DOI: https://doi.org/10.21203/rs.3.rs-23407/v1
Background
With more than 1 million confirmed cases of coronavirus disease 2019 (COVID-19) worldwide and more than 50,000 deaths, the pandemic of Severe Acute Respiratory Syndrome CoV (SARS-CoV-2) is rapidly evolving. SARS-CoV-2 can also pose a higher risk to pregnant women, due to their immunosuppression during pregnancy. This study investigates the emerging and most UpToDate published scientific literature on the clinical feature and management recommendations for pregnant women with COVID-19.
Method
A wide range of published scientific literature was systematically searched from PubMed, Embase, Scopus, Web of Science, and “Global research on coronavirus disease (COVID-19)” managed by the World Health Organization, published between 1 January 2019 to 27 March 2020. No limitations were used for geographical location, and articles published in English were included in the review. Results for the eligible studies were charted, analyzed, and presented in a narrative format.
Result
Our study identified 52 unique articles, and 29 of those articles were included in this review after fulltext screening. Participants were mostly in their third trimester and presented with fever, dry cough, myalgia, shortness, and difficulty in breathing. Ground-glass opacity in the computerized tomography scan of the chest was the cardinal feature of COVID-19 pneumonia. Except for two participants, severe pneumonia did not occur among pregnant women. Pregnant women with COVID-19 were treated with a wide range of antiviral drugs. Higher episodes of preterm birth and cesarean delivery were observed; however, it cannot be explicitly attributed to the SARS-CoV-2. There is no published evidence on the vertical transmission of SARS-CoV-2. Pregnancy with COVID-19 infection must be managed by a collaborative team of healthcare professionals during antenatal, delivery, or postnatal stage. Detailed contact tracing, investigating travel history, radiological assessment, and laboratory tests with regular fetal health monitoring must be done.
Conclusion
The emerging evidence of higher perinatal complications puts pregnant women in a further vulnerable condition. Cautiousness is imperative during the clinical management of pregnant women with COVID-19, as there is no approved treatment regime available at this moment. More research is necessary to fill the gaps in the knowledge of the clinical spectrum of COVID-19 among pregnant women.
As of 3 April 2020, more than 1 million confirmed coronavirus disease 2019 (COVID-19) cases have been detected worldwide, and more than 50,000 deaths have been attributed to this pandemic (1). COVID-19 is caused by a novel mutation of a previously known coronavirus (CoV) and has been labeled as Severe Acute Respiratory Syndrome CoV (SARS-CoV-2), mostly spreads through respiratory droplets made by sneezing and coughing. This is also known as Wuhan CoV due to its first detection in Wuhan, the capital city of Hubei province in China. Now, this virus has been detected across all regions (195 countries) within the world. This is an enveloped and positive-sense single-stranded ribonucleic acid virus belonging to the ‘Coronaviridae’ family, ‘Nidovairales’ order, and ‘Rivoviria’ realm (2). CoV has also caused SARS (began in 2002) and the Middle East respiratory syndrome (began in 2012) epidemics before COVID-19 (3).
Although a large proportion of people infected with SARS-CoV-2 may suffer from asymptomatic infection to mild to moderate fever or respiratory illness and would recover without any special treatment, older people and people with underlying medical conditions or immunosuppression (e.g., cardiovascular disease, diabetes, and other chronic diseases) may demonstrate a severe form of pneumonia, including deaths (4,5). SARS-CoV-2 can also pose pregnant women at higher risk due to their immunosuppression during pregnancy (6); however, it remains unclear whether this virus is transmitted from mother to child during pregnancy (7). Although new data are coming regarding its origin, microbiological and clinical features, and severity, few previous studies reported its impacts during pregnancy.
Despite the dearth of existing studies, summarizing the existing case reports/series, expert consensus, correspondences, commentaries, opinions, editorials, research letters, original articles, and systematic reviews may help to understand the impacts of SARS-CoV-2 on pregnancy, including clinical management because of little knowledge about these. A scoping review of the existing literature may help identify not only available knowledge but also existing gaps and may direct future research (8). However, despite preliminary evidence and rationale suggesting that SARS-CoV-2 infection during pregnancy may severely impact its outcomes, to our knowledge, no previous studies conducted any scoping review by summarizing all existing studies. We aim to address these knowledge gaps by investigating the most UpToDate published scientific literature to synthesize the growing body of evidence on the clinical feature of COVID-19 among pregnant women and recommendations around their clinical management.
This rapid scoping review was conducted following the steps recommended by Arksey and O’Malley (9), and Levac and colleagues (10). Reporting of the result of the review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses’ Extension for Scoping Reviews (PRISMA-ScR) (11). Development of search strategy and literature search was collaboratively done by MH and TA. Two investigators (MH and GMK) independently performed the study selection by title and abstract, and full-text screening. Due to the limitation of time, data extraction, and synthesis of the result was done collaboratively by MH and GMK. Fig. 1 presents the schematic diagram of the study selection process based on the guidelines of Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA). Ethical approval was not obtained for the review, as all required information was obtained from publicly available literature, and no primary data was collected or generated during the review process.
A rapid scoping review was conducted to identify the relevant scientific literature providing recent evidence on clinical features and management recommendations for COVID-19 among pregnant women. As part of the review process, a systematic and replicable search strategy was developed considering two concepts: (a) pregnant women, and (b) COVID-19. Relevant keywords and index terms associated with these two concepts were identified from the MeSH terms listed in PubMed and from Google Scholar.
The search strategy was implemented between 1 January 2019 to 27 March 2020 across four electronic databases: (a) PubMed (ncbi.nlm.nih.gov/pubmed/), (b) Embase (embase.com), (c) Scopus (scopus.org), and (d) Web of Science (webofknowledge.com). Also, a hand search was conducted in the electronic database “Global research on coronavirus disease (COVID-19)” managed by World Health Organization (WHO) (https://www.who.int/emergencies/diseases/novel-coronavirus-2019/global-research-on-novel-coronavirus-2019-ncov). Literature search from PubMed generated 28 records published between 01 January 2019 to 27 March 2020 (Dated 27 March 2020). The search strategy for PubMed is presented in Table 1, and the details of the individual search strategy for the other databases are provided in the supplementary material.
Table 1: PubMed Search Strategy on pregnancy and Coronavirus Disease 2019 (COVID-19) implemented on 27 March 2020
Database |
Concept |
Key Words |
Results |
|
PubMed |
Pregnant women |
Line 1 |
(Pregnant Woman[MESH] OR Pregnan*[tw] OR Gestation[tw] OR Gravid*[tw] OR natal*[tw] OR Antenatal[tw] OR Perinatal[tw] OR Postnatal[tw] OR partum*[tw] OR Antepartum*[tw] OR peripartum*[tw] OR postpartum*[tw] OR puerperium[tw]) AND |
28 |
Coronavirus disease-19 |
Line 2 |
Wuhan coronavirus"[tw] OR "Wuhan seafood market pneumonia virus"[tw] OR "COVID19 virus"[tw] OR "COVID-19 virus"[tw] OR "coronavirus disease 2019 virus"[tw] OR "SARS-CoV-2"[tw] OR "SARS2"[tw] OR "2019-nCoV"[tw] OR "2019 novel coronavirus"[tw] OR "2019 novel coronavirus infection"[tw] OR "2019-nCoV infection"[tw] OR "COVID-19 pandemic"[tw] OR "coronavirus disease-19"[tw] OR "2019-nCoV disease" OR "COVID19"[tw] OR "2019 novel coronavirus disease"[tw] OR "coronavirus disease 2019"[tw]) AND |
||
Time frame |
Line 3 |
("2019/01/01"[PDat] : "2020/03/27"[PDat]) |
Search results from the five electronic databases resulted in 69 initially identified literature, which was imported into Covidence systematic review software (covidence.org) to implement the selection process. At this stage, 17 duplicates were removed. Next, titles and the abstracts of 52 uniquely identified studies were screened, and an additional 11 studies were found to be irrelevant based on the set of a priori inclusion and exclusion criteria (Table 2).
Table 2: Inclusion and exclusion criteria for the record selection process associated with pregnancy and Coronavirus Disease 2019 (COVID-19)
|
Inclusion Criteria |
Exclusion Criteria |
Theme |
Evidence of Coronavirus disease-19 among pregnant women |
Records which did not provide any findings or recommendation related to Coronavirus disease-19 among pregnant women |
Evidence characteristics |
Original research |
Author's reply |
Case studies or case reports |
Research highlight |
|
Expert consensus |
News or media watch |
|
Correspondence, commentary, opinion or editorials |
|
|
Systematic, scoping or rapid review |
|
|
Research letter |
|
|
Time frame |
1 January 2019 to 27 March 2020 |
|
Reporting characteristics |
Records published in scientific journals |
Records not published in English |
For the eligible literature presenting the subject matter of the scoping review, full documents were obtained and imported into Covidence. For full-text screening, the same set of criteria was used by the investigators. Studies published in scientific journals and written in English were included. Due to the methodological plasticity of scoping review, a variety of published literature was included in the studies, which includes original research, case studies or reports, expert consensus, correspondence, reviews, etc. However, author's reply, research highlights, and news or media watches were excluded from the review.
Investigator charted data on study characteristics (the type of study, location of the study), population characteristics (number of pregnant women, the clinical features of the women), and type of evidence presented in the study. The charted data was summarized by two thematic areas: (a) clinical feature of pregnant women with COVID-19, and (b) recommendations for clinical management of COVID-19 during pregnancy. The collated evidence is presented in a narrative format with the help of tables.
Due to the sparsity of data and the evolving nature of the evidence, the quality of the published literature was not assessed for robustness or generalizability in the rapid scoping review (9,12,13). While Levac and colleagues (10) recommended expert consultation, due to time limitation, it was not performed as a part of this scoping review. No patients or populations were included in the conception and conduct of the scoping review.
Out of the 69 extracted publications, 29 full-text publications were included for the scoping review (6,14–41) (Table 3). Among the included studies, 16 presented clinical findings of COVID-19 among pregnant women, which includes six original articles (15,16,23–25,41), three case reports (18,35,36), two case-reviews (32,39), two research letters (21,40), and one correspondence (37), rapid review (27) and systematic review and meta-analysis (17) each. Out of these 16 studies, only 13 reported original data (15,16,18,21,23–25,27,35–37,40,41) and three study (17,32,34) reviewed data from existing studies (Table 4). From the 16 studies which presented clinical findings of COVID-19, 15 articles were from China and only one from Honduras (40). Cumulatively clinical features of 229 pregnant women were reported in the studies included in this review – ranging from a single (21,35–37,40) to 41 pregnant women (17,24). One of the original articles from Zhu and colleagues (41) was originally presented the clinical findings from 10 neonates. However, we only included the relevant information on the pregnant COVID-19 cases from that study. It is possible that duplication of clinical cases presents between studies – however – we have actively tried to remove duplicate findings from the result.
Table 3: Specifications of published studies (1 January 2019 to 27 March 2020) on pregnancy and Coronavirus Disease 2019 (COVID-19) between
Reference |
Study Type |
Country |
Number of Pregnant Woman |
Original Finding Reported |
Recommendation Reported |
Chen et al.(14) |
Expert consensus |
.. |
.. |
No |
Yes |
Chen et al. (15) |
Original article |
China |
9 |
Yes |
No |
Chen et al. (16) |
Original article |
China |
17 |
Yes |
Yes |
Di Mascio et al. (17) |
Systematic review & meta-analysis |
China |
41a |
No |
Yes |
Fan et al. (18) |
Case report |
China |
2 |
Yes |
Yes |
Favre et al. (19) |
Correspondence |
.. |
.. |
No |
Yes |
Jiao(20) |
Commentary |
.. |
.. |
No |
Yes |
Li et al. (21) |
Research letter |
China |
1 |
Yes |
Yes |
Liang & Acharya (22) |
Special editorial |
.. |
.. |
No |
Yes |
Liu et al. (23) |
Original article |
China |
15 |
Yes |
No |
Liu et al. (6) |
Review article |
.. |
.. |
No |
Yes |
Liu et al. (24) |
Original article |
China |
41b |
Yes |
No |
Liu et al. (25) |
Original article |
China |
13 |
Yes |
No |
Moro et al. (26) |
Correspondence |
.. |
.. |
No |
Yes |
Mullins et al. (27) |
Rapid review |
.. |
32 |
Yes |
Yes |
Poon et al. (28) |
Opinion |
.. |
.. |
No |
Yes |
Qiao (29) |
Comment |
.. |
.. |
No |
Yes |
Rasmussen & Jamieson (30) |
Commentary |
.. |
.. |
No |
Yes |
Rasmussen et al. (31) |
Expert review |
.. |
.. |
No |
Yes |
Schwartz (32) |
Case review |
China |
38 |
No |
No |
Schwartz & Graham (33) |
Correspondence |
.. |
.. |
No |
No |
Wang et al. (34) |
Correspondence |
China |
.. |
No |
Yes |
Wang et al. (35) |
Case report |
China |
1 |
Yes |
No |
Wang et al. (36) |
Case report |
China |
1 |
Yes |
No |
Wen et al. (37) |
Correspondence |
China |
1 |
Yes |
No |
Yang et al. (38) |
Opinion |
.. |
.. |
No |
Yes |
Yu et al. (39) |
Case review |
China |
7 |
No |
Yes |
Zambrano et al. (40) |
Research letter |
Honduras |
1 |
Yes |
No |
Zhu et al. (41) |
Original article |
China |
9 |
Yes |
Yes |
Note: a = Out of the 79 pregnancies affected by Corona Virus infections, 41 were affected by SARS-CoV-2 |
Table 4: Findings on pregnancy and Coronavirus Disease 2019 (COVID-19) reported in published literature (1 January 2019 to 27 March 2020)
Reference |
Study Type |
Patients Characteristics |
Findings |
Chen et al. (15) |
Original article |
All nine pregnant women were confirmed COVID-19 were in their third trimester |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Chen et al. (16) |
Original article |
All 17 pregnant women were tested positive by RT-PCR for SARS-CoV-2 |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Di Mascio et al. (17) |
Systematic review and meta-analysis |
All nine pregnant women were confirmed COVID-19 were in their third trimester |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Fan et al. (18) |
Case report |
Both pregnant women were physicians with confirmed COVID-19 were in their third trimester |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Li et al. (21) |
Research Letter |
The pregnant women were in 35th week of pregnancy with confirmed COVID-19 |
|
|
|||
|
|||
|
|||
|
|||
Liu et al. (23) |
Original article |
All 15 pregnant women were confirmed for COVID-19 pneumonia with gestational age ranging from 12-38 weeks |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Liu et al. (24) |
Original article |
Among 41 pregnant women 16 were laboratory positive SARS-CoV-2, 25 were clinically-diagnosed COVID-19 cases. Their gestational age ranging from 22-40 weeks |
|
|
|||
|
|||
|
|||
|
|||
Liu et al. (25) |
Original article |
Among 13 pregnant women with SARS-CoV-2 positive, two women were less than 28 weeks of gestation, and 11 were in their third trimester |
|
|
|||
|
|||
|
|||
|
|||
|
|||
Mullins et al. (27) |
Rapid review |
32 pregnant women with confirmed SARS-CoV-2 infection |
|
|
|||
|
|||
|
|||
Rasmussen et al. (31) |
Expert review |
-- |
|
|
|||
|
|||
|
|||
|
|||
Schwartz (32) |
Case review |
All 38 pregnant women were in their third trimester in pregnancy, and 37 had confirmed SARS-CoV-2 infection |
|
|
|||
|
|||
|
|||
|
|||
|
|||
Wang et al. (35) |
Case report |
The pregnant women were in her 40th week of pregnancy with COVID-19 |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Wang et al. (36) |
Case report |
A 30-week pregnant woman with COVID-19 |
|
|
|||
|
|||
|
|||
|
|||
Wen et al. (37) |
Correspondence |
A 30-week pregnant woman with COVID-19 |
|
|
|||
|
|||
|
|||
Yu et al. (39) |
Original article |
Seven pregnant women with COVID-19 between 37 weeks to 41 weeks of the gestational period |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
|||
Zambrano et al. (40) |
Research letter |
Pregnant women with 31 weeks of gestation with COVID-19 |
|
|
|||
Zhu et al. (41) |
Original article |
Nine pregnant women were confirmed with COVID-19 (gestational age 31-39 weeks) |
|
|
|||
|
|||
|
|||
|
|||
|
|||
|
Most of the pregnant women suffering from COVID-19 cases were in their third trimester. Liu et al. (23) presented a case of early pregnancy in its 12th week. All the studies reported that COVID-19 confirmation had been done by real-time reverse transcription-polymerase chain reaction (RT-PCR) test; however, Liu and colleagues (24) included 25 participants (out of 41) who were laboratory negative SARS-CoV-2 but had clinical features of COVID-19.
Seven studies reported both clinical findings and recommendations for the management of COVID-19 during pregnancy, which included four original articles (15,16,24,41), two case-reports (18,36), and one correspondence (37). On the other hand, 12 studies exclusively discussed the recommendation of management of COVID-19 during pregnancy without providing any original findings. Among these studies, three were correspondences (19,26,34), two were commentaries (29,30), two were opinion pieces (28,38), one of case review (39), expert consensus (14), expert review (31), review article (6), and special editorial (22) each.
The most common and earliest clinical presentation of COVID-19 is fever, which is often accompanied by dry cough, myalgia, and malaise. Among initial respiratory symptoms, sore throat is most common; however, shortness and difficulty in breathing (dyspnea) and chest distress were reported by pregnant women. Four studies reported gastrointestinal symptoms such as diarrhea (16,23,37,39). Among the atypical findings, abdominal rash (18), and bilateral conjunctival hyperemia (40).
Apart from the RT-PCR result, computerized tomography (CT) scan of the chest was the primary mode of investigation used by the majority of the study to diagnose COVID-19 infection. Patchy ground-glass opacity (GGO) with or without consolidation was the most common feature of COVID-19 pneumonia, which resolved with time. Liu et al. (23) further elaborated on the progression of the lesion into paving patterns and consolidations. In addition to the lung parenchymal change, one of the atypical findings was found in a 30-week pregnant woman who presented with small pleural effusion on the left side.
Common laboratory finding among COVID-19 patients includes lymphopenia (lower-than-normal quantity of lymphocytes in the blood) and elevated C-reactive protein (indicator of inflammation) (15–18,23,31,32,35,36,39). Impaired liver function was also observed, which is reflected by increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (15,21,32,35,39). Among other laboratory findings, three studies reported neutrophilia (24,35,39); one study reported leukocytosis (24); one study stated a lower level of albumin (36); one study reported elevated D-dimer and thrombocytopenia (39) among the pregnant women.
The antiviral drug was most commonly used to treat pregnant women with COVID-19, and the most frequently used four antiviral drugs were atomized inhalation of interferon-ALPHA (35,37,39,41), Oseltamivir (18,37,41), Lopinavir (21,37,37), and Ritonavir (21,36,37). Among other antiviral drugs, Ganciclovir (35) and Arbidol (36,39) were reported to be used in two studies each. The use of a wide range of antibiotics for the treatment of secondary bacterial pneumonia after the COVID-19 was also common, which included – Beta-lactam (35,36) (Abipenem and Sulbactam Sodium), Cephalosporins (18,36,39) (Cefoperazone Sodium and Ceftazidime), Macrolides(18,38) (Azithromycin), and Quinolones (35,38) (Moxifloxacin).
Besides, supportive treatment with methylprednisolone was provided for pneumonia (18,21,35,39). Two studies (18,39) reported the use of traditional Chinese medications along with antiviral and antibiotic treatment. In his case study, Wang et al. (36) reported a 30-week pregnant woman with COVID-19 was given Human Serum Albumin, dexamethasone, and magnesium sulfate to prepare her for an emergency cesarean delivery. The clinical condition of all the pregnant women – except two (25,27) – improved after the treatment. However, none of the studies commented on the efficacy or effectiveness of the medication given to the pregnant women for management of COVID-19.
According to Rasmussen and colleagues (31), currently, there is no evidence suggesting higher susceptibility of COVID-19 among pregnant women, and no maternal death was reported in any study included in this scoping review. The incubation period among pregnant women ranges from two to nine days (39). The development of severe pneumonia was not reported by the majority of the studies. Two studies – Liu et al. (25) and Mullins et al. (27) – reported that two pregnant women developed severe pneumonia, which required mechanical ventilation support in the intensive care unit (ICU).
It is essential to mention that, except for one pregnant woman – in her 12 weeks of gestation (23) – most confirmed COVID-19 cases were in their third trimester of pregnancy. Therefore, little is known about COVID-19 in the earlier stages of pregnancy. In their systematic review, Di Mascio et al. (17) reported no evidence was obtained of miscarriage in the first trimester, which was related to COVID-19 infection. However, with a limited number of cases and without proper controls, we cannot assume the association between miscarriages and SARS-CoV-2 infection.
Eight studies (15,18,21,27,32,36,39,41) specifically mentioned the duration of onset of symptoms to delivery which ranged from one (15,32,41) to 13 days (27). The duration of hospitalization was inconsistently mentioned across studies. Preterm births emerged to be a common feature among pregnant COVID-19 cases. Seven studies – including original articles (25,41), case review (32), research letter (21), and reviews(17,27) – reported preterm births. In some of the pregnancies, preterm births were also accompanied by other pregnancy-related complications – such as preterm rupture of membranes (17,32,41), abnormality of amniotic fluid (35,41), pre-eclampsia (17), intrauterine distress (41), abnormality of the umbilical cord (41), and placenta previa (41). While pregnancy-related complications may be an indication of the cesarean section, the majority of the pregnancies underwent cesarean section (15,16,18,21,23,25,27,32,35,36,39,41), and the indication of deliveries was not always reported. Two of the articles specified that type of anesthetic agent (either epidural or general) used in the cesarean sections, and Chen et al. (16) reported 12 out of 14 pregnant women who received epidural anesthesia experience intraoperative hypotension. Only three vaginal deliveries were reported (23,41), and no peripartum or postpartum complications were mentioned for them.
Except for one stillbirth (25) – from a 34 weeks pregnant woman with fever and sore throat – all pregnancies resulted in live births. The study conducted by Zhu et al. (41) – and this similar finding was reported by Schwartz (32) in his review – reported several newborns presented gastrointestinal (gastric bleeding, refusal to feed, bloating and food intolerance) and respiratory symptoms (abnormalities in chest radiography, respiratory distress syndrome and pneumothorax) afterbirths. Two children developed thrombocytopenia. One premature newborn died on the 9th day due to multiple organ failure, refractory shock, and disseminated intravascular coagulation, which was the only postnatal death of newborns reported in the studies (32,41). Vertical transmission of SARS-CoV-2 was not reported by any studies (15–18,21,23–25,27,31,32,36,39,41), as – after delivery – the newborns or any products of conception was not tested positive for SARS-CoV-2. Yu et al. (39) reported that one neonate was tested positive for SARS-CoV-2 after 36 hours of birth. However, it was also reported that the placenta and cord blood of the mother of the child tested negative for SARS-CoV-2 after delivery. Thus, it is not clear if this is a case of intrauterine vertical transmission.
While a wide range of management recommendation was given in these studies, we reported our findings across the following thematic area: prevention, isolation and screening, diagnostic procedures, management of suspected cases, management of confirmed cases, clinical monitoring of confirmed cases, antenatal stage, delivery stage, and postnatal stage. While the itemized recommendation and associated cautionary measures were listed in Table 5, the critical points of the findings of the scoping review were stated below.
Table 5: Recommendation related to pregnancy and Coronavirus Disease 2019 (COVID-19) reported in the published literature (1 January 2019 to 27 March 2020)
Recommendation |
Caution |
References |
Prevention |
||
|
|
(22,31) |
|
(22,28,30) |
|
|
(22) |
|
Isolation and screening |
||
|
|
(31,34) |
|
(14,22,28–31,34,41) |
|
|
(14,28,31,34,41) |
|
|
(14,30,31) |
|
Diagnostic procedures |
||
|
|
(14,19,22,23,28,31,34) |
|
|
(6,14,22,27,28,34) |
|
(34) |
|
|
(26) |
|
|
(22,28,31) |
|
Management of suspected cases |
||
|
|
(28,31) |
|
(28) |
|
|
(28) |
|
|
(28) |
|
|
(28) |
|
Management of confirmed cases |
(28) |
|
|
|
(14,22,28,31,41) |
|
(14,19,22,28) |
|
|
(28,31,34,39) |
|
|
(22) |
|
|
(14,22,28,30,31) |
|
|
(14,28) |
|
|
|
(14,22,28) |
|
|
(14,22,23,27,28,34) |
|
(22,27) |
|
|
|
(22) |
|
(14) |
|
|
(25,31) |
|
|
(34) |
|
Clinical monitoring of confirmed cases |
||
|
|
(14,22) |
|
(14) |
|
|
(14) |
|
|
(14,22) |
|
|
(14,28) |
|
|
(14) |
|
Management during the antenatal stage |
||
|
|
(20,6) |
|
(19,28,31) |
|
|
(14,28–30,34) |
|
|
(19,22,28,34) |
|
Management during the delivery stage |
||
|
|
(14,34) |
|
|
(14,17,19,22,28,31,39) |
|
(14,19,22,28,38) |
|
|
|
(14,16,28) |
|
(14) |
|
|
|
(28) |
|
(28) |
|
|
(14,28) |
|
|
(14,16,21,22,28,38) |
|
Management during the postnatal stage |
||
|
|
(14,22,27,28) |
|
(14,22,28,29,31,38,41) |
|
|
|
(14,18,27–29,31,34) |
|
(28) |
Prevention (22,28,30,31)
Maintaining personal and social hygiene is the main recommendation for preventing COVID-19. Due to the long incubation period, an asymptomatic individual can infect an unaware pregnant woman. Thus, maintaining the social distancing measures (such as limiting unnecessary travel, avoiding the crowd and public transport), frequently washing hands using soap, using hand sanitizer, and avoid touching face (the areas around the mouth, chins, nose, and eyes) are extremely necessary. Also, it is crucial to take care of the mental health of pregnant women by providing her necessary psychological support to prevent stress and anxiety.
Isolation and screening (14,22,28–31,34,41)
Innovative use of technology can greatly help the screening of suspected pregnant women with COVID-19 infection. Initial screening and triage of the probable cases using telephone or mobile or online portal – whenever possible – can reduce the chance of limiting the exposure or reducing the spread of the infection. Within a healthcare facility, it is paramount to immediately isolate any suspected pregnant women in a single room – if possible, with negative pressure – for screening, contact tracing, and history taking.
Diagnostic procedures (6,14,19,22,26–28,31,34)
Even if asymptomatic, a pregnant woman with a travel history within the previous 14 days or reported contact with a confirmed SARS-CoV-2 patient should be tested for SARS-CoV-2 as soon as possible using an RT-PCR test. As indicated from the clinical findings, CT scan is providing more diagnostic support for COVID-19 cases. Imaging is particularly important as a pregnant woman with imaging characteristics of COVID-19 should be considered as a clinically diagnosed case even if laboratory confirmation of SARS-CoV-2 is negative. Proper precautions need to be taken while using the CT scan, and radiation exposure need to at its lowest achievable limit. It is also important to assess the risk-benefit for each CT examination, and informed consent must be acquired after proper communication(42). The blood sample should be collected and analyzed for microbial cultures to investigate any secondary bacterial infection for post-viral infection pneumonia and sepsis.
One study recommended the application of lung ultrasound to identify pathological lesion indicative of COVID-19 (26). While this is a novel idea and Moro and colleagues (26) provided details description where obstetricians/gynecologists can perform lung ultrasound of the pregnant women. While the RT-PCR test is yet not available everywhere, the existing infrastructure for ultrasound tests can significantly improve the accessibility of the diagnostic and treatment of COVID-19.
Management of suspected cases (28,31)
Management of probable cases of COVID-19 among pregnant women mostly includes supportive treatment and monitoring of the health status while keeping her in isolation. Supportive treatment must ensure adequate rest, sleep, and caloric intake; maintain electrolyte and fluid balance; and provide symptomatic medications such as antipyretic, and antidiarrheal. In addition, oxygen saturation and vital signs need to be assessed, and arterial blood gas analysis, chest imaging, and fetal ultrasound or doppler assessment need to be performed as monitoring purposes.
Management of confirmed cases (6,14,19,22,25,27,28,31,34,39,41)
Treatment of pregnant women with COVID-19 needs to be performed in a negative pressure room – if possible – or in the isolation ward. Worsening cases of COVID-19 pneumonia must be transferred to the intensive care unit with mechanical ventilation support. Integrating the support from an obstetrician, intensive care medicine specialist, microbiologist, pathologist, anesthetist, and neonatologist, a multidisciplinary team should provide the care for pregnant women with COVID-19 infection. Apart from providing supportive treatment, when providing antiviral and antibiotic therapy to a pregnant woman, it is necessary to understand the teratogenic effect of the drugs, which may impact on fetal growth and development.
Clinical monitoring of confirmed cases (14,22,28)
Based on the limited data available, it appears that preterm delivery and associated obstetric complications are more prevalent among pregnant women with COVID-19 infection. Also, existing comorbidity of COVID-19 patients may lead to life-threating conditions (43). Thus, clinical monitoring of the patient during pregnancy is critical. Monitoring fetal health using ultrasound or Doppler assessment may also provide waning for the maternal condition. Any abnormality of fetal heart rate may indicate an early sign of the mother's respiratory deterioration (31). Amniocentesis is not recommended at this stage as it can lead to intrauterine transmission of the infection.
Management during antenatal stage (6,14,19,20,22,28–31,34)
Due to the evolving pandemic, very little is known about the effect of COVID-19 during the first and second trimester of the pregnancy. Thus, asymptomatic pregnant women with laboratory-confirmed SARS-CoV-2 infection are recommended to self-monitor their health by isolating themselves at home for 14 days. One should not stop receiving routine antenatal care due to COVID-19. Moreover, special attention must be given to monitor fetal health and growth.
Management during delivery stage (14,16,17,19,21,22,28,31,34,38,39)
COVID-19 is not an indication of pregnancy termination or conducting an emergency cesarean section. Here, the mother's clinical status, gestational age, and fetal well-being need to be prioritized, and the mode of delivery should be based on obstetric indications. Delivery should be performed in a negative pressure room –whenever possible – with proper biosafety precautions for medical staff. While COVID-19 alone is not an indication of cesarean section, new and emerging obstetric or health complications (such as acute organ failure, septic shock, or fetal distress) may prompt for emergency cesarean section. The anesthesiology team should indicate the mode of analgesia. Evidence suggests, either epidural or general anesthesia can be safely used during cesarean delivery. The use of neuraxial anesthesia may reduce pulmonary complications due to intubation.
As preterm births appear to be more prevalent among COVID-19 patients, the use of steroids (dexamethasone or betamethasone) for lung maturation of the fetus needs to be evaluated by physicians as it can worsen the maternal disease condition. Tocolysis is not recommended to delay spontaneous preterm labor for administering antenatal steroids. No records included in this scoping review indicated vertical transmission of the SARS-CoV-2. All pregnancy-related by-product needs to be treated as biohazardous waste, and disposal of them needs to abide by the proper biosafety regulation.
Management during postnatal stage (14,18,22,28,29,31,34,38,41)
Though recommendation varies across studies, several studies did not recommend delayed cord-clamping to prevent potential vertical transmission of SARS-CoV-2. Newborns should be isolated from suspected or diagnosed COVID-19 positive mother for 14 days. Recommendation on breastfeeding in not also conclusive. However, to prevent human-to-human transmission (via direct contact, fomites, or potential aerosol), direct breastfeeding is discouraged. Pumping breast milk can be an alternative option considering proper hygiene is maintained. However, the use of mother’s milk for feeding neonates is not recommended if the mother is taking antiviral drugs. Last but not least, it is imperative to provide psychological support for the mother to prevent stress and anxiety.
In summary, with the limited evidence reported until now (27 March 2020), it is evident that pregnant women with COVID-19 infection present similar clinical features as others. The majority of the cases develop pneumonia, which is overtly diagnosed with radiological findings. Pregnant women with COVID-19 were treated with a wide range of antiviral drugs – mostly in China – however, to date, there is no official guideline from World Health Organization (44) or Center for Disease Control (45) (dated 1 April 2020). Several of these drugs are under clinical trial (46). Pregnant women with COVID-19 presented higher episodes of preterm birth and cesarean delivery, though, it cannot be explicitly attributed to the SARS-CoV-2. There is no published evidence on the vertical transmission of SARS-CoV-2.
Pregnancy – being an immunocompromised physiological state – with COVID-19 infection needs to be treated as a priority case and needed to be treated in a higher level healthcare facility. Management of pregnant women during antenatal, delivery, or postnatal stage must be conducted in isolation or negative pressure room whenever possible. A collaborative team of intensive care medicine specialists, obstetricians, anesthetists, neonatologist, microbiologist, and pathologist is necessary to manage critical COVID-19 patients. Healthcare professionals should protect themselves using proper personal protection equipment. Detail history taking (especially for contact tracing and travel history), radiological assessment, and laboratory testing with regular monitoring of fetal health need to be done at every stage of the pregnancy during COVID-19. Though reported only once (26), the effectiveness of lung ultrasound should be evaluated as a more accessible and cost-effective measure of investigation.
The literature did not suggest early termination or use of cesarean section for uncomplicated cases of COVID-19. While vertical transmission of SARS-CoV-2 was not reported, every effort should be made to prevent mother to child transmission of SARS-CoV-2 or iatrogenic infection, during and after the delivery. At the postnatal stage, infants need to be isolated form suspected or confirmed COVID-19 mother. More evidence is needed to conclude the safety of breastfeeding at this stage.
As the COVID-19 pandemic is evolving across the world, more and more evidence is being generated. As a part of this scoping review, we have included a wide range of published literature. This literature – which is mostly observational studies – with a small number of cases and mostly without proper control, quality of the evidence considered to be variable. However, it is essential to acknowledge the contribution of the physicians and researchers who went above and beyond their capacity to produce these initial sets of evidence to highlight critical findings for pregnant women with COVID-19 cases. “Standing on the shoulders of giants” – our rapid scoping review is an effort to collate and report the existing evidence on clinical findings and management recommendations of published scientific literature (dated 27 March 2020). We have tried to use a mostly narrative form of synthesis to connect the results across the literature.
There are several limitations of this scoping review. Due to the methodological design of the scoping review, a quality appraisal of the evidence was not conducted as a part of the review. The time frame of the study was bounded between 1 January 2019 to 27 March 2020, as most of the COVID-19 related literature was published between this timeframe. All study which presented clinical findings of pregnant COVID-19 patients were based on hospital and mostly in their late stage of the pregnancy. Thus, very little is known about the patients who had mild/no clinical symptoms or in their early stages of pregnancy. Except for one study from Honduras (40), all study was based in China. Therefore, the outcomes of pregnancy may be different in other settings.
The selection of the study question was limited to pregnant women, and we did not extend our research questions and search criteria to include neonatal clinical presentation and management recommendations for them. We felt an over encompassing review of maternal, neonatal, and infantile findings would not be feasible at this stage. Thus, we recommend further research and systematic synthesis of the data.
COVID-19 = Coronavirus disease 2019; CoV = Coronavirus; SARS-CoV-2 = Severe Acute Respiratory Syndrome CoV; PRISMA = Preferred Reporting Items for Systematic reviews and Meta-Analyses; RT-PCR = real-time reverse transcription-polymerase chain reaction; CT = computerized tomography; GGO = ground-glass opacity, ALT = Alanine aminotransferase; AST = Aspartate aminotransferase; ICU = Intensive care unit;
Ethical Approval
No ethical approval is required for the study.
Availability of data and materials
Data sharing is not applicable to this article as no datasets were generated or analysed during the current study.
Competing interests
All authors declare no competing interests.
Funding
None.
Authors' contributions
MH conceptualized the research question and led to the development of the methodology. Development of literature search strategy, and implementation of the literature search was performed by MH and TA. MH and GMK independently performed the study selection by title and abstract and full-text screening. MH and GMK equally contributed to the analysis and interpretation of the data. MH took the lead to develop the first draft. Both MH and GMK finalized the manuscript and the abstract. All authors contributed to the manuscript revision and read and approved the submitted version of the manuscript.
Acknowledgment
We thank Welch Library of Johns Hopkins University for the access to Covidence systematic review software (covidence.org) software and freely providing the full-text version of the studies which did not have open access.