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Clinical manifestations, risk factors, and maternal and perinatal outcomes of coronavirus disease 2019 in pregnancy: living systematic review and meta-analysis

BMJ 2020; 370 doi: https://doi.org/10.1136/bmj.m3320 (Published 01 September 2020) Cite this as: BMJ 2020;370:m3320

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Evidence based care for pregnant women with covid-19

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Efficient, timely, and funded living evidence syntheses on maternal and newborn health during the pandemic

  1. John Allotey, lecturer in epidemiology and women’s health12,
  2. Elena Stallings, researcher34,
  3. Mercedes Bonet, medical officer5,
  4. Magnus Yap, medical student6,
  5. Shaunak Chatterjee, medical student6,
  6. Tania Kew, medical student6,
  7. Luke Debenham, medical student6,
  8. Anna Clavé Llavall, medical student6,
  9. Anushka Dixit, medical student6,
  10. Dengyi Zhou, medical student6,
  11. Rishab Balaji, medical student6,
  12. Siang Ing Lee, researcher1,
  13. Xiu Qiu, chief consultant of women’s health789,
  14. Mingyang Yuan, researcher17,
  15. Dyuti Coomar, research fellow1,
  16. Jameela Sheikh, medical student6,
  17. Heidi Lawson, medical student6,
  18. Kehkashan Ansari, researcher2,
  19. Madelon van Wely, clinical epidemiologist10,
  20. Elizabeth van Leeuwen, medical specialist11,
  21. Elena Kostova, managing editor10,
  22. Heinke Kunst, senior lecturer and consultant in respiratory medicine1213,
  23. Asma Khalil, professor of obstetrics and maternal-fetal medicine14,
  24. Simon Tiberi, infectious disease consultant1213,
  25. Vanessa Brizuela, doctor of public health5,
  26. Nathalie Broutet, medical officer5,
  27. Edna Kara, public health specialist3,
  28. Caron Rahn Kim, medical officer5,
  29. Anna Thorson, professor in global infectious disease epidemiology5,
  30. Ramón Escuriet, head15,
  31. Olufemi T Oladapo, head of maternal and perinatal health unit5,
  32. Lynne Mofenson, paediatric infectious disease specialist16,
  33. Javier Zamora, professor of biostatistics234,
  34. Shakila Thangaratinam, professor of maternal and perinatal health218
  35. on behalf of the PregCOV-19 Living Systematic Review Consortium
  1. 1Institute of Applied Health Research, University of Birmingham, Birmingham, UK
  2. 2WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
  3. 3Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
  4. 4CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
  5. 5UNDP/UNFPA/UNICEF/WHO/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Sexual and Reproductive Health and Research, World Health Organization, Geneva, Switzerland
  6. 6Birmingham Medical School, University of Birmingham, Birmingham, UK
  7. 7Division of Birth Cohort Study, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
  8. 8Department of Woman and Child Health Care, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
  9. 9Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
  10. 10Netherlands Satellite of the Cochrane Gynaecology and Fertility Group, Amsterdam University Medical Centre, Amsterdam, Netherlands
  11. 11Department of Obstetrics and Gynaecology, Amsterdam University Medical Centre, Amsterdam, Netherlands
  12. 12Blizard Institute, Queen Mary University of London, London, UK
  13. 13Barts Health NHS Trust, London, UK
  14. 14St George’s, University of London, London, UK
  15. 15Sexual and Reproductive Health care, Catalan Health Service, Barcelona, Catalonia, Spain
  16. 16Elizabeth Glaser Paediatric AIDS Foundation, Washington, DC, USA
  17. 17Women’s Health Research Unit, Queen Mary University of London, London, UK
  18. 18Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK
  1. Correspondence to: S Thangaratinam s.thangaratinam.1{at}bham.ac.uk (or @thangaratinam on Twitter)
  • Accepted 23 August 2020
  • Final version accepted 2 February 2021

Abstract

Objective To determine the clinical manifestations, risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed coronavirus disease 2019 (covid-19).

Design Living systematic review and meta-analysis.

Data sources Medline, Embase, Cochrane database, WHO COVID-19 database, China National Knowledge Infrastructure (CNKI), and Wanfang databases from 1 December 2019 to 6 October 2020, along with preprint servers, social media, and reference lists.

Study selection Cohort studies reporting the rates, clinical manifestations (symptoms, laboratory and radiological findings), risk factors, and maternal and perinatal outcomes in pregnant and recently pregnant women with suspected or confirmed covid-19.

Data extraction At least two researchers independently extracted the data and assessed study quality. Random effects meta-analysis was performed, with estimates pooled as odds ratios and proportions with 95% confidence intervals. All analyses will be updated regularly.

Results 192 studies were included. Overall, 10% (95% confidence interval 7% to 12%; 73 studies, 67 271 women) of pregnant and recently pregnant women attending or admitted to hospital for any reason were diagnosed as having suspected or confirmed covid-19. The most common clinical manifestations of covid-19 in pregnancy were fever (40%) and cough (41%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to have symptoms (odds ratio 0.28, 95% confidence interval 0.13 to 0.62; I2=42.9%) or report symptoms of fever (0.49, 0.38 to 0.63; I2=40.8%), dyspnoea (0.76, 0.67 to 0.85; I2=4.4%) and myalgia (0.53, 0.36 to 0.78; I2=59.4%). The odds of admission to an intensive care unit (odds ratio 2.13, 1.53 to 2.95; I2=71.2%), invasive ventilation (2.59, 2.28 to 2.94; I2=0%) and need for extra corporeal membrane oxygenation (2.02, 1.22 to 3.34; I2=0%) were higher in pregnant and recently pregnant than non-pregnant reproductive aged women. Overall, 339 pregnant women (0.02%, 59 studies, 41 664 women) with confirmed covid-19 died from any cause. Increased maternal age (odds ratio 1.83, 1.27 to 2.63; I2=43.4%), high body mass index (2.37, 1.83 to 3.07; I2=0%), any pre-existing maternal comorbidity (1.81, 1.49 to 2.20; I2=0%), chronic hypertension (2.0, 1.14 to 3.48; I2=0%), pre-existing diabetes (2.12, 1.62 to 2.78; I2=0%), and pre-eclampsia (4.21, 1.27 to 14.0; I2=0%) were associated with severe covid-19 in pregnancy. In pregnant women with covid-19, increased maternal age, high body mass index, non-white ethnicity, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pre-eclampsia were associated with serious complications such as admission to an intensive care unit, invasive ventilation and maternal death. Compared to pregnant women without covid-19, those with the disease had increased odds of maternal death (odds ratio 2.85, 1.08 to 7.52; I2=0%), of needing admission to the intensive care unit (18.58, 7.53 to 45.82; I2=0%), and of preterm birth (1.47, 1.14 to 1.91; I2=18.6%). The odds of admission to the neonatal intensive care unit (4.89, 1.87 to 12.81, I2=96.2%) were higher in babies born to mothers with covid-19 versus those without covid-19.

Conclusion Pregnant and recently pregnant women with covid-19 attending or admitted to the hospitals for any reason are less likely to manifest symptoms such as fever, dyspnoea, and myalgia, and are more likely to be admitted to the intensive care unit or needing invasive ventilation than non-pregnant women of reproductive age. Pre-existing comorbidities, non-white ethnicity, chronic hypertension, pre-existing diabetes, high maternal age, and high body mass index are risk factors for severe covid-19 in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and could have an increased risk of maternal death and of being admitted to the intensive care unit. Their babies are more likely to be admitted to the neonatal unit.

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. This version is update 1 of the original article published on 1 September 2020 (BMJ 2020;370:m3320), and previous updates can be found as data supplements (https://www.bmj.com/content/370/bmj.m3320/related#datasupp). When citing this paper please consider adding the update number and date of access for clarity.

Footnotes

  • Contributors: ST, MB, and JA conceptualised the study. MY, SC, LD, TK, ACL, AD, DZ, RB, SL, XQ, MYuan, JS, HL, and KA selected the studies. JA, ES, MY, LD, DZ, XQ, and MYuan extracted the data. JZ conducted the analyses. JA and ES are joint first authors. All coauthors contributed to the writing of the manuscript and approved the final version. ST, JA, ES, and JZ are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted

  • Funding: The project was partially funded by the World Health Organization and UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a cosponsored programme executed by the World Health Organization (WHO). The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.

  • Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: partial funding by the World Health Organization and HRP; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work.

  • Ethical approval: Not required.

  • Data sharing: No additional data available.

  • The corresponding author (ST) affirms that the manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned have been disclosed.

  • Dissemination to participants and related patient and public communities: The PregCov-19 LSR Group will disseminate the findings through a dedicated website (www.birmingham.ac.uk/research/who-collaborating-centre/pregcov/index.aspx) and social media.

  • Provenance and peer review: Not commissioned; externally peer reviewed.

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