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.

Fluid Responsiveness and Management in Obstetrics using Point-of-Care Ultrasound.

Fluid management in obstetric care is crucial due to the complex physiological conditions of pregnancy, which complicate clinical manifestations and fluid balance management. This expert review examines the use of point-of-care ultrasound (POCUS) to evaluate and monitor the response to fluid therapy in pregnant patients. Pregnancy induces significant physiological changes, including increased cardiac output and glomerular filtration rate, decreased systemic vascular resistance, and plasma oncotic pressure. Conditions like preeclampsia further complicate fluid management due to decreased intravascular volume and increased capillary permeability. Traditional methods of assessing fluid volume status, such as physical examination and invasive monitoring, are often unreliable or inappropriate. POCUS provides a non-invasive, rapid, and reliable means to assess fluid responsiveness, which is essential in managing fluid therapy in pregnant patients. This review details various POCUS modalities used to measure dynamic changes in fluid status, focusing on the evaluation of the inferior vena cava (IVC), lung ultrasound (Lung US), and the left ventricular outflow tract (LVOT). IVC ultrasound in spontaneously breathing patients determines diameter variability, predicting fluid responsiveness and being feasible even late in pregnancy. Lung ultrasound is critical for detecting early signs of pulmonary edema before clinical symptoms arise and is more accurate than traditional radiography. The LVOT velocity-time integral (VTI) assesses stroke volume response to fluid challenges, providing a quantifiable measure of cardiac function, especially beneficial in critical care settings where rapid and accurate fluid management is essential. The expert review synthesizes current evidence and practice guidelines, suggesting integrating POCUS 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 over-resuscitation.

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.

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.

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. But 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. METHODS: An analysis of data from the prospective Nulliparous Pregnancy Outcomes Study-Monitoring Mothers-to-Be (nuMoM2b) 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 CVD (ASCVD, composite of fatal and non-fatal 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 4,309 nulliparous individuals at baseline, the median age was 27 years (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 % (adj. ß: 0.41; 95% CI: 0.19, 0.63) compared with those in the lowest tertile; and those living in the top two 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 (aRR: 2.21; 95% CI: 1.21, 4.02) and total CVD ≥10% (aRR: 1.35; 95% CI: 1.08, 1.69). CONCLUSIONS: 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.

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.

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..

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..

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 U.S. STUDY DESIGN: We conducted a descriptive study of trends in TXA administration using the Cerner Real-World DatabaseTM. 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 co-morbidities. The timing of TXA administration and differences in TXA timing by mode of delivery were also collected. RESULTS: In our cohort, 21,433 patients (1.4%) 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 weeks and 41 weeks and 6 days (81.4%). The TXA group had a higher prevalence of medical co-morbidities including obesity (32.9% versus 19.0%, p<0.00001), pre-eclampsia (19.6% versus 6.81%, p<0.00001), and pre-gestational diabetes (3.27% versus 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 while 35.7% received TXA between 10 and 24 hours after delivery. 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.

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..

Postpartum Outcomes in Patients Receiving Venous Thromboembolism Prophylaxis during Antepartum Admission.

OBJECTIVE: We evaluated if venous thromboembolism (VTE) prophylaxis in the inpatient antepartum period was associated with wound hematomas, VTE occurrence, and other adverse outcomes. STUDY DESIGN: This study is a secondary analysis of a retrospective cohort of patients who delivered at University of Alabama at Birmingham (UAB). Patients receiving outpatient anticoagulation (AC) were excluded. We grouped patients into those who received inpatient antepartum prophylactic AC and those who did not. The primary outcome was wound hematomas from delivery to 6 weeks postpartum (PP). Secondary outcomes included VTE occurrence and select adverse outcomes, including other wound complications, unplanned procedures, mode of anesthesia, and intensive care unit (ICU) admission. Analyses were performed with no AC group as the reference. A sensitivity analysis excluding those who received inpatient PP AC was performed. RESULTS: Of 1,035 included patients, only 169 patients received inpatient prophylactic AC. They were older, had higher body mass indices, and more comorbidities. Patients receiving inpatient antepartum AC had higher wound hematomas (adjusted odds ratio [aOR] 23.81; 95% confidence interval [CI] 7.04-80.47). They had similar risk for developing VTE as the control group (aOR 2.68; 95% CI 0.19-37.49) but were more likely to have wound complications (aOR 2.36; 95% CI 1.24-4.47), maternal deaths (p < 0.05), and require PP ICU admission (aOR 13.38; 95% CI 4.79-37.35). When excluding those receiving any PP AC, there was no difference in bleeding complications between the two groups and VTE rates remained unchanged. Rates of maternal deaths and PP ICU admissions remained higher in those who received inpatient antepartum AC prophylaxis. CONCLUSION: In this small cohort study, increased wound hematomas were found in those who received inpatient antepartum AC prophylaxis with no difference in VTE occurrence. While adverse events were increased in the inpatient AC group, this was mostly associated with PP AC prophylaxis. Larger studies should be conducted to describe the true benefits and risks of antepartum AC prophylaxis and determine efficacy of this widely used practice. KEY POINTS: · Peripartum chemoprophylaxis is associated with increased wound hematomas.. · VTE is rare, despite its association with significant peripartum morbidity/mortality.. · Large studies are needed to guide practices that optimize the risk/benefit ratio of chemoprophylaxis..

Maternal Pre-Conception Omega-6, Omega-3, and Omega-6:Omega-3 Intake and Uterine Artery Indices in Mid-Gestation.

OBJECTIVE: Maternal preconception diet influences pregnancy health and fetal outcomes. We examined the relationship between preconception fatty acid (FA) intake and uterine artery indices in mid-gestation in a large, heterogeneous cohort of nulliparous individuals. STUDY DESIGN: This is a secondary analysis of the nuMom2b study. Dietary ꞷ-6 and ꞷ-3 FA intake was assessed with food frequency questionnaires and uterine artery indices were obtained via doppler studies in the second trimester. For our primary outcome of pulsatility index (PI) > 1.6, we compared proportions by each dichotomous FA exposure and tested differences with chi-square. RESULTS: For PI >1.6, OR for the unfavorable FA quartile compared to remaining quartiles for the exposures were 0.96 - 1.25, p 0.157 (ꞷ-6 FA); 0.97 - 1.26, p 0.124 (ꞷ-3 FA); 0.87 -1.14, p 1.00 (ꞷ-6:ꞷ-3 FA ratio). CONCLUSION: No significant associations between self-reported maternal preconception ꞷ-6 and ꞷ-3 FA intake and uterine artery doppler indices measured during the second trimester were observed.

Factors Associated with Refractory Severe Hypertension in Patients with Preeclampsia.

OBJECTIVE: This study aimed to identify factors associated with refractory severe hypertension that does not resolve after an initial dose of antihypertensive medication in patients with preeclampsia. STUDY DESIGN: This was a retrospective study of all pregnant and postpartum individuals with a diagnosis of preeclampsia, superimposed preeclampsia, HELLP (hemolysis, elevated liver enzymes, low platelet) syndrome, or eclampsia who delivered at 22 weeks or greater at a single academic institution from 2010 to 2020. Inclusion criteria were patients with preeclampsia who developed severe hypertension (systolic pressure ≥160 mm Hg or diastolic pressure ≥110 mm Hg) and received antihypertensive medications for acute severe hypertension. We defined refractory severe hypertension as a systolic blood pressure of ≥160 mm Hg or a diastolic blood pressure of ≥110 mm Hg that did not improve after receiving the initial treatment. To evaluate for factors associated with refractory severe hypertension, we developed multivariable modified Poisson regression using all variables with p-value <0.1 on bivariable analysis and calculated adjusted relative risks (aRRs) with 95% confidence intervals (95% CIs). RESULTS: Of 850, 386 (45.4%) had refractory severe hypertension and 464 (54.6%) responded to the initial antihypertensive medications. Factors associated with refractory severe hypertension included higher body mass index (BMI), chronic hypertension, and higher systolic pressure. Every 5 kg/m2 increase in BMI was associated with a 7% increased risk of refractory severe hypertension (aRR = 1.07; 95% CI: 1.02-1.12). Every 10 mm Hg increase in systolic blood pressure was associated with a 10% increased risk of refractory severe hypertension (aRR = 1.10; 95% CI: 1.04-1.17). Chronic hypertension was associated with a 25% increased risk of refractory severe hypertension (aRR = 1.25; 95% CI: 1.01-1.56) in the diastolic pressure model. CONCLUSION: Refractory severe hypertension was associated with elevated BMI, chronic hypertension, and higher systolic blood pressure. KEY POINTS: · Risk factors for refractory severe hypertension are not well-known.. · Almost half of the patients had refractory severe hypertension.. · Higher BMI, chronic hypertension, and higher systolic pressure were the risk factors.. · These patients would require closer follow-up and prompt response to vital signs..