Main findings
The results of this systematic review showed that the clinical manifestations of pregnant women with COVID-19 were similar to those of general COVID-19 patients [
33], including fever, cough, myalgia, shortness of breath, and diarrhea. The common laboratory changes of patients included lymphopenia, leukocytosis, decreased platelet counts, supraphysiological concentrations of transaminase, C-reactive protein, and D-dimer. The majority of chest CT scans showed typical imaging manifestations of COVID -19 pneumonia.
Common obstetric complications, such as gestational hypertension, preeclampsia, and gestational diabetes mellitus, may affect the outcomes. More than 80% of the patients were mild cases. Asymptomatic infections were reported in pregnant women. The proportion of mechanical ventilation was 5.19%, which was slightly lower than that of the general population [
33]. The case-fatality rate (0.43%) is lower than the mortality of COVID-19 patients reported by World Health Organization (6.80%) and the Chinese Center for Disease Control and Prevention (2.29%) [
34,
35] and similar to the overall maternal mortality rate worldwide (1 in 180) [
36].
Most patients were in the third trimester of pregnancy. A total of 124 (80.52%) patients underwent a cesarean section. The most common adverse pregnancy outcome, premature delivery, occurred in up to 24.74% of pregnant women. Premature rupture of membranes, fetal distress, and even fetal death were also reported.
There was more evidence for vertical transmission of COVID-19. Under strict protection during delivery and postpartum isolation measures, 3.91% (5/128) of newborns were tested positive for SARS-CoV-2 nucleic acid, and elevation of IgM against SARS-CoV-2 was found in 3/8 newborns with negative of SARS-CoV-2 nucleic acid results. However, more details, including nucleic acid test results of vaginal secretions, breast milk, amniotic fluid, placenta tissues, and cord blood, did not support vertical transmission. In particular, newborns with a positive SARS-CoV-2 nucleic acid test or elevated serum antibody were all delivered by cesarean section. From the perspectives of disinfection and protection, breastfeeding may not cause neonatal infection.
Strengths and limitations
Several reviews have summarized the situation of pregnant women infected with COVID-19 [
37‐
39], however, knowledge needs to be summarized in a timely manner. The strengths are as follows. First, the databases were comprehensive; therefore, we enrolled as many timely articles as possible. Second, we carefully and strictly reviewed articles to remove as much duplicated data as possible. Finally, we summarized comprehensive details related to vertical transmission.
One of our limitations is the inclusion of case reports, which may be inclined to report more severe cases. Another limitation is that all included articles were retrospective studies. Prospective studies will lead to a better understanding of pregnant women with COVID-19.
Interpretation
Pregnant women are at high risk of infection or may be already infected with COVID-19. Psychological stress and viral infections are both risk factors for miscarriage [
40]. The psychological pressure brought by COVID-19 has driven several patients to terminate their pregnancies [
24]. More information about pregnant women with COVID-19 is urgently needed to relieve their anxiety and guide them to make beneficial decisions.
According to our results, most patients are asymptomatic or mildly ill. They come to the hospital because of their pregnancy and the need for medical care for childbirth. Then, the detection of coronavirus infection reveals that these patients are in an early stage of infection, with milder symptoms, or may even be asymptomatic or have very few symptoms, which may be one of the contributors to their favorable prognosis. However, asymptomatic infections do not seem to be a minority. A report of new cases indicates that up to four-fifths of people are asymptomatic [
41], and 32.6% of pregnant women with COVID-19 had no symptoms in a New York hospital [
25]. Isolation at home and travel restrictions protect people from infection but disrupt routine prenatal examinations and the discovery of abnormal pregnancies in time. Pregnant women are in states of anxiety and worry regarding issues such as the epidemic’s status, the impacts on maternal and child health, the safety of CT examination, and treatment prognosis for the fetus and the mother [
42]. Pregnant women may be worried about being infected and may demand psychological consultation [
43]. We agree that measures such as pregnant women being screened and followed up, being offered more flexible birth inspection strategies [
44], and receiving more concern for their mental health are required [
45].
SARS infection during pregnancy has been correlated with a high incidence of spontaneous abortion and premature delivery [
37,
46]. Similar phenomena have also been observed in pregnant women with COVID-19. In three placental pathology reports, no pathological alternation of villitis and chorioamnionitis was observed [
47]. To understand the underlying mechanism, more placental pathological reports, especially those with adverse neonatal outcomes, are needed.
Regarding delivery mode, cesarean section and vaginal delivery have their respective short- and long-term advantages and disadvantages [
48,
49]. During vaginal delivery, amniotic fluid, vaginal bleeding, and vaginal discharge increase the difficulty of infection control. Cesarean section seems to benefit both patients and medical staff [
50], but there is no clear evidence on whether vaginal delivery or cesarean section is more beneficial [
51]. This review shows that more pregnant women with COVID-19 delivered by cesarean section instead of via the vagina. On the one hand, a high incidence of intraoperative hypotension has been noted in pregnant COVID-19 patients during cesarean section [
52,
53]; on the other hand, no evidence of vertical transmission was observed with vaginal delivery.
About a decade ago, the limited publications on pregnant women with SARS reported no evidence of vertical transmission [
3,
54]. Here, we included some single-center studies to summarize the possibility of vertical transmission of COVID-19 [
30,
31,
47,
55‐
58]. Although strict isolation measures are taken, a few newborns still show positive results on the SARS-CoV-2 nucleic acid test. Possible mechanisms for vertical transmission (from the mother to the fetus or newborn) mainly include: trans-placental transmission after the virus infects the placenta, intrapartum transmission via ingestion or aspiration of cervical vaginal secretions during delivery, and postpartum transmission by breastfeeding [
59]. Evidence supporting intrauterine transmission is the discovery of elevated IgM and IgG against SARS-CoV-2 in infants [
31,
32]. Unlike IgG, IgM is not usually transferred from mother to fetus because of its larger macromolecular structure. Therefore, it is probably produced by the fetus after infection. Vertical transmission could be considered when both IgM and IgG are elevated conservatively. Paradoxically, angiotensin-converting enzyme 2(ACE 2), the receptor of SARS-CoV-2, is poorly expressed in various cell types at the maternal–fetal interface [
60], and SARS-CoV-2 was undetected in the placenta histopathology of infected parturients [
47]. Though the evidence is inconclusive, no vertical transmission phenomenon or evidence of the vaginal delivery process has been found. According to the cautious advice of experts [
61,
62], the vast majority of newborns were separated from their COVID-19 confirmed mothers and fed formula milk powder. The WHO recommends that mothers can share a room with their infants and provide breast feeding after SARS-CoV-2 testing is negative in their breast milk [
63]. Mothers should wear masks, practice hand hygiene [
64], and disinfect all containers of expressed human milk [
65].
Only 6.5% of the newborns with negative PCR results were also tested for serum antibodies against SARS-CoV-2. It will not be representative and convincing to calculate the vertical transmission probability with such a small sample size and possible biased data. One study showed that the sensitivity of RT-PCR to detect viral nucleic acids was only 71% [
66]. Collecting a variety of samples, in addition to nasopharyngeal swabs, can improve the positive detection rate [
67]. Serum antibodies against SARS-CoV-2 should be tested more frequently and multiple samples should be included in pathogenic testing.