Idiopathic polyhydramnios and postnatal outcomes of children: The role of exome sequencing.

OBJECTIVES: The objective of our study was to evaluate the long-term outcome of children born from a pregnancy complicated by idiopathic polyhydramnios. The secondary objective was to investigate factors associated with adverse outcomes. METHODS: We conducted a retrospective study in two prenatal diagnosis centers between January 1, 2009 and December 31, 2020. Inclusion criteria were pregnancies with a diagnosis of idiopathic polyhydramnios, defined by a deepest pocket greater than 8 cm, no detectable abnormality at ultrasound and a negative amniotic fluid assessment including karyotype, chromosomal microarray, biochemical assays (electrolytes and digestive enzymes), and viruses (parvovirus B19 and cytomegalovirus). One-year outcomes of these children were collected. The primary endpoint was adverse postnatal outcome, defined by at least one of the following criteria: stillbirth, neonatal death, or serious and incurable condition diagnosed in the first year of life. RESULTS: Of the 245 women referred for isolated polyhydramnios, 73 were diagnosed with idiopathic polyhydramnios after prenatal investigations. The mean age at follow-up of children was 28 months (95% CI 20-36). An adverse outcome occurred in 25% of cases (18/73), with one stillbirth, two neonatal deaths, and 15 severe conditions diagnosed postnatally, including a rate of monogenic disorders of 8.2% (6/73). Pediatric follow-up was normal for 75% of the children (55/73), including a rate of 9% (5/55) of curable conditions. Repeated amnioreduction was independently associated with an adverse outcome. CONCLUSION: Pregnant women with polyhydramnios should be informed of the increased risk of 25% of perinatal mortality and serious conditions diagnosed after birth.

The role of pre- and postnatal investigations in suspected isolated hypospadias.

INTRODUCTION: Prenatal investigations are usually performed to diagnose severe or associated forms of hypospadias. However, the value of this workup and the correlation with the postnatal diagnosis and follow-up have not been studied in the literature. The aims of the study were to describe postnatal outcomes. MATERIAL AND METHODS: We conducted a single-center retrospective study. We included fetuses with a prenatal suspicion of isolated hypospadias (no associated ultrasound abnormality). Postnatal findings were described including neonatal examination with confirmation of the diagnosis or not of hypospadias, the diagnosis of isolated or associated hypospadias, investigations and management. RESULTS: A total of 21 patients with a suspicion of isolated hypospadias on prenatal ultrasound and available postnatal follow-up were included. The diagnosis of hypospadias was confirmed at neonatal examination for 17/21 (81 %) children. All 17 confirmed cases underwent at least one urological surgical procedure. Postnatally, the diagnosis of hypospadias in 4/17(23.5 %) cases was found to be associated with the following diagnosis: Denys-Drash syndrome, deletion of chromosome9 and duplication of chromosome20 involved in genital development, significant duplication of the short arm of chromosome 16, mosaic karyotypic abnormality [45, X (64 %)/46, XY (36 %)]. The hormonal assessment revealed 3/17(17.6 %) abnormalities: one diagnosis of partial androgen insensitivity syndrome and two cases of gonadal dysgenesis with low AMH and inhibin B. CONCLUSION: Prenatal diagnosis of isolated hypospadias may be associated with postnatal genetic abnormalities. In this context, a prenatal assessment by amniocentesis with chromosomal microarray analysis can be an option after discussion with the woman.

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

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

[Preeclampsia: Guidelines for clinical practice from the French College of Obstetricians and Gynecologists]. / La pré-éclampsie : recommandations pour la pratique clinique du Collège national des gynécologues obstétriciens français.

OBJECTIVE: To identify strategies to reduce maternal and neonatal morbidity related to preeclampsia. MATERIAL AND METHODS: The quality of evidence of the literature was assessed following the GRADE® method with questions formulated in the PICO format (Patients, Intervention, Comparison, Outcome) and outcomes defined a priori and classified according to their importance. An extensive bibliographic search was performed on PubMed, Cochrane, EMBASE and Google Scholar databases. The quality of the evidence was assessed (high, moderate, low, very low) and recommendations were formulated as a (i) strong, (ii) weak or (iii) no recommendation. The recommendations were reviewed in two rounds with external reviewers (Delphi survey) to select the consensus recommendations. RESULTS: Preeclampsia is defined by the association of gestational hypertension (systolic blood pressure≥140mmHg and/or diastolic blood pressure≥90mmHg) and proteinuria≥0.3g/24h or a Proteinuria/Creatininuria ratio≥30mg/mmol occurring after 20 weeks of gestation. Data from the literature do not show any benefit in terms of maternal or perinatal health from implementing a broader definition of preeclampsia. Of the 31 questions, there was agreement between the working group and the external reviewers on 31 (100%). In general population, physical activity during pregnancy should be encouraged to reduce the risk of preeclampsia (Strong recommendation, Quality of the evidence low) but an early screening based on algorithms (Weak recommendation, Quality of the evidence low) or aspirin administration (Weak recommendation, Quality of the evidence very low) is not recommended to reduce maternal and neonatal morbidity related to preeclampsia. In women with preexisting diabetes or hypertension or renal disease, or multiple pregnancy, the level of evidence is insufficient to determine whether aspirin administration during pregnancy is useful to reduce maternal and perinatal morbidity (No recommendation, Quality of the evidence low). In women with a history of vasculo-placental disease, low dose of aspirin (Strong recommendation, Quality of the evidence moderate) at a dosage of 100-160mg per day (Weak recommendation, Quality of the evidence low), ideally before 16 weeks of gestation and not after 20 weeks of gestation (Strong recommendation, Quality of the evidence low) until 36 weeks of gestation (Weak recommendation, Quality of the evidence very low) is recommended. In a high-risk population, additional administration of low molecular weight heparin is not recommended (Weak recommendation, Quality of the evidence moderate). In case of preeclampsia (Weak recommendation, Quality of the evidence low) or suspicion of preeclampsia (Weak recommendation, Quality of the evidence moderate, the assessment of PlGF concentration or sFLT-1/PlGF ratio is not routinely recommended) in the only goal to reduce maternal or perinatal morbidity. In women with non-severe preeclampsia antihypertensive agent should be administered orally when the systolic blood pressure is measured between 140 and 159mmHg or diastolic blood pressure is measured between 90 and 109mmHg (Weak recommendation, Quality of the evidence low). In women with non-severe preeclampsia, delivery between 34 and 36+6 weeks of gestation reduces severe maternal hypertension but increases the incidence of moderate prematurity. Taking into account the benefit/risk balance for the mother and the child, it is recommended not to systematically induce birth in women with non-severe preeclampsia between 34 and 36+6 weeks of gestation (Strong recommendation, Quality of evidence high). In women with non-severe preeclampsia diagnosed between 37+0 and 41 weeks of gestation, it is recommended to induce birth to reduce maternal morbidity (Strong recommendation, Low quality of evidence), and to perform a trial of labor in the absence of contraindication (Strong recommendation, Very low quality of evidence). In women with a history of preeclampsia, screening maternal thrombophilia is not recommended (Strong recommendation, Quality of the evidence moderate). Because women with a history of a preeclampsia have an increased lifelong risk of chronic hypertension and cardiovascular complications, they should be informed of the need for medical follow-up to monitor blood pressure and to manage other possible cardiovascular risk factors (Strong recommendation, Quality of the evidence moderate). CONCLUSION: The purpose of these recommendations was to reassess the definition of preeclampsia, and to determine the strategies to reduce maternal and perinatal morbidity related to preeclampsia, during pregnancy but also after childbirth. They aim to help health professionals in their daily clinical practice to inform or care for patients who have had or have preeclampsia. Synthetic information documents are also offered for professionals and patients.

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.

Effectiveness and Costs of Molecular Screening and Treatment for Bacterial Vaginosis to Prevent Preterm Birth: The AuTop Randomized Clinical Trial.

Importance: Bacterial vaginosis (BV) is a well-known risk factor for preterm birth. Molecular diagnosis of BV is now available. Its impact in the screening and treatment of BV during pregnancy on preterm births has not been evaluated to date. Objective: To evaluate the clinical and economic effects of point-of-care quantitative real-time polymerase chain reaction screen and treat for BV in low-risk pregnant women on preterm birth. Design, Setting, and Participants: The AuTop trial was a prospective, multicenter, parallel, individually randomized, open-label, superiority trial conducted in 19 French perinatal centers between March 9, 2015, and December 18, 2017. Low-risk pregnant women before 20 weeks' gestation without previous preterm births or late miscarriages were enrolled. Data were analyzed from October 2021 to November 2022. Interventions: Participants were randomized 1:1 to BV screen and treat using self-collected vaginal swabs (n = 3333) or usual care (n = 3338). BV was defined as Atopobium vaginae (Fannyhessea vaginae) load of 108 copies/mL or greater and/or Gardnerella vaginalis load of 109 copies/mL or greater, using point-of-care quantitative real-time polymerase chain reaction assays. The control group received usual care with no screening of BV. Main Outcomes and Measures: Overall rate of preterm birth before 37 weeks' gestation and total costs were calculated in both groups. Secondary outcomes were related to treatment success as well as maternal and neonate health. Post hoc subgroup analyses were conducted. Results: Among 6671 randomized women (mean [SD] age, 30.6 [5.0] years; mean [SD] gestational age, 15.5 [2.8] weeks), the intention-to-treat analysis of the primary clinical and economic outcomes showed no evidence of a reduction in the rate of preterm birth and total costs with the screen and treat strategy compared with usual care. The rate of preterm birth was 3.8% (127 of 3333) in the screen and treat group and 4.6% (153 of 3338) in the control group (risk ratio [RR], 0.83; 95% CI, 0.66-1.05; P = .12). On average, the cost of the intervention was €203.6 (US $218.0) per participant, and the total average cost was €3344.3 (US $3580.5) in the screen and treat group vs €3272.9 (US $3504.1) in the control group, with no significant differences being observed. In the subgroup of nulliparous women (n = 3438), screen and treat was significantly more effective than usual care (RR, 0.62; 95% CI, 0.45-0.84; P for interaction = .003), whereas no statistical difference was found in multiparous (RR, 1.30; 95% CI, 0.90-1.87). Conclusion and Relevance: In this clinical trial of pregnant women at low risk of preterm birth, molecular screening and treatment for BV based on A vaginae (F vaginae) and/or G vaginalis quantification did not significantly reduce preterm birth rates. Post hoc analysis suggests a benefit of screen and treat in low-risk nulliparous women, warranting further evaluation in this group. Trial Registration: ClinicalTrials.gov Identifier: NCT02288832.

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.

International registry of congenital porto-systemic shunts: a multi-centre, retrospective and prospective registry of neonates, children and adults with congenital porto-systemic shunts.

BACKGROUND: Congenital portosystemic shunts (CPSS) are rare vascular malformations associated with the risk of life-threatening systemic conditions, which remain underdiagnosed and often are identified after considerable diagnostic delay. CPSS are characterized by multiple signs and symptoms, often masquerading as other conditions, progressing over time if the shunt remains patent. Which patients will benefit from shunt closure remains to be clarified, as does the timing and method of closure. In addition, the etiology and pathophysiology of CPSS are both unknowns. This rare disorder needs the strength of numbers to answer these questions, which is the purpose of the international registry of CPSS (IRCPSS). METHOD: A retrospective and prospective registry was designed using secuTrial® by the ISO certified Clinical Research Unit. Given that a significant number of cases entered in the registry are retrospective, participants have the opportunity to use a semi-structured minimal or complete data set to facilitate data entry. In addition, the design allows subjects to be entered into the IRCPSS according to clinically relevant events. Emphasis is on longitudinal follow-up of signs and symptoms, which is paramount to garner clinically relevant information to eventually orient patient management. The IRCPSS includes also three specific forms to capture essential radiological, surgical, and cardiopulmonary data as many times as relevant, which are completed by the specialists themselves. Finally, connecting the clinical data registry with a safe image repository, using state-of-the-art pseudonymization software, was another major focus of development. Data quality and stewardship is ensured by a steering committee. All centers participating in the IRCPSS have signed a memorandum of understanding and obtained their own ethical approval. CONCLUSION: Through state-of-the-art management of data and imaging, we have developed a practical, user-friendly, international registry to study CPSS in neonates, children, and adults. Via this multicenter and international effort, we will be ready to answer meaningful and urgent questions regarding the management of patients with CPSS, a condition often ridden with significant diagnostic delay contributing to a severe clinical course.

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.

Risk of hypoglycemia by anthropometric measurements in neonates of mothers with diabetes.

Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. This study aimed to study the association between anthropometric measurements and hypoglycemia in neonates of mothers treated for gestational diabetes. This is a secondary analysis of the INDAO trial study conducted between May 2012 and November 2016 in 13 French tertiary care university hospitals in 890 pregnant women with gestational diabetes treated with either insulin or glyburide. Neonatal anthropometric measurements were birthweight and weight-length ratio (WLR, defined as birth weight/length). Neonatal hypoglycemia was defined as capillary blood glucose below 36 mg/dL (2 mmol/L) or below 45 mg/dL (2.5 mmol/L) associated with clinical signs after 2 h of life. Their relationships were modeled with logistic regressions using fractional polynomials. Extreme categories of birthweight or WLR adjusted for gestational age at birth and sex were defined as Z-score < -1.28 or > 1.28. These categories were compared to Z-score between -1.28 and 1.28 by estimating odds ratios and confidence intervals for neonatal hypoglycemia. Neonatal hypoglycemia occurred in 9.1% of cases. The relationship between birthweight and WLR Z-scores and neonatal risk of hypoglycemia adjusted for maternal treatment was a U-shaped curve. Adjusted odds ratios for the risk of hypoglycemia were 9.6 (95% CI 3.5, 26.8) and 2.3 (95% CI 1.1, 4.9) for WLR Z-score below -1.28 and above 1.28, respectively, compared with WLR Z-score between -1.28 and 1.28.    Conclusion: Birthweight Z-score was associated with the risk of neonatal hypoglycemia in neonates from mothers treated for gestational diabetes. The risk of neonatal hypoglycemia was increased for both extreme birthweight Z-scores, regardless of maternal treatment. Small for gestational age neonates of diabetic mothers require special attention for the risk of neonatal hypoglycemia. What is Known: • Macrosomia in neonates of diabetic women is a risk factor for neonatal hypoglycemia, with an over-risk for asymmetric macrosomia. Few retrospective studies have assessed the risk for neonatal hypoglycemia among small for gestational age neonates born to diabetic mothers. What is New: • The risk of neonatal hypoglycemia among neonates of diabetic mothers increased for both low and high weight-length ratio, regardless of maternal medicinal treatment, gestational age at birth, and sex of the newborn.

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.

Survival Without Severe Neonatal Morbidity in Very Preterm Twins According to Planned Mode of Delivery.

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

Term prelabor rupture of membranes: guidelines for clinical practice from the French College of Gynaecologists and Obstetricians (CNGOF).

OBJECTIVE: To determine the management of patients with term prelabor rupture of membranes. METHODS: Synthesis of the literature from the PubMed and Cochrane databases and the recommendations of French and foreign societies and colleges. RESULTS: Term prelabor rupture of membranes is considered a physiological process until 12 h have passed since rupture (professional consensus). In cases of expectant management and with a low rate of antibiotic prophylaxis, home care may be associated with an increase in neonatal infections (LE3), compared with hospitalization, especially for women with group B streptococcus (GBS) colonization (LE3). Home care is therefore not recommended (grade C). In the absence of spontaneous labor within 12 h of rupture, antibiotic prophylaxis may reduce the risk of maternal intrauterine infection but not of neonatal infection (LE3). Its use after 12 h of rupture in term prelabor rupture of the membranes is therefore recommended (grade C). When antibiotic prophylaxis is indicated, intravenous beta-lactams are recommended (grade C). Induction of labor with oxytocin (LE1), prostaglandin E2 (LE1), or misoprostol (LE1) is associated with shorter rupture-to-delivery intervals than expectant management; immediate induction is not, however, associated with lower rates of neonatal infection (LE1), even among women with a positive GBS vaginal swab (LE2). Thus, expectant management can be offered without increasing the risk of neonatal infection (grade B). Induction of labor is not associated with either an increase or decrease in the cesarean rate (LE2), regardless of parity (LE2) or Bishop score at admission (LE3). Induction can thus be proposed without increasing the risk of cesarean delivery (grade B). No induction method (oxytocin, dinoprostone, misoprostol, or Foley catheter) has demonstrated superiority over any another method for reducing rates of intrauterine or neonatal infection or of cesarean delivery or for shortening the rupture-to-delivery intervals, regardless of parity or the Bishop score. CONCLUSION: Term prelabor rupture of membranes is a frequent event. A 12-hour interval without onset of spontaneous labor was chosen to differentiate a physiological condition from a potentially unsafe situation that justifies antibiotic prophylaxis. Expectant management or induction of labor can each be proposed, even in case of positive screening for group streptococcus. The decision should depend on the woman's wishes and maternity unit organization (professional consensus).

Evaluation of the usefulness of ultrasound measurement of the lower uterine segment before delivery of women with a prior cesarean delivery: a randomized trial.

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

Guidelines for the management of women with severe pre-eclampsia.

OBJECTIVE: To provide national guidelines for the management of women with severe pre-eclampsia. DESIGN: A consensus committee of 26 experts was formed. A formal conflict-of-interest (COI) policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industrial funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE®) system to guide assessment of quality of evidence. The potential drawbacks of making strong recommendations in the presence of low-quality evidence were emphasised. METHODS: The last SFAR and CNGOF guidelines on the management of women with severe pre-eclampsia were published in 2009. The literature is now sufficient for an update. The aim of this expert panel guidelines is to evaluate the impact of different aspects of the management of women with severe preeclampsia on maternal and neonatal morbidities separately. The experts studied questions within 7 domains. Each question was formulated according to the PICO (Patients Intervention Comparison Outcome) model and the evidence profiles were produced. An extensive literature review and recommendations were carried out and analysed according to the GRADE® methodology. RESULTS: The SFAR/CNGOF experts panel provided 25 recommendations: 8 have a high level of evidence (GRADE 1+/-), 9 have a moderate level of evidence (GRADE 2+/-), and for 7 recommendations, the GRADE method could not be applied, resulting in expert opinions. No recommendation was provided for 3 questions. After one scoring round, strong agreement was reached between the experts for all the recommendations. CONCLUSIONS: There was strong agreement among experts who made 25 recommendations to improve practices for the management of women with severe pre-eclampsia.