RUNX1 is required in granulocyte-monocyte progenitors to attenuate inflammatory cytokine production by neutrophils.

The transcription factor RUNX1 is mutated in familial platelet disorder with associated myeloid malignancy (FPDMM) and in sporadic myelodysplastic syndrome and leukemia. RUNX1 was shown to regulate inflammation in multiple cell types. Here we show that RUNX1 is required in granulocyte-monocyte progenitors (GMPs) to epigenetically repress two inflammatory signaling pathways in neutrophils: Toll-like receptor 4 (TLR4) and type I interferon (IFN) signaling. RUNX1 loss in GMPs augments neutrophils' inflammatory response to the TLR4 ligand lipopolysaccharide through increased expression of the TLR4 coreceptor CD14. RUNX1 binds Cd14 and other genes encoding proteins in the TLR4 and type I IFN signaling pathways whose chromatin accessibility increases when RUNX1 is deleted. Transcription factor footprints for the effectors of type I IFN signaling-the signal transducer and activator of transcription (STAT1::STAT2) and interferon regulatory factors (IRFs)-were enriched in chromatin that gained accessibility in both GMPs and neutrophils when RUNX1 was lost. STAT1::STAT2 and IRF motifs were also enriched in the chromatin of retrotransposons that were derepressed in RUNX1-deficient GMPs and neutrophils. We conclude that a major direct effect of RUNX1 loss in GMPs is the derepression of type I IFN and TLR4 signaling, resulting in a state of fixed maladaptive innate immunity.

Efficient hemogenic endothelial cell specification by RUNX1 is dependent on baseline chromatin accessibility of RUNX1-regulated TGFß target genes.

Hematopoietic stem and progenitor cells (HSPCs) are generated de novo in the embryo from hemogenic endothelial cells (HECs) via an endothelial-to-hematopoietic transition (EHT) that requires the transcription factor RUNX1. Ectopic expression of RUNX1 alone can efficiently promote EHT and HSPC formation from embryonic endothelial cells (ECs), but less efficiently from fetal or adult ECs. Efficiency correlated with baseline accessibility of TGFß-related genes associated with endothelial-to-mesenchymal transition (EndoMT) and participation of AP-1 and SMAD2/3 to initiate further chromatin remodeling along with RUNX1 at these sites. Activation of TGFß signaling improved the efficiency with which RUNX1 specified fetal ECs as HECs. Thus, the ability of RUNX1 to promote EHT depends on its ability to recruit the TGFß signaling effectors AP-1 and SMAD2/3, which in turn is determined by the changing chromatin landscape in embryonic versus fetal ECs. This work provides insight into regulation of EndoMT and EHT that will guide reprogramming efforts for clinical applications.

Transcriptional regulatory network controlling the ontogeny of hematopoietic stem cells.

Hematopoietic stem cell (HSC) ontogeny is accompanied by dynamic changes in gene regulatory networks. We performed RNA-seq and histone mark ChIP-seq to define the transcriptomes and epigenomes of cells representing key developmental stages of HSC ontogeny in mice. The five populations analyzed were embryonic day 10.5 (E10.5) endothelium and hemogenic endothelium from the major arteries, an enriched population of prehematopoietic stem cells (pre-HSCs), fetal liver HSCs, and adult bone marrow HSCs. Using epigenetic signatures, we identified enhancers for each developmental stage. Only 12% of enhancers are primed, and 78% are active, suggesting the vast majority of enhancers are established de novo without prior priming in earlier stages. We constructed developmental stage-specific transcriptional regulatory networks by linking enhancers and predicted bound transcription factors to their target promoters using a novel computational algorithm, target inference via physical connection (TIPC). TIPC predicted known transcriptional regulators for the endothelial-to-hematopoietic transition, validating our overall approach, and identified putative novel transcription factors, including the broadly expressed transcription factors SP3 and MAZ. Finally, we validated a role for SP3 and MAZ in the formation of hemogenic endothelium. Our data and computational analyses provide a useful resource for uncovering regulators of HSC formation.

Social determinants of health and obstetric outcomes: A report and recommendations of the workshop of the Society for Maternal-Fetal Medicine.

This article is a report of a 2-day workshop, entitled "Social determinants of health and obstetric outcomes," held during the Society for Maternal-Fetal Medicine 2022 Annual Pregnancy Meeting. Participants' fields of expertise included obstetrics, pediatrics, epidemiology, health services, health equity, community-based research, and systems biology. The Commonwealth Foundation and the Alliance of Innovation on Maternal Health cosponsored the workshop and the Society for Women's Health Research provided additional support. The workshop included presentations and small group discussions, and its goals were to accomplish the following.

Racism in obstetric care: a psychometric study of the Gendered Racial Microaggressions Scale among Global Majority birthing people in obstetric contexts.

In the United States, maternal health inequities disproportionately affect Global Majority (e.g., Asian, Black, and Hispanic) populations. Despite a substantial body of research underscoring the influence of racism on these inequities, little research has examined how experiences of gendered racial microaggressions during pregnancy and birth impact racially and ethnically diverse Global Majority pregnant and birthing people in obstetric hospital settings. We evaluated the psychometric properties of an adapted version of Lewis & Neville's Gendered Racial Microaggressions Scale, using data collected from 417 Global Majority birthing people. Findings from our study indicate that our adapted GRMS is a valid tool for assessing the experiences of gendered racial microaggressions in hospital-based obstetric care settings among Global Majority pregnant and birthing people whose preferred languages are English or Spanish. Item Response Theory (IRT) analysis demonstrated high construct validity of the adapted GRMS scale (Root Mean Square Error of Approximation = 0.1089 (95% CI 0.0921, 0.1263), Comparative Fit Index = 0.977, Standardized Root Mean Square Residual = 0.075, log-likelihood c2 = -85.6, df = 8). IRT analyses demonstrated that the unidimensional model was preferred to the bi-dimensional model as it was more interpretable, had lower AIC and BIC, and all items had large discrimination parameters onto a single factor (all discrimination parameters > 3.0). Given that we found similar response profiles among Black and Hispanic respondents, our Differential Item Functioning analyses support validity among Black, Hispanic, and Spanish-speaking birthing people. Inter-item correlations demonstrated adequate scale reliability, α = 0.97, and empirical reliability = 0.67. Pearsons correlations was used to assess the criterion validity of our adapted scale. Our scale's total score was significantly and positively related to postpartum depression and anxiety. Researchers and practitioners should seek to address instances of gendered racial microaggressions in obstetric settings, as they are manifestations of systemic and interpersonal racism, and impact postpartum health.

Diversity and transparency in gynecologic oncology clinical trials.

PURPOSE: Clinical trials advance the standard of care for patients. Patients enrolled in trials should represent the population who would benefit from the intervention in clinical practice. The aim of this study was to assess whether clinical trials enrolling patients with gynecologic cancers report racial and ethnic participant composition and to examine the level of diversity in clinical trials. METHODS: Using ClinicalTrials.gov, we identified clinical trials enrolling patients with ovarian, uterine/endometrial, cervical, vaginal, and vulvar cancers from 1988 to 2019. Race and ethnicity data were extracted from participant demographics. Descriptive statistics on race, ethnicity, cancer type, location, study status, and sponsor type were calculated. Among trials which reported race and/or ethnicity, sub-analyses were performed on composition of race and ethnicity by funding source, location, and completed study status. RESULTS: A total of 1,882 trials met inclusion criteria; only 179 trials (9.5%) reported race information. Of these, the racial distribution of enrollees was 66.9% White, 8.6% Asian, 8.5% Black/African American, 0.4% Indian/Alaskan Native, 0.1% Native Hawaiian/Pacific Islander, 1.0% more than one race, and 14.5% unknown. Only 100 (5.3%) trials reported ethnicity. Except for trials enrolling patients with cervical cancer which enrolled 65.2% White and 62.1% Non-Hispanic/Latino/a patients, enrollees in trials for other gynecologic cancers were over 80% White and 88% Non-Hispanic/Latino/a. Industry funded trials enrolled higher proportions of White (68.4%) participants than non-industry funded trials (57.5%). Domestic trials report race (11.5%) and ethnicity (7.6%) at higher rates than international trials (6.9% and 2.3%, respectively). Reporting of race (1.7% vs. 13.9%) and ethnicity (1.7% vs. 11.1%) has increased over time for patients enrolled in 2000 vs. 2018. CONCLUSION: Less than 10% of trials enrolling patients with gynecologic malignancies report racial/ethnic participant composition on ClinicalTrials.gov. Accurate reporting of participant race/ethnicity is imperative to ensuring minority representation in clinical trials.

Understanding the spectrum of malignant bowel obstructions in gynecologic cancers and the application of the Henry score.

OBJECTIVE: Malignancy-associated bowel obstruction (MBO) is a potential sequela of advanced gynecologic cancers, adversely impacting both quality of life and prognosis. The Henry score (HS) was developed in a gastrointestinal cancer-predominant population to predict 30-day mortality. We aim to characterize MBO in gynecologic cancers and assess the utility of the HS in this population. METHODS: This is a retrospective review of patients with gynecologic cancer and MBO admitted to a single academic institution from 2016 to 2021. The primary outcome is to characterize malignant small and large bowel obstructions in primary and recurrent gynecologic cancer using readmission and mortality rates. Secondary outcomes are to assess the Henry score and inpatient MBO management. RESULTS: 179 patients totaling 269 were admissions identified, most commonly affecting patients with ovarian cancer. The majority (89.4%) were managed non-operatively while 10.6% were managed surgically. No significant differences were observed in survival for medical versus surgical management. Thirty-day mortality increased with increasing HS (0%, 0-1; 14.3%, 2-3; 40.9%, 4-5). Over 1/3 (34.1%) of patients were readmitted for recurrent or persistent MBO. Goals of care conversations were documented for 56.8% of patients with HS 4-5. Mortality rates across the entire cohort were high-20.1% and 60.9% had died by 1 and 6 months, respectively. CONCLUSIONS: Survival rates following an initial MBO admission are poor. The HS has utility in gynecologic cancers for assessing 30-day mortality and may be a useful tool to aid in the management and counseling of patients with gynecologic cancer and MBO.

Scholarly activity following National Institutes of Health Women's Reproductive Health Research K12 training-a cohort study.

BACKGROUND: National Institutes of Health funding to address basic reproductive health for common female conditions remains disproportionately low, in part because of low success rates of grant applications by obstetrician-gynecologists. OBJECTIVE: This study aimed to evaluate the scholarly productivity of individuals supported by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Women's Reproductive Health Research K12 career development award, created to advance careers of obstetrician-gynecologist physician-scientists. STUDY DESIGN: We performed a cohort study of individuals who completed at least 2 years of Women's Reproductive Health Research training by June 30, 2015, and had at least 5-year follow-up. Earliest training start date was December 1, 1998. Primary outcomes from public data sources (National Institutes of Health RePORTER, PubMed, iCite) were (1) number of total and R01 National Institutes of Health grants as principal investigator; (2) numbers of total and first and last author publications; and (3) median and highest publication impact factor measured by the relative citation ratio. Secondary outcomes from an email survey subcohort were total number of research grants, federally funded grants, and number of National Institutes of Health grants as coinvestigator; institutional promotions and academic appointments, national and National Institutes of Health leadership roles; and career and mentorship satisfaction. Outcomes were recorded at 5, 10, and 15 years postgraduation, and aggregate anonymized data were divided into 3 groups using Women's Reproductive Health Research completion dates: June 30 of 2005, 2010, and 2015. Temporal trends were assessed. Results were stratified by gender, number of awarded grant cycles (1-2 vs 3-4), and specialty type. Analyses used Fisher exact or Pearson chi-square tests, and Mantel-Haenszel tests of trend. RESULTS: The distribution of the cohort (N=178) by graduation completion date was: on or before June 30, 2005 (57 [32%]); July 1, 2005 to June 30, 2010 (60 [34%]); and July 1, 2010 to June 30, 2015 (61 [34%]). Most participants were female (112 [64%]) and maternal-fetal medicine trained (53 [30%]), followed by no fellowship (50 [28%]). Of the 178 participants, 72 (40%) received additional National Institutes of Health funding as a principal investigator, 45 (25%) received at least 1 R01, and 23 (13%) received 2 to 5 R01s. There were 52 (31%) scholars with >10 first author publications, 66 (39%) with >10 last author publications, and 108 (63%) with ≥25 publications. The highest relative citation ratio was a median of 8.07 (interquartile range, 4.20-15.16). There were 121 (71%) scholars with relative citation ratio ≥5, indicating >5-fold greater publication impact than that of other National Institutes of Health-funded scientists in similar areas of research. No differences by gender, institution, or temporal trends were observed. Of the full cohort, 69 (45.7%) responded to the survey; most self-identified as women (50 [73%]) and White (51 [74%]). CONCLUSION: Our findings suggest that the infrastructure provided by an institutional K award is an advantageous career development award mechanism for obstetrician-gynecologists, a group of predominantly women surgeons. It may serve as a corrective for the known inequities in National Institutes of Health funding by gender.

Development of a prediction model of postpartum hospital use using an equity-focused approach.

BACKGROUND: Racial inequities in maternal morbidity and mortality persist into the postpartum period, leading to a higher rate of postpartum hospital use among Black and Hispanic people. Delivery hospitalizations provide an opportunity to screen and identify people at high risk to prevent adverse postpartum outcomes. Current models do not adequately incorporate social and structural determinants of health, and some include race, which may result in biased risk stratification. OBJECTIVE: This study aimed to develop a risk prediction model of postpartum hospital use while incorporating social and structural determinants of health and using an equity approach. STUDY DESIGN: We conducted a retrospective cohort study using 2016-2018 linked birth certificate and hospital discharge data for live-born infants in New York City. We included deliveries from 2016 to 2017 in model development, randomly assigning 70%/30% of deliveries as training/test data. We used deliveries in 2018 for temporal model validation. We defined "Composite postpartum hospital use" as at least 1 readmission or emergency department visit within 30 days of the delivery discharge. We categorized diagnosis at first hospital use into 14 categories based on International Classification of Diseases-Tenth Revision diagnosis codes. We tested 72 candidate variables, including social determinants of health, demographics, comorbidities, obstetrical complications, and severe maternal morbidity. Structural determinants of health were the Index of Concentration at the Extremes, which is an indicator of racial-economic segregation at the zip code level, and publicly available indices of the neighborhood built/natural and social/economic environment of the Child Opportunity Index. We used 4 statistical and machine learning algorithms to predict "Composite postpartum hospital use", and an ensemble approach to predict "Cause-specific postpartum hospital use". We simulated the impact of each risk stratification method paired with an effective intervention on race-ethnic equity in postpartum hospital use. RESULTS: The overall incidence of postpartum hospital use was 5.7%; the incidences among Black, Hispanic, and White people were 8.8%, 7.4%, and 3.3%, respectively. The most common diagnoses for hospital use were general perinatal complications (17.5%), hypertension/eclampsia (12.0%), nongynecologic infections (10.7%), and wound infections (8.4%). Logistic regression with least absolute shrinkage and selection operator selection retained 22 predictor variables and achieved an area under the receiver operating curve of 0.69 in the training, 0.69 in test, and 0.69 in validation data. Other machine learning algorithms performed similarly. Selected social and structural determinants of health features included the Index of Concentration at the Extremes, insurance payor, depressive symptoms, and trimester entering prenatal care. The "Cause-specific postpartum hospital use" model selected 6 of the 14 outcome diagnoses (acute cardiovascular disease, gastrointestinal disease, hypertension/eclampsia, psychiatric disease, sepsis, and wound infection), achieving an area under the receiver operating curve of 0.75 in training, 0.77 in test, and 0.75 in validation data using a cross-validation approach. Models had slightly lower performance in Black and Hispanic subgroups. When simulating use of the risk stratification models with a postpartum intervention, identifying high-risk individuals with the "Composite postpartum hospital use" model resulted in the greatest reduction in racial-ethnic disparities in postpartum hospital use, compared with the "Cause-specific postpartum hospital use" model or a standard approach to identifying high-risk individuals with common pregnancy complications. CONCLUSION: The "Composite postpartum hospital use" prediction model incorporating social and structural determinants of health can be used at delivery discharge to identify persons at risk for postpartum hospital use.

Predictors and Trends in First-Trimester Hemoglobin A1c Screening in New York City, 2009 to 2017.

Glycated hemoglobin is an adjunct tool in early pregnancy to assess glycemic control. We examined trends and maternal predictors for those who had A1c screening in early pregnancy using hospital discharge and vital registry data between 2009 and 2017 linked with the New York City A1C Registry (N = 798,312). First-trimester A1c screening increased from 2.3% in 2009 to 7.7% in 2017. The likelihood of screening became less targeted to high-risk patients over time, with a decrease in mean A1c values from 5.8% (95% confidence interval [CI]: 5.8, 5.9) to 5.3 (95% CI: 5.3, 5.4). The prevalence of gestational diabetes mellitus increased while testing became less discriminate for those with high-risk factors, including pregestational type 2 diabetes, chronic hypertension, obesity, age over 40 years, as well as Asian or Black non-Hispanic race/ethnicity. KEY POINTS: · First-trimester A1c screening increased from 2.3% in 2009 to 7.7% in 2017 in New York City.. · The likelihood of screening became less targeted to high-risk patients over time.. · The prevalence of gestational diabetes mellitus increased, while testing became less discriminate..

Developmental trajectory of prehematopoietic stem cell formation from endothelium.

Hematopoietic stem and progenitor cells (HSPCs) in the bone marrow are derived from a small population of hemogenic endothelial (HE) cells located in the major arteries of the mammalian embryo. HE cells undergo an endothelial to hematopoietic cell transition, giving rise to HSPCs that accumulate in intra-arterial clusters (IAC) before colonizing the fetal liver. To examine the cell and molecular transitions between endothelial (E), HE, and IAC cells, and the heterogeneity of HSPCs within IACs, we profiled ∼40 000 cells from the caudal arteries (dorsal aorta, umbilical, vitelline) of 9.5 days post coitus (dpc) to 11.5 dpc mouse embryos by single-cell RNA sequencing and single-cell assay for transposase-accessible chromatin sequencing. We identified a continuous developmental trajectory from E to HE to IAC cells, with identifiable intermediate stages. The intermediate stage most proximal to HE, which we term pre-HE, is characterized by increased accessibility of chromatin enriched for SOX, FOX, GATA, and SMAD motifs. A developmental bottleneck separates pre-HE from HE, with RUNX1 dosage regulating the efficiency of the pre-HE to HE transition. A distal candidate Runx1 enhancer exhibits high chromatin accessibility specifically in pre-HE cells at the bottleneck, but loses accessibility thereafter. Distinct developmental trajectories within IAC cells result in 2 populations of CD45+ HSPCs; an initial wave of lymphomyeloid-biased progenitors, followed by precursors of hematopoietic stem cells (pre-HSCs). This multiomics single-cell atlas significantly expands our understanding of pre-HSC ontogeny.

Society for Maternal-Fetal Medicine Special Statement: Race in maternal-fetal medicine research- Dispelling myths and taking an accurate, antiracist approach.

Profound inequities in maternal and infant outcomes based on race exist, and the maternal-fetal medicine community has an important role in eliminating these disparities. Accurately employing race and ethnicity as social constructs within research that guides clinical practice is essential to achieving health equity. We must abandon commonly propagated myths that race is a surrogate for genetics or economic status and that data are exempt from potential bias. These myths can lead to harmful misconceptions that exacerbate racial disparities in maternal and infant health outcomes. Furthermore, these myths obscure racism as the true underlying etiology of racial disparities. Understanding that race is a social construct and using an antiracist approach to research are essential in combating racism and eliminating unacceptable disparities in maternal and infant health. This document provides specific suggestions to approach the research process with an antiracist framework.

Economic Evaluation of Prenatal and Postpartum Care in Women With Gestational Diabetes and Hypertensive Disorders of Pregnancy: A Systematic Review.

OBJECTIVES: This study aimed to summarize evidence on the economic outcomes of prenatal and postpartum interventions for the management of gestational diabetes mellitus and hypertensive disorders of pregnancy (HDP), assess the quality of each study, and identify research gaps that may inform future research. METHODS: Electronic databases including PubMed/MEDLINE, Embase, the Cochrane Library, and Cochrane Central Register of Controlled Trials were searched from January 1, 2000, to October 1, 2021. Selected studies were included in narrative synthesis and extracted data were presented in narrative and tabular forms. The quality of each study was assessed using the Consolidated Health Economic Evaluation Reporting Standards and Consensus on Health Economic Criteria list. RESULTS: Among the 22 studies identified through the systematic review, 19 reported favorable cost-effectiveness of the intervention. For prenatal management of HDP, home blood pressure monitoring was found to be cost-effective compared with in-person visits in improving maternal and neonatal outcomes. For postpartum care, regular screening for hypertension or metabolic syndrome followed by subsequent treatment was found to be cost-effective compared with no screening in women with a history of gestational diabetes mellitus or HDP. CONCLUSIONS: Existing economic evaluation studies showed that prenatal home blood pressure monitoring and postpartum screening for hypertension or metabolic syndrome were cost-effective. Nevertheless, limitations in the approach of the current economic evaluations may dampen the quality of the evidence and warrant further investigation.

SARS-CoV-2 during pregnancy and associated outcomes: Results from an ongoing prospective cohort.

BACKGROUND: The COVID-19 pandemic is an ongoing global health threat, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Questions remain about how SARS-CoV-2 impacts pregnant individuals and their children. OBJECTIVE: To expand our understanding of the effects of SARS-CoV-2 infection during pregnancy on pregnancy outcomes, regardless of symptomatology, by using serological tests to measure IgG antibody levels. METHODS: The Generation C Study is an ongoing prospective cohort study conducted at the Mount Sinai Health System. All pregnant individuals receiving obstetrical care at the Mount Sinai Healthcare System from 20 April 2020 onwards are eligible for participation. For the current analysis, we included participants who had given birth to a liveborn singleton infant on or before 22 September 2020. For each woman, we tested the latest prenatal blood sample available to establish seropositivity using a SARS-CoV-2 serologic enzyme-linked immunosorbent assay. Additionally, RT-PCR testing was performed on a nasopharyngeal swab taken during labour. Pregnancy outcomes of interest (i.e., gestational age at delivery, preterm birth, small for gestational age, Apgar scores, maternal and neonatal intensive care unit admission, and length of neonatal hospital stay) and covariates were extracted from medical records. Excluding individuals who tested RT-PCR positive at delivery, we conducted crude and adjusted regression models to compare antibody positive with antibody negative individuals at delivery. We stratified analyses by race/ethnicity to examine potential effect modification. RESULTS: The SARS-CoV-2 seroprevalence based on IgG measurement was 16.4% (95% confidence interval 13.7, 19.3; n=116). Twelve individuals (1.7%) were SARS-CoV-2 RT-PCR positive at delivery. Seropositive individuals were generally younger, more often Black or Hispanic, and more often had public insurance and higher pre-pregnancy BMI compared with seronegative individuals. None of the examined pregnancy outcomes differed by seropositivity, overall or stratified by race/ethnicity. CONCLUSION: Seropositivity for SARS-CoV-2 without RT-PCR positivity at delivery (suggesting that infection occurred earlier during pregnancy) was not associated with selected adverse maternal or neonatal outcomes among live births in a cohort sample from New York City.

COVID-19 pandemic-related change in racial and ethnic disparities in exclusive breastmilk feeding during the delivery hospitalization: a differences-in-differences analysis.

OBJECTIVE: Exclusive breastmilk feeding during the delivery hospitalization, a Joint Commission indicator of perinatal care quality, is associated with longer-term breastfeeding success. Marked racial and ethnic disparities in breastfeeding exclusivity and duration existed prior to COVID-19. The pandemic, accompanied by uncertainty regarding intrapartum and postpartum safety practices, may have influenced disparities in infant feeding practices. Our objective was to examine whether the first wave of the COVID-19 pandemic in New York City was associated with a change in racial and ethnic disparities in exclusive breastmilk feeding during the delivery stay. METHODS: We conducted a cross-sectional study of electronic medical records from 14,964 births in two New York City hospitals. We conducted a difference-in-differences (DID) analysis to compare Black-white, Latina-white, and Asian-white disparities in exclusive breastmilk feeding in a pandemic cohort (April 1-July 31, 2020, n=3122 deliveries) to disparities in a pre-pandemic cohort (January 1, 2019-February 28, 2020, n=11,842). We defined exclusive breastmilk feeding as receipt of only breastmilk during delivery hospitalization, regardless of route of administration. We ascertained severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status from reverse transcription-polymerase chain reaction tests from nasopharyngeal swab at admission. For each DID model (e.g. Black-white disparity), we used covariate-adjusted log binomial regression models to estimate racial and ethnic risk differences, pandemic versus pre-pandemic cohort risk differences, and an interaction term representing the DID estimator. RESULTS: Exclusive breastmilk feeding increased from pre-pandemic to pandemic among white (40.8% to 46.6%, p<0.001) and Asian (27.9% to 35.8%, p=0.004) women, but not Black (22.6% to 25.3%, p=0.275) or Latina (20.1% to 21.4%, p=0.515) women overall. There was an increase in the Latina-white exclusive breastmilk feeding disparity associated with the pandemic (DID estimator=6.3 fewer cases per 100 births (95% CI=-10.8, -1.9)). We found decreased breastmilk feeding specifically among SARS-CoV-2 positive Latina women (20.1% pre-pandemic vs. 9.1% pandemic p=0.013), and no change in Black-white or Asian-white disparities. CONCLUSIONS: We observed a pandemic-related increase in the Latina-white disparity in exclusive breastmilk feeding, urging hospital policies and programs to increase equity in breastmilk feeding and perinatal care quality during and beyond this health emergency.

Improving Postpartum Care: Identifying Opportunities to Reduce Postpartum Emergency Room Visits Among Publicly-Insured Women of Color.

BACKGROUND/OBJECTIVES: The purpose of this study was to explore the postpartum experiences of publicly-insured women of color, and identify how postpartum care can be improved to reduce hospital emergency department usage after delivery. METHODS: We conducted four focus groups with 18 publicly-insured women who primarily self-identified as Black and/or Latina and gave birth between June 1, 2019 and May 1, 2020. We used inductive qualitative analysis to identify prominent themes from focus group discussions. RESULTS: We identified four domains: (1) lack of access to and communication with a medical team; (2) lack of preparation; (3) value of social support; and (4) participant-identified opportunities for improvement. CONCLUSIONS FOR PRACTICE: This study describes the postpartum experiences of publicly-insured women of color with the objective of identifying areas for intervention to reduce postpartum emergency department usage. Our findings suggest that focused efforts on enhancing continuity of care to increase healthcare access, strengthening patient-provider communication by training providers to recognize unconscious bias, increasing postpartum preparation by adapting teaching materials to an online format, and engaging women's caregivers throughout the pregnancy course to bolster social support, may be beneficial.

Developing Tools to Report Racism in Maternal Health for the CDC Maternal Mortality Review Information Application (MMRIA): Findings from the MMRIA Racism & Discrimination Working Group.

PURPOSE: The purpose of this report from the field is to describe the process by which an multidisciplinary workgroup, selected by the CDC Foundation in partnership with maternal health experts, developed a definition of racism that would be specifically appropriate for inclusion on the Maternal Mortality Review Information Application (MMRIA) form. DESCRIPTION: In the United States Black women are nearly 4 times more likely to experience a pregnancy-related death. Recent evidence points to racism as a fundamental cause of this inequity. Furthermore, the CDC reports that 3 of 5 pregnancy related deaths are preventable. With these startling facts in mind, the CDC created the Maternal Mortality Review Information Application (MMRIA) for use by Maternal Mortality Review Committees (MMRC) to support standardized data abstraction, case narrative development, documentation of committee decisions, and analysis on maternal mortality to inform practices and policies for preventing maternal mortality. ASSESSMENT: Charged with the task of defining racism and discrimination as contributors to pregnancy related mortality, the work group established four goals to define their efforts: (1) the desire to create a product that was inclusive of all forms of racism and discrimination experienced by birthing people; (2) an acknowledgement of the legacy of racism in the U.S. and the norms in health care delivery that perpetuate racist ideology; (3) an acknowledgement of the racist narratives surrounding the issue of maternal mortality and morbidity that often leads to victim blaming; and (4) that the product would be user friendly for MMRCs. CONCLUSION: The working group developed three definitions and a list of recommendations for action to help MMRC members provide suggested interventions to adopt when discrimination or racism were contributing factors to a maternal death. The specification of these definitions will allow the systematic tracking of the contribution of racism to maternal mortality through the MMRIA and allow a greater standardization of its identification across participating jurisdictions with MMRCs that use the form.

Stress and the Psychological Impact of the COVID-19 Pandemic on Frontline Obstetrics and Gynecology Providers.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) pandemic rapidly overwhelmed global health care systems in 2020, with New York City (NYC) marking the first epicenter in the United States. High levels of stress amongst health care workers have been reported in pandemics, but less is known about stress amongst Obstetrics and Gynecology (OB/GYN) providers. We sought to describe levels of stress, anxiety, depression, and other aspects of mental health among OB/GYN health care workers during the first wave of the COVID-19 pandemic. STUDY DESIGN: We conducted an anonymous cross-sectional electronic survey of a wide range of OB/GYN clinicians in a large NYC hospital system in the spring of 2020. We used both original survey questions and validated screening tools to assess stress, anxiety, depression, and burnout. We calculated median scores for these tools and compared median score between provider types. We also adapted questions on pandemic-related stressors from the MERS and SARS pandemics to fit the context of the COVID-19 pandemic and OB/GYN providers. RESULTS: A total of 464 providers met study inclusion criteria, and 163 providers completed the survey (response rate = 35.1%). Approximately 35% of providers screened positive for anxiety and 21% for depression. Scores for depression, burnout, and fulfillment varied by provider type, with nurses scoring higher than physicians (p <0.05). The majority of respondents reported stress from pandemic and OB-specific stressors, including the possibility of transmitting COVID-19 to friends and family (83.9%, [95% confidence interval or CI 78.0-89.8%]), uncertainty regarding the pandemic's trajectory (91.3% [86.7-95.8%]), and frequent policy changes on labor and delivery (72.7% [65.1-80.3%]). CONCLUSION: OB/GYN providers reported high levels of stress during the COVID-19 pandemic. The stress of caring for laboring patients during a pandemic may disproportionately affect nurses and trainees and highlights the need to provide interventions to ameliorate the negative impact of a pandemic on the mental health of our OB/GYN health care workers. KEY POINTS: · COVID-19 led to stress amongst OB/GYN providers.. · Some stressors were unique to providing obstetric care.. · Nurses and trainees were more affected by this stress..

Runx1 is sufficient for blood cell formation from non-hemogenic endothelial cells in vivo only during early embryogenesis.

Hematopoietic cells differentiate during embryogenesis from a population of endothelial cells called hemogenic endothelium (HE) in a process called the endothelial-to-hematopoietic transition (EHT). The transcription factor Runx1 is required for EHT, but for how long and which endothelial cells are competent to respond to Runx1 are not known. Here, we show that the ability of Runx1 to induce EHT in non-hemogenic endothelial cells depends on the anatomical location of the cell and the developmental age of the conceptus. Ectopic expression of Runx1 in non-hemogenic endothelial cells between embryonic day (E) 7.5 and E8.5 promoted the formation of erythro-myeloid progenitors (EMPs) specifically in the yolk sac, the dorsal aorta and the heart. The increase in EMPs was accompanied by a higher frequency of HE cells able to differentiate into EMPs in vitro Expression of Runx1 just 1 day later (E8.5-E9.5) failed to induce the ectopic formation of EMPs. Therefore, endothelial cells, located in specific sites in the conceptus, have a short developmental window of competency during which they can respond to Runx1 and differentiate into blood cells.

Racial and Economic Neighborhood Segregation, Site of Delivery, and Morbidity and Mortality in Neonates Born Very Preterm.

OBJECTIVE: To assess the influence of racial and economic residential segregation of home or hospital neighborhood on very preterm birth morbidity and mortality in neonates born very preterm. STUDY DESIGN: We constructed a retrospective cohort of n = 6461 infants born <32 weeks using 2010-2014 New York City vital statistics-hospital data. We calculated racial and economic Index of Concentration at the Extremes for home and hospital neighborhoods. Neonatal mortality and morbidity was defined as death and/or severe neonatal morbidity. We estimated relative risks for Index of Concentration at the Extremes measures and neonatal mortality and morbidity using log binomial regression and the risk-adjusted contribution of delivery hospital using Fairlie decomposition. RESULTS: Infants whose mothers live in neighborhoods with the greatest relative concentration of Black residents had a 1.6 times greater risk of neonatal mortality and morbidity than those with the greatest relative concentration of White residents (95% CI 1.2-2.1). Delivery hospital explained more than one-half of neighborhood differences. Infants with both home and hospital in high-concentration Black neighborhoods had a 38% adjusted risk of neonatal mortality and morbidity compared with 25% of those with both home and hospital high-concentration White neighborhoods (P = .045). CONCLUSIONS: Structural racism influences very preterm birth neonatal mortality and morbidity through both the home and hospital neighborhood. Quality improvement interventions should incorporate a framework that includes neighborhood context.