Severe COVID-19 in pregnancy is almost exclusively limited to unvaccinated women - time for policies to change Comment

Non peer reviewe

Perinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years’ active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies

Perinatal outcomes after admission with COVID-19 in pregnancy:a UK national cohort study

There are few population-based studies of sufficient size and follow-up duration to have reliably assessed perinatal outcomes for pregnant women hospitalised with SARS-CoV-2 infection. The United Kingdom Obstetric Surveillance System (UKOSS) covers all 194 consultant-led UK maternity units and included all pregnant women admitted to hospital with an ongoing SARS-CoV-2 infection. Here we show that in this large national cohort comprising two years’ active surveillance over four SARS-CoV-2 variant periods and with near complete follow-up of pregnancy outcomes for 16,627 included women, severe perinatal outcomes were more common in women with moderate to severe COVID-19, during the delta dominant period and among unvaccinated women. We provide strong evidence to recommend continuous surveillance of pregnancy outcomes in future pandemics and to continue to recommend SARS-CoV-2 vaccination in pregnancy to protect both mothers and babies

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review.

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19

Evolution of National Guidelines on Medicines Used to Treat COVID-19 in Pregnancy in 2020-2022: A Scoping Review

The lack of inclusion of pregnant women in clinical trials evaluating the effectiveness of medicines to treat COVID-19 has made it difficult to establish evidence-based treatment guidelines for pregnant women. Our aim was to provide a review of the evolution and updates of the national guidelines on medicines used in pregnant women with COVID-19 published by the obstetrician and gynecologists' societies in thirteen countries in 2020-2022. Based on the results of the RECOVERY (Randomized Evaluation of COVID-19 Therapy) trial, the national societies successively recommended against prescribing hydroxychloroquine, lopinavir-ritonavir and azithromycin. Guidelines for remdesivir differed completely between countries, from compassionate or conditional use to recommendation against. Nirmatrelvir-ritonavir was authorized in Australia and the UK only in research settings and was no longer recommended in the UK at the end of 2022. After initial reluctance to use corticosteroids, the results of the RECOVERY trial have enabled the recommendation of dexamethasone in case of severe COVID-19 since mid-2020. Some societies recommended prescribing tocilizumab to pregnant patients with hypoxia and systemic inflammation from June 2021. Anti-SARS-CoV-2 monoclonal antibodies were authorized at the end of 2021 with conditional use in some countries, and then no longer recommended in Belgium and the USA at the end of 2022. The gradual convergence of the recommendations, although delayed compared to the general population, highlights the importance of the inclusion of pregnant women in clinical trials and of international collaboration to improve the pharmacological treatment of pregnant women with COVID-19

Variations across Europe in hospitalization and management of pregnant women with SARS-CoV-2 during the initial phase of the pandemic : Multi-national population-based cohort study using the International Network of Obstetric Survey Systems (INOSS)

Funding Information: The national studies reported the following funding sources: The BOSS project was funded by the Belgian Federal Public Service of Health. The NOSS collaboration was supported by the Nordic Federation of Societies of Obstetrics and Gynecology (grant no. 6505, 2020). NOSS‐Denmark was supported by grants from The Region of Southern Denmark and Region Zealand's shared fund for joint health research projects (Reg. no. A767), and EasyTrial provided the data collection software. NOSS‐Finland received grants from the Finnish Medical Society, and from Helsinki University. UKOSS received funding from the National Institute for Health Research HS&DR Programme (11/46/12). The national studies in Italy and the Netherlands did not have specific funding. The multi‐national study received partial funding support from the European Medicines Agency (EMA) under the Framework service contract nr EMA/2018/28/PE. The content of this paper expresses the opinions of the authors and may not be understood or quoted as being made on behalf of or reflecting the position of the EMA or any of its committees or working parties. The research leading to these results was conducted as part of the activities of the EU PE&PV (Pharmacoepidemiology and Pharmacovigilance) Research Network, which is a public academic partnership coordinated by Utrecht University, the Netherlands. The CONSIGN project was scientifically coordinated by the University Medical Center, Utrecht. Funding Information: OB declares support from the European Medicines agency (EMA). HE declares grants from the Nordic Federation of Societies of Obstetrics and Gynecology (NFOG) and Norwegian Research Council (grant no 320181). AA declares a grant from the Region of Southern Denmark and Region Zealand's shared fund for joint health research projects. OA declares grants from the Finnish Medical Association and NFOG. MK declares grants from the National Institute for Health and Care Research, Medical Research Council, Healthcare Quality Improvement Partnership and Wellbeing of Women during the course of the study. MS leads a department that conducts studies on COVID‐19 vaccines for the European Medicines Agency, Pfizer, AstraZeneca and Janssen. All support was according to the ENCePP code of conduct. None of the other authors (NV, RR, SD, EJ, EO, MAS, TS, RV, AV, KB) has anything to disclose. Publisher Copyright: © 2023 The Authors. Acta Obstetricia et Gynecologica Scandinavica published by John Wiley & Sons Ltd on behalf of Nordic Federation of Societies of Obstetrics and Gynecology (NFOG).Introduction: The majority of data on COVID-19 in pregnancy are not from sound population-based active surveillance systems. Material and methods: We conducted a multi-national study of population-based national or regional prospective cohorts using standardized definitions within the International Network of Obstetric Survey systems (INOSS). From a source population of women giving birth between March 1 and August 31, 2020, we included pregnant women admitted to hospital with a positive SARS-CoV-2 PCR test ≤7 days prior to or during admission and up to 2 days after birth. The admissions were further categorized as COVID-19-related or non-COVID-19-related. The primary outcome of interest was incidence of COVID-19-related hospital admission. Secondary outcomes included severe maternal disease (ICU admission and mechanical ventilation) and COVID-19-directed medical treatment. Results: In a source population of 816 628 maternities, a total of 2338 pregnant women were admitted with SARS-CoV-2; among them 940 (40%) were COVID-19-related admissions. The pooled incidence estimate for COVID-19-related admission was 0.59 (95% confidence interval 0.27–1.02) per 1000 maternities, with notable heterogeneity across countries (I2 = 97.3%, P = 0.00). In the COVID-19 admission group, between 8% and 17% of the women were admitted to intensive care, and 5%–13% needed mechanical ventilation. Thromboprophylaxis was the most frequent treatment given during COVID-19-related admission (range 14%–55%). Among 908 infants born to women in the COVID-19-related admission group, 5 (0.6%) stillbirths were reported. Conclusions: During the initial months of the pandemic, we found substantial variations in incidence of COVID-19-related admissions in nine European countries. Few pregnant women received COVID-19-directed medical treatment. Several barriers to rapid surveillance were identified. Investment in robust surveillance should be prioritized to prepare for future pandemics.Peer reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries

Funding Information: M.B.A. holds a Tier 2 Canada Research Chair in the Developmental Origins of Chronic Disease at the University of Manitoba and is a Fellow in the Canadian Institutes for Advanced Research (CIFAR) Humans and the Microbiome Program. Her effort on this project was partly supported by HDR UK and ICODA. K.K.C.M. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G) and grants from C W Maplethorpe Fellowship, National Institute of Health Research UK, European Commission Framework Horizon 2020 and has consulted for IQVIA Ltd. A.S. is supported by ICODA and HDR UK, and has received a research grant from HDR UK to the BREATHE Hub. He participates on the Scottish and UK Government COVID-19 Advisory Committees, unremunerated. S.J.S. is supported by a Wellcome Trust Clinical Career Development Fellowship (209560/Z/17/Z) and HDR UK, and has received personal fees from Hologic and Natera outside the submitted work. D.B. is supported by a National Health and Medical Research Council (Australia) Investigator Grant (GTN1175744). I.C.K.W. declares support from The Innovation and Technology Commission of the Hong Kong Special Administrative Region Government, and Hong Kong Research Grants Council Collaborative Research Fund Coronavirus Disease (COVID-19) and Novel Infectious Disease Research Exercise (Ref: C7154-20G), and grants from Hong Kong Research Grant Council, National Institute of Health Research UK, and European Commission Framework Horizon 2020. H.Z. is supported by a UNSW Scientia Program Award and reports grants from European Commission Framework Horizon 2020, Icelandic Centre for Research, and Australia’s National Health and Medical Research Council. H.Z. was an employee of the UNSW Centre for Big Data Research in Health, which received funding from AbbVie Australia to conduct research, unrelated to the current study. I.I.A.A., C.D.A., K.A., A.I.A., L.C., S.S., G.E.-G., O.W.G., L. Huicho, S.H., A.K., K.L., V.N., I.P., N.R.R., T.R., T.A.H.R., V.L.S., E.M.S., L.T., R.W. and H.Z. received funding from HDRUK (grant #2020.106) to support data collection for the iPOP study. K.H., R.B., S.O.E., A.R.-P. and J.H. receive salary from ICODA. M.B. received trainee funding from HDRUK (grant #2020.106). J.E.M. received trainee funding from HDRUK (grant #2020.109). Other relevant funding awarded to authors to conduct research for iPOP include: M.G. received funding from THL, Finnish Institute for Health and Welfare to support data collection. K.D. received funding from EDCTP RIA2019 and HDRUK (grant #2020.106) to support data collection. R.B. received funding from Alzheimer’s Disease Data Initiative and ICODA for the development of federated analysis. A.D.M. received funding from HDR UK who receives its funding from the UK Medical Research Council, Engineering and Physical Sciences Research Council, Economic and Social Research Council, Department of Health and Social Care (England), Chief Scientist Office of the Scottish Government Health and Social Care Directorates, Health and Social Care Research and Development Division (Welsh Government), Public Health Agency (Northern Ireland), British Heart Foundation (BHF) and the Wellcome Trust; and Administrative Data Research UK, which is funded by the Economic and Social Research Council (grant ES/S007393/1). N.A. received funding from the National Institutes of Health (R35GM138353). O.S received funding from NordForsk (grant #105545). The remaining authors declare no competing interests. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/ ) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Funding Information: Funding and in-kind support: This work was supported by the International COVID-19 Data Alliance (ICODA), an initiative funded by the Bill and Melinda Gates Foundation and Minderoo as part of the COVID-19 Therapeutics Accelerator and convened by Health Data Research (HDR) UK, in addition to support from the HDR UK BREATHE Hub. Several ICODA partners contributed to the study, including: Cytel (statistical support), the Odd Group (data visualization) and Aridhia Informatics (development of federated analysis using a standardized protocol ([Common API] https://github.com/federated-data-sharing/) to be used in future work). Additional contributors: We acknowledge the important contributions from the following individuals: A. C. Hennemann and D. Suguitani (patient partners from Prematuridade: Brazilian Parents of Preemies’ Association, Porto Alegre, Brazil); N. Postlethwaite (implementation of processes supporting the trustworthy collection, governance and analysis of data from ICODA, HDR UK, London, UK); A. S. Babatunde (led data acquisition from University of Uyo Teaching Hospital, Uyo, Nigeria); N. Silva (data quality, revision and visualization assessment from Methods, Analytics and Technology for Health (M.A.T.H) Consortium, Belo Horizonte, Brazil); J. Söderling (data management from the Karolinska Institutet, Stockholm, Sweden). We also acknowledge the following individuals who assisted with data collection efforts: R. Goemaes (Study Centre for Perinatal Epidemiology (SPE), Brussels, Belgium); C. Leroy (Le Centre d'Épidémiologie Périnatale (CEpiP), Brussels, Belgium); J. Gamba and K. Ronald (St. Francis Nsambya Hospital, Kampala, Uganda); M. Heidarzadeh (Tabriz Medical University, Tabriz, Iran); M. J. Ojeda (Pontificia Universidad Católica de Chile, Santiago, Chile); S. Nangia (Lady Hardinge Medical College, New Delhi, India); C. Nelson, S. Metcalfe and W. Luo (Maternal Infant Health Section of the Public Health Agency of Canada, Ottawa, Canada); K. Sitcov (Foundation for Health Care Quality, Seattle, United States); A. Valek (Semmelweis University, Budapest, Hungary); M. R. Yanlin Liu (Mater Data and Analytics, Brisbane, Australia). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript. Publisher Copyright: © 2023, The Author(s).Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from −90% to +30%, were reported in many countries following early COVID-19 pandemic response measures (‘lockdowns’). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95–0.98, P value <0.0001), second (0.96, 0.92–0.99, 0.03) and third (0.97, 0.94–1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96–1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88–1.14, 0.98), third (0.99, 0.88–1.12, 0.89) and fourth (1.01, 0.87–1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02–1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03–1.15, 0.002), third (1.10, 1.03–1.17, 0.003) and fourth (1.12, 1.05–1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways.Peer reviewe

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways

Changes in preterm birth and stillbirth during COVID-19 lockdowns in 26 countries.

Preterm birth (PTB) is the leading cause of infant mortality worldwide. Changes in PTB rates, ranging from -90% to +30%, were reported in many countries following early COVID-19 pandemic response measures ('lockdowns'). It is unclear whether this variation reflects real differences in lockdown impacts, or perhaps differences in stillbirth rates and/or study designs. Here we present interrupted time series and meta-analyses using harmonized data from 52 million births in 26 countries, 18 of which had representative population-based data, with overall PTB rates ranging from 6% to 12% and stillbirth ranging from 2.5 to 10.5 per 1,000 births. We show small reductions in PTB in the first (odds ratio 0.96, 95% confidence interval 0.95-0.98, P value <0.0001), second (0.96, 0.92-0.99, 0.03) and third (0.97, 0.94-1.00, 0.09) months of lockdown, but not in the fourth month of lockdown (0.99, 0.96-1.01, 0.34), although there were some between-country differences after the first month. For high-income countries in this study, we did not observe an association between lockdown and stillbirths in the second (1.00, 0.88-1.14, 0.98), third (0.99, 0.88-1.12, 0.89) and fourth (1.01, 0.87-1.18, 0.86) months of lockdown, although we have imprecise estimates due to stillbirths being a relatively rare event. We did, however, find evidence of increased risk of stillbirth in the first month of lockdown in high-income countries (1.14, 1.02-1.29, 0.02) and, in Brazil, we found evidence for an association between lockdown and stillbirth in the second (1.09, 1.03-1.15, 0.002), third (1.10, 1.03-1.17, 0.003) and fourth (1.12, 1.05-1.19, <0.001) months of lockdown. With an estimated 14.8 million PTB annually worldwide, the modest reductions observed during early pandemic lockdowns translate into large numbers of PTB averted globally and warrant further research into causal pathways