Abstract
Background
In December 2019, a novel coronavirus disease (COVID-19) emerged in Wuhan, China, with an incredible contagion rate. However, the vertical transmission of COVID-19 is uncertain.
Objectives
This is a systematic review of published studies concerning pregnant women with confirmed COVID-19 and their neonates.
Search strategy
We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google Scholar, Scopus, and WHO COVID-19 database using the following keywords: (Coronavirus) OR (novel coronavirus) OR (COVID-19) OR (COVID19) OR (COVID 19) OR (SARS-CoV2) OR (2019-nCoV)) and ((pregnancy) OR (pregnant) OR (vertical transmission) OR (neonate) OR (newborn) OR (placenta) OR (fetus) OR (Fetal)). The search took place in April 2020.
Selection criteria
Original articles published in English were eligible if they included pregnant patients infected with COVID-19 and their newborns.
Data collection and analyses
The outcomes of interest consisted of clinical manifestations of COVID-19 in pregnant patients with COVID-19 and also the effect of COVID-19 on neonatal and pregnancy outcomes.
Main results
37 articles involving 364 pregnant women with COVID-19 and 302 neonates were included. The vast majority of pregnant patients were in their third trimester of pregnancy, and only 45 cases were in the first or second trimester (12.4%). Most mothers described mild to moderate manifestations of COVID-19. Of 364 pregnant women, 25 were asymptomatic at the time of admission. The most common symptoms were fever (62.4%) and cough (45.3%). Two maternal deaths occurred. Some pregnant patients (12.1%) had a negative SARS‐CoV‐2 test but displayed clinical manifestations and abnormalities in computed tomography (CT) scan related to COVID‐19. Twenty‐two (6.0%) pregnant patients developed severe pneumonia. Two maternal deaths occurred from severe pneumonia and multiple organ dysfunction. Studies included a total of 302 neonates from mothers with COVID‐19. Of the studies that provided data on the timing of birth, there were 65 (23.6%) preterm neonates. One baby was born dead from a mother who also died from COVID-19. Of the babies born alive from mothers with COVID‐19, five newborns faced critical conditions, and two later died. A total of 219 neonates underwent nasopharyngeal specimen collection for SARS‐CoV‐2, of which 11 tested positive (5%). Seventeen studies examined samples of the placenta, breast milk, umbilical cord, and amniotic fluid, and all tested negative except one amniotic fluid sample.
Conclusions
A systematic review of published studies confirm that the course of COVID-19 in pregnant women resembles that of other populations. However, there is not sufficient evidence to establish an idea that COVID-19 would not complicate pregnancy.
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Background
The World Health Organization (WHO) announced the novel coronavirus disease (COVID-19) as a Pandemic on March 7, 2020, when the number of confirmed cases just exceeded 100,000 [1]. As of April 21, 2020, COVID-19 has reached all over the world, with about 180,000 deaths of a total of more than 2 million confirmed cases. Moreover, it seems there is an underestimation in the mortality rate of this infectious disease. Studies estimate the real mortality rate to be about 6% in China, rising to about 15% in other countries [2]. Therefore, COVID-19 is, in general, a life-threatening condition.
COVID-19 can affect multiple organs and systems [3,4,5,6,7,8,9,10,11], although it mainly involves the respiratory system, where its involvement can cause a wide range of symptoms from a common cold to severe respiratory distress [12,13,14,15]. In particular, the disease is more severe and deadly in older age groups and people who have pre-existing comorbidity. The immunopathogenesis of the disease is not clear [16,17,18,19,20,21]. However, as for other infectious conditions, immune dysregulation might increase the risk of severe illness and death from COVID-19 [21,22,23,24,25,26,27].
Pregnancy is a particular condition that can have significant effects on the biological systems of a woman’s body. Notably, pregnant women acquire changes so that their immune system will be able to tolerate pregnancy. These changes mostly place the maternal immune system under a down-regulated condition. As a result, pregnant women are generally considered vulnerable to infectious diseases.
Whereas its transmission mainly occurs through human-to-human contact, the novel coronavirus has shown its potential to transmit via multiple transmission routes [28] and affect both children and adults [13, 29]. It, however, remained unclear whether or not this potentially fatal virus can vertically be transmitted and what are the possible effects of the disease on the pregnancy outcomes.
Methods
The present systematic review was developed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement [14]. Before the study begins, the authors developed the study protocol that is available on request.
Literature search
We carried out a systematic search in multiple databases, including PubMed, Web of Science, Google Scholar, Scopus, and WHO COVID-19 database using the following keywords: (Coronavirus) OR (novel coronavirus) OR (COVID-19) OR (COVID19) OR (COVID 19) OR (SARS-CoV2) OR (2019-nCoV)) and ((pregnancy) OR (pregnant) OR (vertical transmission) OR (neonate) OR (newborn) OR (placenta) OR (fetus) OR (Fetal)). The search took place in April 2020 (Fig. 1).
PRISMA flowchart of the literature search
Selection criteria
We sought studies that investigated the potential effect of COVID-19 on pregnancy and neonatal health. Original articles published in English were eligible if they included pregnant patients infected with COVID-19 and their newborns. The outcomes of interest consisted of clinical manifestations of COVID-19 in pregnant patients with COVID-19 and also, the effect of COVID-19 on neonatal and pregnancy outcomes.
Data extraction
For pregnant women infected with COVID-19, we extracted the following data: article title, author, study type, country, number of pregnant women with COVID-19, clinical manifestations of disease in pregnant women, the trimester of pregnancy, diagnostic technique, potential complications related to COVID-19, delivery, and the maternal outcome(s) of COVID-19. For neonates born from mothers with COVID-19, data on the article title, author, study type, country, number of neonates, neonatal maturity, clinical presentation, neonatal complications, a diagnostic test for COVID-19, Apgar score, and neonatal outcome were extracted. Finally, for pregnancy outcomes, we collected data on the article title, author, study type, country, placental test for viral nucleic acid, and pregnancy complications.
Results
Literature search
The systematic search yielded a total of 1068 search results, of which 785 discrete records remained for screening after removing duplicates. During title and abstract screening, we selected 48 articles for detailed review. In the detailed review process, we excluded thirteen articles with the following reasons for exclusion: seven articles not provided data on pregnant patients or neonatal outcomes [28, 30,31,122] while worsening during the pandemic. It is, therefore, important to gather enough data on pregnant women and their neonates in these countries. However, when this study was carried out, the data on less developed countries were too scarce, which may be because of lack of diagnostic facilities in these countries, insufficient referring, or reporting system. So further investigations are necessary to discover the impact of COVID-19 on perinatal events in develo** countries.
Conclusion
The present systematic review suggests that clinical features and prognosis of pregnant women with COVID-19 may not be worse than the general population as well as some previous studies [121]. Still, this result should not lead to pregnant women ignore their suspect signs and symptoms to present themselves to medical care centers. It is crucial to provide optimum health care for pregnant women during the COVID-19 pandemic and follow their health status, especially respiratory signs and symptoms. The current evidence suggests that clinical features, diagnosis, and prognosis of COVID-19 in pregnant women are not different from those of the disease reported in society. Despite the high rate of contagion of COVID-19, vertical transmission of the novel coronavirus may remain a missing piece of the puzzle due to a lack of sufficient evidence. International collaboration remains a fundamental component of any future attempt to solve the puzzle [123,124,125,126,127].
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MM: Conceptualized the study, conducted database search, search results screening, detailed review, and prepared the initial draft. AS: Prepared the final draft. NR: Supervised the project and critically appraised the manuscript. All authors have read and approved the manuscript.
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Mirbeyk, M., Saghazadeh, A. & Rezaei, N. A systematic review of pregnant women with COVID-19 and their neonates. Arch Gynecol Obstet 304, 5–38 (2021). https://doi.org/10.1007/s00404-021-06049-z
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DOI: https://doi.org/10.1007/s00404-021-06049-z