Aspirin 162 mg versus 81 mg for Preeclampsia Prophylaxis in High-risk Obese Individuals: A Comparative Effectiveness Open Label Randomized Trial (ASPREO).

BACKGROUND: In the United States, leading medical societies recommend 81 mg of aspirin daily for the prevention of preeclampsia (PE) in women at risk, whereas the NICE guidelines in the UK recommend a dose as high as 150 mg of aspirin. Recent data also suggest that in the obese population, inadequate dosing or aspirin resistance may impact the efficacy of aspirin at the currently recommend doses. OBJECTIVE: We evaluated whether daily administration of 162 mg aspirin would be more effective compared to 81 mg in decreasing the rate of PE with severe features in high-risk obese pregnant individuals. STUDY DESIGN: We performed a randomized trial between May 2019 and November 2022. Individuals at 12 to 20-weeks gestational age (GA) with a BMI ≥ 30 kg/m2 at time to enrollment, and at least one of three high risk factors: history of PE in a prior pregnancy, at least stage I hypertension documented in the index pregnancy, pre-gestational diabetes or gestational diabetes diagnosed prior to 20 weeks GA were randomized to either 162 mg or 81 mg of aspirin daily till delivery, participants were not blinded to treatment allocation. Exclusion criteria were: multifetal gestation, known major fetal anomalies, seizure disorder, baseline proteinuria, on aspirin due to other indications, or contraindication to aspirin. The primary outcome was PE with severe features (PE or superimposed PE with severe features, eclampsia, or HELLP). Secondary outcomes included rates of preterm birth due to PE, small for gestational age (SGA), postpartum hemorrhage, abruption, and medication side effects. A sample size of 220 was needed using a preplanned Bayesian analysis of the primary outcome to estimate the posterior probability of benefit or harm with a neutral informative prior. RESULTS: Of 343 eligible individuals, 220 (64.1%) were randomized. The primary outcome was available for 209/220 (95%). Baseline characteristics were similar between groups, median gestational age at enrollment was 15.9 weeks in the 162 mg aspirin group and 15.6 weeks in the 81 mg aspirin group. Enrollment prior to 16 weeks occurred in 55/110 of those assigned to 162 mg and 58/110 of those assigned to 81 mg of aspirin. The primary outcome occurred in 35% in the 162 mg aspirin group and in 40% in the 81 mg aspirin group (posterior relative risk, 0.88; 95% credible interval, 0.64-1.22). Bayesian analysis indicated a 78% probability of a reduction in the primary outcome with 162 mg aspirin compared to 81 mg aspirin dose. Rates of indicated preterm birth due to preeclampsia (21% vs 21%), SGA (6.5% vs 2.9%), abruption (2.8% vs 3.0%) and postpartum hemorrhage (10% vs 8.8%) were similar between groups. Medication adverse effects were also similar. CONCLUSION: Among high-risk obese individuals, there was 78% probability of benefit that 162 mg aspirin compared to 81 mg will decrease the rate of PE with severe features. With a best estimate of a 12% reduction when using 162 mg of aspirin in comparison to 81 mg of aspirin in this population. This trial supports doing a larger multicenter trial.

Permissive Intrapartum Glucose Control: An Equivalence Randomized Control Trial (PERMIT).

BACKGROUND: There is limited high quality data to determine best practices for maternal blood glucose management during labor. OBJECTIVE: We compared permissive care (target maternal blood glucose 70-180 mg/dL) to usual care (blood glucose 70-110 mg/dL) among laboring individuals with diabetes. STUDY DESIGN: This was a two-site equivalence randomized control trial for individuals with diabetes (pregestational or gestational) at ≥ 34 weeks in labor. Individuals were randomly allocated to usual care or permissive care. Maternal blood glucose was evaluated by capillary blood glucose monitoring in latent and active labor every 4 and 2 hours. Insulin drip was initiated if maternal blood glucose exceeded the upper bounds of the allocated target. The primary outcome was first neonatal heel stick glucose within two hours of birth before feeding. We assumed a mean first neonatal blood glucose of 50 ±10 mg/dL. To ensure that the use of permissive care did not increase or decrease the first neonatal blood glucose >10 mg/dL (two-tailed, α= 0.05, ß= 0.1), 96 total participants were required. We calculated adjusted relative risk (aRR) and 95% confidence intervals (CI) in an intention-to-treat analysis. A Bayesian analysis was preplanned to estimate the probability of equivalence with a neutral informative prior. RESULTS: Of 511 deliveries with diabetes assessed for eligibility (10/2022 - 6/2023), 280 (54.8%) met eligibility criteria, and 96 (34.3%) agreed and were randomized. In the usual care group, 17% required an insulin drip compared to none in permissive care. There was equivalence in the primary outcome between usual and permissive care (57.9 vs. 57.1 mg/dL, adjusted mean difference -0.72, 95% CI -8.87,7.43). Bayesian analysis indicated 98% posterior probability of mean difference not being greater than ±10 mg/dL. The rate of neonatal hypoglycemia was 25% in the usual care group and 29% in permissive group (adjusted relative risk 1.14, 95% CI 0.60, 2.17). There was no difference in other neonatal or maternal outcomes. CONCLUSION: In this randomized control trial, while almost 1 in 6 individuals with diabetes required an insulin drip with usual intrapartum maternal blood glucose care, permissive care was associated with equivalent neonatal blood glucose.

Trends and Outcomes among Pregnancy and Nonpregnancy-Related Hospitalizations with Diabetic Ketoacidosis.

OBJECTIVE: The study's primary objective was to evaluate adverse outcomes among reproductive-age hospitalizations with diabetic ketoacidosis (DKA), comparing those that are pregnancy-related versus nonpregnancy-related and evaluating temporal trends. STUDY DESIGN: We conducted a retrospective cross-sectional study using the National Inpatient Sample to identify hospitalizations with DKA among reproductive-age women (15-49 years) in the United States (2016-2020). DKA in pregnancy hospitalizations was compared with DKA in nonpregnant hospitalizations. Adverse outcomes evaluated included mechanical ventilation, coma, seizures, renal failure, prolonged hospital stay, and in-hospital death. Multivariable Poisson regression models with robust error variance were used to estimate adjusted relative risk (aRR) and 95% confidence interval (CI). Annual percent change (APC) was used to calculate the change in DKA rate over time. RESULTS: Among 35,210,711 hospitalizations of reproductive-age women, 447,600 (1.2%) were hospitalized with DKA, and among them, 13,390 (3%) hospitalizations were pregnancy-related. The rate of nonpregnancy-related DKA hospitalizations increased over time (APC = 3.8%, 95% CI = 1.5-6.1). After multivariable adjustment, compared with pregnancy-related hospitalizations with DKA, the rates of mechanical ventilation (aRR = 1.56, 95% CI = 1.18-2.06), seizures (aRR = 2.26, 95% CI = 1.72-2.97), renal failure (aRR = 2.26, 95% CI = 2.05-2.50), coma (aRR = 2.53, 95% CI = 1.68-3.83), and in-hospital death (aRR = 2.38, 95% CI = 1.06-5.36) were higher among nonpregnancy-related hospitalizations with DKA. CONCLUSION: A nationally representative sample of hospitalizations indicates that over the 5-year period, the rate of nonpregnancy-related DKA hospitalizations increased among reproductive age women, and a higher risk of adverse outcomes was observed when compared with pregnancy-related DKA hospitalizations. KEY POINTS: · Over 5 years, the rate of pregnancy-related DKA hospitalizations was stable.. · Over 5 years, the rate of nonpregnancy-related DKA hospitalizations increased.. · There is a higher risk of adverse outcomes with DKA outside of pregnancy..

A Machine Learning Algorithm using Clinical and Demographic Data for All-Cause Preterm Birth Prediction.

OBJECTIVE: Preterm birth remains the predominant cause of perinatal mortality throughout the United States and the world, with well-documented racial and socioeconomic disparities. To develop and validate a predictive algorithm for all-cause preterm birth using clinical, demographic, and laboratory data using machine learning. STUDY DESIGN: We performed a cohort study of pregnant individuals delivering at a single institution using prospectively collected information on clinical conditions, patient demographics, laboratory data, and health care utilization. Our primary outcome was all-cause preterm birth before 37 weeks. The dataset was randomly divided into a derivation cohort (70%) and a separate validation cohort (30%). Predictor variables were selected amongst 33 that had been previously identified in the literature (directed machine learning). In the derivation cohort, both statistical (logistic regression) and machine learning (XG-Boost) models were used to derive the best fit (C-Statistic) and then validated using the validation cohort. We measured model discrimination with the C-Statistic and assessed the model performance and calibration of the model to determine whether the model provided clinical decision-making benefits. RESULTS: The cohort includes a total of 12,440 deliveries among 12,071 individuals. Preterm birth occurred in 2,037 births (16.4%). The derivation cohort consisted of 8,708 (70%) and the validation cohort consisted of 3,732 (30%). XG-Boost was chosen due to the robustness of the model and the ability to deal with missing data and collinearity between predictor variables. The top five predictor variables identified as drivers of preterm birth, by feature importance metric, were multiple gestation, number of emergency department visits in the year prior to the index pregnancy, initial unknown body mass index, gravidity, and prior preterm delivery. Test performance characteristics were similar between the two populations (derivation cohort area under the curve [AUC] = 0.70 vs. validation cohort AUC = 0.63). CONCLUSION: Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth with moderate precision. KEY POINTS: · Machine learning can be used to create models to predict preterm birth.. · In our model, all-cause preterm birth can be predicted with moderate precision.. · Clinical, demographic, and laboratory information can be useful to predict all-cause preterm birth..

Pregnancy-Associated Stroke and Outcomes Related to Timing and Hypertensive Disorders.

OBJECTIVE: To estimate temporal trends of stroke in the peripartum period and to assess the relationship between stroke and maternal adverse outcomes vis-à-vis timing and hypertension. METHODS: We conducted a retrospective, cross-sectional study using the National Inpatient Sample to identify hospitalizations with pregnancy-associated stroke in the United States (2016-2019). Temporal trends in pregnancy-associated stroke were examined according to timing of stroke (antepartum vs postpartum) and both prepregnancy and pregnancy hypertensive disorders (yes vs no). Multivariable Poisson regression models with robust error variance were used to examine the association among maternal adverse outcomes, timing of stroke, and hypertensive disorders. RESULTS: Among 15,977,644 pregnancy hospitalizations, 6,100 hospitalizations (38.2/100,000 hospitalizations) were with pregnancy-associated stroke. Of these, 3,635 (59.6%) had antepartum pregnancy-associated stroke and 2,465 (40.4%) had postpartum pregnancy-associated stroke; alternatively, 2,640 (43.3%) had hypertensive disorders, and 3,460 (56.7%) were without hypertensive disorders. From 2016 to 2019, the overall rate of pregnancy-associated stroke (37.5 to 40.8/100,000 pregnancy hospitalizations, P =.028), rate of postpartum pregnancy-associated stroke (14.6 to 17.6/100,000 pregnancy hospitalizations, P =.005), and rate of pregnancy-associated stroke with hypertensive disorders (14.9 to 17.2/100,000 pregnancy hospitalizations, P =.013) increased. Antepartum pregnancy-associated stroke and pregnancy-associated stroke without hypertensive disorders, however, remained stable. Despite higher risk of maternal morbidity in postpartum stroke hospitalizations, including mechanical ventilation and pneumonia, there was no significant difference in in-hospital mortality between antepartum and postpartum stroke. Similarly, between pregnancy-associated stroke with hypertensive disorders and stroke without hypertensive disorders, an increased risk of mechanical ventilation, seizure, and prolonged hospital stay was seen for stroke with hypertensive disorders without an increase in mortality. CONCLUSION: A nationally representative sample of hospitalizations in the United States indicates an increasing trend in the rate of postpartum stroke. Almost half of hospitalizations with pregnancy-associated stroke have concomitant hypertensive disorders. Risk of adverse outcomes, but not mortality, is elevated in patients with stroke occurring in the postpartum period and stroke associated with hypertensive disorders.

Postpartum readmission for hypertension and pre-eclampsia: development and validation of a predictive model.

OBJECTIVE: To develop a model for predicting postpartum readmission for hypertension and pre-eclampsia at delivery discharge and assess external validation or model transportability across clinical sites. DESIGN: Prediction model using data available in the electronic health record from two clinical sites. SETTING: Two tertiary care health systems from the Southern (2014-2015) and Northeastern USA (2017-2019). POPULATION: A total of 28 201 postpartum individuals: 10 100 in the South and 18 101 in the Northeast. METHODS: An internal-external cross validation (IECV) approach was used to assess external validation or model transportability across the two sites. In IECV, data from each health system were first used to develop and internally validate a prediction model; each model was then externally validated using the other health system. Models were fit using penalised logistic regression, and accuracy was estimated using discrimination (concordance index), calibration curves and decision curves. Internal validation was performed using bootstrapping with bias-corrected performance measures. Decision curve analysis was used to display potential cut points where the model provided net benefit for clinical decision-making. MAIN OUTCOME MEASURES: The outcome was postpartum readmission for either hypertension or pre-eclampsia <6 weeks after delivery. RESULTS: The postpartum readmission rate for hypertension and pre-eclampsia overall was 0.9% (0.3% and 1.2% by site, respectively). The final model included six variables: age, parity, maximum postpartum diastolic blood pressure, birthweight, pre-eclampsia before discharge and delivery mode (and interaction between pre-eclampsia × delivery mode). Discrimination was adequate at both health systems on internal validation (c-statistic South: 0.88; 95% confidence interval [CI] 0.87-0.89; Northeast: 0.74; 95% CI 0.74-0.74). In IECV, discrimination was inconsistent across sites, with improved discrimination for the Northeastern model on the Southern cohort (c-statistic 0.61 and 0.86, respectively), but calibration was not adequate. Next, model updating was performed using the combined dataset to develop a new model. This final model had adequate discrimination (c-statistic: 0.80, 95% CI 0.80-0.80), moderate calibration (intercept -0.153, slope 0.960, Emax 0.042) and provided superior net benefit at clinical decision-making thresholds between 1% and 7% for interventions preventing readmission. An online calculator is provided here. CONCLUSIONS: Postpartum readmission for hypertension and pre-eclampsia may be accurately predicted but further model validation is needed. Model updating using data from multiple sites will be needed before use across clinical settings.

Continuous Glucose Monitoring and Time in Range: Association with Adverse Outcomes among People with Type 2 or Gestational Diabetes Mellitus.

OBJECTIVE: Continuous glucose monitoring (CGM) has become available for women with type 2 diabetes mellitus (T2DM) or gestational diabetes mellitus (GDM) during pregnancy. The recommended time in range (TIR, blood glucose 70-140 mg/dL) and its correlation with adverse pregnancy outcomes in this group is unknown. Our aim was to compare maternal and neonatal outcomes in pregnant people with T2DM or GDM with average CGM TIR values >70 versus ≤ 70%. STUDY DESIGN: We conducted a retrospective cohort study of all individuals using CGM during pregnancy from January 2017 to June 2022. Individuals with type 1 diabetes mellitus, or those missing CGM or delivery data were excluded. Primary composite neonatal outcome included any of the following: large for gestational age, NICU admission, need for intravenous glucose, respiratory support, or neonatal death. Secondary outcomes included other maternal and neonatal outcomes. Regression models were used to estimate adjusted odds ratio (aOR) and 95% confidence interval (CI). RESULTS: During the study period, 141 individuals with diabetes utilized CGM during pregnancy, with 65 (46%) meeting inclusion criteria. Of the study population, 28 (43%) had TIR ≤70% and 37 (57%) had TIR > 70%. Compared with those with TIR > 70%, the primary composite outcome occurred more frequently in neonates of individuals TIR ≤70% (71.4 vs. 37.8%, aOR: 4.8, 95% CI: 1.6, 15.7). Furthermore, individuals with TIR ≤70% were more likely to have hypertensive disorders (42.9 vs. 16.2%, OR: 3.9, 95% CI: 1.3, 13.0), preterm delivery (54 vs. 27%, OR: 3.1, 95% CI: 1.1, 9.1): , and cesarean delivery (96.4 vs. 51.4%, OR: 4.6, 95% CI: 2.2, 15.1) compared with those with TIR >70%. CONCLUSION: Among people with T2DM or GDM who utilized CGM during pregnancy, 4 out 10 individuals had TIR ≤70% and, compared with those with TIR > 70%, they had a higher likelihood of adverse neonatal and maternal outcomes. KEY POINTS: · Time in range can be utilized as a metric for pregnant patients using continuous glucose monitor.. · Time in range >70% is achievable by 6 out of 10 patients.. · Time in range below goal is associated with adverse neonatal and maternal outcomes..

The Compliance of Prescribed Activity Restriction in Women at High Risk for Preterm Birth.

OBJECTIVE: Despite lack of evidence to support efficacy, activity restriction is one of the most commonly prescribed interventions used for the prevention of preterm birth. We have a departmental policy against the use of activity restriction but many practitioners still prescribe it in an effort to prevent preterm birth. We sought to evaluate the rate and compliance of women who are prescribed activity restriction during pregnancy to prevent preterm birth. STUDY DESIGN: This was a single-site retrospective questionnaire study at a tertiary care, academic affiliated medical center. Women with a history of preterm delivery or short cervix were included. Once patients were identified, each patient was contacted and administered a questionnaire. We assessed the rates of activity restriction prescription and compliance. Secondary outcomes included details regarding activity restriction and treatment in pregnancy. Continuous variables were compared with t-test and categorical variables with Chi-square test. The value p < 0.05 was considered significant. RESULTS: Among the 52 women who responded to the questionnaire, 18 reported being placed on activity restriction by a physician, with 1 self-prescribing activity restriction, giving a rate of our primary outcome of 19 of 52 (36.5%). All women reported compliance with prescribed activity restriction (100%). Gestational age at delivery was not different in women placed on activity restriction. CONCLUSION: This questionnaire suggests that approximately one in three high-risk women were placed on activity restriction during their pregnancy despite a departmental policy against its use. The 100% compliance rate in patients placed on activity restriction is a strong reminder of the impact prescribing patterns of physicians can have on patients. KEY POINTS: · One in three women are placed on activity restriction in pregnancy.. · Women are compliant with prescribed activity restriction.. · Activity restriction does not reduce rates of preterm birth..

Antenatal corticosteroids in the late preterm period for growth-restricted pregnancies.

BACKGROUND: Recently, the Antenatal Late Preterm Steroids study reported that antenatal corticosteroids administered in the late preterm period (34.0-36.6 weeks' gestation) reduced the rate of neonatal respiratory complications at birth. The utility of this intervention in women with fetal growth restriction remains unclear. OBJECTIVE: This study aimed to determine whether administration of antenatal corticosteroids in the late preterm period in pregnancies with growth restriction decreased the need for respiratory support at delivery and other neonatal morbidities. STUDY DESIGN: This was a single-center retrospective cohort study that included growth-restricted pregnancies delivered in the late preterm period. Growth restriction was defined as either a diagnosis of fetal growth restriction or small for gestational age by birthweight less than 10%. The primary composite outcome consisted of any 1 of the following occurring in a single neonate: requirement of continuous positive airway pressure or high-flow nasal cannula for 2 hours or more, oxygen requirement with fraction of inspired oxygen of ≥30% for 4 hours or more, mechanical ventilation at any time, stillbirth, or neonatal death. The primary outcome was compared between steroid naive pregnancies and pregnancies exposed to betamethasone in the late preterm period. Univariable and multivariable statistical analysis was performed and P<.05 was considered statistically significant. RESULTS: A total of 247 women with a diagnosis of growth restriction or small for gestational age met all inclusion criteria, 111 of whom did not receive antenatal corticosteroids and 136 received late preterm antenatal corticosteroids. Demographics were similar between the groups, with the exception of those who received betamethasone being more likely to be nulliparous (P=.01) and to receive a diagnosis of preeclampsia (P=.001). The primary outcome did not differ between the 2 groups (16.2% [18/111] vs 12.5% [17/136]; P=.41). Multivariable modeling controlling for parity and preeclampsia indicated that the rate of the primary composite respiratory outcome was similar between the exposure groups (adjusted odds ratio, 0.63; P=.29). Neonatal hypoglycemia (<40 mg/dL) was more common in newborns exposed to steroids (25.2% [28 /111] vs 40.4% [55/136]; P=.012). CONCLUSION: Administration of antenatal corticosteroids in the late preterm period for pregnancies with growth restriction did not significantly decrease the need for respiratory support in newborns at our institution. The rate of neonatal hypoglycemia increased after exposure to antenatal corticosteroids. This special population may not benefit from late preterm steroids.