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This article presents the findings of a retrospective analysis of prenatal ultrasound reports in the South France region for newborns and children diagnosed with congenital heart disease (CHD) postnatally. The study aimed to assess the quality of the ultrasound images and their relationship to the type of heart disease. The analysis revealed that while the intrinsic image quality was satisfactory, the quality of obtaining anatomical landmarks was suboptimal. Additionally, 15% of CHDs could have been identified through better image quality. The study highlights the importance of improving the quality of prenatal ultrasound for the early detection of CHD. [Extracted from the article]

Objective: We investigated the missed treatment opportunities affecting programmes using mid-upper arm circumference (MUAC) as the sole anthropometric criterion for identification and monitoring of children suffering from severe acute malnutrition (SAM)., Design: Alongside MUAC, we assessed weight-for-height Z -score (WHZ) in children screened and treated according to the national MUAC only protocol in Pakistan. Besides, we collected parents' perceptions regarding the treatment received by their children through qualitative interviews., Setting: Data were collected from October to December 2021 in Tando Allah Yar District, Sindh., Subjects: All children screened in the health facilities ( n 8818) and all those discharged as recovered ( n 686), throughout the district, contributed to the study. All children screened in the community in the catchment areas of five selected health facilities also contributed ( n 8459). Parents of forty-one children randomly selected from these same facilities participated in the interviews., Results: Overall, 80·3 % of the SAM cases identified during community screening and 64·1 % of those identified in the health facilities presented a 'WHZ-only' diagnosis. These figures reached 93·9 % and 84·5 %, respectively, in children aged over 24 months. Among children treated for SAM and discharged as recovered, 25·3 % were still severely wasted according to WHZ. While parents positively appraised the treatment received by their children, they also recommended to extend eligibility to other malnourished children in their neighbourhood., Conclusion: In this context, using MUAC as the sole anthropometric criterion for treatment decisions (referral, admission and discharge) resulted in a large number of missed opportunities for children in need of timely and adequate care.

Despite a growing catalog of secreted factors critical for lymphatic network assembly, little is known about the mechanisms that modulate the expression level of these molecular cues in blood vascular endothelial cells (BECs). Here, we show that a BEC-specific transcription factor, SOX7, plays a crucial role in a non-cell-autonomous manner by modulating the transcription of angiocrine signals to pattern lymphatic vessels. While SOX7 is not expressed in lymphatic endothelial cells (LECs), the conditional loss of SOX7 function in mouse embryos causes a dysmorphic dermal lymphatic phenotype. We identify novel distant regulatory regions in mice and humans that contribute to directly repressing the transcription of a major lymphangiogenic growth factor (Vegfc) in a SOX7-dependent manner. Further, we show that SOX7 directly binds HEY1, a canonical repressor of the Notch pathway, suggesting that transcriptional repression may also be modulated by the recruitment of this protein partner at Vegfc genomic regulatory regions. Our work unveils a role for SOX7 in modulating downstream signaling events crucial for lymphatic patterning, at least in part via the transcriptional repression of VEGFC levels in the blood vascular endothelium., (© 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)

Introduction: Relevance of fetal brain magnetic resonance imaging (MRI) in cases of cleft lip and/or palate (CL/P) is still discussed to date. The aim of our study was to review the contribution of fetal brain MRI for detecting cerebral anomalies in cases of CL/P comparing antenatal data with neonatal outcomes., Methods: A retrospective multicenter study was conducted from January 2010 to October 2020 in two multidisciplinary prenatal diagnosis centers among women with a fetal ultrasound (US) diagnosis of CL/P. Prenatal imaging and genetic analysis data were collected, as well as postnatal data, including outcomes of children who had an abnormal prenatal MRI., Results: Among the 202 fetuses with a US diagnosis of CL/P, 96 underwent US and fetal brain MRI. 19 brain MRIs were found to be abnormal: 14 (73.7%) involved CL/P associated with other US abnormalities and five (26.3%) involved isolated clefts, of which four were cleft lip and alveolus and secondary palate (CLP). MRI identified severe abnormalities that changed the prognoses of 3 cases of clefts associated with other US abnormalities. In contrast, MRI found only minor abnormalities for the five isolated clefts, with no postnatal disorders found in these children., Conclusion: Fetal brain MRI should be proposed in cases of clefts associated with other anomalies or if US examination is limited by local conditions. MRI could also be discussed in cases of isolated CLP but should not be performed in cases of isolated cleft lip., (© 2023 S. Karger AG, Basel.)

Antenatal ear examination is an integral part of the thorough examination of the fetal face. The discovery of an anomaly, whether it is made by chance or during a complementary in-depth examination, leads the practitioner to determine its isolated or associated character, in order to characterise its possible belonging to a syndromic entity. In this context, the realization of genetic analysis more precise and wider allowing a return of the results in a time compatible with an evolutive pregnancy, gives to the geneticist a central role in the management of these couples. The main challenge lies in obtaining a set of concordant clinical and biological clues, enabling the genetic results identified to be interpreted correctly, the optimised functioning of the ultrasound practitioner - geneticist duo is therefore fundamental. This results in a complex information to deliver, in the fact that the clinical translation of an ear anomaly in antenatal can go from an isolated aesthetic anomaly to a genetic syndrome with neurodevelopmental disorder. The objective of this work is to describe, from a methodological analysis of antenatal ears, the accessible malformative entities, isolated or associated, and to discuss the problems in the need or not to propose their screening., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Observations of vertical transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection from mother to fetus have recently been described in the literature. However, the consequences of such transmission, whether fetal or neonatal, are poorly understood., Methods: From a case of in utero fetal death at 24+2 weeks of gestation that occurred 7 days after the diagnosis of symptomatic SARS-CoV-2 infection in the mother, we isolated the incriminating virus by immunochemistry and molecular techniques in several fetal tissues, with a variant analysis of the SARS-CoV-2 genome., Results: The fetal demise could be explained by the presence of placental histological lesions, such as histiocytic intervillositis and trophoblastic necrosis, in addition to fetal tissue damage. We observed mild fetal growth retardation and visceral damage to the liver, causing hepatocellular damage and hemosiderosis. To the best of our knowledge, this is the first report in the literature of fetal demise secondary to maternal-fetal transmission of SARSCoV- 2 with a congenital infection and a pathological description of placental and fetal tissue damage., Conclusions: SARS-CoV-2 was identified in both specimens using 3 independent techniques (immunochemistry, real-time quantitative polymerase chain reaction, and realtime digital polymerase chain reaction). Furthermore, the incriminating variant has been identified., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Facial cleft are the most frequent craniofacial anomalies with an incidence of one for 1000 births, all births combined, and require specialized multidisciplinary care. Since 2005, the systematic realization of two ultrasound views (nose-lip and profile) is recommended for the exploration of the fetal face in the 2nd trimester of pregnancy. Application of these recommendations should allow screening of the majority of cleft lip and palate. However, cleft palates, without labiomaxillary involvement, are currently largely underdiagnosed at prenatal ultrasound, although they can be associated with a syndromic diagnosis in up to 30% of cases. The aim of this work is to describe, from embryology to surgical consultation, the complete ultrasound examination of a fetus with a classic facial cleft., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Objective: To determine whether bladder size is associated with an unfavorable neonatal outcome, in the case of first-trimester megacystis., Materials and Methods: This was a retrospective observational study between 2009 and 2019 in two prenatal diagnosis centers. The inclusion criterion was an enlarged bladder (> 7 mm) diagnosed at the first ultrasound exam between 11 and 13+6 weeks of gestation. The main study endpoint was neonatal outcome based on bladder size. An adverse outcome was defined by the completion of a medical termination of pregnancy, the occurrence of in utero fetal death, or a neonatal death. Neonatal survival was considered as a favorable outcome and was defined by a live birth, with or without normal renal function, and with a normal karyotype., Results: Among 75 cases of first-trimester megacystis referred to prenatal diagnosis centers and included, there were 63 (84%) adverse outcomes and 12 (16%) live births. Fetuses with a bladder diameter of less than 12.5 mm may have a favorable outcome, with or without urological problems, with a high sensitivity (83.3%) and specificity (87.3%), area under the ROC curve = 0.93, 95% CI (0.86-0.99), p< 0.001. Fetal autopsy was performed in 52 (82.5%) cases of adverse outcome. In the 12 cases of favorable outcome, pediatric follow-up was normal and non-pathological in 8 (66.7%)., Conclusion: Bladder diameter appears to be a predictive marker for neonatal outcome. Fetuses with smaller megacystis (7-10 mm) have a significantly higher chance of progressing to a favorable outcome. Urethral stenosis and atresia are the main diagnoses made when first-trimester megacystis is observed. Karyotyping is important regardless of bladder diameter., Competing Interests: The authors have declared that no competing interests exist.

Background: One newly proposed approach to determining eligibility of children aged 6-59 months for therapeutic feeding programs (TFPs) is to use mid-upper arm circumference (MUAC) < 115 mm, bilateral oedema or Weight-for-Age Z-score (WAZ) < - 3 as admission criteria (MUAC+SWAZ). We explored potential consequences of this approach on the eligibility for treatment, as compared with the existing WHO normative guidance. We also compared sensitivity and specificity parameters of this approach for detecting wasted children to the previously described "Expanded MUAC" approach., Methods: We analyzed data from 558 population representative cross-sectional cluster surveys conducted since 2007. We retrieved all children classified as severe acute malnutrition (SAM), moderate acute malnutrition (MAM), and those who are both wasted and stunted (WA + ST), and calculated proportions of previously eligible children who would now be excluded from treatment, as well as proportions of non-malnourished children among those who would become eligible. We also analyzed the expected changes in the number and demographics (sex, age) of the selected populations of children according to the different admission approaches., Results: Both MUAC+SWAZ and Expanded MUAC case detection approaches substantially increase the sensitivity in detecting SAM, as compared to an approach which restricts detection of SAM cases to MUAC< 115 mm and oedema. Improved sensitivity however is attained at the expense of specificity and would require a very large increase of the size of TFPs, while still missing a non-negligible proportion (20-25%) of the SAM caseload. While our results confirm the sensitivity of the MUAC+SWAZ case detection approach in detecting WA + ST (over 80%), they show, on the other hand, that about half of the additional target detected by using SWAZ criterion will be neither SAM nor WA + ST., Conclusions: These results suggest that recently promoted approaches to case detection inflate TFPs' targets through the allocation of treatment to large numbers of children who have not been shown to require this type of support, including a significant proportion of non-acutely malnourished children in the MUAC+SWAZ approach. Considering the scarcity of resources for the implementation of TFPs, the rationale of abandoning the use of WHZ and of these alternative case detection strategies need to be critically reviewed.

Propranolol is an approved non-selective β-adrenergic blocker that is first line therapy for infantile hemangioma. Despite the clinical benefit of propranolol therapy in hemangioma, the mechanistic understanding of what drives this outcome is limited. Here, we report successful treatment of pericardial edema with propranolol in a patient with Hypotrichosis-Lymphedema-Telangiectasia and Renal (HLTRS) syndrome, caused by a mutation in SOX18 . Using a mouse pre-clinical model of HLTRS, we show that propranolol treatment rescues its corneal neo-vascularisation phenotype. Dissection of the molecular mechanism identified the R(+)-propranolol enantiomer as a small molecule inhibitor of the SOX18 transcription factor, independent of any anti-adrenergic effect. Lastly, in a patient-derived in vitro model of infantile hemangioma and pre-clinical model of HLTRS we demonstrate the therapeutic potential of the R(+) enantiomer. Our work emphasizes the importance of SOX18 etiological role in vascular neoplasms, and suggests R(+)-propranolol repurposing to numerous indications ranging from vascular diseases to metastatic cancer., Competing Interests: JO, FF, JW, MM, LH, MM, IC, EL, JP, JZ, EP, ES, YG, MH, KK, GA, JB, MF No competing interests declared, (© 2019, Overman et al.)

Aim: To assess the factors associated with lower rate of caesarean deliveries in the South of France, based on the characteristics and organisation of the region's 40 maternity facilities and the characteristics of the practitioners in these facilities., Method: A retrospective study from 1 January 2012 to 31 December 2015. Data were collected by the Mediterranean network and a declarative survey was completed by each maternity facility in the region to study factor which could be associated with lower caesarean rate by univariate and multivariate analysis., Results: 250 564 women gave birth during this period, of which 55 097 by caesarean section. The mean caesarean delivery rate over the four years was 22.0%. The rate was significantly higher in private maternity facilities [23.9% (21.9%- 25.8%), p<0.05] and type III (maximum care level) maternity facilities [24.2% (21.3%- 27.1%), p<0.05]. After a stepwise regression, the factors associated with a decrease in the caesarean delivery rate were audits concerning caesarean delivery (19.83%, β = - 2.48, p = 0.03 over the four years) and the provision of training to trainee doctors at the maternity facility (20.28%, β = - 1.08, p = 0.04 over the four years)., Conclusion: Performing audits in relation to caesarean deliveries could affect the caesarean. Teaching trainee doctors could be an indicator of quality of caesarean practices. They should be encouraged in maternity facilities to reduce the rate of caesareans., Competing Interests: The authors have declared that no competing interests exist.

Despite the essential role of the lymphatic vasculature in tissue homeostasis and disease, knowledge of the organ-specific origins of lymphatic endothelial progenitor cells remains limited. The assumption that most murine embryonic lymphatic endothelial cells (LECs) are venous derived has recently been challenged. Here, we show that the embryonic dermal blood capillary plexus constitutes an additional, local source of LECs that contributes to the formation of the dermal lymphatic vascular network. We describe a novel mechanism whereby rare PROX1-positive endothelial cells exit the capillary plexus in a Ccbe1 -dependent manner to establish discrete LEC clusters. As development proceeds, these clusters expand and further contribute to the growing lymphatic system. Lineage tracing and analyses of Gata2 -deficient mice confirmed that these clusters are endothelial in origin. Furthermore, ectopic expression of Vegfc in the vasculature increased the number of PROX1-positive progenitors within the capillary bed. Our work reveals a novel source of lymphatic endothelial progenitors employed during construction of the dermal lymphatic vasculature and demonstrates that the blood vasculature is likely to remain an ongoing source of LECs during organogenesis, raising the question of whether a similar mechanism operates during pathological lymphangiogenesis., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2018. Published by The Company of Biologists Ltd.)

Arterial specification and differentiation are influenced by a number of regulatory pathways. While it is known that the Vegfa-Notch cascade plays a central role, the transcriptional hierarchy controlling arterial specification has not been fully delineated. To elucidate the direct transcriptional regulators of Notch receptor expression in arterial endothelial cells, we used histone signatures, DNaseI hypersensitivity and ChIP-seq data to identify enhancers for the human NOTCH1 and zebrafish notch1b genes. These enhancers were able to direct arterial endothelial cell-restricted expression in transgenic models. Genetic disruption of SoxF binding sites established a clear requirement for members of this group of transcription factors (SOX7, SOX17 and SOX18) to drive the activity of these enhancers in vivo Endogenous deletion of the notch1b enhancer led to a significant loss of arterial connections to the dorsal aorta in Notch pathway-deficient zebrafish. Loss of SoxF function revealed that these factors are necessary for NOTCH1 and notch1b enhancer activity and for correct endogenous transcription of these genes. These findings position SoxF transcription factors directly upstream of Notch receptor expression during the acquisition of arterial identity in vertebrates., Competing Interests: Competing interestsThe authors declare no competing or financial interests., (© 2017. Published by The Company of Biologists Ltd.)

The detection of abnormalities of the fetal urinary system in the first trimester of pregnancy is constantly improving, namely owing to the improved resolution of the image, the use of the endovaginal approach and thanks to sonographers' constant training. The pathological aspects, usually detected in the second trimester of pregnancy, can be suspected early in the first trimester and range from kidneys' cavity dilation to bilateral renal agenesis, polycystic kidney disease, multi-cystic dysplasia and bladder megavessia or bladder exstrophy. A poly-malformative syndrome is to be found out. The detection of an abnormality of the urinary tract requires a close ultrasound check. Very often, the pathological aspects tend to disappear spontaneously. In particular, the non-visualization of the bladder requires repeated examinations during the same session or even a little later in the pregnancy. We will carry out a review of the literature by pointing out the usual and unusual aspects of the fetal urinary system visible in the first trimester and we will as well propose an algorithm describing how to deal with abnormalities of the urinary tract that can be found out at first trimester ultrasound., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Objective: To evaluate professional practices relative to episiotomies in the Provence Alpes Côte d'Azur (PACA) region by analysing their incidence in maternity hospitals, by type and by sector of activity. Following this, to analyse maternal and obstetric characteristics associated with episiotomies and the occurrence of perineal tears in Marseille's university hospitals (CHU)., Methods: Data were extracted from the database for the period from 1st January 2012 to 31 December 2014. The sample included 41 maternity hospitals: 13 private and 28 public. Twenty of the maternity hospitals were level 1, 15 were level 2, and 2 were level 3 (Nice and AP-HM)., Results: In the PACA region, 176,573 patients gave birth by vaginal delivery. The incidence of episiotomy over the 3 years was 21.6% (0.50% - 76.13%) with a statistically significant reduction in the incidence between 2012 and 2014 (P<0.001). There was a significant difference by sector (P<0.001) and level (P<0.001) of maternity hospitals. In the Marseille CHU, 21.6% of women had an episiotomy (66.4% in primiparas - 33.6% in multiparous) and 43% had perineal tears (62.3% in primiparas - 37.7% in multiparous). After multivariate analysis, gender, weight of the newborn, presentation, gestational age, and mode of delivery were shown to be factors significantly associated with occurrence of episiotomy and occurrence of perineal tear (P<0.001)., Conclusion: A significant decrease in the incidence of episiotomy was observed in the PACA region from 2012 to 2014, associated with a wide variation in rates depending on the maternity hospitals, their types and their sectors., (Copyright © 2017 Elsevier Masson SAS. All rights reserved.)

Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics., Competing Interests: The authors declare that no competing interests exist.

This pictorial essay will initially present the origin, definitions, objectives and main principles of the segmental approach to congenital heart diseases. Then, through ultrasound scans iconography we will consider its practical applications to prenatal screening. Eventually, through both ultrasound and MRI cases, we will discuss its potential use in fetal diagnostic evaluation., (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)

Mutations in SOX18, VEGFC and Vascular Endothelial Growth Factor 3 underlie the hereditary lymphatic disorders hypotrichosis-lymphedema-telangiectasia (HLT), Milroy-like lymphedema and Milroy disease, respectively. Genes responsible for hereditary lymphedema are key regulators of lymphatic vascular development in the embryo. To identify novel modulators of lymphangiogenesis, we used a mouse model of HLT (Ragged Opossum) and performed gene expression profiling of aberrant dermal lymphatic vessels. Expression studies and functional analysis in zebrafish and mice revealed one candidate, ArfGAP with RhoGAP domain, Ankyrin repeat and PH domain 3 (ARAP3), which is down-regulated in HLT mouse lymphatic vessels and necessary for lymphatic vascular development in mice and zebrafish. We position this known regulator of cell behaviour during migration as a mediator of the cellular response to Vegfc signalling in lymphatic endothelial cells in vitro and in vivo. Our data refine common mechanisms that are likely to contribute during both development and the pathogenesis of lymphatic vascular disorders.

In contrast to the developing testis, molecular pathways driving fetal ovarian development have been difficult to characterise. To date no single master regulator of ovarian development has been identified that would be considered the female equivalent of Sry. Using a genomic approach we identified a number of novel protein-coding as well as non-coding genes that were detectable at higher levels in the ovary compared to testis during early mouse gonad development. We were able to cluster these ovarian genes into different temporal expression categories. Of note, Lrrc34 and AK015184 were detected in XX but not XY germ cells before the onset of sex-specific germ cell differentiation marked by entry into meiosis in an ovary and mitotic arrest in a testis. We also defined distinct spatial expression domains of somatic cell genes in the developing ovary. Our data expands the set of markers of early mouse ovary differentiation and identifies a classification of early ovarian genes, thus providing additional avenues with which to dissect this process.