COVID-19 and the production of knowledge regarding recommendations during pregnancy: a scoping review

Objective to map the production of knowledge regarding recommendations for providing care to pregnant women dealing with the novel coronavirus. Method scoping review, using a broadened strategy to search databases and repositories, as well as the reference lists in the sources used. Data were collected and analyzed by two independent reviewers. Data were analyzed and synthesized in the form of a narrative. Results the final sample was composed of 24 records, the content of which was synthesized in these conceptual categories: clinical manifestations, diagnosis, treatment, working pregnant women, vaccine development, complications, prenatal care, vertical transmission, and placental transmissibility. It is recommended to confirm pregnancy and disease early on, to use technological resources for screening and providing guidance and support to pregnant women. Conclusion recommendations emphasize isolation, proper rest, sleep, nutrition, hydration, medications, and in the more severe cases, oxygen support, monitoring of vital signs, emotional support, and multiprofessional and individualized care. Medications should be used with caution due to a lack of evidence. Future research is needed to analyze the impact of the infection at the beginning of pregnancy and the psychological aspects of pregnant women infected with the virus.


Introduction
On December 31 st , 2019 China reported to the World Health Organization pneumonia cases of unknown etiology in the city of Wuhan, province of Hubei.
On January 9 th , 2020 the coronavirus, scientifically known as Severe Acute Respiratory Syndrome-Coronavirus (SARS-CoV-2), was identified as the most recent microorganism causing the human infection called COVID-19. Since then, this virus has crossed Chinese borders and caused a devastating pandemic, challenging health services and the society and leading to high levels of mortality that varies according to each country's epidemiological and social characteristics (1)(2)(3)(4) .
The dissemination of this disease led the WHO to declare on January 30 th , 2020 a "Public Health Emergency of International Importance", which requires actions to prevent its transmission and decrease the occurrence of new infections. Recommendations include the early detection of the disease, social isolation for the entire community, the reporting of cases, and to investigate and properly manage cases (5)(6) .
It is known that the main routes of SARS-COV-2 transmission are droplets of secretions from the respiratory tract of symptomatic or asymptomatic individuals who carry the virus, and contaminated objects. There is evidence that this pathogen is transmitted through feces (4) . There has been much effort to contain the contamination, considering that individuals with the SARS-COV-2 virus may be asymptomatic. When symptomatic, people tend to experience: fever, running nose, nasal congestion, dyspnea, malaise, loss of taste, and even more severe symptoms such as SARS. Complications are most common, and even lethal, among elderly individuals, immunosuppressed individuals, women during pregnancy and post-partum, and those with comorbidities (3,7) .
There is a gap in the knowledge concerning the implications of SARS-COV-2 during pregnancy.
Initially, the number of pregnant women infected was proportionally smaller than the population in general, however, when infected, these women became more vulnerable to the more severe manifestations of the disease (8)(9)(10) .
In this sense, in March 2020, the Brazilian Ministry of Health included pregnant women as a risk group for COVID-19 based on physiological changes that take place during pregnancy, which tend to aggravate infectious conditions due to the low tolerance to hypoxia observed in this population (6,11) . The decision to include pregnant women as risk group took into account prior knowledge regarding other viruses and even respiratory infectious caused by the H1N1 virus among pregnant women, which resulted in high rates of complications and mortality (11) .
Despite the sensible concern of international and national health agencies (4,11) , there is little scientific evidence on the novel coronavirus and even less evidence regarding the management of pregnant women testing positive for SARS-CoV-2 or suspected to have the infection. Therefore, given this scenario, the objective of this review is to map the production of knowledge regarding recommendations on care provided to pregnant women dealing with the novel coronavirus.

Method
This is a scoping review, defined as a way to map the main concepts that ground a field of research.
Because of the emergency of this topic and the low availability of scientific evidence on the topic, the choice for this methodology is justified because it contemplates all kinds of scientific literature, going beyond issues concerning the effectiveness of an intervention or experience with treatments or care. Five stages were followed in this study, as listed by Arksey and O'Malley, namely: identification of the research question, identification of relevant studies, selection of studies, mapping of information, and grouping, summary and report of results (12)(13) .
The question guiding this review was: "What is the The search strategy used in the different databases is described in Figure 1:
The Endnote Web software available online was used to properly store and organize the references obtained in the search. It allows for more than one researcher to automatically access the references, which is an important resource during the study selection process. Two independent reviewers accessed the same search results and verified the relevance of the studies identified. Disagreements regarding the inclusion of papers were resolved through a discussion among peers or the assessment of a third reviewer.
The methodological quality of the primary studies was not assessed, as this aspect is not taken into account in scoping reviews, however, data were collected using a form recommended by JBI, which is intended to facilitate the synthesis of information and quality of recommendations (14) .
Data were collected using an instrument that was adapted from this form to map information. This instrument addresses: publication information (year, authors, country of origin); study's objectives; methodological characteristics (characteristics of the study population); main results (outcome measures and main findings or contributions); context (care setting and relevant cultural and social factors) (12,13) .
The results collected were presented in tables and discussed in the form of a narrative, based on the classification of conceptual categories.
The PRISMA checklist was adopted to ensure the quality of this study as it ensures the parts composing this review are appropriate (15) .

Results
Regarding the selection and inclusion of papers, the specific PRISMA extension for scoping reviews (PRISMA-ScR) was used, which is ideal to describe in detail the decision process of research considering the method used (16) . As shown in Figure  All the studies were published in 2020, were written in English and published in different periodicals, not limited to those specifically from the fields of Rev. Latino-Am. Enfermagem 2020;28:e3348.
obstetrics and gynecology, but also included the fields of epidemiology, infectious diseases, microbiology, immunology, pathology, radiology, and pediatrics. The studies' specific characteristics are presented in detail in Figure 3.

Regarding the papers' methodological designs,
there were empirical studies (n=12) and theoretical studies (n=12). Eight were retrospective descriptive studies, six were reviews, five were opinion papers, three were case studies, and two were experience reports.  Rev. Latino-Am. Enfermagem 2020;28:e3348.
CLINICAL MANIFESTATIONS: the pregnant women's clinical aspects are similar to those of the general population DIAGNOSIS (guide pregnant women regarding the COVID-19 signs and symptoms and make an initial assessment through telephone)

Laboratory and imaging exams:
-Polymerase chain reaction with reverse transcriptase (RT PCR); -Molecular panel of respiratory viruses; -Blood count; -Blood culture; -C-reactive protein -Liver function tests -Imaging exams.

Recent mobility history:
-Frequently ask the history of travels and mobility of pregnant women (recommend isolation and investigation); -Isolation may lead to anxiety and depression, thus psychological support is recommended.
TREATMENT: there is no official protocol to be followed with a definitive treatment for COVID-19, however, care converges to the following pillars: 1-Admit the patient to an isolation ward 2-Provide supportive care 3-Assess the results of exams 4-Closely monitor vital signs and hemodynamic stability

5-Monitor obstetrical care
Antiviral therapy: use of retroviral agents, little scientific evidence.
-Remdesivir: acts on viral nucleotides inhibiting their replication and has shown to be effective when used in SARS-COV-2 in vitro; -Lopinavir-ritonavir: viral protease inhibitor drug that has been chosen as a drug regimen because it is relatively safe during pregnancy; -Interferon-alpha-2a: inhibits viral replication and stimulates the body's immune response. Its use in early pregnancy can affect fetal growth and development; -Chloroquine phosphate: antimalarial with antiviral activity, which interrupts the reception of the virus by cells and their chain of transmission. In pregnant women, a higher dose is required, but systolic hypotension was identified as a side effect.

Contraindicated for pregnant women: even though promising in the treatment of COVID-19
-Ribavirin: antiviral with a teratogenicity effect that induces embryonic lethality or craniofacial and embryonic limb deformities; -Baricitinib: animal studies have shown potential embryotoxicity.
Antibiotic therapy: part of the treatment plan of most individuals infected by SARS-CoV-2, due to extensive lung damage caused by the virus. When starting the antibiotic therapy is a controversial topic as opinions diverge.
Corticosteroids: have been contraindicated because by delaying infection control, it worsens one's respiratory condition and is associated with poor neonatal outcomes.

Exceptions:
methylprednisolone: in the short term for severe dyspnea and hypoxemia. Avoid in pregnant women for additional assessments. Have been used only in the postoperative of C-sections; -betamethasone: recommended in cases of premature births or when there is a need to resolve a pregnancy in advance.

WORKING PREGNANT WOMEN
-More flexible working opportunities; -Decrease physical contact: telephones, videoconference, and administrative activities to avoid direct interpersonal contact; -Pregnant women with gestational age greater than 28 weeks or with risk factors/underlying comorbidities should consider leaving the workplace and staying at home. -Recommend the use of telemedicine videoconference platforms as well as technological resources to clarify doubts and screen for signs and symptoms; -Health workers providing face-to-face consultations should pay attention to fetal vitality, movement, and heart rate, especially in the third trimester of pregnancy with increased maternal anxiety; -Heart rate monitoring and ultrasounds are essential for assessing fetal wellbeing; -Health workers can assess some parameters remotely such as measurement of uterine height, waist circumference, weight, fetal movement, and blood pressure.  recommendations as they tend to present poor outcomes when contaminated (8)(9)11) .
The pandemic caused by the novel coronavirus remains very serious, highly contagious, and has affected the world population beyond risk groups. Note the importance of sensitizing and making individuals aware of its severity to reinforce preventive measures to decrease and control this infection (4,(41)(42) .
Most of the studies were conducted in China because it is where the novel coronavirus originated. Additionally, even though most studies present few clinical cases, attention should be paid to these studies as they report evidence that is currently available and it is extremely relevant to identify the main clinical manifestations dealing with this disease during pregnancy.
Nevertheless, a review addressing COVID-19 during pregnancy reports other signs and symptoms, which even if at a lower frequency, may occur and should be taken into account to reach an early diagnosis (29) .
In terms of diagnosis, there is a concern with early detection of the disease. Thus, pregnant women should be recommended to learn about the specific signs of COVID-19 in order to decrease their exposure to health services. An initial assessment performed online is recommended to determine whether a faceto-face consultation is necessary (17) . Note, however, that a retrospective study (33) compared the clinical aspects of pregnant and non-pregnant women and verified that symptoms are atypical among pregnant women, which would probably hinder the disease's early detection in this group.
Comparative studies indicate that CT scans are more sensitive than RT-PCR, as well as more precise and time-efficient, presenting a lower number of falsenegatives. The clinical findings of imaging exams of pregnant women are similar to those of non-pregnant patients (28)(29)33,35) . Despite its various advantages, the routine use of CT scans should be avoided due to the risk of exposure to radiation. Note that none of the radiological exams replaces the molecular confirmation of COVID-19 (18) .
As for the treatment of positive pregnant women, there is not a consensual and official protocol so far. and monitoring the intake of fluids and electrolytes.
Vital signs and oxygen saturation levels should be closely monitored, as well as the frequency of the fetus' heart rate to observe the progression of the pregnancy, planning individualized delivery, and having a multiprofessional team to provide care (17)(18)22,29,36,39) . The studies also highlight that this time requires pregnant women have more flexible work opportunities, being able to leave from work when gestational age is greater than 28 weeks or when there are risk factors or underlying comorbidities (31,(39)(40) . These precautions are needed considering that being infected by COVID-19 during pregnancy tends to result in negative outcomes, such as spontaneous abortion, premature rupture of membranes, restricted intrauterine growth, fetal distress, and premature labor and birth (18)(19)24,(27)(28)(29)32,34,36,(38)(39)(40) .
Thus, in this context, prenatal care is essential throughout the pregnancy, especially during the third trimester when the final stages of development take place and maternal anxiety is at its highest, a period that requires a larger number of prenatal inspections.
Therefore, monitoring heart rate and ultrasound are essential to assess fetal wellbeing, and especially among women infected with the novel coronavirus (18,23,26) .
This scoping review's limitations include the fact that the recent beginning of the pandemic and intense flow of information prevents the supply of stable