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      Maternal and neonatal outcomes associated with COVID-19 infection: A systematic review

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          Abstract

          Background

          COVID-19 has created an extraordinary global health crisis. However, with limited understanding of the effects of COVID-19 during pregnancy, clinicians and patients are forced to make uninformed decisions.

          Objectives

          To systematically evaluate the literature and report the maternal and neonatal outcomes associated with COVID-19.

          Search strategy

          PubMed, MEDLINE, and EMBASE were searched from November 1 st, 2019 and March 28 th, 2020.

          Selection criteria

          Primary studies, reported in English, investigating COVID-19-positive pregnant women and reporting their pregnancy and neonatal outcomes.

          Data collection and analysis

          Data in relation to clinical presentation, investigation were maternal and neonatal outcomes were extracted and analysed using summary statistics. Hypothesis testing was performed to examine differences in time-to-delivery. Study quality was assessed using the ICROMS tool.

          Main results

          Of 73 identified articles, nine were eligible for inclusion (n = 92). 67.4% (62/92) of women were symptomatic at presentation. RT-PCR was inferior to CT-based diagnosis in 31.7% (26/79) of cases. Maternal mortality rate was 0% and only one patient required intensive care and ventilation. 63.8% (30/47) had preterm births, 61.1% (11/18) fetal distress and 80% (40/50) a Caesarean section. 76.92% (11/13) of neonates required NICU admission and 42.8% (40/50) had a low birth weight. There was one indeterminate case of potential vertical transmission. Mean time-to-delivery was 4.3±3.08 days (n = 12) with no difference in outcomes (p>0.05).

          Conclusions

          COVID-19-positive pregnant women present with fewer symptoms than the general population and may be RT-PCR negative despite having signs of viral pneumonia. The incidence of preterm births, low birth weight, C-section, NICU admission appear higher than the general population.

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          Most cited references33

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          Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

          Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p<0·0001), and d-dimer greater than 1 μg/mL (18·42, 2·64–128·55; p=0·0033) on admission. Median duration of viral shedding was 20·0 days (IQR 17·0–24·0) in survivors, but SARS-CoV-2 was detectable until death in non-survivors. The longest observed duration of viral shedding in survivors was 37 days. Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.
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            Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

            Summary Background Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection. Methods Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation. Findings All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus. Interpretation The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy. Funding Hubei Science and Technology Plan, Wuhan University Medical Development Plan.
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              Sensitivity of Chest CT for COVID-19: Comparison to RT-PCR

              Summary In a series of 51 patients with chest CT and RT-PCR assay performed within 3 days, the sensitivity of CT for COVID-19 infection was 98% compared to RT-PCR sensitivity of 71% (p<.001). Introduction In December 2019, an outbreak of unexplained pneumonia in Wuhan [1] was caused by a new coronavirus infection named COVID-19 (Corona Virus Disease 2019). Noncontrast chest CT may be considered for early diagnosis of viral disease, although viral nucleic acid detection using real-time polymerase chain reaction (RT-PCR) remains the standard of reference. Chung et al. reported that chest CT may be negative for viral pneumonia of COVID-19 [2] at initial presentation (3/21 patients). Recently, Xie reported 5/167 (3%) patients who had negative RT-PCR for COVID-19 at initial presentation despite chest CT findings typical of viral pneumonia [3]. The purpose of this study was to compare the sensitivity of chest CT and viral nucleic acid assay at initial patient presentation. Materials and Methods The retrospective analysis was approved by institutional review board and patient consent was waived. Patients at Taizhou Enze Medical Center (Group) Enze Hospital were evaluated from January 19, 2020 to February 4, 2020. During this period, chest CT and RT-PCR (Shanghai ZJ Bio-Tech Co, Ltd, Shanghai, China) was performed for consecutive patients who presented with a history of 1) travel or residential history in Wuhan or local endemic areas or contact with individuals with individuals with fever or respiratory symptoms from these areas within 14 days and 2) had fever or acute respiratory symptoms of unknown cause. In the case of an initial negative RT-PCR test, repeat testing was performed at intervals of 1 day or more. Of these patients, we included all patients who had both noncontrast chest CT scan (slice thickness, 5mm) and RT-PCR testing within an interval of 3 days or less and who had an eventual confirmed diagnosis of COVID-19 infection by RT-PCR testing (Figure 1). Typical and atypical chest CT findings were recorded according to CT features previously described for COVD-19 (4,5). The detection rate of COVID-19 infection based on the initial chest CT and RT-PCR was compared. Statistical analysis was performed using McNemar Chi-squared test with significance at the p <.05 level. Figure 1: Flowchart for patient inclusion. Results 51 patients (29 men and 22 women) were included with median age of 45 (interquartile range, 39- 55) years. All patients had throat swab (45 patients) or sputum samples (6 patients) followed by one or more RT-PCR assays. The average time from initial disease onset to CT was 3 +/- 3 days; the average time from initial disease onset to RT-PCR testing was 3 +/- 3 days. 36/51 patients had initial positive RT-PCR for COVID-19. 12/51 patients had COVID-19 confirmed by two RT-PCR nucleic acid tests (1 to 2 days), 2 patients by three tests (2-5 days) and 1 patient by four tests (7 days) after initial onset. 50/51 (98%) patients had evidence of abnormal CT compatible with viral pneumonia at baseline while one patient had a normal CT. Of 50 patients with abnormal CT, 36 (72%) had typical CT manifestations (e.g. peripheral, subpleural ground glass opacities, often in the lower lobes (Figure 2) and 14 (28%) had atypical CT manifestations (Figure 3) [2]. In this patient sample, difference in detection rate for initial CT (50/51 [98%, 95% CI 90-100%]) patients was greater than first RT-PCR (36/51 [71%, 95%CI 56-83%]) patients (p<.001). Figure 2a: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2b: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2c: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 2d: Examples of typical chest CT findings compatible with COVID-19 pneumonia in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 74 years old with fever and cough for 5 days. Axial chest CT shows bilateral subpleural ground glass opacities (GGO). B, female, 55 years old, with fever and cough for 7 days. Axial chest CT shows extensive bilateral ground glass opacities and consolidation; C, male, 43 years old, presenting with fever and cough for 1 week. Axial chest CT shows small bilateral areas of peripheral GGO with minimal consolidation; D, female, 43 years old presenting with fever with cough for 5 days. Axial chest CT shows a right lung region of peripheral consolidation. Figure 3a: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3b: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3c: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Figure 3d: Examples of chest CT findings less commonly reported in COVID-19 infection (atypical) in patients with epidemiological and clinical presentation suspicious for COVID-19 infection. A, male, 36 years old with cough for 3 days. Axial chest CT shows a small focal and central ground glass opacity (GGO) in the right upper lobe; B, female, 40 years old. Axial chest CT shows small peripheral linear opacities bilaterally. C, male, 38 years old. Axial chest CT shows a GGO in the central left lower lobe; D, male, 31 years old with fever for 1 day. Axial chest CT shows a linear opacity in the left lower lateral mid lung. Discussion In our series, the sensitivity of chest CT was greater than that of RT-PCR (98% vs 71%, respectively, p<.001). The reasons for the low efficiency of viral nucleic acid detection may include: 1) immature development of nucleic acid detection technology; 2) variation in detection rate from different manufacturers; 3) low patient viral load; or 4) improper clinical sampling. The reasons for the relatively lower RT-PCR detection rate in our sample compared to a prior report are unknown (3). Our results support the use of chest CT for screening for COVD-19 for patients with clinical and epidemiologic features compatible with COVID-19 infection particularly when RT-PCR testing is negative.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: ValidationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Data curationRole: Formal analysisRole: InvestigationRole: VisualizationRole: Writing – original draftRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: InvestigationRole: Project administrationRole: Writing – review & editing
                Role: SupervisionRole: Writing – review & editing
                Role: SupervisionRole: ValidationRole: Writing – review & editing
                Role: SupervisionRole: ValidationRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                4 June 2020
                2020
                4 June 2020
                : 15
                : 6
                : e0234187
                Affiliations
                [1 ] Department of Obstetrics and Gynaecology, Monash University, Clayton, Victoria, Australia
                [2 ] School of Public Health and Preventive Medicine, Monash University, Melbourne, Victoria, Australia
                [3 ] Fetal Monitoring Unit, Monash Medical Centre, Monash Health, Clayton, Victoria, Australia
                [4 ] Melbourne Medical School, The University of Melbourne, Parkville, Victoria, Australia
                [5 ] Department of Pharmacy, University of Copenhagen, København, Denmark
                [6 ] Newborn Services, Western Health, Sunshine, Victoria, Australia
                [7 ] Department of Gynecology and Obstetrics, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, São Paulo, Brazil
                Univesity of Iowa, UNITED STATES
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-6099-3671
                http://orcid.org/0000-0002-9125-043X
                Article
                PONE-D-20-12795
                10.1371/journal.pone.0234187
                7272020
                32497090
                308d0739-b20e-4deb-b7a8-470f23bb5f3e
                © 2020 Smith et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 1 May 2020
                : 11 May 2020
                Page count
                Figures: 3, Tables: 2, Pages: 13
                Funding
                The authors received no specific funding for this work.
                Categories
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