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.

Foetal achondroplasia: Prenatal diagnosis, outcome and perspectives.

Background: Achondroplasia, due to a specific pathogenic variant in FGFR3, is the most common viable skeletal dysplasia and the diagnosis is mostly done in the prenatal period. Since 2021, the use of Vosoritide, a specific treatment for achondroplasia, validated in phase 3 placebo-controlled trials, has been recommended to significantly increase the height of children and infants. In the light of these new therapeutic prospects, a complete understanding of the pathophysiology of skeletal damages occurring from foetal life is required.

[Use of anti-IL-1 drugs during pregnancy].

Anti-Interleukin-1 (Anti-IL-1) drugs are used to treat some chronic rheumatic diseases that can affect young people, including women of childbearing age. Two anti-IL-1 drugs are available in France: anakinra and canakinumab. Data on their use during pregnancy are still limited.

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.

The effect of valacyclovir on secondary prevention of congenital cytomegalovirus infection, following primary maternal infection acquired periconceptionally or in the first trimester of pregnancy. An individual patient data meta-analysis.

Objective: Recent studies have shown that a dosage of 8 g/d of oral valacyclovir reduces substantially the vertical transmission rate of cytomegalovirus in women with primary cytomegalovirus infection acquired periconceptionally or during the first trimester of pregnancy. This individual patient data meta-analysis aimed to assess the effectiveness and safety of valacyclovir treatment in the secondary prevention of congenital cytomegalovirus infection.

Data Sources: MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, the US registry of clinical trials (www.

Secondary prevention of congenital cytomegalovirus infection with valacyclovir following maternal primary infection in early pregnancy.

Objective: Cytomegalovirus (CMV) maternal primary infection (MPI) in early pregnancy is the main risk factor for congenital CMV (cCMV) infection with long-term sequelae. Our aim was to evaluate, in a single center offering CMV serology screening at 11-14 gestational weeks, secondary prevention of cCMV by administration of high-dosage maternal oral valacyclovir (VACV) in the first trimester of pregnancy.

Methods: This was a case-control study in a longitudinal cohort of pregnancies with CMV-MPI diagnosed prior to 14 weeks of gestation by serology screening (immunoglobulin (Ig) M and IgG measurement and IgG avidity) between 2009 and 2020.

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.

Maternal infections: revisiting the need for screening in pregnancy.

The decision to implement screening for infections during pregnancy depends upon epidemiological, economic, therapeutic and test performance criteria. It therefore varies with public health priorities from country to country. When screening is implemented, the first trimester has become the best time slot to build individual care pathways in this field.

Protein expression of angiotensin-converting enzyme 2, a SARS-CoV-2-specific receptor, in fetal and placental tissues throughout gestation: new insight for perinatal counseling.

Objective: Pregnant women can be infected by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), yet the incidence of perinatal infection is low. We hypothesized that this could be related to low expression of the membrane receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), in the fetoplacental unit. We evaluated protein expression of ACE2 at various gestational ages in both placentae and fetal organs from pregnancies not infected with SARS-CoV-2.

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.

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.

Refining the prognosis of fetuses infected with Cytomegalovirus in the first trimester of pregnancy by serial prenatal assessment: a single-centre retrospective study.

Objective: To define the predictive value (PV) of known prognostic factors of fetal infection with Cytomegalovirus following maternal primary infection <14 weeks of gestation, at different time points of pregnancy: the end of the second trimester; following prenatal magnetic resonance imaging (MRI) at 32 weeks of gestation; and using all ultrasound scans performed in the third trimester (US3rdT).

Design: A retrospective study.

Setting: Reference fetal medicine unit.

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.

Placental transfer of elvitegravir and cobicistat in an ex-vivo human cotyledon double perfusion model.

Objective: To determine the transplacental pharmacokinetics of the HIV integrase strand transfer inhibitor elvitegravir and of cobicistat, a cytochrome P450 inhibitor used as a pharmacoenhancer in antiretroviral therapy.

Design And Methods: Maternal-to-fetal transfer across the term human placenta was investigated with the ex-vivo dually perfused cotyledon model, in seven open-circuit experiments and 10 closed-circuit (recirculating) experiments. Elvitegravir and cobicistat were added to a maternal perfusate containing 2 g/l of human serum albumin and antipyrine, as a marker to validate the cotyledon's viability.