Cytomegalovirus infection during pregnancy: cross-sectional survey of knowledge and prevention practices of healthcare professionals in French-speaking Switzerland.

BACKGROUND: Lack of Cytomegalovirus (CMV) knowledge among healthcare professionals has been proven to be the main threat to pregnant women's awareness, preventing them from reducing the risk of infection. The aims of this study were to assess the knowledge and practices of French-speaking Swiss perinatal professionals in terms of CMV prevention, as well as the sociodemographic-professional factors that influence them. METHODS: This observational study used a cross-sectional design to collect data-via an anonymous electronic questionnaire in French distributed to gynecologists-obstetricians, general practitioners and midwives via various channels: e-mails and social networks of partner centers, professional associations, and conferences. The 41-item questionnaire collected data on sociodemographic and professional characteristics, general CMV knowledge, national recommendation knowledge and prevention practices. Univariable and multivariable analyses were performed. RESULTS: A total of 110 gynecologist-obstetricians, 5 general practitioners and 226 midwives participated in the study. While more than 80% of practitioners were familiar with protective hygiene measures, significant gaps were highlighted concerning the transmission routes, as well as the signs of short- and long-term congenital CMV infection. Regarding practice, 63.3% of participants provided information on CMV to their patients, mainly during the first antenatal visit. Among those who did not, lack of knowledge and forgetfulness were the two main reasons cited. Concerning systematic screening, 45.7% of participants offered it to their patients, and 37.3% only offered it to "at risk" groups. The existence of national guidelines on CMV was known by 62.0% of participants. Multivariable analysis revealed that working as a gynecologist-obstetrician was independently associated with higher score of preventive practices, while performing ultrasound or preconception consultations was independently associated with a higher score of general CMV knowledge, and working in a university hospital was independently associated with a higher score of Swiss recommendation knowledge. A level of training higher than the basic medical or midwifery diploma and participation in fetal medicine symposia both promote a higher score of CMV knowledge and prevention practices in line with current recommendations. CONCLUSION: This study confirms the significant gaps in CMV knowledge among French-speaking Swiss caregivers along with the heterogeneity of their prevention practices. To raise awareness among pregnant women and reduce the burden of congenital CMV infections, improving professional knowledge through access to specific training and standardizing practices should be a national priority.

Contribution of fetal blood sampling to determining the prognosis of congenital cytomegalovirus infections: a case-cohort study in Switzerland.

BACKGROUND: Cytomegalovirus is responsible for the most common congenital infection, affecting 0.5% to 1.0% of live births in Europe. Congenital cytomegalovirus infection can be diagnosed during pregnancy by viral DNA amplification in the amniotic fluid, but the prognosis of fetuses without severe brain abnormalities remains difficult to establish on the basis of prenatal imaging alone. OBJECTIVE: To identify predictors of moderate to severe symptomatic cytomegalovirus infection among fetal blood parameters and to propose an algorithm on the basis of these parameters and on prenatal imaging that would provide the best positive and negative predictive values. STUDY DESIGN: Fetal blood sampling at 21-28 weeks gestation was performed in fetuses with congenital cytomegalovirus infection confirmed by amniocentesis after maternal infection in the first-trimester or periconceptional period. We compared the levels of hemoglobin, thrombocytes, γ-glutamyl transpeptidase, aspartate aminotransferase, alanine aminotransferase, ß2-microglobulin, immunoglobulins G and M, and cytomegalovirus DNA viral loads in amniotic fluid and fetal blood between those with moderate to severe symptomatic infection and those with asymptomatic to mild infection (median follow-up of 36 months for live births). RESULTS: Among 58 fetuses included, 25 (43%) had a moderate to severe symptomatic infection: 16 with severe cerebral abnormalities, 5 with multiple signs or symptoms at birth, 2 with bilateral sensorineural hearing loss, and 2 with neurodevelopmental delay. The values of thrombocytes, aspartate aminotransferase, ß2 microglobulin, Immunoglobulin M, and cytomegalovirus viral loads differed significantly between fetuses with moderate to severe symptomatic infection and those with asymptomatic to mild infection. The optimal strategy to predict moderate to severe symptomatic infection was to first perform fetal brain imaging, followed by fetal blood sampling with the following cutoffs: thrombocytes <120,000/mL, viremia ≥5 log10/mL, and ß2 microglobulin ≥12 mg/L). This recursive algorithm had a negative predictive value of 100% for moderately to severely symptomatic infection. CONCLUSION: The combination of thrombocytes, ß2-microglobulin, and cytomegalovirus viral load in fetal blood can be used for prognosis determination, particularly in cytomegalovirus-infected fetuses without severe brain abnormalities at the time of prenatal diagnosis. Future studies should evaluate whether these parameters remain useful in infected fetuses who have been treated with valacyclovir before fetal blood sampling.

Emerging and re-emerging infectious diseases in pregnant women in an amazonian region: a large retrospective study from French Guiana.

PURPOSE: Over the past decade, the Amazon basin has faced numerous infectious epidemics. Our comprehension of the actual extent of these infections during pregnancy remains limited. This study aimed to clarify the clinical and epidemiological features of emerging and re-emerging infectious diseases during pregnancy in western French Guiana and along the Maroni River over the previous nine years. METHODS: This retrospective cohort study enrolled pregnant women living in west French Guiana territory and giving birth in the only local referral center after 22 weeks of gestation between 2013 and 2021. Data on symptomatic or asymptomatic biologically confirmed emerging or re-emerging diseases during pregnancy was collected. RESULTS: Six epidemic waves were experienced during the study period, including 498 confirmed Zika virus infections (2016), 363 SARS-CoV-2 infections (2020-2021), 87 chikungunya virus infections (2014), 76 syphilis infections (2013-2021), and 60 dengue virus infections (2013-2021) at different gestational ages. Furthermore, 1.1% (n = 287) and 1.4% (n = 350) of pregnant women in west French Guiana were living with HIV and HTLV, respectively. During the study period, at least 5.5% (n = 1,371) faced an emerging or re-emerging infection during pregnancy. CONCLUSION: These results highlight the diversity, abundance, and dynamism of emerging and re-emerging infectious agents faced by pregnant women in the Amazon basin. Considering the maternal and neonatal adverse outcomes associated with these infections, increased efforts are required to enhance diagnosis, reporting, and treatment of these conditions.

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.

Prenatal Diagnosis of Gómez-López-Hernández Syndrome.

INTRODUCTION: Gómez-López-Hernández syndrome (GLHS), also known as cerebello-trigeminal-dermal dysplasia, is an extremely rare neurocutaneous disease, classically described by the triad of rhombencephalosynapsis (RES), bilateral focal alopecia, and trigeminal anesthesia. The clinical and radiographic spectrum of GLHS is now known to be broader, including craniofacial and supratentorial anomalies, as well as neurodevelopmental issues. CASE PRESENTATION: Here, we present a case of antenatally diagnosed GLHS with RES, hydrocephaly, and craniofacial anomalies identified on ultrasound (low-set ears with posterior rotation, hypertelorism, midface hypoplasia, micrognathia, and anteverted nares) which were confirmed by autopsy after termination of pregnancy at 23 weeks of gestation. DISCUSSION: As no known genetic causes have been identified and the classical triad is not applicable to prenatal imaging, prenatal diagnosis of GLHS is based on neuroimaging and the identification of supporting features. In presence of an RES associated with craniofacial abnormalities in prenatal (brachycephaly, turricephaly, low-set ears, midface retrusion, micrognathia), GLHS should be considered as "possible" according to postnatal criteria.

Tonate Virus and Fetal Abnormalities, French Guiana, 2019.

We report a case of vertical transmission of Tonate virus in a pregnant woman from French Guiana. The fetus showed severe necrotic and hemorrhagic lesions of the brain and spinal cord. Clinicians should be made aware of possible adverse fetal outcomes in pregnant women infected with Tonate virus.

Impact of the first wave of the COVID-19 pandemic on birth rates in Europe: a time series analysis in 24 countries.

STUDY QUESTION: Did the first wave of the COVID-19 pandemic have an impact on monthly birth rates in Europe? SUMMARY ANSWER: Using datasets on live births per month in Europe, collected from the Human Fertility Database, we found a -14.1% decline in live births in January 2021 (i.e. 9-10 months after the epidemic peaks and first lockdowns), compared to the average number of live births in January 2018 and 2019. WHAT IS KNOWN ALREADY: Previous pandemics in the 20th and 21st centuries have been associated with a decline in birth rates 9 months after their peak, and a rebound in births over time. Lockdowns were necessary to control the first wave of the COVID-19 pandemic and may have had an impact on subsequent birth rates. STUDY DESIGN, SIZE, DURATION: Monthly time series data on live births from January 2018 to March 2021 were extracted to provide a time-series analysis of birthrates during and after the first wave of the COVID-19 pandemic in 24 European countries. PARTICIPANTS/MATERIALS, SETTING, METHODS: We conducted a random-effect generalized least squares regression to assess the seasonality of births from January 2018 to March 2021, and to identify potential differences in monthly live births after the first wave of the COVID-19 pandemic, considering the seasonality of births. To quantify these potential differences, we estimated the variation rate between the monthly live births observed during 2020 and 2021 and the mean of the 2018-2019 monthly live births in Europe. Factors potentially associated with a variation in monthly birth rates were assessed using univariable and multivariable generalized linear regressions. MAIN RESULTS AND THE ROLE OF CHANCE: When considering the seasonality of births, January 2021 was the only month with a significant difference in live births. A drop of -14.1% was observed compared to the average number of live births in January 2018 and 2019. At the national level, this drop was observed 9-10 months after the epidemic peaks in 13 countries. The duration of lockdowns was the variable that had the stronger association with this decrease, whereas higher incomes per capita could be a factor limiting this decline. A rebound in births compared to the previous years occurred in March 2021 in 13 countries. LIMITATIONS, REASONS FOR CAUTION: Our data are based on national data, limiting the power in the multivariable models used and the identification of other potential factors contributing to a decrease or an increase in birth rates. In addition, we collected only live births up to April 2021, which precludes the identification of a difference in births seasonality in 2021. WIDER IMPLICATIONS OF THE FINDINGS: As with previous pandemics, the COVID-19 outbreak was associated with a decline in births 9 months after its first wave. This trend may be associated with the duration of the lockdowns. Although there was a rebound in births in the following months, it does not seem to compensate for this decline. STUDY FUNDING/COMPETING INTEREST(S): The authors receive no external funding and have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

Prenatal diagnosis of Aicardi syndrome based on a suggestive imaging pattern: A multicenter case-series.

OBJECTIVES: To characterize a suggestive prenatal imaging pattern of Aicardi syndrome using ultrasound and MR imaging. METHODS: Based on a retrospective international series of Aicardi syndrome cases from tertiary centers encountered over a 20-year period (2000-2020), we investigated the frequencies of the imaging features in order to characterize an imaging pattern highly suggestive of the diagnosis. RESULTS: Among 20 cases included, arachnoid cysts associated with a distortion of the interhemispheric fissure were constantly encountered associated with complete or partial agenesis of the corpus callosum (19/20, 95%). This triad in the presence of other CNS disorganization, such as polymicrogyria (16/17, 94%), heterotopias (15/17, 88%), ventriculomegaly (14/20, 70%), cerebral asymmetry [14/20, 70%]) and less frequently extra-CNS anomaly (ocular anomalies [7/11, 64%], costal/vertebral segmentation defect [4/20, 20%]) represent a highly suggestive pattern of Aicardi syndrome in a female patient. CONCLUSION: Despite absence of genetic test to confirm prenatal diagnosis of AS, this combination of CNS and extra-CNS fetal findings allows delineation of a characteristic imaging pattern of AS, especially when facing dysgenesis of the corpus callosum.

Prolonged Maternal Zika Viremia as a Marker of Adverse Perinatal Outcomes.

Whether prolonged maternal viremia after Zika virus infection represents a risk factor for maternal-fetal transmission and subsequent adverse outcomes remains unclear. In this prospective cohort study in French Guiana, we enrolled Zika virus-infected pregnant women with a positive PCR result at inclusion and noninfected pregnant women; both groups underwent serologic testing in each trimester and at delivery during January-July 2016. Prolonged viremia was defined as ongoing virus detection >30 days postinfection. Adverse outcomes (fetal loss or neurologic anomalies) were more common in fetuses and neonates from mothers with prolonged viremia (40.0%) compared with those from infected mothers without prolonged viremia (5.3%, adjusted relative risk [aRR] 7.2 [95% CI 0.9-57.6]) or those from noninfected mothers (6.6%, aRR 6.7 [95% CI 3.0-15.1]). Congenital infections were confirmed more often in fetuses and neonates from mothers with prolonged viremia compared with the other 2 groups (60.0% vs. 26.3% vs. 0.0%, aRR 2.3 [95% CI 0.9-5.5]).

Mental health status of pregnant and breastfeeding women during the COVID-19 pandemic-A multinational cross-sectional study.

INTRODUCTION: Evidence on perinatal mental health during the coronavirus disease 2019 (COVID-19) pandemic and its potential determinants is limited. Therefore, this multinational study aimed to assess the mental health status of pregnant and breastfeeding women during the pandemic, and to explore potential associations between depressive symptoms, anxiety, and stress and women's sociodemographic, health, and reproductive characteristics. MATERIAL AND METHODS: A cross-sectional, web-based study was performed in Ireland, Norway, Switzerland, the Netherlands, and the UK between 16 June and 14 July 2020. Pregnant and breastfeeding women up to 3 months postpartum who were older than 18 years of age were eligible. The online, anonymous survey was promoted through social media and hospital websites. The Edinburgh Depression Scale (EDS), the Generalized Anxiety Disorder seven-item scale (GAD-7), and the Perceived Stress Scale (PSS) were used to assess mental health status. Regression model analysis was used to identify factors associated with poor mental health status. RESULTS: In total, 9041 women participated (including 3907 pregnant and 5134 breastfeeding women). The prevalence of major depressive symptoms (EDS ≥ 13) was 15% in the pregnancy cohort and and 13% the breastfeeding cohort. Moderate to severe generalized anxiety symptoms (GAD ≥ 10) were found among 11% and 10% of the pregnant and breastfeeding women. The mean (±SD) PSS scores for pregnant and breastfeeding women were 14.1 ± 6.6 and 13.7 ± 6.6, respectively. Risk factors associated with poor mental health included having a chronic mental illness, a chronic somatic illness in the postpartum period, smoking, having an unplanned pregnancy, professional status, and living in the UK or Ireland. CONCLUSIONS: This multinational study found high levels of depressive symptoms and generalized anxiety among pregnant and breastfeeding women during the COVID-19 outbreak. The study findings underline the importance of monitoring perinatal mental health during pandemics and other societal crises to safeguard maternal and infant mental health.

SARS-CoV-2 in the context of past coronaviruses epidemics: Consideration for prenatal care.

Since December 2019, the novel SARS-CoV-2 outbreak has resulted in millions of cases and more than 200 000 deaths worldwide. The clinical course among nonpregnant women has been described, but data about potential risks for women and their fetus remain scarce. The SARS and MERS epidemics were responsible for miscarriages, adverse fetal and neonatal outcomes, and maternal deaths. For COVID-19 infection, only nine cases of maternal death have been reported as of 22 April 2020, and pregnant women seem to develop the same clinical presentation as the general population. However, severe maternal cases, as well as prematurity, fetal distress, and stillbirth among newborns have been reported. The SARS-CoV-2 pandemic greatly impacts prenatal management and surveillance and raise the need for clear unanimous guidelines. In this narrative review, we describe the current knowledge about coronaviruses (SARS, MERS, and SARS-CoV-2) risks and consequences on pregnancies, and we summarize available current candidate therapeutic options for pregnant women. Finally, we compare current guidance proposed by The Royal College of Obstetricians and Gynaecologists, The American College of Obstetricians and Gynecologists, and the World Health Organization to give an overview of prenatal management which should be utilized until future data appear.

Ultrasound features of fetal toxoplasmosis: A contemporary multicenter survey in 88 fetuses.

OBJECTIVE: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT). METHODS: We retrospectively analyzed all cases of fetal infection with Toxoplasma gondii with ultrasound anomalies described by fetal medicine experts in 2009 to 2019 in 30 French centers. RESULTS: Eighty-eight cases of CT were included. Forty-five (51.1%) had one or more cerebral signs only, 35 (39.8%) had cerebral plus extracerebral signs and 8 (9.1%) had extracerebral signs only. The main cerebral signs were intracranial hyperechogenic nodular foci (n = 60) of which 20 were isolated, ventriculomegalies (n = 44) which generally increased during follow-up, and periventricular abscesses (n = 12). The main extracerebral signs were hepatomegaly and/or splenomegaly (n = 14), small for gestational age (n = 14), ascites (n = 14, including 2 with hydrops), and hyperechogenic bowel (n = 11). Maternal infection occurred mostly in the first or second trimester (81 cases), periconceptionally in one and in the third trimester in six cases. The first ultrasound signs were detected after a median of 7 weeks (range: 1.4; 24.0) following maternal toxoplasmosis seroconversion. CONCLUSION: While no sign was specific of CT, there were typical associations of cerebral signs with or without extracerebral signs. Detailed ultrasound examination could improve prognostic evaluation, as well as diagnosis of CT in settings lacking serological screening.

Another piece of the Zika puzzle: assessing the associated factors to microcephaly in a systematic review and meta-analysis.

BACKGROUND: Although it is known that Zika virus (ZIKV) infection during pregnancy may lead to microcephaly in the fetus, the prognostic factors associated with this tragic disorder remain unclear. We conducted a systematic review and meta-analysis to assess the prognostic factors associated with the incidence of microcephaly in congenital ZIKV infection. METHODS: We conducted a comprehensive search in Ovid MEDLINE, Ovid MEDLINE (R) Epub ahead of print, Embase, Embase Classic, Web of Science, CINAHL, Cochrane CENTRAL, LILACS, and various thesis databases to identify human studies reporting microcephaly associated with congenital ZIKV infection. We requested primary data from the authors of the included studies to calculate summary estimates and conduct the meta-analysis of the most prevalent factors. RESULTS: We screened 4106 titles and abstracts, and identified 12 studies for inclusion in the systematic review. The assessment of ZIKV infection and the definition of microcephaly varied among studies. A total of 6154 newborns/fetuses were enrolled; of those, 1120 (18.20%) had a diagnostic of ZIKV infection, of which 509 (45.45%) were diagnosed with microcephaly. Nine studies addressed the link between congenital ZIKV infection and neurological findings in newborns/fetuses. Half of the studies provided primary data. Three out of 11 factors of interest seem to be prognostic factors of microcephaly: infant's sex - males compared to females: Relative Risk (RR) 1.30, 95% Confidence Interval (95% CI) 1.14 to 1.49; the stage of pregnancy when infection occurred - infection in the first trimester of pregnancy compared to infection at other stages of pregnancy: RR 1.41, 95% CI 1.09 to 1.82; and asymptomatic infection compared to symptomatic infection during pregnancy: RR 0.68; 95% CI 0.60 to 0.77. CONCLUSION: Our findings support the female-biased resistance hypothesis and reinforce the risk associated with the stage of pregnancy when ZIKV infection occurs. Continued surveillance of ZIKV infection during pregnancy is needed to identify additional factors that could contribute to developing microcephaly in affected fetuses. PROTOCOL REGISTRATION: This systematic review was registered with the International Prospective Register of Systematic Reviews (PROSPERO), registration no. CRD 42018088075.

[COVID-19 and pregnancy]. / COVID-19 et grossesse.

The current COVID-19 pandemic has resulted in an unprecedented worldwide health crisis. The increased vulnerability of pregnant women as well as past experience from previous coronavirus epidemics are cause for concern of maternal and fetal complications. The rapid outbreak of the disease combined with the uncertainty, as a direct result of the lack of strong scientific data, has forced obstetricians to adapt their current practices pragmatically. This article reviews obstetrical management of pregnant patients infected by SARS-CoV-2 based on the current knowledge.

L'actuelle pandémie de COVID-19 est à l'origine d'une crise sanitaire mondiale sans précédent. La vulnérabilité des femmes enceintes aux infections ainsi que l'expérience des précédentes épidémies de coronavirus ont fait naître des interrogations quant aux risques de complications materno-fœtales. La rapidité avec laquelle l'infection a progressé, ainsi que l'incertitude de son impact sur la grossesse due à l'absence de données scientifiques solides a forcé les obstétriciens à adapter leur pratique en se basant sur des attitudes pragmatiques. Cet article revoit la prise en charge obstétricale des patientes infectées par SARS-CoV-2 sur la base des connaissances actuelles.