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.

Placental Pathology of COVID-19 with and without Fetal and Neonatal Infection: Trophoblast Necrosis and Chronic Histiocytic Intervillositis as Risk Factors for Transplacental Transmission of SARS-CoV-2.

The mechanism(s) by which neonates testing positive for coronavirus disease 2019 (COVID-19) acquire their infection has been largely unknown. Transmission of the etiological agent, SARS-CoV-2, from mother to infant has been suspected but has been difficult to confirm. This communication summarizes the spectrum of pathology findings from pregnant women with COVID-19 based upon the infection status of their infants and addresses the potential interpretation of these results in terms of the effects of SARS-CoV-2 on the placenta and the pathophysiology of maternal-fetal infection. Placentas from pregnant women with COVID-19 and uninfected neonates show significant variability in the spectrum of pathology findings. In contrast, placentas from infected maternal-neonatal dyads are characterized by the finding of mononuclear cell inflammation of the intervillous space, termed chronic histiocytic intervillositis, together with syncytiotrophoblast necrosis. These placentas show prominent positivity of syncytiotrophoblast by SARS-CoV-2, fulfilling the published criteria for transplacental viral transmission as confirmed in fetal cells through identification of viral antigens by immunohistochemistry or viral nucleic acid using RNA in situ hybridization. The co-occurrence of chronic histiocytic intervillositis and trophoblast necrosis appears to be a risk factor for placental infection with SARS-CoV-2 as well as for maternal-fetal viral transmission, and suggests a potential mechanism by which the coronavirus can breach the maternal-fetal interface.

Impact of SARS-CoV-2 (COVID-19) on pregnancy: a systematic review and meta-analysis protocol.

INTRODUCTION: The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has been growing at an accelerating rate, and has become a public health emergency. Pregnant women and their fetuses are susceptible to viral infection, and outcomes in this population need to be investigated. METHODS AND ANALYSIS: PubMed, Web of Science, Embase, CINAHAL, Latin American and Caribbean Health Sciences Literature, clinicaltrials.gov, SCOPUS, Google Scholar and Cochrane Central Controlled Trials Registry will be searched for observational studies (cohort and control cases) published from December 2019 to present. This systematic review and meta-analysis will include studies of pregnant women at any gestational stage diagnosed with COVID-19. The primary outcomes will be maternal and foetal morbidity and mortality. Three independent reviewers will select the studies and extract data from the original publications. The risk of bias will be assessed using the Newcastle-Ottawa Scale for observational studies. To evaluate the strength of evidence from the included data, we will use Grading of Recommendation Assessment, Development, and Evaluation method. Data synthesis will be performed using Review Manager software V.5.2.3. To assess heterogeneity, we will compute the I2 statistics. Additionally, a quantitative synthesis will be performed if the included studies are sufficiently homogenous. ETHICS AND DISSEMINATION: This study will be a review of the published data, and thus it is not necessary to obtain ethical approval. The findings of this systematic review will be published in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER: PROSPERO 2020: CRD42020181519.

Is highly expressed ACE 2 in pregnant women "a curse" in times of COVID-19 pandemic?

Angiotensin-converting enzyme 2 (ACE 2) is a membrane-bound enzyme that cleaves angiotensin II (Ang II) into angiotensin (1-7). It also serves as an important binding site for SARS-CoV-2, thereby, facilitating viral entry into target host cells. ACE 2 is abundantly present in the intestine, kidney, heart, lungs, and fetal tissues. Fetal ACE 2 is involved in myocardium growth, lungs and brain development. ACE 2 is highly expressed in pregnant women to compensate preeclampsia by modulating angiotensin (1-7) which binds to the Mas receptor, having vasodilator action and maintain fluid homeostasis. There are reports available on Zika, H1N1 and SARS-CoV where these viruses have shown to produce fetal defects but very little is known about SARS-CoV-2 involvement in pregnancy, but it might have the potential to interact with fetal ACE 2 and enhance COVID-19 transmission to the fetus, leading to fetal morbidity and mortality. This review sheds light on a path of SARS-CoV-2 transmission risk in pregnancy and its possible link with fetal ACE 2.

Maternal and fetal outcomes of COVID-19, SARS, and MERS: a narrative review on the current knowledge.

OBJECTIVE: Coronavirus infections, including SARS, MERS and COVID-19 have significant impact on global health as well as on pregnancies. The aim of this review was to enlighten and summarize the cumulative knowledge regarding the relationship between Coronavirus outbreaks and pregnancy. MATERIALS AND METHODS: Literature search was commenced in order to analyze the maternofetal effects of Coronavirus outbreaks. RESULTS: Fever and cough are the most common presenting symptoms of COVID-19 which mostly affects pregnant women in their 3rd trimester with a maternal mortality rate of  0-77%  and fetal and neonatal mortality rates of 1.2%. Fetal demise is common in critically ill pregnant. Pregnancy seems as a worsening factor for SARS and MERS epidemics and both infections affect prominently 3rd trimester pregnancies, although abortion (57%) is a significant risk for cases of early pregnancy. Clinical course of COVID-19, SARS and MERS may be rapid and worse in pregnant women than non-pregnant individuals. Cesarean section is the choice of delivery in most reported women due to mostly obstetrical reasons, although vaginal delivery seems not a worsening factor for the disease. CONCLUSIONS: COVID-19, SARS and MERS have significant detrimental effect on pregnancy. Rapid intervention, treatment, and intensive care support are essential for infected pregnant. Timely delivery is important in order to avoid intrauterine fetal death.