key: cord-0855591-v96n5drf
authors: Wake, Addisu Dabi
title: Intrauterine Vertical Transmission of SARS-CoV-2 Infection Among Confirmed Cases of Pregnant Women: “A Double Burden for the Pregnant Women”—A Systematic Review
date: 2022-03-30
journal: Glob Pediatr Health
DOI: 10.1177/2333794x221089765
sha: 465885e7df7f65b8ec3ec428c1f61eaa079e1605
doc_id: 855591
cord_uid: v96n5drf

Introduction. The world health organization (WHO) has declared the outbreak of novel coronavirus (2019-nCoV), which is now known as Coronavirus Disease 2019 (COVID-19). Whereas, its quick global spread has resulted in a worldwide pandemic. The present review article was intended to evaluate intrauterine vertical transmission of SARS-CoV-2 infection among confirmed cases of pregnant women. Methods. Web of Science, EMBASE, PubMed, African Journals OnLine, Scopus, PsycINFO, HINARI, Cochrane Library, Wiley Online Library, and Google scholar were used for search. Result. A total of 43 articles were included in to this systematic review. A total of 1,300 neonates born from pregnant women confirmed for COVI-19 were tested for SARS-CoV-2 infection by real-time reverse transcriptase–polymerase chain reaction (RT-PCR). From the 1,300 neonates tested for SARS-CoV-2 infection, 93 neonates were found positive for this infection by RT-PCR. From this systematic review finding, the vertical transmission rate of SARS-CoV-2 infection was 7.15%. This pandemic has stressed the entire public, particularly pregnant women and healthcare providers, while it challenged antenatal care and postnatal care by far. Thus, even being under lockdown in the middle of a global pandemic is stressful enough. Therefore, imagine the added burden of being pregnant, which could be a double burden for these women. Conclusion. There is no concrete evidence of vertical transmission of SARS-CoV-2. Therefore, due to the limited number of clinical evidences, obstetricians, pediatricians, and other healthcare providers should continuously update their knowledge and be conscious about the transmission of SARS-CoV-2 vertically during pregnancy.

The COVID-19 pandemic was initially reported from Wuhan, China. [1] [2] [3] [4] The outbreak of infection with SARS-CoV-2 has developed in China and has spread across different countries since December 2019. 5 Emergency action have been taken by Chinese government to control this outbreak. 6 It has been brought to worldwide attention and stated as a pandemic by the WHO. 7 Since this pandemic is an extremely contagious disease, 8 it is spreading swiftly. 9 It is spreading globally, 10, 11 and remains a worldwide challenge. 12 This pandemic has a substantial mortality and morbidity rates, 1, 9, 13 while it also causes an extensive economic crisis. 14 This burden has required drastic measures across all continents. 15 The COVID-19 has the potential to devastatingly influence young children's development globally. 16 Due to this, mental health is a key community problem. 17 It has an enormous influence on the mental health of youth. 18 Moreover, fears are growing regarding the impact of the virus on the sexual and reproductive health of women and girls. This is due to that the virus has an devastating effect on them. 19 This pandemic has also put massive stress on healthcare workers, patients, and healthcare systems. The pregnancy care and fetal diagnosis should be continued. 20 It has an extreme effect on pregnant mothers and women in the early postpartum period emotional wellbeing. 21 There is the potential for pregnant women to be susceptible to mental problems during this pandemic. 22 The governments have applied lockdowns to limit the movements of people as methods to control the spread this pandemic. 23 Several countries have employed physical distancing, lockdowns, and stay-at-home actions to control it. 24 Its spread has formed several of the problems for the society because of the absence of a vaccine and effective treatment. 25 The extent of the COVID-19 crisis represents an extraordinary global challenge. 26 This has resulted in problems such as isolation, mental health problems and economic instability. 25 This pandemic has brought major deviations to social behavior. 27 There has been a hasty increase in the study in reply to the outbreak of this pandemic. Despite the researches are pertinent to control this pandemic, further quality study is required to offer reliable strategies to manage this health crisis in a short term and long term. 28 Therefore, this systematic review was intended to evaluate the potential intrauterine vertical transmission of a novel SARS-CoV-2 among confirmed cases of pregnant women. 

The study subject for this systematic review was newborns delivered by COVID-19 infected women.

Pregnant women infected by COVID-19 confirmed by RT-PCR laboratory were considered for this study.

Web of Science, EMBASE, PubMed, African Journals OnLine, Scopus, PsycINFO, HINARI, Cochrane Library, Wiley Online Library, and Google scholar were used for search. All electronic sources of information were searched for the articles. "COVID-19," "SARS-CoV-2," "pregnancy," "neonates," and "Newborn" were the search terms used to find the related articles. To integrate these search terms; "AND" and "OR" Boolean operators were used.

The inclusion criteria for this study were; (1) articles which reported findings from newborn/s born by pregnant women infected by COVID-19 (confirmed by RT-PCR laboratory) and for which the laboratory test was done and reported with in the article; and (2) articles published in English language. Whereas, the articles which didn't reported the test results for newborn/s and pregnant women, articles with poor quality and articles which were not fully accessible were excluded from this study.

The primary outcome of this study was the potential vertical transmission of a novel SARS-CoV-2 infection in pregnant women. Thus, the outcome variable was the positive/negative vertical transmission of a novel SARS-CoV-2infection in pregnant women as per the report of the included studies.

Data were exported to Thomson Reuters EndNote version 8 after retrieval of the articles from the databases used. The articles were checked for the relevance of the title and abstracts to be included in to this study according to a pre-setted study selection criterion. A Microsoft Excel worksheet was used to extract the data from the selected articles. The prepared format has incorporated first author name, year of publication, sample size, study country, participants, study design, possible vertical transmission, and sample type and results.

The quality of each article was checked to include in to this study. The quality of articles which were case report and case series were assessed by the "Methodological quality and synthesis of case series and case reports" prepared by Murad et al 29 The Newcastle-Ottawa Scale (NOS) quality assessment criteria was used for other studies. 30, 31 For this study, a modified NOS was used and ≥5 from 10 scores was used to classify the article as a high quality score and to include the articles in this study. 32 This systematic review was conducted on the vertical transmission of a novel COVID-19 infection among pregnant women. For study screening, selection, and inclusion in to this systematic review, a PRISMA flowchart diagram, 33, 34 and PRISMA checklist 34 were used.

This study is a systematic review which was done by reviewing different articles published on different journals worldwide. There was no data collected from human. Therefore, Ethics approval and consent to participate were not applicable for this study.

A total of 7098 articles were identified through a search made by all the above listed databases. From these, 4090 articles were excluded because of the duplications found. From the remaining 3008 articles, 2862 were excluded by title and abstract due to irrelevance. From the total 146 articles screened for full text, 36 articles were omitted because of full text were not accessible. From the remaining 110 articles screened for eligibility, 25 articles excluded due to full text not in English, 23 articles excluded due to the outcome variable not well defined, and 19 articles excluded because of poor quality. Finally, 43 articles were included in to this systematic review ( Figure 1 ).

A total of 43 articles were included in to this systematic review. This systematic review has included various articles from different countries such as China, Spain, United states, Central America, India, Iran, Italy, Timisoara, Rome, French Guiana, United states, and Brazil (Table 1) .

A total of 1300 neonates born from pregnant women confirmed for COVI-19 were tested for SARS-CoV-2 infection by RT-PCR. From the 1300 neonates tested for SARS-CoV-2 infection, 93 neonates were found positive for this infection by RT-PCR. From this systematic review findings, the vertical transmission rate of SARS-CoV-2 infection was 7.15% (Table 1) .

Below is a brief summary of studies conducted among COVID-19 positive pregnant mothers who gave birth. According to these studies, there are controversies upon the outcome of neonates born from confirmed cases of COVID-19 women. Discrepancies were seen between the currently existing literatures. Some of the studies are reported that there were no positive infants born from COVID-19 positive pregnant women. This because of that the findings from some studies showed that there were SARS-CoV-2 positive infants born to SARS-CoV-2 positive women 62-77 (Table 1 ).

A total of 43 articles were included in to this study. This systematic review has included various articles from different countries such as China, Spain, United States, Central America, India, Iran, Italy, Timisoara, Rome, French Guiana, United states, and Brazil. A total of 1300 neonates born from confirmed COVI-19 pregnant women who were tested for SARS-CoV-2 infection by RT-PCR. From the 1300 neonates tested for SARS-CoV-2 infection, 93 neonates were found positive for this infection by RT-PCR. From this systematic review finding, the vertical transmission rate of SARS-CoV-2 infection was 7.15%. According to the studies, there are controversies upon the outcome of neonates born from confirmed cases of COVID-19. Discrepancies were seen between the currently existing literatures. Some of the studies are reported that there were no positive infants born from COVID-19 positive pregnant women. This because of that the findings from some studies showed that there were SARS-CoV-2 positive infants born to SARS-CoV-2 positive women. [62] [63] [64] [65] [66] [67] [68] [69] [70] [71] [72] [73] [74] [75] [76] [77] The vertical transmission of several microorganisms to the fetus from an infected mother can lead to shocking consequences. This can be happened during antenatal or per-partum, but perinatal or postnatal transmission can have severe results. 78 The evidence revealed that COVD-19 causes some histopathological changes. Even though the vertical transmission of the virus is clear not yet, however, the available data indicated that there was an indirect effect of the virus on the fetus. 79 The earliest data have reported as there is no concrete evidence for vertical transmission of SARS-CoV-2 virus because of intrauterine infections. 52,80-88 It will probably be a rare that fetuses will be uninfected at the time of their birth, if intrauterine transmission of SARS-CoV-2 occur. 83 There is no information found for vertical transmission of this virus from confirmed pregnant mothers to fetuses. However, the women could be at augmented risk for more severe respiratory complications. 84 The available data revealed that the vertical transmission of this virus from infected mothers in a third trimester maybe doesn't happen. 85 The vertically transmission, short-term, and long-term harm of SARS-CoV-2 to offspring is still uncertain. 52 Currently, there is no strong evidence of intrauterine transmission of SARS-CoV-2. 86 The earliest data showed that COVID-19 may not lead to the augmented risk in the pregnant population. Besides, they were not confirmed the vertical transmission. 87 The earliest study showed that the clinical features of infected pregnant women with this virus in late pregnancy were found to be similar to those of nonpregnant patients. 80 However, since the impact of this virus on pregnant women is still limited, they should be given a consideration including their newborns, about COVID-19 management and •

Sample size is explained in number of newborn/s included in the articles. prevention means. 89 The pregnant mother must be focused as high-risk for COVID-19 and need to lessen the contact. 90 They may be more prone to this virus which is because of the immunological and physiological changes. So that, they must apply routine preventive actions. 91 COVID-19 in pregnancy were found to be related to maternal morbidity and preterm birth. The associated risk factors were age of women beyond 35 years, being overweight, and obesity. 92 Besides, miscarriage, fetal distress, respiratory distress, and preterm delivery can be caused by COVID-19. 81 Contrary, most of the experts have accepted approach the approach of isolating the infants from women suspected or confirmed with COVID-19 as a means of decreasing the risk of transmission to baby. 93 Those infected pregnant women should obtain better consideration. This pandemic virus could asymptotically arise at gestation time. However, they get diagnosed after delivery. 94 The study done among asymptomatic and symptomatic pregnant women in New York showed that the severity of this disease in pregnant women was mild, severe, and critical; appears similar to that in nonpregnant in 86%, 9.3%, and 4.7% of them respectively. 95 According to the research conducted on 9 pregnant women with confirmed cases; 7 out of 9 were died, 1 out of 9 was remains critically ill, and 1 out of 9 was recovered after long hospitalization at the time of reporting. 96 In pregnancy, the management of this pandemic comprises such as; infection control procedures, oxygen therapy, early isolation, avoidance of fluid overload, consideration of empiric antibiotics, laboratory testing, fetal monitoring, uterine contraction monitoring, separated delivery planning, early mechanical ventilation, and multidisciplinary consultation. 97

If the pregnant mothers are confirmed for infection of COVID-19, the choice of delivery judgment would be better if individualized depending on factors like maternal, fetal, gestational age, and delivery circumstances. Vaginal delivery via induction of labor, with eventual instrumental delivery to prevent maternal fatigue, should be selected to prevent needless surgical consequences. 98 Besides, a study suggested that COVID-19 management for positive pregnant mothers must be adopted and performed by a multi-disciplinary team method. [98] [99] [100] A multidisciplinary team which includes obstetricians, intensivists, maternal-fetal medicine subspecialists, virologists, obstetric anesthetists, neonatologists, internal medicine, midwives, and infectious disease specialists are better to be undertaken during managing these patients. 100 Furthermore, recognizing the extent to which COVID-19 affects women and men differently will be the essential to understand the bigger influence of this disease both during the crisis and during individual and societal recovery. 101 Overall, Since the SARS-CoV-2 vertical transmission has no evidence till now, it is important to keep all the specimens of SARS-CoV-2 infected and suspected pregnant women and their newborns for in-depth study and continuous follow-up observation of future generations. 52 The study described that if the exposure arose at a delivery time, the virus may need a longer incubation period prior to test swabs show positive outcomes. As a result, nasopharyngeal testing instantly after delivery may not be the ideal method to assess vertical transmission. Particularly, the existence of viral RNA in placental and membranes samples by RT-PCR during the delivery shows the requirement for more research for likelihood of vertical transmission. 102

The quick global spread of COVID-19 has resulted in a worldwide pandemic. This pandemic remains a global challenge. Currently, it is a major and critical global health emergency. From this systematic review findings, out of 1300 neonates tested for SARS-CoV-2 infection, 93 neonates were found positive for this infection by RT-PCR. The rate of vertical transmission of SARS-CoV-2 infection was 7.15%. The present review found that the possibility of a vertical transmission of COVID-19 is recently a highly controversial issues across the worldwide. This is because there is a discrepancy of literatures were found. Some studies stated as the were no vertical transmission of SARS-CoV-2 in neonates born of COVID-19 confirmed women, whereas the other studies reported that as there was a vertical transmission of this virus.

To counteract and control this aggressive pandemic virus, the global healthcare system should update and modify their tools and practices accordingly with time manner. There is an increasing requirement for information concerning to the mother and neonate outcomes during COVID-19 pandemic. This study has addressed the significant issues for healthcare providers giving care for COVID-19 confirmed cases of pregnant, for stakeholders, for health policy makers and implementers, and for the pregnant populations as the whole.

The available data regarding to the pregnant mothers with COVID-19 provides a favorable outcome. However, the risks for maternal, and fetal should not be underrated. The available information is limited to the mothers who developed the COVID-19 in late gestation and mothers who delivered shortly after the diagnosis of COVID-19. But, the baby outcome from a long-standing of COVID-19 disease diagnosed mother, which occurred in early gestation are unknown. Because of the inadequate figure of clinical evidences, pediatricians, obstetricians, and other healthcare providers should continually update their knowledge and be conscious regarding the transmissions of SARS-CoV-2 vertically during pregnancy. Furthermore, it is expected that the future researches would offer more evidence on maternal and baby circumstances for obstetrical interventions. Lastly, the present review recommends that a further high-quality study is needed to conclude this critical issue of confusion concerning to the vertical transmission surely.

The author made a substantial contribution to this study on the entire aspects.

The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The author(s) received no financial support for the research, authorship, and/or publication of this article.

Addisu Dabi Wake https://orcid.org/0000-0003-1219-0836

Understanding novel COVID-19: its impact on organ failure and risk assessment for diabetic and cancer patients

What we know so far: COVID-19 current clinical knowledge and research

World Health Organization declares global emergency: a review of the 2019 novel coronavirus (COVID-19)

Analyzing the epidemiological outbreak of COVID-19: a visual exploratory data analysis approach

A patient with SARS-CoV-2 infection during pregnancy in Qingdao

The transmission and diagnosis of 2019 novel coronavirus infection disease (COVID-19): a Chinese perspective

Epidemiology, Pathogenesis, and control of COVID-19

Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence

COVID-19: towards understanding of pathogenesis

Understanding of COVID-19 based on current evidence

Understanding and addressing sources of anxiety among health care professionals during the COVID-19 Pandemic

COVID-19: transmission, prevention, and potential therapeutic opportunities

Coronavirus disease (COVID-19) and neonate: what neonatologist need to know

COVID-19 pandemic, a war to be won: understanding its economic implications for Africa. Appl Health Econ Health Policy

Coronavirus disease 2019 (COVID-19) pandemic and pregnancy

Effects of the global coronavirus disease-2019 pandemic on early childhood development: short-and long-term risks and mitigating program and policy actions

Risk factors for anxiety and depression among pregnant women during the COVID-19 pandemic: a web-based cross-sectional survey

The effect of COVID-19 on Youth Mental Health

COVID-19 has "devastating" effect on women and girls

Fetal diagnosis and therapy during the COVID-19 pandemic: guidance on behalf of the International Fetal Medicine and Surgery Society

Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic: a call for action

Maternal mental health in the time of the COVID-19 pandemic

Using social media data for assessing children's exposure to violence during the COVID-19 pandemic

Addressing violence against children, women and older people during the COVID-19 pandemic: key actions

Gender-based violence during COVID-19 pandemic: a mini-review. Front Glob Womens Health

The impact of the COVID-19 pandemic response on other health research

Health behaviour changes during COVID-19 and the potential consequences: a minireview

Epidemiology, causes, clinical manifestation and diagnosis, prevention and control of coronavirus disease (COVID-19) during the early outbreak period: a scoping review

Methodological quality and synthesis of case series and case reports

Panethnic differences in blood pressure in Europe: a systematic review and meta-analysis

The Newcastle-Ottawa Scale (NOS) for Assessing the Quality of Nonrandomized Studies in Meta-Analyses

Prevalence of antidiabetic medication adherence and determinant factors in Ethiopia: a systemic review and meta-analysis

The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration

Preferred Reporting Items for systematic reviews and Meta-Analyses: the PRISMA Statement

Infants born to mothers with a new Coronavirus (COVID-19)

Clinical characteristics and intrauterine vertical transmission potential of COVID-19 infection in nine pregnant women: a retrospective review of medical records

Possible vertical transmission of SARS-CoV-2 from an infected mother to her newborn

Perinatal transmission of 2019 Coronavirus disease-Associated Severe Acute Respiratory Syndrome Coronavirus 2: should We Worry?

Clinical characteristics of 19 neonates born to mothers with COVID-19

Asymptomatic COVID-19 infection in late pregnancy indicated no vertical transmission

Clinical course of coronavirus disease-2019 in pregnancy

Clinical course of severe and critical coronavirus disease 2019 in hospitalized pregnancies: a United States cohort study

An analysis of 38 pregnant women with COVID-19, their newborn infants, and maternal-fetal transmission of SARS-CoV-2: maternal Coronavirus infections and Pregnancy Outcomes

Impact of COVID-19 infection on pregnancy outcomes and the risk of maternal-to-neonatal intrapartum transmission of COVID-19 during natural birth

Lack of vertical transmission of severe Acute Respiratory Syndrome Coronavirus 2, China. Emerg Infect Dis

Unlikely SARS-CoV-2 vertical transmission from mother to child: a case report

Vaginal delivery report of a healthy neonate born to a convalescent mother with COVID-19

Clinical features and outcomes of pregnant women suspected of coronavirus disease 2019

A pregnant woman with COVID-19 in Central America

Clinical analysis of 10 neonates born to mothers with 2019-nCoV pneumonia

Antibodies in infants born to mothers with COVID-19 pneumonia

A case report of Neonatal 2019 Coronavirus disease in China

Maternal and neonatal outcomes of pregnant women with Coronavirus Disease 2019 (COVID-19) pneumonia: a case-control study

Analysis of vaginal delivery outcomes among pregnant women in Wuhan, China during the COVID-19 pandemic

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Pregnancy In China: A Retrospective Cohort Study. 2020. medRxiv

Clinical characteristics and risk assessment of newborns born to mothers with COVID-19

Coronavirus disease 2019 in pregnancy

Assessing SARS-CoV-2 vertical transmission and neonatal complications

Pregnancy outcomes and vertical transmission capability of SARS-CoV-2 infection among asymptomatic females: a cross-sectional study in a tertiary care rural hospital

Risk factors associated with COVID-19 symptoms and potential vertical transmission during pregnancy: a retrospective cohort study

Vaginal delivery in SARS-CoV-2-infected pregnant women in Northern Italy: a retrospective analysis

Possible early vertical transmission of COVID-19 from an infected pregnant female to her neonate: a Case Report

Coronavirus disease 2019 in pregnant women: a report based on 116 cases

Possible vertical transmission of COVID-19 to the newborn; a case report

Maternal and fetal effects of COVID-19 virus on a complicated triplet pregnancy: a case report

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vertical transmission in neonates born to mothers with Coronavirus Disease 2019 (COVID-19) pneumonia

Clinical Features and the Maternal and Neonatal Outcomes of Pregnant Women With Coronavirus Disease 2019. 2020. medRxiv

Clinical features and obstetric and neonatal outcomes of pregnant patients with COVID-19 in Wuhan, China: a retrospective, single-centre, descriptive study

Preterm delivery, maternal death, and vertical transmission in a pregnant woman with COVID-19 infection

Neonatal early-onset infection with SARS-CoV-2 in 33 neonates born to mothers with COVID-19 in Wuhan, China

Consequences of early separation of maternal-newborn dyad in neonates born to SARS-CoV-2 positive mothers: an Observational Study

Maternal, fetal and neonatal outcomes of large series of SARS-CoV-2 positive pregnancies in peripartum period: a single-center prospective comparative study

Clinical profiles of neonates born to mothers with COVID-19

Early-onset symptomatic neonatal COVID-19 infection with high probability of vertical transmission

Management and short-term outcomes of neonates born to mothers with active perinatal SARS-CoV-2 infection

Vertical transmission of SARS-CoV2 during pregnancy: a highrisk cohort

Evidence for and against vertical transmission for severe acute respiratory syndrome coronavirus 2

Being pregnant in the COVID-19 pandemic: effects on the placenta in all aspects

Risks of novel Coronavirus disease (COVID-19) in pregnancy; a narrative review

Novel coronavirus infection and pregnancy

Infections in pregnancy with COVID-19 and other respiratory RNA virus diseases are rarely, if ever, transmitted to the fetus: experiences with coronaviruses, Parainfluenza, Metapneumovirus respiratory syncytial virus, and Influenza

Vertical transmission of Coronavirus disease 19 (COVID-19) from infected pregnant mothers to neonates: a Review

Perinatal aspects on the covid-19 pandemic: a practical resource for perinatalneonatal specialists

Intrauterine vertical transmission of SARS-CoV-2: what we know so far

Considerations for obstetric care during the COVID-19 Pandemic

Coronavirus disease 2019 (COVID-19) during pregnancy in patients with rheumatic diseases

Pregnancy and breastfeeding during covid-19 pandemic: a systematic review of published pregnancy cases

Severe COVID-19 during pregnancy and possible vertical transmission

Novel coronavirus disease 2019 and perinatal outcomes

Coronavirus disease 2019 in pregnancy was associated with maternal morbidity and preterm birth

Should infants be separated from mothers with COVID-19? First, Do No harm

Clinical analysis of pregnant women with 2019 novel coronavirus pneumonia

Coronavirus disease 2019 infection among asymptomatic and symptomatic pregnant women: two weeks of confirmed presentations to an affiliated pair of New York City hospitals

Maternal death due to COVID-19

Coronavirus Disease 2019 (COVID-19) and pregnancy: what obstetricians need to know

Guidelines for pregnant women with suspected SARS-CoV-2 infection

Novel corona virus disease (COVID-19) in pregnancy: what clinical recommendations to follow?

Global interim guidance on coronavirus disease 2019 (COVID-19) during pregnancy and puerperium from FIGO and allied partners: information for Health Care Professionals

Covid-19 and women's triple burden: vignettes from Sri Lanka, Malaysia, Vietnam and Australia

Detection of severe acute respiratory syndrome coronavirus 2 in placental and fetal membrane samples