Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV

Mental health in pregnant individuals during the COVID-19 pandemic based on a Swiss online survey.

The aim of our study was to evaluate the mental health of pregnant individuals during the early COVID-19 pandemic and the potential factors associated. A Swiss online survey was proposed to individuals who gave birth during the pandemic period from March 2020. The Edinburgh Postnatal Depression Scale (EPDS), Generalized Anxiety Disorder 7 questions (GAD-7), and Impact Event Scale-Revised (IES-R) were evaluated and used to defined mental health impairment as a composite outcome. From October, 2020 to February, 2021, 736 participants responded. The anxiety GAD-7 score was moderate in 9.6% and severe in 2.0%. The EPDS was moderate in 21.5% and severe in 32.9%. The IES-R was moderate in 10.3% and severe in 3.9%. Mental health impairment was reported in 37.0%. The association between the risk of mental health impairment and foreign nationality was significant (OR = 1.48; 95%CI [1.06-2.05]) as well as fetal and pregnancy worries because of coronavirus (OR = 1.46; 95% CI [1.08-1.98]) and 1.65; 95% CI [1.22-2.24]). Adjusted ORs were significant for foreign nationality (aOR = 1.51; 95%CI [1.07-2.13]) and pregnancy worries because of coronavirus (aOR = 1.62; 95%CI [1.10-2.40]). Pregnant people and especially foreign national have a high risk of mental health impairment during the pandemic

Determinants of Vaccination and Willingness to Vaccinate against COVID-19 among Pregnant and Postpartum Women during the Third Wave of the Pandemic: A European Multinational Cross-Sectional Survey.

With COVID-19 vaccination hesitancy at around 50% in the obstetric population, it is critical to identify which women should be addressed and how. Our study aimed to assess COVID-19 vaccination willingness among pregnant and postpartum women in Europe and to investigate associated determinants. This study was a cross-sectional, web-based survey conducted in Belgium, Norway, Switzerland, The Netherlands, and United Kingdom (UK) in June-August 2021. Among 3194 pregnant women, the proportions of women vaccinated or willing to be vaccinated ranged from 80.5% in Belgium to 21.5% in Norway. The associated characteristics were country of residence, chronic illness, history of flu vaccine, trimester of pregnancy, belief that COVID-19 is more severe during pregnancy, and belief that the COVID-19 vaccine is effective and safe during pregnancy. Among 1659 postpartum women, the proportions of women vaccinated or willing to be vaccinated ranged from 86.0% in the UK to 58.6% in Switzerland. The associated determinants were country of residence, chronic illness, history of flu vaccine, breastfeeding, and belief that the COVID-19 vaccine is safe during breastfeeding. Vaccine hesitancy in the obstetric population depends on medical history and especially on the opinion that the vaccine is safe and on the country of residence

COVID-19-related medicine utilization study in pregnancy: The COVI-PREG cohort

AIM The objective of this study was to describe the use of COVID-19-related medicines during pregnancy and their evolution between the early/late periods of the pandemic. METHODS Pregnant women who tested positive for SARS-CoV-2 from March 2020 to July 2021 were included using the COVI-PREG registry. Exposure to the following COVID-19-related medicines was recorded: antibiotics, antivirals, hydroxychloroquine, corticosteroids, anti-interleukin-6 and immunoglobulins. We described the prevalence of medicines used, by trimester of pregnancy, maternal COVID-19 severity level and early/late period of the pandemic (before and after 1 July 2020). FINDINGS We included 1964 pregnant patients who tested positive for SARS-CoV-2. Overall, 10.4% (205/1964) received at least one COVID-19-related medicine including antibiotics (8.6%; 169/1694), corticosteroids (3.2%; 62/1964), antivirals (2.0%; 39/1964), hydroxychloroquine (1.4%; 27/1964) and anti-interleukin-6 (0.3%; 5/1964). The use of at least one COVID-19-related medicine was 3.1% (12/381) in asymptomatic individuals, 4.2% (52/1233) in outpatients, 19.7% (46/233) in inpatients without oxygen, 72.1% (44/61) in those requiring standard oxygen, 95.7% (22/23) in those requiring high flow oxygen, 96.2% (25/26) in patients who required intubation and 57.1% (4/7) among patients who died. The proportion who received medicines to treat COVID-19 was higher before than after July 2020 (16.7% vs. 7.7%). Antibiotics, antivirals and hydroxychloroquine had lower rates of use during the late period. CONCLUSION Medicine use in pregnancy increased with disease severity. The trend towards increased use of corticosteroids seems to be aligned with changing guidelines. Evidence is still needed regarding the effectiveness and safety of COVID-19-related medicines in pregnancy

Datamama, bringing pregnancy research into the future: design, development, and evaluation of a citizen science pregnancy mobile application

Background: Pregnancy mobile applications (apps) have grown in popularity over the past decade, with some being used to promote study recruitment or health behaviors. However, no app serves as an all-in-one solution for collecting general data for research purposes and providing women with useful and desirable features. Aim: To create and develop a Swiss pregnancy mobile app as an innovative means to collect research data and provide users with reliable information. Methods: Determining the key features of the app involved a review of the literature and assessment of popular apps in the Swiss AppStore. A team of engineers developed the app, which includes a pregnancy timeline, questionnaires for data collection, medical and psychological articles and a checklist with appointment reminders. The content was written and reviewed by healthcare providers considered experts in the topics adressed. The questionnaires are distributed based on the user’s gestational age, by a chatbot. The project was authorized by the ethics commission in the canton of Vaud. An online survey of ten questions, advertised on Datamama’s home screen, was conducted to assess the users’ use of the app (27.11- 19.12.2022). Results: A review of 84 articles and 25 popular apps showed the need for a comprehensive pregnancy app. The development of Datamama took 2 years and included the creation of 70 medical and psychological articles and 29 questionnaires covering 300 unique variables. Six months after the launch, there were 800 users with a 73% average participation rate in the questionnaires. Sixty-five women completed the survey, with 70.8% using the app once to multiple times per week. The primary reason for using the app was to help research by answering the questionnaires, followed by access to reliable medical information. The reason most frequently ranked first for using the app was to help research by answering the questionnaires (42/65, 67% of women rated it first), followed by access to reliable medical information (34/65, 54% women rated it second). Women rated the information as clear, understandable, and interesting with a trust rating in data handling at 98.5%. The average grade for recommending the app was 8/10, with suggestions for increasing the amount of medical content and tailoring it based on gestational age. Conclusion: Datamama is the first pregnancy app to address the needs of both patients and researchers. Initial feedback from users was positive, highlighting future challenges for success. Future work will consist in improving the app, validating the data and use it to answer specific pregnancy-related research questions

Maternal and perinatal outcomes following pre-Delta, Delta, and Omicron SARS-CoV-2 variants infection among unvaccinated pregnant women in France and Switzerland: a prospective cohort study using the COVI-PREG registry.

BACKGROUND SARS-CoV-2 positive pregnant women are at higher risk of adverse outcomes, but little evidence is available on how variants impact that risk. We aim to evaluate maternal and perinatal outcomes among unvaccinated pregnant women that tested positive for SARS-CoV-2, stratified by pre-Delta, Delta, and Omicron periods. METHODS This prospective study enrolled women from March 2020 to September 2022. Exposure to the different SARS-CoV-2 variants was defined by their periods of predominance. The primary outcome was severe maternal adverse outcome defined as either intensive care unit admission, acute respiratory distress syndrome, advanced oxygen supplementation, or maternal death. The secondary outcomes were preterm birth and other perinatal outcomes. FINDINGS Overall, 1402, 262, and 391 SARS-CoV-2 positive pregnant women were enrolled during the pre-Delta, Delta, and Omicron periods respectively. Severe maternal adverse outcome was reported in 3.4% (n = 947/1402; 95% confidence intervals (95%CI) 2.5-4.5), 6.5% (n = 7/262; 95%CI 3.8-10.2), and 1.0% (n = 4/391; 95%CI 0.3-2.6) of women during the pre-Delta, Delta, and Omicron periods. The risk of severe maternal adverse outcome was higher during the Delta vs pre-Delta period (adjusted risk ratio (aRR) = 1.8; 95%CI 1.1-3.2) and lower during the Omicron vs pre-Delta period (aRR = 0.3; 95%CI, 0.1-0.8). The risks of hospitalization for COVID-19 were 12.6% (n = 176/1402; 95%CI 10.9-14.4), 17.2% (n = 45/262; 95%CI 12.8-22.3), and 12.5% (n = 49/391; 95%CI 9.4-16.2), during the pre-Delta, Delta, and Omicron period, respectively. Pregnancy complications occurred after SARS-CoV-2 exposure in 30.0% (n = 363/1212; 95%CI 27.4-32.6), 35.2% (n = 83/236; 95%CI 29.1-41.6), and 30.3% (n = 105/347; 95%CI 25.5-35.4) of patients during the pre-Delta, Delta, and Omicron periods, respectively. Stillbirths were reported in 0.5% (n = 6/1159; 95%CI 0.2-1.1), 2.8% (n = 6/210; 95%CI 1.0-6.0), and 0.9% (n = 2/213; 95%CI 0.1-3.4) or patients during the pre-Delta, Delta, and Omicron periods respectively. INTERPRETATION The Delta period was associated with a higher risk of severe maternal adverse outcome and the Omicron period with a lower risk of severe adverse outcome compared to pre-Delta era. The reported risk of hospitalization was high during the Omicron period and should not be trivialized. FUNDING Swiss Federal Office of Public Health, Fondation CHUV

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Emerging virus infections in adverse pregnancy outcomes ::Special Issue

Viruses that emerged in the past decades, such as arboviruses and SARS-coronaviruses, are increasingly recognized as potential risk factors for adverse pregnancy outcomes. On the fetal side, arboviruses have proved their ability to cross the placental barrier, at different stages of pregnancy, and have been associated with fetal losses, fetal malformations (Zika, West Nile, and Venezuelan equine encephalitis viruses) and adverse neonatal outcomes (Dengue and Chikungunya viruses). The SARS-COV-2 has also be associated with rare maternal-fetal transmission and placental affection leading to fetal losses. More common viruses, like cytomegalovirus, are also well-known causes of fetal and childhood sequelae, and recent research on its prognosis factors and in-utero treatment may be welcome. On the maternal side, SARS-COV-2 might compromise maternal health, as well as Dengue viruses have been associated with high risks of adverse obstetrical outcomes, including maternal death, pre-eclampsia or post-partum hemorrhage. Thus, research on the maternal physiopathology would also be welcome. In this Special Issue of Viruses, we aim for original researchs, reviews and commentaries that contribute to an improved understanding of viral infection of placenta and fetal cells, or that report on the maternal and fetal outcomes after an emerging viral infection during pregnancy