Pregnancy-Associated Extracorporeal Membrane Oxygenation in the United States.

OBJECTIVE: The use of extracorporeal membrane oxygenation (ECMO) therapy has increased in the adult population. Studies from the H1N1 influenza pandemic suggest that ECMO deployment in pregnancy is associated with favorable outcomes. With increasing numbers of pregnant women affected by COVID-19 (coronavirus disease 2019) and potentially requiring this life-saving therapy, we sought to compare comorbidities, costs, and outcomes between pregnancy- and nonpregnancy-associated ECMO therapy among reproductive-aged female patients. STUDY DESIGN: We used the 2013 to 2019 National Readmissions Database. Diagnosis and procedural coding were used to identify ECMO deployment, potential indications, comorbid conditions, and pregnancy outcomes. The primary outcome was in-hospital mortality during the patient's initial ECMO stay. Secondary outcomes included length of stay and hospital charges/costs, occurrence of thromboembolic or bleeding complications during ECMO hospitalization, and mortality and readmissions up to 330 days following ECMO stay. Univariate and multivariate regression models were used to model the associations between pregnancy status and outcomes. RESULTS: The sample included 324 pregnancy-associated hospitalizations and 3,805 nonpregnancy-associated hospitalizations, corresponding to national estimates of 665 and 7,653 over the study period, respectively. Pregnancy-associated ECMO had lower incidence of in-hospital death (adjusted odds ratio [aOR]: 0.56, 95% confidence interval [CI]: 0.41-0.75) and bleeding complications (aOR: 0.67, 95% CI: 0.49-0.93). Length of stay was significantly shorter (adjusted rate ratio (aRR): 0.86, 95% CI: 0.77-0.96) and total hospital costs were less (aRR: 0.83, 95% CI: 0.75-0.93). Differences in the incidence of thromboembolic events (aOR: 1.04, 95% CI: 0.78-1.38) were not statistically significant. CONCLUSION: Pregnancy-associated ECMO therapy had lower incidence of in-hospital death, bleeding complications, total inpatient cost, and length of stay when compared with nonpregnancy-associated ECMO therapy without increased thromboembolic complications. Pregnancy-associated ECMO therapy should be offered to eligible patients. KEY POINTS: · Pregnancy-related ECMO use was compared with nonpregnant use.. · Outcomes were equal or favored pregnancy-related deployment.. · These data may be useful when considering ECMO use in pregnancy..

Long-Term Fine Particulate Matter Concentrations and Prevalence of Severe Acute Respiratory Syndrome Coronavirus 2: Differential Relationships by Socioeconomic Status Among Pregnant Individuals in New York City.

We aimed to determine whether long-term ambient concentrations of fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5)) were associated with increased risk of testing positive for coronavirus disease 2019 (COVID-19) among pregnant individuals who were universally screened at delivery and whether socioeconomic status (SES) modified this relationship. We used obstetrical data collected from New-York Presbyterian Hospital/Columbia University Irving Medical Center in New York, New York, between March and December 2020, including data on Medicaid use (a proxy for low SES) and COVID-19 test results. We linked estimated 2018-2019 PM2.5 concentrations (300-m resolution) with census-tract-level population density, household size, income, and mobility (as measured by mobile-device use) on the basis of residential address. Analyses included 3,318 individuals; 5% tested positive for COVID-19 at delivery, 8% tested positive during pregnancy, and 48% used Medicaid. Average long-term PM2.5 concentrations were 7.4 (standard deviation, 0.8) µg/m3. In adjusted multilevel logistic regression models, we saw no association between PM2.5 and ever testing positive for COVID-19; however, odds were elevated among those using Medicaid (per 1-µg/m3 increase, odds ratio = 1.6, 95% confidence interval: 1.0, 2.5). Further, while only 22% of those testing positive showed symptoms, 69% of symptomatic individuals used Medicaid. SES, including unmeasured occupational exposures or increased susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to concurrent social and environmental exposures, may explain the increased odds of testing positive for COVID-19 being confined to vulnerable pregnant individuals using Medicaid.

ACC-AHA Diagnostic Criteria for Hypertension in Pregnancy Identifies Patients at Intermediate Risk of Adverse Outcomes.

OBJECTIVE: The aim of the study is to compare maternal and neonatal outcomes among patients who are normotensive, hypertensive by Stage I American College of Cardiology-American Heart Association (ACC-AHA) criteria, and hypertensive by American College of Obstetricians and Gynecologists (ACOG) criteria. STUDY DESIGN: Secondary analysis of a prospective first trimester cohort study between 2007 and 2010 at three institutions in Baltimore, MD, was conducted. Blood pressure at 11 to 14 weeks' gestation was classified as (1) normotensive (systolic blood pressure [SBP] <130 mm Hg and diastolic blood pressure [DBP] <80 mm Hg); (2) hypertensive by Stage I ACC-AHA criteria (SBP 130-139 mm Hg or DBP 80-89 mm Hg); or (3) hypertensive by ACOG criteria (SBP ≥140 mm Hg or DBP ≥90 mm Hg). Primary outcomes included preeclampsia, small for gestational age (SGA) neonate, and preterm birth. RESULTS: Among 3,422 women enrolled, 2,976 with delivery data from singleton pregnancies of nonanomalous fetuses were included. In total, 20.2% met hypertension criteria (Stage I ACC-AHA n = 254, 8.5%; ACOG n = 347, 11.7%). The Stage I ACC-AHA group's risk for developing preeclampsia was threefold higher than the normotensive group (adjusted relative risk [aRR] 3.70, 95% confidence interval [CI] 2.40-5.70). The Stage I ACC-AHA group had lower preeclampsia risk than the ACOG group but the difference was not significant (aRR 0.87, 95% CI 0.55-1.37). The Stage I ACC-AHA group was more likely than the normotensive group to deliver preterm (aRR 1.44, 95% CI 1.02-2.01) and deliver an SGA neonate (aRR 1.51, 95% CI 1.07-2.12). The Stage I ACC-AHA group was less likely to deliver preterm compared with the ACOG group (aRR 0.65, 95% CI 0.45-0.93), but differences in SGA were not significant (aRR 1.31, 95% CI 0.84-2.03). CONCLUSION: Pregnant patients with Stage I ACC-AHA hypertension in the first trimester had higher rates of preeclampsia, preterm birth, and SGA neonates compared with normotensive women. Adverse maternal and neonatal outcomes were numerically lower in the Stage I ACC-AHA group compared with the ACOG group, but these comparisons only reached statistical significance for preterm birth. Optimal pregnancy management for first trimester Stage I ACC-AHA hypertension requires active study. KEY POINTS: · Women with first trimester American College of Cardiology-American Heart Association (ACC-AHA) Stage I hypertension were more likely to develop preeclampsia, deliver preterm, and deliver a small-for-gestational age neonate than normotensive women.. · Women with first trimester American College of Obstetricians and Gynecologists (ACOG) hypertension (consistent with stage II ACC-AHA hypertension) had the highest numeric rate of adverse outcomes; however, compared with Stage I ACC-AHA hypertension, there was only statistically significant difference for preterm delivery.. · The risk profile for pregnant women with Stage I ACC-AHA hypertension and women with hypertension by conventional ACOG criteria may be more similar than previously understood..

Reduction in preterm birth among COVID-19-vaccinated pregnant individuals in the United States.

BACKGROUND: Most studies investigating preterm birth and COVID-19 vaccination have suggested no difference in preterm birth rates between vaccinated and unvaccinated pregnant individuals; however, 1 recent study suggested a protective effect of COVID-19 vaccination on preterm birth rates in Australia. OBJECTIVE: This study aimed to determine whether a similar association and protective effect of COVID-19 vaccination on preterm birth would be found in our multistate, US cohort. STUDY DESIGN: A cohort study was conducted using the Vizient Clinical Database, which included data from 192 hospitals in 38 states. Pregnant individuals who delivered between January 2021 and April 2022 were included. Propensity score matching was used to match a "treated" group of pregnant individuals with any COVID-19 vaccination (incomplete or complete vaccination) to a group that had not received any COVID-19 vaccination (the "untreated" group). A complete vaccination series of ≥2 doses of the Moderna or Pfizer vaccines or at least 1 dose of the Johnson & Johnson vaccine was considered. An incomplete series was receipt of 1 dose of the Pfizer or Moderna vaccine. We examined the association between COVID-19 vaccination status and preterm birth at <28, <34, and <37 weeks of gestation. Multivariable logistic regression models were used to adjust for potential confounders, with adjusted odds ratios as the measure of treatment effect. RESULTS: Matching with replacement was performed for 5749 treated participants. After propensity score matching, there was no difference in maternal demographics of age, race, insurance status, parity, or comorbid conditions. Vaccinated individuals were 26% less likely to deliver at <37 weeks of gestation (adjusted odds ratio, 0.74; 95% confidence interval, 0.73-0.75; P<.001), 37% less likely to deliver at <34 weeks of gestation (adjusted odds ratio, 0.63; 95% confidence interval, 0.61-0.64; P<.001), and 43% less likely to deliver at <28 weeks of gestation (adjusted odds ratio, 0.57; 95% confidence interval, 0.55-0.60; P<0.001) than unvaccinated individuals. CONCLUSION: Vaccination against COVID-19 may be protective against preterm birth.

The relationship between COVID-19 vaccination status in pregnancy and birthweight.

BACKGROUND: Despite findings that maternal COVID-19 infection in pregnancy is associated with low birthweight (weight of ≤2500 g), previous studies demonstrate no difference in low birthweight risk between COVID-19 vaccinated and unvaccinated pregnant persons. Few studies, however, have examined the association between unvaccinated, incomplete vaccination, and complete vaccination on low birthweight, and they have been limited by small sample sizes and lack of adjustment for covariates. OBJECTIVE: We sought to address key limitations of prior work and evaluate this association between unvaccinated, incomplete, and complete COVID-19 vaccination status in pregnancy and low birthweight. We predicted a protective association of vaccination on low birthweight that varies by number of doses received. STUDY DESIGN: We performed a population-based retrospective study using the Vizient clinical database, which included data from 192 hospitals in the United States. Our sample included pregnant persons who delivered between January 2021 and April 2022 at hospitals that reported maternal vaccination data and birthweight at delivery. Pregnant persons were categorized into 3 groups as follows: unvaccinated; incompletely vaccinated (1 dose of Pfizer or Moderna); or completely vaccinated (1 dose of Johnson & Johnson or ≥2 doses of Moderna or Pfizer). Demographics and outcomes were analyzed using standard statistical tests. We performed multivariable logistic regression to account for potential confounders between vaccination status and low birthweight in the original cohort. Propensity score matching was used to reduce bias related to the likelihood of vaccination, and the multivariable logistic regression model was then applied to the propensity score-matched cohort. Stratification analysis was performed for gestational age and race and ethnicity. RESULTS: Of the 377,995 participants, 31,155 (8.2%) had low birthweight, and these participants were more likely to be unvaccinated than those without low birthweight (98.8% vs 98.5%, P<.001). Incompletely vaccinated pregnant persons were 13% less likely to have low birthweight neonates compared to unvaccinated persons (odds ratio, 0.87; 95% confidence interval, 0.73-1.04), and completely vaccinated persons were 21% less likely to have low birthweight neonates (odds ratio, 0.79; 95% confidence interval, 0.79-0.89). After controlling for maternal age, race or ethnicity, hypertension, pregestational diabetes, lupus, tobacco use, multifetal gestation, obesity, use of assisted reproductive technology, and maternal or neonatal COVID-19 infections in the original cohort, these associations remained significant for only complete vaccination (adjusted odds ratio, 0.80; 95% confidence interval, 0.70-0.91) and not incomplete vaccination (adjusted odds ratio, 0.87; 95% confidence interval, 0.71-1.04). In the propensity score-matched cohort, pregnant persons who were completely vaccinated against COVID-19 were 22% less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals (adjusted odds ratio, 0.78; 95% confidence interval, 0.76-0.79). CONCLUSION: Pregnant persons who were completely vaccinated against COVID-19 were less likely to have low birthweight neonates compared to unvaccinated and incompletely vaccinated individuals. This novel association was observed among a large population after adjusting for confounders of low birthweight and factors influencing the likelihood of receiving the COVID-19 vaccine.

Mode of delivery among women with maternal cardiac disease.

OBJECTIVE: To determine if maternal cardiac disease affects delivery mode and to investigate maternal morbidity. STUDY DESIGN: Retrospective cohort study performed using electronic medical record data. Primary outcome was mode of delivery; secondary outcomes included indication for cesarean delivery, and rates of severe maternal morbidity. RESULTS: Among 14,160 deliveries meeting inclusion criteria, 218 (1.5%) had maternal cardiac disease. Cesarean delivery was more common in women with maternal cardiac disease (adjusted odds ratio 1.63 [95% confidence interval 1.18-2.25]). Patients delivered by cesarean delivery in the setting of maternal cardiac disease had significantly higher rates of severe maternal morbidity, with a 24.38-fold higher adjusted odds of severe maternal morbidity (95% confidence interval: 10.56-54.3). CONCLUSION: While maternal cardiac disease was associated with increased risk of cesarean delivery, most were for obstetric indications. Additionally, cesarean delivery in the setting of maternal cardiac disease is associated with high rates of severe maternal morbidity.

Racial disparities in care escalation for postpartum hemorrhage requiring transfusion.

BACKGROUND: Postpartum hemorrhage is a leading cause of maternal morbidity and mortality in the United States and disproportionately affects pregnant persons of color. OBJECTIVE: This study aimed to identify the demographic and obstetrical characteristics of those who received different levels of antihemorrhagic intervention in the setting of severe postpartum hemorrhage requiring blood transfusion. STUDY DESIGN: This was a retrospective cohort study of patients with documented postpartum hemorrhage (estimated blood loss of ≥1000 mL) and blood product transfusion. Moreover, 3 levels of antihemorrhagic intervention were defined as follows: level 1, administration of uterotonics only; level 2, performance of a procedure (ie, B-Lynch suture, O'Leary stitch, Bakri balloon, dilation and curettage, laceration repair, or embolization); and level 3, hysterectomy. Maternal demographics, obstetrical characteristics, and comorbidities were extracted from electronic health records. Ordinal logistic regression was used to estimate the odds of higher intervention levels adjusting for maternal demographic and obstetrical characteristics. RESULTS: Of note, 365 patients were included in this study, with a racial or ethnic composition of 30% White, 42% Black, 18% Hispanic, and 10% other. Moreover, 233 patients (64%) received level 1 intervention, 98 patients (27%) received level 2 intervention, and 34 patients (9%) received level 3 intervention. Patients receiving higher levels of intervention were more likely to have greater estimated blood loss (P<.001), have more transfusions (P<.001), and be of advanced maternal age (P=.004). Black and Hispanic patients were less likely to have received higher levels of intervention than White patients (P=.034). After adjusting for estimated blood loss, advanced maternal age, placenta accreta spectrum, and fibroids, Black patients remained significantly less likely to receive higher levels of intervention (adjusted odds ratio, 0.55; 95% confidence interval, 0.30-0.98). This difference persisted at an estimated blood loss of ≥3000 mL, with Black and Hispanic patients being significantly less likely to receive higher levels of intervention than White patients (odds ratio, 0.31 [95% confidence interval, 0.10-0.92] and 0.10 [95% confidence interval, 0.01-0.53], respectively). CONCLUSION: Among patients experiencing postpartum hemorrhage and receiving transfusion, Black patients are less likely to receive higher levels of antihemorrhagic intervention. This disparity is concerning in this high-risk population and requires further attention and investigation.

Educational note: addressing special cases of bias that frequently occur in perinatal epidemiology.

The epidemiologic study of pregnancy and birth outcomes may be hindered by several unique and challenging issues. Pregnancy is a time-limited period in which severe cohort attrition takes place between conception and birth and adverse outcomes are complex and multi-factorial. Biases span those familiar to epidemiologists: selection, confounding and information biases. Specific challenges include conditioning on potential intermediates, how to treat race/ethnicity, and influential windows of prolonged, seasonal and potentially time-varying exposures. Researchers studying perinatal outcomes should be cognizant of the potential pitfalls due to these factors and address their implications with respect to formulating questions of interest, choice of an appropriate analysis approach and interpretations of findings given assumptions. In this article, we catalogue some of the more important potential sources of bias in perinatal epidemiology that have more recently gained attention in the literature, provide the epidemiologic context behind each issue and propose practices for dealing with each issue to the extent possible.

Venous thromboembolism incidence among patients recommended for pharmacologic thromboembolism prophylaxis after cesarean delivery in selected guidelines.

BACKGROUND: Multiple guidelines regarding risk stratification for venous thromboembolism (VTE) incidence following cesarean delivery have been promulgated. OBJECTIVE: To estimate the percentage of cesarean delivery patients for which pharmacologic VTE would be recommended and subsequent incidence of VTE, based on several guidelines. PATIENTS/METHODS: This retrospective cohort study used data from the Nationwide Readmissions Database from October 2015 through December 2017. Diagnosis and procedure codes were used to identify patients undergoing cesarean delivery, incidence of VTE, and risk factors used to stratify risk in the existing guidelines. Time-to-event analysis was used to analyze data, stratified by risk categorization in 2011 American College of Obstetricians and Gynecologists (ACOG), 2012 American College of Chest Physicians (ACCP), 2015 Royal College of Obstetricians and Gynaecologists (RCOG), and 2018 American Society of Hematology (ASH) guidelines. RESULTS/CONCLUSIONS: In a cohort of 1 235 149 cesarean deliveries, VTE incidence was 2.1 per 1000 deliveries at 330 days following delivery (95% confidence interval: 2.0-2.2). Proportions of patients that would be recommended for pharmacologic prophylaxis ranged from 0.2% in 2018 ASH guidelines to 73.4% in 2015 RCOG criteria. Among groups considered at elevated risk for VTE for which pharmacologic prophylaxis would be recommended, VTE incidence varied from 35.2 per 1000 deliveries based on 2018 ASH criteria to 2.5 per 1000 in 2015 RCOG criteria. In a large cohort of cesarean deliveries in the United States, application of different risk stratification guidelines identified widely different proportions at risk of VTE following delivery, with implications for being categorized as having elevated risk.

Hospitalization Duration Following Uncomplicated Cesarean Delivery: Predictors, Facility Variation, and Outcomes.

Objectives This study was designed to: (1) characterize stay duration following cesarean delivery, (2) ascertain whether facility variation exists, and (3) determine whether shorter stays are associated with rates of readmission or costs. Study Design The 2017 Nationwide Readmissions Database was used to identify uncomplicated cesarean deliveries. Hierarchical logistic regression was used to assess for facility variation in percentage of patients discharged within 2 days. Similar models were used to assess for associations between probability of readmission within 30 days and facility-level rates of discharge within 2 days. Results In total, 456,312 patients from 1,535 hospitals were included. The median facility discharged 46.8% of patients within 2 days, with the 25th percentile of hospitals 23.7% and the 75th percentile 71.2%. In adjusted regression, there was significant facility heterogeneity ( p < 0.0001). The overall readmission rate was 1.7%, and proportion of patients discharged within 2 days of cesarean delivery was not associated with readmission probability (adjusted relative risk: 1.02, confidence interval: 0.90-1.16), but was associated with lower inpatient costs (adjusted incremental cost: $111, confidence interval: -181 to -41). Conclusion Unexplained facility variation in percentage of patients discharged within 2 days of cesarean delivery was not associated with differences in readmissions. Key Points We find significant facility-level variation in outcomes following uncomplicated cesarean delivery in the United States.High rates of early (postoperative day 2) discharge was not associated with differences in readmission rates in adjusted analyses but was associated with lower inpatient costs.

A feasibility study of conducting the Montreal Cognitive Assessment remotely in individuals with movement disorders.

Remote assessments of individuals with a neurological disease via telemedicine have the potential to reduce some of the burdens associated with clinical care and research participation. We aim to evaluate the feasibility of conducting the Montreal Cognitive Assessment remotely in individuals with movement disorders. A pilot study derived from two telemedicine trials was conducted. In total, 17 individuals with movement disorders (8 with Parkinson disease and 9 with Huntington disease) had Montreal Cognitive Assessment examinations evaluated in-person and remotely via web-based video conferencing to primarily determine feasibility and potential barriers in its remote administration. Administering the Montreal Cognitive Assessment remotely in a sample of movement disorder patients with mild cognitive impairment is feasible, with only minor common complications associated with technology, including delayed sound and corrupted imaging for participants with low connection speeds. The Montreal Cognitive Assessment has the potential to be used in remote assessments of patients and research participants with movement disorders.

Virtual research visits and direct-to-consumer genetic testing in Parkinson's disease.

OBJECTIVE: The purpose of this study was to conduct a proof-of-concept study to evaluate remote recruitment and assessment of individuals ("virtual research visits") with Parkinson's disease who have pursued direct-to-consumer genetic testing. METHODS: Participants in 23andMe's "Parkinson's Research Community" were contacted by 23andMe. Fifty willing participants living in 23 states underwent a remote, standardized assessment including cognitive and motor tests by a neurologist via video conferencing and then completed a survey. Primary outcomes assessed were (a) proportion of participants who completed the remote assessments; (b) level of agreement (using Cohen's kappa coefficient) of patient-reported data with that of a neurologist; and (c) interest in future virtual research visits. RESULTS: The self-reported diagnosis of Parkinson's disease was confirmed in all cases (k = 1.00). The level of agreement for age of symptom onset (k = 0.97) and family history (k = 0.85) was very good but worse for falling (k = 0.59), tremor (k = 0.56), light-headedness (k = 0.31), and urine control (k = 0.15). Thirty-eight (76%) of the 50 participants completed a post-assessment survey, and 87% of respondents said they would be more or much more willing to participate in future clinical trials if they could do research visits remotely. CONCLUSION: Remote clinical assessments of individuals with known genotypes were conducted nationally and rapidly from a single site, confirmed self-reported diagnosis, and were received favorably. Direct-to-consumer genetic testing and virtual research visits together may enable characterization of genotype and phenotype for geographically diverse populations.

Depressed mood and suicidality in individuals exposed to tetrabenazine in a large Huntington disease observational study.

BACKGROUND: Tetrabenazine, a treatment for chorea in Huntington disease, carries a boxed warning due to safety, especially related to suicidality. OBJECTIVE: To compare the frequency of depressed mood and suicidality among a closely monitored cohort of individuals with Huntington disease who were exposed and not exposed to tetrabenazine. METHODS: A longitudinal prospective study involving 1360 individuals with HD evaluated at 48 research centers in Australia, Canada, and the United States was examined for frequency of depressed mood that triggered a risk assessment, suicidal thoughts, suicide attempts, and completed suicide among individuals with prior, new, and no exposure to tetrabenazine.. Seventy-seven individuals were on tetrabenazine at study enrollment (prior exposure), 64 individuals were exposed to tetrabenazine during the study's course (new exposure), and 1219 individuals had no exposure to tetrabenazine. RESULTS: The hazard ratio for depressed mood among those with prior exposure to tetrabenazine compared to no exposure was 0.9 (95% CI, 0.5-1.6) and for those with new exposure compared to no exposure was 1.2 (95% CI, 0.8-1.9). One individual (1.3%) with prior exposure, one individual (1.6%) with new exposure, and 35 individuals (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard ratio for suicidal ideation among those with prior exposure to tetrabenazine compared to no exposure was 0.5 (95% CI, 0.1-3.8) and for those with new exposure to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1-4.4). Among individuals with prior or new exposure to tetrabenazine, no suicide attempts or suicides occurred. Among those with no exposure to tetrabenazine 17 suicide attempts (1.4%) and four suicides (0.3%) occurred. CONCLUSIONS: In a large observational study with close clinical supervision, tetrabenazine treatment was not associated with an increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide.