An overview of newborn care in the COVID-19 context: an integrative review

Juliane Pagliari Araujo1, Katiucy Sturião dos Santos Campana1, Kelle Vieira Bussú1, Morgana Sczindrowski1, Luzia Borges Leal1, Adriana Valongo Zani1

1 State University of Londrina, PR, Brazil.

ABSTRACT

Objective: To investigate clinical manifestations, risk factors, treatment, and prevention of newborns affected by COVID-19 reported in the scientific literature. Method: This was an integrative review carried out in May 2020 in the LILACS, MEDLINE, and Virtual Health Library databases, via the combination of the controlled terms newborn, COVID-19, SARS-CoV-2. Results: Seven studies composed the final sample, five of which were from China, where the first cases of neonatal infection were reported. Discussion: Evidence-based practice is essential for neonatal care in light of the current pandemic context, which requires constant updates about therapeutic approaches. Conclusion: Prevention measures are important, because there are gaps related to COVID-19 treatment in newborns. Clinical manifestations can vary from respiratory symptoms to gastrointestinal and cutaneous symptoms. Although the cases reported seem to have been acquired in the postnatal period, more studies and evidence are needed to clarify the risk of vertical transmission.

DESCRIPTORS: Newborn; Coronavirus Infections; COVID-19; Respiratory Tract Diseases; Signs and symptoms; Disease Prevention.

INTRODUCTION

At the beginning of 2020, the world saw the emergence of a new virus, initially called the novel coronavirus. It was later officially classified by the International Committee on Taxonomy of Viruses as the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), and the disease that it caused was called the Coronavirus Disease-2019 (COVID-19)(1). The first case of the novel coronavirus was reported in the city of Wuhan, China, on December 31, 2019, and due to the rapid progression of cases, on March 11, 2020, it was declared a pandemic, causing profound repercussions in the health area and social and economic consequences in the world population(2-3). 

In general, SARS-CoV-2 presents low pathogenicity; however it can develop serious infections when it affects children, older adults, the immunosuppressed, and patients with comorbidities(4).

Considering the growing and elevated number of cases, health departments and hospitals have sought to develop and implement guidelines and protocols focusing on diagnosing, treating and preventing the spread of COVID-19. However, little quality evidence is available, increasing conflicting information(5). 

In the pediatric and neonatal population, this scarcity is even greater. Children are little affected by the disease, and most are asymptomatic or present mild symptoms. In this age group, the highest reported proportion of patients with severe disease was 10.6%, in infants younger than one year old, followed by 7.3% in children between one to five years old(6). Regarding newborns (NBs) and infections in neonatal intensive care units (NICUs), there are still few findings about severe acute neonatal diseases due to SARS-CoV-2.  However, many questions arise with regard to the transmission, treatment, clinical manifestations and prevention among this population(5).

Due to the absence of evidence about this topic and given the current pandemic reality, the present study aimed to investigate clinical manifestations, risk factors, treatment and prevention of newborns affected by COVID-19 reported in the scientific literature. 

METHOD

This was an integrative literature review, with the aim to broadly gather and summarize the results of studies and critically review relevant studies about a given topic, contributing to the deepening of knowledge about the investigated matter(7-8). 

This review was developed in six stages: 1) developing the guiding hypothesis or question according to the Population Interest Context (PICo) strategy, considering the following structure: P-newborns, I-prevention, Co-novel coronavirus pandemic. The guiding question was "What clinical manifestations, possible risk factors, treatments, and prevention of newborns with COVID-19 have been reported in the scientific literature?"

2) Defining the descriptors. The following descriptors were selected from the Descriptors in Health Sciences (DeCS) and MeSH (Medical Subject Headings: newborn, COVID-19, SARS-CoV-2. The terms were combined with Boolean operators "and" and "or" to ensure a broad search. 

3) sample selection: determining inclusion and exclusion criteria – a time to establish transparency to provide depth, quality and reliability of the selection. The studies were selected by five independent reviewers to ensure the reliability of the process. The inclusion criteria were studies published in full in the format of scientific articles, editorials, and recommendation manuals by institutions specialized in publications related to newborns and that answered at least one of the criteria of the guiding questions, given that the topic is extremely recent and little known, with no language or time limitations. Exclusion criteria were review articles, while duplicate articles were considered only once. Studies were extracted from the following databases: Latin American and Caribbean Health Sciences Literature (Lilacs) and Medical Literature Analysis and Retrieval System OnLine (MedLine) via PubMed (National Library of Medicine) and the Virtual Health Library (VHL). The search took place online in May 2020. The full publications were accessed via the Virtual Health Library (VHL) and PubMed portals. To select the scientific productions, the titles and abstracts were read according to the inclusion and exclusion criteria.

4) Critical analysis of the studies. In this stage, the researchers must have the necessary knowledge to observe the strong levels of evidence of the analyzed studies. To assess methodological quality, the following evidence classification was used:  Level 1: Systematic review of randomized clinical trials; Level 2: randomized clinical trials; Level 3: non-randomized clinical trials; Level 4: cohort and case-control; Level 5: systematic reviews of qualitative studies; and Level 6: expert opinions, case description(9).

5) Discussion of the results. In this phase, the studies were discussed in order to understand the topic under investigation. 6) Presentation of the integrative review. For purposes of clarity and organization, the information was presented in tables containing the most relevant information extracted from the article(10-11). In each table, the articles included in this review were identified with the letter A (article), followed by the numeral in the order in which they were described in Table 1. 

RESULTS

The search for studies was carried out considering studies between January and May 2020 in the following databases: the National Library of Medicine (MEDLINE/PubMed), the Virtual Health Library and LILACS. The descriptors registered in DeCS (Descriptors in Health Science) and MeSH (Medical Subject Headings) as well as keywords not located as controlled descriptors were combined as follows to create search strategies: COVID-19 or Coronavirus or SARS-CoV-2 and newborn. Therefore, the search identified a total of 58 studies, eight in VHL and 50 in MEDLINE/PUBMED. A first analysis was performed, based on an initial reading of the title and abstracts. Those that did not answer the guiding question, did not meet the previously established inclusion criteria, were review articles or were duplicates were excluded (n=49) resulting in 9 studies selected for full reading and analysis. After reading the 9 selected articles in full, two were excluded because the population was not NBs. Thus, seven studies composed the final sample of this integrative review. The flowchart regarding the selection of the studies is presented in Figure 1.

Figure 1- Flowchart of the study selection process. 2020. Londrina, Paraná, Brazil.

Source: Created by the authors.

Of the seven studies selected, five were from China, where the virus originated from and where the first cases of neonatal infection were reported. One manuscript was published in Iran, reporting a case of neonatal infection, and another publication was from the USA. Regarding language of publication, four studies were written in English and three in Chinese. All manuscripts were published in 2020.

The main information extracted from the selected studies was divided into: 1) general characteristics of the studies (title, year of publication, authors, journal, level of evidence and objective); 2) knowledge about the main results (clinical manifestations, risk factors, treatment and prevention) and 3) conclusions and considerations of the studies, which are presented respectively in Tables 1, 2 and 3.

Table 1- Design and objectives of the selected studies. 2020. Londrina, Paraná, Brazil.

Source: Created by the authors.

As for the information found in the studies about the main clinical manifestations observed, associated risk factors, and possible treatments and prevention, these are summarized and presented in Table 2.

Table 2-Main results related to clinical manifestations, risk factors, treatment and prevention. 2020. Londrina, Paraná, Brazil. 

  Source: Created by the authors.

A brief summary of the main considerations and conclusions of the selected studies is presented in Table 3.

Table 3 - Main conclusions and considerations of the selected studies. 2020. Londrina, Paraná, Brazil.

Source: Created by the authors. 

DISCUSSION

As of January 2021, more than 99 million cases of COVID-19 worldwide had been confirmed; however, the proportion of newborns with the disease has been extremely low. The studies indicated that transmission seems to occur in the postnatal period (5,13-14,18). However, some researchers considered the risk of vertical transmission(19-20). 

Regarding diagnostic procedures, the studies recommend screening all newborns admitted to NICUs by taking family history, testing for SARS-CoV-2 and isolation(13-14, 16-17), as well as conducting computerized tomography, blood count, arterial blood gas, chest x-ray, and stool and urine cultures, because differential diagnosis is essential to exclude other common upper respiratory tract viruses that cause pneumonia(14,16). 

With the exception of one study that did not mention clinical manifestations of COVID-19 infection in NBs(12,15), the others reported that symptoms can vary from mild respiratory symptoms to more severe evolutions with significant respiratory impairment and multiple organ failure, and that febrile condition may or may not be associated with the other symptoms(13-15, 17).

In relation to respiratory symptoms, NBs may have difficulty breathing, including tachypnea associated with mild subcostal retraction(16). Despite the scarce amount of evidence available about how this disease affects this population, authors suggest that respiratory distress may be related to pulmonary surfactant dysfunction in infants with the infection(13).

Because of their pulmonary immaturity, preterm newborns (PNB) may present surfactant dysfunction since it is a substance that begins to be produced around week 24 to 28 of gestation and reaching its peak around 35 weeks. The role of surfactant is to reduce the tension of the alveolar surface and thus avoid atelectasis and respiratory distress. However, when this does not occur, PNBs will present respiratory distress, which can be mild or even very severe depending on gestational age and the severity of the hyaline membrane disease caused by surfactant dysfunction. This condition can cause difficulty in differentiating the diagnosis of COVID-19, when NBs present risk factors, such as when a mother is diagnosed with COVID-19(21).

In addition to respiratory symptoms, other nonspecific symptoms were also observed. In one of the studies, a 17-day old NB presented gastrointestinal symptoms, such as vomiting, refusal of milk and diarrhea(14). Another case of COVID-19 in NBs was reported in Iran, and in addition to respiratory symptoms, the other clinical manifestations were skin rashes(16). These findings suggest that the clinical course of the disease in the NBs does not present similarly in all, and, because of the low prevalence of COVID-19 in this population, ongoing research is necessary to help identify suspected cases. 

Of all the cases of newborns affected by COVID-19 included in this review, none evolved with severity, and, despite little evidence available about the newborn population, to date, studies have shown that the clinical course of the disease is milder than in adult patients(16).

The provision of respiratory care for NBs should continue according to the current standards, and major changes in practice should be widely discussed to minimize possible harm(5). Furthermore, further discussions should also highlight symptomatic and individualized treatment(18). Some authors recommend administering surfactant and nitric oxide to NBs in severe cases(13,18), prescribing antivirals, but with caution due to the scarcity of evidence regarding its safety and efficacy in this population13, in addition to antibiotic therapy(16).

In confirmed cases of neonatal SARS-CoV-2 infection, it is essential to implement safe respiratory practices, including adequate isolation of the NB, adequate personal protective equipment (PPE) for all professionals involved in the care of these babies and use of expiratory viral filters in any respiratory device(5).

Regarding the prevention of COVID-19, the first step is screening all NBs according to family history, followed by individual isolation and testing for SARS-CoV-2.13-14,16,18 In cases in which mothers have tested positive, the recommendation is to clean the NB immediately after birth, maintain isolation for 14 days(14,16,18) and, after two negative maternal swabs, keep mother and child together(15,17).

Discontinuation of breastfeeding is indicated in some studies(15,17). However, in Brazil, the recommendation of the Ministry of Health and the Brazilian Society of Pediatrics is that breastfeeding should be stimulated and promoted, regardless of mothers suspected or confirmed COVID-19 diagnosis; however following the guidelines of mask use and hand washing before and after feeding(22-23). It is worth noting that to date, there is no evidence of vertical transmission through breastfeeding, so breast milk should be offered, as it is the best source of nutrients for the newborn(23-24).

It is necessary to pay attention to home care when handling utensils used in NB care, disinfecting pacifiers and bottles at high temperatures, hand sanitization before and after diaper changes, handling NBs and bottle preparation and mask use by parents. Other care measures related to the environment are also essential, such as keeping windows open for air circulation and frequently disinfecting floors and furniture(14-15).

Newborns of suspected or confirmed mothers should be transferred to reference units for COVID-19 treatment, and the following measures should be taken, such as: effective communication with the reference hospital, use of PPE by professionals, transportation of the baby in an incubator with suitable equipment available for emergency care, NBs should be kept in isolation in units with negative pressure and disinfecting equipment after use(14). Considering the importance of ensuring safe transportation for both suspected or confirmed NBs and health teams, one of the studies included in this review aimed to develop a management plan for the entire transfer process of suspected or confirmed NBs, focusing on how to manage the transfer organization, strategies for the prevention of health professionals, and measures to prevent the spread of the virus during this process(18).

It is important to emphasize that information is changing rapidly and health professionals should pay attention to updates as the state of knowledge evolves and new evidence is published(5).

Considering that, in the present literature review, none of the studies that composed the sample presented a level of evidence I or II, further research is needed to produce results with strong levels of scientific evidence that can inform neonatal care.

Limitations of this study include the scarcity of studies about the topic, the difficulty of accessing case reports with details about clinical manifestations, as well as the interventions and number of cases of newborns with confirmed COVID-19 cases. However, the contemporaneity of the disease is a predominant factor that justifies the incipient nature of the studies and divergent findings among authors in the area. 

CONCLUSION

Studies indicate that prevention measures are important for this population group, since there are gaps related to treatment. The use of PPE by health professionals during neonatal care is necessary and indispensable. Since the clinical manifestation of the infection can range from respiratory symptoms and also include nonspecific symptoms, such as gastrointestinal and even cutaneous manifestations, it is of utmost importance to screen suspected NBs for diagnostic confirmation to reduce the risks of horizontal transmission. Although the reported cases appeared to have been acquired in the postnatal period, more studies and evidence are needed to clarify whether there is a risk of vertical transmission.

This study was necessary considering the pandemic situation that we are currently experiencing. Although scarce, the findings are important for newborn care, and continuous updates are necessary to guide professionals on the best management and control of COVID-19 in the neonatal population.

REFERENCES

1. Brasil. Agência Nacional de Vigilância Sanitária (Anvisa).  Orientações para a prevenção e o controle de infecções pelo novo coronavírus (SARS-CoV-2) em instituições de longa permanência para idosos (ILPI). Nota Técnica GVIMS/GGTES/ANVISA Nº 05/2020: Brasília: Anvisa [Internet]. 2020 [cited 2020 jun 24]. Available from:  https://www20.anvisa.gov.br/segurancadopaciente/index.php/alertas/item/nota-tecnica-n-05-2020-gvims-ggtes-anvisa-orientacoes-para-a-prevencao-e-ocontrole-de-infeccoes-pelo-novo-coronavirus-sars-cov-2-ilpi 

2. World Health Organization. Clinical Management of Severe Acute Respiratory Infection when Novel Coronavirus (nCoV) Infection Is Suspected: Interim Guidance [Internet]. 2020 [cited 2020 jun 24] Available from: https://www.who.int/docs/default-source/coronaviruse/clinical-management-ofnovel-cov.pdf 

3. Chandrasekharan P, Vento M, Trevisanuto D, Partridge E, Underwood MA, Wiedeman J, et al. Neonatal Resuscitation and Postresuscitation Care of Infants Born to Mothers with Suspected or Confirmed SARS-CoV-2 Infection. Am J Perinatol [Internet]. 2020 [cited 2020 jun 24];37(8):813-824. Available from: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/s-00401709688. doi: https://doi.org/10.1055/s-0040-1709688 

4. Brasil. Ministério da Saúde. Secretaria de Atenção Especializada à Saúde. Departamento de Atenção Hospitalar, Domiciliar e de Urgência. Protocolo de Tratamento do Novo Coronavírus (2019-nCoV) [Internet]. Brasília: Ministério da Saúde; 2020 [cited 2020 maio 30]; Available from: https://portalarquivos2.saude.gov.br/images/pdf/2020/fevereiro/05/Protocolode-manejo-clinico-para-o-novo-coronavirus-2019- ncov.pdf. 

5. Shalish W, Lakshminrusimha S, Manzoni P, Keszler M, Sant'Anna GM. COVID-19 and Neonatal Respiratory Care: Current Evidence and Practical Approach. Am J Perinatol [Internet]. 2020 [cited 2020 set 20];37(8):780-791. Available from: https://www.thiemeconnect.de/products/ejournals/abstract/10.1055/s00401710522.    doi:org/10.1055%2Fs-0040-1710522

6 Sociedade Brasileira de Pneumologia e Tisiologia - SBPT. COVID-19: orientações da SBPT sobre o tratamento de crianças [Internet]. 2020 [cited 08 jul 2020]. Available from:https://sbpt.org.br/portal/wpcontent/uploads/2020/04/pneumopediatria_covid_19.pdf

7. Mendes KDS, Sasso RS, Pereira CC, Galvao CM. Revisão integrativa: método de pesquisa para a incorporação de evidências na saúde e na enfermagem. Texto Contexto - Enferm [Internet]. 2008 [cited 2020 jun 08];17(4):758-764.Available from: https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0104-07072008000400018&lng=pt&tlng=pt.  doi: https://doi.org/10.1590/S0104-07072008000400018  

8. Ercole FF, Melo LS, Alcoforado CLGC. Revisão integrativa versus sistemática. Rer Min Enferm [Internet]. 2014 [cited 2020 jun 08];18(1):10.Available from: https://www.reme.org.br/artigo/detalhes/904.  doi: http://www.dx.doi.org/10.5935/1415-2762.20140001. 

9. Melnyk BM, Fineout-Overholt E. Making the case for evidence-based practice. In: Melnyk BM, Fineout-Overholt E, editors. Evidence-Based Practice in Nursing & Healthcare. A Guide to Best Practice. Philadelphia: Lippincott Williams & Wilkins; 2011. p.3-24.

10. Souza MT, Silva MD, Carvalho R. Integrative review: what is it? How to do it? Einstein (São Paulo). [Internet] 2010 [cited 2020 jun 08];8(1):102-6. Available from: https://www.scielo.br/pdf/eins/v8n1/1679-4508-eins-8-1-0102.pdf.  doi: http://dx.doi.org/10.1590/s1679-45082010rw1134  

11. Whittemore R, Knafl K. The integrative review: updated methodology. J Adv Nurs. [Internet] 2005 [cited 2020 ago 08];52(5):546-53. Available from: https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1365-2648.2005.03621.x.  doi:  https://doi.org/10.1111/j.1365-2648.2005.03621.x 

12. Chen Z, DU Li-Z, FU J-F, Shu Q. Emergency plan for inter-hospital transfer of newborns with SARS-CoV-2 infection. CJCP [Internet]. 2020 [cited 2020 maio 10]; 22(3):226-230. Available from: https://www.researchgate.net/publication/340163405_Emergency_plan_for_inter-hospital_transfer_of_newborns_with_SARS-CoV-2_infection.  doi:https://doi.org/10.7499/j.issn.1008-8830.2020.03.009. [included in the review]

13. Wang J, Shi Y. Managing neonates with respiratory failure due to SARS-CoV-2. Lancet Child Adolesc Health [Internet]. 2020 [cited 2020 maio 10];4(4):e9.  Available from: https://www.thelancet.com/journals/lanchi/article/PIIS2352-4642(20)30072-9/fulltext.  doi: https://doi.org/10.1016/S2352-4642(20)30072-9   [included in the review]

14. Wang LS, Hu XJ, Zhou WH. An interpretation on perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition). China J Contemp Pediatr [Internet].2020 [cited 2020 maio 10];22(3):199–204. Available from: https://pesquisa.bvsalud.org/controlecancer/resource/pt/mdl-32204753.  doi: https://10.7499/j.issn.1008-8830.2020.03.004  [included in the review]

15. Wang S, Zhou X, Lin X, Liu Y, Wu J, Sharifu LM, et al. Experience of Clinical Management for Pregnant Women and Newborns with Novel Coronavirus Pneumonia in Tongji Hospital, China. CURR MED SCI [Internet]. 2020 [cited 2020 maio 10];40:285–289. Available from: https://link.springer.com/article/10.1007/s11596-020-2174-4 . doi: https://doi.org/10.1007/s11596-020-2174-4 [included in the review]

16. Kamali AM, Jafari N, Eftekhari K. Novel coronavirus in a 15-day-old neonate with clinical signs of sepsis, a case report.  Infect Dis (Lond) [Internet]. 2020 [cited 2020 maio 10];52:427–429.  Available from: https://www.tandfonline.com/doi/full/10.1080/23744235.2020.1747634.  doi: https://dx.doi.org/10.1080%2F23744235.2020.1747634  [included in the review]

17. Schwartz DA, Graham AL. Potential maternal and infant outcomes from (Wuhan) Coronavirus 2019-nCoV infecting pregnant women: lessons from SARS, MERS, and Other human Coronavirus infections. Viruses [Internet]. 2020 [cited 2020 maio 10];12(2):194. .Available from: https://www.mdpi.com/1999-4915/12/2/194.  doi: https://dx.doi.org/10.3390%2Fv12020194  [included in the review]

18. Zhou WH. Perinatal and neonatal management plan for prevention and control of SARS-CoV-2 infection (2nd Edition) China J Contemp Pediatr [Internet]. 2020 [cited 2020 maio 10];22(3):195-198. Available from: http://www.zgddek.com/CN/10.7499/j.issn.1008-8830.2020.03.003.  doi: https://dx.doi.org/10.7499/j.issn.1008-8830.2020.03.003  [included in the review]

19. Wang L, Shi Y, Xiao T. Chinese expert consensus on the perinatal and neonatal management for the prevention and control of the 2019 novel coronavirus infection (First edition). Ann Transl Med [Internet] 2020 [cited 10 set 2020]. Available from: http://atm.amegroups.com/article/view/35751/html.  doi: https://dx.doi.org/10.21037%2Fatm.2020.02.20 

20. Chen D, Yang H, Cao Y. Expert consensus for managing pregnant women and neonates born to mothers with suspected or confirmed novel coronavirus (COVID‐19) infection. Int J Gynecol Obstet [Internet]. 2020 [cited 2020 set 15]; 149: 130– 136. Available from: https://obgyn.onlinelibrary.wiley.com/doi/full/10.1002/ijgo.13146.  doi: https://doi.org/10.1002/ijgo.13146 

21. Pacifici GM. Effects of surfactants on preterm infant lungs. Medic Express [Internet]. 2015 [cited 10 set 2020];2(2): M150106. Available from: http://www.scielo.br/scielo.php?script=sci_arttext&pid=S2358042920150002000 06&lng=en. Doi: https://doi.org/10.5935/MedicalExpress.2015.02.06  

22. Brasil. Ministério da Saúde. Secretaria de Atenção Primária à Saúde. Fluxo de Decisão para Amamentação no contexto da COVID-19. [cited 2020 maio 29]. Available from: https://portaldeboaspraticas.iff.fiocruz.br/atencao-crianca/covid-19-e-aleitamento-materno-orientacoes-da-sbp-e-rblh/ 

23. Sociedade Brasileira de Pediatria (SBP). Aleitamento Materno em tempos de COVID-19 – recomendações na maternidade e após a alta. 2020 [cited 2020 maio 22]. Available from: https://www.sbp.com.br/fileadmin/user_upload/22467f-NA_-_AleitMat_tempos_COVID-19-_na_matern_e_apos_alta.pdf  

24. Freitas BMBM, Alves MDSM, Gaíva MAM. Prevention and control measures for neonatal COVID-19 infection: a scoping review. Rev Bras Enferm [Internet] 2020 [cited 2020 set 10];73(Suppl2):e20200467. Available from: https://www.scielo.br/scielo.php?script=sci_arttext&pid=S003471672020001400301&tlng=en.  doi: http://dx.doi.org/10.1590/0034-7167-2020-0467 

AUTHOR'S  CONTRIBUTION

Study design: Araujo JP, Zani AV

Data collection: Zani, AV

Data analysis and interpretation: Araujo JP, Campana KSS, Bussú KV, Sczindrowski M, Leal, LB, Zani AV,

Discussion of results: Araujo JP, Campana KSS, Bussú KV, Sczindrowski M, Leal LB, Zani AV

Writing and/or critical review of content: Araujo JP, Campana KSS, Bussú KV, Sczindrowski M, Leal LB, Zani AV

Review and final approval of the final version: Araujo JP, Campana KSS, Bussú KV, Sczindrowski M, Leal LB, Zani AV

Received: 10/13/2020

Revised:11/25/2020

Approved: 01/21/2021