Tranexamic acid for postpartum bleeding: a systematic review and individual patient data meta-analysis of randomised controlled trials.

BACKGROUND: Tranexamic acid is a recommended treatment for women with a clinical diagnosis of postpartum haemorrhage, but whether it can prevent bleeding is unclear. We conducted a systematic review and individual patient data (IPD) meta-analysis of randomised controlled trials to assess the effects of tranexamic acid in women giving birth. METHODS: In this systematic review and IPD meta-analysis, we searched the WHO International Clinical Trials Registry Platform from database inception to Aug 4, 2024 for randomised trials that assessed the effects of tranexamic acid in women giving birth. Trials were eligible if they were prospectively registered, placebo-controlled, included more than 500 women, and had a low risk of bias for random sequence generation and allocation concealment. IPD were requested from the trial investigators. The primary outcomes were the numbers of women with life-threatening bleeding and thromboembolic events. We used a one-stage model to analyse the data and explored whether the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia, or timing of administration (before or after a diagnosis of postpartum haemorrhage). This study is registered with PROSPERO, CRD42022345775. FINDINGS: We analysed data on 54 404 women from five trials. We obtained IPD for 43 409 women from four trials and aggregate data on 10 995 women from one trial. All trials had a low risk of bias. Life-threatening bleeding occurred in 178 (0·65%) of 27 300 women in the tranexamic acid group versus 230 (0·85%) of 27 093 women in the placebo group (pooled odds ratio [OR] 0·77 [95% CI 0·63-0·93]; p=0·008). There was no evidence that the effect of tranexamic acid varied by the underlying risk of life-threatening bleeding, type of birth, presence of moderate or severe anaemia or timing of administration. No significant difference was identified between tranexamic acid and placebo groups with regard to thromboembolic events: 50 (0·2%) of 26 571 women in the tranexamic acid group had fatal or non-fatal thromboembolic events versus 52 (0·2%) of 26 373 women in the placebo group (pooled OR 0·96 [0·65-1·41]; p=0·82) with no significant heterogeneity identified in the subgroup analyses. INTERPRETATION: Tranexamic acid reduces the risk of life-threatening postpartum bleeding. We found no evidence that tranexamic acid increases the risk of thrombosis. Although we do not recommend the use of tranexamic acid in all women giving birth, consideration should be given to its use before a diagnosis of postpartum haemorrhage in women at high risk of death. FUNDING: The Bill & Melinda Gates Foundation.

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.

Posttraumatic stress disorder 2 months after cesarean delivery: a multicenter prospective study.

BACKGROUND: The prevalence and risk factors of posttraumatic stress disorder after cesarean delivery, outside high-risk contexts, remain unclear. OBJECTIVE: This study aimed to assess posttraumatic stress disorder prevalence and risk factors at 2 months postpartum among a general population of women with cesarean delivery. STUDY DESIGN: This was a prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, conducted in 27 French hospitals from 2018 to 2020, enrolling women expected to undergo cesarean delivery before or during labor at ≥34 weeks of gestation. After randomization, characteristics of the cesarean delivery and postpartum blood loss were prospectively collected. Two months after childbirth, posttraumatic stress disorder profile (presence of posttraumatic stress disorder symptoms) and provisional diagnosis (positive screening for diagnosis consistent with a posttraumatic stress disorder) were assessed by 2 self-administered questionnaires (Impact of Event Scale - Revised and Traumatic Event Scale). The corrected posttraumatic stress disorder prevalence was estimated with inverse probability weighting to take nonresponse into account. Associations between potential risk factors and posttraumatic stress disorder were analyzed by multivariate logistic or linear regression modeling according to the type of dependent variable. RESULTS: In total, 2785 of 4431 women returned the Impact of Event Scale - Revised questionnaire and 2792 the Traumatic Event Scale (response rates of 62.9% and 63.0%). The prevalence of posttraumatic stress disorder profile was 9.0% (95% confidence interval, 7.8%-10.3%) and of provisional diagnosis 1.7% (95% confidence interval, 1.2%-2.4%). Characteristics associated with a higher risk of posttraumatic stress disorder profile were prepregnancy vulnerability factors (young age, high body mass index, and African-born migrant) and cesarean delivery-related obstetrical factors (cesarean delivery after induced labor [adjusted odds ratio, 1.81; 95% confidence interval, 1.14-2.87], postpartum hemorrhage [adjusted odds ratio, 1.61; 95% confidence interval, 1.04-2.46] and high-intensity pain during the postpartum stay [adjusted odds ratio, 1.90; 95% confidence interval, 1.17-3.11]). Women who had immediate skin-to-skin contact with their newborn were at lower risk of posttraumatic stress disorder (adjusted odds ratio, 0.66; 95% confidence interval, 0.46-0.98), and women with bad memories of delivery on day 2 postpartum were at higher risk (adjusted odds ratio, 3.20; 95% confidence interval, 1.97-5.12). The Impact of Event Scale - Revised and the Traumatic Event Scale yielded consistent results. CONCLUSION: Approximately 1 in 11 women with cesarean deliveries had posttraumatic stress disorder symptoms at 2 months postpartum. Some obstetrical interventions and components of cesarean delivery management may influence this risk.

Prevalence and risk factors for postpartum depression 2 months after a vaginal delivery: a prospective multicenter study.

BACKGROUND: Very little is known about the prevalence and risk factors of postpartum depression among women with vaginal births without major pregnancy complications. OBJECTIVE: This study aimed to assess the prevalence of postpartum depression and identify its characteristics 2 months after singleton vaginal delivery at or near term. STUDY DESIGN: This was an ancillary cohort study of the TRanexamic Acid for Preventing Postpartum Hemorrhage After Vaginal Delivery randomized controlled trial, which was conducted in 15 French hospitals in 2015-2016 and enrolled women with singleton vaginal deliveries after 35 weeks of gestation. After randomization, the characteristics of labor, delivery, and the immediate postpartum experience, including the experience of childbirth, were prospectively collected. Medical records provided women's other characteristics, particularly any psychiatric history. Of note, 2 months after childbirth, provisional postpartum depression diagnosis was defined as a score of ≥13 on the Edinburgh Postnatal Depression Scale, a validated self-administered questionnaire. The corrected prevalence of postpartum depression was calculated with the inverse probability weighting method to take nonrespondents into account. Associations between potential risk factors and postpartum depression were analyzed by multivariate logistic regression. Moreover, an Edinburgh Postnatal Depression Scale cutoff value of ≥11 was selected to perform a sensitivity analysis. RESULTS: The questionnaire was returned by 2811 of 3891 women (72.2% response rate). The prevalence rates of the provisional diagnosis were 9.9% (95% confidence interval, 8.6%-11.3%) defined by an Edinburgh Postnatal Depression Scale score of ≥13 and 15.5% (95% confidence interval, 14.0%-17.1%) with a cutoff value of ≥11. The characteristics associated with higher risks of postpartum depression in multivariate analysis were mostly related to prepregnancy characteristics, specifically age of <25 years (adjusted odds ratio, 1.8; 95% confidence interval, 1.1-2.9) and advanced age (adjusted odds ratio, 1.8; 95% confidence interval, 1.2-2.6), migration from North Africa (adjusted odds ratio, 2.9; 95% confidence interval, 1.9-4.4), previous abortion (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), and psychiatric history (adjusted odds ratio, 2.9; 95% confidence interval, 1.8-4.8). Some characteristics of labor and delivery, such as induced labor (adjusted odds ratio, 1.5; 95% confidence interval, 1.1-2.0) and operative vaginal delivery (adjusted odds ratio, 1.4; 95% confidence interval, 1.0-2.0), seemed to be associated with postpartum depression. In addition, bad memories of childbirth in the immediate postpartum were strongly associated with postpartum depression symptoms at 2 months after giving birth (adjusted odds ratio, 2.4; 95% confidence interval, 1.3-4.2). CONCLUSION: Approximately 10% of women with vaginal deliveries have postpartum depression symptoms, assessed by a score of ≥13 on the depression scale that was used at 2 months. Prepregnancy vulnerability factors; obstetrical characteristics, such as induced labor and operative vaginal delivery; and bad memories of childbirth 2 days after delivery were the main factors associated with this provisional diagnosis. A screening approach that targets risk factors may help to identify women at risk of postpartum depression who could benefit from early intervention.

Prevalence and risk factors for postpartum depression two months after cesarean delivery: a prospective multicenter study.

BACKGROUND: The prevalence and risk factors of postpartum depression after cesarean delivery remain unclear. OBJECTIVE: To assess the prevalence of postpartum depression and its risk factors 2 months after cesarean delivery. METHODS: Prospective ancillary cohort study of the Tranexamic Acid for Preventing Postpartum Hemorrhage after Cesarean Delivery (TRAAP2) trial, conducted in 27 French hospitals in 2018-2020 and enrolling women undergoing cesarean delivery before or during labor at 34 or more weeks of gestation. After randomization, characteristics of the cesarean delivery, postpartum blood loss, and immediate postpartum period, including memories of delivery and postoperative pain, were prospectively collected. Women's characteristics, particularly any psychiatric history, were collected from medical records. Two months after childbirth, a postpartum depression provisional diagnosis was defined as a score of 13 or higher on the Edinburgh Postnatal Depression Scale, a validated self-administered questionnaire. The corrected prevalence of postpartum depression was calculated with the inverse probability weighting method to take nonrespondents into account. Multivariate logistic regression analyzed associations between potential risk factors and postpartum depression. A sensitivity analysis used an EPDS cutoff value of 11 or higher. RESULTS: The questionnaire was returned by 2793/4431 women (63.0% response rate). The corrected prevalence of postpartum depression provisional diagnosis was 16.4% (95% confidence interval (CI), 14.9-18.0%) with an EPDS score of 13 or higher and 23.1% (95%CI, 21.4-24.9%) with a cutoff value of 11 or higher. Characteristics associated with a higher risk of postpartum depression were pre-pregnancy characteristics such as young age (aOR 0.83, 95%CI 0.74-0.93 for each 5-year increase in maternal age) and non-European country of birth (aOR 2.58, 95%CI 1.85-3.59 for North Africa; aOR 1.57, 95%CI 1.09-2.26 for Sub-Saharan Africa and aOR 1.99, 95%CI 1.28-3.10 for other country of birth; reference: Europe) and some aspects of the cesarean delivery, notably its timing and context, emergency before labor (aOR 1.70, 95%CI 1.15-2.50; reference: before labor without emergency) and during labor after induction of labor (aOR 1.36, 95%CI 1.03-1.84; reference: before labor without emergency). Also at higher risk were women reporting high intensity pain during the postpartum stay (aOR 1.73, 95%CI 1.32-2.26) and bad memories of delivery on day 2 postpartum (aOR 1.67, 95%CI 1.14-2.45). Conversely, women who had social support in the operating room had a lower risk of postpartum depression (aOR 0.73, 95%CI 0.53-0.97). CONCLUSION: Around one woman in six had postpartum depression symptoms 2 months after cesarean delivery. Some cesarean-related obstetric factors may increase this risk: cesareans before labor for emergency situations or during labor after medically indicated induction of labor, severe postoperative pain and bad memories of delivery before discharge. Specific subgroups of at-risk women could benefit from early screening or intervention to reduce the onset of postpartum depression. Perinatal professionals should pay particular attention to postoperative pain management.

Shock index as a predictor of postpartum haemorrhage after vaginal delivery: Secondary analysis of a multicentre randomised controlled trial.

OBJECTIVE: To describe the shock index (SI) distribution during the first 2 hours after delivery and to evaluate its performance when measured 15 and 30 minutes after delivery for predicting postpartum haemorrhage (PPH) occurrence in the general population of parturients after vaginal delivery. DESIGN: Secondary analysis of a multicentre randomised controlled trial testing prophylactic administration of tranexamic acid versus placebo in addition to prophylactic oxytocin to prevent PPH. SETTING: 15 French maternity units in 2015-2016. SAMPLE: 3891 women with a singleton live fetus ≥35 weeks, born vaginally. METHODS: For each PPH-related predicted outcome, we calculated the area under the receiver operating characteristic curve (AUROC) values of the SI at 15 and 30 minutes after delivery and its predictive performance for SI cut-off values of 0.7, 0.9 and 1.1. MAIN OUTCOME MEASURES: Quantitative blood loss ≥1000 ml (QBL ≥1000 ml) measured in a graduated collector bag and provider-assessed clinically significant PPH (cPPH). RESULTS: Prevalence of QBL ≥1000 ml and cPPH was respectively 2.7% (104/3839) and 9.1% (354/3891). The distributions of the SI at 15 and 30 minutes after delivery were similar with a median value of 0.73 and 97th percentile of 1.11 for both. The AUROC values of the 15-minute SI for discriminating QBL ≥1000 ml and cPPH were respectively 0.66 (lower limit of the 95% confidence interval [LCI] 0.60) and 0.56 (LCI 0.52); and for the 30-minute SI 0.68 (LCI 0.61) and 0.49 (LCI 0.43). CONCLUSIONS: The shock index at 15 and 30 minutes after delivery did not satisfactorily predict either QBL ≥1000 ml or clinical PPH.

Trends in Maternal Mortality From Obstetric Hemorrhage in France: 15 Years of Confidential Enquiry Into Maternal Deaths.

BACKGROUND: The aim of this study was to assess temporal trends in incidence and underlying causes of maternal deaths from obstetric hemorrhage in France and to describe clinical care before and after implementation of the first national guidelines published in 2004 and updated in 2014. METHODS: Data from all hemorrhage-related maternal deaths between 2001 and 2015 were extracted from the French Confidential Enquiry into Maternal Deaths. We compared the maternal mortality ratio (MMR), cause of obstetric hemorrhage, and death preventability by triennium. Critical care, transfusion, and obstetric management among women who died were described for 2001 to 2003 and 2013 to 2015. RESULTS: The MMR from obstetric hemorrhage significantly decreased over time from 2.3 of 100,000 livebirths (54 of 2,391,551) in 2001 to 2003 to 0.8 of 100,000 livebirths (19 of 2,412,720) in 2013 to 2015. In 2001 to 2003, uterine atony accounted for 50% (27 of 54) of maternal deaths vs 21% (4 of 19) in 2013 to 2015. As compared to 2001 to 2003, an increased proportion of women had hemodynamic continuous monitoring in 2013 to 2015 (30%, 9 of 30, vs 47%, 8 of 18) and received vasopressor infusion therapy (57%, 17 of 30, vs 72%, 13 of 18), and a smaller proportion was extubated during active hemorrhage (17%, 5 of 30, vs 0 of 18). Transfusion therapy was initiated more frequently and earlier in 2013 to 2015 (71 vs 58 minutes). In 2013 to 2015, 88% of maternal deaths due to hemorrhage remained preventable. The main identified improvable care factors were related to delays in diagnosis and surgical management, particularly after cesarean delivery. CONCLUSIONS: Maternal mortality by obstetric hemorrhage decreased dramatically in France between 2001 and 2015, particularly mortality due to uterine atony. Among women who died, we detected fewer instances of substandard transfusion management or critical care. Nevertheless, opportunities for improvement were observed in most of the recent cases.

Maternal mortality due to obstetric hemorrhage by surgical injury during cesarean section: A nationwide study.

INTRODUCTION: Obstetric hemorrhage remains a largely preventable cause of maternal mortality globally. The contribution of uterine atony to hemorrhage-related maternal mortality has decreased in France, while the contribution of other causes of obstetric hemorrhage such as surgical injury during cesarean has been reported to increase. However, little evidence exists regarding the risk factors and care processes of women who died from this cause of hemorrhage. Therefore, we aimed to describe the clinical profile, underlying mechanisms, and preventability factors among women who died from obstetric hemorrhage by surgical injury during cesarean section. MATERIAL AND METHODS: Nationwide analysis of all hemorrhage-related maternal deaths by surgical injury during cesarean in France identified by the nationwide permanent enhanced maternal mortality surveillance system (ENCMM) between 2007 and 2018. We described the characteristics of the women, delivery hospitals, circumstances of hemorrhage, features of obstetric and resuscitation/transfusion care, and main preventability factors. RESULTS: Between 2007 and 2018, hemorrhage-related maternal mortality in France decreased from 1.6/100 000 live births (95% CI 1.1-2.2) (39/2 472 650) in 2007-2009 to 0.8/100 000 live births (95% CI 0.5-1.3) (19/2 311 783) in 2016-2018. Hemorrhage-related maternal mortality ratio due to surgical injury during cesarean increased from 0.08 (95% CI 0.01-0.3) (2/2 472 650) to 0.2 (95% CI 0.07-0.5) (5/2 311 783) per 100 000 live births. Among the 18 women who died from surgical injury during cesarean over the 12-year study period, we report a high prevalence of obesity (67%, 12/18), previous cesarean (72%, 13/18), and second-stage cesareans (56%, 10/18). In 22% (4/18), cesarean section was performed in a hospital providing <1000 births annually, with no blood bank (39%, 7/18) or no adult intensive care (44%, 8/18) on-site. Overall preventability of deaths was 94% (17/18). Main preventability factors were related to delay in hemorrhage diagnosis (77%, 14/18) due to late recognition of abnormal parameters (33%, 6/18) and late bedside ultrasound (56%, 10/18), and delay in management due to insufficient surgical skills (56%, 10/18). CONCLUSIONS: In France, surgical injury during cesarean section is an increasing, largely preventable contributor to hemorrhage-related maternal mortality, as other causes of fatal hemorrhage have become less frequent. The profile of these women showed a high prevalence of obesity, previous cesarean, second-stage cesarean, and delivery in hospitals with limited medical and surgical resources, which suggests explanatory mechanisms for the fatal outcome and opportunities for prevention.

Association between migration and severe maternal outcomes in high-income countries: Systematic review and meta-analysis.

BACKGROUND: Literature focusing on migration and maternal health inequalities is inconclusive, possibly because of the heterogeneous definitions and settings studied. We aimed to synthesize the literature comparing the risks of severe maternal outcomes in high-income countries between migrant and native-born women, overall and by host country and region of birth. METHODS AND FINDINGS: Systematic literature review and meta-analysis using the Medline/PubMed, Embase, and Cochrane Library databases for the period from January 1, 1990 to April 18, 2023. We included observational studies comparing the risk of maternal mortality or all-cause or cause-specific severe maternal morbidity in high-income countries between migrant women, defined by birth outside the host country, and native-born women; used the Newcastle-Ottawa scale tool to assess risk of bias; and performed random-effects meta-analyses. Subgroup analyses were planned by host country and region of birth. The initial 2,290 unique references produced 35 studies published as 39 reports covering Europe, Australia, the United States of America, and Canada. In Europe, migrant women had a higher risk of maternal mortality than native-born women (pooled risk ratio [RR], 1.34; 95% confidence interval [CI], 1.14, 1.58; p < 0.001), but not in the USA or Australia. Some subgroups of migrant women, including those born in sub-Saharan Africa (pooled RR, 2.91; 95% CI, 2.03, 4.15; p < 0.001), Latin America and the Caribbean (pooled RR, 2.77; 95% CI, 1.43, 5.35; p = 0.002), and Asia (pooled RR, 1.57, 95% CI, 1.09, 2.26; p = 0.01) were at higher risk of maternal mortality than native-born women, but not those born in Europe or in the Middle East and North Africa. Although they were studied less often and with heterogeneous definitions of outcomes, patterns for all-cause severe maternal morbidity and maternal intensive care unit admission were similar. We were unable to take into account other social factors that might interact with migrant status to determine maternal health because many of these data were unavailable. CONCLUSIONS: In this systematic review of the existing literature applying a single definition of "migrant" women, we found that the differential risk of severe maternal outcomes in migrant versus native-born women in high-income countries varied by host country and region of origin. These data highlight the need to further explore the mechanisms underlying these inequities. TRIAL REGISTRATION: PROSPERO CRD42021224193.

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.

Incidence and risk factors for severe postpartum haemorrhage in women with anterior low-lying or praevia placenta and prior caesarean: Prospective population-based study.

OBJECTIVE: To assess the incidence and risk factors for severe postpartum haemorrhage (PPH) in women with an anterior low-lying or praevia placenta, prior caesarean and no prenatal suspicion of placenta accreta spectrum (PAS). DESIGN: Population-based study in 176 maternity units in France. POPULATION: All women with anterior low-lying (0-19 mm from the cervical internal os) or praevia placenta, diagnosed prospectively before birth, prior caesarean and no prenatal suspicion of PAS. METHODS: Multivariable logistic regression to identify risk factors for severe PPH in the main population and after exclusion of women with PAS diagnosed only at birth. MAIN OUTCOME MEASURES: Severe PPH defined by a composite criterion either estimated blood loss of ≥1500 ml, transfusion of ≥4 or more units of packed red blood cells, embolisation or surgical treatment. RESULTS: Of the 520 114 women constituting the source population, 230 (0.44/1000 women; 95% confidence interval [CI] 0.38-0.50) met the inclusion criteria. Severe PPH rate was 24.8% (95% CI 19.2-30.4) overall, 27.5% (95% CI 21.8-33.3) in women with placenta praevia and 15.4% (95% CI 10.7-20.0) in women with low-lying placenta. PAS was diagnosed at birth in 22 women (9.9%; 95% CI 5.8-13.4), although previously unsuspected. After their exclusion, severe PPH incidence was 17.3% (95% CI 12.4-22.2). In multivariate analysis, the only factor associated with a higher severe PPH risk was placenta previa (aOR, 3.65; 95%CI, 1.20-15.8). CONCLUSION: Severe PPH is frequent among women with anterior low-lying or praevia placenta and prior caesarean, even after exclusion of women with PAS. The risk of severe PPH for those with praevia is nearly twice that with low-lying placenta.

Maternal sudden death: A nationwide retrospective study.

OBJECTIVE: To determine the prevalence of maternal sudden death (MSD) and to compare the characteristics of death between women with explained and unexplained sudden death. DESIGN: A national retrospective study in France. POPULATION: Maternal deaths related to an unexpected sudden cardiac arrest were extracted from the French National Confidential Enquiry into Maternal Deaths database for 2007-2012. METHODS: Maternal, pregnancy, sudden death characteristics and maternal investigations were compared between women with explained and unexplained cause of death. RESULTS: A total of 83 maternal sudden deaths and 4 949 890 live births occurred over the period studied, thus accounting for 16% of all maternal deaths (n = 510). Death was explained in 51 (61%) women and unexplained in 32 women (39%). Compared with women with unexplained death, women with explained death were more often found to have in-hospital cardiac arrest (47% versus 12%, P < 0.01), witnessed cardiac arrest (86% versus 62%, P = 0.03) and in-hospital death (82% versus 47%, P < 0.01). Postmortem investigations such as autopsy and/or CT scan (65% versus 31%, P < 0.01) were also more often carried out in women with explained death. The proportion of deaths for which the preventability factors could not be assessed was 58% among unexplained MSD and 7% among explained MSD. CONCLUSION: Maternal sudden death is a rare event but accounts for a high proportion of all maternal deaths. This highlights the importance of providing training in diagnostic and management strategy for care providers. Systematic postmortem investigations are required to help understand causes and improve practices.

Incidence and outcomes of uterine rupture in women with unscarred, preterm or prelabour uteri: data from the international network of obstetric survey systems.

OBJECTIVE: Analysis of atypical cases of uterine rupture, namely, uterine rupture occurring in unscarred, preterm or prelabour uteri. DESIGN: Descriptive multi-country population-based study. SETTING: Ten high-income countries within the International Network of Obstetric Survey Systems. POPULATION: Women with unscarred, preterm or prelabour ruptured uteri. METHODS: We merged prospectively collected individual patient data in ten population-based studies of women with complete uterine rupture. In this analysis, we focused on women with uterine rupture of unscarred, preterm or prelabour ruptured uteri. MAIN OUTCOME MEASURES: Incidence, women's characteristics, presentation and maternal and perinatal outcome. RESULTS: We identified 357 atypical uterine ruptures in 3 064 923 women giving birth. Estimated incidence was 0.2 per 10 000 women (95% CI 0.2-0.3) in the unscarred uteri, 0.5 (95% CI 0.5-0.6) in the preterm uteri, 0.7 (95% CI 0.6-0.8) in the prelabour uteri, and 0.5 (95% CI 0.4-0.5) in the group with no previous caesarean. Atypical uterine rupture resulted in peripartum hysterectomy in 66 women (18.5%, 95% CI 14.3-23.5%), three maternal deaths (0.84%, 95% CI 0.17-2.5%) and perinatal death in 62 infants (19.7%, 95% CI 15.1-25.3%). CONCLUSIONS: Uterine rupture in preterm, prelabour or unscarred uteri are extremely uncommon but were associated with severe maternal and perinatal outcome. We found a mix of risk factors in unscarred uteri, most preterm uterine ruptures occurred in caesarean-scarred uteri and most prelabour uterine ruptures in 'otherwise' scarred uteri. This study may increase awareness among clinicians and raise suspicion of the possibility of uterine rupture under these less expected conditions.

Postpartum haemorrhage in high-resource settings: Variations in clinical management and future research directions based on a comparative study of national guidelines.

OBJECTIVE: To compare guidelines from eight high-income countries on prevention and management of postpartum haemorrhage (PPH), with a particular focus on severe PPH. DESIGN: Comparative study. SETTING: High-resource countries. POPULATION: Women with PPH. METHODS: Systematic comparison of guidance on PPH from eight high-income countries. MAIN OUTCOME MEASURES: Definition of PPH, prophylactic management, measurement of blood loss, initial PPH-management, second-line uterotonics, non-pharmacological management, resuscitation/transfusion management, organisation of care, quality/methodological rigour. CONCLUSIONS: Our study highlights areas where strong evidence is lacking. There is need for a universal definition of (severe) PPH. Consensus is required on how and when to quantify blood loss to identify PPH promptly. Future research may focus on timing and sequence of second-line uterotonics and non-pharmacological interventions and how these impact maternal outcome. Until more data are available, different transfusion strategies will be applied. The use of clear transfusion-protocols are nonetheless recommended to reduce delays in initiation. There is a need for a collaborative effort to develop standardised, evidence-based PPH guidelines. RESULTS: Definitions of (severe) PPH varied as to the applied cut-off of blood loss and incorporation of clinical parameters. Dose and mode of administration of prophylactic uterotonics and methods of blood loss measurement were heterogeneous. Recommendations on second-line uterotonics differed as to type and dose. Obstetric management diverged particularly regarding procedures for uterine atony. Recommendations on transfusion approaches varied with different thresholds for blood transfusion and supplementation of haemostatic agents. Quality of guidelines varied considerably.

Tranexamic acid for reduction of blood loss after Caesarean delivery: a cost-effectiveness analysis of the TRAAP2 trial.

BACKGROUND: Prophylactic administration of tranexamic acid is associated with a reduction of blood loss after Caesarean delivery, but cost-effectiveness for this indication has not been assessed. METHODS: We used data from the TRAAP2 trial, a multicentre, double-blinded, RCT aimed at estimating the efficacy of tranexamic acid for preventing postpartum haemorrhage among women undergoing Caesarean delivery. Women recruited at 27 French maternity hospitals from 2018 to 2020 were enrolled before the procedure if they had a Caesarean delivery before or during labour at 34 or more weeks of gestation. The main outcomes were the cost of hospital stay for delivery and the incremental cost per delivery without complication within 90 days after delivery with tranexamic acid compared with placebo. Differences in costs and the incremental net monetary benefit (INMB) were estimated using linear regression models, and the cost-effectiveness probability of tranexamic acid compared with placebo was estimated through the parametric distribution of the INMB. RESULTS: The proportion of women without complications at day 90 was 70.7% in the tranexamic acid group and 66.0% in the placebo group. Mean total costs until occurrence of a complication of interest were €3321 in the tranexamic acid group and €3260 in the placebo group, resulting in a difference between the two groups of 7.2% and €55 after multiple imputation. The adjusted incremental cost-effectiveness ratio was €762 per additional Caesarean delivery without a complication at 90 days after delivery. At a cost-effectiveness threshold of €10,000, the cost-effectiveness probability of tranexamic acid compared with placebo was 99.9%, varying from 5.8% to 100.0% for thresholds from €0 to €10,000 per additional delivery without a complication at day 90. CONCLUSION: Tranexamic acid for the prevention of blood loss is cost-effective in reducing complications after Caesarean delivery at day 90 postpartum. However, the effect size (in cost and effectiveness) is very low. CLINICAL TRIAL REGISTRATION: NCT03431805.

Association between language barrier and inadequate prenatal care utilization among migrant women in the PreCARE prospective cohort study.

BACKGROUND: Inadequate prenatal care utilization (PCU) is involved in the higher risk of adverse maternal outcomes among migrant vs. native women. Language barrier may be a risk factor for inadequate PCU. We aimed to assess the association between this barrier and inadequate PCU among migrant women. METHODS: This analysis took place in the French multicentre prospective PreCARE cohort study, conducted in four university hospital maternity units in the northern Paris area. It included 10 419 women giving birth between 2010 and 2012. Migrants' language barrier to communication in French were categorized into three groups: migrants with no, partial or total language barrier. Inadequate PCU was assessed by the date prenatal care began, the proportion of recommended prenatal visits completed and ultrasound scans performed. The associations between these language barrier categories and inadequate PCU were tested with multivariable logistic regression models. RESULTS: Among the 4803 migrant women included, the language barrier was partial for 785 (16.3%) and total for 181 (3.8%). Compared to migrants with no language barrier, those with partial [risk ratio (RR) 1.23, 95% confidence interval (CI) 1.13-1.33] and total (RR 1.28, 95% CI 1.10-1.50) language barrier were at higher risk of inadequate PCU. Adjustment for maternal age, parity and region of birth did not modify these associations, which were noted particularly among socially deprived women. CONCLUSION: Migrant women with language barrier have a higher risk of inadequate PCU than those without. These findings underscore the importance of targeted efforts to bring women with language barrier to prenatal care.

Hypertensive disorders of pregnancy and onset of chronic hypertension in France: the nationwide CONCEPTION study.

AIMS: Hypertensive disorders of pregnancy (HDP) are a leading cause of maternal and foetal morbidity and mortality. We aimed to estimate the impact of HDP on the onset of chronic hypertension in primiparous women in the first years following childbirth. METHODS AND RESULTS: This nationwide cohort study used data from the French National Health Data System (SNDS). All eligible primiparous women without pre-existing chronic hypertension who delivered between 2010 and 2018 were included. Women were followed up from six weeks post-partum until onset of hypertension, a cardiovascular event, death, or the study end date (31 December 2018). The main outcome was a diagnosis of chronic hypertension. We used Cox models to estimate hazard ratios (HRs) of chronic hypertension for all types of HDP. Overall, 2 663 573 women were included with a mean follow-up time of 3.0 years. Among them, 180 063 (6.73%) had an HDP. Specifically 66 260 (2.16%) had pre-eclampsia (PE) and 113 803 (4.27%) had gestational hypertension (GH). Compared with women who had no HDP, the fully adjusted HRs of chronic hypertension were 6.03 [95% confidence interval (CI) 5.89-6.17] for GH, 8.10 (95% CI 7.88-8.33) for PE (all sorts), 12.95 (95% CI 12.29-13.65) for early PE, 9.90 (95% CI 9.53-10.28) for severe PE, and 13.17 (95% CI 12.74-13.60) for PE following GH. Hypertensive disorders of pregnancy exposure duration was an additional risk factor of chronic hypertension for all PE subgroups. Women with HDP consulted a general practitioner or cardiologist more frequently and earlier. CONCLUSION: Hypertensive disorders of pregnancy exposure greatly increased the risk of chronic hypertension in the first years following delivery.

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.