A systematic review and meta-analysis of pregnancy and COVID-19: Signs and symptoms, laboratory tests, and perinatal outcomes

Abstract Background Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 appeared in December 2019 in Wuhan, China. Objective To investigate the clinical manifestations including signs and symptoms, laboratory results, and perinatal outcomes in pregnant women with COVID-19. Materials and Methods Scholarly databases such as PubMed via LitCovid hub, Embase, Scopus, Web of sciences, and Google scholar were searched on April 7, 2020. Meta-analysis was performed via comprehensive meta-analysis software using the Mantel-Haenszel method. The event rate with 95% CI was calculated for each variable. Results Ten studies were selected. The pooled prevalence for fever, post-partum fever, cough, myalgia, fatigue, dyspnea, sore throat, and diarrhea were 66.8%, 37.1%, 35%, 24.6 %, 14.9%, 14.6%, 11.5%, and 7.6%, respectively. Laboratory test results were 49.8% for lymphopenia, 47.7% for leukocytosis, 83.7% for elevated neutrophil ratio, 57% for elevated C-reactive protein, and 71.4% for decreased lymphocyte ratio. The rate of cesarean section for delivery in all cases was 84%. Of the newborns of the corona-positive mothers, only one had a positive test result. Also, there was only one death due to a decreased lymphocyte ratio. Conclusion Fever was the most common sign and symptom in pregnant women with COVID-19. Among the laboratory tests, the highest amount was related to elevated neutrophil ratio. It seems that due to the differences between pregnant women and the general population, special measures should be considered to treat these patients.


Introduction
Coronavirus  (3,4). In some cases, the disease can lead to a sensitive respiratory condition, many of which require specialized management in the intensive care unit (ICU) (5).
Moreover, respiratory droplets along with close contact transmission are the considerable routes of transmission. Aerosol transmission is also possible in a close environment when exposed to high concentrations of aerosol for a protracted period (6). On the other hand, touching surfaces or objects that are touched by an infected person can also transmit the disease (7). A study has also shown that older age and comorbidity play an important role in determining the severity and clinical consequences of the disease (8).
Because most studies have focused on patients infected with the new coronavirus in the general population, bounded details are available regarding pregnancy outcomes in women infected with COVID-19. It has caused particular concern among pregnant women, as both SARS-CoV and MERS-CoV viruses have been shown to cause severe side effects in pregnant women (9,10). In 2004, Wong and colleagues conducted a study on pregnant women with SARS in Hong Kong and observed that the pregnant women showed higher rates of death and mortality (11). Similarly, a study by Mertz and colleague showed that women infected with influenza were at a higher risk than healthy pregnant women (12). Chen and co-authors also reported that pregnancy with pneumonia could be associated with the risk of cesarean delivery, preterm delivery, a decrease in the baby's Apgar score, weight loss at birth, etc. (13).
It is obvious that a parturient woman has a relatively depressed immunity or immune suppression, and in theory, they could be more at risk of contracting the virus. Also, confronting the SARS-CoV-2 during pregnancy is a serious threat to pregnant women and their fetuses (14,15

Eligibility criteria
All included studies were investigated COVID-19 in pregnant women or during pregnancy and were in the English language. Studies were excluded if the researchers didn't have access to the full-text of the article or the data about the outcomes were not sufficient.
Also, studies that were not peer reviewed were excluded.

Study selection
After importing the records to EndNote X7, the duplicate records were removed and then screened based on the title, abstract, and full-text considering the eligibility criteria. All stages were conducted using two independent reviewers and the potential disagreements were solved through consultation with a third reviewer.

Outcomes measures
The investigated outcomes were signs and

Description of search
After searching all international databases,

Characteristics of included studies
Based on the geographical location, all included studies were performed in China.

Quality assessment
Based on the results of the quality assessment, seven studies were good quality and three were average (Table II).

Heterogeneity
Based on the data analysis, a high level of heterogeneity was not observed in the findings. In some cases with high heterogeneity, the random effect was used (Table III).  (Figure 3, Table III).

Type of delivery
According to the results, the rate of cesarean section for delivery in all cases was 84% (95% CI; 74-90.7) (Figure 4, Table III).

Perinatal outcomes
According to the results, of the newborns of the corona-positive mothers, only one had a positive test result. Also, there was only one death due to DIC (Table IV).

Results of meta-regression
According to the findings, the only factor that could be examined in this section was the mean age of pregnant women. Data analysis showed that older pregnant women have a significantly higher fever rate (Coefficient = 0.477, p = 0.033). For the type of delivery, the higher average age of pregnant women significantly associated with a higher rate in cesarean delivery (Coefficient = 0.433, p = 0.016) ( Table V).

Publication bias
Visual inspection of funnel plot and Egger's tests did not indicate evidence of publication bias (p = 0.127).

Identification
Additional records identified through other sources (n = 12) Records after duplicates removed (n = 3985)

Eligibility
Full-text articles assessed for eligibility (n = 17)

Included
Studies included in qualitative synthesis (n = 10) Studies included in quantitative synthesis (meta-analysis) (n = 10)
These summary findings help healthcare workers better manage pregnant women with COVID-19, which could potentially reduce the side effects for women as well as their newborns.
The common clinical manifestations of pregnant women with COVID-19 include fever and cough, and the less common symptoms are sore throat and diarrhea. Postpartum fever is also more common in women after childbirth. However, the rate of fever in our study was lower than that of Guan  In our study, the majority of pregnancies ended up with cesarean section, which is much higher than the WHO's recommendation for vaginal route delivery (35), which can be determined by a gynecologist to prevent maternal respiratory distress during pregnancy.
In the current study, which examined 135 Fourth, all included studies were from China.

Conclusion
In conclusion, pregnant women with COVID-19 pneumonia had diverse symptoms; however, fever and cough were the main clinical symptoms in those women. Although one infant was born with COVID-19 in the included studies, there was little evidence that COVID-19 was transmitted from mother to infant in late pregnancy. Therefore, the study of long-term outcomes on mother and child, as well as the vertical transfer of mother to child in second-trimester pregnancies and the first months after delivery, requires further studies.