Maternal and perinatal outcomes with COVID-19: A systematic review of 108 pregnancies.

INTRODUCTION: The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has exposed vulnerable populations to an unprecedented global health crisis. The knowledge gained from previous human coronavirus outbreaks suggests that pregnant women and their fetuses are particularly susceptible to poor outcomes. The objective of this study was to summarize the clinical manifestations and maternal and perinatal outcomes of COVID-19 during pregnancy. MATERIAL AND METHODS: We searched databases for all case reports and series from 12 February to 4 April 2020. Multiple terms and combinations were used including COVID-19, pregnancy, maternal mortality, maternal morbidity, complications, clinical manifestations, neonatal morbidity, intrauterine fetal death, neonatal mortality and SARS-CoV-2. Eligibility criteria included peer-reviewed publications written in English or Chinese and quantitative real-time polymerase chain reaction (PCR) or dual fluorescence PCR-confirmed SARS-CoV-2 infection. Unpublished reports, unspecified date and location of the study or suspicion of duplicate reporting, cases with suspected COVID-19 that were not confirmed by a laboratory test, and unreported maternal or perinatal outcomes were excluded. Data on clinical manifestations, maternal and perinatal outcomes including vertical transmission were extracted and analyzed. RESULTS: Eighteen articles reporting data from 108 pregnancies between 8 December 2019 and 1 April 2020 were included in the current study. Most reports described women presenting in the third trimester with fever (68%) and coughing (34%). Lymphocytopenia (59%) with elevated C-reactive protein (70%) was observed and 91% of the women were delivered by cesarean section. Three maternal intensive care unit admissions were noted but no maternal deaths. One neonatal death and one intrauterine death were also reported. CONCLUSIONS: Although the majority of mothers were discharged without any major complications, severe maternal morbidity as a result of COVID-19 and perinatal deaths were reported. Vertical transmission of the COVID-19 could not be ruled out. Careful monitoring of pregnancies with COVID-19 and measures to prevent neonatal infection are warranted.

Adverse pregnancy outcomes during the COVID-19 lockdown. A descriptive study.

BACKGROUND: The ongoing spread coronavirus disease worldwide has caused major disruptions and led to lockdowns. Everyday lifestyle changes and antenatal care inaccessibility during the coronavirus disease 2019 (COVID-19) pandemic have variable results that affect pregnancy outcomes. This study aimed to assess the alterations in stillbirth, neonatal-perinatal mortality, preterm birth, and birth weight during the COVID-19 national lockdown. METHODS: We used the data from the Jordan stillbirths and neonatal death surveillance system to compare pregnancy outcomes (gestational age, birth weight, small for gestational age, stillbirth, neonatal death, and perinatal death) between two studied periods (11 months before the pandemic (May 2019 to March 2020) vs. 9 months during the pandemic (April 2020 to March 1st 2020). Separate multinomial logistic and binary logistic regression models were used to compare the studied outcomes between the two studied periods after adjusting for the effects of mother's age, income, education, occupation, nationality, health sector, and multiplicity. RESULTS: There were 31106 registered babies during the study period; among them, 15311 (49.2%) and 15795 (50.8%) births occurred before and during the COVID-19 lockdown, respectively. We found no significant differences in preterm birth and stillbirth rates, neonatal mortality, or perinatal mortality before and during the COVID-19 lockdown. Our findings report a significantly lower incidence of extreme low birth weight (ELBW) infants (<1kg) during the COVID-19 lockdown period than that before the lockdown (adjusted OR 0.39, 95% CI 0.3-0.5: P value <0.001) CONCLUSIONS: During the COVID-19 lockdown period, the number of infants born with extreme low birth weight (ELBW) decreased significantly. More research is needed to determine the impact of cumulative socio-environmental and maternal behavioral changes that occurred during the pandemic on the factors that contribute to ELBW infants.

Perinatal outcomes in women with severe acute respiratory syndrome coronavirus 2 infection: comparison with contemporary and matched pre-COVID-19 controls.

OBJECTIVES: To compare perinatal outcomes in women with vs. without severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. METHODS: Perinatal outcomes in SARS-CoV-2 positive pregnant women who delivered at our institution between October 27th 2020 and January 31st 2021 were compared to SARS-CoV-2 negative pregnancies (contemporary controls) and historical 2019 controls matched by maternal age, pre-pregnancy body mass index and parity. Testing was performed based on symptoms or close contact at any time during pregnancy and as part of universal screening at hospital admission. Multivariable log-linear regression models were used adjusting for potential confounders (p < 0.05 statistically significant). RESULTS: One thousand three hundred seventeen women delivered at our institution during the study period. 1,124 (85%) tested negative and 193 (15%) positive for SARS-CoV-2. 189 (98%) were infected during third trimester. 19 (10%) were asymptomatic, 171 (89%) had mild to moderate coronavirus disease 2019 (COVID-19), and 3 (2%) were critically ill with one case of maternal death. There were no significant differences in preterm birth, small-for-gestational-age birth weight, congenital anomalies, operative delivery, intrapartum hypoxia, and perinatal mortality in SARS-CoV-2 positive pregnancies compared to contemporary reference group or historical controls from pre-COVID-19 period. Labor was more commonly induced in SARS-CoV-2 positive women compared to reference SARS-CoV-2 negative group (68 [35%] vs. 278 [25%], adjusted odds ratio 1.62; 95% confidence interval 1.14-2.28). CONCLUSIONS: SARS-CoV-2 infection in pregnancy was not strongly associated with adverse perinatal outcomes. While the majority of SARS-CoV-2 positive women had no or mild/moderate symptoms, 2% were critically ill, with one case of maternal death.

Effectiveness of neonatal "near miss" audits in reducing perinatal morbidity and mortality: a systematic review protocol.

OBJECTIVE: This review will assess the effectiveness of neonatal near-miss audits in reducing perinatal mortality and morbidity, as implemented in health care facilities. INTRODUCTION: Every year, 2.5 million newborns die and 2.6 million more are stillborn worldwide. While many perinatal deaths are preventable, their reduction has been markedly slower than the decline of maternal or child mortality rates. It is hypothesized that neonatal near miss is part of the spectrum of stillbirth-neonatal death and that auditing these cases might reduce perinatal mortality and morbidity. INCLUSION CRITERIA: This review will consider neonatal near-miss audits implemented in health care facilities worldwide. Randomized controlled trials, cluster-randomized trials, quasi-randomized controlled trials, controlled before-and-after studies, interrupted time series, case-control, cohort studies, cross-sectional studies, and case series will be included. Conference abstracts, letters, studies duplicating validation data from previous studies, gray literature, and unpublished studies will be excluded. METHODS: Using the JBI guidelines for conducting systematic reviews of effectiveness, the review will search the following electronic bibliographic databases: MEDLINE, Embase, Scopus, CINAHL, LILACS, and SciELO. No publication date or language limits will be imposed. Two independent reviewers will screen titles, abstracts, and full-text studies, assessing methodological quality with the JBI critical appraisal tools. GRADE will be used to assess the confidence in the findings. Covidence will be used for data extraction and management. A meta-analysis will be performed if the selected studies are sufficiently homogeneous. If not, the results will be discussed as a narrative synthesis. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO (CRD42021224090).

Disease Severity and Perinatal Outcomes of Pregnant Patients With Coronavirus Disease 2019 (COVID-19).

OBJECTIVE: To describe coronavirus disease 2019 (COVID-19) severity in pregnant patients and evaluate the association between disease severity and perinatal outcomes. METHODS: We conducted an observational cohort study of all pregnant patients with a singleton gestation and a positive test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) who delivered at 1 of 33 U.S. hospitals in 14 states from March 1 to July 31, 2020. Disease severity was classified by National Institutes of Health criteria. Maternal, fetal, and neonatal outcomes were abstracted by centrally trained and certified perinatal research staff. We evaluated trends in maternal characteristics and outcomes across COVID-19 severity classes and associations between severity and outcomes by multivariable modeling. RESULTS: A total of 1,219 patients were included: 47% asymptomatic, 27% mild, 14% moderate, 8% severe, 4% critical. Overall, 53% were Hispanic; there was no trend in race-ethnicity distribution by disease severity. Those with more severe illness had older mean age, higher median body mass index, and pre-existing medical comorbidities. Four maternal deaths (0.3%) were attributed to COVID-19. Frequency of perinatal death or a positive neonatal SARS-CoV-2 test result did not differ by severity. Adverse perinatal outcomes were more frequent among patients with more severe illness, including 6% (95% CI 2-11%) incidence of venous thromboembolism among those with severe-critical illness compared with 0.2% in mild-moderate and 0% in asymptomatic (P<.001 for trend across severity). In adjusted analyses, severe-critical COVID-19 was associated with increased risk of cesarean birth (59.6% vs 34.0%, adjusted relative risk [aRR] 1.57, 95% CI 1.30-1.90), hypertensive disorders of pregnancy (40.4% vs 18.8%, aRR 1.61, 95% CI 1.18-2.20), and preterm birth (41.8% vs 11.9%, aRR 3.53, 95% CI 2.42-5.14) compared with asymptomatic patients. Mild-moderate COVID-19 was not associated with adverse perinatal outcomes compared with asymptomatic patients. CONCLUSION: Compared with pregnant patients with SARS-CoV-2 infection without symptoms, those with severe-critical COVID-19, but not those with mild-moderate COVID-19, were at increased risk of perinatal complications.

Resilience and vulnerability of maternity services in Zimbabwe: a comparative analysis of the effect of Covid-19 and lockdown control measures on maternal and perinatal outcomes, a single-centre cross-sectional study at Mpilo Central Hospital.

BACKGROUND: On the 27th of March 2020 the Zimbabwean government declared the Covid-19 pandemic a 'national disaster'. Travel restrictions and emergency regulations have had significant impacts on maternity services, including resource stock-outs, and closure of antenatal clinics during the lockdown period. Estimates of the indirect impact of Covid-19 on maternal and perinatal mortality was expected it to be considerable, but little data was yet available. This study aimed to examine the impact of Covid-19 and lockdown control measures on non-Covid outcomes in a government tertiary level maternity unit in Bulawayo, Zimbabwe, by comparing maternal and perinatal morbidity and mortality before, and after the lockdown was implemented. METHODS: This was a retrospective, observational study, using a cross-sectional design to compare routine monthly maternal and perinatal statistics three months before and after Covid-19 emergency measures were implemented at Mpilo Central Hospital. RESULTS: Between January-March and April-June 2020, the mean monthly deliveries reduced from 747.3 (SD ± 61.3) in the first quarter of 2020 to 681.0 (SD ± 17.6) during lockdown, but this was not statistically significant, p = 0.20. The Caesarean section rates fell from a mean of 29.8% (SD ± 1.7) versus 28.0% (SD ± 1.7), which was also not statistically significant, p = 0.18. During lockdown, the percentage of women delivering at Mpilo Central Hospital who were booked at the hospital fell from a mean of 41.6% (SD ± 1.1) to 35.8% (SD ± 4.3) which was statistically significant, p = 0.03. There was no significant change, however, in maternal mortality or severe maternal morbidity (such as post-partum haemorrhage (PPH), uterine rupture, and severe preeclampsia/eclampsia), stillbirth rate or special care baby unit admission. There was an increase in the mean total number of early neonatal deaths (ENND) (mean 18.7 (SD ± 2.9) versus 24.0 (SD ± 4.6), but this was not statistically significant, p = 0.32. CONCLUSIONS: Overall, maternity services at Mpilo showed resilience during the lockdown period, with no significant change in maternal and perinatal adverse outcomes, with the same number of man-hours worked before and during the lockdown Maternal and perinatal outcomes should continue to be monitored to assess the impact of Covid-19 and the lockdown measures as the pandemic in Zimbabwe unfolds. Further studies would be beneficial to explore women's experiences and understand how bookings and deliveries at local clinics changed during this time.

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.

Maternal and perinatal outcomes in pregnant women infected by SARS-CoV-2: A meta-analysis.

Evidence concerning coronavirus disease-19 (covid-19) in pregnancy is still scarce and scattered. This meta-analysis aims to evaluate maternal and neonatal outcomes in covid-19 pregnancies and identify factors associated with perinatal viral transmission. Medline, Scopus, CENTRAL, Web of Science and Google Scholar databases were systematically searched to 3 June 2020. Overall, 16 observational studies and 44 case reports/series were included. Fever was the most frequent maternal symptom, followed by cough and shortness of breath, while about 15 % of infected were asymptomatic. Severe disease was estimated to occur in 11 % of women in case reports/series and in 7 % (95 % CI: 4 %-10 %) in observational studies. Two maternal deaths were reported. The rate of neonatal transmission did not differ between women with and without severe disease (OR: 1.94, 95 % CI: 0.50-7.60). Preterm birth occurred in 29.7 % and 16 % (95 % CI: 11 %-21 %) in data obtained from case series and observational studies, respectively. Stillbirth occurred in 3 cases and 2 neonatal deaths were observed. Vertical transmission was suspected in 4 cases. Fever was the most common neonatal symptom (40 %), followed by shortness of breath (28 %) and vomiting (24 %), while 20 % of neonates were totally asymptomatic. In conclusion, the maternal and neonatal clinical course the infection is typically mild, presenting low mortality rates. The risk of vertical transmission is suggested to be low and may not be affected by the severity of maternal disease. Further large-scale studies are needed to clarify the risk factors associated with viral transmission and severe infection in the neonatal population.

Gestation and COVID-19: clinical and microbiological observational study (Gesta-COVID19).

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) is a novel disease which has been having a worldwide affect since December 2019. Evidence regarding the effects of SARS-CoV-2 during pregnancy is conflicting. The presence of SARS-CoV-2 has been demonstrated in biological samples during pregnancy (placenta, umbilical cord or amniotic fluid); however, maternal and fetal effects of the virus are not well known. METHODS: Descriptive, multicentre, longitudinal, observational study in eight tertiary care hospitals throughout Spain, that are referral centres for pregnant women with COVID-19. All pregnant women with positive SARS-CoV-2 real-time reverse transcriptase polymerase chain reaction during their pregnancy or 14 days preconception and newborns born to mothers infected with SARS-CoV-2 will be included. They will continue to be followed up until 4 weeks after delivery. The aim of the study is to investigate both the effect of COVID-19 on the pregnancy, and the effect of the pregnancy status with the evolution of the SARS-CoV-2 disease. Other samples (faeces, urine, serum, amniotic fluid, cord and peripheral blood, placenta and breastmilk) will be collected in order to analyse whether or not there is a risk of vertical transmission and to describe the behaviour of the virus in other fluids. Neonates will be followed until 6 months after delivery to establish the rate of neonatal transmission. We aim to include 150 pregnant women and their babies. Ethics approval will be obtained from all the participating centres. DISCUSSION: There is little information known about COVID-19 and its unknown effects on pregnancy. This study will collect a large number of samples in pregnant women which will allow us to demonstrate the behaviour of the virus in pregnancy and postpartum in a representative cohort of the Spanish population.

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.

Impact of the COVID-19 Pandemic on Excess Perinatal Mortality and Morbidity in Israel.

OBJECTIVE: The 2020 COVID-19 pandemic has been associated with excess mortality and morbidity in adults and teenagers over 14 years of age, but there is still limited evidence on the direct and indirect impact of the pandemic on pregnancy. We aimed to evaluate the effect of the first wave of the COVID-19 pandemic on obstetrical emergency attendance in a low-risk population and the corresponding perinatal outcomes. STUDY DESIGN: This is a single center retrospective cohort study of all singleton births between February 21 and April 30. Prenatal emergency labor ward admission numbers and obstetric outcomes during the peak of the first COVID-19 pandemic of 2020 in Israel were compared with the combined corresponding periods for the years 2017 to 2019. RESULTS: During the 2020 COVID-19 pandemic, the mean number of prenatal emergency labor ward admissions was lower, both by daily count and per woman, in comparison to the combined matching periods in 2017, 2018, and 2019 (48.6 ± 12.2 vs. 57.8 ± 14.4, p < 0.0001 and 1.74 ± 1.1 vs. 1.92 ± 1.2, p < 0.0001, respectively). A significantly (p = 0.0370) higher rate of stillbirth was noted in the study group (0.4%) compared with the control group (0.1%). All study group patients were negative for COVID-19. Gestational age at delivery, rates of premature delivery at <28, 34, and 37 weeks, pregnancy complications, postdate delivery at >40 and 41 weeks, mode of delivery, and numbers of emergency cesarean deliveries were similar in both groups. There was no difference in the intrapartum fetal death rate between the groups. CONCLUSION: The COVID-19 pandemic stay-at-home policy combined with patient fear of contracting the disease in hospital could explain the associated higher rate of stillbirth. This collateral perinatal damage follows a decreased in prenatal emergency labor ward admissions during the first wave of COVID-19 in Israel. KEY POINTS: · Less obstetrical ER attendance is observed during the pandemic.. · There is a parallel increase in stillbirth rate.. · Stillbirth cases tested negative for COVID-19.. · Lockdown and pandemic panic are possible causes..

Maternal and perinatal outcomes and pharmacological management of Covid-19 infection in pregnancy: a systematic review protocol.

BACKGROUND: Over 4.2 million confirmed cases and more than 285,000 deaths, COVID-19 pandemic continues to harm significant number of people worldwide. Several studies have reported the impact of COVID-19 in general population; however, there is scarcity of information related to pharmacological management and maternal and perinatal outcomes during the pandemic. Altered physiological, anatomical, and immunological response during pregnancy makes it more susceptible to infections. Furthermore, during pregnancy, a woman undergoes multiple interactions with the health care system that increases her chance of getting infected; therefore, managing pregnant population presents a unique challenge. RESEARCH QUESTIONS: This systematic review seeks to answer the following questions in relation to COVID-19: What are the different clinical characteristics presented in maternal and perinatal population? What are the different maternal and perinatal outcome measures reported? What are the distinct therapeutic interventions reported to treat COVID-19? Is it safe to use "medications" used in the treatment of COVID-19 during antenatal, perinatal, postnatal, and breastfeeding? METHOD: The search will follow a comprehensive, sequential three step search strategy. Several databases relevant to COVID-19 and its impact on pregnancy including Medline, CINAHL, and LitCovid will be searched from the inception of the disease until the completion of data collection. The quality of this search strategy will be assessed using Peer Review of Electronic Search Strategies Evidence-Based Checklist (PRESS EBC). An eligibility form will be developed for a transparent screening and inclusion/exclusion of studies. All studies will be sent to RefWorks, and abstraction will be independently performed by two researchers. Risk of bias will be assessed using Cochrane Risk of Bias tool for randomized controlled trials, Newcastle-Ottawa Quality Assessment Scale for non-randomized studies, and for case reports, Murad et al. tool will be used. Decision to conduct meta-analysis will be based on several factors including homogeneity and outcome measures reported; otherwise, a narrative synthesis will be deemed appropriate. DISCUSSION: This systematic review will summarize the existing data on effect of COVID-19 on maternal and perinatal population. Furthermore, to the best of our knowledge, this is the first systematic review addressing therapeutic management and safety of medicines to treat COVID-19 during pregnancy and breastfeeding. SYSTEMATIC REVIEW REGISTRATION: This systematic review has been registered and published with Prospero ( CRD42020172773 ).