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Research

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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Efficient, timely, and funded living evidence syntheses on maternal and newborn health during the pandemic
  1. John Allotey, lecturer in epidemiology and women’s health1,
  2. Silvia Fernandez, researcher2,
  3. Mercedes Bonet, medical officer3,
  4. Elena Stallings, researcher2 4,
  5. Magnus Yap, medical student5,
  6. Tania Kew, medical student5,
  7. Dengyi Zhou, medical student5,
  8. Dyuti Coomar, research fellow1,
  9. Jameela Sheikh, medical student5,
  10. Heidi Lawson, medical student5,
  11. Kehkashan Ansari, researcher1,
  12. Shruti Attarde, medical student5,
  13. Megan Littmoden, medical student5,
  14. Adeolu Banjoko, medical student5,
  15. Kathryn Barry, medical student5,
  16. Oluwadamilola Akande, medical student5,
  17. Dharshini Sambamoorthi, medical student5,
  18. Madelon van Wely, clinical epidemiologist6,
  19. Elisabeth van Leeuwen, medical specialist7,
  20. Elena Kostova, managing editor6,
  21. Heinke Kunst, senior lecturer and consultant in respiratory medicine8 9,
  22. Asma Khalil, professor of obstetrics and maternal-fetal medicine10,
  23. Simon Tiberi, infectious disease consultant8 9,
  24. Vanessa Brizuela, doctor of public health3,
  25. Nathalie Broutet, medical officer3,
  26. Edna Kara, public health specialist3,
  27. Caron Rahn Kim, medical officer3,
  28. Anna Thorson, professor in global infectious disease epidemiology3,
  29. Ramón Escuriet, head11,
  30. Sami Gottlieb, medical officer3,
  31. Van T Tong, epidemiologist12,
  32. Sascha Ellington, epidemiologist12,
  33. Olufemi T Oladapo, head of maternal and perinatal health unit3,
  34. Lynne Mofenson, paediatric infectious disease specialist13,
  35. Javier Zamora, professor of biostatistics1 2 4,
  36. Shakila Thangaratinam, professor of maternal and perinatal health1 14
  37. on behalf of the PregCOV-19 Living Systematic Review Consortium
  1. 1WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
  2. 2Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
  3. 3UNDP/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
  4. 4CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
  5. 5Birmingham Medical School, University of Birmingham, Birmingham, UK
  6. 6Netherlands Satellite of the Cochrane Gynaecology and Fertility Group, Amsterdam University Medical Centre, Amsterdam, Netherlands
  7. 7Department of Obstetrics and Gynaecology, Amsterdam University Medical Centre, Amsterdam, Netherlands
  8. 8Blizard Institute, Queen Mary University of London, London, UK
  9. 9Barts Health NHS Trust, London, UK
  10. 10St George’s, University of London, London, UK
  11. 11Sexual and Reproductive Health care, Catalan Health Service, Barcelona, Catalonia, Spain
  12. 12CDC COVID-19 Response, Atlanta, GA, USA
  13. 13Elizabeth Glaser Paediatric AIDS Foundation, Washington, DC, USA
  14. 14Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK
  15. Correspondence to: S Thangaratinam s.thangaratinam.1{at}bham.ac.uk (or @thangaratinam on Twitter)
  • Accepted 23 August 2020
  • Final version accepted 7 May 2022

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 27 April 2021, 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 or risk difference and proportions with 95% confidence intervals. All analyses are updated regularly.

Results 435 studies were included. Overall, 9% (95% confidence interval 7% to 10%; 149 studies, 926 232 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 and cough (both 36%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever, dyspnoea, cough, and myalgia. The odds of admission to an intensive care unit (odds ratio 2.61, 95% confidence interval 1.84 to 3.71; I2=85.6%), and invasive ventilation (2.41, 2.13 to 2.71; I2=0%) were higher in pregnant and recently pregnant than non-pregnant women of reproductive age. Overall, 970 pregnant women (0.2%, 123 studies, 179 981 women) with confirmed covid-19 died from any cause. In pregnant women with covid-19, non-white ethnicity, increased maternal age, high body mass index, any pre-existing maternal comorbidity including chronic hypertension and diabetes, and pregnancy specific complications such as gestational diabetes and pre-eclampsia, were associated with serious complications (severe covid-19, 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 6.09, 95% confidence interval 1.82 to 20.38; I2=76.6%), of admission to the intensive care unit (5.41, 3.59 to 8.14; I2=57.0%), caesarean section (1.17, 1.01 to 1.36; I2=80.3%), and of preterm birth (1.57, 1.36 to 1.81; I2=49.3%). The odds of stillbirth (1.81, 1.38 to 2.37, I2=0%), and admission to the neonatal intensive care unit (2.18, 1.46 to 3.26, I2=85.4%) were higher in babies born to women 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, cough, dyspnoea, and myalgia, but 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 outcomes in pregnancy. Pregnant women with covid-19 versus without covid-19 are more likely to deliver preterm and 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 intensive care 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 2 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. 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 supported by the German Federal Ministry of Health (BMG) COVID-19 Research and development support to the World Health Organization (WHO) and UNDP-UNFPA-UNICEF-WHO-World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), a co-sponsored programme executed by 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 WHO and HRP for the submitted work; 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.

  • 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.

Data availability statement

No additional data available.

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