Pregnancy Outcomes of Nifedipine Compared With Labetalol for Oral Treatment of Mild Chronic Hypertension.

OBJECTIVE: To evaluate maternal and neonatal outcomes by type of antihypertensive used in participants of the CHAP (Chronic Hypertension in Pregnancy) trial. METHODS: We conducted a planned secondary analysis of CHAP, an open-label, multicenter, randomized trial of antihypertensive treatment compared with standard care (no treatment unless severe hypertension developed) in pregnant patients with mild chronic hypertension (blood pressure 140-159/90-104 mm Hg before 20 weeks of gestation) and singleton pregnancies. We performed three comparisons based on medications prescribed at enrollment: labetalol compared with standard care, nifedipine compared with standard care, and labetalol compared with nifedipine. Although active compared with standard care groups were randomized, medication assignment within the active treatment group was not random but based on clinician or patient preference. The primary outcome was the occurrence of superimposed preeclampsia with severe features, preterm birth before 35 weeks of gestation, placental abruption, or fetal or neonatal death. The key secondary outcome was small for gestational age (SGA) neonates. We also compared medication adverse effects between groups. Relative risks (RRs) and 95% CIs were estimated with log binomial regression to adjust for confounding. RESULTS: Of 2,292 participants analyzed, 720 (31.4%) received labetalol, 417 (18.2%) received nifedipine, and 1,155 (50.4%) received no treatment. The mean gestational age at enrollment was 10.5±3.7 weeks; nearly half of participants (47.5%) identified as non-Hispanic Black; and 44.5% used aspirin. The primary outcome occurred in 217 (30.1%), 130 (31.2%), and 427 (37.0%) in the labetalol, nifedipine, and standard care groups, respectively. Risk of the primary outcome was lower among those receiving treatment (labetalol use vs standard adjusted RR 0.82, 95% CI, 0.72-0.94; nifedipine use vs standard adjusted RR 0.84, 95% CI, 0.71-0.99), but there was no significant difference in risk when labetalol was compared with nifedipine (adjusted RR 0.98, 95% CI, 0.82-1.18). There were no significant differences in SGA or serious adverse events between participants receiving labetalol and those receiving nifedipine. CONCLUSION: No significant differences in predetermined maternal or neonatal outcomes were detected on the basis of the use of labetalol or nifedipine for treatment of chronic hypertension in pregnancy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT02299414.

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.

Large-Scale Proteomics in Early Pregnancy and Hypertensive Disorders of Pregnancy.

Importance: There is no consensus regarding the best method for prediction of hypertensive disorders of pregnancy (HDP), including gestational hypertension and preeclampsia. Objective: To determine predictive ability in early pregnancy of large-scale proteomics for prediction of HDP. Design, Setting, and Participants: This was a nested case-control study, conducted in 2022 to 2023, using clinical data and plasma samples collected between 2010 and 2013 during the first trimester, with follow-up until pregnancy outcome. This multicenter observational study took place at 8 academic medical centers in the US. Nulliparous individuals during first-trimester clinical visits were included. Participants with HDP were selected as cases; controls were selected from those who delivered at or after 37 weeks without any HDP, preterm birth, or small-for-gestational-age infant. Age, self-reported race and ethnicity, body mass index, diabetes, health insurance, and fetal sex were available covariates. Exposures: Proteomics using an aptamer-based assay that included 6481 unique human proteins was performed on stored plasma. Covariates were used in predictive models. Main Outcomes and Measures: Prediction models were developed using the elastic net, and analyses were performed on a randomly partitioned training dataset comprising 80% of study participants, with the remaining 20% used as an independent testing dataset. Primary measure of predictive performance was area under the receiver operating characteristic curve (AUC). Results: This study included 753 HDP cases and 1097 controls with a mean (SD) age of 26.9 (5.5) years. Maternal race and ethnicity were 51 Asian (2.8%), 275 non-Hispanic Black (14.9%), 275 Hispanic (14.9%), 1161 non-Hispanic White (62.8% ), and 88 recorded as other (4.8%), which included those who did not identify according to these designations. The elastic net model, allowing for forced inclusion of prespecified covariates, was used to adjust protein-based models for clinical and demographic variables. Under this approach, no proteins were selected to augment the clinical and demographic covariates. The predictive performance of the resulting model was modest, with a training set AUC of 0.64 (95% CI, 0.61-0.67) and a test set AUC of 0.62 (95% CI, 0.56-0.68). Further adjustment for study site yielded only minimal changes in AUCs. Conclusions and Relevance: In this case-control study with detailed clinical data and stored plasma samples available in the first trimester, an aptamer-based proteomics panel did not meaningfully add to predictive utility over and above clinical and demographic factors that are routinely available.

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.

Diet quality, community food access, and glycemic control among nulliparous individuals with diabetes.

Better diet quality regardless of community food access was associated with a higher likelihood of glycemic control in early pregnancy among nulliparous individuals with pregestational diabetes. These findings highlight the need for interventions that address nutrition insecurity for pregnant individuals living with diabetes.

Optimizing Opioid Prescription Quantity After Cesarean Delivery: A Randomized Controlled Trial.

OBJECTIVE: To test whether an individualized opioid-prescription protocol (IOPP) with a shared decision-making component can be used without compromising postcesarean pain management. METHODS: In this multicenter randomized controlled noninferiority trial, we compared IOPP with shared decision making with a fixed quantity of opioid tablets at hospital discharge. We recruited at 31 centers participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Study participants had uncomplicated cesarean births. Follow-up occurred through 12 weeks postdischarge. Individuals with complicated cesarean births or history of opioid use in the pregnancy were excluded. Participants were randomized 1:1 to IOPP with shared decision making or fixed quantity (20 tablets of 5 mg oxycodone). In the IOPP group, we calculated recommended tablet quantity based on opioid use in the 24 hours before discharge. After an educational module and shared decision making, participants selected a quantity of discharge tablets (up to 20). The primary outcome was moderate to severe pain (score 4 or higher [possible range 0-10]) on the BPI (Brief Pain Inventory) at 1 week after discharge. A total sample size of 5,500 participants was planned to assess whether IOPP with shared decision making was not inferior to the fixed quantity of 20 tablets. RESULTS: From September 2020 to March 2022, 18,990 individuals were screened and 5,521 were enrolled (n=2,748 IOPP group, n=2,773 fixed-quantity group). For the primary outcome, IOPP with shared decision making was not inferior to fixed quantity (59.5% vs 60.1%, risk difference 0.67%; 95% CI, -2.03% to 3.37%, noninferiority margin -5.0) and resulted in significantly fewer tablets received (median 14 [interquartile range 4-20] vs 20, P<.001) through 90 days postpartum. CONCLUSION: Compared with fixed quantity, IOPP with shared decision making was noninferior for outpatient postcesarean analgesia at 1 week postdischarge and resulted in fewer prescribed opioid tablets at discharge. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT04296396.

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..

Neonatal outcomes in term and preterm infants following adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery.

OBJECTIVE: It is currently unknown whether adjunctive azithromycin prophylaxis at the time of non-elective cesarean has differential effects on neonatal outcomes in the context of prematurity. The objective of this study was to compare whether neonatal outcomes differ in term and preterm infants exposed to adjunctive azithromycin prophylaxis before non-elective cesarean delivery. STUDY DESIGN: A planned secondary analysis of a multi-center randomized controlled trial that enrolled women with singleton pregnancies ≥24 weeks gestation undergoing non-elective cesarean delivery (during labor or ≥4 h after membrane rupture). Women received standard antibiotic prophylaxis and were randomized to either adjunctive azithromycin (500 mg) or placebo. The primary composite outcome was neonatal death, suspected or confirmed neonatal sepsis, and serious neonatal morbidities (NEC, PVL, IVH, BPD). Secondary outcomes included NICU admission, neonatal readmission, culture positive infections and prevalence of resistant organisms. Odds ratios (OR) for the effect of azithromycin versus placebo were compared between gestational age strata (preterm [less than 37 weeks] versus term [37 weeks or greater]). Tests of interaction examined homogeneity of treatment effect with gestational age. RESULTS: The analysis includes 2,013 infants, 226 preterm (11.2%) and 1,787 term. Mean gestational ages were 34 and 39.5 weeks, respectively. Within term and preterm strata, maternal and delivery characteristics were similar between the azithromycin and placebo groups. There was no difference in the odds of composite neonatal outcome between those exposed to azithromycin versus placebo in preterm neonates (OR 0.82, 95% CI 0.48-1.41) and in term neonates (OR 1.06, 95% CI 0.77-1.46), with no difference between gestational age strata (p = 0.42). Analysis of secondary outcomes also revealed no differences in treatment effects within or between gestational age strata. CONCLUSION: Exposure to adjunctive azithromycin antibiotic prophylaxis for non-elective cesarean delivery does not increase neonatal morbidity or mortality in term or preterm infants. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov, NCT01235546.

Continuous glucose monitoring vs. self-monitoring in pregnant individuals with type 1 diabetes: an economic analysis.

BACKGROUND: In the United States, approximately 1% of pregnancies are complicated by pregestational diabetes. Individuals with type 1 diabetes have an increased risk of adverse maternal and neonatal outcomes. While continuous glucose monitoring has demonstrated benefits for patients with type 1 diabetes, its cost is higher than traditional intermittent fingerstick monitoring, particularly if used only during pregnancy. OBJECTIVE: To develop an economic analysis model to compare in silico the cost of continuous glucose monitoring and self-monitoring of blood glucose in a cohort of pregnant individuals with type 1 diabetes mellitus. STUDY DESIGN: We developed an economic analysis model to compare two glucose monitoring strategies in pregnant individuals with type 1 diabetes: continuous glucose monitoring and self-monitoring. The model considered hypertensive disorders of pregnancy, large for gestational age, cesarean delivery, neonatal intensive care unit (NICU) admission, and neonatal hypoglycemia. The primary outcome was the total cost per strategy in 2022 USD from a health system perspective, with self-monitoring as the reference group. Probabilities, relative risks, and costs were extracted from the literature, and the costs were adjusted to 2022 US dollars. Sensitivity analyses were conducted by varying parameters based on the probability, relative risk, and cost distributions. The robustness of the results was tested through 1000 Monte Carlo simulations. RESULTS: In the base-case analysis, the cost of pregnancy using continuous glucose monitoring was $26,837 compared to $29,039 for self-monitoring, resulting in a cost reduction of $2,202 per individual. The parameters with the greatest effect on the incremental cost included the relative risk of NICU admission, cost of NICU admission, continuous glucose monitoring costs, and usual care costs. Monte Carlo simulations indicated that continuous glucose monitoring was the optimal strategy 98.7% of the time. One-way sensitivity analysis showed that continuous glucose monitoring was more economical if the relative risk of NICU admission with continuous glucose monitoring vs. self-monitoring was below 1.15. CONCLUSION: Compared to self-monitoring, continuous glucose monitoring is an economical strategy for pregnant individuals with type 1 diabetes mellitus.

Racial and Ethnic Disparities in Severe Maternal Morbidity from Pregnancy through 1-year Postpartum.

BACKGROUND: Previous studies examining racial and ethnic disparities in severe maternal morbidity (SMM) have mainly focused on intrapartum hospitalization. There is limited information regarding the racial and ethnic distribution of SMM occurring in the antepartum and postpartum periods, including SMM occurring beyond the traditional 6 weeks postpartum period. OBJECTIVE: To examine the racial and ethnic distribution of SMM during antepartum, intrapartum, and postpartum hospitalizations through 1-year postpartum, overall and stratified by maternal sociodemographic factors, and to estimate the percent increase in SMM by race and ethnicity and maternal sociodemographic factors within each racial and ethnic group after accounting for both antepartum and postpartum SMM through 1-year postpartum rather than just SMM occurring during the intrapartum hospitalization. STUDY DESIGN: We conducted a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from Michigan, Oregon, and South Carolina from 2008-2020. We examined the distribution of non-transfusion SMM and total SMM per 10,000 cases during antepartum, intrapartum, and postpartum hospitalizations through 365 days postpartum by race and ethnicity and by maternal education and insurance type within each racial and ethnic group. We subsequently examined "SMM cases added" by race and ethnicity and by maternal education and insurance type within each racial and ethnic group. The "SMM cases added" represent cases among unique individuals that are identified by considering the antepartum and postpartum periods but that would be missed if only the intrapartum hospitalization cases were included. RESULTS: Among 2,584,206 birthing individuals, a total of 37,112 (1.4%) individuals experienced non-transfusion SMM and 64,661 (2.5%) experienced any SMM during antepartum, intrapartum, and/or postpartum hospitalization. Black individuals had the highest rate of antepartum, intrapartum, and postpartum non-transfusion and total SMM followed by American Indian individuals. Asian individuals had the lowest rate of non-transfusion and total SMM during antepartum and postpartum hospitalizations while White individuals had the lowest rate of non-transfusion and total SMM during the intrapartum hospitalization. Black individuals were 1.9 times more likely to experience non-transfusion SMM during the intrapartum hospitalization than White individuals, which increased to 2.8 times during the antepartum period and to 2.5 times during the postpartum period. Asian and Hispanic individuals were less likely to experience SMM in the postpartum period than White individuals. Including antepartum and postpartum hospitalizations resulted in disproportionately more cases among Black and American Indian individuals than among White, Hispanic, and Asian individuals. The additional cases were also more likely to occur among individuals with lower educational levels and individuals on government insurance. CONCLUSION: Racial disparities in SMM are underreported in estimates that focus on the intrapartum hospitalization. Additionally, individuals with low socio-economic status bear the greatest burden of SMM occurring during the antepartum and postpartum periods. Approaches that focus on mitigating SMM during the intrapartum period only do not address the full spectrum of health disparities.

Early vs. delayed amniotomy in individuals undergoing pre-induction cervical ripening with transcervical Foley balloon: A meta-analysis.

OBJECTIVES: To systematically review randomized controlled trials (RCTs) and perform a meta-analysis comparing early amniotomy with delayed amniotomy in individuals undergoing pre-induction cervical ripening by Foley balloon. The primary outcome was the rate of cesarean delivery. Understanding the impact of the timing of amniotomy on the rate of cesarean delivery is crucial for obstetricians and healthcare providers when making decisions about the management of labor induction. DATA SOURCES: Data were sourced from electronic databases, including PubMed, OVID, Cochrane Library, Web of Science, and ClinicalTrials.gov through February 2024. The review adhered to Preferred Reporting Item for Systematic Reviews guidelines and registered with PROSPERO (ID CRD42023454520). STUDY ELIGIBILITY CRITERIA: Inclusion criteria comprised RCTs comparing early amniotomy with delayed amniotomy in individuals undergoing cervical ripening by Foley balloon. Early amniotomy was defined as amniotomy soon after cervical ripening. Delayed amniotomy was defined as withholding amniotomy until after the onset of the active phase of labor, until at least 4 hours from either initiation of oxytocin or Foley balloon removal/expulsion, or until achieving > 4 cm of dilation. Participants included nulliparous or multiparous individuals with singleton pregnancies undergoing labor induction at 37 weeks or later. STUDY APPRAISAL AND SYNTHESIS: A systematic literature search was conducted using defined search terms including "early amniotomy", "delayed amniotomy", "induction of labor", "cervical ripening", and "Foley balloon", and "Foley catheter." The quality of the included trials was assessed using the Cochrane Risk of Bias Tool for randomized controlled trials. The primary outcome was cesarean delivery. Secondary outcomes included outcomes related to labor duration and neonatal outcomes. Pooled relative risks (RR) and weighted mean differences (WMD) with 95% confidence intervals were calculated. RESULTS: Five trials involving 849 participants undergoing induction and cervical ripening by Foley balloon were included. The rate of cesarean delivery did not differ between individuals randomly assigned to the early amniotomy group compared with those assigned to the delayed amniotomy group (22.9% vs 23.3%; RR 1.00; 95%CI, 0.65-1.55). Early amniotomy compared to delayed amniotomy was associated with a higher proportion of delivery within 24 hours (79.9% vs. 67.1%; RR 1.19; 95%CI 1.04-1.36). Early amniotomy compared with delayed amniotomy was associated with a shorter interval from oxytocin to delivery (WMD -1.5 hours; 95%CI -2.1- -0.8), from Foley expulsion to vaginal delivery (WMD -2.5 hours; 95%CI -4.8- -0.1), and from the start of oxytocin to vaginal delivery (WMD -1.8 hours; 95%CI -3.2- -0.4). Other outcomes were not significantly different. CONCLUSION: Early amniotomy following cervical ripening by Foley balloon in individuals with singleton pregnancies did not impact rates of cesarean delivery compared with delayed amniotomy but led to shorter duration for various labor progress outcomes.

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.

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.

Mean Arterial Pressure and Neonatal Outcomes in Pregnancies Complicated by Mild Chronic Hypertension.

OBJECTIVE: To estimate the association between mean arterial pressure during pregnancy and neonatal outcomes in participants with chronic hypertension using data from the CHAP (Chronic Hypertension and Pregnancy) trial. METHODS: A secondary analysis of the CHAP trial, an open-label, multicenter randomized trial of antihypertensive treatment in pregnancy, was conducted. The CHAP trial enrolled participants with mild chronic hypertension (blood pressure [BP] 140-159/90-104 mm Hg) and singleton pregnancies less than 23 weeks of gestation, randomizing them to active treatment (maintained on antihypertensive therapy with a goal BP below 140/90 mm Hg) or standard treatment (control; antihypertensives withheld unless BP reached 160 mm Hg systolic BP or higher or 105 mm Hg diastolic BP or higher). We used logistic regression to measure the strength of association between mean arterial pressure (average and highest across study visits) and to select neonatal outcomes. Unadjusted and adjusted odds ratios (per 1-unit increase in millimeters of mercury) of the primary neonatal composite outcome (bronchopulmonary dysplasia, retinopathy of prematurity, necrotizing enterocolitis, or intraventricular hemorrhage grade 3 or 4) and individual secondary outcomes (neonatal intensive care unit admission [NICU], low birth weight [LBW] below 2,500 g, and small for gestational age [SGA]) were calculated. RESULTS: A total of 2,284 participants were included: 1,155 active and 1,129 control. Adjusted models controlling for randomization group demonstrated that increasing average mean arterial pressure per millimeter of mercury was associated with an increase in each neonatal outcome examined except NEC, specifically neonatal composite (adjusted odds ratio [aOR] 1.12, 95% CI, 1.09-1.16), NICU admission (aOR 1.07, 95% CI, 1.06-1.08), LBW (aOR 1.12, 95% CI, 1.11-1.14), SGA below the fifth percentile (aOR 1.03, 95% CI, 1.01-1.06), and SGA below the 10th percentile (aOR 1.02, 95% CI, 1.01-1.04). Models using the highest mean arterial pressure as opposed to average mean arterial pressure also demonstrated consistent associations. CONCLUSION: Increasing mean arterial pressure was positively associated with most adverse neonatal outcomes except NEC. Given that the relationship between mean arterial pressure and adverse pregnancy outcomes may not be consistent at all mean arterial pressure levels, future work should attempt to further elucidate whether there is an absolute threshold or relative change in mean arterial pressure at which fetal benefits are optimized along with maternal benefits. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov , NCT02299414.

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..

Teratogenesis, Perinatal, and Neurodevelopmental Outcomes After In Utero Exposure to Antiseizure Medication: Practice Guideline From the AAN, AES, and SMFM.

This practice guideline provides updated evidence-based conclusions and recommendations regarding the effects of antiseizure medications (ASMs) and folic acid supplementation on the prevalence of major congenital malformations (MCMs), adverse perinatal outcomes, and neurodevelopmental outcomes in children born to people with epilepsy of childbearing potential (PWECP). A multidisciplinary panel conducted a systematic review and developed practice recommendations following the process outlined in the 2017 edition of the American Academy of Neurology Clinical Practice Guideline Process Manual. The systematic review includes studies through August 2022. Recommendations are supported by structured rationales that integrate evidence from the systematic review, related evidence, principles of care, and inferences from evidence. The following are some of the major recommendations. When treating PWECP, clinicians should recommend ASMs and doses that optimize both seizure control and fetal outcomes should pregnancy occur, at the earliest possible opportunity preconceptionally. Clinicians must minimize the occurrence of convulsive seizures in PWECP during pregnancy to minimize potential risks to the birth parent and to the fetus. Once a PWECP is already pregnant, clinicians should exercise caution in attempting to remove or replace an ASM that is effective in controlling generalized tonic-clonic or focal-to-bilateral tonic-clonic seizures. Clinicians must consider using lamotrigine, levetiracetam, or oxcarbazepine in PWECP when appropriate based on the patient's epilepsy syndrome, likelihood of achieving seizure control, and comorbidities, to minimize the risk of MCMs. Clinicians must avoid the use of valproic acid in PWECP to minimize the risk of MCMs or neural tube defects (NTDs), if clinically feasible. Clinicians should avoid the use of valproic acid or topiramate in PWECP to minimize the risk of offspring being born small for gestational age, if clinically feasible. To reduce the risk of poor neurodevelopmental outcomes, including autism spectrum disorder and lower IQ, in children born to PWECP, clinicians must avoid the use of valproic acid in PWECP, if clinically feasible. Clinicians should prescribe at least 0.4 mg of folic acid supplementation daily preconceptionally and during pregnancy to any PWECP treated with an ASM to decrease the risk of NTDs and possibly improve neurodevelopmental outcomes in the offspring.

Severe maternal morbidity from pregnancy through 1 year postpartum.

BACKGROUND: Few recent studies have examined the rate of severe maternal morbidity occurring during the antenatal and/or postpartum period to 42 days after delivery. However, little is known about the rate of severe maternal morbidity occurring beyond 42 days after delivery. OBJECTIVE: This study aimed to examine the distribution of severe maternal morbidity and its indicators during antenatal, delivery, and postpartum hospitalizations to 365 days after delivery and to estimate the increase in severe maternal morbidity rate and its indicators after accounting for antenatal and postpartum severe maternal morbidity to 365 days after delivery. STUDY DESIGN: This was a retrospective cohort study using birth and fetal death certificate data linked to hospital discharge records from Michigan, Oregon, and South Carolina from 2008 to 2020. This study examined the distribution of severe maternal morbidity, nontransfusion severe maternal morbidity, and severe maternal morbidity indicators during antenatal, delivery, and postpartum hospitalizations to 365 days after delivery. Subsequently, this study examined "severe maternal morbidity cases added," which represent cases among unique individuals that are included by considering the antenatal and postpartum periods but that would be missed if only the delivery hospitalization cases were included. RESULTS: A total of 64,661 (2.5%) individuals experienced severe maternal morbidity, whereas 37,112 (1.4%) individuals experienced nontransfusion severe maternal morbidity during antenatal, delivery, and/or postpartum hospitalization. A total of 31% of severe maternal morbidity cases were added after accounting for severe maternal morbidity occurring during the antenatal or postpartum hospitalization to 365 days after delivery, whereas 49% of nontransfusion severe maternal morbidity cases were added after accounting for nontransfusion severe maternal morbidity occurring during the antenatal or postpartum periods. Severe maternal morbidity occurring between 43 and 365 days after delivery contributed to 12% of all severe maternal morbidity cases, whereas nontransfusion severe maternal morbidity occurring between 43 and 365 days after delivery contributed to 19% of all nontransfusion severe maternal morbidity cases. CONCLUSION: Our study showed that a total of 31% of severe maternal morbidity and 49% of nontransfusion severe maternal morbidity cases were added after accounting for severe maternal morbidity occurring during the antenatal or postpartum hospitalization to 365 days after delivery. Our findings highlight the importance of expanding the severe maternal morbidity definition beyond the delivery hospitalization to better capture the full period of increased risk, identify contributing factors, and design strategies to mitigate this risk. Only then can we improve outcomes for mothers and subsequently the quality of life of their infants.