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

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.

Conflict of interest statement

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; 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.

© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Fig 1

Study selection process. *Twitter, national reports, blog by J Thornton, ObG Project, COVID-19 and Pregnancy Cases, https://ripe-tomato.org/2020/05/15/covid-19-in-pregnancy-101-onwards/; EPPI-Centre, COVID-19: a living systematic map of evidence, http://eppi.ioe.ac.uk/cms/Projects/DepartmentofHealthandSocialCare/Publishedreviews/COVID-19Livingsystematicmapoftheevidence/tabid/3765/Default.aspx; Norwegian Institute of Public Health, NIPH systematic and living map on COVID-19 evidence, www.nornesk.no/forskningskart/NIPH_mainMap.html; Johns Hopkins University Center for Humanitarian Health; COVID-19, Maternal and Child Health, Nutrition, http://hopkinshumanitarianhealth.org/empower/advocacy/covid-19/covid-19-children-and-nutrition/; ResearchGate, COVID-19 research community, www.researchgate.net/community/COVID-19; and Living Overview of the Evidence, Coronavirus disease (COVID-19), https://app.iloveevidence.com/loves/5e6fdb9669c00e4ac072701d?population=5d062d5fc80dd41e58ba8459

Fig 2

Prevalence of severe acute respiratory syndrome coronavirus 2 in pregnant and recently pregnant women identified by various sampling strategies. Meta-analysis includes one study (Liao 2020) screened using National Health Commission China criteria with no events

Fig 3

Rates of clinical manifestations of coronavirus disease 2019 (covid-19) in pregnant women and recently pregnant women with suspected or confirmed covid-19 and associated maternal and perinatal outcomes. ECMO=extracorporeal membrane oxygenation; ARDS=acute respiratory distress syndrome; PPROM=preterm premature rupture of membranes

Fig 4

Clinical manifestations of coronavirus disease 2019 (covid-19) in pregnant and recently pregnant women compared with non-pregnant women of reproductive age with covid-19 (part 1)

Fig 5

Clinical manifestations of coronavirus disease 2019 (covid-19) in pregnant and recently pregnant women compared with non-pregnant women of reproductive age with covid-19 (part 2)

Fig 6

Risk factors associated with severe coronavirus disease 2019 (covid-19) and all cause maternal death in pregnant and recently pregnant women (part 1). ICU=intensive care unit; NE=not estimable. Cut-off threshold is ≥35 years for age and ≥30 for body mass index. *Includes one or more studies with continuous measurement of risk factor

Fig 7

Risk factors associated with severe coronavirus disease 2019 (covid-19) and all cause maternal death in pregnant and recently pregnant women (part 2). ICU=intensive care unit; NE=not estimable