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.).

Balloon catheters versus vaginal prostaglandins for labour induction (CPI Collaborative): an individual participant data meta-analysis of randomised controlled trials.

BACKGROUND: Induction of labour is one of the most common obstetric interventions globally. Balloon catheters and vaginal prostaglandins are widely used to ripen the cervix in labour induction. We aimed to compare the effectiveness and safety profiles of these two induction methods. METHODS: We did an individual participant data meta-analysis comparing balloon catheters and vaginal prostaglandins for cervical ripening before labour induction. We systematically identified published and unpublished randomised controlled trials that completed data collection between March 19, 2019, and May 1, 2021, by searching the Cochrane Library, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform, and PubMed. Further trials done before March 19, 2019, were identified through a recent Cochrane review. Data relating to the combined use of the two methods were not included, only data from women with a viable, singleton pregnancy were analysed, and no exclusion was made based on parity or membrane status. We contacted authors of individuals trials and participant-level data were harmonised and recoded according to predefined definitions of variables. Risk of bias was assessed with the ROB2 tool. The primary outcomes were caesarean delivery, indication for caesarean delivery, a composite adverse perinatal outcome, and a composite adverse maternal outcome. We followed the intention-to-treat principle for the main analysis. The primary meta-analysis used two-stage random-effects models and the sensitivity analysis used one-stage mixed models. All models were adjusted for maternal age and parity. This meta-analysis is registered with PROSPERO (CRD42020179924). FINDINGS: Individual participant data were available from 12 studies with a total of 5460 participants. Balloon catheters, compared with vaginal prostaglandins, did not lead to a significantly different rate of caesarean delivery (12 trials, 5414 women; crude incidence 27·0%; adjusted OR [aOR] 1·09, 95% CI 0·95-1·24; I2=0%), caesarean delivery for failure to progress (11 trials, 4601 women; aOR 1·20, 95% CI 0·91-1·58; I2=39%), or caesarean delivery for fetal distress (10 trials, 4441 women; aOR 0·86, 95% CI 0·71-1·04; I2=0%). The composite adverse perinatal outcome was lower in women who were allocated to balloon catheters than in those allocated to vaginal prostaglandins (ten trials, 4452 neonates, crude incidence 13·6%; aOR 0·80, 95% CI 0·70-0·92; I2=0%). There was no significant difference in the composite adverse maternal outcome (ten trials, 4326 women, crude incidence 22·7%; aOR 1·02, 95% CI 0·89-1·18; I2=0%). INTERPRETATION: In induction of labour, balloon catheters and vaginal prostaglandins have comparable caesarean delivery rates and maternal safety profiles, but balloon catheters lead to fewer adverse perinatal events. FUNDING: Australian National Health and Medical Research Council and Monash Health Emerging Researcher Fellowship.

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.

Arabin pessary to prevent adverse perinatal outcomes in twin pregnancies with a short cervix: a multicenter randomized controlled trial (PESSARONE).

BACKGROUND: The number of twin pregnancies continues to increase worldwide as both the number of pregnancies obtained by medically assisted reproduction and age at first pregnancy keep rising. Preterm delivery is the major complication associated with twin pregnancies. The effectiveness of preventive treatments such as progesterone or cervical cerclage for women with a short cervix is doubtful in twin pregnancies. The effectivity of cervical pessaries in preventing preterm birth and its associated morbidity and mortality is also controversial. OBJECTIVE: We sought to investigate if the Arabin pessary reduces adverse neonatal outcomes in twin pregnancies with a short cervix. STUDY DESIGN: This open-label, multicenter, randomized controlled trial on twin pregnancies with a cervical length of <35 mm compared pessary placement at 16+0 to 24+0 weeks' gestation with standard care alone. The primary endpoint was a composite of adverse neonatal outcomes, namely peripartum or neonatal death or significant neonatal morbidity before hospital discharge, defined as at least 1 of the following complications: bronchopulmonary dysplasia, intraventricular hemorrhage grade III to IV, periventricular leukomalacia, necrotizing enterocolitis grade II or higher, culture-proven sepsis, and retinopathy requiring treatment. A sample size of 308 pregnancies was planned to ensure 80% power to compare the proportions of women with at least 1 infant with an adverse neonatal outcome. The intention-to-treat analysis after multiple imputation of missing data, was supplemented with a secondary analysis that controlled for gestational age and cervical length, both at inclusion. The primary endpoint was also compared between randomization groups in the per-protocol population, which excluded patients with prespecified major protocol violations (mostly cervical cerclage and/or progesterone after inclusion). Secondary endpoints included preterm birth, spontaneous preterm birth, and pessary side effects. RESULTS: In total, 315 women were randomized to either receive a pessary (n=157) or standard management (n=158). Overall, 10.8% (34 women) of participants had a missing value for the primary endpoint, mostly (79%) because of the lack of paternal consent for neonatal data collection. In the intention-to-treat analysis, the adverse neonatal outcome occurred in 16.8% of the pessary group vs in 22.5% of the control group (risk ratio, 0.69; 95% confidence interval, 0.39-1.23; P=.210). The per-protocol analysis did not show any significant difference between groups (risk ratio, 0.78; 95% confidence interval, 0.47-1.28; P=.320). The occurrence of preterm birth or spontaneous preterm birth did not differ significantly between groups. No serious side effects were associated with pessary use. CONCLUSION: Pessary use in our study did not significantly reduce adverse neonatal outcomes in twin pregnancies with a short cervix.

Conservative management or cesarean hysterectomy for placenta accreta spectrum: the PACCRETA prospective study.

BACKGROUND: Placenta accreta spectrum is a life-threatening condition that has increased dramatically in recent decades along with cesarean rates worldwide. Cesarean hysterectomy is widely practiced in women with placenta accreta spectrum; however, the maternal outcomes after cesarean hysterectomy have not been thoroughly compared with the maternal outcomes after alternative approaches, such as conservative management. OBJECTIVE: This study aimed to compare the severe maternal outcomes between women with placenta accreta spectrum treated with cesarean hysterectomy and those treated with conservative management (leaving the placenta in situ). STUDY DESIGN: From a source population of 520,114 deliveries in 176 hospitals (PACCRETA study), we designed an observational cohort of women with placenta accreta spectrum who had either a cesarean hysterectomy or a conservative management (the placenta left in situ) during cesarean delivery. Clinicians prospectively identified women meeting the inclusion criteria and included them at delivery. Data collection started only after the women had received information and agreed to participate in the study in the immediate postpartum period. The primary outcome was the transfusion of >4 units of packed red blood cells within 6 months after delivery. Secondary outcomes were other maternal complications within 6 months. We used propensity score weighting to account for potential indication bias. RESULTS: Here, 86 women had conservative management and 62 women had cesarean hysterectomy for placenta accreta spectrum during cesarean delivery. The primary outcome occurred in 14 of 86 women in the conservative management group (16.3%) and 36 of 61 (59.0%) in the cesarean hysterectomy group (risk ratio in propensity score weighted model, 0.29; 95% confidence interval, 0.19-0.45). The rates of hysterectomy, total estimated blood loss exceeding 3000 mL, any blood product transfusion, adjacent organ injury, and nonpostpartum hemorrhage-related severe maternal morbidity were lower with conservative management than with cesarean hysterectomy (all adjusted, P≤.02); but, the rates of arterial embolization, endometritis, and readmission within 6 months of discharge were higher with conservative management than with cesarean hysterectomy. CONCLUSION: Among women with placenta accreta spectrum who underwent cesarean delivery, conservative management was associated with a lower risk of transfusion of >4 units of packed red blood cells within 6 months than cesarean hysterectomy.

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.

What is the impact of blood pressure on neurological symptoms and the risk of ESKD in primary and secondary thrombotic microangiopathies based on clinical presentation: a retrospective study.

BACKGROUND: The impact of blood pressure on neurological symptoms and risk of end-stage kidney disease (ESKD) is unknown in primary and secondary thrombotic microangiopathies (TMAs). METHODS: We measured baseline systolic (SBP) and diastolic (DBP) BP in consecutive 563 patients with adjudicated primary and secondary TMAs, and assessed its association with the risk of ESKD. RESULTS: Normal BP, grade 1, 2 and 3 hypertension were present in 243 (43.1%), 132 (23.4%), 101 (17.9%) and 88 (15.6%), respectively. Significant BP differences were noted in relation to the cause of TMA: highest BP values were found in patients with atypical hemolytic-uremic syndrome (aHUS), pregnancy, transplantation and auto-immune-related TMAs. Normal BP or grade 1 hypertension was found in 17/18 (94.4%) patients with thrombotic thrombocytopenic patients (only 1/18 (5.6%) had a SBP value>150 mmHg). In contrast, BP values could not differentiate isolated "essential" malignant hypertension (MH) from MH associated with aHUS (isolated MH (n=15): BP (median (IQR)): 220 (182-249)/132 (101-150) mmHg; MH with aHUS (n=5): BP: 223 (196-245)/131 (111-144) mmHg). The risk of vigilance disturbances (6.9%, 15.0%, 25.0%, respectively), epileptic seizures (1.5%, 4.0%, 12.5%, respectively) and posterior reversible encephalopathy syndrome (0.76%, 2.97%, 6.82%, respectively) increased with increasing baseline BP values from grade 1 to grade 3 hypertension. ESKD occurred in 35/563 (6.2%) patients (1.23%, 2.27%, 11.9% and 19.3% of patients with normal BP, grade 1, 2 and 3 hypertension, respectively). As compared to patients with normal BP (<120/139 mmHg), grade 1, grade 2 and grade 3 hypertension were associated with a greater risk of ESKD in univariate (OR: 1.91 [0.83-4.40], 13.2 [3.56-48.9] and 34.8 [9.31-130], respectively) and multivariate (OR: 0.89 [0.30-2.69], 7.00 [1.57-31.3] and 19.7 [4.53-85.2], respectively) analyses. The association between BP and the risk of ESRD was unchanged after adjustment on eculizumab use (OR: 3.46 [1.41-8.49], 17.7 [4.44-70.0] and 70.6 [8.61-579], respectively). Patients with MH, regardless of its cause, had a greater risk of ESKD (OR: 26.4 [10.0-69.8] vs other patients). CONCLUSIONS: Baseline BP differs in primary and secondary TMAs. High BP reduces the neurological tolerance of TMAs and is a powerful independent risk factor of ESKD, even after adjustment on TMA's cause.

Cervical ripening in prolonged pregnancies by silicone double balloon catheter versus vaginal dinoprostone slow release system: The MAGPOP randomised controlled trial.

BACKGROUND: Prolonged pregnancies are a frequent indication for induction of labour. When the cervix is unfavourable, cervical ripening before oxytocin administration is recommended to increase the likelihood of vaginal delivery, but no particular method is currently recommended for cervical ripening of prolonged pregnancies. This trial evaluates whether the use of mechanical cervical ripening with a silicone double balloon catheter for induction of labour in prolonged pregnancies reduces the cesarean section rate for nonreassuring fetal status compared with pharmacological cervical ripening by a vaginal pessary for the slow release of dinoprostone (prostaglandin E2). METHODS AND FINDINGS: This is a multicentre, superiority, open-label, parallel-group, randomised controlled trial conducted in 15 French maternity units. Women with singleton pregnancies, a vertex presentation, ≥41+0 and ≤42+0 weeks' gestation, a Bishop score <6, intact membranes, and no history of cesarean delivery for whom induction of labour was decided were randomised to either mechanical cervical ripening with a Cook Cervical Ripening Balloon or pharmacological cervical ripening by a Propess vaginal pessary serving as a prostaglandin E2 slow-release system. The primary outcome was the rate of cesarean for nonreassuring fetal status, with an independent endpoint adjudication committee determining whether the fetal heart rate was nonreassuring. Secondary outcomes included delivery (time from cervical ripening to delivery, number of patients requiring analgesics), maternal and neonatal outcomes. Between January 2017 and December 2018, 1,220 women were randomised in a 1:1 ratio, 610 allocated to a silicone double balloon catheter, and 610 to the Propess vaginal pessary for the slow release of dinoprostone. The mean age of women was 31 years old, and 80% of them were of white ethnicity. The cesarean rates for nonreassuring fetal status were 5.8% (35/607) in the mechanical ripening group and 5.3% (32/609) in the pharmacological ripening group (proportion difference: 0.5%; 95% confidence interval (CI) -2.1% to 3.1%, p = 0.70). Time from cervical ripening to delivery was shorter in the pharmacological ripening group (23 hours versus 32 hours, median difference 6.5 95% CI 5.0 to 7.9, p < 0.001), and fewer women required analgesics in the mechanical ripening group (27.5% versus 35.4%, difference in proportion -7.9%, 95% CI -13.2% to -2.7%, p = 0.003). There were no statistically significant differences between the 2 groups for other delivery, maternal, and neonatal outcomes. A limitation was a low observed rate of cesarean section. CONCLUSIONS: In this study, we observed no difference in the rates of cesarean deliveries for nonreassuring fetal status between mechanical ripening with a silicone double balloon catheter and pharmacological cervical ripening with a pessary for the slow release of dinoprostone. TRIAL REGISTRATION: ClinicalTrials.gov NCT02907060.

Amniotic fluid peptides predict postnatal kidney survival in developmental kidney disease.

Although a rare disease, bilateral congenital anomalies of the kidney and urinary tract (CAKUT) are the leading cause of end stage kidney disease in children. Ultrasound-based prenatal prediction of postnatal kidney survival in CAKUT pregnancies is far from accurate. To improve prediction, we conducted a prospective multicenter peptidome analysis of amniotic fluid spanning 140 evaluable fetuses with CAKUT. We identified a signature of 98 endogenous amniotic fluid peptides, mainly composed of fragments from extracellular matrix proteins and from the actin binding protein thymosin-ß4. The peptide signature predicted postnatal kidney outcome with an area under the curve of 0.96 in the holdout validation set of patients with CAKUT with definite endpoint data. Additionally, this peptide signature was validated in a geographically independent sub-cohort of 12 patients (area under the curve 1.00) and displayed high specificity in non-CAKUT pregnancies (82 and 94% in 22 healthy fetuses and in 47 fetuses with congenital cytomegalovirus infection respectively). Change in amniotic fluid thymosin-ß4 abundance was confirmed with ELISA. Knockout of thymosin-ß4 in zebrafish altered proximal and distal tubule pronephros growth suggesting a possible role of thymosin ß4 in fetal kidney development. Thus, recognition of the 98-peptide signature in amniotic fluid during diagnostic workup of prenatally detected fetuses with CAKUT can provide a long-sought evidence base for accurate management of the CAKUT disorder that is currently unavailable.

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 .).

Is laterality of congenital diaphragmatic hernia a reliable prognostic factor? French national cohort study.

OBJECTIVES: The objective of this study was to assess whether the laterality of congenital diaphragmatic hernia (CDH) was a prognostic factor for neonatal survival. METHODS: This was a cohort study using the French national database of the Reference Center for Diaphragmatic Hernias. The principal endpoint was survival after hospitalization in intensive care. We made a comparative study between right CDH and left CDH by univariate and multivariate analysis. Terminations and stillbirths were excluded from analyses of neonatal outcomes. RESULTS: A total of 506 CDH were included with 67 (13%) right CDH and 439 left CDH (87%). Rate of survival was 49% for right CDH and 74% for left CDH (P < .01). Multivariate analysis showed two factors significantly associated with mortality: thoracic herniation of liver (OR 2.27; IC 95% [1.07-4.76]; P = .03) and lung-to-head-ratio over under expected (OR 2.99; IC 95% [1.41-6.36]; P < .01). Side of CDH was not significantly associated with mortality (OR 1.87; IC 95% [0.61-5.51], P = .26). CONCLUSION: Rate of right CDH mortality is more important than left CDH. Nevertheless after adjusting for lung-to-head-ratio and thoracic herniation of liver, right CDH does not have a higher risk of mortality than left CDH.

Impact of antenatal corticosteroids on head circumference of full-term newborns: A French multicenter cohort study.

INTRODUCTION: Our main objective was to evaluate whether antenatal corticosteroids increase the risk of small head circumference in children born at term. Secondary objectives were to evaluate whether they increase the risk of small birthweight and birth length among those children. MATERIAL AND METHODS: A historical cohort included 275 270 live term born children between 2000 and 2013 in 175 French maternity units. The rate of head circumference below the 5th percentile among children born at term and exposed to antenatal corticosteroids was compared with that of two unexposed groups: those children born at term whose mothers had an episode of threatened preterm labor without corticosteroids and those whose mothers had neither threatened preterm labor nor corticosteroids. The association between this treatment and head circumference was evaluated by calculating adjusted risk ratios (aRRs) and their 95% confidence intervals (CIs). The main outcome measure was a head circumference below the 5th percentile at birth, adjusted for sex, and gestational age according to the Pediatric, Obstetrics, and Gynecology Electronic Records Users Association (AUDIPOG) curves. Secondary outcomes were birthweight and birth length below the 5th percentile. RESULTS: The rate of head circumference below the 5th percentile was 5.8% (n = 3388) among children exposed to antenatal corticosteroids and 4.3% (n = 7077) and 4.6% (n = 198 462), respectively, for the two unexposed groups. After adjustment, the risk of having a head circumference below the 5th percentile did not differ between the exposed group and the two control groups (aRR 1.28, 95% confidence interval [CI] 0.97-1.69] and aRR 0.91, 95% CI 0.74-1.13). We did not find an association between antenatal corticosteroids and the rate of birthweight below the 5th percentile. Children exposed to antenatal corticosteroids had a higher risk of a birth length below the 5th percentile when compared with those not exposed to threatened preterm labor or corticosteroids. CONCLUSIONS: We found no association between antenatal corticosteroids and increased risk of head circumference below the 5th percentile in children born at term.

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.

Neonatal Outcomes in Extremely Preterm Newborns Admitted to Intensive Care after No Active Antenatal Management: A Population-Based Cohort Study.

OBJECTIVE: To evaluate the association between active antenatal management and neonatal outcomes in extremely preterm newborns admitted to a neonatal intensive care unit (NICU). STUDY DESIGN: This population-based cohort study was conducted in 25 regions of France. Infants born in 2011 between 220/7 and 266/7 weeks of gestation and admitted to a NICU were included. Infants with lethal congenital malformations or death in the delivery room were excluded. A multilevel multivariable analysis was performed, accounting for clustering by mother (multiple pregnancies) and hospital plus individual characteristics, to estimate the association between the main exposure of no active antenatal management (not receiving antenatal corticosteroids, magnesium sulfate, or cesarean delivery for fetal indications) and a composite outcome of death or severe neonatal morbidity (including severe forms of brain or lung injury, retinopathy of prematurity, and necrotizing enterocolitis). RESULTS: Among 3046 extremely preterm births, 783 infants were admitted to a NICU. Of these, 138 (18%) did not receive active antenatal management. The risk of death or severe morbidity was significantly higher for infants without active antenatal management (crude OR, 2.60; 95% CI, 1.44-4.66). This finding persisted after adjustment for gestational age (OR, 2.08; 95% CI, 1.19-3.62) and all confounding factors (OR, 1.86; 95% CI, 1.09-3.20). CONCLUSIONS: The increased risk of severe neonatal outcomes for extremely preterm babies admitted to a NICU without optimal antenatal management should be considered in individual-level decision making and in the development of professional guidelines for the management of extremely preterm births.

Prenatal therapy with pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission of toxoplasmosis: a multicenter, randomized trial.

BACKGROUND: The efficacy of prophylaxis to prevent prenatal toxoplasmosis transmission is controversial, without any previous randomized clinical trial. In France, spiramycin is usually prescribed for maternal seroconversions. A more potent pyrimethamine + sulfadiazine regimen is used to treat congenital toxoplasmosis and is offered in some countries as prophylaxis. OBJECTIVE: We sought to compare the efficacy and tolerance of pyrimethamine + sulfadiazine vs spiramycin to reduce placental transmission. STUDY DESIGN: This was a randomized, open-label trial in 36 French centers, comparing pyrimethamine (50 mg qd) + sulfadiazine (1 g tid) with folinic acid vs spiramycin (1 g tid) following toxoplasmosis seroconversion. RESULTS: In all, 143 women were randomized from November 2010 through January 2014. An amniocentesis was later performed in 131 cases, with a positive Toxoplasma gondii polymerase chain reaction in 7/67 (10.4%) in the pyrimethamine + sulfadiazine group vs 13/64 (20.3%) in the spiramycin group. Cerebral ultrasound anomalies appeared in 0/73 fetuses in the pyrimethamine + sulfadiazine group, vs 6/70 in the spiramycin group (P = .01). Two of these pregnancies were terminated. Transmission rates, excluding 18 children with undefined status, were 12/65 in the pyrimethamine + sulfadiazine group (18.5%), vs 18/60 in the spiramycin group (30%, P = .147), equivalent to an odds ratio of 0.53 (95% confidence interval, 0.23-1.22) and which after adjustment tended to be stronger (P = .03 for interaction) when treatment started within 3 weeks of seroconversion (95% confidence interval, 0.00-1.63). Two women had severe rashes, both with pyrimethamine + sulfadiazine. CONCLUSION: There was a trend toward lower transmission with pyrimethamine + sulfadiazine, but it did not reach statistical significance, possibly for lack of statistical power because enrollment was discontinued. There were also no fetal cerebral toxoplasmosis lesions in the pyrimethamine + sulfadiazine group. These promising results encourage further research on chemoprophylaxis to prevent congenital toxoplasmosis.

Induction of labour versus expectant management for large-for-date fetuses: a randomised controlled trial.

BACKGROUND: Macrosomic fetuses are at increased risk of shoulder dystocia. We aimed to compare induction of labour with expectant management for large-for-date fetuses for prevention of shoulder dystocia and other neonatal and maternal morbidity associated with macrosomia. METHODS: We did this pragmatic, randomised controlled trial between Oct 1, 2002, and Jan 1, 2009, in 19 tertiary-care centres in France, Switzerland, and Belgium. Women with singleton fetuses whose estimated weight exceeded the 95th percentile, were randomly assigned (1:1), via computer-generated permuted-block randomisation (block size of four to eight) to receive induction of labour within 3 days between 37(+0) weeks and 38(+6) weeks of gestation, or expectant management. Randomisation was stratified by centre. Participants and caregivers were not masked to group assignment. Our primary outcome was a composite of clinically significant shoulder dystocia, fracture of the clavicle, brachial plexus injury, intracranial haemorrhage, or death. We did analyses by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00190320. FINDINGS: We randomly assigned 409 women to the induction group and 413 women to the expectant management group, of whom 407 women and 411 women, respectively, were included in the final analysis. Mean birthweight was 3831 g (SD 324) in the induction group and 4118 g (392) in the expectant group. Induction of labour significantly reduced the risk of shoulder dystocia or associated morbidity (n=8) compared with expectant management (n=25; relative risk [RR] 0·32, 95% CI 0·15-0·71; p=0·004). We recorded no brachial plexus injuries, intracranial haemorrhages, or perinatal deaths. The likelihood of spontaneous vaginal delivery was higher in women in the induction group than in those in the expectant management group (RR 1·14, 95% CI 1·01-1·29). Caesarean delivery and neonatal morbidity did not differ significantly between the groups. INTERPRETATION: Induction of labour for suspected large-for-date fetuses is associated with a reduced risk of shoulder dystocia and associated morbidity compared with expectant management. Induction of labour does not increase the risk of caesarean delivery and improves the likelihood of spontaneous vaginal delivery. These benefits should be balanced with the effects of early-term induction of labour. FUNDING: Assistance Publique-Hôpitaux de Paris and the University of Geneva.

Study protocol. TRAAP - TRAnexamic Acid for Preventing postpartum hemorrhage after vaginal delivery: a multicenter randomized, double-blind, placebo-controlled trial.

BACKGROUND: Postpartum hemorrhage (PPH) is a major cause of maternal mortality, accounting for one quarter of all maternal deaths worldwide. Estimates of its incidence in the literature vary widely, from 3 % to 15 % of deliveries. Uterotonics after birth are the only intervention that has been shown to be effective in preventing PPH. Tranexamic acid (TXA), an antifibrinolytic agent, has been investigated as a potentially useful complement to uterotonics for prevention because it has been proved to reduce blood loss in elective surgery, bleeding in trauma patients, and menstrual blood loss. Randomized controlled trials for PPH prevention after cesarean (n = 10) and vaginal (n = 2) deliveries show that women who received TXA had significantly less postpartum blood loss without any increase in their rate of severe adverse effects. However, the quality of these trials was poor and they were not designed to test the effect of TXA on the reduction of PPH incidence. Large, adequately powered, multicenter randomized controlled trials are required before the widespread use of TXA to prevent PPH can be recommended. METHODS AND DESIGN: A multicenter, double-blind, randomized controlled trial will be performed. It will involve 4000 women in labor for a planned vaginal singleton delivery, at a term ≥ 35 weeks. Treatment (either TXA 1 g or placebo) will be administered intravenously just after birth. Prophylactic oxytocin will be administered to all women. The primary outcome will be the incidence of PPH, defined by blood loss ≥500 mL, measured with a graduated collector bag. This study will have 80 % power to show a 30 % reduction in the incidence of PPH, from 10.0 % to 7.0 %. DISCUSSION: In addition to prophylactic uterotonic administration, a complementary component of the management of third stage of labor acting on the coagulation process may be useful in preventing PPH. TXA is a promising candidate drug, inexpensive, easy to administer, and simple to add to the routine management of deliveries in hospitals. This large, adequately powered, multicenter, randomized placebo-controlled trial seeks to determine if the risk-benefit ratio favors the routine use of TXA after delivery to prevent PPH. TRIAL REGISTRATION: ClinicalTrials.gov NCT02302456 (November 17, 2014).

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

This study aimed to identify the risk factors for placenta accreta spectrum (PAS) in women who had at least one previous cesarean delivery and a placenta previa or low-lying. The PACCRETA prospective population-based study took place in 12 regional perinatal networks from 2013 through 2015. All women with one or more prior cesareans and a placenta previa or low lying were included. Placenta accreta spectrum (PAS) was diagnosed at delivery according to standardized clinical and histological criteria. Of the 520,114 deliveries, 396 fulfilled inclusion criteria; 108 were classified with PAS at delivery. Combining the number of prior cesareans and the placental location yielded a rate ranging from 5% for one prior cesarean combined with a posterior low-lying placenta to 63% for three or more prior cesareans combined with placenta previa. The factors independently associated with PAS disorders were BMI ≥ 30, previous uterine surgery, previous postpartum hemorrhage, a higher number of prior cesareans, and a placenta previa. Finally, in this high-risk population, the rate of PAS disorders varies greatly, not only with the number of prior cesareans but also with the exact placental location and some of the women's individual characteristics. Risk stratification is thus possible in this population.

Second-trimester uterine artery Doppler, PlGF, sFlt-1, sEndoglin, and lipid-related markers for predicting preeclampsia in a high-risk population.

OBJECTIVE: This study aimed to determine if screening for preeclampsia could be improved between 20 and 24 weeks of gestation by uterine artery Doppler (UAD), biomarkers and lipid-related markers. METHOD: Women at high risk of preeclampsia according to obstetric and medical characteristics and history were prospectively enrolled. Transabdominal UAD, serum biomarkers (placenta growth factor (PlGF), soluble Fms-like tyrosine kinase-1 and sEndoglin) and lipid-related markers (total and high-density lipoprotein cholesterol, triglycerides and leptin) were prospectively collected between 20 and 24 weeks of gestation. The main endpoint was preeclampsia. UAD indices and biomarker levels were compared for the groups with and without preeclampsia. Multivariate analyses took into account the laboratory and ultrasound variables significantly associated with preeclampsia in the univariate analysis and age and nulliparity. RESULTS: The study at Tours University Hospital took place from March 2003 to February 2008 and included 235 women: 56 (23.8%) developed preeclampsia, 42 were severe (17.8%) and 14 occurred before 34 weeks of gestation (5.9%). The group with preeclampsia had a higher UAD pulsatility index (p = 0.0003), more frequent bilateral notches (p = .0001), lower PlGF levels (239.90 vs 302.00 pg/mL; p = 0.0015), and higher triglyceride (1.95 vs 1.70 mmol/l; p = 0.0068) and leptin levels (37.40 vs 22.55 ng/mL; p = < 0.001). No significant differences were observed for other markers. Screening for preeclampsia using these Doppler and laboratory findings produced an area under the curve of 0.795. CONCLUSION: Second-trimester UAD findings, and PlGF, triglyceride and leptin levels could help to predict preeclampsia.