Introduction Intérêt (évaluation pronostique, prise en charge précoce), dans certaines indications, d’une analyse moléculaire prénatale en cas de signe d’appel échographique. Objectif Évaluer l’intérêt clinique d’un « séquençage d’exome prénatal urgent » (SEp) dans certains cas d’anomalies rénales fœtales. Matériel et méthodes Douze premiers cas d’anomalies échographiques évoquant une maladie rénale testés par SEp dans notre centre. ACPA sans déséquilibre. Résultats Analyse conclusive dans 8 cas sur 12. Le SEp a permis d’être rassurant (et de monitorer les apports en vitamine D) dans 2 cas avec variants bialléliques SLC34A1, de diminuer fortement le risque de syndrome néphrotique congénital, de ciliopathie syndromique, ou de maladie rénale grave dans 4 cas. Un variant de novo PKD1 également vécu comme une nouvelle plutôt rassurante par les parents. Un cas portant à la fois un variant pathogène biallélique SLC34A1 et variant pathogène biallélique DYNC2H1 décédé dans la période néonatale (diagnostic rétrospectif d’hypercalcémie infantile chez un premier enfant). Dans 3 cas, les résultats ont conduit à une demande d’IMG qui a été acceptée (2 cas avec variants bialléliques PKHD1, un cas avec variant de novo ACTG2). Dans un cas, le résultat (variant pathogène biallélique AGT) a été contemporain de la naissance prématurée d’un enfant qui est décédé dans la période néonatale. Un diagnostic incident a été rapporté aux parents après la naissance (variant connu de susceptibilité au SHUa, de novo, dans C3). Conclusion Dans certaines indications, utilité du SEp qui rassure dans certains cas, y compris lorsqu’une cause génétique est identifiée.

Background Newborn screening (NBS) has progressively expanded through technological innovations, from tandem mass spectrometry enabling expanded NBS (eNBS) to the prospect of genomic NBS (gNBS). While these developments promise earlier diagnosis and richer information, they also raise concerns regarding actionability, uncertainty, equity and psychosocial impact. As technological feasibility alone does not ensure public confidence, parental perspectives are central to evaluating future expansions. Using acceptability concept as an anticipatory lens, this study assessed parental views on NBS expansion in France, examining its determinants, distinguishing test modalities, and exploring whether genomics raises specific concerns. Methods A nationwide cross-sectional survey (September 2022–February 2023) included 1,640 parents recruited postpartum in maternity wards and through an online quota panel. Acceptability of eNBS and gNBS, intermediate evaluative components, and sociodemographic characteristics were assessed. Analyses combined descriptive statistics, multivariable regression, and thematic analysis of free-text comments. Results Support was very high for eNBS (93%) and remained high for gNBS (89%), with genetics mainly shifting responses from complete to partial acceptability. Affective attitude and perceived effectiveness were the strongest predictors of both outcomes, while ethical concerns distinguished assured from conditional support. Most parents prioritised minimising uncertain results, whereas a smaller subgroup accepted greater ambiguity. Foreign-born and single parents reported lower levels of complete acceptability, while health-sector workers and parents with rare-disease experience were more supportive. No independent association with the age of the youngest child was observed. Conclusion Parental acceptability of eNBS and gNBS is high but nuanced, shaped primarily by anticipated health benefits, emotional orientation and tolerance for uncertainty, with trust and social distance modulating support. As genomic expansion progresses, implementation will require proportionate, culturally adapted information and clear governance, and should be informed by real-world evidence from pilots such as PERIGENOMED. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ClinicalTrials.gov, [NCT06111456][1]. Last verified: October 2023. ### Funding Statement Yes ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The protocol, data collection tools, and information sheets for families were approved by the Ethics Committee for Research of the University of Burgundy-Franche-Comté on September 8, 2022 (S7 File). Participation was voluntary. All participants received written information describing the study objectives, procedures, data collected, and their rights. In accordance with French regulations for non-interventional research, participation was based on informed non-opposition, documented by completion of the questionnaire after receipt of the information notice. For Population 1, information was provided on-site by trained research staff during the maternity stay, using a written information and non-opposition notice. For Population 2, the same information was provided on the first page of the online questionnaire. Data were collected anonymously and analysed in accordance with applicable data protection regulations. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The data underlying the results of this study contain sensitive personal information collected from parents in a postpartum context and cannot be shared publicly due to ethical and legal restrictions, in accordance with the approval granted by the Ethics Committee for Research of the University of Burgundy–Franche-Comté. An anonymised dataset is available from the corresponding author for researchers who meet the criteria for access to confidential data, subject to approval by the relevant ethics committee and the signing of a data use agreement. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT06111456&atom=%2Fmedrxiv%2Fearly%2F2026%2F02%2F24%2F2026.02.22.26346822.atom

BACKGROUND:Newborn screening (NBS) has progressively expanded through technological innovations, from tandem mass spectrometry enabling expanded NBS (eNBS) to the prospect of genomic NBS (gNBS). While these developments promise earlier diagnosis and richer information, they also raise concerns regarding actionability, uncertainty, equity and psychosocial impact. As technological feasibility alone does not ensure public confidence, parental perspectives are central to evaluating future expansions. This study assessed parental views on NBS expansion in France, examining its determinants and whether genomics raises specific concerns. METHODS:A nationwide cross-sectional survey (September 2022-February 2023) included 1,640 parents recruited postpartum in maternity wards and through an online quota panel. Acceptability of eNBS and gNBS was assessed alongside intermediate components from the Theoretical Framework of Acceptability (affective attitude, perceived effectiveness, ethicality), a technical trade-off scenario, and individual characteristics. Analyses combined descriptive statistics, multivariable regression, and thematic analysis of free-text comments. RESULTS:Support was very high for eNBS (93%) and remained high for gNBS (89%), with genetics mainly shifting responses from complete to partial acceptability. Affective attitude and perceived effectiveness were the strongest predictors of both outcomes, while ethical concerns distinguished assured from conditional support. Most parents prioritised minimising uncertain results, whereas a smaller subgroup accepted greater ambiguity. Foreign-born and single parents reported lower levels of complete acceptability, while health-sector workers and parents with rare-disease experience were more supportive. No independent association with the age of the youngest child was observed. CONCLUSION:Parental acceptability of eNBS and gNBS is high but nuanced, shaped primarily by anticipated health benefits, emotional orientation and tolerance for uncertainty, with trust and social distance modulating support. As genomic expansion progresses, implementation will require proportionate, culturally adapted information and clear governance, and should be informed by real-world evidence from pilots such as PERIGENOMED.

Objectif Évaluer l’évolution des grossesses poursuivies après un diagnostic prénatal de pathologie fœtale d’une particulière gravité pouvant relever d’une interruption médicale de grossesse (IMG), ainsi que les issues périnatales associées. Méthodes Nous avons conduit une étude de séries temporelles à partir des données de l’Institut national de la statistique et des études économiques et de l’Agence nationale de la biomédecine (2008–2022). Les indicateurs, exprimés pour 1000 naissances vivantes (NV), incluaient : le nombre de pathologies fœtales d’une particulière gravité, les attestations d’IMG délivrées, les grossesses poursuivies après diagnostic prénatal, et les issues de grossesse en cas de poursuite. Résultats Entre 2008 et 2022, le nombre de pathologies fœtales d’une particulière gravité identifiées a augmenté de 8,70 à 12,09 pour 1000 NV. Le nombre de grossesses poursuivies est passé de 0,60 à 2,69 pour 1000 NV. Cette augmentation est moins marquée que celle du nombre total de pathologies d’une particulière gravité diagnostiquées (p<0,001). En cas de poursuite de grossesse, la proportion de nouveau-nés vivants à j28 a augmenté. La mortalité néonatale après poursuite a également augmenté, mais à un rythme inférieur à celui des poursuites de grossesse, sans contribution spécifique à l’évolution de la mortalité néonatale globale. Conclusions Ces résultats mettent en évidence une évolution des issues de grossesse après diagnostic prénatal de pathologie fœtale d’une particulière gravité, soulevant des enjeux cliniques, éthiques et organisationnels majeurs, et soulignant la nécessité de renforcer les indicateurs périnataux afin d’éclairer les politiques de santé publique.

ABSTRACT First-trimester (T1) cytomegalovirus (CMV) screening relies on IgG, IgM, and IgG avidity testing, but assay performance may vary according to the infection timing. To evaluate the ability of two IgM and three IgG avidity assays to detect maternal primary CMV infection (MPI) occurring in T1 or the periconceptional period. We analyzed 176 serum samples from 94 pregnant women with precisely dated MPI based on seroconversion. Samples were tested using two IgM assays (LIAISON CMV IgM II, Alinity i CMV IgM) and three IgG avidity assays (VIDAS CMV IgG Avidity II, LIAISON CMV IgG Avidity II, Alinity i CMV IgG avidity). For detection of MPI within 4 months, the IgM sensitivity was 99% (122/123) with LIAISON and 92% (94/102) with Alinity i. IgG avidity sensitivity for excluding MPI <4 months was 99% (124/125) with LIAISON, 98% (121/123) with VIDAS, and 92% (111/120) with Alinity i. The positive predictive value of low avidity was highest with VIDAS, followed by LIAISON and Alinity i. Retesting intermediate-avidity results with a second assay improved the estimation of MPI timing. All three avidity assays reliably excluded T1 MPI. Alinity i showed reduced sensitivity for ruling out periconceptional infection, supporting confirmatory testing in equivocal cases. IMPORTANCE In the context of universal first-trimester cytomegalovirus (CMV) screening and the demonstrated efficacy of valacyclovir to prevent vertical transmission, reliable identification of recent maternal primary infection has become crucial. In this study, we compared the performance of two CMV IgM kits (LIAISON CMV IgM II [DiaSorin]; Alinity i CMV IgM [Abbott Diagnostics]) and three CMV IgG avidity kits (LIAISON CMV IgG Avidity II [DiaSorin]; VIDAS CMV IgG Avidity II [Biomérieux]; Alinity i CMV IgG avidity [Abbott Diagnostics]). Our study assesses the performance of commonly used CMV IgM and IgG avidity assays in a large cohort of pregnant women with precisely dated primary infections, a setting rarely available for assay validation. We provide gestational age-specific performance data and highlight the limited positive predictive value of intermediate-IgG avidity results. Based on these findings, we propose a pragmatic diagnostic algorithm aimed at reducing misclassification and inappropriate clinical management.

OBJECTIVES:To evaluate trends in continued pregnancies following a prenatal diagnosis of severe fetal conditions eligible for termination under French law, as well as the associated perinatal outcome. METHODS:We conducted a time-series analysis from 2008 to 2022 using public data from the French National Institute of Statistics and the Biomedicine Agency. Indicators, expressed per 1000 live births, included the number of severe fetal conditions identified antenatally, authorizations for termination of pregnancy, continued pregnancies, overall neonatal mortality, and pregnancy outcomes in case of continuation. RESULTS:Between 2008 and 2022, the number of severe fetal conditions identified antenatally increased from 8.70 to 12.09 per 1000 live births. Over the same period, the rate of continued pregnancies rose from 0.60 to 2.69 per 1000 live births. This increase was significantly less pronounced than the overall rise in severe fetal conditions diagnosed antenatally (P<0.001). Among continued pregnancies, the proportion of neonates alive at day 28 increased. Neonatal mortality following pregnancy continuation also increased, but at a slower rate than pregnancy continuation, without a specific contribution to the overall trend in neonatal mortality. CONCLUSIONS:Our findings highlight an evolution in pregnancy outcomes following prenatal diagnosis of severe fetal conditions, raising major clinical, ethical, and organizational challenges, and underscoring the need to strengthen perinatal indicators to better inform public health policies.

BACKGROUND:Congenital cytomegalovirus infection is the leading nongenetic cause of sensorineural hearing loss and is associated with a broad spectrum of neurodevelopmental outcomes. A possible association between congenital cytomegalovirus and autism spectrum disorder has been hypothesized for several decades, based on case reports and small retrospective studies. OBJECTIVE:The objective was to estimate the strength of the association between congenital cytomegalovirus and neurodevelopmental abnormalities including autism spectrum disorder, their dependence on the timing of maternal infection, and their potential neuroanatomical correlates. STUDY DESIGN:We conducted a prospective observational cohort study including children with confirmed congenital cytomegalovirus infection followed at a single tertiary referral center in France between 2001 and 2024. Maternal cytomegalovirus infections were classified and dated using centralized serological assessment. Children underwent standardized longitudinal follow-up, including audiological, neurological, behavioral, and neuroimaging evaluations, up to 48 months of age. Fetal brain magnetic resonance imaging was available for cases diagnosed antenatally. Outcomes of interest included hearing loss, neurodevelopmental impairment, and autism spectrum disorder. RESULTS:Among 642 children with confirmed congenital cytomegalovirus infection, 504 (78.5%) were exposed to a maternal primary infection with known timing. Of these, 288 (57.1%) followed first-trimester infection, 144 (28.6%) second-trimester infection, and 72 (14.3%) third-trimester infection. Long-term congenital cytomegalovirus-related sequelae, including hearing loss and neurodevelopmental impairment, were observed exclusively in children exposed to first-trimester maternal primary infection. Autism spectrum disorder was diagnosed in 11 children (1.7%), all of whom were symptomatic at birth; all cases following maternal primary infection occurred after first-trimester exposure. Compared with estimates from the general French population, prevalence in children with congenital cytomegalovirus was 4-fold higher (odds ratio, 4.25; 95% confidence interval, 1.63-21.33). In all children diagnosed with autism spectrum disorder, temporal lobe white matter abnormalities, especially in the temporal poles, were identified on postnatal magnetic resonance imaging and were present on antenatal imaging in fetuses who underwent prenatal magnetic resonance imaging. The review of all fetal magnetic resonance imagings from the prenatally diagnosed subgroup revealed that temporal lobe white matter abnormalities were present in a minority of cases and no child without temporal lobe abnormality developed autism spectrum disorder. CONCLUSION:In this large prospective cohort, adverse long-term outcomes following maternal primary infection were observed only after first-trimester exposure. Autism spectrum disorder occurred exclusively in this group and was consistently associated with temporal lobe white matter abnormalities. These findings support a time-restricted window of fetal vulnerability to cytomegalovirus-related brain injury and suggest that neuroimaging findings may contribute to prenatal and neonatal risk stratification and help inform prenatal and postnatal counseling.

Auricular anomalies, including microtia and preauricular tags (PATs), are frequently overlooked findings on prenatal ultrasound, yet they may represent the earliest and sometimes the only clue to a wide spectrum of craniofacial and multisystem disorders. Distinguishing isolated anomalies from syndromic conditions remains a major diagnostic challenge in fetal medicine. In this illustrated, state of the art case-based review, we propose a practical, imaging-driven diagnostic framework for the prenatal evaluation of auricular anomalies. Drawing on a decade of clinical experience and a curated series of representative cases, we integrate high-resolution ultrasound features with a structured anatomical approach and current advances in molecular genetics. Syndromes associated with microtia and PATs are organized into 3 clinically relevant groups: branchial arch disorders, overlapping syndromic entities, and conditions in which auricular findings are non-specific. Our approach is based on systematic assessment of 3 key craniofacial regions: the auricle and pretragal area, the mandible, and the zygomatic-mandibular complex, combined with evaluation of craniofacial symmetry and targeted screening of extra craniofacial structures. This strategy enables pattern recognition that refines differential diagnosis and guides the appropriate use of genetic testing. Although molecular analyses contribute to etiologic characterization, their diagnostic yield remains limited in certain conditions, particularly craniofacial microsomia, reinforcing the pivotal role of detailed morphological assessment. This integrated imaging-genomic approach provides a clinically applicable framework for improving diagnostic orientation, prenatal counseling, and perinatal management, and highlights the central role of ultrasound in navigating the complexity of auricular anomalies.

OBJECTIVES:Oral administration of valacyclovir at 8g/day significantly reduces the rate of vertical transmission of CMV in women with a primary CMV infection acquired during the periconceptional period or the first trimester. The aim of this study is to expand the findings of previously published studies by including all recent cohorts on the subject. METHODS:The MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), and "clinical trial" registry (www. CLINICALTRIALS:gov) were consulted. Randomized controlled trials and cohort studies administering oral valacyclovir at 8g/day to pregnant women with a primary CMV infection acquired during the periconceptional period or the first trimester were included. Cochrane's Risk of Bias 2 and ROBINS-I tools were used to assess the risk of bias. The result of the CMV PCR in the amniotic fluid was the primary outcome. A two-step individual patient data meta-analysis was conducted, and a subgroup analysis was performed, evaluating periconceptional and first-trimester infections separately. RESULTS:Four studies (1 RCT and 3 cohorts) were included in the analysis (n=860 women). A significant reduction in the rate of the CMV vertical transmission was observed in the Valacyclovir group (aOR=0.39, 95% CI 0.25-0.59). This reduction was significant for both the periconceptional period (aOR=0.30, 95% CI 0.13-0.68) and the first trimester (aOR=0.47, 95% CI 0.28-0.78). Valacyclovir also reduced the rate of neonatal infections, aOR=0.45 (95% CI 0.25-0.83), for both periods considered (aOR=0.42, 95% CI 0.20-0.90, and aOR=0.54, 95% CI 0.29-0.99). CONCLUSIONS:The current evidence suggests that oral valacyclovir (8g/day) is associated with reduction of the rate of vertical transmission of CMV following maternal primary infection acquired during the periconceptional period or the first trimester of pregnancy.

BACKGROUND:The long interval between the serologic diagnosis of maternal primary infection in the first trimester of pregnancy and the prenatal diagnosis of fetal infection by amniocentesis at 17 weeks of gestation may cause anxiety and distress. Cytomegalovirus polymerase chain reaction in chorionic villi sampled by chorionic villus sampling at 14 weeks of gestation can diagnose trophoblastic infection. OBJECTIVE:This study aimed to assess the diagnosis and prognostic value of cytomegalovirus polymerase chain reaction in chorionic villi in pregnant women with cytomegalovirus maternal primary infection for predicting vertical transmission and related symptoms at birth. STUDY DESIGN:This single-center retrospective cohort study enrolled pregnant women referred for cytomegalovirus maternal primary infection in early pregnancy identified by serologic screening before 14 weeks of gestation between October 2019 and December 2024. Secondary prevention with valaciclovir was offered. The primary outcome was vertical transmission, defined by a positive cytomegalovirus polymerase chain reaction in chorionic villi, amniotic fluid obtained by amniocentesis at 17 weeks of gestation, and neonatal saliva/urine at birth (or positive in situ hybridization in terminated pregnancies). The secondary outcomes were symptomatic congenital infection in live-born infants, defined according to the European Congenital Infection Initiative criteria, and sensorineural hearing loss. RESULTS:Overall, 422 women were diagnosed with maternal primary infection, and 330 women had both chorionic villus sampling and amniocentesis. Cytomegalovirus polymerase chain reaction was positive in the trophoblast in 19 of 330 women (5.7%) and associated with maternal-fetal transmission during the course of pregnancy in 89.4% of women, mostly before 17 weeks of gestation (73.7%). No fetal infection occurred in "triple negative cytomegalovirus polymerase chain reaction" in trophoblast, maternal blood, and urine in the first trimester of pregnancy. Overall, the sensitivity, specificity, positive predictive value, and negative predictive value of cytomegalovirus polymerase chain reaction in trophoblast to predict congenital infection were 48.28%, 98.34%, 73.68%, and 95.18%. Among the 16 infected newborns who were symptomatic at birth, 2 had bilateral severe-to-profound sensorineural hearing loss (all with positive cytomegalovirus polymerase chain reaction in chorionic villi), and 5 had unilateral sensorineural hearing loss. The specificity and negative predictive values of cytomegalovirus polymerase chain reaction on trophoblasts to predict symptoms at birth were 97.12% and 97.74%, respectively; 96.26% and 99.68% for sensorineural hearing loss at birth, respectively; and 96.55% and 99.35% for long-term symptoms, respectively. CONCLUSION:Cytomegalovirus polymerase chain reaction on chorionic villi showed high specificity and negative predictive value for fetal infection and related symptoms at birth.

Ciliopathies are rare genetic disorders characterized by significant genetic and phenotypic variability. Over 140 proteins localized to primary cilia, which are sensory organelles essential for vertebrate development, are implicated. TMEM17 encodes a transmembrane protein at the ciliary transition zone and was previously proposed as a potential ciliopathy gene, based on reports of individuals from two families with orofaciodigital syndrome type 6 (OFD6) and Joubert syndrome (JS). Here, we report two unrelated fetuses with occipital encephalocele, polydactyly, and kidney cysts, in whom exome sequencing identified a founder homozygous missense variant (Arg94Trp) in TMEM17, affecting a highly conserved residue. This expands the TMEM17-associated phenotypic spectrum to include Meckel syndrome (MKS). Comprehensive functional analyses of all known TMEM17 variants, using patient tissues/cells and a C. elegans model system, demonstrate a loss-of-function mechanism. Our study reveals severe functional consequences, including TMEM17 destabilization and mislocalization, anomalies in cilium composition and function, and abrogation of Sonic Hedgehog signaling. These experiments confirm the pathogenicity of all TMEM17 variants and underscore its essential role at the ciliary transition zone. Collectively, our findings establish TMEM17 as a bona fide ciliopathy gene, associated with a wide phenotypic spectrum ranging from viable syndromes (OFD6 and JS) to a fetal-lethal condition (MKS).

Ciliopathies are rare genetic diseases marked by considerable phenotypic heterogeneity and overlap. Among the key mechanisms of cilium biology, its compartmentalization is achieved through gating complexes and active transport such as intraflagellar transport (IFT). Among the IFT components, IFT27 plays a role in BBSome-mediated transport of ciliary membrane proteins required for ciliary signaling. While this gene was first linked to Bardet-Biedl syndrome, we next expanded its phenotypic spectrum to a fetal lethal ciliopathy. Here, we identified a second fetal case with short ribs, polydactyly, hypodysplastic kidneys, imperforate anus, and situs inversus. Genome sequencing identified novel biallelic variants in IFT27. Functional analysis of tissues from both fetal cases revealed that all the identified variants lead to mRNA decay. Immunohistochemistry on fetal kidney sections showed that those variants are associated with altered ciliogenesis. Overall, we showed that complete loss of IFT27 function leads to a severe phenotypic spectrum overlapping with short ribs polydactyly and Pallister-Hall syndromes. In addition, our results argue for a role of IFT27 in ciliogenesis in humans.

BACKGROUND:Cytomegalovirus (CMV) serology in the first trimester (T1) of pregnancy relies on immunoglobulin (Ig) G (IgG) and IgM testing, followed by IgG avidity measurement when both IgG and IgM are positive. Valacyclovir is proposed to prevent vertical transmission in maternal primary infection (MPI) during T1. Our objective was to assess the risk of transmission, with and without valacyclovir, based on IgG avidity values and MPI timing. METHODS:Cases (2012-2024) with positive or equivocal IgM, intermediate or low IgG avidity (VIDAS and/or LIAISON) in T1, and a CMV PCR performed in amniotic fluid were retrieved from the laboratory software. The MPI date was estimated using a logarithmic model based on VIDAS avidity results. RESULTS:Five hundred and sixty one women (58% untreated, 42% treated) were included. In cases with low avidity and no treatment, transmission was 34% and 31% with VIDAS and LIAISON assays, respectively. Intermediate avidities and no treatment were also associated with high transmission rates (14% and 22%). VIDAS avidity values ≥0.60 or ≥0.50 in samples collected before 12 weeks were associated with 0% and 5% transmission rates, respectively. Without treatment, transmission occurred in 26% (9/34) of women with a LIAISON avidity value between 0.250 and 0.350. Valacyclovir significantly reduced transmission to 2%, 5%, and 16% in preconceptional, periconceptional, and T1 periods, respectively (P = .034, .003, and <.001). CONCLUSIONS:Our results suggest that the LIAISON threshold for high avidity should be >0.250. Except for VIDAS avidity values ≥0.60 before 12 weeks, treatment is beneficial for women with positive IgM and low/intermediate avidity, regardless of MPI timing.

Objectifs La prise orale de valaciclovir à 8g/jour réduit significativement le taux de transmission verticale du CMV chez les femmes présentant une primo-infection à CMV acquise en période périconceptionnelle ou au cours du premier trimestre. L’objectif de cette étude est d’élargir les résultats des études déjà publiées en incluant toutes les cohortes récentes sur le sujet. Méthodes Les bases de données MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central) ainsi que le registre « clinical trial (www.clinicaltrials.gov) ont été consultés. Les essais contrôlés randomisés et les études de cohorte administrant du valaciclovir per os à 8g/jour chez des femmes enceintes avec une primo-infection à CMV acquise en périconception ou au cours du premier trimestre ont été inclus. Les outils Cochrane's Risk of Bias 2 et Robins I ont été utilisés pour l’évaluation du risque de biais. Le résultat de la PCR CMV dans le liquide amniotique était le critère de jugement principal. Une méta-analyse à deux étapes des données individuelles des patientes a été réalisée, et une analyse de sous-groupes a été effectuée, en évaluant séparément les infections périconceptionnelles et celles du premier trimestre. Résultats Quatre études (1 essais contrôlés randomisés et 3 cohorte) ont été incluses dans l’analyse (n=860 femmes). Une réduction significative du taux de transmission verticale du CMV est observée dans le groupe valaciclovir (aOR)=0,39 (IC à 95% 0,25–0,59). Cette réduction était significative tant pour la période périconceptionnelle (aOR=0,30 (IC à 95% 0,13–0,68)) que pour le premier trimestre (aOR=0,47 (IC à 95% 0,28–0,78)). La valaciclovir a également réduit le taux d’infections néonatales, aOR=0,45 (IC à 95% 0,25–0,83), à partir des 2 périodes considérées (aOR=0,42 (IC à 95% 0,20–0,90)) et (aOR=0,54 (IC à 95% 0,29–0,99)). Conclusions Ainsi, les données actuelles suggèrent que le valaciclovir per os (8g/jour) est associé à une réduction du taux de transmission verticale du CMV à la suite d’une primo-infection maternelle acquise en période péri-conceptionnelle ou au cours du premier trimestre de la grossesse.

Introduction Les grossesses monochoriales représentent 20 % des grossesses gémellaires. Elles sont à haut risque de complications et nécessitent une prise en charge spécifique. Dans les grossesses monochoriales, les deux fœtus partagent le même placenta ; il existe des anastomoses vasculaires (artério-artérielles, artérioveineuses ou veino-veineuses) qui relient les deux cordons ombilicaux et qui sont responsables d’échanges entre les deux fœtus. Ce sont ces échanges qui induisent les complications spécifiques telles que le syndrome transfuseur-transfusé (STT) qui est la plus fréquente, mais également le retard de croissance sélectif et sévère (retard de croissance intra-utérin sélectif [RCIU]), l’anémie polyglobulie (Twin Anemia Polycythemia Sequence [TAPS]) et la masse acardiaque (Twin-Reversed Arterial Perfusion). Matériels et méthodes Le STT, qui est la complication la plus fréquente, se définit échographiquement et repose sur l’association d’un hydramnios polyurique dans la poche amniotique du jumeau désigné donc comme receveur, avec une grande citerne mesurée à plus de 8cm avant 20 semaines d’aménorrhée (SA) et plus de 10cm après 20SA, et d’un oligoamnios anurique dans celle du jumeau désigné comme donneur avec une grande citerne mesurée à moins de 2cm. La classification de Quintero est utilisée pour évaluer la gravité du STT. Les stades ne sont pas des étapes évolutives obligatoires et globalement les stades supérieurs à 3–4 ont un moins bon pronostic global que les 1–2. Résultats La fœtoscopie pour photocoagulation sélective au laser des vaisseaux anastomotiques est le seul traitement du STT avant 26SA qui existe aujourd’hui et qui a démontré son efficacité. De façon pragmatique, la coagulation fœtoscopique permet de passer d’une angioarchitecture placentaire anastomotique spécifique des grossesses monochoriales à une vascularisation individuelle « étanche » de type bichoriale. Elle permet un taux global de plus de 80 % de survie d’au moins un enfant avec moins de 10 % de séquelles. Dans le RCIU, la discussion d’une interruption sélective du fœtus le plus atteint peut être abordée avec la patiente. L’intervention est alors réalisée par coagulation du cordon ombilical du fœtus le plus atteint sous contrôle échographique, ce qui entraîne son décès mais permet de protéger son cojumeau. Les options thérapeutiques des TAPS sont fonction de la gravité et du terme du diagnostic. Impacts Les grossesses gémellaires monochoriales compliquées doivent être adressées aux centres de référence répartis largement sur le territoire et regroupés au sein du centre de référence maladies rares PaRaDiGM. Ces équipes entraînées assureront une prise en charge adaptée à la situation. Conclusion Il est important de diffuser au mieux les critères de diagnostic des grossesses gémellaires monochoriales et de leurs complications afin d’assurer la meilleure prise en charge de ces pathologies.

It has been established recently that oral valacyclovir 8g/day reduces significantly the vertical CMV transmission rate in pregnancies with primary Cytomegalovirus (CMV) infection acquired periconceptionally or during the first trimester. Aim of the present study is to expand the result of the previous studies by including any recent cohort study on the topic. MEDLINE, Scopus, Cochrane Central Register of Controlled Trials (Central), the US Registry of clinical trials (www.clinicaltrials.gov) and grey literature sources were searched. Randomized controlled trials and cohort studies administering oral valacyclovir 8g/day in pregnancies with primary CMV infection acquired periconceptionally or during the first trimester were included. Cochrane's Risk of Bias 2 and Robins I tools were used for the risk of bias assessment. The result of amniocentesis was the primary outcome of interest. Two-stages individual patient data meta-analysis was performed and a subgroup analysis was carried out, assessing separately the periconceptional period and the first trimester infections. Four studies were included in the analysis (n = 860 participants). Valacyclovir reduced the vertical transmission rate, adjusted odds ratio (a0R) = 0.39 (95 % CI 0.25-0.59). This reduction was apparent both for periconceptional period aOR = 0.30 (95 % CI 0.13-0.68) and first trimester aOR = 0.47 (95 % CI 0.28-0.78) infections. Valacyclovir also reduced the rate of neonatal infection, a0R = 0.45 (95 % CI 0.25-0.83), both in periconceptional period aOR = 0.42 (95 % CI 0.20-0.90)] and in first trimester aOR = 0.54 (95 % CI 0.29-0.99) infections. Oral valacyclovir (8 g/day) reduces the vertical transmission rates of CMV following primary maternal infection acquired periconceptionally or in the first trimester.

OBJECTIVE:To investigate long-term hearing evolution in children with congenital cytomegalovirus (cCMV) and to identify predictive factors for hearing impairment. STUDY DESIGN:A retrospective, single-center study in a tertiary pediatric otolaryngology referral center in Paris. The study included 244 patients with cCMV born between January 2013 and December 2018, with documented infection and at least 4 years of hearing follow-up. Data collected included prenatal history, diagnosis, birth symptoms, additional investigations, and therapy. Hearing thresholds were measured every 6 months for 2 years and then annually. RESULTS:At birth, cCMV-related sensorineural hearing loss (SNHL) prevalence in this cohort was 10%. At age 4, prevalence increased to 15% overall (35% of symptomatic and 2% of asymptomatic patients). No significant fluctuations were observed except with intercurrent otitis media with effusion. Risk factors for SNHL included cerebral imaging abnormalities (OR = 7.4 [95% CI 3-20.1], P < .001), clinical symptoms at birth (OR = 5.9 [95% CI 1.8-19.6], P < .01), affected contralateral ear at birth (OR = 6.7 [95% CI 2.9-15.4], P < .001), and first-trimester infection (OR = 3.7 [95% CI 1.6-9.6], P < .01). CONCLUSIONS:Identifiable risk factors for SNHL may guide management and parental counseling of patients with cCMV.

BACKGROUND:Inherited glycosylphosphatidylinositol (GPI) deficiencies are a heterogeneous group of inherited disorders of glycosylation, caused by mutations in genes involved in GPI-anchored proteins (GPI-AP) biosynthesis. PIGW is a gene known to be involved in the early steps of the GPI-anchor biosynthesis, as well as functional studies for most patients. Biallelic mutations in PIGW have been previously linked to hyperphosphatasia with mental retardation syndrome 5, also known as glycosylphosphatidylinositol biosynthesis defect 11 (GPIBD11). METHODS:We report seven individuals, including two fetuses from six unrelated families. Whole exome sequencing and chromosome analysis were performed, with variant interpretation based on ACMG and AMP guidelines. Magnetic resonance imaging (MRI) was also conducted on some of the patients. Blood samples were collected from patients to analyze GPI-AP expression using flow cytometry on markers like CD16, CD24, and FLAER. Functional analyses were performed using PIGW KO HEK 293 cells generated with CRISPR/Cas9 technology. The cells were transfected with rat Pigw cDNA that contained patient variants. The restoration of GPI-AP expression was measured by flow cytometry. Western blotting was used to assess protein expression. RESULTS:Affected patients exhibited a wide range of clinical features. Some patients presented classic GPIBD11 symptoms like developmental delay, hyperphosphatasia, and intellectual disability. Other patients showed atypical or milder phenotypes. The magnetic resonance imaging scans revealed variable neurological abnormalities in the affected individuals. Whole exome sequencing results identified PIGW mutations in all patients, which confirms the genetic basis of the disorder. Flow cytometry analysis of blood samples from patients P1, P4, and P5 using various markers showed a significant reduction in GPI-AP expression. The CD16 marker decreased to 1.8% in P1 and 21% in P5 compared to controls. CD24 was reduced to 22% in P1 granulocytes. Also, a minor decrease in CD14 on monocytes was observed in P4, as well as a slight reduction in the expression of FLAER in lymphocytes. Functional studies on PIGW-deficient CHO cells and HEK293 cells, using flow cytometry, showed that GPI-AP expression is affected by the PIGW variants. Western blotting showed reduced PIGW protein expression, except for P153L and R36G, which were similar to wild-type levels. CONCLUSIONS:To date, six patients and two fetuses with biallelic variants in PIGW have been reported. Here, we describe five new patients and two fetuses harboring homozygous or compound heterozygous variants in the PIGW gene. Our results illustrate the clinical variability of GPIBD11, highlighting the importance of broad genomic sequencing assays for patients who do not show typical symptoms. Therefore, our study expands the clinical and molecular spectrum of PIGW-associated disorder.