Racial and ethnic disparities in eligibility for postpartum venous thromboembolism prophylaxis in the United States.

BACKGROUND: Postpartum venous thromboembolism (VTE) incidence differs by race and ethnicity in the United States. However, it is unclear whether the eligibility criteria for postpartum VTE prophylaxis mirror this disparity. OBJECTIVE: To characterize the prevalence of risk factors and eligibility for postpartum VTE prophylaxis, among US Birthing people, stratified by race and ethnicity. METHODS: We analyzed the National Inpatient Sample from October 2015 to December 2019, using diagnosis and procedure codes to identify postpartum individuals and their VTE risk factors. We compared proportion of delivery hospitalizations meeting eligibility for thromboprophylaxis stratified by race or ethnicity, according to American College of Gynecology and Obstetrics, American College of Chest Physicians, Royal College of Obstetricians and Gynecologists (RCOG), and American Society for Hematology guidelines. RESULTS: Among a national estimate of 14 967 861 delivery hospitalizations in the United States, the proportion of individuals eligible for thromboprophylaxis using the RCOG, American College of Chest Physicians, American College of Gynecology and Obstetrics, and American Society for Hematology guidelines were 32.9%, 8.0%, 0.2%, and 0.2%, respectively. Using the RCOG criteria, non-Hispanic Black individuals had the highest proportion of thromboprophylaxis eligibility (39.7%), whereas it was lowest among Hispanic individuals (30.8%). Racial disparities in thromboprophylaxis eligibility were driven by differences in clinical risk factors (38.8% non-Hispanic Black population vs 30.5% Hispanic population) and cesarean section rates (35.9% vs 32.2%), rather than history of VTE (0.3% vs 0.1%), inherited thrombophilia (0.2% vs 0.2%), or sickle cell disease (0.4% vs <0.1%). CONCLUSION: Non-Hispanic Black individuals were most likely to qualify for postpartum thromboprophylaxis, attributable to clinical risk factors rather than inherited risk factors. An urgent need exists to better understand ethno-racial disparities in thromboprophylaxis use and to equitably address modifiable risk factors for postpartum VTE.

Maternal and Pregnancy Outcomes Following Heart Transplantation in the United States.

BACKGROUND: Improved survival following heart transplantation (HT) has led to more recipients contemplating pregnancy, but data on outcomes are limited. OBJECTIVES: The authors used a national data set to investigate and describe outcomes of pregnancies and deliveries in the United States in HT recipients. METHODS: Diagnosis and procedure codes from the 2010-2020 Nationwide Readmissions Database identified delivery hospitalizations, history of HT, comorbid conditions, and outcomes. The authors compared rates of severe maternal morbidity (SMM), nontransfusion SMM, cardiovascular SMM (cSMM), and preterm birth from delivery hospitalization between HT recipients and no-HT recipients. The authors evaluated readmission to 330 days postpartum. Logistic and proportional hazard regressions were performed, adjusting for age, socioeconomic and facility characteristics, and clinical comorbidities. RESULTS: Among 19,399,521 deliveries, 105 were HT recipients. Compared with no-HT, HT recipients were at higher risk for all SMM (24.8% vs 1.7%), nontransfusion SMM (20.8% vs 0.7%), cSMM (7.3% vs 0.12%), and preterm birth (43.3% vs 8.2%), all P < 0.001. In adjusted analyses, HT recipients had 16-fold greater odds of SMM, 28-fold greater odds of nontransfusion SMM, 38-fold greater odds of cSMM, and 7-fold greater odds of preterm birth. HT recipients had higher morbidity rates during delivery hospitalization and higher readmission rates within 1 year following delivery (26.9% vs 3.8%; adjusted HR: 6.03 [95% CI: 3.73-9.75]). CONCLUSIONS: Delivery with history of HT is associated with significantly increased rates of SMM, preterm birth, and hospital readmission. These results provide data regarding pregnancy outcomes for use when counseling patients with HT history who are considering pregnancy or who are pregnant.

Maternal and neonatal outcomes in patients with hepatitis C and intrahepatic cholestasis of pregnancy: The sum of the parts.

OBJECTIVE: Hepatitis C virus and intrahepatic cholestasis of pregnancy (ICP) are well-known independent risk factors for adverse outcomes in pregnancy. In addition, it is well-established that there is an association between Hepatitis C and ICP. This study's objective was to describe the impact of having both Hepatitis C and ICP on maternal and obstetric outcomes compared to patients having either Hepatitis C or ICP. METHODS: We conducted a retrospective cohort study of the Nationwide Readmissions Database, an all-payor sample of discharges from approximately 60% of US hospitalizations. Deliveries at 24-42+ weeks between 10/2015 and 12/2020 were included. Diagnosis of Hepatitis C and ICP, and outcomes related to severe maternal morbidity were identified using International Classification of Disease-10 codes. Patients were categorized based on Hepatitis C and ICP status. Weighted logistic and negative binomial regression analyses were used to evaluate the association between Hepatitis C and ICP status and outcomes, adjusting for patient and hospital characteristics. The primary outcome was any severe maternal morbidity; secondary outcomes included acute respiratory distress syndrome, acute kidney injury, sepsis, gestational diabetes, cesarean delivery, preterm birth, and hospital length of stay. We modeled interaction terms between ICP and Hepatitis C to assess whether there was a greater or lesser effect from having both conditions on outcomes than we would expect from additive combination of the individual components (i.e., synergy or antagonism). RESULTS: A total of 10,040,850 deliveries between 24-42+ weeks were identified. Of these, 45,368 had Hepatitis C only; 84,582 had ICP only; and 1,967 had both Hepatitis C and ICP. Patients with both Hepatitis C and ICP had 1.5-fold higher odds of developing severe maternal morbidity compared to having neither. There was an also an increased odds of severe maternal morbidity in patients with both Hepatitis C and ICP compared to patients with only Hepatitis C or ICP. Having both was also associated with higher odds of preterm birth and length of stay compared to having only Hepatitis C, only ICP, or neither (preterm birth: aOR 5.09, 95% CI 4.87-5.33 vs. neither; length of stay: 46% mean increase, 95% CI 35-58% vs. neither). Associations were additive-no significant interactions between hepatitis C and cholestasis were found on rates of severe maternal morbidity, acute respiratory distress syndrome, acute kidney injury, sepsis, cesarean section, or preterm birth (all p>0.05), and was minimal for gestational diabetes and length of stay. CONCLUSION: Hepatitis C and ICP are independent, additive risk factors for adverse maternal and obstetric outcomes. Despite physiologic plausibility, no evidence of a synergistic effect of these two diagnoses on outcomes was noted. These data may be useful in counseling patients regarding their increased risk of adverse outcomes when ICP presents in association with Hepatitis C versus ICP alone.

Maternal morbidity and mortality among patients with cancer at time of delivery.

BACKGROUND: Individuals with cancer during pregnancy are a medically complex patient population that is anticipated to grow. A better understanding of this population and patterns of risk at time of delivery would offer an opportunity for providers to mitigate maternal morbidity. OBJECTIVE: This study aimed to estimate the prevalence in the United States of concurrent cancer diagnoses at time of delivery by cancer type and associated maternal morbidity and mortality. STUDY DESIGN: Using the National Inpatient Sample, we identified delivery-associated hospitalizations between 2007 and 2018. Concurrent cancer diagnoses were classified using the Clinical Classifications Software. Main outcomes included severe maternal morbidity, as defined by the Centers for Disease Control and Prevention indicators, and mortality during delivery hospitalization. We calculated adjusted rates for cancer diagnosis at time of delivery and adjusted odds ratios of severe maternal morbidity and maternal death during hospitalization using survey-weighted multivariable logistic regression models. RESULTS: In this sample of 9,418,761 delivery-associated hospitalizations, 63 per 100,000 deliveries had a concurrent cancer diagnosis (95% confidence interval, 60-66; national weighted estimate, 46,654,042). The most common cancer types were breast cancer (8.4 per 100,000 deliveries), leukemia (8.4 per 100,000 deliveries), Hodgkin lymphoma (7.4 per 100,000 deliveries), non-Hodgkin lymphoma (5.4 per 100,000 deliveries), and thyroid cancer (4.0 per 100,000 deliveries). Patients with cancer were at significantly higher risk for any severe maternal morbidity (adjusted odds ratio, 5.25; 95% confidence interval, 4.73-5.83) and maternal death (adjusted odds ratio, 67.5; 95% confidence interval, 45.1-101.4). Risks of hysterectomy (adjusted odds ratio, 16.92; 95% confidence interval, 13.96-20.52), acute respiratory distress (adjusted odds ratio, 12.76; 95% confidence interval, 9.92-16.42), sepsis (adjusted odds ratio, 11.91; 95% confidence interval, 8.68-16.32), and embolism (adjusted odds ratio, 11.12; 95% confidence interval, 6.94-17.82) were particularly heightened among patients with cancer. Patients with leukemia, specifically, had the highest risk of adverse maternal outcomes (adjusted rate, 113 per 1000 deliveries; 95% confidence interval, 91-135 per 1000) when evaluating risk by cancer type. CONCLUSION: Patients with cancer are at markedly increased risk of maternal morbidity and all-cause mortality during delivery-associated hospitalization. Risk is distributed unevenly within this population, with certain cancer types carrying unique risks for specific morbidity events.

High rates of venous thromboembolism among deliveries complicated by cancer.

BACKGROUND: Venous thromboembolism (VTE) risk is increased independently by both cancer and pregnancy. OBJECTIVES: To estimate VTE risk in the postpartum period among patients delivering with a cancer diagnosis, stratified by cancer type and delivery route. METHODS: We performed a retrospective cohort study utilizing the large, all-payer Nationwide Readmissions Database from October 2015 through December 2020. We identified delivery hospitalizations, cancer diagnoses, and VTE using patient demographics and diagnosis codes. The primary outcome was VTE incidence at 42 and 330 days from delivery admission date, comparing patients with and without cancer diagnoses. A secondary analysis included VTE risk stratified by cancer diagnosis and delivery route. Outcomes were compared using inverse probability-weighted survival curves. RESULTS: The study population included 9 793 503 delivery hospitalizations (weighted estimate, 18 207 346), with a weighted estimate of 10 428 (0.06%) pregnant patients with cancer. Individuals with cancer were older, with higher rates of comorbid conditions, than those without cancer. VTE incidence in individuals with cancer at 42 and 330 days was 1.11% and 2.19%, respectively, vs 0.11% and 0.14%, respectively, in those without cancer. At 330 days, this finding was significant in both unadjusted (relative risk, 15.52; 95% CI, 11.54-19.51) and adjusted (relative risk, 9.68; 95% CI, 7.18-12.18) models. Stratification by cancer type and delivery route demonstrated elevated VTE risk across cancer types, with cesarean delivery conferring a greater risk. CONCLUSION: Cancer in pregnancy confers excess thromboembolic risk extending beyond the immediate postpartum period. Further study is needed to identify optimal VTE prophylactic strategies for this population.

Risk of stillbirth in United States patients with diagnosed intrahepatic cholestasis of pregnancy.

BACKGROUND: Intrahepatic cholestasis of pregnancy is associated with a 4- to 10-fold increase in the risk of stillbirth in the absence of intervention, leading to recommendations for antenatal assessment, ursodiol use, and often preterm or early term delivery. OBJECTIVE: This study aimed to determine whether current management strategies for intrahepatic cholestasis of pregnancy mitigate the elevated risk of stillbirth at a population level. STUDY DESIGN: This was a retrospective cohort study using the 2015-2020 National Readmissions Database, an administrative database developed by the United States Agency for Healthcare Research and Quality. Our study identified delivery hospitalizations, gestational age at delivery, occurrence of intrahepatic cholestasis of pregnancy and stillbirth, and comorbid conditions using the International Classification of Diseases diagnosis and procedure codes. Moreover, this study compared the timing of delivery and stillbirth rates of pregnant patients with intrahepatic cholestasis of pregnancy vs those without intrahepatic cholestasis of pregnancy at the time of delivery hospitalization. RESULTS: This study identified a cohort of 9,987,705 delivery hospitalizations in the National Readmissions Database, corresponding to a weighted national estimate of 18,609,207 births. Of these births, 152,040 (0.8%) were noted to have an intrahepatic cholestasis of pregnancy diagnosis. Patients with an intrahepatic cholestasis of pregnancy diagnosis were older, with small differences in comorbidities, such as a higher rate of gestational diabetes mellitus, than patients without an intrahepatic cholestasis of pregnancy diagnosis at delivery hospitalization. The overall rates of stillbirth were lower among those with intrahepatic cholestasis of pregnancy than among those without intrahepatic cholestasis of pregnancy (252 vs 386 per 100,000 deliveries; risk difference, 133 fewer per 100,000 deliveries; 95% confidence interval, 98-170), a finding that persisted after adjustment for insurance status, socioeconomic factors, and comorbid conditions (risk difference, 160 fewer stillbirths per 100,000 deliveries; 95% confidence interval, 127-194). Furthermore, although patients with intrahepatic cholestasis of pregnancy were more likely to deliver before term than those without intrahepatic cholestasis of pregnancy (30.1% vs 9.3%; P<.001), increased rates of stillbirth were not noted at any point after stratification of the cohort by gestational age at delivery. CONCLUSION: Patients with intrahepatic cholestasis of pregnancy diagnosis codes delivered earlier than those without intrahepatic cholestasis of pregnancy diagnosis codes, but the percentage of births affected by stillbirth was lower, even when stratifying for gestational age at birth. These results may provide reassurance to patients receiving an intrahepatic cholestasis of pregnancy diagnosis that current management does mitigate stillbirth risk in intrahepatic cholestasis of pregnancy.

Demographic and Clinical Predictors of Postpartum Blood Pressure Screening Attendance.

Background: Hypertensive disorders of pregnancy (HDP) cause substantial preventable maternal morbidity and mortality. Postpartum hypertension that worsens after women are discharged is particularly dangerous, as it can go undiagnosed and cause complications. The American College of Obstetricians and Gynecologists recommends women with HDP undergo blood pressure (BP) screening 7-10 days after delivery to detect postpartum hypertension. This study aimed to describe predictors of postpartum BP screening attendance among a high-risk safety-net population in Atlanta, Georgia. Materials and Methods: We conducted a population-based cohort study of pregnant women who delivered at a large public hospital in Atlanta between July 1, 2016, and June 30, 2018. We manually abstracted demographic and clinical data from electronic medical records and used multivariable log binomial regression to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (95% CIs) for associations with BP screening attendance. Results: Of 1260 women diagnosed with HDP, 13.7% attended a BP screening visit within 10 days of delivery. Women with preeclampsia with severe features were more likely to attend a BP visit than women with gestational hypertension (aRR 2.10, 95% CI 1.35-3.27). Rates of BP screening attendance were lower for women with inadequate (aRR 0.42, 95% CI 0.26-0.67) and intermediate (aRR 0.40, 95% CI 0.21-0.74) prenatal care utilization relative to women with adequate utilization. Conclusions: Among a high-risk safety-net population with HDP, most women did not attend a BP screening visit within 10 days of delivery. Addressing this gap requires further research and creative solutions to address barriers at the individual, provider, and system levels.

Hypertensive Disorders of Pregnancy, Cesarean Delivery, and Severe Maternal Morbidity in an Urban Safety-Net Population.

Hypertensive disorders of pregnancy (HDP) are a leading cause of severe maternal morbidity (SMM), yet mediation by cesarean delivery is largely unexplored. We investigated the association between HDP and SMM in a cohort of deliveries at a safety-net institution in Atlanta, Georgia, during 2016-2018. Using multivariable generalized linear models, we estimated adjusted risk differences, adjusted risk ratios, and 95% confidence intervals for the association between HDP and SMM. We examined interactions with cesarean delivery and used mediation analysis with 4-way decomposition to estimate excess relative risks. Among 3,723 deliveries, the SMM rate for women with and without HDP was 124.4 per 1,000 and 52.0 per 1,000, respectively. The adjusted risk ratio for the total effect of HDP on SMM was 2.55 (95% confidence interval (CI): 2.15, 3.39). Approximately 55.2% (95% CI: 25.7, 68.5) of excess relative risk was due to neither interaction nor mediation, 24.9% (95% CI: 15.4, 50.0) was due to interaction between HDP and cesarean delivery, 9.6% (95% CI: 3.4, 15.2) was due to mediation, and 10.3% (95% CI: 5.4, 20.3) was due to mediation and interaction. HDP are a potentially modifiable risk factor for SMM; implementing evidence-based interventions for the prevention and treatment of HDP is critical for reducing SMM risk.

Porcine Esophageal Submucosal Gland Culture Model Shows Capacity for Proliferation and Differentiation.

BACKGROUND & AIMS: Although cells comprising esophageal submucosal glands (ESMGs) represent a potential progenitor cell niche, new models are needed to understand their capacity to proliferate and differentiate. By histologic appearance, ESMGs have been associated with both overlying normal squamous epithelium and columnar epithelium. Our aim was to assess ESMG proliferation and differentiation in a 3-dimensional culture model. METHODS: We evaluated proliferation in human ESMGs from normal and diseased tissue by proliferating cell nuclear antigen immunohistochemistry. Next, we compared 5-ethynyl-2'-deoxyuridine labeling in porcine ESMGs in vivo before and after esophageal injury with a novel in vitro porcine organoid ESMG model. Microarray analysis of ESMGs in culture was compared with squamous epithelium and fresh ESMGs. RESULTS: Marked proliferation was observed in human ESMGs of diseased tissue. This activated ESMG state was recapitulated after esophageal injury in an in vivo porcine model, ESMGs assumed a ductal appearance with increased proliferation compared with control. Isolated and cultured porcine ESMGs produced buds with actively cycling cells and passaged to form epidermal growth factor-dependent spheroids. These spheroids were highly proliferative and were passaged multiple times. Two phenotypes of spheroids were identified: solid squamous (P63+) and hollow/ductal (cytokeratin 7+). Microarray analysis showed spheroids to be distinct from parent ESMGs and enriched for columnar transcripts. CONCLUSIONS: Our results suggest that the activated ESMG state, seen in both human disease and our porcine model, may provide a source of cells to repopulate damaged epithelium in a normal manner (squamous) or abnormally (columnar epithelium). This culture model will allow the evaluation of factors that drive ESMGs in the regeneration of injured epithelium. The raw microarray data have been uploaded to the National Center for Biotechnology Information Gene Expression Omnibus (accession number: GSE100543).