Findings from the ECHO Cohorts Regarding the Effects of the COVID-19 Pandemic

Background: Studies suggest perinatal infection with SARSCoV- 2 can induce adverse birth outcomes, but studies published to date have substantial limitations. Most have identified cases based upon their presentation for clinical care, and very few have examined pandemic-related stress which may also impact adverse birth outcomes. Objective(s): To evaluate the relationships between SARSCoV- 2 infection in pregnancy and pandemic-related stress with birth outcomes. Study Design: We conducted an observational study of 211 mother-newborn dyads in three urban cohorts participating in the Environmental Influences on Child Health Outcomes (ECHO) Program. Serology for SARS-CoV-2 was assessed in a convenience sample of prenatal maternal, cord serum or dried blood spots from births occurring between January 2020-September 2021. Specimens were assessed for IgG, IgM, and IgA antibodies to nucleocapsid, S1 spike, S2 spike, and receptor-binding domain. A Pandemic-related Traumatic Stress (PTS) scale was based on the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition Acute Stress Disorder criteria. Result(s): 36% were positive for at least one antibody type, chiefly IgG. Self-report of infection was not significantly correlated with combined serology. There were no differences in gestational age (GA), birth weight, preterm birth (PTB), or low birth weight (LBW) among seropositive mothers. However, IgM seropositive mothers had children with lower BW (434g, 95% CI: 116- 752), BW Z score-for-GA (0.73 SD, 95% CI 0.10-1.36) and were more likely to deliver preterm (OR 8.75, 95% CI 1.22-62.4). Associations with LBW sustained in sensitivity analyses limited to pre-vaccine samples, and PTS symptoms were not associated with birth outcomes. The addition of PTS did not substantially change associations with BW, although associations with PTB attenuated to near-significance. Conclusion(s): We identified decreased birth weight and increased prematurity in mothers IgM seropositive to SARS-CoV-2, independent of PTS. Though there are limits to interpretation, the data support efforts to prevent SARS-CoV-2 infections in pregnancy.

Covid-19: Is the placenta a safe space

Problem: Several large studies have demonstrated that COVID-19 pregnant individuals are at a significant risk for severe disease and adverse pregnancy outcomes. The mechanisms underlying these phenomena remain to be elucidated and are the focus of our project. Although fetal and placental infection is rare, placental abnormalities and adverse pregnancy outcomes associated with placental dysfunction in COVID-19 cases have been widely reported. In particular, placental thrombosis and lesions consistent with maternal vascular malperfusion (MVM) of the placenta are common in individuals with COVID-19. Since thrombotic complications have been associated with COVID-19, it is not surprising that pregnant individuals with COVID- 19 are at risk for placental thrombosis. Method of Study: Placentas were evaluated histologically. Extracellular vesicles were isolated by serial centrifugation. Result(s): Adverse pregnancy outcomes associated with these placental lesions, including hypertensive disorders of pregnancy (gestational hypertension and preeclampsia), small for gestational age (SGA, birthweight < 10th percentile for gestational age), and preterm birth (PTB, < 37 weeks) are significantly increased among pregnant individuals with COVID-19. Placental infection with SARSCoV- 2 is uncommon, but multiple inflammatory and metabolic factors are likely to affect the placenta, including circulating extracellular vesicles (EVs) derived from various organs that have been associated with COVID-19 pathology and disease severity.We have analyzed over 500 placentas from COVID-19 pregnancies and found marked changes in placental morphology, characterized by abnormal maternal and fetal vessels, intervillous thrombi, and fibrin deposition, even in the face of mild or asymptomatic disease. We detected increased levels of small EVs in maternal serum from COVID-19 cases compared to controls and increased levels of mitochondrial DNA in EVs from COVID-19 cases. In in vitro experiments, we found increased oxidative stress in uterine endothelial cells and primary trophoblasts. Syncytialization of trophoblast cells following exposure to EVs from pregnant COVID-19 patients was markedly reduced. RNAseq of trophoblast cells exposed to EVs from pregnant COVID-19 patients revealed disruption of multiple pathways related to mitochondria function, oxidative stress, coagulation defects, and inflammation. Timing of infection during pregnancy (first, second, and third trimester) altered EV size distribution, cargo content, and functional consequences of trophoblast EV exposure. Conclusion(s): Our studies show that COVID-19 infection during pregnancy has profound effects on placenta morphology and function. It remains to be determined what the long-term consequences are on the offspring.

Obesity and risk of severe COVID-19.

Obesity represents a higher risk of severe COVID-19 infection, which may lead to the requirement of a mechanical ventilation in intensive care units and premature death. The underlying mechanisms are multiple: alteration of the respiratory performance, presence of comorbidities such as diabetes, hypertension or obstructive sleep apnea, finally inadequate and excessive immunological responses, possibly aggravated by ectopic intrathoracic fat depots. Thus, COVID-19 may challenge the so-called <<obesity paradox>> commonly reported by intensivists in patients with acute respiratory distress syndrome. These findings require reinforced preventive and curative measures among obese patients to limit the risk of progression towards an unfavorable outcome in case of COVID-19.Copyright © 2020 Editions Medecine et Hygiene. All rights reserved.

Pregnancy Outcomes in Women with Sickle Cell Disease in Ireland: A Retrospective Review

Background: Sickle cell disease (SCD) is one of the most common single gene disorders worldwide and is characterised by significant morbidity and early mortality.[1] Pregnancy in SCD is associated with an increased risk of maternal and foetal complications.[2,3] The 2011 RCOG and the 2021 BSH guidelines[5,6] on the management of pregnancy in SCD have provided the basis for best practice care in the UK over the past decade and is the guidance which we follow in Ireland. To date, there is no published data on outcomes for pregnant women with SCD in Ireland. The number of Irish patients with SCD has risen over the past 20 years. Without a national database, the exact prevalence is not known but currently there are at least 600 adults and children with SCD in Ireland, whose population is just over 5 million.[4] Aims: Our study assesses outcomes of pregnant patients with SCD from 2015 to 2022. Our aims were to: * Assess adherence to current guidelines * Assess pregnancy outcomes and maternal complications * Assess transfusion rates amongst our patient cohort. Method(s): This is a retrospective cohort study. We do not have a directly matched cohort, but have compared our findings to published data on Irish pregnancy outcomes from the Irish Maternity Indicator System National Report and have correlated our findings with studies of women with SCD who were managed in UK centres.[8,9,10] Results: We reviewed outcomes of 29 pregnancies in 19 women over a 7-year period. The median age was 29 (range 20-41) and the predominant maternal sickle genotype was HbSS (65.5%). Before conception, 55.2% of cases had pre-existing complications of SCD, including acute chest syndrome (ACS), pulmonary hypertension (PHTN) and prior stroke. In accordance with current guidelines, 100% of women (n=29) were prescribed folic acid, penicillin, and aspirin prophylaxis. 51.7% (n=15) of women had documented maternal complications during pregnancy, including ACS (34%), vaso-occlusive crisis (34%), gestational diabetes (10%), VTE (3%) and UTI (3%). Two women (7%) developed Covid-19 pneumonitis despite vaccination. There was one case of maternal bacteraemia (3%). 65.5% of cases (n=19) required blood transfusion during pregnancy. One woman was already on a blood transfusion programme for disease modification prior to pregnancy. In 6 cases (20.6%), a transfusion programme was commenced during pregnancy due to prior pregnancy complications or intrauterine growth restriction. During pregnancy, 27.6% (n=8) of women required emergency red cell exchange for ACS. Prior studies have suggested that between 30% and 70% of pregnant women with SCD require at least one blood transfusion during pregnancy.[8,9,10] By comparison, only 2.6% of the Irish general obstetric population required transfusion during pregnancy.[7] 20.6% (n=6) of births were preterm at <37 weeks' gestation. There was one live preterm birth (3%) at <34 weeks and one intrauterine death (3%) at 23 weeks' gestation. Similar to UK data[9], 31% of women required critical care stay (n=9) during pregnancy, in comparison with 1.44% nationwide in 2020.[7] Conclusion(s): It is well established that pregnancy in SCD is high risk, and despite adherence to current guidelines, we have shown very high rates of critical care admission, significant transfusion requirement and hospital admissions. Our findings are comparable to published UK outcomes and they further support the need for a comprehensive specialist care setting for this patient cohort.

COVID-19 Infection and Vaccination in Pregnancy: What Do We Know Now?

SARS-CoV-2 infection during pregnancy has significant implications for both mothers and their offspring. Pregnant individuals are more likely to progress to severe or critical COVID-19 than nonpregnant reproductiveaged women. Similarly, COVID-19 is associated with a number of pregnancy complications including preterm birth, hypertensive disorders of pregnancy, and cesarean delivery. These adverse outcomes and the morbidity for pregnant people with COVID-19 are closely linked to the severity of COVID-19, and the variant of SARS-CoV-2. Recent data demonstrate that the worst maternal and fetal outcomes were present during the time period of the Delta variant of SARS-CoV-2. Specifically, there was an increase in stillbirth observed in association mostly with the Delta variant due to placental damage, and a greater risk of intensive care unit admission when compared to time periods when other non-Delta strains were predominant. Like other populations, pregnant individuals with other comorbidities such as obesity and chronic hypertension are at increased risk of more severe disease. Early in the pandemic, pregnant patients were much less likely than the general population to be vaccinated, due to a lack of data for vaccine efficacy and safety in pregnancy. As reassuring data have emerged, the vaccination rate of the pregnant population has increased, resulting in decreased disease severity and improved maternal outcomes. Vaccination also has beneficial implications for early neonatal health. The long-term implications of SARSCoV- 2 infection during pregnancy for both mothers and their children remain largely unknown and are a subject of ongoing investigation.

The Impact of Prenatal Maternal Mental Health during the COVID-19 Pandemic on Birth Outcomes: A Study within CONCEPTION Cohort

Background: External natural events, such as hurricanes, floods, and the COVID-19 pandemic can contribute to increased populational stress, especially for pregnant persons. Exposure to crises can produce short- and longterm health effects on pregnant persons and their offspring. There has been much interest in the association between maternal depression, anxiety, and stress during pregnancy and perinatal outcomes such as preterm birth (PTB) and low birth weight (LBW), before and since the COVID-19 pandemic, however results are controversial. Objective(s): Assess the association between prenatal mental health during the COVID-19 pandemic and preterm birth (delivery <37 weeks gestation) and low birthweight (<2,500 grams). Method(s): Pregnant individuals, >18 years, were recruited in Canada and provided data through a web-based questionnaire. We analyzed data on persons recruited between 06/2020-08/2021 who completed questionnaires while pregnant and two months post-partum. Data on maternal sociodemographics, comorbidities, medication use, mental health (Edinburgh Postnatal Depression Scale, General Anxiety Disorder-7, stress), pandemic hardship (CONCEPTION - Assessment of Stress from COVID-19), and on gestational age at delivery and birth weight, were selfreported. Crude and adjusted relative risks (aRR) with 95% confidence interval (95%CI) were calculated to quantify the association between PTB/LBW and maternal mental health. Result(s): A total of 1,265 and 1,233 participants were included in the analyses of PTB and LBW, respectively. No associations between PTB and prenatal mental health (depression [aRR 1.01, 95%CI 0.91-1.11], anxiety [aRR 1.04, 95%CI 0.93-1.17], stress [aRR 0.88, 95%CI 0.71-1.10], nor hardship [aRR 1.00, 95%CI 0.96-1.04]) after adjusting for potential confounders. The risk of PTB was increased with nonwhite ethnicity/race (aRR 3.85, 95%CI 1.35-11.00), consistently with the literature. Similar findings were observed for LBW (depression [aRR 1.03, 95%CI 0.96- 1.13], anxiety [aRR 1.05, 95%CI 0.95-1.17], COVID stress [aRR 0.92, 95%CI 0.77-1.09], or overall hardship [aRR 0.97, 95%CI 0.94-1.01]). Conclusion(s): No association was found between prenatal mental health nor hardship during the COVID-19 pandemic and the risk of PTB or LBW. However, it is imperative to continue the follow-up of mothers and their offspring to detect long-term health problems early.

Maternal and neonatal outcomes of Covid infections

SARS-CoV-2 was first detected in December 2019 and rapidly spread to become a pandemic. The disease associated with this infection (COVID-19) disproportionally affect pregnant people and their offspring, making them a high-risk group for morbidity and mortality. Infection with SARS-CoV-2 in pregnancy is associated with increased risk of progression to severe/critical disease and maternal death. It is also associated with adverse pregnancy outcomes including hypertensive disorders and prematurity. While vaccination is one of the most effective approaches to stem the COVID-19 pandemic, pregnant people were originally excluded from all randomized vaccine trials. Following studies examining the effects of COVID vaccine in pregnancy have focused on three general areas: maternal and fetal antibody production, short-term fetal safety, and overall pregnancy outcomes. In this presentation, we will summarize the COVID-19 disease phenotype in pregnancy, describe the association between COVID-19 and adverse pregnancy outcomes, and describe the safety and efficacy of COVID-19 therapeutics and vaccines in pregnancy.

Maternal-fetal complications in pandemic infection with SARS-CoV 2 virus

Introduction: The pandemic caused by the SARS-CoV2 virus is a challenge for global health systems and generates problems both in socio-economic and individual levels. Objectives: The aim of the study was the general presentation of viral pathogenesis, its transmissibility and maternal-fetal complications that occur following SARS-CoV2 virus infection that have been identified in the literature and its prevention. Results: This paper is a systematic review that includes a summary of the literature using the PubMed database with a selection of studies from January 2020 to July 2022. Many studies have reported a slightly increased severity of COVID-19 among pregnant women compared to non-pregnant women due to complications during pregnancy that resulted in miscarriages, premature births or preeclampsia. Conclusion: Therefore, further investigations are needed to elucidate how COVID-19 affects pregnant women and newborns as well as the long-term impact of SARS-CoV2 infection on women who have given birth, regardless of immunological status at birth.

Pandemic stress induces systemic immune changes and placental inflammation independently of SARS-CoV-2 infection in pregnancies

Problem: Environmental stress during pregnancy has known impacts on both maternal and fetal health. In terms of theCOVID-19 pandemic, the majority of published work has focused on the impact of the infection itself, without considering the potential immune impact of pandemic related-stress.We, therefore, assessed the impact of pandemic stress, independently of SARS-CoV-2 infection, on the circulating and placental immune profiles of pregnant individuals. Method(s): Placentas from 239 patients were collected at the Sainte- Justine Hospital, Montreal, Canada. Of these, 199 patients delivered during the pandemic and were exposed to pandemic stress with (+: 79) or without (-: 120) SARS-CoV-2 infection, the latter exposed to pandemic stress only. Pre-pandemic historic controls (uncomplicated pregnancies, Ctrl: 40), were also included. Placental biopsies were collected to assess cytokine levels by ELISAs and histopathological lesions. A sub-study with 35 pre-pandemic pregnancies (unexposed) and 20 who delivered during the pandemic (exposed) was also conducted. The latter (exposed/unexposed) were all uncomplicated pregnancies. We collected maternal blood prior to delivery for immunophenotyping, and plasma/peripheral blood mononuclear cells (PBMCs) were isolated. Inflammatory mediators in the plasma were quantified by ELISAs. Co-culture assays with PBMCs and human umbilical vein endothelial cells (HUVECs) were performed to assess endothelial activation. Demographical/obstetrical data were obtained through chart review. Result(s): SARS-CoV-2+ patients were multiethnic (63.4%), had higher pre-pregnancyBMI (28.9 vs. 24.8 inCtrl, P<.05), and elevated preterm birth rate (16.5% vs. 5.8% in SARS-CoV-2-, P < .05 and 0.0% in Ctrl, P < .01). In the placentas, we observed an increase in the levels of IL- 1Ra (P < .05) and CRP (P < .05) in both SARS-CoV-2 groups, while IL-6 (P = .0790) and MCP-1 (P < .001) were elevated solely in SARS-CoV- 2-. These changes were predominant in placentas with inflammatory lesions on histopathological analysis. Moreover, we observed elevated CD45+ cells (P < .001) in the placentas from both SARS-CoV-2 groups versus Ctrl. Considering that the differences we observed were important in the SARS-CoV-2- group, we performed a study solely on uncomplicated pregnancies, either exposed or unexposed to pandemic stress. At the systemic level, we observed a decrease in the percentage of Th2 cells (P < .001), leading to a pro-inflammatory Th1/Th2 imbalance in exposed individuals. Decreased Treg (P < .05) and Th17 (P < .05) versus unexposed was also observed. Surprisingly, decreased levels of circulating IL-6 (P < .05), MCP-1 (P < .01), and CRP (P<.05) were seen in exposed versus unexposed individuals. Finally,we observed increased secretion of ICAM, a marker of endothelial activation, solely in endothelial cells co-cultured with PBMCs from exposed individuals. Conclusion(s): Overall, placental inflammatory profiles differed between pregnant individuals exposed to pandemic stress with or without SARS-CoV-2 infection. Moreover, we observed that the pandemic stress exposed group presented a systemic pro-inflammatory bias. This highlights the need to understand the differences between the effects of pandemic-related stress and the added burden of SARS-CoV-2 infection itself on maternal and fetal health. Our work also supports an association between an increased risk of hypertension/ preeclampsia and SARS-CoV-2 infection that might be driven in part by pandemic-related stress.

COVID-19 Infection and Medicines in Pregnancy in Canada

Background: Although over 100 million pregnant women worldwide are at risk of infection with SARS-CoV-2, little data exists on the impact of COVID-19 and related treatments on maternal/neonatal health. Objective(s): (1) To quantify the prevalence of medication use in pregnancy to treat COVID-19, and (2) To quantify and compare the risk of adverse pregnancy/neonatal outcomes in those with and without COVID-19. Method(s): In the Canadian Mother-Child population-based cohort (CAMCCO), two sub-cohorts were identified using prospective data collection of medical services, prescription drugs, hospitalization archives data, and COVID-19 surveillance testing program (02/28/2020- 2021). The first cohort included all pregnant women during the study period regardless of pregnancy status (delivery, induced/planned or spontaneous abortion);this cohort was further stratified on COVID-19 status. The second cohort included all nonpregnant women (aged 15-45) with a positive COVID-19 test. COVID-19 in pregnant or nonpregnant women was assessed using COVID-19 test results or ICD-10CM code U07.1 from hospital data. COVID-19 severity was categorized based on hospital admission. Women were considered exposed to COVID-19 medications if they filled at least one prescription for a medicine included in the WHO list in the 30 days pre- or 30 days post-COVID-19 positive test/diagnosis. Considering potential confounders, association between COVID-19 during pregnancy, treated vs not, and perinatal outcomes were quantified using log-binomial regression models. Result(s): 150,345 pregnant women (3,464 (2.3%) had COVID-19), and 112,073 nonpregnant women with COVID-19 diagnoses were included. Pregnant women with COVID-19 were more likely to have severe infections compared to nonpregnant women with COVID-19 (11.4% vs 1.6%, p<0.001). The most frequent medications used in pregnancy to treat COVID-19 were antibacterials (13.96%), psychoanaleptics (7.35%), and medicines for obstructive airway disease (3.20%). In pregnancy COVID-19 was associated with spontaneous abortions (adjRR 1.76, 95%CI 1.37, 2.25), gestational diabetes (adjRR 1.52, 95%CI 1.18, 1.97), prematurity (adjRR 1.30, 95%CI 1.01, 1.67), NICU admissions (adjRR 1.32, 95%CI 1.10, 1.59);COVID-19 severity was increasing these risks but exposures to COVID-19 medications reduced all risks. Conclusion(s): COVID-19 severity was higher in pregnancy. Antibacterials, psychoanaleptics, and medicines for obstructive airway disease were the most used overall. COVID-19 was associated with adverse outcomes for mothers and newborns.

The Impact of The Neonatology Improving Projects on Neonatal Services In Bisha City During Covid 19 Pandemic

Introduction: It is thought of as a necessary service to provide high-quality care during pregnancy, labour, and the postpartum period. The fields of obstetrics/midwifery and neonatology, which are generally referred to as perinatology, have reduced maternal and newborn mortality and morbidity globally, but the COVID-19 pandemic brought on by the SARS-CoV-2-related COVID-19 virus posed a threat to the security of healthcare. Material(s) and Method(s): A prospective comparative study was conducted in a tertiary care hospital, Bisha city. I want to compare the outcome for 2 years (July 2020-June 2022) after shifting to the new unit with previous 2 years before shifting (July 2018-June 2020) in different aspect: The days on the mechanical ventilation, The IVH rate, The Mortality rate. In this study, I want to compare neonatal services outcomes (for preterm babies less than 37 weeks gestational age) after developing the infrastructure, manpower, Supplies and Policies after the shifting to the new department. Result(s): This is a prospective comparative study conducted in the department of neonatology, in a tertiary care hospital, Bisha city. Mean gestational age in before shifting to new unit, after shifting were 31, 33.34 respectively. Average weight were 1496, 1565 in before shifting to new unit, after shifting respectively. In our study, Average days on the mechanical ventilation were 14.78 days in before shifting to new unit group. Average days on the mechanical ventilation were 4.33 days in after shifting to new unit group. Conclusion(s): The provision of high quality and evidence-based perinatal care must remain a priority, even in the face of a pandemic. Restructuring in health care facility with New advance mechanical ventilators supporting Volume-targeted ventilation, 9 single rooms isolation for septic babies, T-piece resuscitator (in all OR suits, Delivery suits and ER), Total parental nutrition and also the all NICU policies updated especially for Caffeine citrate and fluconazole administration to preterm babies according to the AAP guidelines. Also all the department stuff completed the NRP and STABLE provider course as mandatory requirement to work in the NICU department. IVH rate, mortality rate was drastically reduced after shifting to the new unit than before shifting to new unit. Hence hospital restructuring in neonatology plays a crucial role to reduce mortality rate.Copyright © 2021 Muslim OT et al.

Current situation and prospect of teleophthalmology.

With the development of technology, doctors can diagnose and treat many diseases through telemedicine. At present, teleophthalmology is mainly used in screening and diagnosing some ocular diseases, monitoring chronic ocular diseases, as well as teleconsultation. With the increasing demand and application of teleophthalmology, some problems will gradually become prominent, such as insufficient equipment and staff, medical risks, patient acceptance and satisfaction, network security, privacy, and covering of medical insurance. The global pandemic of COViD-19 has unexpectedly brought telemedicine to the forefront of ophthalmic services, and may continue to change the way of ophthalmic diagnosis and treatment. With the development of artificial intelligence technology, the expansion of 5G communication network coverage, the standardized training of primary medical staff, and the introduction of relevant laws and regulations, teleophthalmology will become more improved, universal, and widely applied, so as to provide patients with sustainable medical services of higher quality.Copyright © 2021, Peking Union Medical College Hospital. All rights reserved.

Analysis of Cardiovascular Complications during Delivery Admissions Associated with COVID-19

BACKGROUND: Persons with Coronavirus Disease 2019 (COVID-19) infection have an increased risk of pregnancy-related complications. However, data on acute cardiovascular complications during delivery admissions remain limited. OBJECTIVE(S): To determine whether birthing individuals with COVID-19 have an increased risk of acute peripartum cardiovascular complications during their delivery admission. METHOD(S): This population-based retrospective cohort study used the National Inpatient Sample (2020) by utilizing ICD-10 codes to identify delivery admissions with a diagnosis of COVID-19. A multivariable logistic regression model was developed to report an adjusted odds ratio for the association between COVID-19 and acute peripartum cardiovascular complications. RESULT(S): A total of 3,458,691 weighted delivery admissions were identified, of which 1.3% were among persons with COVID-19 (n=46,375). Persons with COVID-19 were younger (median 28 vs. 29 years, p<0.01) and had a higher prevalence of gestational diabetes mellitus (GDM), preterm births and Cesarean delivery (p<0.01). After adjustment for age, race/ethnicity, comorbidities, insurance, and income, COVID-19 remained an independent predictor of peripartum cardiovascular complications including preeclampsia (aOR 1.33 [1.29-1.37]), peripartum cardiomyopathy (aOR 2.09 [1.54-2,84]), acute coronary syndrome (ACS) (aOR 12.94 [8.85-18.90]), and cardiac arrhythmias (aOR 1.55 [1.45-1.67]) compared with no COVID-19. Likewise, the risk of in-hospital mortality, AKI, stroke, pulmonary edema, and VTE was higher with COVID-19. For resource utilization, cost of hospitalization ($5,374 vs. $4,837, p<0.01) was higher for deliveries among persons with COVID-19. CONCLUSION(S): Persons with COVID-19 had a higher risk of preeclampsia, peripartum cardiomyopathy, ACS, arrhythmias, in-hospital mortality, pulmonary edema, AKI, stroke, and VTE during delivery hospitalizations. This was associated with an increased cost of hospitalization. Keywords: COVID-19, Pregnancy, GDM, PCOS, Preeclampsia, CVD, Cardiovascular Disease Abbreviations: COVID-19: Coronavirus disease-2019, GDM: Gestational Diabetes Mellitus, PCOS: Polycystic Ovary Syndrome, National Inpatient Sample: NIS, AHRQ: Agency for Healthcare Research and Quality, HCUP: the Healthcare Cost and Utilization Project Funding and Conflicts of Interest Dr. Michos reports Advisory Board participation for Amgen, AstraZeneca, Amarin, Bayer, Boehringer Ingelheim, Esperion, Novartis, Novo Nordisk, and Pfizer. The remaining authors have nothing to disclose.Copyright © 2023

Evolution in Infectious Causes of Death in Liveborn Children in a Major Tertiary Children's Hospital: A Retrospective Autopsy Review of over 1200 Cases

Background: Infections have historically been a leading cause of death, particularly in children. Medical advances, including vaccines and antimicrobials, have significantly decreased infection-related deaths, but infections remain a cause of pediatric mortality, especially in premature infants. The types of infections implicated in childhood deaths have changed with these advances, for example, meningitis and meningococcal infections were leading causes in 1981 but not in the later period. The incidence and etiologies of infection- related deaths may be altered by major events that modify not only medical practices but also societal attitudes and activities. Examples of such events include the HIV/AIDS epidemic that began in the early 1980s and the more recent COVID-19 pandemic. In order to investigate changes in infection-related pediatric deaths over time, we analyzed and compared autopsy cases performed during 5-year span prior to both the HIV/AIDS epidemic and the COVID-19 pandemic in which infections contributed to death. Method(s): Review of all autopsy cases performed at our institution between 1/1/1975-1/1/1980 and between 1/1/2015-1/1/2020 was performed to identify cases in which infection directly contributed to death, comprising 1262 cases. Only liveborn children were considered, and neonatal sepsis from amniotic sac infections was excluded. Comparison of decedent characteristics and infectious etiologies between the two time periods was performed, identifying age, race, sex, gestational age (for decedents less than 3 months of age), and etiologic class of agent (bacterial, viral, fungal or parasitic). TORCH infections and vaccine-preventable illnesses were specifically assessed. Proportions were compared using 1 (assessing TORCH, vaccine-preventable, and prematurity deaths)- or 2-tailed (all others) z-tests, with significance calculated at the < 0.05 level. Result(s): In the 1970s cohort, 300 infectious autopsy cases were identified in liveborn children;73 were identified in the 2010s. Compared to the 2010s cohort, the 1970s decedents were more likely to be white (85% v 53%, p=0.012), comprise children aged 1-5 and 13+ (22% v 6.8% [p=0.003] and 16.4% v 8.3% [p=0.036]), and were less likely to be premature (66.7% v 80.4%, p=0.039). Vaccine-preventable illnesses (for example: measles) accounted for 36 deaths in the 1970s cohort but only 2 in the 2010s cohort (p=0.009). Thirteen children died of TORCH infections (CMV, toxoplasmosis and HSV) versus 5 in the 2010s (CMV and HSV), which did not reach statistical significance. Conclusion(s): Pediatric mortality secondary to infections has decreased significantly compared to fifty years ago, especially in younger children and in relation to vaccine-preventable infections such as meningococcal disease. This drop is largely attributed to medical advances, including vaccines and antimicrobial medications. Additional contributing factors could include practices adopted post-HIV/AIDS, especially in the community. Further exploration of how such changes in medical and social practice impacted mortality and comparing them to changes occurring in the intra/post-COVID-19 era, is helpful. Yet, with the increased survival of premature infants, they remain at risk of devastating consequences from infections.

Integrating Bioethics and Neonatal Palliative Care in a Pandemic: The Scope of Advocacy and Online Collaboration for Exceptional Life-Sustaining Medical and Surgical Interventions in a Regional Neonatal Intensive Care Unit

Purpose of Study: The regional NICU is an essential healthcare resource for families of newborns with serious life-threatening illnesses. Mechanical ventilation, cardiovascular therapies, therapeutic hypothermia, and neonatal surgeries are common life-sustaining interventions. Our NICU serves an underprivileged population in a resource poor environment and several ethical questions frequently emerge when facing extremes of innovative therapies. The pandemic and rapidly changing institutional protocols accentuated challenges faced by frontline NICU teams caring for newborns at risk for devastating illnesses and death. Concurrently, evolving paradigms in neonatal ethics required urgent and high quality palliative care in a background of racial and socioeconomic inequities, restrictive visitation policies, and limited healthcare resources. The purpose of this study was to ensure that neonates and their families receive ethically sound care, timely referrals for innovative therapies, and specialized palliative care in the strained and uncertain environment of the COVID-19 pandemic. Methods Used: The key steps consisted of structured and impromptu discussion forums for specialized palliative care and medical ethics, perinatal case conferences and pediatrics grand rounds on virtual platforms, educational webinars for interdisciplinary teams, and improved electronic communication. Online collaboration and innovative combinations of in-person and virtual meetings were utilized for urgently Incorporating clinical updates. Summary of Results: 1. A neonate with severe HIE and postnatally diagnosed congenital diaphragmatic hernia required emergent ECMO center referral. NICU providers utilized a structured bioethics and palliative care framework for providing family support and discussing the prognostication challenges of acute illnesses. 2. Many important bioethical questions emerged while caring for infants with life-threatening chromosomal abnormalities. Ethical tension was addressed by teaching tools, quality of life and pediatrics ethics conversations, mitigation of moral distress, contemporary clinical and surgical experience, community engagement, and family perspectives. 3. Ethical conflicts are central in the decision to resuscitate neonates born between 22 and 23 weeks of gestation. To provide urgent prenatal consultations and attend high risk deliveries, we collaborated across geographically distant healthcare systems, unified management strategies and analyzed outcomes data. 4. NEC in several extremely preterm babies had devastating outcomes and the team respected each family's voice with compassionate, shared decision-making for both curative care surgeries and palliative care. Conclusion(s): The new workflows, telephone and video conferences, and redirection to telehealth based family meetings did not change important outcomes during the pandemic. Advocacy and education for integrating bioethics and palliative care were vital facets of neonatal critical care in a resource poor and ever-changing pandemic environment.

Post-partum Maternal Vascular Function Is Reduced in Preeclampsia and Preterm Births: A Pilot Study

Introduction: Women with a history of preeclampsia (PreE) or preterm (PreT) birth are at elevated risk of future hypertension, ischemic heart disease, and stroke. Mechanisms for this increased risk are unknown. Flow-mediated dilation of the brachial artery (FMD) is an established surrogate for cardiovascular risk.Hypothesis: In this pilot study, we hypothesize that maternal vascular dysfunction associated with PreE is reversible, and the extent of recovery is predicated on specific maternal characteristics. Method(s): In this prospective study, subjects were recruited to three groups: PreE with delivery at 27-34 weeks;PreT delivery at 27-34 weeks without preeclampsia;and healthy controls at 39-40 weeks. Vascular function (FMD), nutrition (validated questionnaire), and physical activity (accelerometers) data were collected at 1-2 days post-partum and 3 months. Result(s): Fourteen subjects were enrolled (mean age 32+/-6 years). Systolic blood pressure was higher for PreE subjects (average 131+/-6) compared to controls (109 +/- 9, p=0.004) and PreT (110+/-8, p=0.008) at visit 1. This difference resolved at visit 2. Though non-significant, FMD (mean+/-SE) was higher in controls compared to PreE and PreT groups at visit 1 (7.7%+/-0.8 v. 7.4%+/-0.7 and 6.9%+/-1.0, Figure 1). FMD remains depressed at 3 months, but subject follow-up was impacted by the Covid 19 pandemic. Alternate Healthy Eating Index scores were non-significantly higher in the PreT group than PreE and controls. PreT subjects were less sedentary and more physically active (higher moderate-vigorous physical activity, higher total steps). Conclusion(s): Maternal FMD is reduced immediately post-partum in PreE and PreT births. The PreT group had lower FMD despite better nutrition and physical activity scores. This is a pilot study, and we are not powered for significance. Data from our small cohort support the ability to collect meaningful data in these understudied populations which could inform future studies of long-term cardiovascular risk.

STAYING AFLOAT - COORDINATING A PREGNANCY RANDOMISED CLINICAL TRIAL during A GLOBAL PANDEMIC

Background: The COVID-19 pandemic affected numerous global industry sectors. Impacts on pre-existing randomised clinical trials, however, have largely been unaddressed. The Perth-based Preterm Birth Prevention Study (PTBPS), a trial assessing a new microbial DNA test and treatment regimen for prevention of preterm birth, was plunged into uncertainty two years into recruitment, and had to rapidly adapt to a constantly changing environment to survive. Method(s): Recruitment was moved from patient-facing to telephone and internet. Study information was included in antenatal mailouts in place of antenatal visits. Sample collection predominantly occurred off-site, in many cases from participant's homes. Where necessary, study medications were delivered to participants. Additional funding was sought and additional study sites were added. Result(s): COVID-19 associated restrictions and later, dissemination of COVID-19 into the Western Australian community, badly impacted study recruitment. Financial burden was high;the initial national lockdown alone cost the project $71 590. Two philanthropic donations and a state government grant allowed trial continuation, ensuring a sufficiently powered interim data analysis will occur at the end of 2023. Using a combination of adaptive recruitment methods (e-recruitment and off-site participant consultations), combined with two additional study sites, trial recruitment continued throughout the majority of the pandemic, albeit at a greatly diminished rate. Conclusion(s): The PTBPS was one of many NHMRC-funded clinical trials impacted by the COVID-19 pandemic. Unlike many others, it was fortunate enough to continue operating during times of uncertainty through a combination of philanthropic and state government generosity and protocol changes to match the dynamic clinical environment.

GESTATIONAL CANNABIS USE and MATERNAL DOMESTIC VIOLENCE before and since the COVID-19 PANDEMIC in AN AUSTRALIAN TERTIARY LEVEL ANTENATAL SERVICE

Background: Recent studies describe increasing rates of cannabis use among pregnant women. Gestational cannabis use has been associated with adverse neonatal outcomes and maternal reports of domestic violence. Domestic violence reportedly increased in Australia during the COVID-19 pandemic. We examined trends and outcomes of gestational cannabis use before and during the COVID-19 pandemic and sought associations with domestic violence. Method(s): The study population comprised women who attended the antenatal clinic and childbirth between 1 January 2019 and 31 December 2021 at an Australian tertiary hospital. Maternal socio-demographic, pregnancy progress and neonatal outcomes were recorded from the clinical records. We sought associations between maternal cannabis use and self-reported domestic violence during the study period, and the relationship with pregnancy outcomes. Result(s): Cannabis use was reported by 165/10,263 (1.6%) pregnant women. Cannabis use remained consistent during the study period, but reports of domestic violence increased from 2.9% pre-COVID to 6.7% during the COVID-19 pandemic. During the pandemic, women with gestational cannabis use were more likely to be young (40% <25 years vs. 11.8% .25 years), underweight (3.5% vs. 2.4%) and reported more domestic violence (33.0% vs. 6.3%), compared with non-users. The most common co-consumed substances by cannabis-users were tobacco (63.5%), alcohol (13.9%) and amphetamines (9.6%). Gestational cannabis use was associated with smaller neonates (median birth weight 2900 vs. 3330 g), higher preterm births (33% vs. 8.6%) and increased stillbirths (1.7% vs. 0.4%) Conclusion(s): Although domestic violence increased, gestational cannabis use remained constant during the COVID-19 pandemic and was associated with worse neonatal outcomes.

IMPACT of COVID-19 LOCKDOWN on STILLBIRTHS and PRETERM BIRTHS among WOMEN with TWIN PREGNANCIES in MELBOURNE

Background: Melbourne's 2020 pandemic lockdown was associated with an increase in stillbirths and a reduction in preterm births (PTB) among singleton pregnancies. Twin pregnancies may be particularly susceptible due to higher background risk. We aimed to compare the rates of adverse pregnancy outcomes in twin pregnancies exposed and unexposed to Melbourne's lockdown. Method(s): Multicentre retrospective cohort study of all twin pregnancies > 20 weeks birthing in all 12 public maternity hospitals in Melbourne. Multivariable log-binominal regressions were used to compare outcomes between a pre-pandemic control group ('unexposed') independently with two lockdown-exposed groups: exposure 1 from 22 March 2020 to 21 March 2021 (pre-vaccination era) and exposure 2 from 22 March 2021 to 27 March 2022 (vaccination era). Result(s): We included 2259 pregnancies. There were fewer PTBs < 37 weeks during exposure 1 compared with the pre-pandemic era (63.1% vs. 68.3%;adjusted risk-ratio (aRR) 0.95;95% confidence interval (CI) 0.88-0.98, P = 0.01). This lower rate was most prominent in iatrogenic PTB for suspected fetal compromise (13.4% vs. 20.3%;aRR 0.94 95% CI 0.90-0.99, P = 0.01). There were correspondingly fewer special care nursery admissions during exposure 1 (38.5% vs. 43.5%;aRR 0.91 95% CI 0.87-0.95, P < 0.001), but no changes in stillbirth (1.5% vs. 1.4%;aRR 1.00, 95% CI 0.99-1.01, P = 0.85). Compared with the pre-pandemic period, exposure 2 was associated with a trend to more PTB < 28 weeks and significantly higher neonatal intensive care unit admissions (25.0% vs. 19.6%;aRR 1.06 95% CI 1.03-1.10, P < 0.001). Conclusion(s): Melbourne's first lockdown-exposure period was associated with fewer preterm twin births for suspected fetal compromise, without any increase in stillbirth.

2023 ABSTRACT: COVID-19 INFECTION in PREGNANCY - WHO IS MOST at RISK of ADVERSE OUTCOMES?

Background: COVID-19 infection during pregnancy is associated with increased rates of adverse perinatal outcomes. The mechanism by which this occurs is not understood. We have previously reported increased rates of placental histopathological lesions in these pregnancies. Aim(s): We hypothesise that, 1. trimester of infection, and 2. vaccination status, affects placental histopathology and neonatal outcomes. Method(s): Pregnant women infected with COVID-19 between January 2020 and May 2022 were retrospectively identified from Monash Health records. Maternal and neonatal data were collected alongside placental histopathological changes as categorised by the Amsterdam Criteria. Result(s): 942/21838 women had COVID-19 infection during pregnancy. Placental histopathology was available in 638 cases. Analysis of infection by trimester revealed that earlier infection was associated with increased preterm birth rate (13.5% vs. 10.3% vs. 4.5%, P = 0.0012), reduced birth weight (3108 vs. 3216 vs. 3345 g, P = 0.0061) and increased fetal loss rate (2.7% vs. 1.8% vs. 0%, P = 0.0023, in T1 vs. T2 vs. T3, respectively) (Table 1). Placental weight increased with trimester of infection (416 vs. 469 vs. 487 g, P = 0.0267). There were no differences in histopathological lesions. 300 patients were unvaccinated (>=1 dose) versus 642 double vaccinated (>=2 doses) against COVID-19 (Table 2). Double vaccination resulted in fewer placental histopathological lesions (59.0% vs. 69.9%, P = 0.0089), particularly maternal vascular malperfusion lesions (20.7% vs. 28.2%, P = 0.0127) but no difference in perinatal outcomes. Conclusion(s): COVID-19 infection earlier in pregnancy is associated with poorer perinatal outcomes. Vaccination reduced the rate of placental lesions but did not change adverse neonatal outcomes.