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.

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.).

Closed- or open-glottis pushing for vaginal delivery: a planned secondary analysis of the TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery study.

BACKGROUND: The effect on obstetrical outcomes of closed- or open-glottis pushing is uncertain among both nulliparous and parous women. OBJECTIVE: This study aimed to assess the association between open- or closed-glottis pushing and mode of delivery after an attempted singleton vaginal birth at or near term. STUDY DESIGN: This was an ancillary planned cohort study of the TRAAP (TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery) randomized controlled trial, conducted in 15 French maternity units from 2015 to 2016 that enrolled women with an attempted singleton vaginal delivery after 35 weeks' gestation. After randomization, characteristics of labor and delivery were prospectively collected, with special attention to active second-stage pushing and a specific planned questionnaire completed immediately after birth by the attending care provider. The exposure was the mode of pushing, classified into 2 groups: closed- or open-glottis. The main endpoint was operative vaginal delivery. Secondary endpoints were items of maternal morbidity, including severe perineal laceration, episiotomy, postpartum hemorrhage, duration of the second stage of labor, and a composite severe neonatal morbidity outcome. We also assessed immediate maternal satisfaction, experience of delivery, and psychological status 2 months after delivery. The associations between mode of pushing and outcome were analyzed by multivariate logistic regression to control for confounding bias, with multilevel mixed-effects analysis, and a random intercept for center. RESULTS: Among 3041 women included in our main analysis, 2463 (81.0%) used closed-glottis pushing and 578 (19.0%) open-glottis pushing; their respective operative vaginal delivery rates were 19.1% (n=471; 95% confidence interval, 17.6-20.7) and 12.5% (n=72; 95% confidence interval, 9.9-15.4; P<.001). In an analysis stratified according to parity and after controlling for available confounders, the rate of operative vaginal delivery did not differ between the groups among nulliparous women: 28.7% (n=399) for the closed-glottis and 27.5% (n=64) for the open-glottis group (adjusted odds ratio, 0.93; 95% confidence interval, 0.65-1.33; P=.7). The operative vaginal delivery rate was significantly lower for women using open- compared with closed-glottis pushing in the parous population: 2.3% (n=8) for the open- and 6.7% (n=72) for the closed-glottis groups (adjusted odds ratio, 0.43; 95% confidence interval, 0.19-0.90; P=.03). Other maternal and neonatal outcomes did not differ between the 2 modes of pushing among either the nulliparous or parous groups. CONCLUSION: Among nulliparous women with singleton pregnancies at term, the risk of operative vaginal birth did not differ according to mode of pushing. These results will inform shared decision-making about the mode of pushing during the second stage of labor.

Validity of a Delphi consensus definition of growth restriction in the newborn for identifying neonatal morbidity.

BACKGROUND: Small for gestational age is defined as a birthweight below a birthweight percentile threshold, usually the 10th percentile, with the third or fifth percentile used to identify severe small for gestational age. Small for gestational age is used as a proxy for growth restriction in the newborn, but small-for-gestational-age newborns can be physiologically small and healthy. In addition, this definition excludes growth-restricted newborns who have weights more than the 10th percentile. To address these limits, a Delphi study developed a new consensus definition of growth restriction in newborns on the basis of neonatal anthropometric and clinical parameters, but it has not been evaluated. OBJECTIVE: To assess the prevalence of growth restriction in the newborn according to the Delphi consensus definition and to investigate associated morbidity risks compared with definitions of Small for gestational age using birthweight percentile thresholds. STUDY DESIGN: Data come from the 2016 and 2021 French National Perinatal Surveys, which include all births ≥22 weeks and/or with birthweights ≥500 g in all maternity units in France over 1 week. Data are collected from medical records and interviews with mothers after the delivery. The study population included 23,897 liveborn singleton births. The Delphi consensus definition of growth restriction was birthweight less than third percentile or at least 3 of the following criteria: birthweight, head circumference or length <10th percentile, antenatal diagnosis of growth restriction, or maternal hypertension. A composite of neonatal morbidity at birth, defined as 5-minute Apgar score <7, cord arterial pH <7.10, resuscitation and/or neonatal admission, was compared using the Delphi definition and usual birthweight percentile thresholds for defining small for gestational age using the following birthweight percentile groups: less than a third, third to fourth, and fifth to ninth percentiles. Relative risks were adjusted for maternal characteristics (age, parity, body mass index, smoking, educational level, preexisting hypertension and diabetes, and study year) and then for the consensus definition and birthweight percentile groups. Multiple imputation by chained equations was used to impute missing data. Analyses were carried out in the overall sample and among term and preterm newborns separately. RESULTS: We identified that 4.9% (95% confidence intervals, 4.6-5.2) of newborns had growth restriction. Of these infants, 29.7% experienced morbidity, yielding an adjusted relative risk of 2.5 (95% confidence intervals, 2.2-2.7) compared with newborns without growth restriction. Compared with birthweight ≥10th percentile, morbidity risks were higher for low birthweight percentiles (less than third percentile: adjusted relative risk, 3.3 [95% confidence intervals, 3.0-3.7]; third to fourth percentile: relative risk, 1.4 [95% confidence intervals, 1.1-1.7]; fifth to ninth percentile: relative risk, 1.4 [95% confidence intervals, 1.2-1.6]). In adjusted models including the definition of growth restriction and birthweight percentile groups and excluding birthweights less than third percentile, which are included in both definitions, morbidity risks remained higher for birthweights at the third to fourth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.1-1.7]) and fifth to ninth percentile (adjusted relative risk, 1.4 [95% confidence intervals, 1.2-1.6]), but not for the Delphi definition of growth restriction (adjusted relative risk, 0.9 [95% confidence intervals, 0.7-1.2]). Similar patterns were found for term and preterm newborns. CONCLUSION: The Delphi consensus definition of growth restriction did not identify more newborns with morbidity than definitions of small for gestational age on the basis of birthweight percentiles. These findings illustrate the importance of evaluating the results of Delphi consensus studies before their adoption in clinical practice.

Re-evaluating fetal scalp pH thresholds: An examination of fetal pH variations during labor.

INTRODUCTION: Since the 1970s, fetal scalp blood sampling (FSBS) has been used as a second-line test of the acid-base status of the fetus to evaluate fetal well-being during labor. The commonly employed thresholds that delineate normal pH (>7.25), subnormal (7.20-7.25), and pathological pH (<7.20) guide clinical decisions. However, these experienced-based thresholds, based on observations and common sense, have yet to be confirmed. The aim of the study was to investigate if pH drop rate accelerates at the common thresholds (7.25 and 7.20) and to explore the possibility of identifying more accurate thresholds. MATERIAL AND METHODS: A retrospective study was conducted at a tertiary maternity hospital between June 2017 and July 2021. Patients with at least one FSBS during labor for category II fetal heart rate and delivery of a singleton cephalic infant were included. The rate of change in pH value between consecutive samples for each patient was calculated and plotted as a function of pH value. Linear regression models were used to model the evolution of the pH drop rate estimating slope and standard errors across predefined pH intervals. Exploration of alternative pH action thresholds was conducted. To explore the independence of the association between pH value and pH drop rate, multiple linear regression adjusted on age, body mass index, parity, oxytocin stimulation and suspected small for gestational age was performed. RESULTS: We included 2047 patients with at least one FSBS (total FSBS 3467); with 2047 umbilical cord blood pH, and a total of 5514 pH samples. Median pH values were 7.29 1 h before delivery, 7.26 30 min before delivery. The pH drop was slow between 7.40 and 7.30, then became more pronounced, with median rates of 0.0005 units/min at 7.25 and 0.0013 units/min at 7.20. Out of the alternative pH thresholds, 7.26 and 7.20 demonstrated the best alignment with our dataset. Multiple linear regression revealed that only pH value was significantly associated to the rate of pH change. CONCLUSIONS: Our study confirms the validity and reliability of current guideline thresholds for fetal scalp pH in category II fetal heart rate.

Moderate or intensive management of the active phase of second-stage labor and risk of urinary and anal incontinence: results of the PASST randomized controlled trial.

BACKGROUND: Incontinence occurs frequently in the postpartum period. Several theoretical pathophysiological models may underlie the hypothesis that different types of management of the active phase of the second stage of labor have different effects on pelvic floor muscles and thus perhaps affect urinary and anal continence. OBJECTIVE: This study aimed to evaluate the impact of "moderate pushing" on the occurrence of urinary or anal incontinence compared with "intensive pushing," and to determine the factors associated with incontinence at 6 months postpartum. STUDY DESIGN: This was a planned analysis of secondary objectives of the PASST (Phase Active du Second STade) trial, a multicenter randomized controlled trial. PASST included nulliparous women with singleton term pregnancies and epidural analgesia, who were randomly assigned at 8 cm of dilatation to either the intervention group that used "moderate" pushing (pushing only twice during each contraction, resting regularly for 1 contraction in 5 without pushing, and no time limit on pushing) or the control group following the usual management of "intensive" pushing (pushing 3 times during each contraction, with no contractions without pushing, with an obstetrician called to discuss operative delivery after 30 minutes of pushing). Data about continence were collected with validated self-assessment questionnaires at 6 months postpartum. Urinary incontinence was defined by an ICIQ-UI SF (International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form) score ≥1 and anal incontinence by a Wexner score ≥2. A separate analysis was also performed among the more severely affected women (ICIQ-UI SF ≥6 and Wexner ≥5). Factors associated with incontinence were assessed with univariate and multivariable analyses. RESULTS: Among 1618 women initially randomized, 890 (55%) returned the complete questionnaire at 6 months. The rate of urinary incontinence was 36.6% in the "moderate" pushing group vs 38.5% in the "intensive" pushing group (relative risk, 0.95; 95% confidence interval, 0.80-1.13), whereas the rate of anal incontinence was 32.2% vs 34.6% (relative risk, 0.93; 95% confidence interval, 0.77-1.12). None of the obstetrical factors studied related to the second stage of labor influenced the occurrence of urinary or anal incontinence, except operative vaginal delivery, which increased the risk of anal incontinence (adjusted odds ratio, 1.50; 95% confidence interval, 1.04-2.15). CONCLUSION: The results of the PASST trial indicate that neither moderate nor intensive pushing efforts affect the risk of urinary or anal incontinence at 6 months postpartum among women who gave birth under epidural analgesia.

Influence of the maternity unit and region of delivery on episiotomy practice in France: a nationwide population-based study.

INTRODUCTION: Our objective was to identify factors associated with episiotomy practice in France, in particular, characteristics of the maternity units and regions of delivery. MATERIAL AND METHODS: We performed a national cross-sectional population-based study in all French maternity units in 2016 including 9284 women with vaginal delivery. Our outcome was the performance of an episiotomy. After stratification for parity, associations of episiotomy practice with individual and organizational characteristics and the region of delivery were estimated with multilevel logistic regression models. The variability in maternity unit episiotomy rates explained by the characteristics studied was estimated by the proportional change in variance. RESULTS: A total of 19.9% of the women had an episiotomy. The principal factors associated with episiotomy practice were maternal and obstetric and delivery in a maternity unit with <2000 annual deliveries. After adjusting for individual, obstetric and organizational characteristics, the practice of episiotomy was strongly associated with women's region of delivery. Additionally, women's individual characteristics did not explain the significant variability in episiotomy rates between maternity units (P < 0.001) but maternity unit characteristics partly did (proportion of variance explained: 7.2% for primiparas and 13.6% for multiparas) and regional differences still more (18% and 30.7%, respectively). CONCLUSIONS: Episiotomy practices in France in 2016 varied strongly between maternity units, largely due to regional differences. Targeted actions by the regional perinatal care networks may reduce the national episiotomy rate and standardize practices.

Gestational weight gain adequacy and intrapartum oxytocin and cesarean section use: Observational population-based study in France.

INTRODUCTION: Research on maternal prepregnancy weight suggests adiposity is associated with dysfunctional labor, but knowledge about how gestational weight gain (GWG) affects labor is sparse. Our objective was to evaluate associations between GWG adequacy and intrapartum obstetric interventions (oxytocin administration; cesarean section) necessitated by labor dysfunction. MATERIAL AND METHODS: Using national, population-based French National Perinatal Survey 2016 data, we included term cephalic singleton pregnancies involving trial of labor (n = 9724). For the intrapartum oxytocin administration analysis, we included only women with spontaneous labor (n = 7352). GWG was calculated as the difference between end of pregnancy and prepregnancy weight (both self-reported) and categorized as insufficient, adequate (reference group), or excessive by prepregnancy body mass index (BMI; underweight <18.5, normal weight 18.5-24.9, overweight 25-29.9, obese ≥30 kg/m2 ) using the 2009 Institute of Medicine thresholds. Multilevel generalized estimating equation logistic regression models, unadjusted and adjusted for a priori confounders, evaluated intervention-GWG adequacy associations within BMI categories (under/normal weight combined), stratified by parity (primiparas; multiparas). RESULTS: GWG adequacy was associated with oxytocin use among under/normal weight women (primiparas: insufficient 57.3%, adequate 60.8%, excessive 65.0%, p = 0.014; multiparas: insufficient 27.2%, adequate 29.1%, excessive 36.2%, p < 0.001) and overweight primiparas (insufficient 56.0%, adequate 58.7%, excessive 72.5%, p = 0.002). In unadjusted and adjusted models, trends of increased odds of oxytocin administration among women with excessive GWG were found regardless of parity and prepregnancy BMI. Similarly, among under/normal weight women, GWG adequacy was associated with intrapartum cesarean section (primiparas: insufficient 10.7%, adequate 12.7%, excessive 15.3%, p = 0.014; multiparas: insufficient 3.1%, adequate 3.5%, excessive 6.3%, p < 0.001) with increased cesarean section among multiparas with excessive GWG persisting in adjusted models (adjusted odds ratio 1.9, 95% confidence interval 1.3-2.7). However, intrapartum cesarean section was reduced among multiparas with overweight and obese prepregnancy BMI and excessive GWG. CONCLUSIONS: Excessive GWG was associated with intrapartum oxytocin administration, regardless of parity or prepregnancy BMI, and cesarean section among women with under/normal weight prepregnancy BMI, providing evidence for benefits of healthy GWG for normal labor progression. Additional research is needed to verify our findings and understand differences by BMI.

Preferences for labor and childbirth, expressed orally or as a written birth plan: Prevalence and determinants from a nationwide population-based study.

BACKGROUND: Shared decision-making is an important component of a patient-centered healthcare system. We assessed the prevalence of parturients with preferences for their labor and childbirth, expressed verbally in the birthing room or as a written birth plan, and studied maternal, obstetric, and organizational factors associated with their expression. METHODS: Data came from the 2016 National Perinatal Survey, a cross-sectional nationwide population-based survey conducted in France. Preferences for labor and childbirth were studied in three categories: expressed verbally, in writing (birth plan), or unexpressed or nonexistent. Analyses used multinomial multilevel logistic regression. RESULTS: The analysis included 11,633 parturients: 3.7% had written a birth plan, 17.3% expressed their preferences verbally, and 79.0% either did not have or did not express any preferences. Compared with the latter group, written or verbal preferences were both significantly associated with prenatal care by independent midwives (respectively, adjusted odds ratio (aOR) 2.19; 95% confidence interval (CI), [1.59-3.03], and aOR 1.43; 95% CI [1.19-1.71]) and with attendance at childbirth education classes (respectively, aOR 4.99; 95% CI [3.49-7.15], and aOR 2.27; 95% CI [1.98-2.62]). As years in traditional schooling increased, so did its association with preferences. Conversely, parturients from African countries were significantly less likely than French mothers to express preferences. A written birth plan was also associated with characteristics of maternity unit organization. CONCLUSION: Only one in five parturients reported having expressed preferences for labor and childbirth to healthcare professionals in the birthing room. This expression of preferences was associated with maternal characteristics and the organization of care.

Gestational weight gain adequacy among twin pregnancies in France.

The objective of this paper is to describe gestational weight gain (GWG), to assess the applicability of the 2009 Institute of Medicine (IOM) guidelines, and to derive a GWG adequacy classification within a French cohort. We included twins from the national, prospective, population-based JUmeaux MODe d'Accouchement (JUMODA) cohort study (2014-2015). Following the IOM approach, we selected a 'standard' population of term pregnancies with 'optimal' birthweight (≥2500 g; n = 2562). GWG adequacy (insufficient; adequate; excessive) was defined using IOM recommendations (normal body mass index [BMI]: 16.8-24.5 kg [also utilized for underweight BMI]; overweight: 14.1-22.7 kg; obese: 11.4-19.1 kg). Additionally, using the IOM approach, we determined the 25th and 75th percentiles of GWG in our standard population to create a JUMODA-derived GWG adequacy classification. GWG and GWG adequacy were described, overall and by BMI and parity. In the JUMODA standard population of term twin livebirths with optimal birthweight, mean GWG was 16.1 kg (standard deviation 6.3). Using IOM recommendations, almost half (46.5%) of the women had insufficient and few (10.0%) had excessive GWG, with similar results regardless of BMI or parity. The 25th and 75th percentiles of GWG in the JUMODA standard population (underweight: 13-21 kg; normal weight: 13-20 kg; overweight: 11-19 kg; obese: 7-16 kg) were lower than the IOM recommendations. The IOM recommendations classified a relatively high percentage of French women as having insufficient and a low percentage as having excessive GWG. Additional research to evaluate recommendations in relation to adverse perinatal outcomes is needed to determine whether the IOM recommendations or the JUMODA-derived classification is more appropriate for French twin gestations.

Alternative to intensive management of the active phase of the second stage of labor: a multicenter randomized trial (Phase Active du Second STade trial) among nulliparous women with an epidural.

BACKGROUND: There is no consensus on an optimal strategy for managing the active phase of the second stage of labor. Intensive pushing could not only reduce pushing duration, but also increase abnormal fetal heart rate because of cord compression and reduced placental perfusion and oxygenation resulting from the combination of uterine contractions and maternal expulsive forces. Therefore, it may increase the risk of neonatal acidosis and the need for operative vaginal delivery. OBJECTIVE: This study aimed to assess the effect of the management encouraging "moderate" pushing vs "intensive" pushing on neonatal morbidity. STUDY DESIGN: This study was a multicenter randomized controlled trial, including nulliparas in the second stage of labor with an epidural and a singleton cephalic fetus at term and with a normal fetal heart rate. Of note, 2 groups were defined: (1) the moderate pushing group, in which women had no time limit on pushing, pushed only twice during each contraction, and observed regular periods without pushing, and (2) the intensive pushing group, in which women pushed 3 times during each contraction and the midwife called an obstetrician after 30 minutes of pushing to discuss operative delivery (standard care). The primary outcome was a composite neonatal morbidity criterion, including umbilical arterial pH of <7.15, base excess of >10 mmol/L, lactate levels of >6 mmol/L, 5-minute Apgar score of <7, and severe neonatal trauma. The secondary outcomes were mode of delivery, episiotomy, obstetrical anal sphincter injuries, postpartum hemorrhage, and maternal satisfaction. RESULTS: The study included 1710 nulliparous women. The neonatal morbidity rate was 18.9% in the moderate pushing group and 20.6% in the intensive pushing group (P=.38). Pushing duration was longer in the moderate group than in the intensive group (38.8±26.4 vs 28.6±17.0 minutes; P<.001), and its rate of operative delivery was 21.1% in the moderate group compared with 24.8% in the intensive group (P=.08). The episiotomy rate was significantly lower in the moderate pushing group than in the intensive pushing group (13.5% vs 17.8%; P=.02). We found no significant difference for obstetrical anal sphincter injuries, postpartum hemorrhage, or maternal satisfaction. CONCLUSION: Moderate pushing has no effect on neonatal morbidity, but it may nonetheless have benefits, as it was associated with a lower episiotomy rate.

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.

No pain management for labour: individual and organisational determinants: A secondary analysis of the 2016 French National Perinatal Survey.

BACKGROUND: Disparities in access to pain management have been identified in several care settings, such as emergency departments and intensive care units, but with regard to labour analgesia, it remains poorly explored. OBJECTIVES: To determine the proportion of women without pain management during labour and its individual and organisational determinants. DESIGN: Secondary analysis of a nationwide cross-sectional population-based study, the 2016 French National Perinatal Survey. SETTINGS: All maternity units in France. PARTICIPANTS: Ten thousand and eleven women who attempted vaginal delivery with a labour duration at least 15 min. MAIN OUTCOME MEASURE: Absence of pain management, defined as absence of any pharmacological or nonpharmacological analgesic method during labour. RESULTS: Among the 10 011 women included, 542 (5.4%) had no labour pain management: 318 (3.7%) of the 8526 women who initially preferred to use neuraxial analgesia and 222 (15.8%) of the 1402 who did not. Using generalised estimating equations stratified according to the maternal antenatal preference for neuraxial analgesia, the common determinants of no labour pain management in both groups were no attendance at childbirth education classes and admission to a delivery unit during the night. Among women who initially preferred to use neuraxial analgesia, those who delivered in units with <1500 annual deliveries compared with units with 2000 to 3499 annual deliveries, were more likely to do without pain management [adjusted odds ratio (OR) = 1.96; 95% confidence interval (CI), 1.39 to 2.78]; among those who did not prefer to use it, women born abroad were more likely to do without labour pain management (adjusted OR = 1.64; 95% CI, 1.12 to 2.40). CONCLUSION: In France, 1 : 20 women had no labour pain management, and this proportion was three times higher among women who preferred not to use neuraxial analgesia. Enhancing maternal information on labour pain and its management, especially nonpharmacological methods, and rethinking care organisation, could improve access to analgesia of any kind.

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 .).

Overuse of antenatal visits and ultrasounds in low-risk women: A national population-based study.

BACKGROUND: A better understanding of the overuse of antenatal care is needed to improve its organisation to deal with limited medical resources and doctor shortages. OBJECTIVES: To assess the proportion of women who overuse antenatal care and the associations of overuse with maternal characteristics and the qualifications of healthcare providers. METHODS: We used the 2016 National Perinatal Survey, a cross-sectional population-based survey, performed in all maternity units in France, including 13,132 women. Based on the French national guidelines, 6-8 antenatal visits were defined as adequate, 9-11 as high use, and ≥12 as overuse, while 3 ultrasounds were considered adequate, 4-5 as high use, and ≥6 as overuse. We performed binary modified Poisson regressions-with adequate care as the reference-including maternal social and medical characteristics and the healthcare professionals' qualifications. RESULTS: After women with inadequate care were excluded, 19.2% of low-risk women had at least 12 visits and 30.5% at least 6 ultrasounds. Overuse of visits was associated with primiparity, average to high income, less than good psychological well-being, and care by an obstetrician. The risks of overuse of ultrasounds were higher among primiparous, women with average to high income and those receiving care from a public-sector obstetrician (adjusted relative risk 1.17, 95% CI, 1.13, 1.21) or private obstetrician (adjusted relative risk 1.12, 95% CI, 1.07, 1.16), compared with a public-sector midwife. CONCLUSIONS: Antenatal care overuse is very common in France and associated with some maternal characteristics and also the qualification of care provider. Antenatal care should be customised according to women's needs, in particular for primiparae and those with poor well-being, and available medical resources.

A core outcome set development for a French national prospective study about the effect of mediolateral episiotomy on obstetric anal sphincter injury during operative vaginal delivery (INSTRUMODA).

BACKGROUND: We aimed at developing a core outcome and variables of interest set to investigate the effects of mediolateral episiotomy on Obstetric Anal Sphincter Injury (OASI) during and after operative delivery in nulliparous women in a large-scale one-year observational French study including 15,000 women (INSTRUMODA). METHODS: A list of outcomes and variables of interest was suggested to obstetricians participating in the INSTRUMODA study using online questionnaires divided into 7 categories: the woman's history and course of pregnancy, course of labor, modalities of operative delivery, episiotomy characteristics, immediate maternal morbidity, one-year maternal morbidity, immediate neonatal morbidity. We used a three-round DELPHI method to reach a consensus. In the first round, outcomes and variables considered as essential by 70% or more of obstetricians were included in the corpus whereas they were excluded when 70% rated them as "not important". In the second round, non-consensual outcomes and variables were reassessed and excluded or definitively included if considered as "not important" or essential by 50% or more of the obstetricians. During the first round, obstetricians were invited to suggest new outcomes and/or variables that were then assessed in the second and third round. We used the same method to develop a core outcome and variables of interest set in a population of women in the community recruited via an association of patients. At the end of the procedure the core outcome and variables of interest sets were merged to provide the final core outcome set for the INSTRUMODA study. RESULTS: Fifty-three obstetricians and 16 women filled out questionnaires. After the 3 rounds of Delphi procedure in each population, 74 outcomes and variables were consensually reported by obstetricians and 92 by women in the community. By mixing these two consensual corpora we reported a final consensual list of 114 variables of interest and outcomes for both obstetricians and women. CONCLUSION: We established a core outcome and variables of interest set among obstetricians and women in the community to investigate the association between mediolateral episiotomy and OASI during operative delivery. TRIAL REGISTRATION: The INSTRUMODA study was registered on https://clinicaltrials.gov on June 25, 2020 ( NCT04446780 ).

Contemporary duration of spontaneous labor and association with maternal characteristics: A French national population-based study.

BACKGROUND: The objective of this study was to describe labor duration of women managed with current obstetric practices in a French national population-based cohort and to assess the association of age and BMI on this duration. METHODS: All women in the French perinatal survey of 2016 with a singleton cephalic fetus, delivering at term after a spontaneous labor were included. Duration of labor was defined as time between admission to the labor ward and birth. Duration of total labor and first and second stage of labor were described. Then, duration of labor was estimated according to maternal age and BMI, using Kaplan-Meier's method and compared with the log-rank test after stratification on parity. Intrapartum cesarean birth was considered as a censoring event. Multivariable modeling was performed using Cox's proportional hazard's method. RESULTS: Data of 3120 nulliparous and 4385 multiparous women were analyzed. Median labor duration was 6.1 hours ([5th; 95th percentile]) [1.4; 12.6] and 3.1 hours [0.3; 8.5] in nulliparous and multiparous women. Multivariable Cox analysis showed no independent association of maternal age and duration of labor. Nulliparous obese women had significantly lower odds of having a shorter labor than women with a BMI < 25 kg/m2 , HR: 0.75; 95% CI [0.64-0.88], but BMI was not associated with labor duration in multiparous women. CONCLUSIONS: Our study provides important information for both women and care practitioners on what to expect when entering the labor ward. There appears to be little association between maternal characteristics and labor duration, with the exception of BMI in nulliparous women.

Increased risk of severe maternal morbidity in women with twin pregnancies resulting from oocyte donation.

STUDY QUESTION: Is there a difference in the risk of serious maternal complications during pregnancy and the postpartum in twin pregnancies according to mode of conception: natural conception, non-IVF fertility treatment, IVF, ICSI or oocyte donation? SUMMARY ANSWER: Women with twin pregnancies after medically assisted reproduction (MAR) had an overall risk of serious maternal complications 30% higher compared with women with natural twin pregnancies, and this association varied according to the MAR procedure; the risk was increased by 50% with IVF using autologous oocytes and by 270% with oocyte donation. WHAT IS KNOWN ALREADY: IVF has been reported as a risk factor for serious maternal complications in several concordant studies of singleton pregnancies. For twin pregnancies, this association is less well documented with imprecise categorisation of the mode of conception, and results are contradictory. STUDY DESIGN, SIZE, DURATION: This is a secondary analysis of the national, observational, prospective, population-based cohort study of twin pregnancies (JUmeaux Mode d'Accouchement), which took place in France from 10 February 2014 through 1 March 2015. All French maternity units performing more than 1500 annual deliveries were invited to participate, regardless of their academic, public or private status or level of care. Of the 191 eligible units, 176 (92%) participated. PARTICIPANTS/MATERIALS, SETTING, METHODS: Women with a twin pregnancy who gave birth at or after 22 weeks of gestation were eligible (N = 8823 women included). We excluded women whose mode of conception was unknown (n = 75). Serious maternal complications were regrouped within the recently emerged concept of severe acute maternal morbidity (SAMM), as a binary composite outcome. The exposure of interest was the mode of conception, studied in five classes: natural conception (reference group), non-IVF fertility treatment including insemination and ovarian stimulation, IVF with autologous oocyte, ICSI with autologous oocyte and oocyte donation. To assess the association between the mode of conception and SAMM, we used multivariate logistic regression to adjust for confounders. Structural equation modelling (SEM) was used to explore the contribution to this association of potential intermediate factors, i.e. factors possibly caused by the mode of conception and responsible for SAMM: non-severe pre-eclampsia, placenta praevia and planned mode of delivery. MAIN RESULTS AND THE ROLE OF CHANCE: Among the 8748 women of the study population, 5890 (67.3%) conceived naturally, 854 (9.8%) had non-IVF fertility treatment, 1307 (14.9%) had IVF with autologous oocytes, 368 (4.2%) had ICSI with autologous oocytes and 329 (3.8%) used oocyte donation. Overall, 538 (6.1%) developed SAMM. Women with twin pregnancy after any type of MAR had a higher risk of SAMM than those with a natural twin pregnancy, after adjustment for confounders (7.9% (227/2858) compared to 5.3% (311/5890), adjusted odds ratio (aOR) 1.3, 95% CI 1.1-1.6). This association varied according to the MAR procedure. The risk of SAMM was higher among women with IVF using either autologous oocytes (8.3%; 108/1307) or oocyte donation (14.0%; 46/329) compared with the reference group (respectively aOR 1.5, 95% CI 1.1-1.9 and aOR 2.7, 95% CI 1.8-4.1) and higher after oocyte donation compared with autologous oocytes (aOR 1.7, 95% CI 1.1-2.6). Conversely, the risk of SAMM for women with non-IVF fertility treatment (6.2%; 53/854) and with ICSI using autologous oocytes (5.4%; 20/368) did not differ from that of the reference group (5.3%; 311/5890) (respectively aOR 1.1, 95% CI 0.8-1.5 and aOR 0.9, 95% CI 0.6-1.5). The tested intermediate factors poorly explained these increased risks. LIMITATIONS, REASONS FOR CAUTION: Beyond the confounders and intermediate factors considered in our analysis, specific causes of infertility and specific aspects of infertility treatments may explain the differences in the risk of SAMM by mode of conception. However, these data were not available. WIDER IMPLICATIONS OF THE FINDINGS: Our study showed an increased risk of SAMM in women with twin pregnancies after MAR, notably after IVF using autologous oocytes and particularly after oocyte donation. To avoid unnecessary exposure to the high-risk combination of MAR and multiple pregnancies, transfer of a single embryo should be encouraged whenever possible. Knowledge of these differential risks may inform discussions between clinicians and women about the mode of conception and help to optimise obstetric care for women in subgroups at higher risk. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by a grant from the French Ministry of Health (Programme Hospitalier de Recherche Clinique, AOM2012). There are no competing interests. TRIAL REGISTRATION NUMBER: Not applicable.

Reducing neonatal morbidity by discontinuing oxytocin during the active phase of first stage of labor: a multicenter randomized controlled trial STOPOXY.

BACKGROUND: Oxytocin is effective in reducing labor duration, but can be associated with fetal and maternal complications such as neonatal acidosis and post-partum hemorrhage. When comparing discontinuing oxytocin in the active phase with continuing oxytocin infusion, previous studies were underpowered to show a reduction in neonatal morbidity. Thus, we aim at evaluating the impact of discontinuing oxytocin during the active phase of the first stage of labor on the neonatal morbidity rate. METHODS: STOPOXY is a multicenter, randomized, open-label, controlled trial conducted in 20 maternity units in France. The first participant was recruited January 17th 2020. The trial includes women with a live term (≥37 weeks) singleton, in cephalic presentation, receiving oxytocin before 4 cm, after an induced or spontaneous labor. Women aged < 18 years, with a lack of social security coverage, a scarred uterus, a multiple pregnancy, a fetal congenital malformation, a growth retardation <3rd percentile or an abnormal fetal heart rate at randomization are excluded. Women are randomized before 6 cm when oxytocin is either continued or discontinued. Randomization is stratified by center and parity. The primary outcome, neonatal morbidity is assessed using a composite variable defined by an umbilical arterial pH at birth < 7.10 and/or a base excess > 10 mmol/L and/or umbilical arterial lactates> 7 mmol/L and/or a 5 min Apgar score < 7 and/or admission in neonatal intensive care unit. The primary outcome will be compared between the two groups using a chi-square test with a p-value of 0.05. Secondary outcomes include neonatal complications, duration of active phase, mode of delivery, fetal and maternal complications during labor and delivery, including cesarean delivery rate and postpartum hemorrhage, and birth experience. We aim at including 2475 women based on a reduction in neonatal morbidity from 8% in the control group to 5% in the experimental group, with a power of 80% and an alpha risk of 5%. DISCUSSION: Discontinuing oxytocin during the active phase of labor could improve both child health, by reducing moderate to severe neonatal morbidity, and maternal health by reducing cesarean delivery and postpartum hemorrhage rates. TRIAL REGISTRATION: Clinical trials NCT03991091 , registered June 19th, 2019.

Target populations to reduce cesarean rates after induced labor: A national population-based cohort study.

INTRODUCTION: Great variations in cesarean rates after induction of labor exist and reasons for these disparities remain unclear. They may be explained by individual characteristics or obstetric practices. Ten-group classification systems have proved their utility to monitor cesarean rates in general population. We aimed to identify groups of women that account for most cesareans after induction of labor using the Nippita reproducible 10-group classification, specifically designed for induced population. MATERIAL AND METHODS: A prospective population-based cohort study was performed in 94 French maternity units, including 3042 women undergoing induction of labor. Women were sorted according to 10 mutually exclusive groups based on parity, weeks of gestation, number of fetuses, fetal presentation and previous cesarean delivery. Relative size, cesarean delivery rate and contribution to the overall cesarean rate were described for each group. Cesarean rates were compared according to the Bishop score at the onset of labor induction. Indications for cesarean delivery were also described in the groups that contributed most to the overall cesarean rate. The MEDIP protocol was registered in ClinicalTrial (NCT02477085). RESULTS: The overall cesarean rate was 21.0% among this population of induced women. Nulliparous women with a term singleton cephalic fetus (groups 1, 2 and 3; at 37-38, 39-40 and ≥41 weeks of gestation, respectively) accounted for two-thirds of the overall cesarean rate because they were the largest group (relative size of 10.6, 16.6 and 18.1%, respectively) and had higher cesarean rates (27.2, 30.9 and 33.0%, respectively). When the Bishop score was <6 (n = 2270/3042), cesarean delivery rates were higher (24.1 vs 10.7% if Bishop score ≥6, P < 0.01), in particular for group 1 (29.1 vs 12.5%, P = 0.02), and group 2 (33.3 vs 19.3%, P = 0.01). In groups 1, 2 and 3, which contributed most to the overall cesarean rate, a significant part of the cesareans were performed before 6 cm of cervical dilation for dystocia only (40.0, 16.7 and 17.6%, respectively). CONCLUSIONS: Nulliparous women with a term singleton cephalic fetus and an unfavorable cervix represent the population to target for auditing induction practices. Specific actions could be implemented among this population to weigh the benefits and risks of induction and improve the management of labor induction.