The ANTENATAL multicentre study to predict postnatal renal outcome in fetuses with posterior urethral valves: objectives and design

Abstract Background Posterior urethral valves (PUV) account for 17% of paediatric end-stage renal disease. A major issue in the management of PUV is prenatal prediction of postnatal renal function. Fetal ultrasound and fetal urine biochemistry are currently employed for this prediction, but clearly lack precision. We previously developed a fetal urine peptide signature that predicted in utero with high precision postnatal renal function in fetuses with PUV. We describe here the objectives and design of the prospective international multicentre ANTENATAL (multicentre validation of a fetal urine peptidome-based classifier to predict postnatal renal function in posterior urethral valves) study, set up to validate this fetal urine peptide signature. Methods Participants will be PUV pregnancies enrolled from 2017 to 2021 and followed up until 2023 in >30 European centres endorsed and supported by European reference networks for rare urological disorders (ERN eUROGEN) and rare kidney diseases (ERN ERKNet). The endpoint will be renal/patient survival at 2 years postnatally. Assuming α = 0.05, 1–β = 0.8 and a mean prevalence of severe renal outcome in PUV individuals of 0.35, 400 patients need to be enrolled to validate the previously reported sensitivity and specificity of the peptide signature. Results In this largest multicentre study of antenatally detected PUV, we anticipate bringing a novel tool to the clinic. Based on urinary peptides and potentially amended in the future with additional omics traits, this tool will be able to precisely quantify postnatal renal survival in PUV pregnancies. The main limitation of the employed approach is the need for specialized equipment. Conclusions Accurate risk assessment in the prenatal period should strongly improve the management of fetuses with PUV

Cholestase intra-hépatique gravidique (pronostic maternel et foetal à propos de 87 observations)

BREST-BU Médecine-Odontologie (290192102) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Etude sur les paramétres influençant le vécu d'une grossesse aboutissant à une interruption médicale de grossesse (IMG) à Brest

L'objectif de cette thèse est d étudier les facteurs qui peuvent influencer le vécu (avec mise en valeur des facteurs positifs) d'une grossesse aboutissant à une IMG au Centre Hospitalier Universitaire de Brest. Dans une première partie, apres avoir rappelé ce qu est le deuil, nous évoquons les aspects historique, législatif, éthique, décisionnel, technique et socio-psychologique de l'lMG ainsi que les indications foetales ayant conduit à une interruption de grossesse sur Brest en 2009 et 2010. Dans la seconde partie, nous présentons et discutons les résultats d'une étude portant sur 8 patientes ayant subi une IMG à Brest entre 2008 et 2010, qui ont répondu à un questionnaire de 47 questions sur divers points (suivi, soutien, ressentis de l annonce, des délais d'attente, de l acte d IMG, de tout ce qui entoure l enfant, de l'anesthésie, etc.) concernant le déroulement de leur grossesse qui a abouti à cette interruption de grossesse. Nous concluons ces discussions en nous appuyant sur les données de la littérature.Enfin, nous achevons ce travail en synthétisant les paramètres qui permettraient de tenter d améliorer le vécu de femmes enceintes d un enfant qui va décéder.BREST-BU Médecine-Odontologie (290192102) / SudocSudocFranceF

[Ankle brachial pressure index (ABPI): color-Doppler versus ultrasound Doppler correlation study in 98 patients after analysis of interobserver reproducibility].

International audienceOBJECTIVE: Ankle Brachial Pressure Index (ABPI) by Doppler ultrasound is the gold standard non invasive method for screening of peripheral arterial disease (PAD). This reference method is little used in routine practice, particularly by vascular disease specialists since the most recent ultrasound devices no longer have continuous wave probes. The purpose of our survey was to assess interobserver reproducibility of color-Doppler measurements made in a first population, then second, to assess the correlation between ABPI measurements made with color-Doppler and with ultrasound Doppler in a second population. METHODS: One hundred twenty patients meeting screening criteria for AOMI defined by the French Health Authorities (HAS, 2006) participated in the study between October 2010 and April 2011 in the Echo Doppler and Vascular Medicine unit of the Brest University teaching hospital: 22 patients for interobserver reproducibility and 98 for color-Doppler - continuous Doppler correlation study. Two independent operators measured the ABPI index in each of the 98 patients using color-Doppler and continuous Doppler in random order, producing 353 measurements. Reliability and reproducibility were assessed using the intraclass correlation coefficient of correlation (ICC) determined with Spearman and the Bland-Altman methods. RESULTS: The ABPI was less than 0.90 in 62% of patients. The color-Doppler reproducibility study showed a mean difference of 0.02 [95% CI: -0.02 to 0.17] using the Bland Altman method with ICC equal to 0.89 (P<0.001). For the intermethod correlation study, the mean difference was 0.03 [95% CI: -0.17 to 0.23], with ICC equal to 0.84 (P<0.001). CONCLUSION: Color-Doppler could be an alternative to Doppler ultrasound for PAD screening or follow-up, depending on the results of further evaluations in larger populations

Prenatal hyperechogenic kidneys in three cases of infantile hypercalcemia associated with SLC34A1 mutations

International audiencePrenatal diagnosis of hyperechogenic kidneys is associated with a wide range of etiologies and prognoses. The recent advances in fetal ultrasound associated with the development of next-generation sequencing for molecular analysis have enlarged the spectrum of etiologies, making antenatal diagnosis a very challenging discipline. Of the various known causes of hyperechogenic fetal kidneys, calcium and phosphate metabolism disorders represent a rare cause. An accurate diagnosis is crucial for providing appropriate genetic counseling and medical follow-up after birth

Nonvisualization of fetal gallbladder increases the risk of cystic fibrosis.

International audienceOBJECTIVE: The aim of our study is to evaluate the prevalence of cystic fibrosis (CF) in fetuses referred for genetic testing because of ultrasonographic sign (nonvisualized fetal gallbladder--NVFGB). METHOD: We reviewed the results of CFTR gene analysis over the period 2002 to 2009 in all consecutive cases referred because of NVFGB in Western France. We correlated these data with the presence of a more classical ultrasonographic finding (fetal echogenic bowel - FEB). RESULTS: Cystic fibrosis was diagnosed in 5 of the 37 fetuses with NVFGB (13.5%, 95% confidence interval (CI): [2.5%; 24.5%]) and in only 9 of the 229 other cases referred because of FEB (3.9%, 95% CI: [3.2%; 14.7%]). In our series, all CF-affected fetuses with NVFGB also had FEB. The risk of CF was 11.6-fold higher in fetuses with both indications (NVFGB + FEB) than in fetuses with isolated FEB (45.5% vs 3.9%, RR = 11.6, 95% CI: [4.7%; 28.8%], p = 0.0001). We also estimated that the residual risk of CF was less than 1 in 68 (1.5%) when a single mutation was identified in the fetus by our molecular protocol. CONCLUSION: Ultrasonographic evidence of NVFGB is an additional risk factor for CF in cases with FEB

Should prenatal chromosomal microarray analysis be offered for isolated fetal growth restriction? A French multicenter study

International audienceBackground: Compared with standard karyotype, chromosomal microarray analysis improves the detection of genetic anomalies and is thus recommended in many prenatal indications. However, evidence is still lacking on the clinical utility of chromosomal microarray analysis in cases of isolated fetal growth restriction.Objective: This study aimed to estimate the proportion of copy number variants detected by chromosomal microarray analysis and the incremental yield of chromosomal microarray analysis compared with karyotype in the detection of genetic abnormalities in fetuses with isolated fetal growth restriction.Study design: This retrospective study included all singleton fetuses diagnosed with fetal growth restriction and no structural ultrasound anomalies and referred to 13 French fetal medicine centers over 1 year in 2016. Fetal growth restriction was defined as an estimated fetal weight of <tenth percentile for gestational age identified in ultrasound reports. For this analysis, we selected fetuses who underwent invasive genetic testing with karyotype and chromosomal microarray analysis results. Data were obtained from medical records and ultrasound databases and postmortem and placental examination reports in case of spontaneous stillbirths and terminations of pregnancy. Following the American College of Medical Genetics and Genomics guidelines, copy number variants were classified into 5 groups as following: pathogenic, likely pathogenic, variant of unknown significance, likely benign, and benign.Results: Of 682 referred fetuses diagnosed with isolated fetal growth restriction, both karyotype and chromosomal microarray analysis were performed in 146 fetuses. Overall, the detection rate of genetic anomalies found by chromosomal microarray analysis was estimated to be 7.5% (11 of 146 [95% confidence interval, 3.3-11.8]), including 10 copy number variants classified as pathogenic and 1 copy number variant classified as likely pathogenic. Among the 139 fetuses with normal karyotype, 5 were detected with pathogenic and likely pathogenic copy number variants, resulting in an incremental yield of 3.6% (95% confidence interval, 0.5-6.6) in chromosomal microarray analysis compared with karyotype. All fetuses detected with pathogenic or likely pathogenic copy number variants resulted in terminations of pregnancy. In addition, 3 fetuses with normal karyotype were detected with a variant of unknown significance (2.1%). Among the 7 fetuses with abnormal karyotype, chromosomal microarray analysis did not detect trisomy 18 mosaicism in all fetuses.Conclusion: Our study found that compared with karyotype, chromosomal microarray analysis improves the detection of genetic anomalies in fetuses diagnosed with isolated fetal growth restriction. These results support the use of chromosomal microarray analysis in addition to karyotype for isolated fetal growth restriction

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

International audienceObjective: To describe the lesions detected by prenatal ultrasound examination in congenital toxoplasmosis (CT).Methods: We retrospectively analyzed all cases of fetal infection with T. gondii with ultrasound anomalies described by fetal medicine experts in 2009-2019 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 extra-cerebral signs and 8 (9.1%) had extra-cerebral 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 extra-cerebral 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 1 and in the third trimester in 6 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

A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes

International audienceMus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, here we report the development of a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and the derivation of a standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. In this work, we show that the GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers opportunities for research focused on how the microbiota shapes host physiology in health and disease

A standardized gnotobiotic mouse model harboring a minimal 15-member mouse gut microbiota recapitulates SOPF/SPF phenotypes

Abstract Mus musculus is the classic mammalian model for biomedical research. Despite global efforts to standardize breeding and experimental procedures, the undefined composition and interindividual diversity of the microbiota of laboratory mice remains a limitation. In an attempt to standardize the gut microbiome in preclinical mouse studies, we developed a simplified mouse microbiota composed of 15 strains from 7 of the 20 most prevalent bacterial families representative of the fecal microbiota of C57BL/6J Specific (and Opportunistic) Pathogen-Free (SPF/SOPF) animals and derived a new standardized gnotobiotic mouse model called GM15. GM15 recapitulates extensively the functionalities found in the C57BL/6J SOPF microbiota metagenome, and GM15 animals are phenotypically similar to SOPF or SPF animals in two different facilities. They are also less sensitive to the deleterious effects of post-weaning malnutrition. The GM15 model provides increased reproducibility and robustness of preclinical studies by limiting the confounding effect of fluctuation in microbiota composition, and offers new opportunities for research focused on how the microbiota shapes host physiology in health and disease