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

Clinical manifestations, prevalence, risk factors, outcomes, transmission, diagnosis and treatment of COVID-19 in pregnancy and postpartum: a living systematic review protocol.

INTRODUCTION: Rapid, robust and continually updated evidence synthesis is required to inform management of COVID-19 in pregnant and postpartum women and to keep pace with the emerging evidence during the pandemic. METHODS AND ANALYSIS: We plan to undertake a living systematic review to assess the prevalence, clinical manifestations, risk factors, rates of maternal and perinatal complications, potential for mother-to-child transmission, accuracy of diagnostic tests and effectiveness of treatment for COVID-19 in pregnant and postpartum women (including after miscarriage or abortion). We will search Medline, Embase, WHO COVID-19 database, preprint servers, the China National Knowledge Infrastructure system and Wanfang databases from 1 December 2019. We will supplement our search with studies mapped by Cochrane Fertility and Gynaecology group, Evidence for Policy and Practice Information and Co-ordinating Centre (EPPI-Centre), COVID-19 study repositories, reference lists and social media blogs. The search will be updated every week and not be restricted by language. We will include observational cohort (≥10 participants) and randomised studies reporting on prevalence of COVID-19 in pregnant and postpartum women, the rates of clinical manifestations and outcomes, risk factors in pregnant and postpartum women alone or in comparison with non-pregnant women with COVID-19 or pregnant women without COVID-19 and studies on tests and treatments for COVID-19. We will additionally include case reports and series with evidence on mother-to-child transmission of SARS-CoV-2 in utero, intrapartum or postpartum. We will appraise the quality of the included studies using appropriate tools to assess the risk of bias. At least two independent reviewers will undertake study selection, quality assessment and data extraction every 2 weeks. We will synthesise the findings using quantitative random effects meta-analysis and report OR or proportions with 95% CIs and prediction intervals. Case reports and series will be reported as qualitative narrative synthesis. Heterogeneity will be reported as I2 and τ2 statistics. ETHICS AND DISSEMINATION: Ethical approval is not required as this is a synthesis of primary data. Regular updates of the results will be published on a dedicated website (https://www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and disseminated through publications, social media and webinars. PROSPERO REGISTRATION NUMBER: CRD42020178076

Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis

OBJECTIVE: Clinical trials evaluating pharmacological and non-pharmacological treatment of COVID-19, either excluded pregnant women or included very few women. Unlike the numerous systematic reviews on prevalence, symptoms and adverse outcomes of COVID-19 in pregnancy, there are very few on the effects of treatment on maternal and neonatal outcomes in pregnancy. We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes. DATA SOURCES: We performed a systematic literature search of the following databases: Medline, Embase, Cochrane database, WHO (World Health Organization) COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 1 December 2020. STUDY ELIGIBILITY CRITERIA: Studies were only included if they involved pregnant or postnatal women who were exposed to pregnancy specific interventions like the mode of delivery and type of anaesthesia, pharmacological or non-pharmacological interventions. STUDY APPRAISAL AND SYNTHESIS METHODS: We first screened the titles and abstracts of studies and then assessed the full text of the selected studies in detail for eligibility. Data on study design, population, type of screening for COVID-19, country, hospital, country status (high or low and middle income), treatment given (mode of delivery, type of anaesthesia, type of pharmacological and non-pharmacological treatment was extracted. The pre-defined maternal outcomes we collected were mode of delivery (vaginal or by caesarean section), severe or critical COVID-19 (as defined by the authors), symptomatic COVID-19, maternal death, maternal hospital admission, ICU admission, mechanical ventilation, ECMO and maternal pneumonia. The pre-defined neonatal outcomes we extracted were preterm birth (<37 weeks), stillbirth, neonatal death, NICU admission, neonatal COVID-19 positive, neonatal acidosis (pH<7.0) and Apgar scores (<8 after 5 minutes). Study quality assessment was performed. RESULTS: From a total of 342 potential eligible studies, we included 27 studies in our systematic review, including 4943 pregnant women (appendix 3). Sixteen studies had a retrospective cohort design and 11 a prospective cohort design. There were no randomised controlled trials. There was a significant association between caesarean section and admission to ICU (OR 4.99, 95% CI 1.24 to 20.12; 4 studies, 153 women, I(2)=0%), and diagnosis of maternal COVID-19 pneumonia as defined by study authors (OR 3.09, 95% CI 1.52 to 6.28; 2 studies, 228 women, I(2)=0%). Women who had a preterm birth were more likely to have the baby via caesarean section (OR 3.03, 95% CI 1.71 to 5.36, 12 studies; 314 women, I(2)=0%). For pharmacological and non-pharmacological we provided estimates of the expected rates of outcomes in women exposed to various treatment of COVID-19. Comparative data for pregnant women, in particular for treatments proven to be effective in the general population, however, is lacking to provide clinically meaningful interpretation. CONCLUSIONS: We found associations for pregnancy specific interventions, like mode of delivery and outcomes of the disease, but there were too few data on pharmacological and non-pharmacological treatments in pregnant women with COVID-19. We report the rates of complications found in the literature. We encourage researchers to include pregnant women in their trials and report the data on pregnant women separately