Barriers to and solutions for representative inclusion across the lifespan and in life course research: The need for structural competency highlighted by the COVID-19 pandemic.

Exclusion of special populations (older adults; pregnant women, children, and adolescents; individuals of lower socioeconomic status and/or who live in rural communities; people from racial and ethnic minority groups; individuals from sexual or gender minority groups; and individuals with disabilities) in research is a pervasive problem, despite efforts and policy changes by the National Institutes of Health and other organizations. These populations are adversely impacted by social determinants of health (SDOH) that reduce access and ability to participate in biomedical research. In March 2020, the Northwestern University Clinical and Translational Sciences Institute hosted the "Lifespan and Life Course Research: integrating strategies" "Un-Meeting" to discuss barriers and solutions to underrepresentation of special populations in biomedical research. The COVID-19 pandemic highlighted how exclusion of representative populations in research can increase health inequities. We applied findings of this meeting to perform a literature review of barriers and solutions to recruitment and retention of representative populations in research and to discuss how findings are important to research conducted during the ongoing COVID-19 pandemic. We highlight the role of SDOH, review barriers and solutions to underrepresentation, and discuss the importance of a structural competency framework to improve research participation and retention among special populations.

COVID Vaccine Information Sources Utilized by Female Healthcare Workers.

BACKGROUND: Clinical trials of the messenger RNA COVID-19 vaccines excluded individuals with active reproductive needs (attempting to conceive, currently pregnant, and/or lactating). Women comprise three-quarters of healthcare workers in the United States-an occupational field among the first to receive the vaccine. Professional medical and government organizations have encouraged shared decision-making and access to vaccination among those with active reproductive needs. OBJECTIVE: This study aimed to characterize the information sources used by pregnancy-capable healthcare workers for information about the COVID-19 vaccines and to compare the self-reported "most important" source by the respondents' active reproductive needs, if any. STUDY DESIGN: This was a web-based national survey of female, US-based healthcare workers in January 2021. Recruitment was done using social media and subsequent sharing via word of mouth. We classified the respondents into 6 groups on the basis of self-reported reproductive needs as follows: (1) preventing pregnancy, (2) attempting pregnancy, (3) currently pregnant, (4) lactating, (5) attempting pregnancy and lactating, and (6) currently pregnant and lactating. We provided respondents with a list of information sources (friends, family, obstetrician-gynecologists, pediatrician, news, social media, government organizations, their employer, and "other") and asked respondents which source(s) they used when looking for information about the vaccine and their most important source. We used descriptive statistics to characterize the information sources and compared the endorsement of government organizations and obstetrician-gynecologists, which were the most important information source between reproductive groups, using the chi-square test. The effect size was calculated using Cramér V. RESULTS: Our survey had 11,405 unique respondents: 5846 (51.3%) were preventing pregnancy, 955 (8.4%) were attempting pregnancy, 2196 (19.3%) were currently pregnant, 2250 (19.7%) were lactating, 67 (0.6%) were attempting pregnancy and lactating, and 91 (0.8%) were currently pregnant and lactating. The most endorsed information sources were government organizations (88.7%), employers (48.5%), obstetrician-gynecologists (44.9%), and social media (39.6%). Considering the most important information source, the distribution of respondents endorsing government organizations was different between reproductive groups (P<.001); it was most common among respondents preventing pregnancy (62.6%) and least common among those currently pregnant (31.5%). We observed an inverse pattern among the respondents endorsing an obstetrician-gynecologist as the most important source; the source was most common among currently pregnant respondents (51.4%) and least common among those preventing pregnancy (5.8%), P<.001. The differences in the endorsement of social media as an information source between groups were significant but had a small effect size. CONCLUSION: Healthcare workers use government and professional medical organizations for information. Respondents attempting pregnancy and those pregnant and/or lactating are more likely to use social media and an obstetrician-gynecologist as information sources for vaccine decision-making. These data can inform public health messaging and counseling for clinicians.

COVID-Severity and Diabetes in Pregnancy

Diabetes and pregnancy are independently associated with increased risk of severe COVID-infection. However, little is known about the relationship between severe COVID-and diabetes in pregnancy. We sought to determine whether diabetes in pregnancy was associated with increased risk of COVID-infection and severity. We conducted a case-control study of all delivering patients at a tertiary hospital from June 2020-September 2021 and accepted universal COVID-testing. Patients with no COVID-test results were excluded. The proportion of patients with any COVID-infection and severe COVID-infection during pregnancy were compared between patients with and without diabetes using chi-square. Severe COVID-was defined as meeting any WHOOSCI or NCPERET criteria (dyspnea, respiratory rate ≥30 breaths per minute, blood oxygen saturation of ≤93%, PaO2/FiO2 <300, lung infiltrates involving >50% on imaging, non-invasive ventilation or high flow oxygen use, intubation and mechanical ventilation, or ventilation with additional organ support) . Of 4,253 patients in our analysis, 292 (6.9%) had COVID-during pregnancy. Demographic characteristics were similar between patients with a COVID-infection in pregnancy and those that were negative;71 (24.3%) had a severe infection, and 451 (10.6%) had diabetes. There was no difference between patients with and without diabetes in incidence of COVID-infection (9.6% vs. 10.7%, p=0.56) or severe COVID-infection (11.3% vs. 9%, p=0.58) . Diabetes in pregnancy was not associated with increased risk of COVID-infection or severe infection. Future research in larger samples may further elucidate the association between diabetes and COVID-infection in pregnancy.

Characterizing initial COVID-19 vaccine attitudes among pregnancy-capable healthcare workers.

BACKGROUND: Healthcare workers were prioritized for COVID-19 vaccination roll-out because of the high occupational risk. Vaccine trials excluded individuals who were trying to conceive and those who are pregnant and lactating, necessitating vaccine decision-making in the absence of data specific to this population. OBJECTIVE: This study aimed to determine the initial attitudes about COVID-19 vaccination in pregnancy-capable healthcare workers by reproductive status and occupational exposure. STUDY DESIGN: We performed a structured survey distributed via social media of US-based healthcare workers involved in patient care since March 2020 who were pregnancy-capable (biologic female sex without history of sterilization or hysterectomy) from January 8, 2021 to January 31, 2021. Participants were asked about their desire to receive the COVID-19 vaccine and their perceived safety of the COVID-19 vaccine using 5-point Likert items with 1 corresponding to "I strongly don't want the vaccine" or "very unsafe for me" and 5 corresponding to "I strongly want the vaccine" or "very safe for me." We categorized participants into the following 2 groups: (1) reproductive intent (preventing pregnancy vs attempting pregnancy, currently pregnant, or currently lactating), and (2) perceived COVID-19 occupational risk (high vs low). We used descriptive statistics to characterize the respondents and their attitudes about the vaccine. Comparisons between reproductive and COVID-19 risk groups were conducted using Mann-Whitney U tests. RESULTS: Our survey included 11,405 pregnancy-capable healthcare workers: 51.3% were preventing pregnancy (n=5846) and 48.7% (n=5559) were attempting pregnancy, currently pregnant, and/or lactating. Most respondents (n=8394, 73.6%) had received a vaccine dose at the time of survey completion. Most participants strongly desired vaccination (75.3%) and very few were strongly averse (1.5%). Although the distribution of responses was significantly different between respondents preventing pregnancy and those attempting conception or were pregnant and/or lactating and also between respondents with a high occupational risk and those with a lower occupational risk of COVID-19, the effect sizes were small and the distribution was the same for each group (median, 5; interquartile range, 4-5). CONCLUSION: Most of the healthcare workers desired vaccination. Negative feelings toward vaccination were uncommon but were significantly higher among those attempting pregnancy and those who are pregnant and lactating and also among those with a lower perceived occupational risk of contracting COVID-19, although the effect size was small. Understanding healthcare workers' attitudes toward vaccination may help guide interventions to improve vaccine education and uptake in the general population.

Changes in the Antenatal Utilization of High-Risk Obstetric Services and Stillbirth Rate during the COVID-19 Pandemic.

OBJECTIVE: The primary objective of this study was to evaluate coronavirus 2019 (COVID-19) pandemic-related changes in the antenatal utilization of high-risk obstetric services. Our secondary objective was to characterize change in stillbirth rate during the pandemic. STUDY DESIGN: This is a retrospective, observational study performed at a single, tertiary care center. Maternal-Fetal Medicine (MFM) visits, ultrasounds, and antenatal tests of fetal well-being during the pandemic epoch (2020), which spans the first 12 weeks of the year to include pandemic onset and implementation of mitigation efforts, were compared with the same epoch of the three preceding years visually and using general linear models to account for week and year effect. An analysis of stillbirth rate comparing the pandemic time period to prepandemic was also performed. RESULTS: While there were decreased MFM visits and antenatal tests of fetal well-being during the pandemic epoch compared with prepandemic epochs, only the decrease in MFM visits by year was statistically significant (p < 0.001). The stillbirth rate during the pandemic epoch was not significantly different when compared with the prepandemic period and accounting for both week (p = 0.286) and year (p = 0.643) effect. CONCLUSION: The COVID-19 pandemic resulted in a significant decrease in MFM visits, whereas obstetric ultrasounds and antenatal tests of fetal well-being remained unchanged. While we observed no change in the stillbirth rate compared with the prepandemic epoch, our study design and sample size preclude us from making assumptions of association. Our findings may support future work investigating how changes in prenatal care for high-risk obstetric patients influence perinatal outcomes. KEY POINTS: · MFM visits significantly decreased during the COVID-19 pandemic epoch.. · The overall stillbirth rate during the COVID-19 pandemic epoch was not significantly changed.. · Larger studies are needed to capitalize on these changes to evaluate rare outcomes such as stillbirth..

SARS-CoV-2 colonization of maternal and fetal cells of the human placenta promotes alteration of local renin-angiotensin system.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection appears to increase the risk of adverse pregnancy outcomes, such as pre-eclampsia in pregnant women. The mechanism(s) by which this occurs remains unclear. METHODS: We investigated the pathophysiology of SARS-CoV-2 at maternal-fetal interface in pregnant women who tested positive for the virus using RNA in situ hybridization (viral RNA), immunohistochemistry, and hematoxylin and eosin staining. To investigate whether viral infection alters the renin angiotensin system (RAS) in placenta, which controls blood pressure, we treated human trophoblasts with recombinant spike protein or a live modified virus with a vesicular stomatitis viral backbone expressing spike protein (VSV-S). FINDINGS: Viral colonization was highest in maternal decidua, fetal trophoblasts, Hofbauer cells, and in placentas delivered prematurely. We localized SARS-CoV-2 to cells expressing angiotensin-converting enzyme 2 (ACE2) and demonstrate that infected placentas had significantly reduced ACE2. In response to both spike protein and VSV-S, cellular ACE2 decreased although angiotensin II receptor type 1 (AT1R) increased with concomitant increase in soluble fms-like tyrosine kinase-1 (sFlt1). Viral infection decreased pro-angiogenic factors, AT2R, and placental growth factor, which competitively binds to sFlt1. Sera from infected pregnant women had elevated levels of sFlt1 and angiotensin II type 1-receptor autoantibodies prior to delivery, both signatory markers of pre-eclampsia. CONCLUSIONS: SARS-CoV-2 colonizes ACE2-expressing maternal and fetal cells in the placenta. Infection in pregnant women correlates with alteration of placental RAS. As RAS regulates blood pressure, SARS-CoV-2 infection may thus increase adverse hemodynamic outcomes, such as pre-eclampsia in pregnant women. FUNDING: NIH/NICHD grants R01 HD091218 and 3R01HD091218-04S1 (RADx-UP Supplement).

Universal Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-COV-2) Testing Uptake in the Labor and Delivery Unit: Implications for Health Equity.

OBJECTIVE: To understand severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing uptake in the labor and delivery unit and rationales for declining testing, and to institute a process to increase equitable testing uptake. METHODS: We conducted a quality-improvement initiative from May 28-June 25, 2020, during the first 4 weeks of universal SARS-CoV-2 testing in the Barnes-Jewish Hospital labor and delivery unit. All consecutive patients presenting for delivery without coronavirus disease 2019 (COVID-19) symptoms were offered testing over four 1-week phases. Phase I documented the rate of testing uptake. Phase II recorded patients' reasons for declining testing. Phase III used phase II findings to create and implement shared decision-making tools. Phase IV offered each patient who declined nasopharyngeal testing an oropharyngeal alternative. The primary outcome was rate of SARS-CoV-2 testing uptake by phase. RESULTS: Of 270 patients, 223 (83%) accepted testing and 47 (17%) declined. Maternal age and mode of delivery were similar between groups, whereas testing uptake was higher among nulliparous, White, Hispanic, or privately insured patients. There was a significant increase in the primary outcome of SARS-CoV-2 testing across phases I-IV, from 68% to 76% to 94% to 95%, respectively (Somers' D 0.45; 95% CI of association 0.30-0.59). The most commonly cited reason for declining testing was concern regarding testing discomfort. In subgroup analyses by race and insurance type, there was a significant increase in testing uptake across phases I-IV for Black patients (56%, 54%, 91%, 92%; Somers' D 0.36; 95% CI of association 0.28-0.64), White patients (76%, 93%, 96%, 100%; Somers' D 0.59; 95% CI of association 0.38-0.8), those with Medicaid insurance (60%, 64%, 88%, 92%; 95%; Somers' D 0.39; CI of association 0.22 to 0.56), and those with private insurance (77%, 96%, 97%, 100%; Somers' D 0.63; 95% CI of association 0.40-0.86). CONCLUSION: Universal SARS-CoV-2 testing uptake significantly increased through a rapid-cycle improvement initiative. Aligning hospital policy with patient-centered approaches led to nearly universally acceptable testing.

Pregnancy as a risk factor for severe coronavirus disease 2019 using standardized clinical criteria.

BACKGROUND: As of November 18, 2020, more than 11 million people have been infected with coronavirus disease 2019 and almost 250,000 people have died from the disease in the United States, less than 1 year since its discovery. Although literature is beginning to emerge on pregnancy as a risk factor for severe coronavirus disease 2019, these studies are heterogeneous and use primary outcomes such as intensive care unit admission or hospitalization as surrogate markers that may subject analyses to misclassification bias in pregnant patients. OBJECTIVE: This study aimed to determine the risk of severe coronavirus disease 2019 among pregnant women with symptomatic coronavirus disease 2019 compared with nonpregnant women using nonadmission-based, standardized clinical criteria for severe disease. STUDY DESIGN: This is a retrospective cohort study of women aged 13 to 45 years and diagnosed as having symptomatic coronavirus disease 2019 between May 28, 2020, and July 22, 2020. The primary outcome was severe coronavirus disease 2019 as defined by 2 sets of nonadmission-based, clinical criteria: the World Health Organization Ordinal Scale for Clinical Improvement and the Novel Coronavirus Pneumonia Emergency Response Epidemiology Team. Adjusted risk ratios were estimated using multivariable logistic regression analyses. RESULTS: Of 262 women aged 13 to 45 years with symptomatic coronavirus disease 2019, 22 (8.4%) were pregnant and 240 (91.6%) were nonpregnant. After adjusting for covariates potentially associated with the primary outcome, symptomatic pregnant women were at a significantly increased risk of severe coronavirus disease 2019 compared with nonpregnant women using both the World Health Organization Ordinal Scale for Clinical Improvement (adjusted relative risk, 3.59; 95% confidence interval, 1.49-7.01) and Novel Coronavirus Pneumonia Emergency Response Epidemiology Team (adjusted relative risk, 5.65; 95% confidence interval, 1.36-17.31) criteria. CONCLUSION: Pregnancy significantly increases the risk of severe coronavirus disease 2019 as defined by nonadmission-based, clinical criteria.