Associations between anxiety, sleep, and blood pressure parameters in pregnancy: a prospective pilot cohort study.

BACKGROUND: The potential effect modification of sleep on the relationship between anxiety and elevated blood pressure (BP) in pregnancy is understudied. We evaluated the relationship between anxiety, insomnia, and short sleep duration, as well as any interaction effects between these variables, on BP during pregnancy. METHODS: This was a prospective pilot cohort of pregnant people between 23 to 36 weeks' gestation at a single institution between 2021 and 2022. Standardized questionnaires were used to measure clinical insomnia and anxiety. Objective sleep duration was measured using a wrist-worn actigraphy device. Primary outcomes were systolic (SBP), diastolic (DBP), and mean (MAP) non-invasive BP measurements. Separate sequential multivariable linear regression models fit with generalized estimating equations (GEE) were used to separately assess associations between anxiety (independent variable) and each BP parameter (dependent variables), after adjusting for potential confounders (Model 1). Additional analyses were conducted adding insomnia and the interaction between anxiety and insomnia as independent variables (Model 2), and adding short sleep duration and the interaction between anxiety and short sleep duration as independent variables (Model 3), to evaluate any moderating effects on BP parameters. RESULTS: Among the 60 participants who completed the study, 15 (25%) screened positive for anxiety, 11 (18%) had subjective insomnia, and 34 (59%) had objective short sleep duration. In Model 1, increased anxiety was not associated with increases in any BP parameters. When subjective insomnia was included in Model 2, increased DBP and MAP was significantly associated with anxiety (DBP: ß 6.1, p = 0.01, MAP: ß 6.2 p < 0.01). When short sleep was included in Model 3, all BP parameters were significantly associated with anxiety (SBP: ß 9.6, p = 0.01, DBP: ß 8.1, p < 0.001, and MAP: ß 8.8, p < 0.001). No moderating effects were detected between insomnia and anxiety (p interactions: SBP 0.80, DBP 0.60, MAP 0.32) or between short sleep duration and anxiety (p interactions: SBP 0.12, DBP 0.24, MAP 0.13) on BP. CONCLUSIONS: When including either subjective insomnia or objective short sleep duration, pregnant people with anxiety had 5.1-9.6 mmHg higher SBP, 6.1-8.1 mmHg higher DBP, and 6.2-8.8 mmHg higher MAP than people without anxiety.

Evaluation and Modification of a Shared Decision-Making Tool for Peanut Allergy Management.

PURPOSE OF REVIEW: Based on shared decision-making (SDM) principles, a decision aid was previously developed to help patients, their caregivers, and physicians decide which peanut allergy management approach best suits them. This study refined the decision aid's content to better reflect patients' and caregivers' lived experience. RECENT FINDINGS: Current standard of care for peanut allergy is avoidance, although peanut oral immunotherapy has been approved by the Food and Drug Administration for use in patients 4-17 years old. An advisory board of allergy therapy experts (n = 3) and patient advocates (n = 3) informed modifications to the decision aid. The revised tool underwent cognitive debriefing interviews (CDIs) among adolescents (12-17 years old) with peanut allergy and caregivers of patients 4-17 years old with peanut allergy to evaluate its relevance, understandability, and usefulness. The 20 CDI participants understood the information presented in the SDM tool and reported it was important and relevant. Some revisions were made based on participant feedback. Results support content validity of the Peanut Allergy Treatment SDM Tool.

Magnesium sulfate and risk of hypoxic-ischemic encephalopathy in a high-risk cohort.

BACKGROUND: Hypoxic-ischemic encephalopathy contributes to morbidity and mortality among neonates ≥36 weeks of gestation. Evidence of preventative antenatal treatment is limited. Magnesium sulfate has neuroprotective properties among preterm fetuses. Hypertensive disorders of pregnancy are a risk factor for hypoxic-ischemic encephalopathy, and magnesium sulfate is recommended for maternal seizure prophylaxis among patients with preeclampsia with severe features. OBJECTIVE: (1) Determine trends in the incidence of hypertensive disorders of pregnancy, antenatal magnesium sulfate, and hypoxic-ischemic encephalopathy; (2) evaluate the association between hypertensive disorders of pregnancy and hypoxic-ischemic encephalopathy; and (3) evaluate if, among patients with hypertensive disorders of pregnancy, the odds of hypoxic-ischemic encephalopathy is mitigated by receipt of antenatal magnesium sulfate. STUDY DESIGN: We analyzed a prospective cohort of live births ≥36 weeks of gestation between 2012 and 2018 within the California Perinatal Quality Care Collaborative registry, linked with the California Department of Health Care Access and Information files. We used Cochran-Armitage tests to assess trends in hypertensive disorders, encephalopathy diagnoses, and magnesium sulfate utilization and compared demographic factors between patients with or without hypertensive disorders of pregnancy or treatment with magnesium sulfate. Hierarchical logistic regression models were built to explore if hypertensive disorders of pregnancy were associated with any severity and moderate/severe hypoxic-ischemic encephalopathy. Separate hierarchical logistic regression models were built among those with hypertensive disorders of pregnancy to evaluate the association of magnesium sulfate with hypoxic-ischemic encephalopathy. RESULTS: Among 44,314 unique infants, the diagnosis of hypoxic-ischemic encephalopathy, maternal hypertensive disorders of pregnancy, and the use of magnesium sulfate increased over time. Compared with patients with hypertensive disorders of pregnancy alone, patients with hypertensive disorders treated with magnesium sulfate represented a high-risk population. They were more likely to be publicly insured, born between 36 and 38 weeks of gestation, be small for gestational age, have lower Apgar scores, require a higher level of resuscitation at delivery, have prolonged rupture of membranes, experience preterm labor and fetal distress, and undergo operative delivery (all P<.002). Hypertensive disorders of pregnancy were associated with hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.13-1.40]; P<.001) and specifically moderate/severe hypoxic-ischemic encephalopathy (adjusted odds ratio, 1.26 [95% confidence interval, 1.11-1.42]; P<.001). Among patients with hypertensive disorders of pregnancy, treatment with magnesium sulfate was associated with 29% reduction in the odds of neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.71 [95% confidence interval, 0.52-0.97]; P=.03) and a 37% reduction in the odds of moderate/severe neonatal hypoxic-ischemic encephalopathy (adjusted odds ratio, 0.63 [95% confidence interval, 0.42-0.94]; P=.03). CONCLUSION: Hypertensive disorders of pregnancy are associated with hypoxic-ischemic encephalopathy and, specifically, moderate/severe disease. Among people with hypertensive disorders, receipt of antenatal magnesium sulfate is associated with a significant reduction in the odds of hypoxic-ischemic encephalopathy and moderate/severe disease in a neonatal cohort admitted to neonatal intensive care unit at ≥36 weeks of gestation. The findings of this observational study cannot prove causality and are intended to generate hypotheses for future clinical trials on magnesium sulfate in term infants.

Validity of ICD-10 diagnosis codes for placenta accreta spectrum disorders.

BACKGROUND: The 10th revision of the International Classification of Diseases, Clinical Modification (ICD-10) includes diagnosis codes for placenta accreta spectrum for the first time. These codes could enable valuable research and surveillance of placenta accreta spectrum, a life-threatening pregnancy complication that is increasing in incidence. OBJECTIVE: We sought to evaluate the validity of placenta accreta spectrum diagnosis codes that were introduced in ICD-10 and assess contributing factors to incorrect code assignments. METHODS: We calculated sensitivity, specificity, positive predictive value and negative predictive value of the ICD-10 placenta accreta spectrum code assignments after reviewing medical records from October 2015 to March 2020 at a quaternary obstetric centre. Histopathologic diagnosis was considered the gold standard. RESULTS: Among 22,345 patients, 104 (0.46%) had an ICD-10 code for placenta accreta spectrum and 51 (0.23%) had a histopathologic diagnosis. ICD-10 codes had a sensitivity of 0.71 (95% CI 0.56, 0.83), specificity of 0.98 (95% CI 0.93, 1.00), positive predictive value of 0.61 (95% CI 0.48, 0.72) and negative predictive value of 1.00 (95% CI 0.96, 1.00). The sensitivities of the ICD-10 codes for placenta accreta spectrum subtypes- accreta, increta and percreta-were 0.55 (95% CI 0.31, 0.78), 0.33 (95% CI 0.12, 0.62) and 0.56 (95% CI 0.31, 0.78), respectively. Cases with incorrect code assignment were less morbid than cases with correct code assignment, with a lower incidence of hysterectomy at delivery (17% vs 100%), blood transfusion (26% vs 75%) and admission to the intensive care unit (0% vs 53%). Primary reasons for code misassignment included code assigned to cases of occult placenta accreta (35%) or to cases with clinical evidence of placental adherence without histopatholic diagnostic (35%) features. CONCLUSION: These findings from a quaternary obstetric centre suggest that ICD-10 codes may be useful for research and surveillance of placenta accreta spectrum, but researchers should be aware of likely substantial false positive cases.

Varying Doses of Epicutaneous Immunotherapy With Viaskin Milk vs Placebo in Children With Cow's Milk Allergy: A Randomized Clinical Trial.

Importance: No approved treatment exists for allergen-specific immunoglobulin E (IgE)-mediated cow's milk allergy (CMA), a common childhood food allergy. Objective: To assess dose, efficacy, and safety of epicutaneous immunotherapy with Viaskin milk in children with IgE-mediated CMA. Design, Setting, and Participants: A phase 1/2, 2-part, randomized, double-blind, placebo-controlled dose-ranging clinical trial in children aged 2 to 17 years with IgE-mediated CMA was conducted between November 2014 through December 2017. It took place at 17 trial sites in the US and Canada. Current CMA was confirmed by double-blind, placebo-controlled food challenge at study entry. Part A assessed the short-term safety of 150 µg, 300 µg, or 500 µg of Viaskin milk; part B evaluated the efficacy and safety of the 3 doses vs placebo over 12 months of treatment. Of the 308 screened participants with physician-diagnosed CMA, 198 met eligibility criteria (including an eliciting dose 300 mg or less) and were randomized. Intervention: Safety of Viaskin milk (150-µg, 300-µg, or 500-µg doses) was evaluated over a 3-week period (part A). In part B, 180 additional participants were randomized to receive Viaskin milk at doses of 150 µg, 300 µg, or 500 µg or placebo (1:1:1:1) for 12 months. Main Outcomes and Measures: The primary outcome was the proportion of treatment responders, defined as a 10-fold or more increase in the cumulative reactive dose of cow's milk protein (reaching at least 144 mg) or a cumulative reactive dose of cow's milk protein at 1444 mg or more at the month 12 double-blind, placebo-controlled food challenge. Results: A total of 95.5% of the randomized participants (mean [SD] age, 8 [4.17] years; 124 of 198 were male [62.6%]) completed treatment. The highest response rate was observed in participants who received Viaskin milk at the 300-µg dose with 24 of 49 responders (49.0%) overall vs 16 of 53 responders (30.2%) in the placebo group (odds ratio, 2.19; 95% CI, 0.91-5.41; P = .09), highest in the 2 to 11 years age group (22 of 38 [57.9%] vs 13 of 40 [32.5%]; P = .04). Most treatment-emergent adverse events were mild or moderate application-site reactions. One participant in the 500-µg Viaskin milk dose group experienced treatment-related anaphylaxis. Conclusions and Relevance: In this randomized clinical trial, 12 months of daily epicutaneous immunotherapy with a dose of Viaskin milk at 300 µg was associated with a statistically significant treatment response in 2- to 11-year-old children with IgE-mediated CMA. Treatment-related anaphylaxis and treatment-related discontinuation rates were low. Further research is needed to explore Viaskin milk as a viable treatment option for children with IgE-mediated CMA. Trial Registration: ClinicalTrials.gov Identifier: NCT02223182.

Validity of Birth Certificate Data Compared With Hospital Discharge Data in Reporting Maternal Morbidity and Disparities.

A growing number of studies are using birth certificate data, despite data-quality concerns, to study maternal morbidity and associated disparities. We examined whether conclusions about the incidence of maternal morbidity, including Black-White disparities, differ between birth certificate data and hospitalization data. Using linked birth certificate and hospitalization data from California and Michigan for 2018 (N=543,469), we found that maternal morbidity measures using birth certificate data alone are substantially underreported and have poor validity. Furthermore, the degree of underreporting in birth certificate data differs between Black and White individuals and results in erroneous inferences about disparities. Overall, Black-White disparities were more modest in the birth certificate data compared with the hospitalization data. Birth certificate data alone are inadequate for studies of maternal morbidity and associated racial disparities.

Trends and Disparities in Severe Maternal Morbidity Indicator Categories during Childbirth Hospitalization in California from 1997 to 2017.

OBJECTIVE: Severe maternal morbidity (SMM) is increasing and characterized by substantial racial and ethnic disparities. Analyzing trends and disparities across time by etiologic or organ system groups instead of an aggregated index may inform specific, actionable pathways to equitable care. We explored trends and racial and ethnic disparities in seven SMM categories at childbirth hospitalization. STUDY DESIGN: We analyzed California birth cohort data on all live and stillbirths ≥ 20 weeks' gestation from 1997 to 2017 (n = 10,580,096) using the Centers for Disease Control and Prevention's SMM index. Cases were categorized into seven nonmutually exclusive indicator categories (cardiac, renal, respiratory, hemorrhage, sepsis, other obstetric, and other medical SMM). We compared prevalence and trends in SMM indicator categories overall and by racial and ethnic group using logistic and linear regression. RESULTS: SMM occurred in 1.16% of births and nontransfusion SMM in 0.54%. Hemorrhage SMM occurred most frequently (27 per 10,000 births), followed by other obstetric (11), respiratory (7), and sepsis, cardiac, and renal SMM (5). Hemorrhage, renal, respiratory, and sepsis SMM increased over time for all racial and ethnic groups. The largest disparities were for Black individuals, including over 3-fold increased odds of other medical SMM. Renal and sepsis morbidity had the largest relative increases over time (717 and 544%). Sepsis and hemorrhage SMM had the largest absolute changes over time (17 per 10,000 increase). Disparities increased over time for respiratory SMM among Black, U.S.-born Hispanic, and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals. Disparities decreased over time for sepsis SMM among Black individuals yet remained substantial. CONCLUSION: Our research further supports the critical need to address SMM and disparities as a significant public health priority in the United States and suggests that examining SMM subgroups may reveal helpful nuance for understanding trends, disparities, and potential needs for intervention. KEY POINTS: · By SMM subgroup, trends and racial and ethnic disparities varied yet Black individuals consistently had highest rates.. · Hemorrhage, renal, respiratory, and sepsis SMM significantly increased over time.. · Disparities increased for respiratory SMM among Black, U.S.-born Hispanic and non-U.S.-born Hispanic individuals and for sepsis SMM among Asian or Pacific Islander individuals..

Perinatal Care Measures Are Incomplete If They Do Not Assess The Birth Parent-Infant Dyad As A Whole.

Measures of perinatal care quality and outcomes often focus on either the birth parent or the infant. We used linked vital statistics and hospital discharge data to describe a dyadic measure (including both the birth parent and the infant) for perinatal care during the birth hospitalization. In this five-state cohort of 2010-18 births, 21.6 percent of birth parent-infant dyads experienced at least one complication, and 9.6 percent experienced a severe complication. Severe infant complications were eight times more prevalent than severe birth parent complications. Among birth parents with a severe complication, the co-occurrence of a severe infant complication ranged from 2 percent to 51 percent, whereas among infants with a severe complication, the co-occurrence of a severe birth parent complication was rare, ranging from 0.04 percent to 5 percent. These data suggest that measures, clinical interventions, public reporting, and policies focused on either the birth parent or the infant are incomplete in their assessment of a healthy dyad. Thus, clinicians, administrators, and policy makers should evaluate dyadic measures, incentivize positive outcomes for both patients (parent and infant), and create policies that support the health of the dyad.

Chronic Hypertension in Pregnancy and Racial-Ethnic Disparities in Complications.

OBJECTIVE: To evaluate whether there are individual- and population-level associations between chronic hypertension and pregnancy complications, and to assess differences across seven racial-ethnic groups. METHODS: This population-based study used linked vital statistics and hospitalization discharge data from all live and stillbirths in California (2008-2018), Michigan (2008-2020), Oregon (2008-2020), Pennsylvania (2008-2014), and South Carolina (2008-2020). We used multivariable log-binomial regression models to estimate risk ratios (RRs) and population attributable risk (PAR) percentages with 95% CIs for associations between chronic hypertension and several obstetric and neonatal outcomes, selected based on prior evidence and pathologic pathways. We adjusted models for demographic factors (race and ethnicity, payment method, educational attainment), age, body mass index, obstetric history, delivery year, and state, and conducted analyses stratified across seven racial-ethnic groups. RESULTS: The study included 7,955,713 pregnancies, of which 168,972 (2.1%) were complicated by chronic hypertension. Chronic hypertension was associated with several adverse obstetric and neonatal outcomes, with the largest adjusted PAR percentages observed for preeclampsia with severe features or eclampsia (22.4; 95% CI 22.2-22.6), acute renal failure (13.6; 95% CI 12.6-14.6), and pulmonary edema (10.7; 95% CI 8.9-12.6). Estimated RRs overall were similar across racial-ethnic groups, but PAR percentages varied. The adjusted PAR percentages (95% CI) for severe maternal morbidity-a widely used composite of acute severe events-for people who were American Indian or Alaska Native, Asian, Black, Latino, Native Hawaiian or Other Pacific Islander, White, and Multiracial or Other were 5.0 (1.1-8.8), 3.7 (3.0-4.3), 9.0 (8.2-9.8), 3.9 (3.6-4.3), 11.6 (6.4-16.5), 3.2 (2.9-3.5), and 5.5 (4.2-6.9), respectively. CONCLUSION: Chronic hypertension accounts for a substantial fraction of obstetric and neonatal morbidity and contributes to higher complication rates, particularly for people who are Black or Native Hawaiian or Other Pacific Islander.

Racial and Ethnic Disparities in Anemia and Severe Maternal Morbidity.

OBJECTIVE: To evaluate antepartum anemia prevalence by race and ethnicity, to assess whether such differences contribute to severe maternal morbidity (SMM), and to estimate the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity. METHODS: We conducted a population-based cohort study using linked vital record and birth hospitalization data for singleton births at or after 20 weeks of gestation in California from 2011 through 2020. Pregnant patients with hereditary anemias, out-of-hospital births, unlinked records, and missing variables of interest were excluded. Antepartum anemia prevalence and trends were estimated by race and ethnicity. Centers for Disease Control and Prevention criteria were used for SMM and nontransfusion SMM indicators. Multivariable logistic regression modeling was used to estimate risk ratios (RRs) for SMM and nontransfusion SMM by race and ethnicity after sequential adjustment for social determinants, parity, obstetric comorbidities, delivery, and antepartum anemia. Population attributable risk percentages were calculated to assess the contribution of antepartum anemia to SMM and nontransfusion SMM by race and ethnicity. RESULTS: In total, 3,863,594 births in California were included. In 2020, Black pregnant patients had the highest incidence of antepartum anemia (21.5%), followed by Pacific Islander (18.2%), American Indian-Alaska Native (14.1%), multiracial (14.0%), Hispanic (12.6%), Asian (10.6%), and White pregnant patients (9.6%). From 2011 to 2020, the prevalence of anemia increased more than100% among Black patients, and there was a persistent gap in prevalence among Black compared with White patients. Compared with White patients, the adjusted risk for SMM was high among most racial and ethnic groups; adjustment for anemia after sequential modeling for known confounders decreased SMM risk most for Black pregnant patients (approximated RR 1.47, 95% CI 1.42-1.53 to approximated RR 1.27, 95% CI 1.22-1.37). Compared with White patients, the full adjusted nontransfusion SMM risk remained high for most groups except Hispanic and multiracial patients. Within each racial and ethnic group, the population attributable risk percentage for antepartum anemia and SMM was highest for multiracial patients (21.4%, 95% CI 17.5-25.0%), followed by Black (20.9%, 95% CI 18.1-23.4%) and Hispanic (20.9%, 95% CI 19.9-22.1%) patients. The nontransfusion SMM population attributable risk percentages for Asian, Black, and White pregnant patients were less than 8%. CONCLUSION: Antepartum anemia, most prevalent among Black pregnant patients, contributed to disparities in SMM by race and ethnicity. Nearly one in five to six SMM cases among Black, Hispanic, American Indian-Alaska Native, Pacific Islander, and multiracial pregnant patients is attributable in part to antepartum anemia.

Feasibility and impact of a mental health chatbot on postpartum mental health: a randomized controlled trial.

BACKGROUND: Perinatal mood disorders are common yet underdiagnosed and un- or undertreated. Barriers exist to accessing perinatal mental health services, including limited availability, time, and cost. Automated conversational agents (chatbots) can deliver evidence-based cognitive behavioral therapy content through text message-based conversations and reduce depression and anxiety symptoms in select populations. Such digital mental health technologies are poised to overcome barriers to mental health care access but need to be evaluated for efficacy, as well as for preliminary feasibility and acceptability among perinatal populations. OBJECTIVE: To evaluate the acceptability and preliminary efficacy of a mental health chatbot for mood management in a general postpartum population. STUDY DESIGN: An unblinded randomized controlled trial was conducted at a tertiary academic center. English-speaking postpartum women aged 18 years or above with a live birth and access to a smartphone were eligible for enrollment prior to discharge from delivery hospitalization. Baseline surveys were administered to all participants prior to randomization to a mental health chatbot intervention or to usual care only. The intervention group downloaded the mental health chatbot smartphone application with perinatal-specific content, in addition to continuing usual care. Usual care consisted of routine postpartum follow up and mental health care as dictated by the patient's obstetric provider. Surveys were administered during delivery hospitalization (baseline) and at 2-, 4-, and 6-weeks postpartum to assess depression and anxiety symptoms. The primary outcome was a change in depression symptoms at 6-weeks as measured using two depression screening tools: Patient Health Questionnaire-9 and Edinburgh Postnatal Depression Scale. Secondary outcomes included anxiety symptoms measured using Generalized Anxiety Disorder-7, and satisfaction and acceptability using validated scales. Based on a prior study, we estimated a sample size of 130 would have sufficient (80%) power to detect a moderate effect size (d=.4) in between group difference on the Patient Health Questionnaire-9. RESULTS: A total of 192 women were randomized equally 1:1 to the chatbot or usual care; of these, 152 women completed the 6-week survey (n=68 chatbot, n=84 usual care) and were included in the final analysis. Mean baseline mental health assessment scores were below positive screening thresholds. At 6-weeks, there was a greater decrease in Patient Health Questionnaire-9 scores among the chatbot group compared to the usual care group (mean decrease=1.32, standard deviation=3.4 vs mean decrease=0.13, standard deviation=3.01, respectively). 6-week mean Edinburgh Postnatal Depression Scale and Generalized Anxiety Disorder-7 scores did not differ between groups and were similar to baseline. 91% (n=62) of the chatbot users were satisfied or highly satisfied with the chatbot, and 74% (n=50) of the intervention group reported use of the chatbot at least once in 2 weeks prior to the 6-week survey. 80% of study participants reported being comfortable with the use of a mobile smartphone application for mood management. CONCLUSION: Use of a chatbot was acceptable to women in the early postpartum period. The sample did not screen positive for depression at baseline and thus the potential of the chatbot to reduce depressive symptoms in this population was limited. This study was conducted in a general obstetric population. Future studies of longer duration in high-risk postpartum populations who screen positive for depression are needed to further understand the utility and efficacy of such digital therapeutics for that population.

Identification of cow milk epitopes to characterize and quantify disease-specific T cells in allergic children.

BACKGROUND: Cow milk (CM) allergy is the most prevalent food allergy in young children in the United States and Great Britain. Current diagnostic tests are either unreliable (IgE test and skin prick test) or resource-intensive with risks (food challenges). OBJECTIVE: We sought to determine whether allergen-specific T cells in CM-allergic (CMA) patients have a distinct quality and/or quantity that could potentially be used as a diagnostic marker. METHODS: Using PBMCs from 147 food-allergic pediatric subjects, we mapped T-cell responses to a set of reactive epitopes in CM that we compiled in a peptide pool. This pool induced cytokine responses in in vitro cultured cells distinguishing subjects with CMA from subjects without CMA. We further used the pool to isolate and characterize antigen-specific CD4 memory T cells using flow cytometry and single-cell RNA/TCR sequencing assays. RESULTS: We detected significant changes in the transcriptional program and clonality of CM antigen-specific (CM+) T cells elicited by the pool in subjects with CMA versus subjects without CMA ex vivo. CM+ T cells from subjects with CMA had increased percentages of FOXP3+ cells over FOXP3- cells. FOXP3+ cells are often equated with regulatory T cells that have suppressive activity, but CM+ FOXP3+ cells from subjects with CMA showed significant expression of interferon-responsive genes and dysregulated chemokine receptor expression compared with subjects without CMA, suggesting that these are not conventional regulatory T cells. The CM+ FOXP3+ cells were also more clonally expanded than the FOXP3- population. We were further able to use surface markers (CD25, CD127, and CCR7) in combination with our peptide pool stimulation to quantify these CM+ FOXP3+ cells by a simple flow-cytometry assay. We show increased percentages of CM+ CD127-CD25+ cells from subjects with CMA in an independent cohort, which could be used for diagnostic purposes. Looking specifically for TH2 cells normally associated with allergic diseases, we found a small population of clonally expanded CM+ cells that were significantly increased in subjects with CMA and that had high expression of TH2 cytokines and pathogenic TH2/T follicular helper markers. CONCLUSIONS: Overall, these findings suggest that there are several differences in the phenotypes of CM+ T cells with CM allergy and that the increase in CM+ FOXP3+ cells is a potential diagnostic marker of an allergic state. Such markers have promising applications in monitoring natural disease outgrowth and/or the efficacy of immunotherapy that will need to be validated in future studies.

Abortion Bans and Resource Utilization for Congenital Heart Disease: A Decision Analysis.

OBJECTIVE: To investigate the implications of potential national abortion ban scenarios on the incidence of neonatal single-ventricle cardiac defects. METHODS: A decision tree model was developed to predict the incidence of neonatal single-ventricle cardiac defects and related outcomes in the United States under four theoretical national abortion bans: 1) abortion restrictions in existence immediately before the June 2022 Dobbs v Jackson Women's Health Organization Supreme Court decision, 2) 20 weeks of gestation, 3) 13 weeks of gestation, and 4) a complete abortion ban. The model included incidence of live births of neonates with single-ventricle cardiac defects, neonatal heart surgery (including heart transplant and extracorporeal membrane oxygenation [ECMO]), and neonatal death. Cohort size was based on national pregnancy incidence and different algorithm decision point probabilities were aggregated from the existing literature. Monte Carlo simulations were conducted with 10,000 iterations per model. RESULTS: In the scenario before the Dobbs decision, an estimated 6,369,000 annual pregnancies in the United States resulted in 1,006 annual cases of single-ventricle cardiac defects. Under a complete abortion ban, the model predicted a 53.7% increase in single-ventricle cardiac defects, or an additional 9 cases per 100,000 live births. This increase would result in an additional 531 neonatal heart surgeries, 16 heart transplants, 77 ECMO utilizations, and 102 neonatal deaths annually. More restrictive gestational age-based bans are predicted to confer increases in cases of neonatal single-ventricle cardiac defects and related adverse outcomes as well. CONCLUSION: Universal abortion bans are estimated to increase the incidence of neonatal single-ventricle cardiac defects, associated morbidity, and resource utilization. States considering limiting abortion should consider the implications on the resources required to care for increasing number of children that will be born with significant and complex medical needs, including those with congenital heart disease.

Hospital-level variation in racial disparities in low-risk nulliparous cesarean delivery rates.

BACKGROUND: Nationally, rates of cesarean delivery are highest among Black patients compared with other racial/ethnic groups. These observed inequities are a relatively new phenomenon (in the 1980s, cesarean delivery rates among Black patients were lower than average), indicating an opportunity to narrow the gap. Cesarean delivery rates vary greatly among hospitals, masking racial disparities that are unseen when rates are reported in aggregate. OBJECTIVE: This study aimed to explore reasons for the current large Black-White disparity in first-birth cesarean delivery rates by first examining the hospital-level variation in first-birth cesarean delivery rates among different racial/ethnic groups. We then identified hospitals that had low first-birth cesarean delivery rates among Black patients and compared them with hospitals with high rates. We sought to identify differences in facility or patient characteristics that could explain the racial disparity. STUDY DESIGN: A population cross-sectional study was performed on 1,267,493 California live births from 2018 through 2020 using birth certificate data linked with maternal patient discharge records. Annual nulliparous term singleton vertex cesarean delivery (first-birth) rates were calculated for the most common racial/ethnic groups statewide and for each hospital. Self-identified race/ethnicity categories as selected on the birth certificate were used. Relative risk and 95% confidence intervals for first-birth cesarean delivery comparing 2019 with 2015 were estimated using a log-binomial model for each racial/ethnic group. Patient and hospital characteristics were compared between hospitals with first-birth cesarean delivery rates <23.9% for Black patients and hospitals with rates ≥23.9% for Black patients. RESULTS: Hospitals with at least 30 nulliparous term singleton vertex Asian, Black, Hispanic, and White patients each were identified. Black patients had a very different distribution, with a significantly higher rate (28.4%) and wider standard deviation (7.1) and interquartile range (6.5) than other racial groups (P<.01). A total of 29 hospitals with a low first-birth cesarean delivery rate among Black patients were identified using the Healthy People 2020 target of 23.9% and compared with 106 hospitals with higher rates. The low-rate group had a cesarean delivery rate of 19.9%, as opposed to 30.7% in the higher-rate group. There were no significant differences between the groups in hospital characteristics (ownership, delivery volume, neonatal level of care, proportion of midwife deliveries) or patient characteristics (age, education, insurance, onset of prenatal care, body mass index, hypertension, diabetes mellitus). Among the 106 hospitals that did not meet the target for Black patients, 63 met it for White patients with a mean rate of 21.4%. In the same hospitals, the mean rate for Black patients was 29.5%. Among Black patients in the group that did not meet the 23.9% target, there were significantly higher rates of all cesarean delivery indications: labor dystocia, fetal concern (spontaneous labor), and no labor (eg, macrosomia), which are all indications with a high degree of subjectivity. CONCLUSION: The statewide cesarean delivery rate of Black patients is significantly higher and has substantially greater hospital variation compared with other racial or ethnic groups. The lack of difference in facility or patient characteristics between hospitals with low cesarean delivery rates among Black patients and those with high rates suggests that unconscious bias and structural racism potentially play important roles in creating these racial differences.

Obstetric Volume and Severe Maternal Morbidity Among Low-Risk and Higher-Risk Patients Giving Birth at Rural and Urban US Hospitals.

Importance: Identifying hospital factors associated with severe maternal morbidity (SMM) is essential to clinical and policy efforts. Objective: To assess associations between obstetric volume and SMM in rural and urban hospitals and examine whether these associations differ for low-risk and higher-risk patients. Design, Setting, and Participants: This retrospective cross-sectional study of linked vital statistics and patient discharge data was conducted from 2022 to 2023. Live births and stillbirths (≥20 weeks' gestation) at hospitals in California (2004-2018), Michigan (2004-2020), Pennsylvania (2004-2014), and South Carolina (2004-2020) were included. Data were analyzed from December 2022 to May 2023. Exposures: Annual birth volume categories (low, medium, medium-high, and high) for hospitals in urban (10-500, 501-1000, 1001-2000, and >2000) and rural (10-110, 111-240, 241-460, and >460) counties. Main Outcome and Measures: The main outcome was SMM (excluding blood transfusion); covariates included age, payer status, educational attainment, race and ethnicity, and obstetric comorbidities. Analyses were stratified for low-risk and higher-risk obstetric patients based on presence of at least 1 clinical comorbidity. Results: Among more than 11 million urban births and 519 953 rural births, rates of SMM ranged from 0.73% to 0.50% across urban hospital volume categories (high to low) and from 0.47% to 0.70% across rural hospital volume categories (high to low). Risk of SMM was elevated for patients who gave birth at rural hospitals with annual birth volume of 10 to 110 (adjusted risk ratio [ARR], 1.65; 95% CI, 1.14-2.39), 111 to 240 (ARR, 1.37; 95% CI, 1.10-1.70), and 241 to 460 (ARR, 1.26; 95% CI, 1.05-1.51), compared with rural hospitals with greater than 460 births. Increased risk of SMM occurred for low-risk and higher-risk obstetric patients who delivered at rural hospitals with lower birth volumes, with low-risk rural patients having notable discrepancies in SMM risk between low (ARR, 2.32; 95% CI, 1.32-4.07), medium (ARR, 1.66; 95% CI, 1.20-2.28), and medium-high (ARR, 1.68; 95% CI, 1.29-2.18) volume hospitals compared with high volume (>460 births) rural hospitals. Among hospitals in urban counties, there was no significant association between birth volume and SMM for low-risk or higher-risk obstetric patients. Conclusions and Relevance: In this cross-sectional study of births in US rural and urban counties, risk of SMM was elevated for low-risk and higher-risk obstetric patients who gave birth in lower-volume hospitals in rural counties, compared with similar patients who gave birth at rural hospitals with greater than 460 annual births. These findings imply a need for tailored quality improvement strategies for lower volume hospitals in rural communities.

Phase 3 Trial of Epicutaneous Immunotherapy in Toddlers with Peanut Allergy.

BACKGROUND: No approved treatment for peanut allergy exists for children younger than 4 years of age, and the efficacy and safety of epicutaneous immunotherapy with a peanut patch in toddlers with peanut allergy are unknown. METHODS: We conducted this phase 3, multicenter, double-blind, randomized, placebo-controlled trial involving children 1 to 3 years of age with peanut allergy confirmed by a double-blind, placebo-controlled food challenge. Patients who had an eliciting dose (the dose necessary to elicit an allergic reaction) of 300 mg or less of peanut protein were assigned in a 2:1 ratio to receive epicutaneous immunotherapy delivered by means of a peanut patch (intervention group) or to receive placebo administered daily for 12 months. The primary end point was a treatment response as measured by the eliciting dose of peanut protein at 12 months. Safety was assessed according to the occurrence of adverse events during the use of the peanut patch or placebo. RESULTS: Of the 362 patients who underwent randomization, 84.8% completed the trial. The primary efficacy end point result was observed in 67.0% of children in the intervention group as compared with 33.5% of those in the placebo group (risk difference, 33.4 percentage points; 95% confidence interval, 22.4 to 44.5; P<0.001). Adverse events that occurred during the use of the intervention or placebo, irrespective of relatedness, were observed in 100% of the patients in the intervention group and 99.2% in the placebo group. Serious adverse events occurred in 8.6% of the patients in the intervention group and 2.5% of those in the placebo group; anaphylaxis occurred in 7.8% and 3.4%, respectively. Serious treatment-related adverse events occurred in 0.4% of patients in the intervention group and none in the placebo group. Treatment-related anaphylaxis occurred in 1.6% in the intervention group and none in the placebo group. CONCLUSIONS: In this trial involving children 1 to 3 years of age with peanut allergy, epicutaneous immunotherapy for 12 months was superior to placebo in desensitizing children to peanuts and increasing the peanut dose that triggered allergic symptoms. (Funded by DBV Technologies; EPITOPE ClinicalTrials.gov number, NCT03211247.).

Clinical and Physician Factors Associated With Failed Operative Vaginal Delivery.

OBJECTIVE: To examine clinical and physician factors associated with failed operative vaginal delivery among individuals with nulliparous, term, singleton, vertex (NTSV) births. METHODS: This was a retrospective cohort study of individuals with NTSV live births with an attempted operative vaginal delivery by a physician between 2016 and 2020 in California. The primary outcome was cesarean birth after failed operative vaginal delivery, identified using linked diagnosis codes, birth certificates, and physician licensing board data stratified by device type (vacuum or forceps). Clinical and physician-level exposures were selected a priori, defined using validated indices, and compared between successful and failed operative vaginal delivery attempts. Physician experience with operative vaginal delivery was estimated by calculating the number of operative vaginal delivery attempts made per physician during the study period. Multivariable mixed effects Poisson regression models with robust standard errors were used to estimate risk ratios of failed operative vaginal delivery for each exposure, adjusted for potential confounders. RESULTS: Of 47,973 eligible operative vaginal delivery attempts, 93.2% used vacuum and 6.8% used forceps. Of all operative vaginal delivery attempts, 1,820 (3.8%) failed; the success rate was 97.3% for vacuum attempts and 82.4% for forceps attempts. Failed operative vaginal deliveries were more likely with older patient age, higher body mass index, obstructed labor, and neonatal birth weight more than 4,000 g. Between 2016 and 2020, physicians who attempted more operative vaginal deliveries were less likely to fail. When vacuum attempts were successful, physicians who conducted them had a median of 45 vacuum attempts during the study period, compared with 27 attempts when vacuum attempts were unsuccessful (adjusted risk ratio [aRR] 0.95, 95% CI 0.93-0.96). When forceps attempts were successful, physicians who conducted them had a median of 19 forceps attempts, compared with 11 attempts when forceps attempts were unsuccessful (aRR 0.76, 95% CI 0.64-0.91). CONCLUSION: In this large, contemporary cohort with NTSV births, several clinical factors were associated with operative vaginal delivery failure. Physician experience was associated with operative vaginal delivery success, more notably for forceps attempts. These results may provide guidance for physician training in maintenance of operative vaginal delivery skills.

Early Postpartum Hospital Encounters among Patients with Genitourinary and Wound Infections during Hospitalization for Birth.

OBJECTIVES: This study aimed to assess the associations between genitourinary and wound infections during the birth hospitalization and early postpartum hospital encounters, and to evaluate clinical risk factors for early postpartum hospital encounters among patients with genitourinary and wound infections during the birth hospitalization. STUDY DESIGN: We conducted a population-based cohort study of births in California during 2016 to 2018 and postpartum hospital encounters. We identified genitourinary and wound infections using diagnosis codes. Our main outcome was early postpartum hospital encounter, defined as a readmission or emergency department (ED) visit within 3 days after discharge from the birth hospitalization. We evaluated the association of genitourinary and wound infections (overall and subtypes) with early postpartum hospital encounter using logistic regression, adjusting for sociodemographic factors and comorbidities and stratified by mode of birth. We then evaluated factors associated with early postpartum hospital encounter among patients with genitourinary and wound infections. RESULTS: Among 1,217,803 birth hospitalizations, 5.5% were complicated by genitourinary and wound infections. Genitourinary or wound infection was associated with an early postpartum hospital encounter among patients with both vaginal births (2.2%; adjusted risk ratio [aRR[: 1.26; 95% confidence interval [CI]: 1.17-1.36) and cesarean births (3.2%; aRR: 1.23; 95% CI: 1.15-1.32). Patients with a cesarean birth and a major puerperal infection or wound infection had the highest risk of an early postpartum hospital encounter (6.4 and 4.3%, respectively). Among patients with genitourinary and wound infections during the birth hospitalization, factors associated with an early postpartum hospital encounter included severe maternal morbidity, major mental health condition, prolonged postpartum hospital stay, and, among cesarean births, postpartum hemorrhage (p-value < 0.05). CONCLUSION: Genitourinary and wound infections during hospitalization for birth may increase risk of a readmission or ED visit within the first few days after discharge, particularly among patients who have a cesarean birth and a major puerperal infection or wound infection. KEY POINTS: · In all, 5.5% of patients giving birth had a genitourinary or wound infection (GWI).. · A total of 2.7% of GWI patients had a hospital encounter within 3 days of discharge after birth.. · Major puerperal infection and wound infection had the highest risk of an early hospital encounter.. · Among GWI patients, several birth complications were associated with an early hospital encounter..

Vaginal Progesterone Is Associated with Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: The frequency of intrahepatic cholestasis of pregnancy (ICP) peaks during the third trimester of pregnancy when plasma progesterone levels are the highest. Furthermore, twin pregnancies are characterized by higher progesterone levels than singletons and have a higher frequency of cholestasis. Therefore, we hypothesized that exogenous progestogens administered for reducing the risk of spontaneous preterm birth may increase the risk of cholestasis. Utilizing the large IBM MarketScan Commercial Claims and Encounters Database, we investigated the frequency of cholestasis in patients treated with vaginal progesterone or intramuscular 17α-hydroxyprogesterone caproate for the prevention of preterm birth. STUDY DESIGN: We identified 1,776,092 live-born singleton pregnancies between 2010 and 2014. We confirmed second and third trimester administration of progestogens by cross-referencing the dates of progesterone prescriptions with the dates of scheduled pregnancy events such as nuchal translucency scan, fetal anatomy scan, glucose challenge test, and Tdap vaccination. We excluded pregnancies with missing data regarding timing of scheduled pregnancy events or progesterone treatment prescribed only during the first trimester. Cholestasis of pregnancy was identified based on prescriptions for ursodeoxycholic acid. We used multivariable logistic regression to estimate adjusted (for maternal age) odds ratios for cholestasis in patients treated with vaginal progesterone, and in patients treated with 17α-hydroxyprogesterone caproate compared with those not treated with any type of progestogen (the reference group). RESULTS: The final cohort consisted of 870,599 pregnancies. Among patients treated with vaginal progesterone during the second and third trimester, the frequency of cholestasis was significantly higher than the reference group (0.75 vs. 0.23%, adjusted odds ratio [aOR]: 3.16, 95% confidence interval [CI]: 2.23-4.49). In contrast, there was no significant association between 17α-hydroxyprogesterone caproate and cholestasis (0.27%, aOR: 1.12, 95% CI: 0.58-2.16) CONCLUSION: Using a robust dataset, we observed that vaginal progesterone but not intramuscular 17α-hydroxyprogesterone caproate was associated with an increased risk for ICP. KEY POINTS: · Previous studies have been underpowered to detect potential association between progesterone and ICP.. · Vaginal progesterone was significantly associated with ICP.. · Intramuscular 17α-hydroxyprogesterone was not associated with ICP..