Tranexamic Acid to Prevent Obstetrical Hemorrhage after Cesarean Delivery.

BACKGROUND: Prophylactic use of tranexamic acid at the time of cesarean delivery has been shown to decrease the calculated blood loss, but the effect on the need for blood transfusions is unclear. METHODS: We randomly assigned patients undergoing cesarean delivery at 31 U.S. hospitals to receive either tranexamic acid or placebo after umbilical-cord clamping. The primary outcome was a composite of maternal death or blood transfusion by hospital discharge or 7 days post partum, whichever came first. Key secondary outcomes were estimated intraoperative blood loss of more than 1 liter (prespecified as a major secondary outcome), interventions for bleeding and related complications, the preoperative-to-postoperative change in the hemoglobin level, and postpartum infectious complications. Adverse events were assessed. RESULTS: A total of 11,000 participants underwent randomization (5529 to the tranexamic acid group and 5471 to the placebo group); scheduled cesarean delivery accounted for 50.1% and 49.2% of the deliveries in the respective groups. A primary-outcome event occurred in 201 of 5525 participants (3.6%) in the tranexamic acid group and in 233 of 5470 (4.3%) in the placebo group (adjusted relative risk, 0.89; 95.26% confidence interval [CI], 0.74 to 1.07; P = 0.19). Estimated intraoperative blood loss of more than 1 liter occurred in 7.3% of the participants in the tranexamic acid group and in 8.0% of those in the placebo group (relative risk, 0.91; 95% CI, 0.79 to 1.05). Interventions for bleeding complications occurred in 16.1% of the participants in the tranexamic acid group and in 18.0% of those in the placebo group (relative risk, 0.90; 95% CI, 0.82 to 0.97); the change in the hemoglobin level was -1.8 g per deciliter and -1.9 g per deciliter, respectively (mean difference, -0.1 g per deciliter; 95% CI, -0.2 to -0.1); and postpartum infectious complications occurred in 3.2% and 2.5% of the participants, respectively (relative risk, 1.28; 95% CI, 1.02 to 1.61). The frequencies of thromboembolic events and other adverse events were similar in the two groups. CONCLUSIONS: Prophylactic use of tranexamic acid during cesarean delivery did not lead to a significantly lower risk of a composite outcome of maternal death or blood transfusion than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development; ClinicalTrials.gov number, NCT03364491.).

Treatment for Mild Chronic Hypertension during Pregnancy.

BACKGROUND: The benefits and safety of the treatment of mild chronic hypertension (blood pressure, <160/100 mm Hg) during pregnancy are uncertain. Data are needed on whether a strategy of targeting a blood pressure of less than 140/90 mm Hg reduces the incidence of adverse pregnancy outcomes without compromising fetal growth. METHODS: In this open-label, multicenter, randomized trial, we assigned pregnant women with mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to receive antihypertensive medications recommended for use in pregnancy (active-treatment group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a composite of preeclampsia with severe features, medically indicated preterm birth at less than 35 weeks' gestation, placental abruption, or fetal or neonatal death. The safety outcome was small-for-gestational-age birth weight below the 10th percentile for gestational age. Secondary outcomes included composites of serious neonatal or maternal complications, preeclampsia, and preterm birth. RESULTS: A total of 2408 women were enrolled in the trial. The incidence of a primary-outcome event was lower in the active-treatment group than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (95% confidence interval [CI], 0.74 to 0.92; P<0.001). The percentage of small-for-gestational-age birth weights below the 10th percentile was 11.2% in the active-treatment group and 10.4% in the control group (adjusted risk ratio, 1.04; 95% CI, 0.82 to 1.31; P = 0.76). The incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75; 95% CI, 0.45 to 1.26), and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77; 95% CI, 0.45 to 1.30). The incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio, 0.79; 95% CI, 0.69 to 0.89), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87; 95% CI, 0.77 to 0.99). CONCLUSIONS: In pregnant women with mild chronic hypertension, a strategy of targeting a blood pressure of less than 140/90 mm Hg was associated with better pregnancy outcomes than a strategy of reserving treatment only for severe hypertension, with no increase in the risk of small-for-gestational-age birth weight. (Funded by the National Heart, Lung, and Blood Institute; CHAP ClinicalTrials.gov number, NCT02299414.).

Body Mass Index, Adverse Pregnancy Outcomes, and Cardiovascular Disease Risk.

BACKGROUND: Obesity is a well-established risk factor for both adverse pregnancy outcomes (APOs) and cardiovascular disease (CVD). However, it is not known whether APOs are mediators or markers of the obesity-CVD relationship. This study examined the association between body mass index, APOs, and postpartum CVD risk factors. METHODS: The sample included adults from the nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-To-Be) Heart Health Study who were enrolled in their first trimester (6 weeks-13 weeks 6 days gestation) from 8 United States sites. Participants had a follow-up visit at 3.7 years postpartum. APOs, which included hypertensive disorders of pregnancy, preterm birth, small-for-gestational-age birth, and gestational diabetes, were centrally adjudicated. Mediation analyses estimated the association between early pregnancy body mass index and postpartum CVD risk factors (hypertension, hyperlipidemia, and diabetes) and the proportion mediated by each APO adjusted for demographics and baseline health behaviors, psychosocial stressors, and CVD risk factor levels. RESULTS: Among 4216 participants enrolled, mean±SD maternal age was 27±6 years. Early pregnancy prevalence of overweight was 25%, and obesity was 22%. Hypertensive disorders of pregnancy occurred in 15%, preterm birth in 8%, small-for-gestational-age birth in 11%, and gestational diabetes in 4%. Early pregnancy obesity, compared with normal body mass index, was associated with significantly higher incidence of postpartum hypertension (adjusted odds ratio, 1.14 [95% CI, 1.10-1.18]), hyperlipidemia (1.11 [95% CI, 1.08-1.14]), and diabetes (1.03 [95% CI, 1.01-1.04]) even after adjustment for baseline CVD risk factor levels. APOs were associated with higher incidence of postpartum hypertension (1.97 [95% CI, 1.61-2.40]) and hyperlipidemia (1.31 [95% CI, 1.03-1.67]). Hypertensive disorders of pregnancy mediated a small proportion of the association between obesity and incident hypertension (13% [11%-15%]) and did not mediate associations with incident hyperlipidemia or diabetes. There was no significant mediation by preterm birth or small-for-gestational-age birth. CONCLUSIONS: There was heterogeneity across APO subtypes in their association with postpartum CVD risk factors and mediation of the association between early pregnancy obesity and postpartum CVD risk factors. However, only a small or nonsignificant proportion of the association between obesity and CVD risk factors was mediated by any of the APOs, suggesting APOs are a marker of prepregnancy CVD risk and not a predominant cause of postpartum CVD risk.

A Trial of Hyperimmune Globulin to Prevent Congenital Cytomegalovirus Infection.

BACKGROUND: Primary cytomegalovirus (CMV) infection during pregnancy carries a risk of congenital infection and possible severe sequelae. There is no established intervention for preventing congenital CMV infection. METHODS: In this multicenter, double-blind trial, pregnant women with primary CMV infection diagnosed before 24 weeks' gestation were randomly assigned to receive a monthly infusion of CMV hyperimmune globulin (at a dose of 100 mg per kilogram of body weight) or matching placebo until delivery. The primary outcome was a composite of congenital CMV infection or fetal or neonatal death if CMV testing of the fetus or neonate was not performed. RESULTS: From 2012 to 2018, a total of 206,082 pregnant women were screened for primary CMV infection before 23 weeks of gestation; of the 712 participants (0.35%) who tested positive, 399 (56%) underwent randomization. The trial was stopped early for futility. Data on the primary outcome were available for 394 participants; a primary outcome event occurred in the fetus or neonate of 46 of 203 women (22.7%) in the group that received hyperimmune globulin and of 37 of 191 women (19.4%) in the placebo group (relative risk, 1.17; 95% confidence interval [CI] 0.80 to 1.72; P = 0.42). Death occurred in 4.9% of fetuses or neonates in the hyperimmune globulin group and in 2.6% in the placebo group (relative risk, 1.88; 95% CI, 0.66 to 5.41), preterm birth occurred in 12.2% and 8.3%, respectively (relative risk, 1.47; 95% CI, 0.81 to 2.67), and birth weight below the 5th percentile occurred in 10.3% and 5.4% (relative risk, 1.92; 95% CI, 0.92 to 3.99). One participant in the hyperimmune globulin group had a severe allergic reaction to the first infusion. Participants who received hyperimmune globulin had a higher incidence of headaches and shaking chills while receiving infusions than participants who received placebo. CONCLUSIONS: Among pregnant women, administration of CMV hyperimmune globulin starting before 24 weeks' gestation did not result in a lower incidence of a composite of congenital CMV infection or perinatal death than placebo. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Center for Advancing Translational Sciences; ClinicalTrials.gov number, NCT01376778.).

Longitudinal associations between urinary biomarkers of phthalates and replacements with novel in vivo measures of placental health.

STUDY QUESTION: What is the longitudinal association between gestational phthalate exposure and in vivo placental outcomes? SUMMARY ANSWER: Phthalates were adversely associated with placental microvasculature, stiffness, and presence of calcification, with different metabolites associated with different outcomes. WHAT IS KNOWN ALREADY: Phthalate exposure is ubiquitous and implicated as a contributor to adverse pregnancy outcomes, possibly through impacts on the placenta. STUDY DESIGN, SIZE, DURATION: A total of 303 women were recruited in early pregnancy and prospectively followed for up to eight visits across gestation in the Human Placenta and Phthalates study. PARTICIPANTS/MATERIALS, SETTING, METHODS: At each visit, women provided urine samples and underwent placental ultrasounds. Urine was analyzed for 18 metabolites of phthalates and replacements. We took the geometric mean of repeated measurements to reflect pregnancy-averaged phthalate or replacement exposure for each participant (n = 303). Placental microvasculature, stiffness, and microcalcification presence were quantified from ultrasounds at each visit. Higher scores reflected worse placental function for all measures. Generalized linear mixed models were created to estimate the association between pregnancy-averaged exposure biomarker concentrations and repeated outcome measurements for microvasculature and stiffness. Gestational age at the time of calcification detection was modeled using Cox proportional hazards models. MAIN RESULTS AND THE ROLE OF CHANCE: Monocarboxyisononyl phthalate and summed di(2-ethylhexyl) phthalate metabolites were associated with impaired microvasculature development, such that an interquartile range increase in concentration was associated with 0.11 standard deviation increase in the microvasculature ratio, indicating poorer vascularization (95% CI: 0.00, 0.22); 0.11 [95% CI: -0.01, 0.22], respectively. Monoethyl phthalate was associated with increased placental stiffness (0.09 [95% CI: -0.01, 0.19]) while summed di-iso-butyl phthalate metabolites and monobenzyl phthalate were associated with increased hazard of calcification detection (hazard ratios: 1.18 [95% CI: 0.98, 1.42]; 1.13 [95% CI: 0.96, 1.34]). LIMITATIONS, REASONS FOR CAUTION: Outcomes used in this study are novel and further investigation is needed to provide clinical context and relevance. WIDER IMPLICATIONS OF THE FINDINGS: We found evidence of associations between select phthalate biomarkers and various aspects of in vivo placental health, although we did not observe consistency across placental outcomes. These findings could illustrate heterogeneous effects of phthalate exposure on placental function. STUDY FUNDING/COMPETING INTEREST(S): This research was supported in part by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (ZIA ES103344), and NIEHS T32ES007018. The authors declare that they have no competing interests to disclose. The findings and conclusions in this report are those of the authors and do not necessarily represent the official position of the Centers for Disease Control and Prevention. Use of trade names is for identification only and does not imply endorsement by the CDC, the Public Health Service, or the US Department of Health and Human Services. TRIAL REGISTRATION NUMBER: N/A.

The role of point-of-care ultrasound to monitor response of fluid replacement therapy in pregnancy.

Fluid management in obstetrical care is crucial because of the complex physiological conditions of pregnancy, which complicate clinical manifestations and fluid balance management. This expert review examined the use of point-of-care ultrasound to evaluate and monitor the response to fluid therapy in pregnant patients. Pregnancy induces substantial physiological changes, including increased cardiac output and glomerular filtration rate, decreased systemic vascular resistance, and decreased plasma oncotic pressure. Conditions, such as preeclampsia, further complicate fluid management because of decreased intravascular volume and increased capillary permeability. Traditional methods for assessing fluid volume status, such as physical examination and invasive monitoring, are often unreliable or inappropriate. Point-of-care ultrasound provides a noninvasive, rapid, and reliable means to assess fluid responsiveness, which is essential for managing fluid therapy in pregnant patients. This review details the various point-of-care ultrasound modalities used to measure dynamic changes in fluid status, focusing on the evaluation of the inferior vena cava, lung ultrasound, and left ventricular outflow tract. Inferior vena cava ultrasound in spontaneously breathing patients determines diameter variability, predicts fluid responsiveness, and is feasible even late in pregnancy. Lung ultrasound is crucial for detecting early signs of pulmonary edema before clinical symptoms arise and is more accurate than traditional radiography. The left ventricular outflow tract velocity time integral assesses stroke volume response to fluid challenges, providing a quantifiable measure of cardiac function, which is particularly beneficial in critical care settings where rapid and accurate fluid management is essential. This expert review synthesizes current evidence and practice guidelines, suggesting the integration of point-of-care ultrasound as a fundamental aspect of fluid management in obstetrics. It calls for ongoing research to enhance techniques and validate their use in broader clinical settings, aiming to improve outcomes for pregnant patients and their babies by preventing complications associated with both under- and overresuscitation.

Association between stillbirth and severe maternal morbidity.

BACKGROUND: Severe maternal morbidity has been increasing in the past few decades. Few studies have examined the risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries. OBJECTIVE: This study aimed to examine the prevalence and risk of severe maternal morbidity among individuals with stillbirths vs individuals with live-birth deliveries during delivery hospitalization as a primary outcome and during the postpartum period as a secondary outcome. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from California (2008-2018), Michigan (2008-2020), Missouri (2008-2014), Pennsylvania (2008-2014), and South Carolina (2008-2020). Relative risk regression analysis was used to examine the crude and adjusted relative risks of severe maternal morbidity along with 95% confidence intervals among individuals with stillbirths vs individuals with live-birth deliveries, adjusting for birth year, state of residence, maternal sociodemographic characteristics, and the obstetric comorbidity index. RESULTS: Of the 8,694,912 deliveries, 35,012 (0.40%) were stillbirths. Compared with individuals with live-birth deliveries, those with stillbirths were more likely to be non-Hispanic Black (10.8% vs 20.5%); have Medicaid (46.5% vs 52.0%); have pregnancy complications, including preexisting diabetes mellitus (1.1% vs 4.3%), preexisting hypertension (2.3% vs 6.2%), and preeclampsia (4.4% vs 8.4%); have multiple pregnancies (1.6% vs 6.2%); and reside in South Carolina (7.4% vs 11.6%). During delivery hospitalization, the prevalence rates of severe maternal morbidity were 791 cases per 10,000 deliveries for stillbirths and 154 cases per 10,000 deliveries for live-birth deliveries, whereas the prevalence rates for nontransfusion severe maternal morbidity were 502 cases per 10,000 deliveries for stillbirths and 68 cases per 10,000 deliveries for live-birth deliveries. The crude relative risk for severe maternal morbidity was 5.1 (95% confidence interval, 4.9-5.3), whereas the adjusted relative risk was 1.6 (95% confidence interval, 1.5-1.8). For nontransfusion severe maternal morbidity among stillbirths vs live-birth deliveries, the crude relative risk was 7.4 (95% confidence interval, 7.0-7.7), whereas the adjusted relative risk was 2.0 (95% confidence interval, 1.8-2.3). This risk was not only elevated among individuals with stillbirth during the delivery hospitalization but also through 1 year after delivery (severe maternal morbidity adjusted relative risk, 1.3; 95% confidence interval, 1.1-1.4; nontransfusion severe maternal morbidity adjusted relative risk, 1.2; 95% confidence interval, 1.1-1.3). CONCLUSION: Stillbirth was found to be an important contributor to severe maternal morbidity.

Early vs delayed amniotomy following transcervical Foley balloon in the induction of labor: a randomized clinical trial.

BACKGROUND: The optimal timing of amniotomy during labor induction is a topic of ongoing debate due to the potential risks associated with both amniotomy and prolonged labor. As such, individuals in the field of obstetrics and gynecology must carefully evaluate the associated benefits and drawbacks of this procedure. While amniotomy can expedite the labor process, it may also lead to complications such as umbilical cord prolapse, fetal distress, and infection. Therefore, a careful and thorough examination of the risks and benefits of amniotomy during labor induction is essential in making an informed decision regarding the optimal timing of this procedure. OBJECTIVE: This study aimed to determine if an amniotomy within 2 hours after Foley balloon removal reduced the duration of active labor and time taken to achieve vaginal delivery when compared with an amniotomy ≥4 hours after balloon removal among term pregnant women who underwent labor induction. STUDY DESIGN: This was an open-label, randomized controlled trial that was conducted at a single academic center from October 2020 to March 2023. Term participants who were eligible for preinduction cervical ripening with a Foley balloon were randomized into 2 groups, namely the early amniotomy (rupture of membranes within 2 hours after Foley balloon removal) and delayed amniotomy (rupture of membranes performed more than 4 hours after Foley balloon removal) groups. Randomization was stratified by parity. The primary outcome was time from Foley balloon insertion to active phase of labor. Secondary outcomes, including time to delivery, cesarean delivery rates, and maternal and neonatal complications, were analyzed using intention-to-treat and per-protocol analyses. RESULTS: Of the 150 participants who consented and were enrolled, 149 were included in the analysis. In the intention-to-treat population, an early amniotomy did not significantly shorten the time between Foley balloon insertion and active labor when compared with a delayed amniotomy (885 vs 975 minutes; P=.08). An early amniotomy was associated with a significantly shorter time from Foley balloon placement to active labor in nulliparous individuals (1211; 584-2340 vs 1585; 683-2760; P=.02). When evaluating the secondary outcomes, an early amniotomy was associated with a significantly shorter time to active labor onset (312.5 vs 442.5 minutes; P=.02) and delivery (484 vs 587 minutes; P=.03) from Foley balloon removal with a higher rate of delivery within 36 hours (96% vs 85%; P=.03). Individuals in the early amniotomy group reached active labor 1.5 times faster after Foley balloon insertion than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1.1-2.2; P=.02). Those with an early amniotomy also reached vaginal delivery 1.5 times faster after Foley balloon removal than those in the delayed group (hazard ratio, 1.5; 95% confidence interval, 1-2.2; P=.03). A delayed amniotomy was associated with a higher rate of postpartum hemorrhage (0% vs 9.5%; P=.01). No significant differences were observed in the cesarean delivery rates, length of hospital stay, maternal infection, or neonatal outcomes. CONCLUSION: Although an early amniotomy does not shorten the time from Foley balloon insertion to active labor, it shortens time from Foley balloon removal to active labor and delivery without increasing complications. The increased postpartum hemorrhage rate in the delayed amniotomy group suggests increased risks with delayed amniotomy.

Prediction of metabolic syndrome following a first pregnancy.

BACKGROUND: The prevalence of metabolic syndrome is rapidly increasing in the United States. We hypothesized that prediction models using data obtained during pregnancy can accurately predict the future development of metabolic syndrome. OBJECTIVE: This study aimed to develop machine learning models to predict the development of metabolic syndrome using factors ascertained in nulliparous pregnant individuals. STUDY DESIGN: This was a secondary analysis of a prospective cohort study (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be Heart Health Study [nuMoM2b-HHS]). Data were collected from October 2010 to October 2020, and analyzed from July 2023 to October 2023. Participants had in-person visits 2 to 7 years after their first delivery. The primary outcome was metabolic syndrome, defined by the National Cholesterol Education Program Adult Treatment Panel III criteria, which was measured within 2 to 7 years after delivery. A total of 127 variables that were obtained during pregnancy were evaluated. The data set was randomly split into a training set (70%) and a test set (30%). We developed a random forest model and a lasso regression model using variables obtained during pregnancy. We compared the area under the receiver operating characteristic curve for both models. Using the model with the better area under the receiver operating characteristic curve, we developed models that included fewer variables based on SHAP (SHapley Additive exPlanations) values and compared them with the original model. The final model chosen would have fewer variables and noninferior areas under the receiver operating characteristic curve. RESULTS: A total of 4225 individuals met the inclusion criteria; the mean (standard deviation) age was 27.0 (5.6) years. Of these, 754 (17.8%) developed metabolic syndrome. The area under the receiver operating characteristic curve of the random forest model was 0.878 (95% confidence interval, 0.846-0.909), which was higher than the 0.850 of the lasso model (95% confidence interval, 0.811-0.888; P<.001). Therefore, random forest models using fewer variables were developed. The random forest model with the top 3 variables (high-density lipoprotein, insulin, and high-sensitivity C-reactive protein) was chosen as the final model because it had the area under the receiver operating characteristic curve of 0.867 (95% confidence interval, 0.839-0.895), which was not inferior to the original model (P=.08). The area under the receiver operating characteristic curve of the final model in the test set was 0.847 (95% confidence interval, 0.821-0.873). An online application of the final model was developed (https://kawakita.shinyapps.io/metabolic/). CONCLUSION: We developed a model that can accurately predict the development of metabolic syndrome in 2 to 7 years after delivery.

Desirability of outcome ranking for obstetrical trials: illustration and application to the ARRIVE trial.

BACKGROUND: In randomized trials, 1 primary outcome is typically chosen to evaluate the consequences of an intervention, whereas other important outcomes are relegated to secondary outcomes. This issue is amplified for many obstetrical trials in which an intervention may have consequences for both the pregnant person and the child. In contrast, desirability of outcome ranking, a paradigm shift for the design and analysis of clinical trials based on patient-centric evaluation, allows multiple outcomes-including from >1 individual-to be considered concurrently. OBJECTIVE: This study aimed to describe desirability of outcome ranking methodology tailored to obstetrical trials and to apply the methodology to maternal-perinatal paired (dyadic) outcomes in which both individuals may be affected by an intervention but may experience discordant outcomes (eg, an obstetrical intervention may improve perinatal but worsen maternal outcomes). STUDY DESIGN: This secondary analysis applies the desirability of outcome ranking methodology to data from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network ARRIVE trial. The original analysis found no substantial difference in the primary (perinatal composite) outcome, but a decreased risk of the secondary outcome of cesarean delivery with elective induction at 39 weeks. In the present desirability-of-outcome-ranking analysis, dyadic outcomes ranging from spontaneous vaginal delivery without severe neonatal complication (most desirable) to cesarean delivery with perinatal death (least desirable) were classified into 8 categories ranked by overall desirability by experienced investigators. Distributions of the desirability of outcome ranking were compared by estimating the probability of having a more desirable dyadic outcome with elective induction at 39 weeks of gestation than with expectant management. To account for various perspectives on these outcomes, a complementary analysis, called the partial credit strategy, was used to grade outcomes on a 100-point scale and estimate the difference in overall treatment scores between groups using a t test. RESULTS: All 6096 participants from the trial were included. The probability of a better dyadic outcome for a randomly selected patient who was randomized to elective induction was 53% (95% confidence interval, 51-54), implying that elective induction led to a better overall outcome for the dyad when taking multiple outcomes into account concurrently. Furthermore, the desirability-of-outcome-ranking probability of averting cesarean delivery with elective induction was 52% (95% confidence interval, 51-53), which was not at the expense of an operative vaginal delivery or a poorer outcome for the perinate (ie, survival with a severe neonatal complication or perinatal death). Randomization to elective induction was also advantageous in most of the partial credit score scenarios. CONCLUSION: Desirability-of-outcome-ranking methodology is a useful tool for obstetrical trials because it provides a concurrent view of the effect of an intervention on multiple dyadic outcomes, potentially allowing for better translation of data for decision-making and person-centered care.

Socioeconomic disadvantage in pregnancy and postpartum risk of cardiovascular disease.

BACKGROUND: Pregnancy is an educable and actionable life stage to address social determinants of health (SDOH) and lifelong cardiovascular disease (CVD) prevention. However, the link between a risk score that combines multiple neighborhood-level social determinants in pregnancy and the risk of long-term CVD remains to be evaluated. OBJECTIVE: To examine whether neighborhood-level socioeconomic disadvantage measured by the Area Deprivation Index (ADI) in early pregnancy is associated with a higher 30-year predicted risk of CVD postpartum, as measured by the Framingham Risk Score. STUDY DESIGN: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be Heart Health Study longitudinal cohort. Participant home addresses during early pregnancy were geocoded at the Census-block level. The exposure was neighborhood-level socioeconomic disadvantage using the 2015 ADI by tertile (least deprived [T1], reference; most deprived [T3]) measured in the first trimester. Outcomes were the predicted 30-year risks of atherosclerotic cardiovascular disease (ASCVD, composite of fatal and nonfatal coronary heart disease and stroke) and total CVD (composite of ASCVD plus coronary insufficiency, angina pectoris, transient ischemic attack, intermittent claudication, and heart failure) using the Framingham Risk Score measured 2 to 7 years after delivery. These outcomes were assessed as continuous measures of absolute estimated risk in increments of 1%, and, secondarily, as categorical measures with high-risk defined as an estimated probability of CVD ≥10%. Multivariable linear regression and modified Poisson regression models adjusted for baseline age and individual-level social determinants, including health insurance, educational attainment, and household poverty. RESULTS: Among 4309 nulliparous individuals at baseline, the median age was 27 years (interquartile range [IQR]: 23-31) and the median ADI was 43 (IQR: 22-74). At 2 to 7 years postpartum (median: 3.1 years, IQR: 2.5, 3.7), the median 30-year risk of ASCVD was 2.3% (IQR: 1.5, 3.5) and of total CVD was 5.5% (IQR: 3.7, 7.9); 2.2% and 14.3% of individuals had predicted 30-year risk ≥10%, respectively. Individuals living in the highest ADI tertile had a higher predicted risk of 30-year ASCVD % (adjusted ß: 0.41; 95% confidence interval [CI]: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top 2 ADI tertiles had higher absolute risks of 30-year total CVD % (T2: adj. ß: 0.37; 95% CI: 0.03, 0.72; T3: adj. ß: 0.74; 95% CI: 0.36, 1.13). Similarly, individuals living in neighborhoods in the highest ADI tertile were more likely to have a high 30-year predicted risk of ASCVD (adjusted risk ratio [aRR]: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSION: Neighborhood-level socioeconomic disadvantage in early pregnancy was associated with a higher estimated long-term risk of CVD postpartum. Incorporating aggregated SDOH into existing clinical workflows and future research in pregnancy could reduce disparities in maternal cardiovascular health across the lifespan, and requires further study.

Postpartum pharmacologic thromboprophylaxis and complications in a US cohort.

BACKGROUND: Venous thromboembolism accounts for approximately 9% of pregnancy-related deaths in the United States. National guidelines recommend postpartum risk stratification and pharmacologic prophylaxis in at-risk individuals. Knowledge on modern rates of postpartum pharmacologic thromboprophylaxis and its associated risks is limited. OBJECTIVE: This study aimed to describe the rate of, and factors associated with, initiation of postpartum pharmacologic prophylaxis for venous thromboembolism, and to assess associated adverse outcomes. STUDY DESIGN: This was a secondary analysis of a multicenter cohort of individuals delivering on randomly selected days at 17 US hospitals (2019-2020). Medical records were reviewed by trained and certified personnel. Those with an antepartum diagnosis of venous thromboembolism, receiving antepartum anticoagulation, or known SARS-CoV-2 infection were excluded. The primary outcome was use of postpartum pharmacologic thromboprophylaxis. Secondary outcomes included bleeding complications, surgical site infection, hospital readmission, and venous thromboembolism through 6 weeks postpartum. The rate of thromboprophylaxis administration was assessed by mode of delivery, institution, and continuance to the outpatient setting. Multivariable regression models were developed using k-fold cross-validation with stepwise backward elimination to evaluate factors associated with thromboprophylaxis administration. Univariable and multivariable logistic models with propensity score covariate adjustment were performed to assess the association between thromboprophylaxis administration and adverse outcomes. RESULTS: Of 21,114 individuals in the analytical cohort, 11.9% (95% confidence interval, 11.4%-12.3%) received postpartum pharmacologic thromboprophylaxis; the frequency of receipt was 29.8% (95% confidence interval, 28.7%-30.9%) following cesarean and 3.5% (95% confidence interval, 3.2%-3.8%) following vaginal delivery. Institutional rates of prophylaxis varied from 0.21% to 34.8%. Most individuals (83.3%) received thromboprophylaxis only as inpatients. In adjusted analysis, cesarean delivery (adjusted odds ratio, 19.17; 95% confidence interval, 16.70-22.00), hysterectomy (adjusted odds ratio, 15.70; 95% confidence interval, 4.35-56.65), and obesity (adjusted odds ratio, 3.45; 95% confidence interval, 3.02-3.95) were the strongest factors associated with thromboprophylaxis administration. Thromboprophylaxis administration was not associated with surgical site infection (0.9% vs 0.6%; odds ratio, 1.48; 95% confidence interval, 0.80-2.74), bleeding complications (0.2% vs 0.1%; odds ratio, 2.60; 95% confidence interval, 0.99-6.80), or postpartum readmission (0.9% vs 0.3%; adjusted odds ratio, 1.38; 95% confidence interval, 0.68-2.81). The overall rate of venous thromboembolism was 0.06% (95% confidence interval, 0.03%-0.10%) and was higher in those receiving prophylaxis (0.2%) compared with those not receiving prophylaxis (0.04%). CONCLUSION: Approximately 1 in 10 patients received postpartum pharmacologic thromboprophylaxis in this US cohort. Rates of prophylaxis varied widely by institution. Cesarean delivery, hysterectomy, and obesity were predominant factors associated with postpartum thromboprophylaxis administration.

Blood Pressure Control in Pregnant Patients with Chronic Hypertension and Diabetes: Should <130/80 be the Target?

BACKGROUND: The Chronic Hypertension and Pregnancy Study (CHAP) demonstrated that a target blood pressure of <140/90 mm Hg during pregnancy is associated with improved perinatal outcomes. Outside of pregnancy, pharmacologic therapy for patients with diabetes and hypertension is adjusted to a target blood pressure of <130/80 mm Hg. During pregnancy, patients with both diabetes and chronic hypertension may also benefit from tighter control with a target blood pressure (BP) <130/80 mm Hg. OBJECTIVE: We compared perinatal outcomes in patients with hypertension and diabetes who achieved BP <130/80 versus 130-139/80-89 mm Hg. STUDY DESIGN: This was a secondary analysis of a multi-center randomized controlled trial. Participants were included in this secondary analysis if they had diabetes diagnosed prior to pregnancy or at <20 weeks' gestation and at least two recorded BP measurements prior to delivery. Average systolic and diastolic BP were calculated using ambulatory antenatal BPs. The primary composite outcome was preeclampsia with severe features, indicated preterm birth <35 weeks, or placental abruption. Secondary outcomes were components of the primary outcome, cesarean delivery, fetal or neonatal death, neonatal intensive care unit (NICU) admission, and small for gestational age (SGA). Comparisons were made between those with an average systolic BP <130 mm Hg and average diastolic BP <80 mm Hg and those with an average systolic blood pressure 130-139 mm Hg or diastolic blood pressure 80-89 mm Hg using Student's t-test and chi-squared tests. Multivariable log-binomial regression models were used to evaluate risk ratios between blood pressure groups for dichotomous outcomes while accounting for baseline covariates. RESULTS: Of 434 participants included, 150 (34.6%) had an average blood pressure less than 130/80 mm Hg. Participants with an average blood pressure less than 130/80 were more likely to be on antihypertensive medications at the start of pregnancy and more likely to have newly diagnosed DM prior to 20 weeks. Participants with an average blood pressure less than 130/80 mm Hg were less likely to have the primary adverse perinatal outcome (19.3% vs 46.5%, adjusted relative risk (aRR) 0.43, 95% CI 0.30-0.61, p<0.01), with decreased risks specifically of preeclampsia with severe features (aRR 0.35, 95% CI 0.23-0.54) and indicated preterm birth prior to 35 weeks (aRR 0.44, 95% CI 0.24-0.79). The risk of NICU admission was lower in the lower blood pressure group (aRR 0.74, 95% CI 0.59-0.94). No differences were noted in cesarean delivery (aRR 1.04, 95% CI 0.90-1.20), fetal or neonatal death (aRR 0.59, 95% CI 0.12-2.92). SGA less than the 10th percentile was lower in the lower blood pressure group (aRR 0.37, 95% CI 0.14-0.96). CONCLUSION: In those with chronic hypertension and diabetes prior to 20 weeks, achieving an average goal blood pressure of <130/80 mm Hg may be associated with improved perinatal outcomes.

Point-of-Care Ultrasound in Critical Care Obstetrics: A Scoping Review of the Current Evidence.

OBJECTIVES: To synthesize the current evidence of maternal point-of-care ultrasound (POCUS) in obstetrics. A scoping review was conducted using PubMed, Clinicaltrials.gov, and the Cochrane library from inception through October 2023. METHODS: Studies were eligible for inclusion if they described the use of POCUS among obstetric or postpartum patients. Two authors independently screened all abstracts. Quantitative, qualitative, and mixed-methods studies were eligible for inclusion. Case reports of single cases, review articles, and expert opinion articles were excluded. Studies describing detailed maternal nonobstetric sonograms or maternal first trimester sonograms to confirm viability and rule out ectopic pregnancy were also excluded. Data were tabulated using Microsoft Excel and summarized using a narrative review and descriptive statistics. RESULTS: A total of 689 publications were identified through the search strategy and 12 studies met the inclusion criteria. Nine studies evaluated the use of lung POCUS in obstetrics in different clinical scenarios. Lung ultrasound (LUS) findings in preeclampsia showed an excellent ability to detect pulmonary edema (area under the receiver operating characteristic 0.961) and findings were correlated with clinical evidence of respiratory distress (21 of 57 [37%] versus 14 of 109 [13%]; P = .001). Three studies evaluated abdominal POCUS, two of the inferior vena cava (IVC) to predict postspinal anesthesia hypotension (PSAH) and fluid receptivity and one to assess the rate of ascites in patients with preeclampsia. Patients with PSAH had higher IVC collapsibility (area under the curve = 0.950, P < .001) and, in patients with severe preeclampsia, there is a high rate of ascites (52%) associated with increased risk of adverse outcomes. There were no studies on the use of subjective cardiac POCUS. CONCLUSION: POCUS use in the management of high-risk obstetrics has increased. LUS has been the most studied modality and appears to have a potential role in the setting of preeclampsia complicated by pulmonary edema. Cardiac and abdominal POCUS have not been well studied. Trials are needed to evaluate its clinical applicability, reliability, and technique standardization before widespread use.

Impact of the ARRIVE Trial on Stillbirth Rates in Nulliparous Individuals.

OBJECTIVE: We aim to examine the population-level rates of induction, stillbirth, perinatal mortality, and neonatal death before and after the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial. STUDY DESIGN: This study was a cross-sectional analysis of publicly available U.S. Live Birth data linked with Infant Death and Fetal Death certificate data from National Vital Statistics Online. We limited analyses to nulliparous individuals with singleton pregnancy and cephalic presentation who delivered at 39 weeks or greater. The pre- and post-ARRIVE periods spanned from August 2016 to July 2018, and from January 2019 to December 2020, respectively. Our primary outcome was a stillbirth. Secondary outcomes included induction of labor, perinatal mortality, and neonatal death. Outcomes were compared between the pre- and post-ARRIVE periods. Modified Poisson regression was used to calculate adjusted relative risks (aRRs). RESULTS: Of 2,817,071 births, there were 1,454,346 births in the pre-ARRIVE period and 1,362,725 in the post-ARRIVE period; there were 1,196 and 1,062 stillbirths in the pre- and post-ARRIVE periods, respectively. Compared to the pre-ARRIVE period, the post-ARRIVE period was not associated with a significant decrease in the risk of stillbirth at 39 weeks or greater (aRR 0.92 [95% confidence interval {95% CI} 0.85-1.00]) and stillbirth at 40 weeks or greater (aRR 0.92 [95% CI 0.82-1.04]). Compared to the pre-ARRIVE trial period, the post-ARRIVE trial was associated with increased rates of induction of labor at 39 weeks (aRR 1.37 [95% CI 1.37-1.38]) and 40 weeks (aRR 1.24 [95% CI 1.24-1.25]. Similar to stillbirth, there was no significant decrease in the risk of perinatal mortality at 39 weeks or greater or 40 weeks or greater. There was also no statistically significant change in neonatal death rates at 39 weeks or greater or at 40 weeks or greater. CONCLUSION: The increase in induction of labor at 39 weeks was not large enough to impact the stillbirth rate at 39 weeks or greater. KEY POINTS: · Post-ARRIVE trial, rate of induction of labor increased at 39 and 40 weeks.. · Post-ARRIVE trial, stillbirth and perinatal mortality rates remained unchanged.. · Induction rate rise post-ARRIVE trial did not impact neonatal death rates..

Neonatal and Maternal Outcomes in Nulliparous Individuals according to Prepregnancy Body Mass Index.

OBJECTIVE: This study aimed to examine the effect of incremental changes in body mass index (BMI, kg/m2) on the association with adverse pregnancy outcomes. STUDY DESIGN: This was a retrospective cohort study of U.S. vital statistics Live Birth and Infant Death linked data from 2011 to 2020. We limited analyses to nulliparas with singleton pregnancies who delivered at 20 weeks or greater. Outcomes were compared according to the prepregnancy BMI category using 5 kg/m2 increments, with each of the other BMI categories sequentially as the referent. The composite neonatal outcome was defined as any neonatal death, neonatal intensive care unit (ICU), surfactant use, ventilation use, or seizure. Severe maternal morbidity was defined as any maternal ICU, transfusion, uterine rupture, and hysterectomy. Adjusted relative risks were calculated for each BMI category as a referent group, using modified Poisson regression and adjusting for confounders. RESULTS: A total of 11,174,890 nulliparous individuals were included. From 2011 to 2020, the proportions of individuals with BMI 40 or greater, BMI 50 or greater, and BMI 60 or greater increased significantly (from 3.1 to 4.9%, from 0.4 to 0.6%, from 0.03 to 0.06%, respectively; all trend p-values < 0.001). As BMI deviated from normal BMI, risks of neonatal and maternal adverse outcomes increased progressively. For example, as BMI deviated from normal BMI (18.5-24.9), the risk of composite neonatal outcome increased by 2% in individuals with BMI < 18.5 and up to 2.11-fold in individuals with BMI 65-69.9. When compared with BMI 40 to 44.9, BMI 35 to 39.9 was associated with an 8% decreased risk of composite neonatal outcome, whereas BMI 45 to 49.9 was associated with an 8% increased risk of composite neonatal outcome. CONCLUSION: Incremental increases in prepregnancy BMI are linked to higher risks of adverse pregnancy outcomes, highlighting the need for effective weight management before conception. KEY POINTS: · Incremental BMI increases raise pregnancy risks.. · Higher BMI linked to adverse neonatal outcomes.. · Elevated BMI heightens severe maternal morbidity..

Impact of the ARRIVE Trial in Nulliparous Individuals with Morbid Obesity: Interrupted Time Series Analysis.

OBJECTIVE: We aimed to examine rates of induction of labor at 39 weeks and cesarean delivery before and after the ARRIVE (A Randomized Trial of Induction Versus Expectant Management) trial stratified by body mass index (BMI; kg/m2) category. STUDY DESIGN: This was a repeated cross-sectional analysis of publicly available U.S. birth certificate data from 2015 to 2021. We limited analyses to nulliparous individuals with a singleton pregnancy, cephalic presentation, without chronic hypertension, diabetes (gestational or pregestational), and fetal anomaly who delivered between 39 and 42 weeks' gestation. The pre-ARRIVE period spanned from August 2016 to July 2018 and the post-ARRIVE period spanned from January 2019 to December 2020. The dissemination period of the ARRIVE trial was from August 2018 to December 2018. Our co-primary outcomes were induction at 39 weeks and cesarean delivery. Our secondary outcomes were overall induction of labor and preeclampsia. We conducted an interrupted time series analysis after stratifying by prepregnancy BMI (<40 or ≥40). Negative binomial regression was used to calculate adjusted incident rate ratios with 95% confidence intervals. RESULTS: Of 2,122,267 individuals that were included, 2,051,050 had BMI <40 and 71,217 had BMI ≥40. In individuals with BMI <40, the post-ARRIVE period compared to the pre-ARRIVE period was associated with an increased rate of induction of labor at 39 weeks, a decreased rate of cesarean delivery, and an increased rate of overall induction of labor. In individuals with BMI ≥40, the post-ARRIVE period compared to the pre-ARRIVE period was associated with an increased rate of induction of labor at 39 weeks, an increased rate of overall induction of labor and a decreased rate of preeclampsia; however, the decrease in the rate of cesarean delivery was not significant. CONCLUSION: An increase in induction of labor at 39 weeks' gestation in individuals with BMI ≥40 was not associated with a decrease in the cesarean delivery rate. KEY POINTS: · The ARRIVE trial increased 39-week labor inductions in BMI <40 and ≥40.. · BMI <40 had fewer cesareans; BMI ≥40 showed no significant decrease.. · Offering labor induction is reasonable as cesarean rates didn't increase..

Trial of Labor versus Repeat Cesarean Delivery in Individuals with Morbid Obesity after Previous Cesarean Delivery.

OBJECTIVE: This study aimed to compare adverse neonatal outcomes associated with the trial of labor after cesarean (TOLAC) at term in pregnancies according to maternal prepregnancy body mass index (BMI; kg/m2) and the presence of previous vaginal delivery (VD). STUDY DESIGN: This was a repeated cross-sectional analysis of individuals with singleton, cephalic, and term deliveries with a history of one or two cesarean deliveries in the Linked Birth/Infant Death data from 2011 to 2020. Outcomes were examined according to the BMI category including BMI <30, 30 to 39.9, and 40 to 69.9 kg/m2. The primary outcome was a composite neonatal outcome, defined as any presence of neonatal death, neonatal intensive care unit admission, assisted ventilation, surfactant therapy, or seizures. Outcomes were compared between TOLAC and elective repeat cesarean delivery (eRCD) after stratifying by BMI category and previous VD. Log-binomial regression was performed to obtain adjusted relative risk (aRR) with 99% confidence intervals, controlling for covariates. RESULTS: Of 4,055,440 individuals, 2,627,131 had BMI <30 kg/m2, 1,108,278 had BMI 30 to 39.9 kg/m2, and 320,031 had BMI 40 to 69.9 kg/m2. In individuals with no previous VD, VD rates after TOLAC were 66.7, 57.2, and 48.1%, respectively. In individuals with previous VD, VD rates after TOLAC were 81.4, 74.7, and 67.3%, respectively. In individuals without previous VD, compared with those who had an eRCD, those who had TOLAC were more likely to experience composite neonatal outcomes in individuals with BMI < 30 kg/m2 (5.0 vs. 6.5%; aRR = 1.33 [1.30-1.36]), BMI 30 to 39.9 kg/m2 (6.1 vs. 7.8%; aRR = 1.29 [1.24-1.34]), and BMI 40 to 69.9 kg/m2 (8.2 vs. 9.0%; aRR = 1.15 [1.07-1.23]). In individuals with previous VD, there was no difference in the composite neonatal outcomes in BMI < 30 kg/m2 (6.2 vs. 5.8%; aRR = 0.98 [0.96-1.00]), BMI 30 to 39.9 kg/m2 (7.4 vs. 7.1%; aRR = 0.99 [0.95-1.02]), and BMI 40 to 69.9 kg/m2 (9.4 vs. 8.7%; aRR = 0.96 [0.91-1.02]). CONCLUSION: TOLAC among obese individuals could be offered in selected cases. KEY POINTS: · TOLAC among obese individuals could be offered selectively, despite their reduced likelihood of attempting or succeeding at it.. · Higher BMI individuals show decreased rates of both attempting and achieving successful TOLAC.. · Despite these trends, attempting TOLAC after a previous vaginal delivery does not heighten neonatal complications..

Temporal Trend in Maternal Morbidity and Comorbidity.

OBJECTIVE: This study aimed to examine the temporal trends of severe maternal morbidity (SMM) in the U.S. population in relation to trends in maternal comorbidity. STUDY DESIGN: We performed a repeated cross-sectional analysis of data from individuals at 20 weeks' gestation or greater using U.S. birth certificate data from 2011 to 2021. Our primary outcome was SMM defined as the occurrence of intensive care unit admission, eclampsia, hysterectomy, uterine rupture, and blood product transfusion. We also examined the proportions of maternal comorbidity. Outcomes of the adjusted incidence rate ratio (IRR) with 99% confidence intervals (99% CIs) for 2021 m12 compared with 2011 m1 were calculated using negative binomial regression, controlling for predefined confounders. RESULTS: There were 42,504,125 births included in the analysis. From 2011 m1 to 2021 m12, there was a significant increase in the prevalence of advanced maternal age (35-39 [45%], 40-44 [29%], and ≥45 [43%] years), morbid obesity (body mass index 40-49.9 [66%], 50-59.9 [91%], and 60-69.9 [98%]), previous cesarean delivery (14%), chronic hypertension (104%), pregestational diabetes (64%), pregnancy-associated hypertension (240%), gestational diabetes (74%), and preterm delivery at 34 to 36 weeks (12%). There was a significant decrease in the incidence of multiple gestation (9%), preterm delivery at 22 to 27 weeks (9%), and preterm delivery at 20 to 21 weeks (22%). From 2011 m1 to 2021 m12, the incidence of SMM increased from 0.7 to 1.0% (crude IRR 1.60 [99% CI 1.54-1.66]). However, the trend was no longer statistically significant after controlling for confounders (adjusted IRR 1.01 [95% CI 0.81-1.27]). The main comorbidity that was associated with the increase in SMM was pregnancy-associated hypertension. CONCLUSION: The rise in the prevalence of comorbidity in pregnancy seems to fuel the rise in SMM. Interventions to prevent SMM should include the management and prevention of pregnancy-associated hypertension. KEY POINTS: · The rise in maternal mortality is related to morbidity.. · Pregnancy-associated hypertension increases morbidity.. · There were increasing trends in age, body mass index, and medical conditions..

When Are Pregnant Patients Receiving Tranexamic Acid during Delivery Hospitalization in the United States?

OBJECTIVE: The World Health Organization recommends tranexamic acid (TXA) in the management of postpartum hemorrhage (PPH). However, the role of TXA in PPH prevention and the optimal timing of TXA administration remain unknown. Our objective was to describe the timing of TXA administration, differences in timing of TXA administration by mode of delivery, and current trends in TXA administration in the United States. STUDY DESIGN: We conducted a descriptive study of trends in TXA administration using the Cerner Real-World Database. We identified 1,544,712 deliveries occurring at greater than 24 weeks' gestation from January 1, 2016, to February 21, 2023. Demographic data were collected including gestational age, mode of delivery, and comorbidities. The timing of TXA administration and differences in TXA timing by mode of delivery were also collected. RESULTS: In our cohort, 21,433 patients (1.39%) received TXA. The majority of patients who received TXA were between ages 25 and 34 years old (55.3%), White (60.7%), and delivered between 37 and 416/7 weeks (81.4%). The TXA group had a higher prevalence of medical comorbidities including obesity (32.9 vs. 19.0%, p < 0.00001), preeclampsia (19.6 vs. 6.81%, p < 0.00001), and pregestational diabetes (3.27 vs. 1.36%, p < 0.00001). Among women who received TXA, 15.4% received it within 3 hours before delivery. Among patients who received TXA after delivery, 23.6% received TXA within 3 hours after delivery, whereas 35.7% received TXA between 10 and 24 hours after delivery. A total of 80.4% of patients who received TXA before delivery had a cesarean delivery. CONCLUSION: While TXA is most commonly administered after delivery, many patients are receiving TXA prior to delivery in the United States without clear evidence to guide the timing of administration. A randomized trial is urgently needed to determine the safety and efficacy of TXA when administered prior to delivery. KEY POINTS: · TXA is used in the treatment of PPH.. · The role of TXA in prevention of PPH is unclear.. · Fewer than 2% of patients in the United States receive TXA at delivery.. · TXA administration before delivery in the United States is rising..