Main findings
The cases discussed in this article involved 160 pregnant women with COVID-19 in China and 76 pregnant women with COVID-19 in America. The pooled results of this meta-analysis showed that among the pregnant women with COVID-19, 71% had positive CT findings, 65% had a caesarean section, 51% had fever, 49% had lymphopenia in laboratory examination, 33% had coexisting disorders, 31% had cough, 29% had fetal distress, 23% had preterm labor and 12% had severe cases or died. Pregnant women with COVID-19 had significantly lower rates of fever and cough than non-pregnant patients with COVID-19.
Strengths and limitations
Currently, there are only meta-analyses of the epidemiology of typical patients infected with COVID-19, and there are few meta-analyses to explore the clinical features and outcomes of pregnant women with COVID-19. This study is helpful to formulate clinical treatment strategies for pregnant women with COVID-19.
The disadvantage of this study was the small sample size and the general quality of the included documents, which lowered the credibility of the meta-analysis results. In addition, all the included articles were retrospective case analyses without control groups, which also biased the results. Furthermore, the funnel plots showed that most indicators may have publication bias. Most of the included patients were Chinese, and the others were American. There are few reports describing the cases outside the two regions. Further research on pregnant women with COVID-19 worldwide is needed.
Interpretation
We referred to the normal population the non-pregnant group to distinguish it from the pregnant group in the subgroup analysis. The subgroup analysis between pregnant women with COVID-19 and non-pregnant patients with COVID-19 showed that the incidences of fever and cough in pregnant women with COVID-19 (51, 31%) were lower than those in normal people (91, 67%), which may be due to the changes in the immune system of pregnant women, and further research is needed. The available data do show no increased or even lower maternal mortality rate after infection [
25], but it does not mean that pregnancy is a protective factor for severe infection. It was reported that severe infection mostly occurred in the elderly (> 60 years old), patients with basic diseases, such as diabetes, obesity, hypertension, coronary heart disease, cerebrovascular diseases, and other chronic diseases [
26‐
30], as well as those who did not receive timely treatment or delay treatment [
31]. Pregnant women are usually younger without primary diseases. Besides, pregnant women are usually more likely to receive attention after the onset of the disease (pregnant women themselves, family members, and medical staff), with fewer delays in treatment. All these can explain the low fatality rate of infected pregnant women. There is no evidence that pregnancy can alleviate the disease yet, which needs further study. Aya Mohr-Sasson et al. compared clinical characteristics between pregnant women and non-pregnant women. The study showed that there were no statistical differences in clinical features such as respiratory symptoms and fever between the two groups [
32]. It was reported that male patients were likely to develop more severe symptoms and have higher prevalence rates and mortality rates than female patients [
33‐
35]. Zeng F et al. showed that compared with male patients, more female patients were generating a relatively high level of SARS-CoV-2 IgG antibody in severe cases, and the IgG antibody presented a stronger production in female patients in disease early phase [
36]. It may be the reason why the clinical characteristics of the pregnant group in this study are better than those of the non-pregnant group. A study from the China CDC showed that 80.9% of Chinese patients were considered to be asymptomatic or to have mild pneumonia [
37]. Desmond Sutton et al. showed that of the 215 pregnant women who gave birth at the New York-Presbyterian Allen Hospital and Columbia University Irving Medical Center, 29 (87.9%) of the 33 patients who were positive for SARS-CoV-2 testing had no symptoms of COVID-19 at the time of admission [
19]. The fact that the asymptomatic rate in the infected general population in China is lower than the rate in infected pregnant women in the New York Medical Center seems to support this conclusion in this study. These findings suggest that the SARS-CoV-2 testing should be universally administered in high-risk areas to improve the isolation of asymptomatic infected individuals. This result is different from the finding that pregnant women infected with SARS-CoV have a worse prognosis than ordinary people infected with SARS-CoV [
38]. It is possible that in pregnant women, the clinical outcome of COVID-19 infection is better than that of SARS-CoV. Yan et al. confirmed that the current mortality rate of COVID-19(2%) is significantly lower than that of SARS (9.6%), which may indicate that SARS is more pathogenic and lethal than COVID-19; thus, pregnant women with COVID-19 infection had better outcomes than those with SARS-CoV [
39]. However, our finding that pregnant women with COVID-19 had better clinical features might be biased owing to the relatively small sample included in this meta-analysis.
A meta-analysis showed that the CT positive rate of COVID-19 in the normal population was 89.76% [
40], which was more than the 71% positive rate in this paper. This finding also corresponded to the conclusion above that the clinical features of pregnant women with COVID-19 were superior to those of the general population. The incidence of positive CT findings was the highest among the selected indicators. Shital J. Patel et al. confirmed that chest CT was considered a low-dose examination, provided the foetus was excluded from the primary beam, and the estimated radiation doses were too low to induce foetus neurologic deficits during any trimester of pregnancy [
41]. It seemed that chest CT was suitable for routine screening of patients. However, there was a large percentage of pregnant women with asymptomatic infections (87.9%) [
19]. If chest CT is used for routine screening, it means that almost all pregnant women need to undergo chest CT. In addition, the WHO defines screening as the presumptive identification of unrecognized disease in an apparently healthy, asymptomatic population by means of tests, examinations or other procedures that can be applied rapidly and easily to the target population [
42]. Consequently, it is not appropriate to perform chest CT as a screening tool for pregnant women with COVID-19. We recommend using chest CT as the routine examination for suspected cases.
The rate of preterm labor in normal pregnant women who are healthy and not infected with any virus worldwide is approximately 11% [
43], which is lower than the result in this article (23%). The possible reason for the higher rate is that women in the third trimester of pregnancy induce delivery early after becoming ill with COVID-19 to proceed with further treatment. Most of these women choose early delivery by caesarean section to avoid a prolonged labor, which may worsen COVID-19 for pregnant women [
44] and increase the risk of infection for the medical staff [
45]. Chen R et al. confirmed that both epidural anesthesia and general anesthesia were safe and effective for women with COVID-19 during caesarean section [
12].
Because the
P value was greater than 0.05, the rate of neonatal COVID-19 infection should not be considered. Wang S et al. reported the first case in China in which a mother with COVID-19 gave birth to an infected baby on February 2, 2020 [
46], and the instant SARS-CoV-2 nucleic acid tests of the umbilical cord blood and placenta were both negative. There were 3 infected neonates in the included literature. Khan S. et al. reported that the swab samples tested within 24 h after delivery were positive in two neonates, and intrauterine tissue samples such as placenta, cord blood or amniotic fluid were not tested [
14]. Yu N et al. reported that the nucleic acid test for the throat swab of one neonate was positive at 36 h after birth [
22]. Without testing the intrauterine tissue samples, we could not confirm whether the SARS-COV-2 infection in the neonate was the result of intrauterine transmission. Two studies also showed that the test for SARS-CoV-2-specific antibodies (IgG and IgM) in neonatal serum samples could be evidence of vertical transmission [
47,
48]. Other literature revealed that almost all the other new-borns from infected women tested negative for SARS-CoV-2 [
10‐
13,
15‐
21,
23,
49‐
52]. Wang C et al. summarized that there was currently no evidence for intrauterine infection caused by vertical transmission in women with COVID-19 during the third trimester of pregnancy, but it was uncertain whether there could be a risk of vertical transmission when the COVID-19 infection occurs in the first or second trimester or when there was a long clinical manifestation-to-delivery interval [
53]. Therefore, we must remain alert to the possibility of vertical transmission.