Transaminitis as a predictor of poor clinical outcomes in pregnant patients infected with COVID-19: retrospective case series (preprint)

Objective: The objective of this study is to identify the effects of Coronavirus Disease 2019 (COVID-19) on liver enzymes in pregnant patients and to determine the significance of transaminitis as a predictor of worse clinical outcomes. Design: Case series. Setting: Tertiary care medical center. Population: 31 pregnant patients with a positive COVID-19 polymerase chain reaction (PCR) test and 20 infants who presented during March 25, 2020, to May 26, 2020. Methods: Maternal and neonatal outcomes were compared between patients with transaminitis and without transaminitis using one tailed Mann-Whitney test for nonparametric data and the fisher’s exact test for categorical data. Main outcome measures: Worse maternal outcomes between the groups were defined as need for intubation, oxygen supplementation, intensive care unit (ICU) admission, maternal death, and length of hospital stay. Results: Of the 31 patients with COVID-19, 10/29 (34.5%) were found to have transaminitis. The patients with transaminitis had increased oxygen requirements, increased rate of intubation and ICU admissions. Neonatal outcomes in patients with transaminitis included earlier gestational age at delivery and lower birth weights, but neither were statistically significant. Conclusion: Our study revealed that patients with COVID-19 and concomitant transaminitis had worse clinical outcomes in the mother when compared to those without transaminitis. Further studies should be conducted to explore this link between abnormal liver studies and poor outcomes in pregnant patients diagnosed with COVID-19. Keywords: Coronavirus, COVID-19, transaminitis, pregnancy Tweetable abstract: Pregnant patients with COVID-19 and transaminitis had worse outcomes than ones without transaminitis.

Validating the InterVA-5 cause of death analytical tool: using mortality data from the Comprehensive Health and Epidemiological Surveillance System in Papua New Guinea.

OBJECTIVE: InterVA-5 is a new version of an analytical tool for cause of death (COD) analysis at the population level. This study validates the InterVA-5 against the medical review method, using mortality data in Papua New Guinea (PNG). DESIGN AND SETTING: This study used mortality data collected from January 2018 to December 2020 in eight surveillance sites of the Comprehensive Health and Epidemiological Surveillance System (CHESS), established by the PNG Institute of Medical Research in six major provinces. METHODS: The CHESS demographic team conducted verbal autopsy (VA) interviews with close relatives of the deceased, who died in communities within the catchment areas of CHESS, using the WHO 2016 VA instrument. COD of the deceased was assigned by InterVA-5 tool, and independently certified by the medical team. Consistency, difference and agreement between the InterVA-5 model and medical review were assessed. Sensitivity and positive predictive value (PPV) of the InterVA-5 tool were calculated with reference to the medical review method. RESULTS: Specific COD of 926 deceased people was included in the validation. Agreement between the InterVA-5 tool and medical review was high (kappa test: 0.72; p<0.01). Sensitivity and PPV of the InterVA-5 were 93% and 72% for cardiovascular diseases, 84% and 86% for neoplasms, 65% and 100% for other chronic non-communicable diseases (NCDs), and 78% and 64% for maternal deaths, respectively. For infectious diseases and external CODs, sensitivity and PPV of the InterVA-5 were 94% and 90%, respectively, while the sensitivity and PPV of the medical review method were both 54% for classifying neonatal CODs. CONCLUSION: The InterVA-5 tool works well in the PNG context to assign specific CODs of infectious diseases, cardiovascular diseases, neoplasms and injuries. Further improvements with respect to chronic NCDs, maternal deaths and neonatal deaths are needed.

Maternal death due to COVID-19: a scoping review / Morte materna em decorrência da COVID-19: revisão de escopo / Muerte materna por COVID-19: revisión de alcance

OBJETIVO: mapear o cenário da morte materna em decorrência da infecção pelo vírus SARS-CoV-2 em gestantes e puérperas. MÉTODO: revisão de escopo conforme o Instituto Joanna Briggs realizada por meio de uma estratégia de pesquisa na literatura disponível nos bancos de dados SciELO, LILACS, PubMed, CINAHL, Web of Science e PUBCOVID19. A análise do material identificado deu-se por dois revisores independentes. Os dados foram extraídos por meio de um instrumento construído pelos autores, analisados, sumarizados e classificados como categorias conceituais. RESULTADOS: dos 231 estudos encontrados, 66 foram elegíveis e tiveram os resultados sumarizados em quatro categorias conceituais: Desfecho morte materna em decorrência da COVID-19; Desfecho morte materna nas pandemias por Coronavírus; Morte materna por grupo obstétrico; Infecção por SARS-CoV-2, morte materna, recursos de saúde e determinantes sociais. CONCLUSÃO: a atenção vigilante, o diagnóstico precoce e o acesso em tempo oportuno foram eventos necessários para evitar a morte materna em 2020.

OBJECTIVE: to map the scenario of maternal death due to infection by the SARS-CoV-2 virus in pregnant and puerperal women. METHOD: A scoping review according to the Joanna Briggs Institute and conducted by means of a research strategy in the literature available in the SciELO, LILACS, PubMed, CINAHL, Web of Science and PUBCOVID19 databases. The analysis of the material identified was carried out by two independent reviewers. The data were extracted using an instrument prepared by the authors, analyzed, summarized and classified as conceptual categories. RESULTS: of the 231 studies found, 66 were eligible and had their results summarized in four conceptual categories: Outcome of maternal death due to COVID-19; Outcome of maternal death in the coronavirus pandemics; Maternal death by obstetric group; SARS-CoV-2 infection, maternal death, health resources and social determinants. CONCLUSION: vigilant care, early diagnosis and timely access were necessary events to prevent maternal death in 2020.

OBJETIVO: mapear las muertes maternas por infección por el virus SARS-CoV-2 en gestantes y puérperas. MÉTODO: revisión de alcance según el Instituto Joanna Briggs realizada mediante una búsqueda en la literatura disponible en las bases de datos SciELO, LILACS, PubMed, CINAHL, Web of Science y PUBCOVID19. El análisis del material identificado fue realizado por dos revisores independientes. Los datos fueron extraídos utilizando un instrumento elaborado por los autores, analizados, resumidos y clasificados en categorías conceptuales. RESULTADOS: de los 231 estudios encontrados, 66 fueron elegibles y los resultados se resumieron en cuatro categorías conceptuales: Desenlace muerte materna por COVID-19; Desenlace muerte materna en pandemias de coronavirus; Muerte materna por grupo obstétrico; Infección por SARS-CoV-2, muerte materna, recursos sanitarios y determinantes sociales. CONCLUSIÓN: la atención de calidad, el diagnóstico precoz y el acceso oportuno fueron eventos necesarios para prevenir la muerte materna en 2020.

Health and economic benefits of achieving contraceptive and maternal health targets in Small Island Developing States in the Pacific and Caribbean.

INTRODUCTION: Reducing unmet need for modern contraception and expanding access to quality maternal health (MH) services are priorities for improving women's health and economic empowerment. To support investment decisions, we estimated the additional cost and expected health and economic benefits of achieving the United Nations targets of zero unmet need for modern contraceptive choices and 95% coverage of MH services by 2030 in select Small Island Developing States. METHODS: Five Pacific (Kiribati, Samoa, Solomon Islands, Tonga and Vanuatu) and four Caribbean (Barbados, Guyana, Jamaica and Saint Lucia) countries were considered based on population survey data availability. For each country, the Lives Saved Tool was used to model costs, health outcomes and economic benefits for two scenarios: business-as-usual (BAU) (coverage maintained) and coverage-targets-achieved, which scaled linearly from 2022 (following COVID-19 disruptions) coverage of evidence-based family planning and MH interventions to reach United Nations targets, including modern contraceptive methods and access to complete antenatal, delivery and emergency care. Unintended pregnancies, maternal deaths, stillbirths and newborn deaths averted by the coverage-targets-achieved scenario were converted to workforce, education and social economic benefits; and benefit-cost ratios were calculated. RESULTS: The coverage-targets-achieved scenario required an additional US$12.6M (US$10.8M-US$15.9M) over 2020-2030 for the five Pacific countries (15% more than US$82.4M to maintain BAU). This additional investment was estimated to avert 126 000 (40%) unintended pregnancies, 2200 (28%) stillbirths and 121 (29%) maternal deaths and lead to a 15-fold economic benefit of US$190.6M (US$67.0M-US$304.5M) by 2050. For the four Caribbean countries, an additional US$17.8M (US$15.3M-US$22.4M) was needed to reach the targets (4% more than US$405.4M to maintain BAU). This was estimated to avert 127 000 (23%) unintended pregnancies, 3600 (23%) stillbirths and 221 (25%) maternal deaths and lead to a 24-fold economic benefit of US$426.2M (US$138.6M-US$745.7M) by 2050. CONCLUSION: Achieving full coverage of contraceptive and MH services in the Pacific and Caribbean is likely to have a high return on investment.

Tracking excess of maternal deaths associated with COVID-19 in Brazil: a nationwide analysis.

BACKGROUND: The COVID-19 pandemic brought a new challenge to maternal mortality in Brazil. Throughout 2020, Brazil registered 549 maternal deaths, mainly in second and third-trimester pregnant women. The objective of this study was to estimate the excess maternal deaths in Brazil caused directly and indirectly by Covid-19 in the year 2020. In addition, we sought to identify clinical, social and health care factors associated with the direct maternal deaths caused by Covid-19. METHODS: We performed nationwide analyses based on data from the Mortality Information System (SIM) for general and maternal deaths and the Influenza Epidemiological Surveillance System (SIVEP-Influenza) for estimates of female and maternal deaths due to COVID-19. Two distinct techniques were adopted. First, we describe maternal deaths directly caused by covid-19 and compare them with the historical series of deaths from covid-19 among women of childbearing age (15 to 49 years). Next, we estimated the total excess maternal mortality. Then, we calculated odds ratios for symptoms, comorbidities, social determination proxies and hospital care aspects between COVID-19 maternal deaths and deaths of women of childbearing age who were not pregnant or no maternal deaths. We chose women of childbearing age (15 to 49 years) as a reference because sex and age introduce differentials in the risk of COVID-19 death. RESULTS: Most maternal deaths occurred during pregnancy compared to postpartum deaths month by month in 2020 (µ = 59.8%, SD = 14.3%). The excess maternal mortality in 2020 in Brazil was 1.40 (95% CI 1.35-1.46). Even considering excess mortality due to COVID-19 for the childbearing age female population (MMR 1.14; 95% CI 1.13-1.15), maternal mortality exceeded the expected number. The odds of being a black woman, living in a rural area and being hospitalized outside the residence municipality among maternal deaths were 44, 61 and 28% higher than the control group. Odds of hospitalization (OR 4.37; 95% CI 3.39-5.37), ICU admission (OR 1.73; 95% CI 1.50-1.98) and invasive ventilatory support use (OR 1.64; CI 95% 1.42-1.86) among maternal deaths were higher than in the control group. CONCLUSIONS: There was excess maternal mortality in 2020 in Brazil. Even with adjustment for the expected excess mortality from Covid-19 in women of childbearing age, the number of maternal deaths exceeds expectations, suggesting that there were deaths among pregnant and postpartum women indirectly caused by the pandemic, compromising access to prenatal care., adequate childbirth and puerperium.

Comparison of maternal and neonatal outcomes of COVID-19 before and after SARS-CoV-2 omicron emergence in maternity facilities in Malawi (MATSurvey): data from a national maternal surveillance platform.

BACKGROUND: Outcomes of omicron-associated COVID-19 in pregnancy have not been reported from low-resource settings, and data from sub-Saharan Africa before the emergence of omicron are scarce. Using a national maternal surveillance platform (MATSurvey), we aimed to compare maternal and neonatal outcomes of COVID-19 in Malawi during the omicron wave to the preceding waves of beta and delta. METHODS: All pregnant and recently pregnant patients, up to 42 days following delivery, admitted to 33 health-care facilities throughout Malawi with symptomatic, test-proven COVID-19 during the second (beta [B.1.351]: January to April, 2021), third (delta [B.1.617.2]: June to October, 2021), and fourth (omicron [B.1.1.529]: December 2021 to March, 2022) waves were included, with no age restrictions. Demographic and clinical features, maternal outcomes of interest (severe maternal outcome [a composite of maternal near-miss events and maternal deaths] and maternal death), and neonatal outcomes of interest (stillbirth and death during maternal stay in the health-care facility of enrolment) were compared between the fourth wave and the second and third waves using Fisher's exact test. Adjusted odds ratios (ORs) for maternal outcomes were estimated using mixed-effects logistic regression. FINDINGS: Between Jan 1, 2021, and March 31, 2022, 437 patients admitted to 28 health-care facilities conducting MATSurvey had symptoms of COVID-19. SARS-CoV-2 infection was confirmed in 261 patients; of whom 76 (29%) had a severe maternal outcome and 45 (17%) died. These two outcomes were less common during the fourth wave (omicron dominance) than the second wave (adjusted OR of severe maternal outcome: 3·96 [95% CI 1·22-12·83], p=0·022; adjusted OR of maternal death: 5·65 [1·54-20·69], p=0·0090) and the third wave (adjusted OR: 3·18 [1·03-9·80], p=0·044; adjusted OR: 3·52 [0·98-12·60], p=0·053). Shortness of breath was the only symptom associated with poor maternal outcomes of interest (p<0·0001), and was less frequently reported in the fourth wave (23%) than in the second wave (51%; p=0·0007) or third wave (50%; p=0·0004). The demographic characteristics and medical histories of patients were similar across the three waves. During the second and third waves, 12 (13%) of 92 singleton neonates were stillborn or died during maternal stay in the health-care facility of enrolment, compared with 0 of the 25 born in the fourth wave (p=0·067 vs preceding waves combined). INTERPRETATION: Maternal and neonatal outcomes from COVID-19 were less severe during the fourth wave of the SARS-CoV-2 pandemic in Malawi, during omicron dominance, than during the preceding beta and delta waves. FUNDING: Bill & Melinda Gates Foundation, Wellcome Trust, and the National Institute for Health and Care Research. TRANSLATION: For the Chichewa translation of the abstract see Supplementary Materials section.

Excess maternal mortality in Brazil: Regional inequalities and trajectories during the COVID-19 epidemic.

BACKGROUND: The COVID-19 pandemic has exceeded 6 million known disease-related deaths and there is evidence of an increase in maternal deaths, especially in low- and middle-income countries. We aimed to estimate excess maternal deaths in Brazil and its macroregions as well as their trajectories in the first 15 months of the COVID-19 epidemic. METHODS: This study evaluated maternal deaths from the Mortality Information System of the Ministry of Health, with excess deaths being assessed between March 2020 and May 2021 by quasi-Poisson generalized additive models adjusted for overdispersion. Observed deaths were compared to deaths expected without the pandemic, accompanied by 95% confidence intervals according to region, age group, and trimester of occurrence. Analyses were conducted in R version 3.6.1 and RStudio version 1.2.1335. RESULTS: There were 3,291 notified maternal deaths during the study period, resulting in a 70% excess of deaths regardless of region, while in the North, Northeast, South and Southeast regions, excess deaths occurred regardless of age group. Excess deaths occurred in the March-May 2021 trimester regardless of region and age group. Excess deaths were observed in the Southeast region for the 25-36-year-old age group regardless of the trimester assessed, and in the North, Central-West and South regions, the only period in which excess deaths were not observed was September-November 2020. Excess deaths regardless of trimester were observed in the 37-49-year-old age group in the North region, and the South region displayed explosive behavior from March-May 2021, with a 375% excess of deaths. CONCLUSIONS: Excess maternal deaths, with geographically heterogenous trajectories and consistently high patterns at the time of the epidemic's greatest impact, reflect not only the previous effect of socioeconomic inequalities and of limited access to maternal health services, but most of all the precarious management of Brazil's health crisis.

Impact of SARS-CoV-2 (COVID-19) on pregnancy and newborn outcome (preprint)

Background: The novel coronavirus disease (COVID-19); It was more devastating in people with comorbidities such as advanced age and immunodeficiency. Another group affected by COVID-19 was pregnant women. Immunological changes during pregnancy and conditions such as gestational diabetes and preeclampsia that occur during pregnancy also have effects on the fetus. Objective: We aimed to analyze the effects of PCR-proven COVID-19 infection during pregnancy on fetus and newborn. Study Design: Data from pregnant women with COVID-19 symptoms or a history of contact with people with COVID-19 who were infected with PCR-proven COVID-19 virus between December 2019 and October 2021 were retrospectively analyzed. Clinical and laboratory data of pregnant women were analyzed. Death data associated with -19 were evaluated. Clinical and laboratory findings of newborns related to COVID-19 and mortality data related to COVID-19 were recorded. Results: 327 pregnant women whose births were terminated by continuing their follow-up in our hospital were evaluated. 185 (56.6%) of the pregnant women had at least one COVID-19-related symptom. Thoracic computed tomography of ten cases included COVID-19 findings. Fifty-three (16.2%) pregnant women were over 35 years old. No significant difference was found between pregnancy over 35 years of age and maternal death. The rate of hospitalization in the intensive care unit of mothers with diabetes was statistically higher (p=0.034). The mortality rate was higher in preeclamptic mothers (p=0.029). A total of 34 infants died; 21 died in the intrauterine period and 13 died in the postnatal period. 5 of the neonatal deaths were due to COVID-19. Conclusion: While COVID-19 infection in pregnancy seriously affects mortality and morbidity in pregnant women, it also causes mortality and morbidity on the fetus.

Comparison of Pregnancy and Birth Outcomes Before vs During the COVID-19 Pandemic.

Importance: Little is known about changes in obstetric outcomes during the COVID-19 pandemic. Objective: To assess whether obstetric outcomes and pregnancy-related complications changed during the COVID-19 pandemic. Design, Setting, and Participants: This retrospective cohort study included pregnant patients receiving care at 463 US hospitals whose information appeared in the PINC AI Healthcare Database. The relative differences in birth outcomes, pregnancy-related complications, and length of stay (LOS) during the pandemic period (March 1, 2020, to April 31, 2021) were compared with the prepandemic period (January 1, 2019, to February 28, 2020) using logistic and Poisson models, adjusting for patients' characteristics, and comorbidities and with month and hospital fixed effects. Exposures: COVID-19 pandemic period. Main Outcomes and Measures: The 3 primary outcomes were the relative change in preterm vs term births, mortality outcomes, and mode of delivery. Secondary outcomes included the relative change in pregnancy-related complications and LOS. Results: There were 849 544 and 805 324 pregnant patients in the prepandemic and COVID-19 pandemic periods, respectively, and there were no significant differences in patient characteristics between periods, including age (≥35 years: 153 606 [18.1%] vs 148 274 [18.4%]), race and ethnicity (eg, Hispanic patients: 145 475 [47.1%] vs 143 905 [17.9%]; White patients: 456 014 [53.7%] vs 433 668 [53.9%]), insurance type (Medicaid: 366 233 [43.1%] vs 346 331 [43.0%]), and comorbidities (all standardized mean differences <0.10). There was a 5.2% decrease in live births during the pandemic. Maternal death during delivery hospitalization increased from 5.17 to 8.69 deaths per 100 000 pregnant patients (odds ratio [OR], 1.75; 95% CI, 1.19-2.58). There were minimal changes in mode of delivery (vaginal: OR, 1.01; 95% CI, 0.996-1.02; primary cesarean: OR, 1.02; 95% CI, 1.01-1.04; vaginal birth after cesarean: OR, 0.98; 95% CI, 0.95-1.00; repeated cesarean: OR, 0.96; 95% CI, 0.95-0.97). LOS during delivery hospitalization decreased by 7% (rate ratio, 0.931; 95% CI, 0.928-0.933). Lastly, the adjusted odds of gestational hypertension (OR, 1.08; 95% CI, 1.06-1.11), obstetric hemorrhage (OR, 1.07; 95% CI, 1.04-1.10), preeclampsia (OR, 1.04; 95% CI, 1.02-1.06), and preexisting chronic hypertension (OR, 1.06; 95% CI, 1.03-1.09) increased. No significant changes in preexisting racial and ethnic disparities were observed. Conclusions and Relevance: During the COVID-19 pandemic, there were increased odds of maternal death during delivery hospitalization, cardiovascular disorders, and obstetric hemorrhage. Further efforts are needed to ensure risks potentially associated with the COVID-19 pandemic do not persist beyond the current state of the pandemic.

Clinical and epidemiological aspects of SARS-CoV-2 infection among pregnant and postpartum women in Mozambique: a prospective cohort study.

BACKGROUND: Although there is a significant increase of evidence regarding the prevalence and impact of COVID-19 on maternal and perinatal outcomes, data on the effects of the pandemic on the obstetric population in sub-Saharan African countries are still scarce. Therefore, the study aims were to assess the prevalence and impact of COVID-19 on maternal and neonatal outcomes in the obstetric population at Central Hospital of Maputo (HCM), Mozambique. METHODS: Prospective cohort study conducted at teaching and referral maternity, HCM, from 20 October 2020 to 22 July 2021. We collected maternal and perinatal outcomes up to 6 weeks postpartum of eligible women (pregnant and postpartum women-up to the 14th day postpartum) screened for COVID-19 (individual test for symptomatic participants and pool testing for asymptomatic). The primary outcome was maternal death, Severe Acute Respiratory Syndrome (SARS) and Intensive Care Unit (ICU) admission. We estimated the COVID-19 prevalence and the unadjusted RR (95% CI) for maternal and perinatal outcomes. We used the chi-square or Fisher's exact test to compare categorical variables (two-sided p-value < 0.05 for statistical significance). RESULTS: We included 239 participants. The overall prevalence of COVID-19 was 9.2% (22/239) and in the symptomatic group was 32.4% (11/34). About 50% of the participants with COVID-19 were symptomatic. Moreover, the most frequent symptoms were dyspnoea (33.3%), cough (28.6%), anosmia (23.8%), and fever (19%). Not having a partner, being pregnant, and alcohol consumption were vulnerability factors for SARS-CoV-2 infection. The risk of adverse maternal and neonatal outcomes (abortion, foetal death, preterm birth, Apgar, and NICU admission) was not significantly increased with COVID-19. Moreover, we did not observe a significant difference in the primary outcomes (SARS, ICU admission and maternal death) between COVID-19 positive and COVID-19 negative groups. CONCLUSION: The prevalence of COVID-19 in the obstetric population is higher than in the general population, and fifty percent of pregnant and postpartum women with COVID-19 infection are asymptomatic. Not having a partner and alcohol consumption were factors of greatest vulnerability to SARS-COV-2 infection. Moreover, being pregnant versus postpartum was associated with increased vulnerability to COVID-19. Data suggest that pregnant women with COVID-19 may have a higher frequency of  COVID-19 infection, reinforcing the need for universal testing, adequate follow-up for this population, and increasing COVID-19 therapy facilities in Mozambique. Moreover, provide counselling during Antenatal care for COVID-19 preventive measures. However, more prospective and robust studies are needed to assess these findings.

The COVID-19 pandemic in Brazilian pregnant and postpartum women: results from the REBRACO prospective cohort study.

Brazil presented a very high number of maternal deaths and evident delays in healthcare. We aimed at evaluating the characteristics of SARS-CoV-2 infection and associated outcomes in the obstetric population. We conducted a prospective cohort study in 15 Brazilian centers including symptomatic pregnant or postpartum women with suspected COVID-19 from Feb/2020 to Feb/2021. Women were followed from suspected infection until the end of pregnancy. We analyzed maternal characteristics and pregnancy outcomes associated with confirmed COVID-19 infection and SARS, determining unadjusted risk ratios. In total, 729 symptomatic women with suspected COVID-19 were initially included. Among those investigated for COVID-19, 51.3% (n = 289) were confirmed COVID-19 and 48% (n = 270) were negative. Initially (before May 15th), only 52.9% of the suspected cases were tested and it was the period with the highest proportion of ICU admission and maternal deaths. Non-white ethnicity (RR 1.78 [1.04-3.04]), primary schooling or less (RR 2.16 [1.21-3.87]), being overweight (RR 4.34 [1.04-19.01]) or obese (RR 6.55 [1.57-27.37]), having public prenatal care (RR 2.16 [1.01-4.68]), planned pregnancies (RR 2.09 [1.15-3.78]), onset of infection in postpartum period (RR 6.00 [1.37-26.26]), chronic hypertension (RR 2.15 [1.37-4.10]), pre-existing diabetes (RR 3.20 [1.37-7.46]), asthma (RR 2.22 [1.14-4.34]), and anaemia (RR 3.15 [1.14-8.71]) were associated with higher risk for SARS. The availability of tests and maternal outcomes varied throughout the pandemic period of the study; the beginning was the most challenging period, with worse outcomes. Socially vulnerable, postpartum and previously ill women were more likely to present SARS related to COVID-19.

Maternal Deaths from COVID-19 in Brazil: Increase during the Second Wave of the Pandemic.

OBJECTIVE: To compare death rates by COVID-19 between pregnant or postpartum and nonpregnant women during the first and second waves of the Brazilian pandemic. METHODS: In the present population-based evaluation data from the Sistema de Informação da Vigilância Epidemiológica da Gripe (SIVEP-Gripe, in the Portuguese acronym), we included women with c (ARDS) by COVID-19: 47,768 in 2020 (4,853 obstetric versus 42,915 nonobstetric) and 66,689 in 2021 (5,208 obstetric versus 61,481 nonobstetric) and estimated the frequency of in-hospital death. RESULTS: We identified 377 maternal deaths in 2020 (first wave) and 804 in 2021 (second wave). The death rate increased 2.0-fold for the obstetric (7.7 to 15.4%) and 1.6-fold for the nonobstetric groups (13.9 to 22.9%) from 2020 to 2021 (odds ratio [OR]: 0.52; 95% confidence interval [CI]: 0.47-0.58 in 2020 and OR: 0.61; 95%CI: 0.56-0.66 in 2021; p < 0.05). In women with comorbidities, the death rate increased 1.7-fold (13.3 to 23.3%) and 1.4-fold (22.8 to 31.4%) in the obstetric and nonobstetric groups, respectively (OR: 0.52; 95%CI: 0.44-0.61 in 2020 to OR: 0.66; 95%CI: 0.59-0.73 in 2021; p < 0.05). In women without comorbidities, the mortality rate was higher for nonobstetric (2.4 times; 6.6 to 15.7%) than for obstetric women (1.8 times; 5.5 to 10.1%; OR: 0.81; 95%CI: 0.69-0.95 in 2020 and OR: 0.60; 95%CI: 0.58-0.68 in 2021; p < 0.05). CONCLUSION: There was an increase in maternal deaths from COVID-19 in 2021 compared with 2020, especially in patients with comorbidities. Death rates were even higher in nonpregnant women, with or without comorbidities.

OBJETIVO: Comparar as taxas de mortalidade por COVID-19 entre gestantes ou puérperas e não gestantes durante a primeira e segunda ondas da pandemia brasileira. MéTODOS: Na presente avaliação dos dados do Sistema de Informação da Vigilância Epidemiológica da Gripe (SIVEP-Gripe), incluímos mulheres com síndrome respiratória aguda grave por COVID-19: 47.768 em 2020 (4.853 obstétricas versus 42.915 não obstétricas) e 66.689 em 2021 (5.208 obstétricas versus 61.481 não obstétricas) e estimamos a frequência de óbito intra-hospitalar. RESULTADOS: Identificamos 377 óbitos maternos em 2020 e 804 em 2021. A taxa de mortalidade por COVID-19 aumentou 2,0 vezes no grupo obstétrico (de 7,7 para 15,4%) e 1,6 vezes no grupo não obstétrico (de 13,9 para 22,9%) de 2020 a 2021 (odds ratio [OR]: 0,52; intervalo de confiança [IC] 95%: 0,47­0,58 em 2020 e OR: 0,61; IC95%: 0,56­0,66 em 2021; p < 0,05). Em mulheres com comorbidades, a taxa de óbitos aumentou 1,7 vezes (de 13,3 para 23,3%) e 1,4 vezes (de 22,8 para 31,4%) para os grupos obstétricos e não obstétricos, respectivamente (OR: 0,52; IC95%: 0,44­0,61 em 2020 para OR: 0,66; IC95%: 0,59­0,73 em 2021; p < 0,05). Em mulheres sem comorbidades, a taxa de mortalidade foi maior para as não obstétricas (2,4 vezes; de 6,6% para 15,7%) do que para mulheres obstétricas (1,8 vezes; de 5,5 para 10,1%; OR: 0,81; IC95%: 0,69­0,95 em 2020 e OR: 0,60; IC95%: 0,58­0,68 em 2021; p < 0,05). CONCLUSãO: Houve aumento das mortes maternas por COVID-19 em 2021 em relação a 2020, principalmente naquelas com comorbidades. As taxas de mortalidade foram ainda maiores em mulheres não grávidas, com ou sem comorbidades.

Maternal mortality and its determining factors among hospitalised mothers in Tehran, Iran, 2013-2020.

The maternal mortality ratio (MMR) is a significant indicator of the quality of a health care system. Despite considerable progress in reducing MMR in Iran in the past few years, we still face a long road ahead in eliminating preventable maternal deaths. In the present study, we evaluated all 80 cases of maternal deaths in 20 hospitals under the supervision of Tehran University of Medical Sciences between March 20 2013 and March 19 2020. During this time, these hospitals recorded 335,216 live births, with an MMR of 24 per 100,000 live births. The average age of deceased mothers was 31.9 ± 6.9 years. Direct causes accounted for 48.75% of maternal deaths, with haemorrhage being the most common direct cause of mortality (17.5%). Moreover, cancer (17.5%) and cardiovascular diseases (17.5%) were the most common indirect causes of maternal mortality. Even after accounting for the COVID-19 pandemic's effects, we have noticed an increase in maternal mortality. As a result, implementing a comprehensive approach for high-risk pregnancies is critical.Impact StatementWhat is already known on this subject? Although we have been able to reduce MMR in Iran to a reasonable level, previous measures would not be sufficient to accomplish future goals. Furthermore, we have a long way to go before reaching the ultimate goal of eradicating avoidable maternal deaths by 2030.What do the results of this study add? The causes, determinants and risk factors of maternal mortality were investigated in this study. With this level of detail, we can observe a steadily increase in MMR in recent years, regardless of the COVID-19 pandemic. The majority of pregnancy-related deaths can be avoided.What are the implications of these findings for clinical practice and/or further research? MMR reduction is a measurable goal that can be attained by improving financial resources, implementing safe delivery, team training, preparing multidisciplinary care with integration for high-risk pregnant women, establishing good provider relationships, and communicating with patients and providers for early warning signs and structural changes.

Clinical characteristics and risk factors for maternal deaths due to COVID-19 in Brazil: a nationwide population-based cohort study.

BACKGROUND: Monitoring the characteristics and associated factors for death among pregnant and postpartum women with coronavirus disease 19 (COVID-19) is necessary. We investigated the clinical characteristics and risk factors associated with maternal deaths in a nationwide cohort of Brazil. METHODS: This was a population-based cohort of all pregnant and postpartum women hospitalised with COVID-19 notified to the Sistema de Informação de Vigilância Epidemiológica da Gripe of Brazil (SIVEP-Gripe), from February 2020 to September 2021. The primary outcome was time to in-hospital death, with risk factors analysed with univariable and multivariable Cox proportional hazards regression models. RESULTS: Cumulative observation time was 248 821 person-days from hospital admission to the end of follow-up for 15 105 individuals. There were 1858 deaths (12.3%) for a maternal mortality rate of 7.5 (95% CI 7.1-7.8) per 1000 patients-days. The cumulative mortality increased over time. Black/Brown ethnicity had a higher risk of death than women self-identifying as White. Women in the North, Northeast, Central-West and Southeast regions had higher risk of death than women in the South region. The characteristics independently associated with death were a postpartum status on admission [adjusted hazard ratio, HR 1.4 (95% confidence interval, CI 1.2-1.6)], pre-existing clinical conditions [adjusted HRs 1.2 (95%CI 1.1-1.3) for one and 1.3 (95%CI 1.1-1.5) for two comorbidities], hypoxaemia on admission [adjusted HR 1.2 (95%CI 1.1-1.4)] and requiring non-invasive [adjusted HR 2.6 (95%CI 2.1-3.3)] or invasive ventilatory support [adjusted HR 7.1 (95%CI 5.6-9.2)]. CONCLUSION: In Brazil, the in-hospital maternal mortality rate due to COVID-19 is high and the risk of death increases with the length of hospitalisation. Socio-demographic and biological factors are associated with an increased risk of maternal death. The presence of respiratory signs and symptoms should be considered early markers of disease severity and an adequate management is necessary. Our findings reinforce the need for vaccination of pregnant and postpartum women against COVID-19.

Comorbidity, poverty and social vulnerability as risk factors for mortality in pregnant women with confirmed SARS-CoV-2 infection: analysis of 13 062 positive pregnancies including 176 maternal deaths in Mexico.

OBJECTIVE: Mortality in pregnancy due to coronavirus disease 2019 (COVID-19) is a current health priority in developing countries. Identification of clinical and sociodemographic risk factors related to mortality in pregnant women with COVID-19 could guide public policy and encourage such women to accept vaccination. We aimed to evaluate the association of comorbidities and socioeconomic determinants with COVID-19-related mortality and severe disease in pregnant women in Mexico. METHODS: This is an ongoing nationwide prospective cohort study that includes all pregnant women with a positive reverse-transcription quantitative polymerase chain reaction result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from the Mexican National Registry of Coronavirus. The primary outcome was maternal death due to COVID-19. The association of comorbidities and socioeconomic characteristics with maternal death was explored using a log-binomial regression model adjusted for possible confounders. RESULTS: There were 176 (1.35%) maternal deaths due to COVID-19 among 13 062 consecutive SARS-CoV-2-positive pregnant women. Maternal age, as a continuous (adjusted relative risk (aRR), 1.08 (95% CI, 1.05-1.10)) or categorical variable, was associated with maternal death due to COVID-19; women aged 35-39 years (aRR, 3.16 (95% CI, 2.34-4.26)) or 40 years or older (aRR, 4.07 (95% CI, 2.65-6.25)) had a higher risk for mortality, as compared with those aged < 35 years. Other clinical risk factors associated with maternal mortality were pre-existing diabetes (aRR, 2.66 (95% CI, 1.65-4.27)), chronic hypertension (aRR, 1.75 (95% CI, 1.02-3.00)) and obesity (aRR, 2.15 (95% CI, 1.46-3.17)). Very high social vulnerability (aRR, 1.88 (95% CI, 1.26-2.80)) and high social vulnerability (aRR, 1.49 (95% CI, 1.04-2.13)) were associated with an increased risk of maternal mortality, while very low social vulnerability was associated with a reduced risk (aRR, 0.47 (95% CI, 0.30-0.73)). Being poor or extremely poor were also risk factors for maternal mortality (aRR, 1.53 (95% CI, 1.09-2.15) and aRR, 1.83 (95% CI, 1.32-2.53), respectively). CONCLUSION: This study, which comprises the largest prospective consecutive cohort of pregnant women with COVID-19 to date, has confirmed that advanced maternal age, pre-existing diabetes, chronic hypertension, obesity, high social vulnerability and low socioeconomic status are risk factors for COVID-19-related maternal mortality. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Clinical characteristics of pregnant women infected with Coronavirus Disease 2019 in China: a nationwide case-control study (preprint)

OBJECTIVETo formally compare the clinical course of Coronavirus disease 2019 (COVID-19) in pregnant women with their nonpregnant counterparts. METHODSClinical data of pregnant women with confirmed COVID-19 in the designated hospitals of mainland China were retrieved up to April 12, 2020 through an epidemic reporting system maintained at the National Health Commission of the Peoples Republic China. Each pregnant patient was randomly matched to a nonpregnant woman with confirmed COVID-19 in the same hospital as control, then their clinical courses were formally compared. RESULTS138 pregnant women had been identified as confirmed COVID-19 cases. Among them, 17 severe cases and 1 maternal death were recorded, which was less than their nonpregnant peers (23 severe cases and 3 death). 57.2% had been infected with SARS-CoV-2 during the third trimester, including 13 severe cases and 1 maternal death. 7.3% of pregnant patients had diarrhea and 3.6% had nausea or vomiting, compared with related proportion as 15.2% (OR: 0.38, 95%CI: 0.15, 0.96) and 10.1% (OR: 0.25, 95%CI: 0.07, 0.89) in nonpregnant patients. Pregnant patients infected with SARS-CoV-2 in early pregnancy presented similar laboratory tests with their nonpregnant peers, however, with pregnancy progresses, increased inflammation, coagulation and hepatic injury markers happened more and more frequently (p<0.001) in pregnant patients. CONCLUSIONSBeing pregnant did not represent a risk for severe condition when compared with their nonpregnant peers. Patients infected with SARS-CoV-2 in early pregnancy were even at lower risk of severe illness than those infected in late pregnancy. What are the novel findings of this work?Compared with non-pregnant COVID-19 patients, pregnant patients tend to present less symptom, had unique laboratory findings, and tend to at lower risk of COVID-19-related death. Patients infected with SARS-CoV-2 in the early pregnancy tend to be in the less severe condition of illness than those infected in late pregnancy. What are the clinical implications of this work?Vital comparisons of the clinical course upon COVID-19 between pregnant and nonpregnant women in childbearing age are, unfortunately, lacking. Through formally comparisons between the two groups, the present study provides more reliable evidence towards the management of pregnant women with COVID-19.