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.).

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.

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.

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.

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..

A Novel Fetal Magnetic Resonance Imaging Lung Volume Nomogram Stratified by Estimated Fetal Weight.

INTRODUCTION: Fetal magnetic resonance imaging (MRI) lung volume nomograms are increasingly used to prognosticate neonatal outcomes in fetuses with suspected pulmonary hypoplasia. However, pregnancies complicated by fetal anomalies associated with pulmonary hypoplasia may also be complicated by fetal growth restriction (FGR). If a small lung volume is suspected in such cases, it is often unclear whether the lungs are "small" because of underlying lung pathology, or small fetal size. Existing MRI lung volume nomograms have mostly been stratified by gestational age (GA), rather than estimated fetal weight (EFW). Therefore, we aimed to develop a novel fetal lung volume nomogram stratified by EFW. METHODS: Consecutive fetal MRIs performed at a quaternary medical center from 2019 to 2021 were analyzed. MRIs performed due to fetal lung anomalies and cases with FGR were excluded. All MRIs were performed without IV contrast on GE 3 or 1.5 Tesla scanners (GE Healthcare). Images were reviewed by three experienced fetal radiologists. Freehand ROI in square centimeter was drawn around the contours of the lungs on consecutive slices from the apex to the base. The volume of the right, left and total lungs were calculated in mL. Lung volumes were plotted by both EFW and GA. RESULTS: Among 301 MRI studies performed during the study period, 170 cases met inclusion criteria and were analyzed. MRIs were performed between 19- and 38-week gestation, and a sonographic EFW was obtained within a mean of 2.9 days (SD ± 5.5 days, range 0-14 days) of each MRI. Nomograms stratified by both EFW and GA were created using 200 g. and weekly intervals respectively. A formula using EFW to predict total lung volume was calculated: LV = 0.07497804 EFW0.88276 (R2 = 0.87). CONCLUSIONS: We developed a novel fetal lung volume nomogram stratified by EFW. If validated, this nomogram may assist clinicians predict outcomes in cases of fetal pulmonary hypoplasia with concomitant FGR.

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.

Validation of ICD-10-CM Diagnosis Codes for Gestational Age at Birth.

BACKGROUND: The International Classification of Diseases , 10th Revision, Clinical Modification (ICD-10-CM) introduced diagnosis codes for week of gestation. Our objective was to assess the validity of these codes among live births, which could have major utility in perinatal research and quality improvement. METHODS: We used linked birth certificate and patient discharge data from births in California during 2016-2019 (N = 1,843,992). We identified gestational age using Z3A.xx ICD-10-CM diagnosis codes in birthing patient discharge data and compared it with the gold standard of obstetric estimate, as recorded on the birth certificate. We further assessed sensitivity and specificity of gestational age categories (≥37 weeks, <37 weeks, <32 weeks, <28 weeks), given these categories are frequently of interest, and evaluated differences in validity of preterm birth (<37 weeks' gestation) by patient characteristics. RESULTS: One-million seven-hundred seventy-thousand one-hundred three patients had a gestational age recorded in patient discharge and birth certificate data. When comparing gestational age in patient discharge data with birth certificate data, the concordance correlation coefficient was 0.96 (95% confidence interval [CI] = 0.96, 0.96) and the mean difference between the two measurements was 0.047 weeks (95% CI = 0.046, 0.047 weeks). Ninety-five percent of the differences between the two measurements were between -1.00 week and +1.09 weeks. Sensitivity and specificity were 0.94 to 1.00 for all gestational age categories and were 0.94 to 1.00 for preterm birth across sociodemographic groups. CONCLUSIONS: We found week-specific gestational age at delivery ICD-10-CM diagnosis codes in patient discharge data to have high validity when compared with the best obstetric estimate on the birth certificate.

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..

Sexual and/or gender minority disparities in obstetrical and birth outcomes.

BACKGROUND: Many sexual and/or gender minority individuals build families through pregnancy and childbirth, but it is unknown whether they experience different clinical outcomes than those who are not sexual and/or gender minority individuals. OBJECTIVE: To evaluate obstetrical and birth outcomes comparing couples who are likely sexual and/or gender minority patients compared with those who are not likely to be sexual and/or gender minority patients. STUDY DESIGN: We performed a population-based cohort study of live birth hospitalizations during 2016 to 2019 linked to birth certificates in California. California changed its birth certificate in 2016 to include gender-neutral fields such as "parent giving birth" and "parent not giving birth," with options for each role to specify "mother," "father," or "parent." We classified birthing patients in mother-mother partnerships and those who identified as a father in any partnership as likely sexual and/or gender minority and classified birthing patients in mother-father partnerships as likely not sexual and/or gender minority. We used multivariable modified Poisson regression models to estimate the risk ratios for associations between likely sexual and/or gender minority parental structures and outcomes. The models were adjusted for sociodemographic factors, comorbidities, and multifetal gestation selected by causal diagrams. We replicated the analyses after excluding multifetal gestations. RESULTS: In the final birthing patient sample, 1,483,119 were mothers with father partners, 2572 were mothers with mother partners, and 498 were fathers with any partner. Compared with birthing patients in mother-father partnerships, birthing patients in mother-mother partnerships experienced significantly higher rates of multifetal gestation (adjusted risk ratio, 3.9; 95% confidence interval, 3.4-4.4), labor induction (adjusted risk ratio, 1.2; 95% confidence interval, 1.1-1.3), postpartum hemorrhage (adjusted risk ratio, 1.4; 95% confidence interval, 1.3-1.6), severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.2-1.8), and nontransfusion severe morbidity (adjusted risk ratio, 1.4; 95% confidence interval, 1.1-1.9). Severe morbidity was identified following the Centers for Disease Control and Prevention "severe maternal morbidity" index. Gestational diabetes mellitus, hypertensive disorders of pregnancy, cesarean delivery, preterm birth (<37 weeks' gestation), low birthweight (<2500 g), and low Apgar score (<7 at 5 minutes) did not significantly differ in the multivariable analyses. No outcomes significantly differed between father birthing patients in any partnership and birthing patients in mother-father partnerships in either crude or multivariable analyses, though the risk of multifetal gestation was nonsignificantly higher (adjusted risk ratio, 1.5; 95% confidence interval, 0.9-2.7). The adjusted risk ratios for the outcomes were similar after restriction to singleton gestations. CONCLUSION: Birthing mothers with mother partners experienced disparities in several obstetrical and birth outcomes independent of sociodemographic factors, comorbidities, and multifetal gestation. Birthing fathers in any partnership were not at a significantly elevated risk of any adverse obstetrical or birth outcome considered in this study.

Leukocyte telomere dynamics across gestation in uncomplicated pregnancies and associations with stress.

BACKGROUND: Short leukocyte telomere length is a biomarker associated with stress and morbidity in non-pregnant adults. Little is known, however, about maternal telomere dynamics in pregnancy. To address this, we examined changes in maternal leukocyte telomere length (LTL) during uncomplicated pregnancies and explored correlations with perceived stress. METHODS: In this pilot study, maternal LTL was measured in blood collected from nulliparas who delivered live, term, singleton infants between 2012 and 2018 at a single institution. Participants were excluded if they had diabetes or hypertensive disease. Samples were collected over the course of pregnancy and divided into three time periods: < 200/7 weeks (Timepoint 1); 201/7 to 366/7 weeks (Timepoint 2); and 370/7 to 9-weeks postpartum (Timepoint 3). All participants also completed a survey assessing a multivariate profile of perceived stress at the time of enrollment in the first trimester. LTL was measured using quantitative polymerase chain reaction (PCR). Wilcoxon signed-rank tests were used to compare LTL differences within participants across all timepoint intervals. To determine whether mode of delivery affected LTL, we compared postpartum Timepoint 3 LTLs between participants who had vaginal versus cesarean birth. Secondarily, we evaluated the association of the assessed multivariate stress profile and LTL using machine learning analysis. RESULTS: A total of 115 samples from 46 patients were analyzed. LTL (mean ± SD), expressed as telomere to single copy gene (T/S) ratios, were: 1.15 ± 0.26, 1.13 ± 0.23, and 1.07 ± 0.21 for Timepoints 1, 2, and 3, respectively. There were no significant differences in LTL between Timepoints 1 and 2 (LTL T/S change - 0.03 ± 0.26, p = 0.39); 2 and 3 (- 0.07 ± 0.29, p = 0.38) or Timepoints 1 and 3 (- 0.07 ± 0.21, p = 0.06). Participants who underwent cesareans had significantly shorter postpartum LTLs than those who delivered vaginally (T/S ratio: 0.94 ± 0.12 cesarean versus 1.12 ± 0.21 vaginal, p = 0.01). In secondary analysis, poor sleep quality was the main stress construct associated with shorter Timepoint 1 LTLs (p = 0.02) and shorter mean LTLs (p = 0.03). CONCLUSIONS: In this cohort of healthy pregnancies, maternal LTLs did not significantly change across gestation and postpartum LTLs were shorter after cesarean than after vaginal birth. Significant associations between sleep quality and short LTLs warrant further investigation.

"Ignored and Invisible": Perspectives from Black Women, Clinicians, and Community-Based Organizations for Reducing Preterm Birth.

OBJECTIVES: The preterm birth rate for Black women in the U.S. is consistently higher than other racial groups. The crisis of preterm birth and adverse birth outcomes among Black people is a historical, systematic confluence of racism, stressors, and an unsupportive and hostile healthcare system. To inform the development of preterm birth risk reduction interventions, this study aimed to collect and synthesize the experiences of Black women who gave birth preterm along with clinicians and community-based organizations who serve them. METHODS: A qualitative study design was employed whereby nine focus groups and 17 key informant interviews that included Black women, clinicians, and representatives from community-based organizations were facilitated in Los Angeles County from March 2019 to March 2020. Participants were recruited through the organizations and the focus groups took place virtually and in person. The process of thematic analysis was employed to analyze the focus group and interview transcripts. RESULTS: Five overarching themes emerged from the data. Black women experience chronic and pregnancy-related stress, and have lasting trauma from adverse maternal health experiences. These issues are exacerbated by racism and cultural incongruence within healthcare and social services systems. Black women have relied on self-education and self-advocacy to endure the barriers related to racism, mistreatment, and their experiences with preterm birth. CONCLUSIONS FOR PRACTICE: Healthcare and social service providers must offer more holistic care that prioritizes, rather than ignores, the racial components of health, placing increased importance on implementing inclusive and culturally-appropriate patient education, attentiveness to patient needs, respectful care, and support for Black women.

Integrating oral immunotherapy into clinical practice.

In 2020, the first food allergy treatment, an oral immunotherapy (OIT) product for peanut allergy, was approved by the Food and Drug Administration, and a peanut epicutaneous immunotherapy patch was under review. As food allergy therapies become available and widespread, allergy offices will need to adjust practices to be able to offer their patients these new treatments. OIT is an intensive therapy that requires commitment from patients and their families, and open communication with the practice is paramount. OIT may not be the right therapy for every patient, and although identifying good candidates is still an area rich for research opportunity, experience from cohorts and clinical trials provides some insight. It is important to understand the scope of practice for each member of the OIT team based on state regulations for a particular location. Staffing and space will likely dictate how many patients at an individual office could be on active OIT at one time. Emergency medications, supplies, and protocols must be in place. Screening, scheduling, visit procedures, monitoring, home dosing, dose modifications, safety precautions, adverse reactions, and maintenance will be addressed in this article. Finally, adjunct therapies under investigation will be reviewed.

AR101 Oral Immunotherapy for Peanut Allergy.

BACKGROUND: Peanut allergy, for which there are no approved treatment options, affects patients who are at risk for unpredictable and occasionally life-threatening allergic reactions. METHODS: In a phase 3 trial, we screened participants 4 to 55 years of age with peanut allergy for allergic dose-limiting symptoms at a challenge dose of 100 mg or less of peanut protein (approximately one third of a peanut kernel) in a double-blind, placebo-controlled food challenge. Participants with an allergic response were randomly assigned, in a 3:1 ratio, to receive AR101 (a peanut-derived investigational biologic oral immunotherapy drug) or placebo in an escalating-dose program. Participants who completed the regimen (i.e., received 300 mg per day of the maintenance regimen for approximately 24 weeks) underwent a double-blind, placebo-controlled food challenge at trial exit. The primary efficacy end point was the proportion of participants 4 to 17 years of age who could ingest a challenge dose of 600 mg or more, without dose-limiting symptoms. RESULTS: Of the 551 participants who received AR101 or placebo, 496 were 4 to 17 years of age; of these, 250 of 372 participants (67.2%) who received active treatment, as compared with 5 of 124 participants (4.0%) who received placebo, were able to ingest a dose of 600 mg or more of peanut protein, without dose-limiting symptoms, at the exit food challenge (difference, 63.2 percentage points; 95% confidence interval, 53.0 to 73.3; P<0.001). During the exit food challenge, the maximum severity of symptoms was moderate in 25% of the participants in the active-drug group and 59% of those in the placebo group and severe in 5% and 11%, respectively. Adverse events during the intervention period affected more than 95% of the participants 4 to 17 years of age. A total of 34.7% of the participants in the active-drug group had mild events, as compared with 50.0% of those in the placebo group; 59.7% and 44.4% of the participants, respectively, had events that were graded as moderate, and 4.3% and 0.8%, respectively, had events that were graded as severe. Efficacy was not shown in the participants 18 years of age or older. CONCLUSIONS: In this phase 3 trial of oral immunotherapy in children and adolescents who were highly allergic to peanut, treatment with AR101 resulted in higher doses of peanut protein that could be ingested without dose-limiting symptoms and in lower symptom severity during peanut exposure at the exit food challenge than placebo. (Funded by Aimmune Therapeutics; PALISADE ClinicalTrials.gov number, NCT02635776 .).

Karyotype of first clinical miscarriage and prognosis of subsequent pregnancy outcome.

RESEARCH QUESTION: Is the karyotype of the first clinical miscarriage in an infertile patient predictive of the outcome of the subsequent pregnancy? DESIGN: Retrospective cohort study of infertile patients undergoing manual vacuum aspiration with chromosome testing at the time of the first (index) clinical miscarriage with a genetic diagnosis and a subsequent pregnancy. Patients treated at two academic-affiliated fertility centres from 1999 to 2018 were included; those using preimplantation genetic testing for aneuploidy were excluded. Main outcome was live birth in the subsequent pregnancy. RESULTS: One hundred patients with euploid clinical miscarriage and 151 patients with aneuploid clinical miscarriage in the index pregnancy were included. Patients with euploid clinical miscarriage in the index pregnancy had a live birth rate of 63% in the subsequent pregnancy compared with 68% among patients with aneuploid clinical miscarriage (adjusted odds ratio [aOR] 0.75, 95% CI 0.47-1.39, P = 0.45, logistic regression model adjusting for age, parity, body mass index and mode of conception). In a multinomial logistic regression model with three outcomes (live birth, clinical miscarriage or biochemical miscarriage), euploid clinical miscarriage for the index pregnancy was associated with similar odds of clinical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage for the index pregnancy (32% versus 24%, respectively, aOR 1.49, 95% CI 0.83-2.70, P = 0.19). Euploid clinical miscarriage for the index pregnancy was not associated with likelihood of biochemical miscarriage in the subsequent pregnancy compared with aneuploid clinical miscarriage (5% versus 8%, respectively, aOR 0.46, 95% CI 0.14-1.55, P = 0.21). CONCLUSION: Prognosis after a first clinical miscarriage among infertile patients is equally favourable among patients with euploid and aneuploid karyotype, and independent of the karyotype of the pregnancy loss.

Birth hospital and racial and ethnic differences in severe maternal morbidity in the state of California.

BACKGROUND: Birth hospital has recently emerged as a potential key contributor to disparities in severe maternal morbidity, but investigations on its contribution to racial and ethnic differences remain limited. OBJECTIVE: We leveraged statewide data from California to examine whether birth hospital explained racial and ethnic differences in severe maternal morbidity. STUDY DESIGN: This cohort study used data on all births at ≥20 weeks gestation in California (2007-2012). Severe maternal morbidity during birth hospitalization was measured using the Centers for Disease Control and Prevention index of having at least 1 of the 21 diagnoses and procedures (eg, eclampsia, blood transfusion, hysterectomy). Mixed-effects logistic regression models (ie, women nested within hospitals) were used to compare racial and ethnic differences in severe maternal morbidity before and after adjustment for maternal sociodemographic and pregnancy-related factors, comorbidities, and hospital characteristics. We also estimated the risk-standardized severe maternal morbidity rates for each hospital (N=245) and the percentage reduction in severe maternal morbidity if each group of racially and ethnically minoritized women gave birth at the same distribution of hospitals as non-Hispanic white women. RESULTS: Of the 3,020,525 women who gave birth, 39,192 (1.3%) had severe maternal morbidity (2.1% Black; 1.3% US-born Hispanic; 1.3% foreign-born Hispanic; 1.3% Asian and Pacific Islander; 1.1% white; 1.6% American Indian and Alaska Native, and Mixed-race referred to as Other). Risk-standardized rates of severe maternal morbidity ranged from 0.3 to 4.0 per 100 births across hospitals. After adjusting for covariates, the odds of severe maternal morbidity were greater among nonwhite women than white women in a given hospital (Black: odds ratio, 1.25; 95% confidence interval, 1.19-1.31); US-born Hispanic: odds ratio, 1.25; 95% confidence interval, 1.20-1.29; foreign-born Hispanic: odds ratio, 1.17; 95% confidence interval, 1.11-1.24; Asian and Pacific Islander: odds ratio, 1.26; 95% confidence interval, 1.21-1.32; Other: odds ratio, 1.31; 95% confidence interval, 1.15-1.50). Among the studied hospital factors, only teaching status was associated with severe maternal morbidity in fully adjusted models. Although 33% of white women delivered in hospitals with the highest tertile of severe maternal morbidity rates compared with 53% of Black women, birth hospital only accounted for 7.8% of the differences in severe maternal morbidity comparing Black and white women and accounted for 16.1% to 24.2% of the differences for all other racial and ethnic groups. CONCLUSION: In California, excess odds of severe maternal morbidity among racially and ethnically minoritized women were not fully explained by birth hospital. Structural causes of racial and ethnic disparities in severe maternal morbidity may vary by region, which warrants further examination to inform effective policies.

Management of acute food protein-induced enterocolitis syndrome emergencies at home and in a medical facility.

OBJECTIVE: Acute food protein-induced enterocolitis syndrome (FPIES) is characterized by delayed repetitive vomiting after ingestion of a trigger food, and severe reactions may lead to dehydration, hypotension, and shock. We provide recommendations on management of FPIES emergencies in a medical facility and at home. DATA SOURCES: This review summarizes the literature on clinical context, pathophysiology, presentation, and treatment of FPIES emergencies. STUDY SELECTIONS: We referred to the 2017 International Consensus Guidelines for the Diagnosis and Management of FPIES and performed a literature search identifying relevant recent primary articles and review articles on clinical management. RESULTS: Management of FPIES emergencies in a medical facility is based on severity of symptoms and involves rehydration, ondansetron, and corticosteroids. A proactive approach for reactions occurring at home involves prescribing oral ondansetron and providing an individualized treatment plan based on the evolution of symptoms and severity of past reactions. A better understanding of the pathophysiology of FPIES and randomized trials on ondansedron and cocorticosteroid use could lead to more targeted treatments. CONCLUSION: Children with FPIES are at risk for severe symptoms constituting a medical emergency. Management of FPIES emergencies is largely supportive, with treatment tailored to the symptoms, severity of the patient's condition, location of reaction, and reaction history.

Association of Maternal Comorbidity With Severe Maternal Morbidity: A Cohort Study of California Mothers Delivering Between 1997 and 2014.

BACKGROUND: Rates of maternal mortality and severe maternal morbidity (SMM) are higher in the United States than in other high-resource countries and are increasing further. OBJECTIVE: To examine the association of maternal comorbid conditions, age, body mass index, and previous cesarean birth with occurrence of SMM. DESIGN: Population-based cohort study using linked delivery hospitalization discharge data and vital records. SETTING: California, 1997 to 2014. PATIENTS: All 9 179 472 mothers delivering in California during 1997 to 2014. MEASUREMENTS: SMM rate, total and without transfusion-only cases; 2019 maternal comorbidity index. RESULTS: Total SMM increased by 160% during this time, and SMM excluding transfusion-only cases increased by 53%. Medical comorbid conditions were associated with an increasing portion of SMM occurrences. Medical comorbid conditions increased over the study period by 111%, and obstetric comorbid conditions increased by 30% to 40%. Identified medical comorbid conditions had high relative risks ranging from 1.3 to 14.3 for total SMM and even higher relative risks for nontransfusion SMM (to 32.4). The obstetric comorbidity index that is most often used may be undervaluing the degree of association with SMM. LIMITATIONS: Hospital discharge diagnosis files and birth certificate records can have misclassifications and may not include all relevant clinical data or social determinants. The period for analysis ended in 2014 to avoid the transition to the International Classification of Diseases, 10th Revision, Clinical Modification, and therefore missed more recent years. CONCLUSION: Obstetric and, particularly, medical comorbid conditions are increasing among women who develop SMM. The maternal comorbidity index is a promising tool for patient risk assessment and case-mix adjustment, but refinement of factor weights may be indicated. PRIMARY FUNDING SOURCE: National Institutes of Health.