Quantification of maternal and fetal valaciclovir exposure in a pharmacokinetic study of cytomegalovirus-infected pregnant women treated to prevent vertical transmission.

Background: In cases of maternal primary infection with cytomegalovirus (CMV-MPI) maternal treatment with oral valaciclovir 8 g/day has been shown to reduce the risk of fetal infection. The pharmacological profile of this high dosage during pregnancy is not yet known.

Objectives: To quantify maternal-fetal exposure to valaciclovir 8 g/day in a population pharmacokinetic (popPK) study.

Virological characterization of Parvovirus B19 isolated during the atypical 2023-2024 outbreak in France.

Background: A Parvovirus B19 (B19V) outbreak has been reported in Europe in 2023-2024. The aims of this study were 1) to describe the incidence of primary cases from 2012 to 2024 in one French hospital 2) to analyze the genome of 2023 strains 3) to identify virological profiles according to the clinical presentations of B19V infection.

Methods: The incidence of B19V primary cases was studied through an interrupted time-series analysis.

In utero treatment of congenital cytomegalovirus infection with valganciclovir: an observational study on safety and effectiveness.

Background: The treatment of congenital cytomegalovirus (CMV) infection is usually administered to neonates after birth; however, it can be anticipated during the prenatal period by treating pregnant women in order to reduce the severity of the congenital disease. The most commonly used treatment for CMV during pregnancy is valaciclovir; however, valganciclovir has a higher potency against CMV and is the first choice for neonates with congenital CMV disease.

Objectives: We investigated neonatal and maternal safety of tertiary prevention in infected fetuses showing ultrasound features of infection using valganciclovir.

SARS-CoV-2 infection as cause of in-utero fetal death: regional multicenter cohort study.

Objective: Placental infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can lead to placental insufficiency and in-utero fetal death (IUFD). The objective of this study was to confirm and quantify the extent to which fetoplacental infection with SARS-CoV-2 is a cause of fetal death.

Methods: This was a multicenter retrospective cohort study of fetal deaths that underwent postmortem examination between January 2020 and January 2022 in three fetal pathology units in Paris, France.

Cytokine Profiling of Amniotic Fluid from Congenital Cytomegalovirus Infection.

Background: Congenital cytomegalovirus (cCMV) infection is frequent and potentially severe. The immunobiology of cCMV infection is poorly understood, involving cytokines that could be carried within or on the surface of extracellular vesicles (EV). We investigated intra-amniotic cytokines, mediated or not by EV, in cCMV infection.

Clinical Value of Serial Quantitative Analysis of Cytomegalovirus DNA in Blood and Saliva Over the First 24 Months of Life in Congenital Infection: The French Cymepedia Cohort.

Objective: To evaluate cytomegalovirus (CMV) viral load dynamics in blood and saliva during the first 2 years of life in symptomatic and asymptomatic infected infants and to identify whether these kinetics could have practical clinical implications.

Study Design: The Cymepedia cohort prospectively included 256 congenitally infected neonates followed for 2 years. Whole blood and saliva were collected at inclusion and months 4 and 12, and saliva at months 18 and 24.

Saliva for molecular detection of SARS-CoV-2 in pre-school and school-age children.

SARS-CoV-2 diagnosis is a cornerstone for the management of coronavirus disease 2019 (COVID-19). Numerous studies have assessed saliva performance over nasopharyngeal sampling (NPS), but data in young children are still rare. We explored saliva performance for SARS-CoV-2 detection by RT-PCR according to the time interval from initial symptoms or patient serological status.

Third trimester placentitis: an underreported complication of SARS-CoV-2 infection.

SARS-CoV-2-related placentitis shows distinctive histologic characteristics, and its impact on perinatal outcomes is increasingly under scrutiny. We present two such cases in the third trimester displaying mild maternal clinical symptoms and associated with maternal coagulopathy, reduced fetal movements, and nonreassuring fetal heart rate tracing. Both cases resulted in emergency cesarean deliveries.

Prior infection by seasonal coronaviruses, as assessed by serology, does not prevent SARS-CoV-2 infection and disease in children, France, April to June 2020.

BackgroundChildren have a low rate of COVID-19 and secondary severe multisystem inflammatory syndrome (MIS) but present a high prevalence of symptomatic seasonal coronavirus infections.AimWe tested if prior infections by seasonal coronaviruses (HCoV) NL63, HKU1, 229E or OC43 as assessed by serology, provide cross-protective immunity against SARS-CoV-2 infection.MethodsWe set a cross-sectional observational multicentric study in pauci- or asymptomatic children hospitalised in Paris during the first wave for reasons other than COVID (hospitalised children (HOS), n = 739) plus children presenting with MIS (n = 36).

Performance of 30 commercial SARS-CoV-2 serology assays in testing symptomatic COVID-19 patients.

We report evaluation of 30 assays' (17 rapid tests (RDTs) and 13 automated/manual ELISA/CLIA assay (IAs)) clinical performances with 2594 sera collected from symptomatic patients with positive SARS-CoV-2 rRT-PCR on a respiratory sample, and 1996 pre-epidemic serum samples expected to be negative. Only 4 RDT and 3 IAs fitted both specificity (> 98%) and sensitivity (> 90%) criteria according to French recommendations. Serology may offer valuable information during COVID-19 pandemic, but inconsistent performances observed among the 30 commercial assays evaluated, which underlines the importance of independent evaluation before clinical implementation.

First-trimester diagnosis of congenital cytomegalovirus infection after maternal primary infection in early pregnancy: feasibility study of viral genome amplification by PCR on chorionic villi obtained by CVS.

Objective: To evaluate the feasibility of amplification of the viral genome by polymerase chain reaction (PCR) analysis of trophoblast samples obtained by chorionic villus sampling (CVS) in cases of maternal primary infection (MPI) with cytomegalovirus (CMV) in early pregnancy.

Methods: This was a prospective study carried out at the Department of Obstetrics and Fetal Medicine, Hopital Necker-E.M.

Placental transfer of Letermovir & Maribavir in the ex vivo human cotyledon perfusion model. New perspectives for in utero treatment of congenital cytomegalovirus infection.

Background: Congenital cytomegalovirus infection can lead to severe sequelae. When fetal infection is confirmed, we hypothesize that fetal treatment could improve the outcome. Maternal oral administration of an effective drug crossing the placenta could allow fetal treatment.

Adaptive and Innate Immune Cells in Fetal Human Cytomegalovirus-Infected Brains.

Background: The understanding of the pathogenesis of cytomegalovirus (CMV)-induced fetal brain lesions is limited. We aimed to quantify adaptive and innate immune cells and CMV-infected cells in fetal brains with various degrees of brain damage.

Methods: In total, 26 archived embedded fetal brains were studied, of which 21 were CMV-infected and classified in severely affected ( = 13) and moderately affected ( = 8), and 5 were uninfected controls.

Quantifying the Burden of Congenital Cytomegalovirus Infection With Long-term Sequelae in Subsequent Pregnancies of Women Seronegative at Their First Pregnancy.

Background: In women seronegative before pregnancy, congenital cytomegalovirus (cCMV)-related sequelae are exclusively seen in those infected in the first trimester of pregnancy. Following a maternal primary infection in the first trimester, up to 30% of infected neonates suffer long-term sequelae. Maternal parity is an established risk factor of cCMV in previously seronegative women.

Sequelae of Congenital Cytomegalovirus Following Maternal Primary Infections Are Limited to Those Acquired in the First Trimester of Pregnancy.

Background: The known relationship between the gestational age at maternal primary infection an the outcome of congenital CMV is based on small, retrospective studies conducted between 1980 and 2011. They reported that 32% and 15% of cases had sequelae following a maternal primary infection in the first and second or the third trimester, respectively. We aimed to revisit this relationship prospectively between 2011 and 2017, using accurate virological tools.

Feasibility of predicting the outcome of fetal infection with cytomegalovirus at the time of prenatal diagnosis.

Background: Congenital cytomegalovirus infection occurs in 0.7% of live births with 15-20% of infected children developing long-term disability including hearing loss and cognitive deficit. Fetal cytomegalovirus infection is established by viral DNA amplification by polymerase chain reaction in amniotic fluid obtained by amniocentesis following maternal seroconversion or after the diagnosis of ultrasound features suggestive of fetal infection.

Congenital cytomegalovirus is the second most frequent cause of bilateral hearing loss in young French children.

Objective: To estimate the prevalence of congenital cytomegalovirus (cCMV) among causes of bilateral hearing loss in young French children.

Study Design: Children <3 years old with hearing loss were prospectively included at their first visit to a referral center. Cytomegalovirus polymerase chain reaction was performed on dried blood spots from Guthrie cards.

Prospective identification of congenital cytomegalovirus infection in newborns using real-time polymerase chain reaction assays in dried blood spots.

Background: Congenital cytomegalovirus (CMV) infection is a public health issue, and implementation of neonatal screening has been debated. Detection of CMV DNA by polymerase chain reaction (PCR) of dried blood spots (DBS) routinely collected for metabolic screening from all newborns has been proposed for congenital CMV infection screening. The goal of this study was to prospectively assess the performance of 2 CMV PCR assays of DBS for CMV neonatal screening in a selected population of neonates.