National surveillance data analysis of COVID-19 vaccine uptake in England by women of reproductive age.

Women of reproductive age are a group of particular concern with regards to vaccine uptake, related to their unique considerations of menstruation, fertility, and pregnancy. To obtain vaccine uptake data specific to this group, we obtained vaccine surveillance data from the Office for National Statistics, linked with COVID-19 vaccination status from the National Immunisation Management Service, England, from 8 Dec 2020 to 15 Feb 2021; data from 13,128,525 such women at population-level, were clustered by age (18-29, 30-39, and 40-49 years), self-defined ethnicity (19 UK government categories), and index of multiple deprivation (IMD, geographically-defined IMD quintiles). Here we show that among women of reproductive age, older age, White ethnicity and being in the least-deprived index of multiple deprivation are each independently associated with higher vaccine uptake, for first and second doses; however, ethnicity exerts the strongest influence (and IMD the weakest). These findings should inform future vaccination public messaging and policy.

COVID-19 vaccination in pregnancy.

Despite a recent endorsement from official and professional bodies unequivocally recommending COVID-19 vaccination, vaccine hesitancy among pregnant people remains high. The accumulated evidence demonstrates that pregnant people are a special risk group for COVID-19, with an increased risk of intensive care unit admission, extracorporeal membranous oxygenation requirement, preterm birth, and perinatal death. These risks are further increased with some variants of concern, and vaccination of pregnant people reduces the COVID-19-related increase in maternal or fetal morbidity. Data from more than 180,000 vaccinated persons show that immunization against COVID-19 with an mRNA vaccine is safe for pregnant people. Many observational studies comparing perinatal outcomes between vaccinated and unvaccinated pregnant people have had reassuring findings and did not demonstrate harmful effects on pregnancy or the newborn. Immunization with mRNA vaccines does not increase the risk of miscarriage, preterm delivery, low birthweight, maternal or neonatal intensive care unit admission, fetal death, fetal abnormality, or pulmonary embolism. Moreover, observational data corroborate the findings of randomized trials that mRNA vaccination is highly effective at preventing severe SARS-CoV-2 infection in pregnant people, emphasizing that the potential maternal and fetal benefits of vaccination greatly outweigh the potential risks of vaccination. Ensuring pregnant people have unrestricted access to COVID-19 vaccination should be a priority in every country worldwide.

Nasopharyngeal SARS-CoV-2 load and perinatal outcomes after maternal infection diagnosed close to delivery.

BACKGROUND: The occurrence of COVID-19 during the pregnancy can cause several negative maternal and neonatal outcomes. Nasopharyngeal viral load is associated with inflammatory markers and might influence the disease severity in non-pregnant patients, but there are no data about the relationship between viral load and perinatal outcomes in pregnant patients. OBJECTIVE: To investigate the hypothesis that nasopharyngeal SARS-CoV-2 load (estimated with real-time polymerase chain reaction delta cycle (ΔCt), measured in hospital clinical laboratories) is associated with perinatal outcomes, when COVID-19 is diagnosed in the third trimester of pregnancy. STUDY DESIGN: International, retrospective, observational, multi-center, cohort study enrolling 390 women (393 neonates, three pairs of twins), analyzed with multivariate generalized linear models with skewed distributions (gamma) and identity link. The analyses were conducted for the whole population and then followed by a subgroup analysis according to the clinical severity of maternal COVID-19. RESULTS: The estimated viral load in maternal nasopharynx is not significantly associated with gestational age at birth (adjusted B: -0.008 (95%CI: -0.04; 0.02); p = 0.889), birth weight (adjusted B: 4.29 (95%CI: -25; 35); p = 0.889), weight Z-score (adjusted B: -0.01 (95%CI: -0.03; 1); p = 0.336), 5' Apgar scores (adjusted B: -0. -9.8e-4 (95%CI: -0.01; 0.01); p = 0.889), prematurity (adjusted OR: -0.97 (95%CI: 0.93; 1.03); p = 0.766) and the small for gestational age status (adjusted OR: 1.03 (95%CI: 0.99; 1.07); p = 0.351). Similar results were obtained in subgroup analyses according to COVID-19 clinical severity. CONCLUSIONS: The estimated maternal nasopharyngeal viral load in pregnant women affected by COVID-19 during the third trimester is not associated with main perinatal outcomes.

Viral pulmonary infection in pregnancy - Including COVID-19, SARS, influenza A, and varicella.

The COVID-19 pandemic has been at the forefront of medicine over the last few years. Pregnant women are often exposed to infectious agents that can be harmful not only to the mother but also to the foetus. Moreover, changes during pregnancy means that pregnant women have increased vulnerability to viral infections, especially pulmonary infections. Epidemiological studies have shown a link between maternal viral infections and miscarriage, preterm birth as well as congenital defects. With potential poor outcomes for both women and their newborns, having a good understanding of the presentation and management of these viral pulmonary infections is essential. The increased risk of adverse outcomes has been highlighted during the COVID-19, SARS and H1N1 influenza pandemics.

A case for vaccinating adolescent girls for protection against COVID-19 during pregnancy and childbirth in resource-limited settings

The coronavirus disease 2019 (COVID-19) pandemic has had severe implications worldwide, including increased adverse maternal and neonatal health outcomes. Vaccination is one way of protecting against these adverse health outcomes. However, in some low-resource settings, vaccine inequity has led to poor uptake of COVID-19 vaccination. There are very high rates of adolescent pregnancy in low-resource settings, which are likely to become even higher as we begin to see the full effects of COVID-19 lockdown measures, including school closures. Although the benefits of COVID-19 vaccination in adolescents are debated, we propose that adolescent girls should be prioritised in COVID vaccination roll out in low-resource settings. This is to provide protection from severe COVID-19 disease in pregnancy, preventing adverse maternal and neonatal health outcomes.

Preparing for Disease X: Ensuring Vaccine Equity for Pregnant Women in Future Pandemics.

Disease X represents a yet unknown human pathogen which has potential to cause a serious international epidemic or pandemic. The COVID-19 pandemic has illustrated that despite being at increased risk of severe disease compared with the general population, pregnant women were left behind in the development and implementation of vaccination, resulting in conflicting communications and changing guidance about vaccine receipt in pregnancy. Based on the COVID-19 experience, the COVAX Maternal Immunization Working Group have identified three key factors and five broad focus topics for consideration when proactively planning for a disease X pandemic, including 10 criteria for evaluating pandemic vaccines for potential use in pregnant women. Prior to any disease X pandemic, collaboration and coordination are needed to close the pregnancy data gap which is currently a barrier to gender equity in health innovation, which will aid in allowing timely access to life-saving interventions including vaccines for pregnant women and their infants.

Systematic review and meta-analysis of the effectiveness and perinatal outcomes of COVID-19 vaccination in pregnancy.

Safety and effectiveness of COVID-19 vaccines during pregnancy is a particular concern affecting vaccination uptake by this vulnerable group. Here we evaluated evidence from 23 studies including 117,552 COVID-19 vaccinated pregnant people, almost exclusively with mRNA vaccines. We show that the effectiveness of mRNA vaccination against RT-PCR confirmed SARS-CoV-2 infection 7 days after second dose was 89·5% (95% CI 69·0-96·4%, 18,828 vaccinated pregnant people, I2 = 73·9%). The risk of stillbirth was significantly lower in the vaccinated cohort by 15% (pooled OR 0·85; 95% CI 0·73-0·99, 66,067 vaccinated vs. 424,624 unvaccinated, I2 = 93·9%). There was no evidence of a higher risk of adverse outcomes including miscarriage, earlier gestation at birth, placental abruption, pulmonary embolism, postpartum haemorrhage, maternal death, intensive care unit admission, lower birthweight Z-score, or neonatal intensive care unit admission (p > 0.05 for all). COVID-19 mRNA vaccination in pregnancy appears to be safe and is associated with a reduction in stillbirth.

Systematic review and critical evaluation of quality of clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy.

OBJECTIVE: To systematically identify and critically assess the quality of clinical practice guidelines for the management of SARS-CoV-2 infection in pregnancy. DATA SOURCES: Medline, Scopus, and ISI Web of Science databases were searched until February 15, 2022. STUDY ELIGIBILITY CRITERIA: Inclusion criteria were clinical practice guidelines on the management of SARS-CoV-2 infection in pregnancy. The risk of bias and quality assessments of the included clinical practice guidelines were performed using the Appraisal of Guidelines for REsearch and Evaluation II tool, which is considered the gold standard for quality assessment of clinical practice guidelines. To define a clinical practice guideline as of good quality, we adopted the cutoff score proposed by Amer et al: if the overall clinical practice guideline score was >60%, it was recommended. METHODS: The following clinical points related to the management of pregnant women with SARS-CoV-2 infection were addressed: criteria for maternal hospitalization, recommendations for follow-up fetal growth scan, specific recommendations against invasive procedures, management of labor, timing of delivery, postpartum care, and vaccination strategy. RESULTS: A total of 28 clinical practice guidelines were included. All recommended hospitalization only for severe disease; 46.1% (6/13) suggested a fetal growth scan after SARS-CoV-2 infection, whereas 23.1% (3/13) did not support this practice. Thromboprophylaxis with low-molecular-weight heparin was recommended in symptomatic women by 77.1% (7/9) of the clinical practice guidelines. None of the guidelines recommended administering corticosteroids only for the presence of SARS-CoV-2 infection in preterm gestation, unless specific obstetrical indication exists. Elective induction of labor from 39 weeks of gestation was suggested by 18.1% (2/11) of the clinical practice guidelines included in the present review, whereas 45.4% (5/11) did not recommend elective induction unless other obstetrical indications coexisted. There were 27% (3/11) of clinical practice guidelines that suggested shortening of the second stage of labor, and active pushing was supported by 18.1% (2/11). There was general agreement among the clinical practice guidelines in not recommending cesarean delivery only for the presence of maternal infection and in recommending vaccine boosters at least 6 months after the primary series of vaccination. The Appraisal of Guidelines for REsearch and Evaluation II standardized domain scores for the first overall assessment of clinical practice guidelines had a mean of 50% (standard deviation±21.82%), and 9 clinical practice guidelines scored >60%. CONCLUSION: A significant heterogeneity was found in some of the main aspects of the management of SARS-CoV-2 infection in pregnancy, as reported by the published clinical practice guidelines.

The effect of the delta SARS-CoV-2 variant on maternal infection and pregnancy.

A greater proportion of pregnant women with COVID-19 have mild disease compared with their non-pregnant counterparts. Paradoxically, however, they are at higher risk of developing severe disease, requiring respiratory support and admission to intensive care. The delta SARS-Cov-2 variant is associated with increased risk of hospitalization and morbidity in unvaccinated pregnant populations. However, it is not known whether the worse pregnancy outcomes associated with the delta variant are due to a direct effect of the virus on the pregnancy, or whether this effect is mediated through more severe maternal infection. Here, we synthesize studies of COVID-19 pregnancies, focusing on the different routes of SARS-CoV-2 infection of lung and placenta, and the mechanisms of syncytial formation for each SARS-CoV-2 variant. To delineate COVID-19 complications in pregnant women, future studies should explore whether the delta variant causes greater placental infection compared to other variants and contributes to increased syncytial formation.

SARS-CoV-2 positivity in offspring and timing of mother-to-child transmission: living systematic review and meta-analysis.

OBJECTIVES: To assess the rates of SARS-CoV-2 positivity in babies born to mothers with SARS-CoV-2 infection, the timing of mother-to-child transmission and perinatal outcomes, and factors associated with SARS-CoV-2 status in offspring. DESIGN: Living systematic review and meta-analysis. DATA SOURCES: Major databases between 1 December 2019 and 3 August 2021. STUDY SELECTION: Cohort studies of pregnant and recently pregnant women (including after abortion or miscarriage) who sought hospital care for any reason and had a diagnosis of SARS-CoV-2 infection, and also provided data on offspring SARS-CoV-2 status and risk factors for positivity. Case series and case reports were also included to assess the timing and likelihood of mother-to-child transmission in SARS-CoV-2 positive babies. DATA EXTRACTION: Two reviewers independently extracted data and assessed study quality. A random effects model was used to synthesise data for rates, with associations reported using odds ratios and 95% confidence intervals. Narrative syntheses were performed when meta-analysis was inappropriate. The World Health Organization classification was used to categorise the timing of mother-to-child transmission (in utero, intrapartum, early postnatal). RESULTS: 472 studies (206 cohort studies, 266 case series and case reports; 28 952 mothers, 18 237 babies) were included. Overall, 1.8% (95% confidence interval 1.2% to 2.5%; 140 studies) of the 14 271 babies born to mothers with SARS-CoV-2 infection tested positive for the virus with reverse transcriptase polymerase chain reaction (RT-PCR). Of the 592 SARS-CoV-2 positive babies with data on the timing of exposure and type and timing of tests, 14 had confirmed mother-to-child transmission: seven in utero (448 assessed), two intrapartum (18 assessed), and five during the early postnatal period (70 assessed). Of the 800 SARS-CoV-2 positive babies with outcome data, 20 were stillbirths, 23 were neonatal deaths, and eight were early pregnancy losses; 749 babies were alive at the end of follow-up. Severe maternal covid-19 (odds ratio 2.4, 95% confidence interval 1.3 to 4.4), maternal death (14.1, 4.1 to 48.0), maternal admission to an intensive care unit (3.5, 1.7 to 6.9), and maternal postnatal infection (5.0, 1.2 to 20.1) were associated with SARS-CoV-2 positivity in offspring. Positivity rates using RT-PCR varied between regions, ranging from 0.1% (95% confidence interval 0.0% to 0.3%) in studies from North America to 5.7% (3.2% to 8.7%) in studies from Latin America and the Caribbean. CONCLUSION: SARS-CoV-2 positivity rates were found to be low in babies born to mothers with SARS-CoV-2 infection. Evidence suggests confirmed vertical transmission of SARS-CoV-2, although this is likely to be rare. Severity of maternal covid-19 appears to be associated with SARS-CoV-2 positivity in offspring. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020178076. READERS' NOTE: This article is a living systematic review that will be updated to reflect emerging evidence. Updates may occur for up to two years from the date of original publication.

Maternal vaccination: a review of current evidence and recommendations.

Maternal vaccination is an effective means of protecting pregnant women, their fetuses, and infants from vaccine-preventable infections. Despite the availability of sufficient safety data to support the use of vaccines during pregnancy, maternal immunization remains an underutilized method of disease prevention, often because of concerns from both healthcare providers and pregnant women about vaccine safety. Such concerns have been reflected in the low uptake of the COVID-19 vaccine among pregnant women seen in many parts of the world. Here, we present an update of the current recommendations for the use of vaccines during pregnancy, including the evidence supporting the use of novel vaccine platforms. We also provide an overview of the data supporting the use of COVID-19 vaccines in pregnancy and an update of the status of vaccines that are currently under development for use in pregnant women.

Placental histopathology after SARS-CoV-2 infection in pregnancy: a systematic review and meta-analysis.

OBJECTIVE: This study aimed to report the spectrum of placental pathology findings in pregnancies complicated by SARS-CoV-2 infection. DATA SOURCES: MEDLINE, Embase, Google Scholar, and the Web of Science databases were searched up to August 11, 2021. STUDY ELIGIBILITY CRITERIA: Histopathologic anomalies included maternal vascular malperfusion, fetal vascular malperfusion, acute inflammatory pathology, chronic inflammatory pathology, increased perivillous fibrin, and intervillous thrombosis. Moreover, subanalyses of symptomatic women only and high-risk pregnancies were performed. METHODS: Histopathologic analysis of the placenta included gross examination, histopathology on hematoxylin and eosin, immunohistochemistry, fluorescence in situ hybridization, quantitative reverse transcription-polymerase chain reaction on placental tissue, and transmission electron microscope. Random-effect meta-analyses were used to analyze the data. RESULTS: A total of 56 studies (1008 pregnancies) were included. Maternal vascular malperfusion was reported in 30.7% of placentas (95% confidence interval, 20.3-42.1), whereas fetal vascular malperfusion was observed in 27.08 % of cases (95% confidence interval, 19.2-35.6). Acute and chronic inflammatory pathologies were reported in 22.68% (95% confidence interval, 16.9-29.0) and 25.65% (95% confidence interval, 18.4-33.6) of cases, respectively. Increased perivillous fibrin was observed in 32.7% (95% confidence interval, 24.1-42.0) of placentas undergoing histopathologic analysis, whereas intervillous thrombosis was observed in 14.6% of cases (95% confidence interval, 9.7-20.2). Other placental findings, including a basal plate with attached myometrial fibers, microscopic accretism, villous edema, increased circulating nucleated red blood cells, or membranes with hemorrhage, were reported in 37.5% of cases (95% confidence interval, 28.0-47.5), whereas only 17.5% of cases (95% confidence interval, 10.9-25.2) did not present any abnormal histologic findings. The subanalyses according to maternal symptoms owing to SARS-CoV-2 infection or the presence of a high-risk pregnancy showed a similar distribution of the different histopathologic anomalies to that reported in the main analysis. Moreover, the risk of placental histopathologic anomalies was higher when considering only case-control studies comparing women with SARS-CoV-2 infection with healthy controls. CONCLUSION: In pregnant women with SARS-CoV-2 infection, a significant proportion of placentas showed histopathologic findings, suggesting placental hypoperfusion and inflammation. Future multicenter prospective blinded studies are needed to correlate these placental lesions with pregnancy outcomes.

Global research priorities for COVID-19 in maternal, reproductive and child health: Results of an international survey.

BACKGROUND: The World Health Organization's "Coordinated Global Research Roadmap: 2019 Novel Coronavirus" outlined the need for research that focuses on the impact of COVID-19 on pregnant women and children. More than one year after the first reported case significant knowledge gaps remain, highlighting the need for a coordinated approach. To address this need, the Maternal, Newborn and Child Health Working Group (MNCH WG) of the COVID-19 Clinical Research Coalition conducted an international survey to identify global research priorities for COVID-19 in maternal, reproductive and child health. METHOD: This project was undertaken using a modified Delphi method. An electronic questionnaire was disseminated to clinicians and researchers in three different languages (English, French and Spanish) via MNCH WG affiliated networks. Respondents were asked to select the five most urgent research priorities among a list of 17 identified by the MNCH WG. Analysis of questionnaire data was undertaken to identify key similarities and differences among respondents according to questionnaire language, location and specialty. Following elimination of the seven lowest ranking priorities, the questionnaire was recirculated to the original pool of respondents. Thematic analysis of final questionnaire data was undertaken by the MNCH WG from which four priority research themes emerged. RESULTS: Questionnaire 1 was completed by 225 respondents from 29 countries. Questionnaire 2 was returned by 49 respondents. The four priority research themes which emerged from the analysis were 1) access to healthcare during the COVID-19 pandemic, 2) the direct and 3) indirect effects of COVID-19 on pregnant and breastfeeding women and children and 4) the transmission of COVID-19 and protection from infection. CONCLUSION: The results of these questionnaires indicated a high level of concordance among continents and specialties regarding priority research themes. This prioritized list of research uncertainties, developed to specifically highlight the most urgent clinical needs as perceived by healthcare professionals and researchers, could help funding organizations and researchers to answer the most pressing questions for clinicians and public health professionals during the pandemic. It is hoped that these identified priority research themes can help focus the discussion regarding the allocation of limited resources to enhance COVID-19 research in MNCH globally.