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

Giesbers, Steven; Goh, Edwina; Kew, Tania; Allotey, John; Brizuela, Vanessa; Kara, Edna; Kunst, Heinke; Bonet, Mercedes; Thangaratinam, Shakila; Chatterjee, Shaunak; Gae, Andrea; Stallings, Elena; Yap, Magnus; Sheikh, Jameela; Lawson, Heidi; Coomar, Dyuti; Dixit, Anushka; Zhou, Dengyi; Balaji, Rishab; Littmoden, Megan; King, Yasmin; Debenham, Luke; Clavé Llavall, Anna; Ansari, Kehkashan; Sandhu, Gurimaan; Banjoko, Adeolu; Fraser, Helen; Rajah, Tanisha; Ramkumar, Anoushka; Khashaba, Alya; Attarde, Shruit; Walker, Kate; Thornton, Jim; van Wely, Madelon; van Leeuwen, Elizabeth; Kostova, Elena; Khalil, Asma; Tiberi, Simon; Broutet, Nathalie; Rahn Kim, Caron; Thorson, Anna; Oladapo, Olufemi T.; Zamora, Javier; Mofenson, Lynne

Authors

Steven Giesbers

Edwina Goh

Tania Kew

John Allotey

Vanessa Brizuela

Edna Kara

Heinke Kunst

Mercedes Bonet

Shakila Thangaratinam

Shaunak Chatterjee

Andrea Gae

Elena Stallings

Magnus Yap

Jameela Sheikh

Heidi Lawson

Dyuti Coomar

Anushka Dixit

Dengyi Zhou

Rishab Balaji

Megan Littmoden

Yasmin King

Luke Debenham

Anna Clavé Llavall

Kehkashan Ansari

Gurimaan Sandhu

Adeolu Banjoko

Helen Fraser

Tanisha Rajah

Anoushka Ramkumar

Alya Khashaba

Shruit Attarde

KATE WALKER Kate.Walker@nottingham.ac.uk
Clinical Professor

Jim Thornton

Madelon van Wely

Elizabeth van Leeuwen

Elena Kostova

Asma Khalil

Simon Tiberi

Nathalie Broutet

Caron Rahn Kim

Anna Thorson

Olufemi T. Oladapo

Javier Zamora

Lynne Mofenson



Abstract

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 We undertook a systematic review of all published and unpublished studies on the effects of pharmacological and non-pharmacological interventions for COVID-19 on maternal and neonatal pregnancy outcomes.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 min). 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, I2 = 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, I2 = 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, I2 = 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.

Citation

Giesbers, S., Goh, E., Kew, T., Allotey, J., Brizuela, V., Kara, E., …Mofenson, L. (2021). Treatment of COVID-19 in pregnant women: A systematic review and meta-analysis. European Journal of Obstetrics and Gynecology and Reproductive Biology, 267, 120-128. https://doi.org/10.1016/j.ejogrb.2021.10.007

Journal Article Type Article
Acceptance Date Oct 1, 2021
Online Publication Date Oct 19, 2021
Publication Date Dec 1, 2021
Deposit Date Jan 11, 2022
Journal European Journal of Obstetrics and Gynecology and Reproductive Biology
Print ISSN 0301-2115
Electronic ISSN 1872-7654
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 267
Pages 120-128
DOI https://doi.org/10.1016/j.ejogrb.2021.10.007
Keywords Obstetrics and Gynaecology; Reproductive Medicine
Public URL https://nottingham-repository.worktribe.com/output/7222689
Publisher URL https://www.ejog.org/article/S0301-2115(21)00496-6/fulltext
Additional Information Authors on behalf of PregCOV-19 Group.

University of Nottingham authors: Kate Walker, Jim Thornton