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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

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          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 26 June 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

          77 studies were included. Overall, 10% (95% confidence interval 7% to14%; 28 studies, 11 432 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 (39%). Compared with non-pregnant women of reproductive age, pregnant and recently pregnant women with covid-19 were less likely to report symptoms of fever (odds ratio 0.43, 95% confidence interval 0.22 to 0.85; I 2=74%; 5 studies; 80 521 women) and myalgia (0.48, 0.45 to 0.51; I 2=0%; 3 studies; 80 409 women) and were more likely to need admission to an intensive care unit (1.62, 1.33 to 1.96; I 2=0%) and invasive ventilation (1.88, 1.36 to 2.60; I 2=0%; 4 studies, 91 606 women). 73 pregnant women (0.1%, 26 studies, 11 580 women) with confirmed covid-19 died from any cause. Increased maternal age (1.78, 1.25 to 2.55; I 2=9%; 4 studies; 1058 women), high body mass index (2.38, 1.67 to 3.39; I 2=0%; 3 studies; 877 women), chronic hypertension (2.0, 1.14 to 3.48; I 2=0%; 2 studies; 858 women), and pre-existing diabetes (2.51, 1.31 to 4.80; I 2=12%; 2 studies; 858 women) were associated with severe covid-19 in pregnancy. Pre-existing maternal comorbidity was a risk factor for admission to an intensive care unit (4.21, 1.06 to 16.72; I 2=0%; 2 studies; 320 women) and invasive ventilation (4.48, 1.40 to 14.37; I 2=0%; 2 studies; 313 women). Spontaneous preterm birth rate was 6% (95% confidence interval 3% to 9%; I 2=55%; 10 studies; 870 women) in women with covid-19. The odds of any preterm birth (3.01, 95% confidence interval 1.16 to 7.85; I 2=1%; 2 studies; 339 women) was high in pregnant women with covid-19 compared with those without the disease. A quarter of all neonates born to mothers with covid-19 were admitted to the neonatal unit (25%) and were at increased risk of admission (odds ratio 3.13, 95% confidence interval 2.05 to 4.78, I 2=not estimable; 1 study, 1121 neonates) than those born to mothers without covid-19.

          Conclusion

          Pregnant and recently pregnant women are less likely to manifest covid-19 related symptoms of fever and myalgia than non-pregnant women of reproductive age and are potentially more likely to need intensive care treatment for covid-19. Pre-existing comorbidities, high maternal age, and high body mass index seem to be risk factors for severe covid-19. Preterm birth rates are high in pregnant women with covid-19 than in pregnant women without the disease.

          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.

          Related collections

          Most cited references71

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            Clinical Characteristics of Coronavirus Disease 2019 in China

            Abstract Background Since December 2019, when coronavirus disease 2019 (Covid-19) emerged in Wuhan city and rapidly spread throughout China, data have been needed on the clinical characteristics of the affected patients. Methods We extracted data regarding 1099 patients with laboratory-confirmed Covid-19 from 552 hospitals in 30 provinces, autonomous regions, and municipalities in mainland China through January 29, 2020. The primary composite end point was admission to an intensive care unit (ICU), the use of mechanical ventilation, or death. Results The median age of the patients was 47 years; 41.9% of the patients were female. The primary composite end point occurred in 67 patients (6.1%), including 5.0% who were admitted to the ICU, 2.3% who underwent invasive mechanical ventilation, and 1.4% who died. Only 1.9% of the patients had a history of direct contact with wildlife. Among nonresidents of Wuhan, 72.3% had contact with residents of Wuhan, including 31.3% who had visited the city. The most common symptoms were fever (43.8% on admission and 88.7% during hospitalization) and cough (67.8%). Diarrhea was uncommon (3.8%). The median incubation period was 4 days (interquartile range, 2 to 7). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (CT) (56.4%). No radiographic or CT abnormality was found in 157 of 877 patients (17.9%) with nonsevere disease and in 5 of 173 patients (2.9%) with severe disease. Lymphocytopenia was present in 83.2% of the patients on admission. Conclusions During the first 2 months of the current outbreak, Covid-19 spread rapidly throughout China and caused varying degrees of illness. Patients often presented without fever, and many did not have abnormal radiologic findings. (Funded by the National Health Commission of China and others.)
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              Presenting Characteristics, Comorbidities, and Outcomes Among 5700 Patients Hospitalized With COVID-19 in the New York City Area

              There is limited information describing the presenting characteristics and outcomes of US patients requiring hospitalization for coronavirus disease 2019 (COVID-19).
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                Author and article information

                Contributors
                Role: senior research fellow in epidemiology and women’s health
                Role: researcher
                Role: medical officer
                Role: medical student
                Role: medical student
                Role: medical student
                Role: medical student
                Role: medical student
                Role: medical student
                Role: medical student
                Role: medical student
                Role: researcher
                Role: chief consultant of women’s health
                Role: researcher
                Role: research fellow
                Role: clinical epidemiologist
                Role: medical specialist
                Role: managing editor
                Role: senior lecturer and consultant in respiratory medicine
                Role: professor of obstetrics and maternal-fetal medicine
                Role: infectious disease consultant
                Role: doctor of public health
                Role: medical officer
                Role: public health specialist
                Role: medical officer
                Role: professor in global infectious disease epidemiology
                Role: acting head of maternal and perinatal health unit
                Role: paediatric infectious disease specialist
                Role: senior lecturer in biostatistics
                Role: professor of maternal and perinatal health
                Journal
                BMJ
                BMJ
                BMJ-UK
                bmj
                The BMJ
                BMJ Publishing Group Ltd.
                0959-8138
                1756-1833
                2020
                01 September 2020
                : 370
                : m3320
                Affiliations
                [1 ]Institute of Applied Health Research, University of Birmingham, Birmingham, UK
                [2 ]WHO Collaborating Centre for Global Women’s Health, Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK
                [3 ]Clinical Biostatistics Unit, Hospital Universitario Ramón y Cajal (IRYCIS), Madrid, Spain
                [4 ]CIBER Epidemiology and Public Health (CIBERESP), Madrid, Spain
                [5 ]UNDP/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 ]Birmingham Medical School, University of Birmingham, Birmingham, UK
                [7 ]Division of Birth Cohort Study, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
                [8 ]Department of Woman and Child Health Care, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
                [9 ]Department of Obstetrics and Gynaecology, Guangzhou Women and Children’s Medical Centre, Guangzhou Medical University, Guangzhou, China
                [10 ]Netherlands Satellite of the Cochrane Gynaecology and Fertility Group, Amsterdam University Medical Centre, Amsterdam, Netherlands
                [11 ]Department of Obstetrics and Gynaecology, Amsterdam University Medical Centre, Amsterdam, Netherlands
                [12 ]Blizard Institute, Queen Mary University of London, London, UK
                [13 ]Barts Health NHS Trust, London, UK
                [14 ]St George’s, University of London, London, UK
                [15 ]Elizabeth Glaser Paediatric AIDS Foundation, Washington DC, USA
                [16 ]Women’s Health Research Unit, Queen Mary University of London, London, UK
                [17 ]Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham, UK
                Author notes
                Correspondence to: S Thangaratinam s. thangaratinam.1@ 123456bham.ac.uk (or @thangaratinam on Twitter)
                Author information
                http://orcid.org/0000-0002-4254-460X
                Article
                allj058888
                10.1136/bmj.m3320
                7459193
                32873575
                74f25f6f-5a17-4558-9ae0-83c44b7a9593
                © 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.

                This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

                History
                : 23 August 2020
                Categories
                Research
                2474

                Medicine
                Medicine

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