Nouvelles approches dans la prise en charge de l'infection congénitale à cytomégalovirus : du dépistage au traitement

Congenital cytomegalovirus (CMV) infection is the most common congenital infection and the leading cause of infectious neurosensory disability in newborns. Thus, we wished to improve the available therapeutic arsenal and to organize the management of women from the beginning of pregnancy allowing access to antenatal treatment. Our work had two complementary objectives: 1) to set up and evaluate the interest of a systematic screening of CMV infection during pregnancy in our type 3 maternity hospital, at the CHRU of Limoges. Our results confirmed our advice on the interest of screening for CMV infection during pregnancy according, nevertheless, to modalities different from those currently implemented in our center. 2) Evaluation of the inhibitory potential of anti-CMV antibodies and new anti-virals, alone or in combination, in cell cultures and from ex vivo models of placental explant cultures. Our trials have shown the efficacy of hyperimmune immunoglobulins in preventing infection transmission, especially when administered weekly. Nevertheless, this management strategy will only be valid if a systematic monthly screening is implemented during the first trimester of pregnancy, the fetal period most at risk of severe sequelae. The range of anti-CMV antivirals is wide and we have shown the interest of combining molecules targeting different mechanisms of the viral cycle to optimize their efficacy without increasing their toxicity, as these molecules alone do not seem to allow a total inhibition of the virus.L’infection congénitale à cytomégalovirus (CMV) est la plus fréquente des infections congénitales et la première cause de handicap neurosensoriel d’origine infectieuse chez les nouveau-nés. Ainsi, nous avons souhaité améliorer l’arsenal thérapeutique disponible et organiser la prise en charge des femmes dès le début de la grossesse permettant l’accès au traitement anténatal. Nos travaux ont visé deux objectifs complémentaires 1) la mise en place et l’évaluation de l’intérêt d’un dépistage systématisé de l’infection à CMV durant la grossesse au sein de notre maternité de type 3, au CHRU de Limoges. Nos résultats nous ont confortée dans notre position sur l’intérêt du dépistage de l’infection à CMV durant la grossesse selon, néanmoins, des modalités différentes de celles actuellement mises en place dans notre centre. 2) l’évaluation du potentiel inhibiteur d’anticorps anti-CMV et de nouveaux anti-viraux seuls ou en association, en cultures cellulaires et à partir de modèles ex vivo de cultures d’explants placentaires. Nos essais ont montré l’efficacité des Immunoglobulines hyperimmunes dans la prévention de la transmission de l’infection, en particulier lorsque celles-ci étaient administrées de façon hebdomadaire. Néanmoins cette stratégie de prise en charge ne pourra être valide que par la mise en place d’un dépistage systématisé mensuel au cours du 1er trimestre de grossesse, période fœtale la plus à risque de séquelles sévères. L’éventail des molécules antivirales anti-CMV est large et nous avons montré l’intérêt de combiner des molécules ciblant différents mécanismes du cycle viral pour optimiser leur efficacité sans augmenter leur toxicité, ces molécules ne semblant pas à elles seules permettre une inhibition totale du virus

New approaches to the management of congenital cytomegalovirus infection : from screening to treatment

L’infection congénitale à cytomégalovirus (CMV) est la plus fréquente des infections congénitales et la première cause de handicap neurosensoriel d’origine infectieuse chez les nouveau-nés. Ainsi, nous avons souhaité améliorer l’arsenal thérapeutique disponible et organiser la prise en charge des femmes dès le début de la grossesse permettant l’accès au traitement anténatal. Nos travaux ont visé deux objectifs complémentaires 1) la mise en place et l’évaluation de l’intérêt d’un dépistage systématisé de l’infection à CMV durant la grossesse au sein de notre maternité de type 3, au CHRU de Limoges. Nos résultats nous ont confortée dans notre position sur l’intérêt du dépistage de l’infection à CMV durant la grossesse selon, néanmoins, des modalités différentes de celles actuellement mises en place dans notre centre. 2) l’évaluation du potentiel inhibiteur d’anticorps anti-CMV et de nouveaux anti-viraux seuls ou en association, en cultures cellulaires et à partir de modèles ex vivo de cultures d’explants placentaires. Nos essais ont montré l’efficacité des Immunoglobulines hyperimmunes dans la prévention de la transmission de l’infection, en particulier lorsque celles-ci étaient administrées de façon hebdomadaire. Néanmoins cette stratégie de prise en charge ne pourra être valide que par la mise en place d’un dépistage systématisé mensuel au cours du 1er trimestre de grossesse, période fœtale la plus à risque de séquelles sévères. L’éventail des molécules antivirales anti-CMV est large et nous avons montré l’intérêt de combiner des molécules ciblant différents mécanismes du cycle viral pour optimiser leur efficacité sans augmenter leur toxicité, ces molécules ne semblant pas à elles seules permettre une inhibition totale du virus.Congenital cytomegalovirus (CMV) infection is the most common congenital infection and the leading cause of infectious neurosensory disability in newborns. Thus, we wished to improve the available therapeutic arsenal and to organize the management of women from the beginning of pregnancy allowing access to antenatal treatment. Our work had two complementary objectives: 1) to set up and evaluate the interest of a systematic screening of CMV infection during pregnancy in our type 3 maternity hospital, at the CHRU of Limoges. Our results confirmed our advice on the interest of screening for CMV infection during pregnancy according, nevertheless, to modalities different from those currently implemented in our center. 2) Evaluation of the inhibitory potential of anti-CMV antibodies and new anti-virals, alone or in combination, in cell cultures and from ex vivo models of placental explant cultures. Our trials have shown the efficacy of hyperimmune immunoglobulins in preventing infection transmission, especially when administered weekly. Nevertheless, this management strategy will only be valid if a systematic monthly screening is implemented during the first trimester of pregnancy, the fetal period most at risk of severe sequelae. The range of anti-CMV antivirals is wide and we have shown the interest of combining molecules targeting different mechanisms of the viral cycle to optimize their efficacy without increasing their toxicity, as these molecules alone do not seem to allow a total inhibition of the virus

Impact of induction of labor in fetal macrosomia: comparative series from 256 cases

International audienc

Analysis of the obstetrician's posture and movements during a simulated forceps delivery

Abstract Background The objective of this study was to identify and qualify, by means of a three-dimensional kinematic analysis, the postures and movements of obstetricians during a simulated forceps birth, and then to study the association of the obstetricians’ experience with the technique adopted. Method Fifty-seven volunteer obstetricians, 20 from the Limoges and 37 from the Poitiers University hospitals, were included in this multi-centric study. They were classified into 3 groups: beginners, intermediates, and experts, beginners having performed fewer than 10 forceps deliveries in real conditions, intermediates between 10 and 100, and experts more than 100. The posture and movements of the obstetricians were recorded between December 2020 and March 2021 using an optoelectronic motion capture system during simulated forceps births. Joint angles qualifying these postures and movements were analysed between the three phases of the foetal traction. These phases were defined by the passage of a virtual point associated with the forceps blade through two anatomical planes: the mid-pelvis and the pelvic outlet. Then, a consolidated ascending hierarchical classification (AHC) was applied to these data in order to objectify the existence of groups of similar behaviours. Results The AHC distinguished four different postures adopted when crossing the first plane and three different traction techniques. 48% of the beginners adopted one of the two raised posture, 22% being raised without trunk flexion and 26% raised with trunk flexion. Conversely, 58% of the experts positioned themselves in a “chevalier servant” posture (going down on one knee) and 25% in a “squatting” posture before initiating traction. The results also show that the joint movement amplitude tends to reduce with the level of expertise. Conclusion Forceps delivery was performed in different ways, with the experienced obstetricians favouring postures that enabled observation at the level of the maternal perineum and techniques reducing movement amplitude. The first perspective of this work is to relate these different techniques to the traction force generated. The results of these studies have the potential to contribute to the training of obstetricians in forceps delivery, and to improve the safety of women and newborns

New therapeutic perspective in the prevention of congenital cytomegalovirus infection

International audienc

Follow-up of increased nuchal translucency: Results of a study of 398 cases

International audienc

Potential of Anti-CMV Immunoglobulin Cytotect CP® In Vitro and Ex Vivo in a First-Trimester Placenta Model

Background: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP® (Biotest, Germany) for congenital infection prevention and treatment. Methods: In vitro neutralization assays were conducted in fibroblasts and retinal epithelial cells on the CMV strains TB40/E and VHL/E to determine the 50% and 90% neutralizing doses (ND50 and ND90). The toxicity was assessed by measuring LDH release. Ex vivo assays were conducted in first-trimester villi explants with the TB40/E strain, namely, neutralization assays, the prevention of villi infection, and the inhibition of viral replication in infected villi. Viability was assessed by β-HCG quantification in supernatants. Results: The in vitro neutralization tests showed that Cytotect CP®® inhibits the development of infection foci (DN50: 0.011–0.014 U/mL for VHL/E and 0.032–0.033 U/mL for TB40E) without any toxicity. In the ex vivo neutralization assays, the DN50 were 0.011 U/mL on day 7 and 0.093 U/mL on day 14. For the prevention of villi infection, the EC50 was 0.024 U/mL on day 7. Cytotect-CP® did not inhibit viral growth in infected villi. No impact on villi viability was observed. Conclusions: These results sustained that Cytotect CP® has the potential to prevent CMV congenital infection

Potential of Anti-CMV Immunoglobulin Cytotect CP^® In Vitro and Ex Vivo in a First-Trimester Placenta Model

Background: Congenital CMV infection is the leading cause of neonatal neurological deficit. We herein studied in vitro and ex vivo the potential of the hyperimmune globulin Cytotect CP® (Biotest, Germany) for congenital infection prevention and treatment. Methods: In vitro neutralization assays were conducted in fibroblasts and retinal epithelial cells on the CMV strains TB40/E and VHL/E to determine the 50% and 90% neutralizing doses (ND50 and ND90). The toxicity was assessed by measuring LDH release. Ex vivo assays were conducted in first-trimester villi explants with the TB40/E strain, namely, neutralization assays, the prevention of villi infection, and the inhibition of viral replication in infected villi. Viability was assessed by β-HCG quantification in supernatants. Results: The in vitro neutralization tests showed that Cytotect CP®® inhibits the development of infection foci (DN50: 0.011–0.014 U/mL for VHL/E and 0.032–0.033 U/mL for TB40E) without any toxicity. In the ex vivo neutralization assays, the DN50 were 0.011 U/mL on day 7 and 0.093 U/mL on day 14. For the prevention of villi infection, the EC50 was 0.024 U/mL on day 7. Cytotect-CP® did not inhibit viral growth in infected villi. No impact on villi viability was observed. Conclusions: These results sustained that Cytotect CP® has the potential to prevent CMV congenital infection

Additional file 1 of Analysis of the obstetrician's posture and movements during a simulated forceps delivery

Supplementary Material 1