Worldwide beliefs among pregnant women on SARS-CoV-2 vaccine: a systematic review.

BACKGROUND: SARS-CoV-2 vaccine has been recommended to pregnant women, but survey studies showed contrasting findings worldwide in relation to the willingness to accept vaccination during pregnancy. OBJECTIVE: To evaluate the evidence from the literature regarding the acceptance rate of the SARS-CoV-2 vaccine in pregnant and breastfeeding women. STUDY DESIGN: We performed a systematic review on the main databases (MEDLINE (PubMed), Scopus, ISI Web of Science) searching for all the peer-reviewed survey studies analyzing the eventual acceptance rate of the SARS-CoV-2 vaccine among pregnant and breastfeeding women. To combine data meta-analyses of proportions and pooled proportions with their 95% confidence intervals (CI) were calculated. RESULTS: 15 studies including 25,839 women were included in the analysis. The proportion of women actually willing to be vaccinated during pregnancy is 49.1% (95% CI, 42.3-56.0), and the proportion of breastfeeding women is 61.6% (95% CI, 50.0-75.0). CONCLUSION: The cumulative SARS-CoV-2 vaccine acceptance rate among pregnant women appears still low. Vaccinal campaign are urgently needed to drive more confidence into the vaccine to help reducing the spread of the infection and the possible consequences during pregnancy.

Stillbirth and fetal capillary infection by SARS-CoV-2.

We presented the case of stillbirth in a paucisymptomatic mother affected by SARS-CoV-2. At gross examination, the placenta showed a diffuse marble appearance and a focal hemorrhagic area. Multiple areas of hemorrhagic or ischemic necrosis with central and peripheral villous infarctions and thrombosis of several maternal and fetal vessels with luminal fibrin and platelet deposition were observed. All lesions seemed to be synchronous. Virus particles were identified within the cytoplasm of endothelial cells using electron microscopy, whereas SARS-CoV-2 RNA was detected in the placental tissue using real-time reverse transcription-polymerase chain reaction. Here, fetal vascular malperfusion was associated with infection; in fact, electron microscopy images showed that marked SARS-CoV-2 endotheliotropism involved the intravillous fetal capillaries. Furthermore, we confirmed that syncytiotrophoblast is the major target cell type for SARS-CoV-2 infection of the placenta. In conclusion, the possible consequences of the action of the placentotropic SARS-CoV-2 included the occurrence of vertical transmission, as reported in the literature, and/or stillbirth: the latter possibility may be triggered by a hampered maternal and/or fetal perfusion of the placenta. The diffuse thrombosis and subsequent ischemia of fetal capillaries induced by COVID-19 cannot be predicted by standard clinical surveillance.

Pregnant women's perspectives on severe acute respiratory syndrome coronavirus 2 vaccine.

BACKGROUND: Since coronavirus disease 2019 vaccines have been distributed, a debate has raised on whether pregnant women should get the vaccine. No available data exist so far regarding the safety, efficacy, and toxicology of these vaccines when administered during pregnancy. Most of the Obstetrics and Gynecology societies suggested that pregnant could agree to be vaccinated, after a thorough counseling of risks and benefits with their gynecologists, thus leading to an autonomous decision. OBJECTIVE: This study aimed to evaluate the attitude to coronavirus disease 2019 vaccination in pregnant and breastfeeding women in Italy. STUDY DESIGN: A survey was made at the University of Naples Federico II and the Ospedale Cristo Re, Tor Vergata University of Rome, on pregnant and breastfeeding women asking their perspectives on the available vaccines after reading the recommendations issued by our national Obstetrics, Gynecology, and Neonatology societies. The questionnaire included 12 items finalized to evaluate general features of the women and 6 items specifically correlated to their attitudes toward the severe acute respiratory syndrome coronavirus 2 vaccination. Chi-square or Fisher's exact tests were used to compare group differences of categorical variables and Wilcoxon signed rank or Mann-Whitney U test for continuous variables. The study was approved by the institutional review boards of the University of Naples Federico II (ref. no. 409/2020) and the Ospedale Cristo Re, Tor Vergata University of Rome (ref. #Ost4-2020). RESULTS: Most of the included women did not agree to eventually receive severe acute respiratory syndrome coronavirus 2 vaccine during pregnancy (40 [28.2%] vs 102 [71.8%]). Being pregnant was considered a determinant factor to refuse the vaccine prophylaxis (99 [69.7%] vs 43 [30.3%]; chi-square test=24.187; P<.001), even if a very large percentage declared to be generally in favor of vaccines (128 [90.1%] vs 14 [9.9%]; chi-square test=6.091; P=.014) and most of them confirmed they received or would receive other recommended vaccines during pregnancy (75 [52.8%] vs 67 [47.2%]; chi-square test=10.996; P=.001). CONCLUSION: Urgent data are needed on the safety, efficacy, and toxicology of severe acute respiratory syndrome coronavirus 2 vaccines during pregnancy to modify this trend and to help obstetricians during the counseling. Furthermore, pregnant women should be included in future vaccine development trials to not incur again in such uncertainty.

Adverse Pregnancy Outcomes Among Individuals With and Without Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): A Systematic Review and Meta-analysis.

OBJECTIVE: To compare the risk of intrauterine fetal death (20 weeks of gestation or later) and neonatal death among individuals who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) compared with those who tested negative for SARS-CoV-2 on admission for delivery. DATA SOURCES: MEDLINE, Ovid, EMBASE, Cumulative Index to Nursing and Allied Health, and Cochrane Library were searched from their inception until July 17, 2020. Hand search for additional articles continued through September 24, 2020. ClinicalTrials.gov was searched on October 21, 2020. METHODS OF STUDY SELECTION: The inclusion criteria were publications that compared at least 20 cases of both pregnant patients who tested positive for SARS-CoV-2 on admission to labor and delivery and those who tested negative. Exclusion criteria were publications with fewer than 20 individuals in either category or those lacking data on primary outcomes. A systematic search of the selected databases was performed, with co-primary outcomes being rates of intrauterine fetal death and neonatal death. Secondary outcomes included rates of maternal and neonatal adverse outcomes. TABULATION, INTEGRATION, AND RESULTS: Of the 941 articles and completed trials identified, six studies met criteria. Our analysis included 728 deliveries to patients who tested positive for SARS-CoV-2 and 3,836 contemporaneous deliveries to patients who tested negative. Intrauterine fetal death occurred in 8 of 728 (1.1%) patients who tested positive and 44 of 3,836 (1.1%) who tested negative (P=.60). Neonatal death occurred in 0 of 432 (0.0%) patients who tested positive and 5 of 2,400 (0.2%) who tested negative (P=.90). Preterm birth occurred in 95 of 714 (13.3%) patients who tested positive and 446 of 3,759 (11.9%) who tested negative (P=.31). Maternal death occurred in 3 of 559 (0.5%) patients who tested positive and 8 of 3,155 (0.3%) who tested negative (P=.23). CONCLUSION: The incidences of intrauterine fetal death and neonatal death were similar among individuals who tested positive compared with negative for SARS-CoV-2 when admitted to labor and delivery. Other immediate outcomes of the newborns were also similar among those born to individuals who tested positive compared with negative for SARS-CoV-2. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020203475.

Outcome of coronavirus spectrum infections (SARS, MERS, COVID-19) during pregnancy: a systematic review and meta-analysis.

Objective: The aim of this systematic review was to report pregnancy and perinatal outcomes of coronavirus spectrum infections, and particularly coronavirus 2019 (COVID-19) disease because of severe acute respiratory syndrome-coronavirus-2 infection during pregnancy. Data Sources: Medline, Embase, Cinahl, and Clinicaltrials.gov databases were searched electronically utilizing combinations of word variants for coronavirus or severe acute respiratory syndrome or SARS or Middle East respiratory syndrome or MERS or COVID-19 and pregnancy. The search and selection criteria were restricted to English language. Study Eligibility Criteria: Inclusion criteria were hospitalized pregnant women with a confirmed coronavirus related-illness, defined as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), or COVID-19. Study Appraisal and Synthesis Methods: We used meta-analyses of proportions to combine data and reported pooled proportions, so that a pooled proportion may not coincide with the actual raw proportion in the results. The pregnancy outcomes observed included miscarriage, preterm birth, preeclampsia, preterm prelabor rupture of membranes, fetal growth restriction, and mode of delivery. The perinatal outcomes observed were fetal distress, Apgar score <7 at 5 minutes, neonatal asphyxia, admission to a neonatal intensive care unit, perinatal death, and evidence of vertical transmission. Results: Nineteen studies including 79 hospitalized women were eligible for this systematic review: 41 pregnancies (51.9%) affected by COVID-19, 12 (15.2%) by MERS, and 26 (32.9%) by SARS. An overt diagnosis of pneumonia was made in 91.8%, and the most common symptoms were fever (82.6%), cough (57.1%), and dyspnea (27.0%). For all coronavirus infections, the pooled proportion of miscarriage was 64.7% (8/12; 95% confidence interval, 37.9-87.3), although reported only for women affected by SARS in two studies with no control group; the pooled proportion of preterm birth <37 weeks was 24.3% (14/56; 95% confidence interval, 12.5-38.6); premature prelabor rupture of membranes occurred in 20.7% (6/34; 95% confidence interval, 9.5-34.9), preeclampsia in 16.2% (2/19; 95% confidence interval, 4.2-34.1), and fetal growth restriction in 11.7% (2/29; 95% confidence interval, 3.2-24.4), although reported only for women affected by SARS; 84% (50/58) were delivered by cesarean; the pooled proportion of perinatal death was 11.1% (5/60; 95% confidence interval, 84.8-19.6), and 57.2% of newborns (3/12; 95% confidence interval, 3.6-99.8) were admitted to the neonatal intensive care unit. When focusing on COVID-19, the most common adverse pregnancy outcome was preterm birth <37 weeks, occurring in 41.1% of cases (14/32; 95% confidence interval, 25.6-57.6), while the pooled proportion of perinatal death was 7.0% (2/41; 95% confidence interval, 1.4-16.3). None of the 41 newborns assessed showed clinical signs of vertical transmission. Conclusion: In hospitalized mothers infected with coronavirus infections, including COVID-19, >90% of whom also had pneumonia, preterm birth is the most common adverse pregnancy outcome. COVID-19 infection was associated with higher rate (and pooled proportions) of preterm birth, preeclampsia, cesarean, and perinatal death. There have been no published cases of clinical evidence of vertical transmission. Evidence is accumulating rapidly, so these data may need to be updated soon. The findings from this study can guide and enhance prenatal counseling of women with COVID-19 infection occurring during pregnancy, although they should be interpreted with caution in view of the very small number of included cases.

Rates of Maternal and Perinatal Mortality and Vertical Transmission in Pregnancies Complicated by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-Co-V-2) Infection: A Systematic Review.

OBJECTIVE: To ascertain the frequency of maternal and neonatal complications, as well as maternal disease severity, in pregnancies affected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. DATA SOURCES: MEDLINE, Ovid, ClinicalTrials.gov, MedRxiv, and Scopus were searched from their inception until April 29, 2020. The analysis was limited to reports with at least 10 pregnant patients with SARS-CoV-2 infection that reported on maternal and neonatal outcomes. METHODS OF STUDY SELECTION: Inclusion criteria were pregnant women with a confirmed diagnosis of SARS-CoV-2 infection. A systematic search of the selected databases was performed by implementing a strategy that included the MeSH terms, key words, and word variants for "coronavirus," "SARS-CoV-2," "COVID-19," and "pregnancy.r The primary outcomes were maternal admission to the intensive care unit (ICU), critical disease, and death. Secondary outcomes included rate of preterm birth, cesarean delivery, vertical transmission, and neonatal death. Categorical variables were expressed as percentages with number of cases and 95% CIs. TABULATION, INTEGRATION, AND RESULTS: Of the 99 articles identified, 13 included 538 pregnancies complicated by SARS-CoV-2 infection, with reported outcomes on 435 (80.9%) deliveries. Maternal ICU admission occurred in 3.0% of cases (8/263, 95% CI 1.6-5.9) and maternal critical disease in 1.4% (3/209, 95% CI 0.5-4.1). No maternal deaths were reported (0/348, 95% CI 0.0-1.1). The preterm birth rate was 20.1% (57/284, 95% CI 15.8-25.1), the cesarean delivery rate was 84.7% (332/392, 95% CI 80.8-87.9), the vertical transmission rate was 0.0% (0/310, 95% CI 0.0-1.2), and the neonatal death rate was 0.3% (1/313, 95% CI 0.1-1.8). CONCLUSION: With data from early in the pandemic, it is reassuring that there are low rates of maternal and neonatal mortality and vertical transmission with SARS-CoV-2. The preterm birth rate of 20% and the cesarean delivery rate exceeding 80% seems related to geographic practice patterns. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42020181497.

Risk factors associated with adverse fetal outcomes in pregnancies affected by Coronavirus disease 2019 (COVID-19): a secondary analysis of the WAPM study on COVID-19.

Objectives To evaluate the strength of association between maternal and pregnancy characteristics and the risk of adverse perinatal outcomes in pregnancies with laboratory confirmed COVID-19. Methods Secondary analysis of a multinational, cohort study on all consecutive pregnant women with laboratory-confirmed COVID-19 from February 1, 2020 to April 30, 2020 from 73 centers from 22 different countries. A confirmed case of COVID-19 was defined as a positive result on real-time reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of nasal and pharyngeal swab specimens. The primary outcome was a composite adverse fetal outcome, defined as the presence of either abortion (pregnancy loss before 22 weeks of gestations), stillbirth (intrauterine fetal death after 22 weeks of gestation), neonatal death (death of a live-born infant within the first 28 days of life), and perinatal death (either stillbirth or neonatal death). Logistic regression analysis was performed to evaluate parameters independently associated with the primary outcome. Logistic regression was reported as odds ratio (OR) with 95% confidence interval (CI). Results Mean gestational age at diagnosis was 30.6±9.5 weeks, with 8.0% of women being diagnosed in the first, 22.2% in the second and 69.8% in the third trimester of pregnancy. There were six miscarriage (2.3%), six intrauterine device (IUD) (2.3) and 5 (2.0%) neonatal deaths, with an overall rate of perinatal death of 4.2% (11/265), thus resulting into 17 cases experiencing and 226 not experiencing composite adverse fetal outcome. Neither stillbirths nor neonatal deaths had congenital anomalies found at antenatal or postnatal evaluation. Furthermore, none of the cases experiencing IUD had signs of impending demise at arterial or venous Doppler. Neonatal deaths were all considered as prematurity-related adverse events. Of the 250 live-born neonates, one (0.4%) was found positive at RT-PCR pharyngeal swabs performed after delivery. The mother was tested positive during the third trimester of pregnancy. The newborn was asymptomatic and had negative RT-PCR test after 14 days of life. At logistic regression analysis, gestational age at diagnosis (OR: 0.85, 95% CI 0.8-0.9 per week increase; p<0.001), birthweight (OR: 1.17, 95% CI 1.09-1.12.7 per 100 g decrease; p=0.012) and maternal ventilatory support, including either need for oxygen or CPAP (OR: 4.12, 95% CI 2.3-7.9; p=0.001) were independently associated with composite adverse fetal outcome. Conclusions Early gestational age at infection, maternal ventilatory supports and low birthweight are the main determinants of adverse perinatal outcomes in fetuses with maternal COVID-19 infection. Conversely, the risk of vertical transmission seems negligible.

Labor and delivery guidance for COVID-19.

This document addresses the current coronavirus disease 2019 (COVID-19) pandemic for providers and patients in labor and delivery (L&D). The goals are to provide guidance regarding methods to appropriately screen and test pregnant patients for COVID-19 prior to, and at admission to L&D reduce risk of maternal and neonatal COVID-19 disease through minimizing hospital contact and appropriate isolation; and provide specific guidance for management of L&D of the COVID-19-positive woman, as well as the critically ill COVID-19-positive woman. The first 5 sections deal with L&D issues in general, for all women, during the COVID-19 pandemic. These include Section 1: Appropriate screening, testing, and preparation of pregnant women for COVID-19 before visit and/or admission to L&D Section 2: Screening of patients coming to L&D triage; Section 3: General changes to routine L&D work flow; Section 4: Intrapartum care; Section 5: Postpartum care; Section 6 deals with special care for the COVID-19-positive or suspected pregnant woman in L&D and Section 7 deals with the COVID-19-positive/suspected woman who is critically ill. These are suggestions, which can be adapted to local needs and capabilities.