BMJ Global Health (Jan 2023)
Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis
- ,
- Chris Gale,
- Marian Knight,
- Kirsty Le Doare,
- Erica M Lokken,
- Laura A Magee,
- Peter von Dadelszen,
- Nathalie Broutet,
- Emily R Smith,
- Deborah Money,
- Stephanie Jones,
- Olof Stephansson,
- Lesley Regan,
- Fouzia Farooq,
- Christoph Lees,
- Julia Townson,
- Sami L Gottlieb,
- Jonas Söderling,
- Jorge Carrillo,
- Anna Thorson,
- Marleen Temmerman,
- Joyce Were,
- Edward Mullins,
- Ajay Reddy,
- Valerie J Flaherman,
- Clayton Onyango,
- Shabir A Madhi,
- Antonio Lanzone,
- Liona C Poon,
- Alice Panchaud,
- Musa Sekikubo,
- Eduard Gratacos,
- Renate Strehlau,
- Cande V. Ananth,
- Jorge E Tolosa,
- Justin S Brandt,
- Jennifer Hill,
- Erich Cosmi,
- Lauren Hookham,
- Raigam Jafet Martínez-Portilla,
- Francesca Crovetto,
- Fatima Crispi,
- Robert Mboizi,
- Jean B Nachega,
- Silvia Visentin,
- Erin Oakley,
- Gargi Wable Grandner,
- Kacey Ferguson,
- Yalda Afshar,
- Mia Ahlberg,
- Homa Ahmadzia,
- Victor Akelo,
- Grace Aldrovandi,
- Beth A Tippett Barr,
- Elisa Bevilacqua,
- Irene Fernández Buhigas,
- Rebecca Clifton,
- Jeanne Conry,
- Camille Delgado-López,
- Hema Divakar,
- Amanda J Driscoll,
- Guillaume Favre,
- Maria M Gil,
- Olivia Hernandez,
- Erkan Kalafat,
- Sammy Khagayi,
- Karen Kotloff,
- Ethan Litman,
- Valentina Laurita Longo,
- Elizabeth M McClure,
- Tori D Metz,
- Emily S Miller,
- Sakita Moungmaithong,
- Marta C Nunes,
- Dickens Onyango,
- Daniel Raiten,
- Gordon Rukundo,
- Daljit Sahota,
- Allie Sakowicz,
- Jose Sanin-Blair,
- Miguel Valencia-Prado,
- Kristina Adams Waldorf,
- Clare Whitehead,
- Murat Yassa,
- Jim M Tielsch,
- Eduard Langenegger,
- Nadia A. Sam-Agudu,
- Onesmus W. Gachuno,
- Denis M. Mukwege,
- Richard Omore,
- Gregory Ouma,
- Kephas Otieno,
- Zacchaeus Abaja Were,
- Pinar Birol İlter,
- Federica Meli,
- Giulia Bonanni,
- Federica Romanzi,
- Eleonora Torcia,
- Chiara di Ilio,
- Haylea Sweat Patrick,
- Vuyelwa Baba,
- Mary Adam,
- Philiswa Mlandu,
- Yasmin Adam
Affiliations
- Leiden University Medical Center, Leiden, The Netherlands
- Chris Gale
- Neonatal Medicine, School of Public Health, Faculty of Medicine, Imperial College London, London, UK
- Marian Knight
- National Perinatal Epidemiology Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK
- Kirsty Le Doare
- MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Wakiso, Uganda
- Erica M Lokken
- Department of Epidemiology, University of Washington, Seattle, Washington, USA
- Laura A Magee
- Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada
- Peter von Dadelszen
- Department of Obstetrics and Gynaecology, The University of British Columbia, Vancouver, British Columbia, Canada
- Nathalie Broutet
- 9 Department of Sexual and Reproductive Health and Research, World Health Organization, Geneve, Switzerland
- Emily R Smith
- Department of Public Health, Baylor University, Waco, Texas, USA
- Deborah Money
- 7University of British Columbia, Vancouver, Canada
- Stephanie Jones
- GOS Institute of Child Health, UCL, London, UK
- Olof Stephansson
- associate professor
- Lesley Regan
- 5 Department of Obstetrics and Gynaecology, St Mary`s Hospital, Imperial College Healthcare NHS Trust, London, UK
- Fouzia Farooq
- 1 Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Christoph Lees
- consultant
- Julia Townson
- Centre for Trials Research, Cardiff University, Cardiff, UK
- Sami L Gottlieb
- Department of Reproductive Health and Research, World Health Organization, Geneve, Switzerland
- Jonas Söderling
- 5 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
- Jorge Carrillo
- IrsiCaixa AIDS Research Institute, Germans Trias i Pujol University Hospital, Badalona, Spain
- Anna Thorson
- 9 Department of Sexual and Reproductive Health and Research, World Health Organization, Geneve, Switzerland
- Marleen Temmerman
- director
- Joyce Were
- Kenya Medical Research Institute/Centers for Disease Control and Prevention Public Health and Research Collaboration, Kisumu, Kenya
- Edward Mullins
- clinical lecturer and consultant obstetrician and gynaecologist
- Ajay Reddy
- Valerie J Flaherman
- Department of Pediatrics, University of California San Francisco, San Francisco, California, USA
- Clayton Onyango
- 2 Centers for Disease Control and Prevention, Atlanta, Georgia, USA
- Shabir A Madhi
- 13 Medical Research Council, Respiratory and Meningeal Pathogens Research Unit, University of the Witwatersrand, Johannesburg, South Africa
- Antonio Lanzone
- Department of Obstetrics and Gynaecology, Fondazione Policlinico Universitario ‘A. Gemelli’, Catholic University of Sacred Heart, Rome, Italy
- Liona C Poon
- 1Harris Birthright Research Centre for Fetal Medicine, King`s College Hospital, London, UK
- Alice Panchaud
- Swiss Teratogen Information Service, University Hospital, Lausanne, Switzerland
- Musa Sekikubo
- Obstetrics and Gynaecology, Makerere University, Kampala, Uganda
- Eduard Gratacos
- Hospital Clinic de Barcelona, Barcelona, Spain
- Renate Strehlau
- Faculty of Health Sciences, Rahima Moosa Mother and Child Hospital, University of the Witwatersrand, Johannesburg, South Africa
- Cande V. Ananth
- Department of Obstetrics and Gynecology, Columbia University College of Physicians and Surgeons;
- Jorge E Tolosa
- 5Department of Obstetrics & Gynecology, Oregon Health & Science University, Portland, Oregon, USA
- Justin S Brandt
- Division of Maternal-Fetal Medicine, Department of Obstetrics, Gynecology, and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA
- Jennifer Hill
- guidelines operations director
- Erich Cosmi
- Obstetrics and Gynecology Clinic, Padua University Hospital, Padova, Italy
- Lauren Hookham
- Department of Infectious Diseases and Tropical Medicine, Guys and St Thomas Hospital, London, UK
- Raigam Jafet Martínez-Portilla
- Clinical Research Division, National Institute of Perinatology, Mexico City, Mexico
- Francesca Crovetto
- 8 BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, University of Barcelona, CIBERER, Barcelona, Spain
- Fatima Crispi
- 8 BCNatal - Barcelona Center for Maternal-Fetal and Neonatal Medicine, Hospital Sant Joan de Déu and Hospital Clínic, University of Barcelona, CIBERER, Barcelona, Spain
- Robert Mboizi
- Makerere University Johns Hopkins University, Kampala, Uganda
- Jean B Nachega
- Center for Global Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
- Silvia Visentin
- 14 Department of Women`s and Children`s Health, University of Padua, Padova, Italy
- Erin Oakley
- 1 Department of Global Health, The George Washington University Milken Institute School of Public Health, Washington, DC, USA
- Gargi Wable Grandner
- 1 Department of Global Health, The George Washington University Milken Institute School of Public Health, Washington, DC, USA
- Kacey Ferguson
- 1 Department of Global Health, The George Washington University Milken Institute School of Public Health, Washington, DC, USA
- Yalda Afshar
- 2 Division of Maternal Fetal Medicine, University of California Los Angeles, Los Angeles, California, USA
- Mia Ahlberg
- 3 Department of Medicine, Solna, Clinical Epidemiology Division, Karolinska Institute, Stockholm, Sweden
- Homa Ahmadzia
- 4 Division of Maternal-Fetal Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Victor Akelo
- 5 Office of the Director, US Centers for Disease Control and Prevention, Kisumu, Kenya
- Grace Aldrovandi
- 6 Department of Pediatrics, University of California Los Angeles, Los Angeles, California, USA
- Beth A Tippett Barr
- 5 Office of the Director, US Centers for Disease Control and Prevention, Kisumu, Kenya
- Elisa Bevilacqua
- 7 Department of Women and Child Health, Women Health Area, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Roma, Italy
- Irene Fernández Buhigas
- 10 Department of Obstetrics and Gynecology, Hospital Universitario de Torrejón, Madrid, Spain
- Rebecca Clifton
- 12 The Biostatistics Center, The George Washington University Milken Institute School of Public Health, Rockville, Maryland, USA
- Jeanne Conry
- 13 International Federation of Gynecology and Obstetrics, London, UK
- Camille Delgado-López
- 16 Surveillance for Emerging Threats to Mothers and Babies, Puerto Rico Department of Health, San Juan, Puerto Rico
- Hema Divakar
- 17 Asian Research and Training Institute for Skill Transfer (ARTIST), Bengaluru, India
- Amanda J Driscoll
- 18 Center for Vaccine Development, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Guillaume Favre
- 19 Materno-Fetal and Obstetrics Research Unit, Department ‘Femme-Mère-Enfant’, Lausanne University Hospital, Lausanne, Switzerland
- Maria M Gil
- 10 Department of Obstetrics and Gynecology, Hospital Universitario de Torrejón, Madrid, Spain
- Olivia Hernandez
- 22 Gynecology and Obstetrics, Felix Bulnes Hospital and RedSalud Clinic, Santiago, Chile
- Erkan Kalafat
- 24 Department of Obstetrics and Gynecology, Koç University School of Medicine, Istanbul, Turkey
- Sammy Khagayi
- 25 Center for Global Health Research, Kenya Medical Research Institute, Kisumu, Kenya
- Karen Kotloff
- 27 Department of Pediatrics, University of Maryland School of Medicine, Baltimore, Maryland, USA
- Ethan Litman
- 4 Division of Maternal-Fetal Medicine, The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
- Valentina Laurita Longo
- 32 Institute of Obstetrics and Gynecology Clinic, Catholic University of Sacred Heart, Rome, Italy
- Elizabeth M McClure
- 35 RTI International, Research Triangle Park, North Carolina, USA
- Tori D Metz
- 36 Departments of Obstetrics and Gynecology, University of Utah Health Sciences Center, Salt Lake, Utah, USA
- Emily S Miller
- 37 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Sakita Moungmaithong
- 39 Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Marta C Nunes
- 23 South African Medical Research Council, Vaccines and Infectious Diseases Analytics Research Unit, University of the Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa
- Dickens Onyango
- 41 Kisumu County Department of Health, Kisumu, Kenya
- Daniel Raiten
- 43 Pediatric Growth and Nutrition Branch, National Institute of Health, Bethesda, Maryland, USA
- Gordon Rukundo
- 28 Uganda Virus Institute and the London School of Hygiene & Tropical Medicine, Entebbe, Uganda
- Daljit Sahota
- 39 Department of Obstetrics and Gynecology, The Chinese University of Hong Kong, Hong Kong, Hong Kong
- Allie Sakowicz
- 37 Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
- Jose Sanin-Blair
- 44 Universidad Pontificia Bolivariana, Medellin, Antioquia, Colombia
- Miguel Valencia-Prado
- 48 Children with Special Medical Needs Division, Puerto Rico Department of Health, San Juan, Puerto Rico
- Kristina Adams Waldorf
- 31 Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington, USA
- Clare Whitehead
- 50 Department of Maternal-Fetal Medicine, The Royal Women`s Hospital, University of Melbourne, Parkville, Victoria, Australia
- Murat Yassa
- 51 Department of Obstetrics and Gynecology, Sancaktepe Sehit Prof Dr Ilhan Varank Training and Research Hospital, Istanbul, Turkey
- Jim M Tielsch
- 1 Department of Global Health, The George Washington University Milken Institute School of Public Health, Washington, DC, USA
- Eduard Langenegger
- Nadia A. Sam-Agudu
- Onesmus W. Gachuno
- Denis M. Mukwege
- Richard Omore
- Gregory Ouma
- Kephas Otieno
- Zacchaeus Abaja Were
- Pinar Birol İlter
- Federica Meli
- Giulia Bonanni
- Federica Romanzi
- Eleonora Torcia
- Chiara di Ilio
- Haylea Sweat Patrick
- Vuyelwa Baba
- Mary Adam
- Philiswa Mlandu
- Yasmin Adam
- DOI
- https://doi.org/10.1136/bmjgh-2022-009495
- Journal volume & issue
-
Vol. 8,
no. 1
Abstract
Introduction Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies.Methods We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale.Results We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection—as compared with uninfected pregnant women—were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias.Conclusions This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.
