1 INTRODUCTION

Since the detection of SARS-CoV-2, responsible for the COVID-19 infection, which was later declared a pandemic by the World Health Organization (WHO), it has infected more than 105 million people and led to more than two million deaths (World Health Organization, WHO, 2021). Pregnancy conveys particular vulnerabilities in relation to this infection. The gestational period is a unique, particular immune status, in which the pregnant woman needs to acquire tolerance to the allogeneic embryo/foetus and, at the same time, protect herself and the concept from pathogens. In this context, three immunological stages are described: pre-inflammatory (moment of implantation of the placenta), which occurs in the first term; anti-inflammatory (when the adaptation provides foetal growth and development), in the second term and, finally, pro-inflammatory, in the third term, which consists in preparing for the expulsion of the foetus (childbirth; Mor et al., 2017).

During pregnancy, the physiological changes in the respiratory tract, such as edema and increased pulmonary expansion, turn the pregnant woman more susceptible to respiratory viral infections. Thus, when SARS-Cov-2 infection is associated with pregnancy, increased inflammatory processes are observed, mainly in the first and third trimesters (pre-and pro-inflammatory states), exacerbating the severity of the cases (Liu, Wang, et al., 2020).

The particularities of pregnancy associated with COVID-19 infection turn obstetric care into a constant challenge (Poon et al., 2020). Hence, as this is an emerging disease, hardly explored concerning the effects on pregnant women/foetuses and infants, and given the severe results of previous pandemics, the development of this study is justified.

The aim of this scoping review was to map clinical characteristics and the evolution of pregnancies in pregnant women with confirmed diagnosis of SARS-CoV-2 infection.

2 METHOD 2.1 Design

Scoping review according to the method of the Joanna Briggs Institute (JBI), aiming to map the scientific evidence associated with key concepts related to a specific phenomenon (Colquhoun et al., 2014; Lockwood & Tricco, 2020; Peters et al., 2015; Tricco et al., 2018. The review was registered at osf.io/hp25n.

2.2 Search methods

The research question was based on the Population, Concept and Context (PCC) strategy, establishing P for population, C for pregnancy and C for clinical and obstetric aspects of SARS-Cov-2/COVID-19 infection. Based on these definitions, the guiding question was ‘What evidence is available in the literature about the clinical and obstetric aspects of SARS-Cov-2 infection during pregnancy?’

Data collection took place on 15 July 2020, and searches were carried out in the U.S. National Library of Medicine National Institutes of Health (PubMed), Latin American and Caribbean Literature in Health Sciences (LILACS), Web of Science and Cumulative Index to Nursing and Allied Health Literature (CINAHL). The choice of the databases was due to the number of primary health articles indexed. PubMed is a free search engine with access to Medline database that registers important publications of American and world literature; CINAHL is a specific database for nursing and health sciences; LILACS contains production from Latin America and the Caribbean, and the Web of Science allows consultation of other databases. The aim of the diversity of bases was to contemplate world production on the theme.

Two reviewers, both holding a PhD, conducted the research independently, using controlled descriptors from the Medical Subject Headings (MeSH), the CINAHL Headings and the Health Sciences Descriptors: ‘COVID-19’, ‘Coronavirus Infections’ and ‘Pregnancy’. The descriptors were combined in different ways, aiming to broaden the searches. The terminological variations in the different languages, as well as synonyms, were used with the Boolean operators AND for simultaneous occurrence of subjects and OR for the occurrence of their respective synonyms.

In this review, we included studies on the subject of coronavirus infection and pregnancy that addressed clinical, obstetric characteristics and outcomes in women with laboratory proof of infection using PCR (polymerase chain reaction), published in Portuguese, Spanish and English, dated 2020. The exclusion criteria included review studies, editorials, expert opinions and studies whose samples included pregnant women with clinical suspicions of the disease in their analysis. The level of evidence was not considered as an exclusion criterion because it is a new topic, with a reduced possibility of finding articles with a better level of evidence. Thus, 553 articles were identified in the four databases, and one article was added in the search based on the references analysed. The PRISMA method—Preferred Reporting Items for Systematic Reviews and Meta-Analyses (Tricco et al., 2018)—was adopted to systematize the inclusion process of the studies (Figure 1).

Selection flow of review articles according to PRISMA

2.3 Search outcomes

In the first stage, the choice of the articles was based on the analysis of titles and abstracts. Then, the full version was read for the final selection, extracting 35 studies from the databases. The sources of the analysed databases were PubMed®, CINAHL, LILACS and Web of Science™. Articles were excluded when duplicates; written in non-established languages; beyond the topic; that did not meet the eligibility criteria (cases without laboratory proof of infection), literature review articles and qualitative research/expert opinion/editorial.

2.4 Quality appraisal

The Joanna Briggs Institute Appraisal Tools (JBI, 2014) were used to evaluate the methodological quality and risk of bias of the included studies. The tools allowed to classify the articles as high risk of bias (scores less than 50%), moderate risk of bias (scores between 50% and 70%) and low risk of bias (scores above 70%). The level of evidence was classified according to the type of study, according to evidence level II of Melnyk and Fineout-Overholt (2005).

2.5 Data extraction and synthesis

The data were synthesized by two pairs of independent researchers. An instrument structured by the researchers, tested through a pilot study, was used to extract the data from the studies, following the guidelines of the JBI (JBI, 2014), which included the identification of the article, year and place of the study; the methodological characteristics; the evaluation of the methodological rigour and the notes and discussions about the thematic focus of this scoping review. The extracted information was tabulated for data synthesis, and the analysis of the results was descriptive, showing a synthesis of each primary study included in this review.

3 RESULTS 3.1 Characterization of the included studies

After the analysis by the four researchers, given the inclusion and exclusion criteria, 35 articles were selected for qualitative synthesis. All the articles were published in 2020, in English. Among the included studies, 77.1% were case studies, 20% descriptive reports and one cohort study (2.9%).

The application of tools to assess the methodological quality and risk of bias from the Joanna Briggs Institute Appraisal Tools revealed a high risk of bias (score = 42%) in one study, moderate risk (scores between 50 and 70%) in seven (20%) and low risk of bias in 27 (77.1%) studies. All of the articles included presented a description of the diagnostic method and used PCR as a reference standard for the diagnosis of COVID-19 in pregnant women. The most neglected item was the complete description of the treatments employed. Despite the methodological limitations found, it was decided not to exclude the articles as this is a recent topic.

Regarding the producer countries, 34.3% of the articles came from China and 31.4% from the United States, although studies on the subject were produced more widely across the world. When adding up the studies, 685 pregnant women were found who had COVID-19, ranging from asymptomatic to severe cases of the disease. The flowchart displays the exclusion diagram, according to each database investigated (Figure 2). Table 1 shows the country of origin, the number of pregnant women included (N) and the methodological quality assessment score by JBI Appraisal Tools.

Article selection flow and reasons for exclusion from the review, according to the PRISMA guidelines, 2020

TABLE 1. Synthesis of outcomes and evidence of selected articles (N = 35), 2020 Country/reference Number of participants Risk of biasa Evidenceb Australia (Lowe & Bopp, 2020) 1 75% VI Canada (Kirtsman et al., 2020) 1 87.50% VI Canada (Koumoutsea et al., 2020) 2 87.50% VI China (Cao et al., 2020) 10 75% VI China (Chen, Guo, et al., 2020) 9 87.50% VI China (Liu et al., 2020) 15 75% V China (Lu et al., 2020) 1 100% VI China (Peng et al., 2020) 1 75% VI China (Wen et al., 2020) 1 87.50% VI China (Wu et al., 2020) 13 50% V China (Xia et al., 2020) 1 75% VI China (Xiong et al., 2020) 1 50% VI China (Yu, Li, et al., 2020) 7 87.50% V China (Yu, Fan, et al., 2020) 1 50% VI China (Zeng et al., 2020) 16 75% V England (Knight et al., 2020) 427 42% IV France (Vivanti et al., 2020) 1 87.50% VI Italy (Ferraiolo et al., 2020) 1 100% VI Peru (Alzamora et al., 2020) 1 87.50% VI Portugal (Lyra et al., 2020) 1 100% VI Spain (Mendoza et al., 2020) 42 50% V Spain (Pereira et al., 2020) 60 100% VI The Netherlands (Grimminck et al., 2020) 1 100% VI Turkey (Kalafat et al., 2020) 1 87.50% VI United States (Baergen & Heller, 2020) 20 62.50% V United States (Blauvelt et al., 2020) 1 87.50% VI United States (Browne et al., 2020) 1 100% VI United States (Futterman et al., 2020) 2 87.50% VI United States (Hantoushzadeh et al., 2020) 9 87.50% VI United States (Iqbal et al., 2020) 1 100% VI United States (Rosen et al., 2020) 1 87.50% VI United States (Shena et al., 2020) 16 62.50% V United States (Silverstein et al., 2020) 2 87.50% VI United States (Vallejo & Ilagan, 2020) 1 87.50% VI United States (Qadri & Mariona, 2020) 16 50% VI a RB: Risk of bias (JBI critical appraisal). b ELII: Evidence level II (Melnyk & Fineout-Overholt, 2005). 3.2 Characterization of pregnant women included in the studies

When the maternal age was analysed, a mean of 31.2 ± 4.5 years was found, obtained by analysing the age or mean ages presented in the studies. The stratification by age group showed a predominance in women over the age of 30 years.

Regarding parity, multiparous women were predominant in 13 case studies, and the prevalence of multiparity ranged from 52.4% to 100% of cases. In the studies evaluated, however, no predominance of cases associated with parity was found.

In the evaluation of the gestational term in which the infection by COVID-19 occurred, infected pregnant women were found in the three trimesters, although with a higher prevalence in the third gestational trimester. The percentage of infection in the third trimester ranged from 38.5% to 100%.

The presence of comorbidities in pregnancy was evaluated in 30 studies (85.7%), and, in eight (26.7%), the pregnant women had no comorbidities. Twenty-two studies described comorbidities, with prevalence rates ranging from 2.3% to 100% of the pregnant women evaluated. Among the most frequent comorbidities, there was a predominance of endocrine and metabolic diseases and/or alterations; obesity was reported in four case studies, ranging between 43% and 69% of the infected pregnant women. Gestational diabetes (GDM) was described in three cases, ranging from 6.7% to 50% of pregnant women, and Type II diabetes mellitus was reported in three studies; hypothyroidism was evidenced in six studies, with a frequency of 5% to 14.5% of pregnant women included in the studies.

Conditions of the cardiovascular system during pregnancy were also associated with COVID-19 infection, with cases of pre-eclampsia. One study pointed out that 15% of the infected pregnant women had hypertensive syndromes. Although less frequent, pregnant women with chronic heart disease infected by COVID-19 were observed. Two studies described the need for differential diagnosis of severe infection by COVID-19 in cases of pre-eclampsia and HELLP.

Other comorbidities such as asthma; chronic neutropenia with recurrent bacterial infections, co-infection by the Influenza virus; thalassemia trait or thalassemia; anaemia; post-fertilization pregnancies; twin pregnancy; deep vein thrombosis, ulcerative colitis; systemic lupus erythematosus without renal impairment and migraine have been described in pregnant women affected by COVID-19.

Pregnancy complications such as intrauterine growth restriction and premature labour have also been reported. One study in particular described Streptococcus B infection; nuchal cord; macrosomal foetus; placenta accreta; postpartum atony and placenta previa with complications. Table 2 describes the variables age, parity, gestational term in which COVID-19 infection occurred and maternal comorbidities.

TABLE 2. Clinical and obstetric characteristics of pregnant women infected by COVID-19 Reference Number of participants Maternal age/average Parity Gestational term of infection Comorbidity Primiparous Multiparous 1st 2nd 3rd Present Cardiovascular Endocrine etabolic Others Alzamora et al. (2020) 01 41 No Yes (G3P2A0) - - Yes Yes - GDM Obese - Baergen and Heller (2020) 20 31.5 (16–40) 20% 80% - - 100% Yes 15% hypertensive syndromes 66% PE 5% DM II 5% HPT - Yesa Blauvelt et al. (2020) 01 34 No Yes (G4P3A0) - - Yes Yes - GDM Obese Asthma and smoking Browne et al. (2020) 01 33 Yes No - Yes - Yes - - - Asthma, migraine, twin pregnancy Cao et al. (2020) 10 30.5 (29–35) NI NI - - 100% Yes 30% PE 10% HPT - 10% anaemia 10% twins Chen, Guo, et al. (2020) 09 29.8 NI NI - - 100% Yes 11% PIH 11% PE - - 11% influenza Ferraiolo et al. (2020) 01 30 Yes No - - Yes No - - - - Futterman et al. (2020) 02 36 No 100% - 50% 50% No - - - - Grimminck et al. (2020) 01 31 Yes No - - Yes Yes HAC - - Lupus Hantoushzadeh et al. (2020) 09 43%—35 to 39 years 33% 67% - 12% 88% 88% - 28% GDM, 14% HPT 43% obese 28% pregnancy post IVF Iqbal et al. (2020) 01 34 No Yes (G7P5A1) - - Yes No - - - - Kalafat et al. (2020) 01 32 Yes No - - Yes Yes - - - Non-anaemic thalassemia Kirtsman et al. (2020) 01 40 No Yes (G2P1A0) - - Yes Yes - GDM> - Neutropenia and recurrent infections Knigth et al. (2020) 427 58%—20 to 34 years 38% 62% 5% 14% 81% Yes 7% PIH 1% cardiopathy 12% GDM,3% DM II 69% obese 7% asthma Koumoutsea et al. (2020) 02 31.5 No Yes - - Yes 100% 100% - 50% GDM 50% obese Asthma, chronic neutropenia, recurrent infections Liu, Li et al. (2020) 15 32 NI NI Yes Yes Yes 13.3% 6.7% Cardiopathy 6.7% GDM - 6.7% thalassemia Lowe and Bopp (2020) 01 31 Yes No - - Yes NI - - - - Lu et al. (2020) 01 22 Yes No - - Yes NI - - - - Lyra et al. (2020) 01 35 Yes No