COVID-19 and its relation to pregnancy and neonates: a systematic review

Gerson Aparecido Foratori-Junior Victor Mosquim Thais Marchini de Oliveira Valarelli Maria Aparecida de Andrade Moreira Machado Silvia Helena de Carvalho Sales-Peres About the authors

Abstract

Objectives:

this study systematically reviewed the literature in order to better understand the association among COVID-19, pregnancy and neonates.

Methods:

MEDLINE, EMBASE, Web of Science, BVS and SCOPUS were assessed, considering the terms: (covid 19 OR covid-19 OR novel coronavirus OR 2019 novel coronavirus OR 2019-nCoV OR sarscov 2 OR sars-cov-2 OR sarscov2 OR sars cov-2) AND (pregnancy OR pregnant OR pregnant women OR gestation OR gestational) AND (infant OR fetal OR neonatal). Thirty full-text were included (408 pregnant women, 11 non-pregnant women and 279 neonates).

Results:

fever (45.83%) and cough (31.61%) were the main symptoms of COVID-19 during the pregnancy. Low levels of lymphocytes (32.10%), elevated levels of C-reactive protein (32.35%); leukocytosis (29.41%); neutrophil (5.88%); and radiographic alterations on chest CT, x-ray or ultrasound (45.84%) were the main laboratorial findings. Cesarean delivery and preterm were registered in 239 and 49 cases, respectively. Ten neonates tested positive for SARS-CoV-2.

Conclusion:

when COVID-19 pneumonia affects women during pregnancy, the symptoms are similar to those experienced by non-pregnant women. In addition, there is still no plausible evidence suggesting vertical transmission of SARS-CoV-2 virus from mother to child.

Key words
COVID-19; SARS-CoV-2; Pregnancy; Childbirth; Newborn

Resumo

Objetivos:

este estudo revisou sistematicamente a literatura para melhor compreender a associação entre COVID-19, gravidez e neonatos.

Métodos:

MEDLINE, EMBASE, Web of Science, BVS e SCOPUS foram acessadas, considerando os termos: (covid 19 OR covid-19 OR novel coronavirus OR 2019 novel coronavirus OR 2019-nCoV OR sarscov 2 OR sars-cov-2 OR sarscov2 OR sars cov-2) AND (pregnancy OR pregnant OR pregnant women OR gestation OR gestational) AND (infant OR fetal OR neonatal). Trinta textos completos foram incluídos (408 gestantes, 11 mulheres nãogestantes e 279 recém-nascidos).

Resultados:

febre (45,83%) e tosse (31,61%) foram os principais sintomas da COVID-19 durante a gestação. Baixos níveis de linfócitos (32,10%), elevados níveis de proteínas Creativa (32,35%); leucocitose (29,41%); neutrófilo (5,88%); e alterações radiográficas sob tomografia computadorizada de tórax, radiografia ou ultrasom (45,84%) foram os principais achados laboratoriais. Parto por cesárea e prematuridade foram registrados em 239 e 49 casos, respectivamente. Dez recém-nascidos testaram positivo para o virus SARS-CoV-2.

Conclusão:

quando a pneumonia COVID-19 afeta mulheres durante a gravidez, os sintomas são semelhantes aos experimentados por mulheres não grávidas. Além disso, ainda não há evidências plausíveis que sugiram a transmissão vertical do vírus SARS-CoV-2 de mãe para filho.

Palavras-chave
COVID-19; SARS-CoV-2; Gravidez; Parto; Recém-nascido

Introduction

Currently known as COVID-19, SARS-CoV-2 virus (Severe Acute Respiratory Syndrome-related coronavirus 2) is a public health emergency of international concern. It has been suggested that previous complications may be risk factors for adverse outcomes related to COVID-19 such as cardiovascular disease, diabetes, hypertension, and chronic obstructive pulmonary disease.11 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinicalfeatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497-506.

2 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinicalcharacteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323 (11): 1061‐9.
-33 Yang J, Zheng Y, Gou X, Pu K, Chen Z, Guo Q, et al.Prevalence of comorbidities in the novel Wuhan coronavirus (COVID-19) infection: a systematic review and meta-analysis. Int J Infect Dis. 2020; 94: 91‐5.

Regarding symptomatology, similarities of clinical features between 2019-nCoV and previous beta coronavirus infections has been found. Most patients present fever, dry cough, dyspnea, and bilateral patchy pattern and/or ground-glass opacities on chest computerized tomography (CT) scans.11 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinicalfeatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497-506. Nonetheless, the report from Huang et al.11 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinicalfeatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497-506. mainly focused on nonpregnant women. Contrasting data are found on maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia.

Prior December 2019, others six coronaviruses were known to infect people: 229E, OC43, NL63, HKU1, SARS-CoV, and MERS-CoV (Middle East Respiratory Syndrome coronavirus). Among these, 229E, OC43, NL63, and HKU1 can be vertically transmitted from mothers to neonates through the placenta,44 Gagneur A, Dirson E, Audebert S, Vallet S, LegrandQuillien MC, Laurent Y, et al. Materno-fetal transmission of human coronaviruses: a prospective pilot study. Eur J Clin Microbiol Infect Dis. 2008; 27 (9): 863-6.,55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60. whilst there is no evidence of vertical transmission of SARS-CoV and MERS-CoV.55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,66 Alserehi H, Wali G, Alshukairi A, Alraddadi B. Impact ofMiddle East Respiratory Syndrome coronavirus (MERSCoV) on pregnancy and perinatal outcome. BMC Infect Dis. 2016; 16: 105. Nevertheless, an epidemiological research presented that 2019-nCoV was more contagious than SARSCoV, although, its nucleotide sequences were very similar (82% homologous with SARS-CoV).77 Chan JF, Kok KH, Zhu Z, Chu H, To KK, Yuan S, et al.Genomic characterization of the 2019 novel human-pathogenic coronavirus isolated from a patient with atypical pneumonia after visiting Wuhan. Emerg Microbes Infect. 2020; 9 (1): 221-36.

Moreover, it has been stated that COVID-19 infections in pregnant women generally result in mild or moderate symptoms, and many infected pregnant women do not present any symptoms,88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.,99 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63. which may also lead to a high risk of neonatal infection during labor. However, the clinical characteristics and potential vertical transmission of COVID19 pneumonia in pregnant women is still new and has not been entirely clarified.88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15. Therefore, it is important to report the most frequent symptoms of this disease in pregnant women and neonates, as well as to understand the risk of infection that labor imposes to the neonates’ health. Based on this rationale, this study aimed to systematically review the available literature in order to better understand the association among COVID-19, pregnancy and neonates.

Methods

This systematic review was conducted without patient involvement. Patients were not involved in any way during the review of the available literature, nor during the writing or editing of this document for readability or accuracy.

The search strategy followed the indications of the National Health Service Center for Reviews and Dissemination and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Also, this systematic review was registered in International Prospective Register of Systematic Reviews (PROSPERO) with protocol CRD42020177354 (https://www.crd.york.ac.uk/ prospero).

A systematic revision of relevant studies published in the literature was conducted on May 22nd, 2020, considering the period between December 1st, 2019 to May 22nd, 2020. The following database were explored: MEDLINE database (Entrez PubMed, www.ncbi.nim.nih.gov) EMBASE, Web of Science, BVS/LILACS and SCOPUS, considering the main MeSH (Medical Subject Headings) terms: (covid 19 OR covid-19 OR novel coronavirus OR 2019 novel coronavirus OR 2019-nCoV OR sarscov 2 OR sars-cov-2 OR sarscov2 OR sars cov-2) AND (pregnancy OR pregnant OR pregnant women OR gestation OR gestational) AND (infant OR fetal OR neonatal). To identify relevant article, titles and abstracts of retrieved papers were exported to Endnote Web where duplicates were identified and removed by two reviewers (GAFJ and VM). It is important to highlight that, in order to identify missing studies, we also hand searched the reference lists of the studies included.

As eligibility criteria, we considered case reports, case series and clinical researches in English, Portuguese and Spanish published in peerreviewed journals, that have addressed epidemiological, clinical features of COVID-19 and its association with pregnancy and neonates. Duplicate publications and articles that did not correspond to the objectives of this review were excluded. Similarly, publications without a research or case report, such as: review articles; descriptive studies; opinion article; correspondence; editorials; letters; and with only children’s cases were also excluded. Figure 1 shows the steps of the literature search.

Two highly experienced researchers (GAFJ and VM) were previously trained regarding to criteria that were defined in this study and after they were responsible for searching the literature, applying inclusion and exclusion criteria, selecting the studies and independently extracting the data. There was a good concordance coefficient between reviewers (Kappa index=0.91). Discordances between the authors were discussed and agreed upon with a third author (SHCSP).

Figure 1
Systematic review steps according to PRISMA 2009.

Studies assessed in this review were classified and stored by: main author, publication year, study design, sample/participants, maternal age, consequences for pregnant women, consequences for neonates, absence/presence of vertical transmission.

The initial search identified 439 studies (181 from PubMed, 135 from EMBASE, 71 from BVS, 33 from Web of Science and 19 from SCOPUS). After, nine sources were manually inserted by analyzing the references list of previous studies. Fifty-five sources remained on screening step after duplicates exclusion.

Following screening of titles and abstracts, 216 sources were excluded due to the following reasons: reviews; author reply/ comment/ correspondence/ expert comment/ guideline/ letter to editor/ in websites; not correspond to the objectives of this review; not peer-reviewed; language. Besides that, one full-text study was not found.

Seventy-eight articles in full text were assessed. Thirty were considered with good relevance, among them: clinical research (n=1); case-control (n=1); retrospective review of cases (n=10); case series (n=4); case reports (n=14). Forty-eight were removed due to the following reasons: reviews (n=24); did not address pregnancy (n=11); not peerreviewed (n=9); Chinese language (n=4).

Results

A total of 408 pregnant women was considered. The mean age of all pregnant women in the 30 studies included in this review was 32.46 years old. Also, among the studies included in this review, 11 nonpregnant women and 279 neonates were considered.

The main symptoms of this disease in pregnant women were fever (45.83%) accompanied or not by fatigue, cough (31.61%), myalgia (15.19%), dyspnea (11.76%), sore throat (3.92%) and diarrhea (1.96%). Other less frequent symptoms, such as shortness of breath, headache and anemia were reported (Table 1).

The most frequent laboratorial features were elevated levels of C-reactive protein (32.35%); low levels of lymphocytes (32.10%); leukocytosis (29.41%); neutrophil levels above the normal range (5.88%); radiographic alterations on chest CT or xray (45.34%), because of viral pneumonia that is characterized by decreased diffuse and unilateral or bilateral ground-glass opacities, patchy lung consolidation and blurred borders (Table 2).

The main findings of this study point out that, of the 279 neonates, only ten tested positive for SARS-CoV-2, indicating a low risk of vertical transmission of the disease (Table 3). Delivery outcomes, characteristics of infants at birth and evidence of vertical transmission are also displayed in Table 3.

Discussion

Due to their immunosuppressed state and physiological and adaptive changes, pregnant women are more susceptible to pneumonia and other respiratory pathogens. Nonetheless, our results highlighted that fever and cough were the main clinical features of COVID-19 during pregnancy, but asymptomatic cases are common. Several studies reported false negative diagnosis by RT-PCR, whilst chest CT and x-rays analyses seem to be a fast and highly reliable diagnostic method. Also, vertical transmission from mother to neonates seems unlikely, yet, the available data addressing this topic is still scarce. Overall, data are limited in relation to the association of the outcomes, since population-based clinical studies are still scarce and most studies have low strength of scientific evidence.

Chen et al.1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15. reported that the main symptoms of SARS-CoV-2 infection in pregnant women are fever and cough, with lower frequency for myalgia, malaise, sore throat, shortness of breath and diarrhea. Laboratorial findings also report that lymphopenia and increased ALT and AST levels are frequent. These findings are in accordance with the findings of this systematic review, where fever (45.83%) and cough (31.61%) were the most frequent symptoms among the 408 pregnant women analyzed in this review, followed by myalgia (15.19%), dyspnea (11.76%), sore throat (3.92%) and diarrhea (1.96%).55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.

9 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.

10 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.

11 Alonso Díaz C, López Maestro M, Moral Pumarega MT,Flores Antón B, Pallás Alonso CR. Primer caso de infección neonatal por SARS-CoV-2 en España [First case of neonatal infection due to SARS-CoV-2 in Spain]. An Pediatr (Barc). 2020; 92 (4): 237-8.

12 Alzamora MC, Paredes T, Caceres D, Webb CM, ValdezLM, La Rosa M. Severe COVID-19 during pregnancy and possible vertical transmission. Am J Perinatol. 2020; 37 (8): 861-5.

13 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.

14 Breslin N, Baptiste C, Miller R, Fuchs K, Goffman D,Gyamfi-Bannerman C, et al. COVID-19 in pregnancy: early lessons. Am J Obstet Gynecol MFM. 2020; 2 (2): 100111.

15 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9.

16 Chen R, Zhang Y, Huang L, Cheng BH, Xia ZY, Meng QT.Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can J Anaesth. 2020; 67 (6): 655-63.

17 Chen Y, Peng H, Wang L, Zhao Y, Zeng L, Gao H, et al.Infants born to mothers with a new coronavirus (COVID19). Front Pediat. 2020; 8: 104.

18 Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinataltransmission of COVID-19 associated SARS-CoV-2: should we worry? Clin Infect Dis. 2020; 72 (5): 862-4.

19 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9.

20 González Romero D, Ocampo Pérez J, González BautistaL, Santana-Cabrera L. Pronóstico perinatal y de la paciente embarazada con infección por COVID-19 [Pregnancy and perinatal outcomeof a womanwith COVID-19 infection]. Rev Clin Esp. 2020; 220 (8): 533-4.

21 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.

22 Iqbal SN, Overcash R, Mokhtari N, Saeed H, Gold S,Auguste T, et al. An uncomplicated delivery in a patient with COVID-19 in the United States. N Engl J Med. 2020; 382 (16): e34.

23 Kalafat E, Yaprak E, Cinar G, Varli B, Ozisik S, Uzun C, etal. Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19. Ultrasound Obstet Gynecol. 2020; 55 (6): 835-7.

24 Li N, Han L, Peng M, Lv Y, Ouyang Y, Liu K, et al.Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin Infect Dis. 2020; 71 (16): 2035-41.

25 Li Y, Zhao R, Zheng S, Chen X, Wang J, Sheng X, et al.Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China. Emerg Infect Dis. 2020; 26 (6): 1335‐6.

26 Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, et al.Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR Am J Roentgenol. 2020; 215 (1): 127-32.

27 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13.

28 Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations andoutcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; S0163-4453(20)30109-2.

29 Song L, Xiao W, Ling K, Yao S, Chen X. Anestheticmanagement for emergent cesarean delivery in a parturient with recent diagnosis of coronavirus disease 2019 (COVID19): a case report. Transl Perioper Pain Med. 2020; 7 (3): 234-7.

30 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.

31 Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A caseof 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis. 2020; 71 (15): 844-6.

32 Xia H, Zhao S, Wu Z, Luo H, Zhou C, Chen X. EmergencyCaesarean delivery in a patient with confirmed coronavirus disease 2019 under spinal anaesthesia. Br J Anaesth. 2020; 124 (5): e216‐e218.

33 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.

34 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64.

35 Zamaniyan M, Ebadi A, Aghajanpoor Mir S, Rahmani Z,Haghshenas M, Azizi S. Preterm delivery in pregnant woman with critical COVID-19 pneumonia and vertical transmission. Prenat Diagn. 2020; 40 (13): 1759-61.
-3636 Zambrano LI, Fuentes-Barahona IC, Bejarano-Torres DA,Bustillo C, Gonzales G, Vallecillo-Chinchilla G, et al. A pregnant woman with COVID-19 in Central America. Travel Med Infect Dis. 2020; 36: 101639. Laboratorial tests reported decreased levels of lymphocytes (32.10%) and increased levels of C-reactive protein (32.35%) as frequent conditions, followed by leukocytosis (29.41%) and increased neutrophil ratio (5.88%).

Medonza et al.3737 Mendoza M, Garcia-Ruiz I, Maiz N, Rodo C, GarciaManau P, Serrano B, et al. Pre-eclampsia-like syndrome induced by severe COVID-19: a prospective observational study. BJOG. 2020; 127 (11): 1374-80. reported that preeclampsia-like syndrome is one symptom of COVID-19, but its cause is different from obstetric preeclampsia and therefore not connected with placental failure. In addition, preeclampsia-like syndrome can resolve spontaneously following recovery from severe pneumonia and may not be an obstetric indication for delivery.

Other main findings seen in the reviewed studies was alterations on chest CT.55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,99 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.,1212 Alzamora MC, Paredes T, Caceres D, Webb CM, ValdezLM, La Rosa M. Severe COVID-19 during pregnancy and possible vertical transmission. Am J Perinatol. 2020; 37 (8): 861-5.,1313 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.,1515 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9.,2020 González Romero D, Ocampo Pérez J, González BautistaL, Santana-Cabrera L. Pronóstico perinatal y de la paciente embarazada con infección por COVID-19 [Pregnancy and perinatal outcomeof a womanwith COVID-19 infection]. Rev Clin Esp. 2020; 220 (8): 533-4.,2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.,2323 Kalafat E, Yaprak E, Cinar G, Varli B, Ozisik S, Uzun C, etal. Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19. Ultrasound Obstet Gynecol. 2020; 55 (6): 835-7.

24 Li N, Han L, Peng M, Lv Y, Ouyang Y, Liu K, et al.Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin Infect Dis. 2020; 71 (16): 2035-41.
-2525 Li Y, Zhao R, Zheng S, Chen X, Wang J, Sheng X, et al.Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China. Emerg Infect Dis. 2020; 26 (6): 1335‐6.,3030 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.,3131 Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A caseof 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis. 2020; 71 (15): 844-6.,3333 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.

34 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64.
-3535 Zamaniyan M, Ebadi A, Aghajanpoor Mir S, Rahmani Z,Haghshenas M, Azizi S. Preterm delivery in pregnant woman with critical COVID-19 pneumonia and vertical transmission. Prenat Diagn. 2020; 40 (13): 1759-61. More than 45% of patients included in this review presented alterations upon chest CT, xray or ultrasound. These findings, along with the study of Liu et al.2727 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13. suggest than CT images seem to be helpful to diagnose virus pneumonia.2727 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13. In their study, some patients tested by real-time reverse transcription polymerase chain reaction assay (RT-PCR) retrieved negative results and presented alterations on chest CT images, such as patchy shadows and/or ground-glass opacities. In this case, chest CT seems to have a high accuracy to diagnose SARS-CoV-2 infections and present low levels of false negative results,99 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1313 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.,1515 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9.,1919 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9.,2323 Kalafat E, Yaprak E, Cinar G, Varli B, Ozisik S, Uzun C, etal. Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19. Ultrasound Obstet Gynecol. 2020; 55 (6): 835-7.,3333 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14. unlike RT-PCR. In addition, relevant clinical examinations such as blood cell counts should be performed together with a comprehensive assessment of the patient's medical history, epidemiological exposure and symptoms in general.88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.

9 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.
-1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1313 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.,2424 Li N, Han L, Peng M, Lv Y, Ouyang Y, Liu K, et al.Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin Infect Dis. 2020; 71 (16): 2035-41.,3333 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.

Table 1
Description of pregnant women’s clinical characteristics in the selected studies.
Table 2
Description of pregnant women’s laboratorial data and radiological characteristics in selected studies.
Table 3
Description of childbirth, babies’ characteristics at birth and vertical transmission in selected studies.

It is important to highlight that, despite chest CT not being frequently conducted on pregnant women due to its level of radiation, in Liu et al.2727 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13. the dose was adjusted to pregnant women to allow the acquirement of images that could present signals of viral infection. This adjustment was responsible for lower-resolution images, but the quality of these images was sufficient to diagnose viral pneumonia and other alterations, such as ground-glass opacities.

All studies included in this review diagnosed patients with SAR-CoV-2 infection by using RTPCR. However, it is important to highlight that several studies reported the possibility of a false negative result for patients who might had been infected by SARS-CoV-2.55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,2727 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13.,3030 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.,3333 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.,3434 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64. Previous evidence has argued that false negative results could have happened due to insufficient viral load, sampling at early or late stage of the illness, and inappropriate swabbing sites.3030 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7. In Fan et al.1818 Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinataltransmission of COVID-19 associated SARS-CoV-2: should we worry? Clin Infect Dis. 2020; 72 (5): 862-4. study a pregnant patient was positive diagnosed with SARS-CoV-2 after two negative samplings, and Liu et al.2727 Liu H, Liu F, Li J, Zhang T, Wang D, Lan W. Clinical andCT imaging features of the COVID-19 pneumonia: Focus on pregnant women and children. J Infect. 2020; 80 (5): e7‐e13. conducted several analyses in 25 pregnant women clinically-diagnosed but they had not received the laboratorial- confirmation.

Due to this uncertainty related to false negative results, almost all reviewed papers reported the election of a cesarean section (n = 239 women) for childbirth.88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.

9 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.

10 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.

11 Alonso Díaz C, López Maestro M, Moral Pumarega MT,Flores Antón B, Pallás Alonso CR. Primer caso de infección neonatal por SARS-CoV-2 en España [First case of neonatal infection due to SARS-CoV-2 in Spain]. An Pediatr (Barc). 2020; 92 (4): 237-8.

12 Alzamora MC, Paredes T, Caceres D, Webb CM, ValdezLM, La Rosa M. Severe COVID-19 during pregnancy and possible vertical transmission. Am J Perinatol. 2020; 37 (8): 861-5.

13 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.

14 Breslin N, Baptiste C, Miller R, Fuchs K, Goffman D,Gyamfi-Bannerman C, et al. COVID-19 in pregnancy: early lessons. Am J Obstet Gynecol MFM. 2020; 2 (2): 100111.

15 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9.

16 Chen R, Zhang Y, Huang L, Cheng BH, Xia ZY, Meng QT.Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can J Anaesth. 2020; 67 (6): 655-63.

17 Chen Y, Peng H, Wang L, Zhao Y, Zeng L, Gao H, et al.Infants born to mothers with a new coronavirus (COVID19). Front Pediat. 2020; 8: 104.

18 Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinataltransmission of COVID-19 associated SARS-CoV-2: should we worry? Clin Infect Dis. 2020; 72 (5): 862-4.

19 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9.

20 González Romero D, Ocampo Pérez J, González BautistaL, Santana-Cabrera L. Pronóstico perinatal y de la paciente embarazada con infección por COVID-19 [Pregnancy and perinatal outcomeof a womanwith COVID-19 infection]. Rev Clin Esp. 2020; 220 (8): 533-4.
-2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.,2323 Kalafat E, Yaprak E, Cinar G, Varli B, Ozisik S, Uzun C, etal. Lung ultrasound and computed tomographic findings in pregnant woman with COVID-19. Ultrasound Obstet Gynecol. 2020; 55 (6): 835-7.

24 Li N, Han L, Peng M, Lv Y, Ouyang Y, Liu K, et al.Maternal and neonatal outcomes of pregnant women with COVID-19 pneumonia: a case-control study. Clin Infect Dis. 2020; 71 (16): 2035-41.

25 Li Y, Zhao R, Zheng S, Chen X, Wang J, Sheng X, et al.Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China. Emerg Infect Dis. 2020; 26 (6): 1335‐6.
-2626 Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, et al.Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR Am J Roentgenol. 2020; 215 (1): 127-32.,2828 Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations andoutcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; S0163-4453(20)30109-2.

29 Song L, Xiao W, Ling K, Yao S, Chen X. Anestheticmanagement for emergent cesarean delivery in a parturient with recent diagnosis of coronavirus disease 2019 (COVID19): a case report. Transl Perioper Pain Med. 2020; 7 (3): 234-7.

30 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.

31 Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A caseof 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis. 2020; 71 (15): 844-6.

32 Xia H, Zhao S, Wu Z, Luo H, Zhou C, Chen X. EmergencyCaesarean delivery in a patient with confirmed coronavirus disease 2019 under spinal anaesthesia. Br J Anaesth. 2020; 124 (5): e216‐e218.

33 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.

34 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64.

35 Zamaniyan M, Ebadi A, Aghajanpoor Mir S, Rahmani Z,Haghshenas M, Azizi S. Preterm delivery in pregnant woman with critical COVID-19 pneumonia and vertical transmission. Prenat Diagn. 2020; 40 (13): 1759-61.
-3636 Zambrano LI, Fuentes-Barahona IC, Bejarano-Torres DA,Bustillo C, Gonzales G, Vallecillo-Chinchilla G, et al. A pregnant woman with COVID-19 in Central America. Travel Med Infect Dis. 2020; 36: 101639. Only 42 cases of pregnant women delivered babies vaginally were reported,55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,88 Ferrazzi E, Frigerio L, Savasi V, Vergani P, Prefumo F,Barresi S, et al. Vaginal delivery in SARS-CoV-2 infected pregnant women in Northern Italy: a retrospective analysis. BJOG. 2020; 127 (9): 1116-21.,99 Wu X, Sun R, Chen J, Xie Y, Zhang S, Wang X. Radiological findings and clinical characteristics of pregnant women with COVID-19 pneumonia. Int J Gynaecol Obstet. 2020; 150 (1): 58-63.,1313 Breslin N, Baptiste C, Gyamfi-Bannerman C, Miller R,Martinez R, Bernstein K, et al. COVID-19 infection among asymptomatic and symptomatic pregnant women: Two weeks of confirmed presentations to an affiliated pair of New York City hospitals. Am J Obstet Gynecol. 2020; 2 (2): 100118.,1717 Chen Y, Peng H, Wang L, Zhao Y, Zeng L, Gao H, et al.Infants born to mothers with a new coronavirus (COVID19). Front Pediat. 2020; 8: 104.,2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.,2222 Iqbal SN, Overcash R, Mokhtari N, Saeed H, Gold S,Auguste T, et al. An uncomplicated delivery in a patient with COVID-19 in the United States. N Engl J Med. 2020; 382 (16): e34.,2626 Liu D, Li L, Wu X, Zheng D, Wang J, Yang L, et al.Pregnancy and perinatal outcomes of women with coronavirus disease (COVID-19) pneumonia: a preliminary analysis. AJR Am J Roentgenol. 2020; 215 (1): 127-32.,3333 Yan J, Guo J, Fan C, Juan J, Yu X, Li J, et al. Coronavirusdisease 2019 (COVID-19) in pregnant women: A report based on 116 cases. Am J ObstetGynecol. 2020; 223 (1): 111.e1-e14.,3636 Zambrano LI, Fuentes-Barahona IC, Bejarano-Torres DA,Bustillo C, Gonzales G, Vallecillo-Chinchilla G, et al. A pregnant woman with COVID-19 in Central America. Travel Med Infect Dis. 2020; 36: 101639. but all newborns were negative for SARS-CoV-2.

Out of the 279 neonates, 17 were delivered by an emergency cesarean section.1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1111 Alonso Díaz C, López Maestro M, Moral Pumarega MT,Flores Antón B, Pallás Alonso CR. Primer caso de infección neonatal por SARS-CoV-2 en España [First case of neonatal infection due to SARS-CoV-2 in Spain]. An Pediatr (Barc). 2020; 92 (4): 237-8.,1515 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9.,1616 Chen R, Zhang Y, Huang L, Cheng BH, Xia ZY, Meng QT.Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can J Anaesth. 2020; 67 (6): 655-63.,1919 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9.,2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.,2525 Li Y, Zhao R, Zheng S, Chen X, Wang J, Sheng X, et al.Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China. Emerg Infect Dis. 2020; 26 (6): 1335‐6.,2828 Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations andoutcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; S0163-4453(20)30109-2.,2929 Song L, Xiao W, Ling K, Yao S, Chen X. Anestheticmanagement for emergent cesarean delivery in a parturient with recent diagnosis of coronavirus disease 2019 (COVID19): a case report. Transl Perioper Pain Med. 2020; 7 (3): 234-7.,3131 Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A caseof 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis. 2020; 71 (15): 844-6.,3232 Xia H, Zhao S, Wu Z, Luo H, Zhou C, Chen X. EmergencyCaesarean delivery in a patient with confirmed coronavirus disease 2019 under spinal anaesthesia. Br J Anaesth. 2020; 124 (5): e216‐e218. For these mothers, an emergency cesarean section was elected due to some complications such as pre-eclampsia,1919 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9.,2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0. gestational hypertension,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1919 Gidlöf S, Savchenko J, Brune T, Josefsson H. COVID-19 inpregnancy with comorbidities: more liberal testing strategy is needed. Acta Obstet Gynecol Scand. 2020; 99 (7): 948-9. fetal bradycardia,1515 Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, SalviS, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020; 56 (1): 106-9. fetal distress,55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1616 Chen R, Zhang Y, Huang L, Cheng BH, Xia ZY, Meng QT.Safety and efficacy of different anesthetic regimens for parturients with COVID-19 undergoing Cesarean delivery: a case series of 17 patients. Can J Anaesth. 2020; 67 (6): 655-63.,2828 Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations andoutcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; S0163-4453(20)30109-2. PROM55 Zhu H, Wang L, Fang C, Peng S, Zhang L, Chang G, et al.Clinical analysis of 10 neonates born to mothers with 2019nCoV pneumonia. Transl Pediatr. 2020; 9 (1): 51‐60.,1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,2828 Liu Y, Chen H, Tang K, Guo Y. Clinical manifestations andoutcome of SARS-CoV-2 infection during pregnancy. J Infect. 2020; S0163-4453(20)30109-2. and decreased fetal movement and oxygen decompensation.2121 Hantoushzadeh S, Shamshirsaz AA, Aleyasin A, SeferovicMD, Aski SK, Arian SE, et al. Maternal Death due to COVID-19 disease. Am J Obstet Gynecol. 2020; S00029378 (20): 30516-0.

Previous studies have reported the pregnant women with viral pneumonia are more likely to have complications during pregnancy and can also lead to spontaneous miscarriage, preterm birth, low birth weight infants, intrauterine growth restriction and five-minute Apgar score <7 compared to healthy pregnant women.3838 Lam CM, Wong SF, Leung TN, Chow KM, Yu WC, Wong TY, et al. A case-controlled study comparing clinical course and outcomes of pregnant and non-pregnant women with severe acute respiratory syndrome. BJOG. 2004; 111 (8): 771‐4. The results of this study have evidenced a high rate of preterm births (n=49), and out of 273 neonates were delivered and six deaths were reported.

Previous studies have shown that SARS-CoV-2 can be transmitted from human-to-human through close contact of the droplets and also via aerosol.11 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinicalfeatures of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020; 395 (10223): 497-506.,22 Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinicalcharacteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020; 323 (11): 1061‐9. However, the potential for transmissibility from mother-to-fetus is still unknown. In this review, among 279 neonates evaluated by different studies, only ten showed a positive result for SARS-CoV-2, after at least 30 hours of childbirth.1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,3030 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.,3434 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64. However, in some cases, the placenta, umbilical cord, amniotic fluid and breast milk were tested and no positive result for the presence of the virus was found.1010 Chen H, Guo J, Wang C, Luo F, Yu X, Zhang W, et al.Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records. Lancet. 2020; 395 (10226): 809-15.,1818 Fan C, Lei D, Fang C, Li C, Wang M, Liu Y, et al. Perinataltransmission of COVID-19 associated SARS-CoV-2: should we worry? Clin Infect Dis. 2020; 72 (5): 862-4.,2525 Li Y, Zhao R, Zheng S, Chen X, Wang J, Sheng X, et al.Lack of vertical transmission of severe acute respiratory syndrome coronavirus 2, China. Emerg Infect Dis. 2020; 26 (6): 1335‐6.,3030 Wang S, Guo L, Chen L, Liu W, Cao Y, Zhang J, et al. Acase report of neonatal COVID-19 infection in China. Clin Infect Dis. 2020; 71 (15): 853-7.,3131 Wang X, Zhou Z, Zhang J, Zhu F, Tang Y, Shen X. A caseof 2019 Novel Coronavirus in a pregnant woman with preterm delivery. Clin Infect Dis. 2020; 71 (15): 844-6.,3434 Yu N, Li W, Kang Q, Xiong Z, Wang S, Lin X, et al.Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study. Lancet Infect Dis. 2020; 20 (5): 559‐64. It is important to consider the possibility of false-negative in these cases, since RTPCR method was adopted, which may have limitations due to the latency period of the virus, as previously mentioned.

Although, some authors believe that vaginal delivery may increase the risk of vertical transmission of COVID-19, the hypothesis that best explains the mother's non-viral transmission to her child was demonstrated by Zheng et al.,3939 Zheng QL, Duan T, Jin LP. Single-cell RNA expressionprofiling of ACE2 and AXL in the human maternal- fetal interface. Reprod Dev Med. 2020; 4 (1): 7-10. who state that the angiotensin-converting enzyme 2 (ACE2) receptor of COVID-19 has very low expression in almost all cell types of the early maternal-fetal interface, suggesting that there may be no cells that are potentially susceptible to COVID-19 in the maternal-fetal interface.

Despite still being unclear and requiring future clinical studies with a larger sample size to guarantee scientific evidence, vertical transmission seems unlikely. However, protocols for the care of pregnant women and newborns should take into account that, although studies have not shown a positive test for SARS-CoV-2 in breast milk, breastfeeding may present risks of contamination due to direct physical contact.4040 Wang CL, Liu YY, Wu CH, Wang CY, Wang CH, Long CY.Impact of COVID-19 on Pregnancy. Int J Med Sci. 2021; 18 (3): 763-7. Despite this, breastfeeding should be encouraged, but mothers should be properly advised on preventive protocols to avoid transmission.

Recently, the medical field has debated about the immunization of pregnant women against SARSCoV-2, but clinical trials involving pregnant women are still scarce.4141 Blumberg D, Sridhar A, Lakshminrusimha S, Higgins RD,Saade G. COVID-19 Vaccine Considerations during Pregnancy and Lactation. Am J Perinatol. 2021; 38 (6): 523-8.

42 Male V. Are COVID-19 vaccines safe in pregnancy? NatRev Immunol. 2021; 21 (4): 200-1.
-4343 Zipursky JS, Greenberg RA, Maxwell C, Bogler T.Pregnancy, breastfeeding and the SARS-CoV-2 vaccine: an ethics-based framework for shared decision-making. CMAJ. 2021; 193 (9): E312-4. A shared decision-making between the mother, her family, and the obstetrician is essential. The discussion should focus on the risks of infection, risk of morbidity and mortality, and the uncertainty regarding the safety of the vaccine in pregnancy and lactation. But it must be emphasized that at this point we do not have biologic reasons to believe that the currently approved vaccines are harmful to pregnant women or infants.4141 Blumberg D, Sridhar A, Lakshminrusimha S, Higgins RD,Saade G. COVID-19 Vaccine Considerations during Pregnancy and Lactation. Am J Perinatol. 2021; 38 (6): 523-8.,4343 Zipursky JS, Greenberg RA, Maxwell C, Bogler T.Pregnancy, breastfeeding and the SARS-CoV-2 vaccine: an ethics-based framework for shared decision-making. CMAJ. 2021; 193 (9): E312-4.

As well known, antibodies can be transmitted from mother to the fetus via placental transport.4444 Carsetti R, Quintarelli C, Quinti I, Piano Mortari E, ZumlaA, Ippolito G, et al. The immune system of children: the key to understanding SARS-CoV-2 susceptibility? Lancet Child Adolesc Health. 2020; 4 (6): 414-6.,4545 Xia Wang, Wang X, Yang P, Zheng J, Liu P, Wei C, et al.Dynamic changes of acquired maternal SARS-CoV-2 IgG in infants. Sci Rep. 2021; 11 (1): 8021. The transportation of antibodies, such as Immunoglobulin-G (IgG), protect the baby from virus infections after birth, and this process is known as passive immunization.4444 Carsetti R, Quintarelli C, Quinti I, Piano Mortari E, ZumlaA, Ippolito G, et al. The immune system of children: the key to understanding SARS-CoV-2 susceptibility? Lancet Child Adolesc Health. 2020; 4 (6): 414-6.,4545 Xia Wang, Wang X, Yang P, Zheng J, Liu P, Wei C, et al.Dynamic changes of acquired maternal SARS-CoV-2 IgG in infants. Sci Rep. 2021; 11 (1): 8021. However, in Wang et al.,4040 Wang CL, Liu YY, Wu CH, Wang CY, Wang CH, Long CY.Impact of COVID-19 on Pregnancy. Int J Med Sci. 2021; 18 (3): 763-7. the IgG levels of infants decreased considerably in the first two months of life, suggesting that the passive immunization of IgG for SARS-CoV-2 provided limited protection for the infants, especially if the mother was infected with the virus for less than two weeks before delivery.

The key question to be answered at this point is whether there is transmissibility of antibodies from the pregnant woman who received the vaccine to the fetus. Rottenstreich et al.4646 Rottenstreich A, Zarbiv G, Oiknine-Djian E, Zigron R, WolfDG, Porat S. Efficient maternofetal transplacental transfer of anti- SARS-CoV-2 spike antibodies after antenatal SARS-CoV-2 BNT162b2 mRNA vaccination. Clin Infect Dis. 2021; ciab266. Epub ahead of print. indicated that immunization of pregnant women may provide maternal and neonatal protection, since they found antibodies (IgG) in umbilical cord serum. This is still unclear, so clinical trials should be conducted to understand the association of these outcomes.

Our study has some limitations. Because of the unprecedented nature of the subject due to the recent pandemic, few population-based clinical studies have been published in the literature assessing the health condition of pregnant women and newborns relating to the involvement of COVID-19. Most of the studies included in this review were case reports and retrospective case report analyzes with a small sample size. We suggest that longitudinal clinical studies with a representative sample be conducted in order to ensure a better understanding of the relationship among COVID-19, pregnancy and neonate outcomes. Also, the percentages of each symptom during pregnancy were calculated based on a ratio between the total number of cases and the studies that have reported such condition. If a paper had not reported a determined symptom, it was inferred that that condition was not present. Moreover, most of the studies published so far have evaluated patients in the 3rd trimester of pregnancy, which makes it impossible to understand the cause-and-effect relationship of the 1st and 2nd trimesters and COVID-19. Finally, future studies should answer some other questions, such as whether vaginal delivery increases the risk of vaginal transmissibility and whether uterine contractions increase the possibility of the virus ascending. As well as, the role of COVID-19, pregnancy and neonate: systematic review women’s vaccination on infants’ protection.

Despite the limitations of this study, this review carried out an extensive search of the literature in different databases, with well-defined criteria and in a standardized protocol, which ensured the inclusion of studies published in high-impact journals.

Based on this review, it can be concluded:
  1. COVID-19 in women during pregnancy results in symptoms similar to those experienced by non-pregnant women when affected by the same disease. There is a high rate of asymptomatic positive cases during pregnancy. When the cases are symptomatic, the disease is revealed in its mildest form. Fever and cough are the clinical signs commonly seen in pregnancy;

  2. There is still no plausible evidence suggesting vertical transmission of SARS-CoV-2 virus from mother to child. However, in this review it was possible to observe that cesarean sections have been performed more frequently. High rates of premature births also have been reported;

  3. As COVID-19 maternal illness does notappear to be as severe as SARS and MERS, the high rate of cesarean section is unreasonable. Obstetricians should assess case by case in order to avoid the indication of unnecessary cesarean sections;

  4. Although there is no evidence of the virus inthe infected woman's breast milk, breastfeeding might lead to the baby's infection due to the close contact. Nevertheless, breastfeeding should be encouraged, but mothers should be given adequate guidance on preventive protocols to avoid transmission.

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Publication Dates

  • Publication in this collection
    25 Oct 2021
  • Date of issue
    Jul-Sep 2021

History

  • Received
    15 Jan 2021
  • Reviewed
    07 May 2021
  • Accepted
    15 July 2021
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