this study proposes new percentiles for parameters from concomitant arterial and venous umbilical cord blood gases.

[Aspirin and preeclampsia]. / Aspirine et prééclampsie.

Indications for aspirin during pregnancy are a matter of debate and there is a recent trend to an extended prescription and an overuse of aspirin in pregnancy. Aspirin is efficient in secondary prevention of preeclampsia essentially in patients with a personal history of preeclampsia. The effect of aspirin on platelet aggregation and on the TXA2/PGI2 balance is dose-dependent. The optimum dosage, from 75mg/day to 150mg/day, needs to be determined. Fetal safety data at 150mg/day are still limited. The efficacy of aspirin seems to be subject to a chronobiological effect. It is recommended to prescribe an evening or bedtime intake. Aspirin, in primary prevention of preeclampsia, given to high-risk patients identified in the first trimester by screening tests, seems to reduce the occurrence of early-onset preeclampsia. Nevertheless, there are insufficient data for the implementation of such screening procedures in practice.

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

BACKGROUND: The use of tranexamic acid reduces mortality due to postpartum hemorrhage. We investigated whether the prophylactic administration of tranexamic acid in addition to prophylactic oxytocin in women with vaginal delivery would decrease the incidence of postpartum hemorrhage. METHODS: In a multicenter, double-blind, randomized, controlled trial, we randomly assigned women in labor who had a planned vaginal delivery of a singleton live fetus at 35 or more weeks of gestation to receive 1 g of tranexamic acid or placebo, administered intravenously, in addition to prophylactic oxytocin after delivery. The primary outcome was postpartum hemorrhage, defined as blood loss of at least 500 ml, measured with a collector bag. RESULTS: Of the 4079 women who underwent randomization, 3891 had a vaginal delivery. The primary outcome occurred in 156 of 1921 women (8.1%) in the tranexamic acid group and in 188 of 1918 (9.8%) in the placebo group (relative risk, 0.83; 95% confidence interval [CI], 0.68 to 1.01; P=0.07). Women in the tranexamic acid group had a lower rate of provider-assessed clinically significant postpartum hemorrhage than those in the placebo group (7.8% vs. 10.4%; relative risk, 0.74; 95% CI, 0.61 to 0.91; P=0.004; P=0.04 after adjustment for multiple comparisons post hoc) and also received additional uterotonic agents less often (7.2% vs. 9.7%; relative risk, 0.75; 95% CI, 0.61 to 0.92; P=0.006; adjusted P=0.04). Other secondary outcomes did not differ significantly between the two groups. The incidence of thromboembolic events in the 3 months after delivery did not differ significantly between the tranexamic acid group and the placebo group (0.1% and 0.2%, respectively; relative risk, 0.25; 95% CI, 0.03 to 2.24). CONCLUSIONS: Among women with vaginal delivery who received prophylactic oxytocin, the use of tranexamic acid did not result in a rate of postpartum hemorrhage of at least 500 ml that was significantly lower than the rate with placebo. (Funded by the French Ministry of Health; TRAAP ClinicalTrials.gov number, NCT02302456 .).