Search

The legal framework governing bioethics in France appeared in 1994. The first laws relating to bioethics concerned respect for the human body, the gift and use of elements and products of the human body, medically assisted procreation (MAP) and prenatal diagnosis. In 2004, a new law came to revise the previous one and in 2011, the law of July 7 provided for a revision of the law by Parliament within a maximum period of 7 years, preceded by the organization of States General . The objective was to take into account advances in science and to better meet the expectations of society. In 2019, a new bill was presented by the Government and after much debate, on August 2, 2021, the new law relating to bioethics was promulgated and modified, among other things, the modalities of MAP and donation of gametes. [ABSTRACT FROM AUTHOR]

The article focuses on prenatal diagnosis of trisomy 21. It mentions the caregiver must give clear and objective information to pregnant women and couples, that can serve as a support for dialogue between the carer and the pregnant woman, between the carer and the couple and allow future parents to discuss and decide whether to commit or not in the screening process.

Résumé: La procédure du dépistage du risque de trisomie 21 est complexe : une succession de tests pouvant aboutir à une amniocentèse est proposée. Le soignant doit donner une information claire et objective aux femmes enceintes, aux couples. Ce dépistage n'est pas obligatoire. Les modalités pour les groupes à risque de trisomie 21 ont été modifiées fin 2018 avec l'introduction du test ADN libre circulant de la trisomie 21 (test ADNlcT21). Un document d'information sur le dépistage combiné de la trisomie 21 avait été élaboré en 2014, en respectant certains critères de la méthodologie de la Haute Autorité de Santé (HAS). Une actualisation de ce document était nécessaire. Les modifications des seuils définissant les groupes à risque, et l'introduction du test ADNlcT21 ont été intégrées au document d'information. Il a été soumis à des groupes de travail composés de soignants et d'usagers. La lisibilité, la compréhension, l'objectivité des informations ont été discutées au sein de chaque groupe et les modifications proposées étaient validées successivement. Le document final a été repris par un graphiste pour en améliorer la présentation. Le document d'information actualisé peut servir de support au dialogue entre le soignant et la femme enceinte, entre le soignant et le couple et permettre aux futurs parents de discuter et décider de s'engager ou non dans le processus de dépistage. Ce document devra faire l'objet d'une évaluation. The procedure for screening risks of Down syndrome is complex : a series of tests that may lead to amniocentesis is offered. The caregiver must provide clear and objective information to pregnant women and/or couples. This screening is not mandatory. The modalities for groups at risk for Down syndrome changed at the end of 2018 with the introduction of the cell-free DNA test for Down syndrome (T21 cf-DNA test). A background document on combined screening for Down syndrome was developed in 2014 following some of the criteria in the methodology from the French High Health Authority (Haute Autorité de Santé – HAS). This document has been updated with changes to the thresholds identifying the groups at risk, and the introduction of the T21 cf-DNA test. Working groups composed of health users and professionals were set up. The readability, clarity and objectivity of the information were discussed within each group, after which proposed changes were validated. The final document was adapted by a graphic designer to improve its presentation. The updated document can be used as a supporting tool in the conversation between the caregiver and the pregnant woman and/or couple and allow future parents to discuss and decide whether to enter the screening process. This document will need to be assessed. [ABSTRACT FROM AUTHOR]

Background: Medical termination of pregnancy (MTP) is done because of medical conditions concerning the fetus - i.e. cardiac pathology, central nervous system malformation, genetic disorders. . .- or the mother, without any delay of restriction. In 2019, 6 848 MTP were performed in France. Prenatal diagnosis organization:MTP is part of a process initially of screening and then of prenatal diagnosis through an obstetric ultrasound. Amedical framework is necessary in order to respect all the different stages allowing a global approach for parents. Given its complexity and in order to avoid any drift, MTP is regulated by a legislative framework which has evolved over time. Deciding factors and prenatal diagnosis limits:MTP decision supposes a progressive way starting by the announcement of fetal malformation or severe maternal pathology. Intrinsic and extrinsic factors will have an impact on the patient's reflecting process and will raise many questions concerning prenatal diagnosis limits. Limits concern both the patient and the medical team. They can be due to ethical or eugenic considerations. Other factors such as the understanding of the language, the socioeducational level, the different socio-economic evolutions or even the religion will have a direct impact on the ability of the patient to decide in full awareness of the outcome of the pregnancy. Finally, another limitation relates to the sometimes fine line between voluntary termination and medical termination of pregnancy. Conclusions: MTP is a complex process which leads to wonder about life and death rights both by the request of the couple and by the acceptance of the multidisciplinary team. MTP is legally regulated in a non-exhaustive way, leaving room for the evolution of medicine, thus making it possible to adapt to each situation. MTP is and must remain a last resort for patient management. MTP must constantly be at the center of ethical debates with a continuous questioning to avoid falling in eugenic practices. Hence the importance to maintain a degree of liberty with a rigid framework. [ABSTRACT FROM AUTHOR]

We conducted a study of five patients with congenital diaphragmatic hernia (CDH) in the department of antenatal diagnosis over a period of two years. Our study highlights the overall benchmarks for this disease and its management as well as the news on prenatal assessment of neonatal prognosis using Lung Over Head Ratio (LHR): ultrasound versus magnetic resonance imaging (MRI) in the third world. The purpose of this study is to evaluate the prognosis of these new-born babies and support parents of a fetus with diaphragmatic hernia. [ABSTRACT FROM AUTHOR]

Fetal brain tumors are rare. Teratoma is the most common histological type. Their evolution is often fatal. Ultrasound and magnetic resonance imaging allows for early antenatal diagnosis. However, definitive diagnosis is based on histologic examination. Placental metastases are rare and complicate more often the course of malignant melanomas, hemopathies, breast and bronchial cancers. In pregnant women who have recently had a cancer, anatomopathologic examination of the placenta should be requested to detect tumor invasion. Similarly, neonatal assessment and extended pediatric follow-up are required. The establishment of registries collecting all cancer cases diagnosed among pregnant woman is essential for a better understanding of the epidemiology of these cancers as well as of maternal and paediatric prognostic factors. We here report a case of fetal brain tumor in a woman with recurrent ovarian cancer. [ABSTRACT FROM AUTHOR]

La transposition des gros vaisseaux est une cardiopathie congénitale cyanogène qui se manifeste en période néonatale par une cyanose sans détresse respiratoire, réfractaire à l'administration de l'oxygène. Elle nécessite toujours une prise en charge urgente avec un transfert rapide vers un centre expert. Dans la majorité des cas, le diagnostic est fait en prénatal permettant l'organisation de la naissance dans un centre susceptible de pratiquer une atrioseptostomie de Rashkind à tout moment. La prise en charge médicale préopératoire repose sur l'administration des prostaglandines et la manœuvre de Rashkind pour optimiser le mélange entre les deux circulations parallèles et donc l'oxygénation tissulaire. Le switch artériel est l'opération de choix habituellement réalisée dans les premières deux semaines de vie. L'intervention rétablit l'anatomie en remettant les gros vaisseaux au-dessus de leurs ventricules appropriés. La mortalité postopératoire est essentiellement liée aux problèmes de réimplantation coronaire dans des distributions complexes notamment celles avec un trajet intramural. Globalement, les résultats postopératoires et le pronostic fonctionnel à long terme sont excellents. Un sujet de préoccupation est l'émergence des troubles du développement neuropsychologique dans certains domaines d'apprentissage chez les enfants et adolescents opérés d'une transposition. Les enfants concernés nécessitent une prise en charge pluridisciplinaire en fonction de leurs déficits. This article aims to update general practitioners and pediatricians on neonatal management of transposition of the great arteries. This cardiac defect always requires urgent postnatal management and transfer to a tertiary care center. In France, prenatal detection rates are high reaching 80–90% in some regions. Prenatal diagnosis allows for scheduling of delivery in a specialist center with the possibility to perform a Rashkind manoeuvre at any time. Medical preoperative management relies on prostagladin infusion and Raskind manoeuvre in order to obtain a sufficient mixing of the two parallel circulations. Ideally minimal efficient doses of prostaglandin should be administered to obtain ductal patency with little side effects. The arterial switch is the surgery of choice mostly performed in the first two weeks of life. This intervention restores physiological anatomic conditions in putting the great arteries at their respective place on the appropriate ventricle. During the procedure the coronary arteries are reimplanted in the neoartic root. Postoperative morbidity and mortality are mostly due to complications after reimplantation of complex coronary pattern, especially those with an intramural course. In general, the postoperative results after arterial switch and the long-term functional prognosis are excellent. A recent concern lies in the growing detection of learning difficulties and altered neuropsychological development in some operated children and adolescents. Children with specific needs should benefit from early pluridisciplinary support. [ABSTRACT FROM AUTHOR]

Multicystic dysplastic kidney (MCDK) is the most common Congenital Abnormalities of Kidney and Urinary Tract (CAKUT) in clinical practice. Its etiology and pathogenesis are still controversial and obstruction is a generally accepted causative assumption. Obstetric ultrasound is the gold standard for prenatal diagnosis and for the detection of other associated malformations. Prenatal management is based on ultrasound monitoring of pregnancy, of the disease, of the occurrence of other anomalies and of the amount of amniotic fluid. This study aims to report our experience in the Department of Gynecology-Obstetrics 2 at the University Hospital Hassan II-Fez in order to clarify the epidemiology of MCDK, highlight the role of obstetric ultrasound in positive and etiological diagnosis while describing the various sonographic appearances. It is essential to schedule for screening tests during pregnancy in order to assess the evolution of the disease diagnosed in the prenatal period, to implement a strategy in postpartum care and to establish a prognosis. [ABSTRACT FROM AUTHOR]

The living fetus has become object of study of medicine only recently, i.e., since the 1960s. The development of prenatal testing and diagnosis has allowed couples and pregnant women to be offered tests that are designed to identify serious in utero conditions, that is, conditions that are considered as incurable at the time of diagnosis. The scientific advances in prenatal diagnosis have also given rise to serious ethical reflections. Jonathan Glover makes a major contribution to this reflection by emphasising the importance of taking into account both the direct consequences and the 'side-effects' of a particular practice. This paper first discusses Glover's perspective on the development of prenatal diagnosis, which he developed over the course of several decades, and focuses then on our current context which is characterized by a so-called "non-invasive" prenatal testing and the development of genomics. Using Glover's approach, which pays particular attention to the effects of a decision, this paper identifies ethical issues that are particular to our time. The paper concludes that prenatal testing, despite being "non-invasive" from a biological point of view, still raises many ethical issues. [ABSTRACT FROM AUTHOR]

Amniotic band syndrome (ABS) comprises of a spectrum of complex congenital malformations mainly interesting the limbs, but even the craniofacial region and the thoracoabdominal axis. There are two major opposing pathophysiological theories: premature rupture of the amniotic sac (exogenous growth theory) would result in the formation of fibrous bands which would lead to strangulation, thus causing the observed abnormalities; the endogenous theory holds that this is a syndrome of vascular origin and that the bands have no causative role. Prognosis depends on the severity of malformations. We here report two cases of lethal malformations in order to discuss the challenges in the diagnosis and treatment of amniotic band syndrome. This study mainly aims to highlight the role of prenatal diagnosis in the therapeutic management of this embryo-fetopathy. [ABSTRACT FROM AUTHOR]

Résumé Objectif L’annonce d’un diagnostic de pathologie fœtale représente pour les couples une situation très difficile, voire traumatogène. La présente étude a porté sur le vécu après l’annonce du diagnostic prénatal d’une pathologie fœtale dans un échantillon français constitué par des femmes enceintes et leurs conjoints. Méthode L’étude a été réalisée auprès de 12 couples hétérosexuels ayant reçu l’annonce du diagnostic d’une pathologie chez le fœtus et qui ont poursuivi la grossesse après le diagnostic. Résultats Les femmes enceintes ont obtenu des scores d’anxiété et d’attachement prénatal au bébé plus élevés que les futurs pères. Pour les femmes enceintes, l’attachement adulte évitant était associé à la plupart des variables psychologiques évaluées. L’attachement adulte évitant a aussi été important pour l’ajustement psychologique des futurs pères mais seulement en ce qui concerne la qualité de la relation conjugale. La détresse psychologique et la qualité de vie étaient négativement associées pour les femmes enceintes et pour les futurs pères. Conclusion L’utilisation de stratégies adaptatives de régulation affective par chaque membre du couple est un facteur de protection important de l’ajustement individuel et conjugal pendant la période périnatale, surtout dans des situations spécifiques, tel le diagnostic d’une pathologie fœtale. Objectives Expectant parents go through a complex and multidimensional experience when the diagnosis of a fetal anomaly is disclosed. This experience incorporates a traumatogenic dimension, regardless of the degree of the illness. The present study aimed to explore the subjective experience of pregnant women and their partners after the disclosure of a fetal anomaly during pregnancy. Materials and methods Twelve heterosexual couples participated in this study. All couples received the diagnostic of a fetal anomaly during the third trimester of pregnancy and decided to continue pregnancy. Three to six weeks after the disclosure of the fetal anomaly pregnant women and expectant fathers completed a questionnaire booklet. Participants completed, among others, the French version of Experiences in Close Relationships (ECR – Brennan et al., 1998), Dyadic Adjustment Scale (DAS – Spanier, 1976), WHOQOL-BREF (WHO, 1991), Hospital Anxiety and Depression Scale (HADS – Zigmond and Snaith, 1983) and Maternal/Paternal Antenatal Attachment Scale (MAAS/PAAS – Condon, 1993). Results Pregnant women obtained significantly higher scores than expectant fathers in parental prenatal attachment and anxiety. For pregnant women, avoidant adult attachment was associated with most of the psychological variables. Avoidant adult attachment was also important for psychological adjustment of expectant fathers but only in what concerns marital quality. Psychological distress and quality of life were negatively associated in both pregnant women and expectant fathers. Conclusions The use of adaptive strategies for affective regulation by both members of the couple after the diagnosis of a fetal anomaly is an important protection factor of individual and marital adjustment. Hence, perinatal health research must consider not only the pregnant women but also the expectant father, mainly in such specific situations as the prenatal diagnosis of a fetal anomaly. The development of the present study will allow to better knowing protection and risk factors in what concerns psychological adjustment of expectant parents to the prenatal diagnosis of a fetal anomaly. [ABSTRACT FROM AUTHOR]

Résumé La thrombopénie fœtale et néonatale allo-immune (TFNAI) est considérée comme une maladie rare du fait de sa faible incidence (1/1000 à 1/2000 naissances). La complication majeure est l’hémorragie intracrânienne (HIC) et les séquelles neurologiques qui en découlent. Le développement des techniques sérologiques et l’avènement de la biologie moléculaire a révolutionné le diagnostic biologique. L’immunisation anti-HPA-1a représente la majorité des cas de TFNAI avec un taux de récurrence élevé des complications sévères hémorragiques. La prise en charge thérapeutique a évolué au cours des années passant d’un concept très invasif associant prélèvement de sang fœtal et transfusion plaquettaire in utero à un traitement anténatal non invasif par injection d’immunoglobulines intraveineuses (IgIV). Cet article a pour but de faire un point de la prise en charge actuelle au regard des évolutions depuis les 30 dernières années. Fetal and neonatal allo-immune thrombocytopenia (FNAIT) is considered as a rare disease due to the incidence (1/1000–1/2000 births). The major complication of severe thrombocytopenia is bleeding and particularly intra-cranial hemorrhage and neurologic sequelae following. Serology and molecular biology developments have reconfigured the platelet immunology diagnosis. Anti-HPA-1a allo-immunisation is responsible for more than 80% FNAIT cases with a high recurrence rate of severe bleeding complications. Therapeutic management has changed over the coming years from an invasive concept associating fetal blood sampling and in utero platelet transfusion to a non invasive treatment by intravenous immunoglobulins injection (IVIg). The purpose of this article is to provide an update on FNAIT management in the light of current developments over the past 30 years. [ABSTRACT FROM AUTHOR]

Collodion baby is a severe form of congenital ichthyosis detected in neonatal period. It often has a characteristic clinical picture. When evolution is not fatal; it often causes dry Ichthyosis. Thanks to molecular biology techniques, prenatal diagnosis can be made since the 10-12 weeks of amenorrhea, allowing genetic counselling. Prognosis depends on several parameters, namely the degree of the initial manifestation, the duration of desquamation, as well as underlying Ichthyosis This rewiew of the literature which aims to clarify the diagnostic aspects and therapeutic treatment as well as the role of the antenatal diagnosis is based on a new observation of a collodion baby born at 34 weeks, of a parturient woman having an index case and of infant deaths occurring in the first day of life. [ABSTRACT FROM AUTHOR]

Meckel Gruber syndrome is a rare autosomal recessive polymalformation syndrome characterized by occipital encephalocele, polydactyly and cystic renal dysplasia. Ultrasound is, at present, the best tool for prenatal screening of this lethal polymalformation and diagnosys is confirmed by karyotyping. We here report a case of Meckel Gruber syndrome detected by ultrasound. Abortion was performed at 25 weeks of amenorrhoea. [ABSTRACT FROM AUTHOR]

Résumé Cette revue iconographique se propose dans un premier temps de faire le point sur les grands principes de l’approche segmentaire des cardiopathies congénitales, son origine, ses définitions et ses objectifs en particulier. Dans un second temps, au travers d’illustrations échographiques nous envisagerons son application pratique en dépistage prénatal. Enfin, par des exemples iconographiques en échographie et en IRM, nous discuterons son utilisation potentielle en évaluation diagnostique fœtale. 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. [ABSTRACT FROM AUTHOR]

Résumé Objectif Évaluer le bilan d’imagerie (échographie ± IRM) dans le diagnostic des malformations lymphatiques kystiques de localisations cervicales. Méthodes Étude rétrospective, descriptive des patientes ayant bénéficié d’un dépistage échographique de masses cervicales antérieures, confirmées en échographie de référence, au Centre pluridisciplinaire de diagnostic prénatal du Centre hospitalier régional universitaire de Lille de 1997 à 2014. Résultats Dix-sept lymphangiomes ont été recensés. Douze (71 %) lymphangiomes étaient diagnostiqués lors de l’échographie de référence et 88 % lors de l’IRM. On retrouvait une extension de la masse pour 10 (62 %) lymphangiomes en échographie et pour 11 (85 %) en IRM. Dans la plupart des cas, on objectivait respectivement en échographie et en IRM : une extension de la face (4, 23 %/6, 46 %), de la base de la langue (3, 18 %/2, 15 %) et du plancher buccal (3, 18 %/3, 15 %). Une atteinte pharyngée (5,38 %) et mandibulaire (4,31 %) était dépistée en IRM et non retrouvée en échographie. Deux (12 %) fœtus étaient porteurs de malformation urogénitale, 1 (6 %) de malformation cardiaque et 1 (6 %) de malformation faciale associée en échographie. Les lymphangiomes restaient stables dans 12 (71 %) des cas et disparaissaient dans 2 (12 %) des cas avant la naissance. Conclusion L’IRM et l’échographie paraissent indissociables pour permettre une évaluation et une prise en charge optimale des masses cervicales. Le bilan des lésions associées semble pouvoir nous aider dans l’orientation diagnostique. Enfin, les lymphangiomes semblent avoir une stabilité au cours de la grossesse et un bon pronostic en cas de masse cervicale lymphatique non compliquée et sans extension péjorative. Objectives Assess imaging (ultrasound ± MRI) in the diagnosis of cervical cystic lymphangioma. Methods Retrospective, descriptive study of the patients who underwent reference ultrasound screening for fetal anterior cervival masses in multidisciplinary prenatal diagnosis center of the Lille Regional University Hospital from 1997 to 2014. Results Seventeen lymphangiomas were identified. Seventy-three percent of lymphangiomas ( n = 12) were diagnosed in the baseline ultrasound and 85% ( n = 11) in MRI. An extra-cervical extension was identified in 10 (62%) with ultrasound and 11 (85%) with MRI. Main sites of mass extension objectived by ultrasound and MRI were respectively the face (4,23%/6,46%), the base of tongue (3, 18%/2, 15%) and buccal floor (3, 18%/3, 15%). Pharyngeal disease (5,38%) and mandible (4,31%) were detected by MRI and not found on ultrasound. Associated malformations detected with ultrasound were 2 (12%) urogenital malformation, 1 (6%) heart defect and 1 (6%) facial anomalies. Lymphangiomas remained stable in volume in 12 (71%) cases and disappeared before birth in 2 (12%) cases. Conclusion MRI and ultrasound seem inseparable to assess and optimally manage fetal cervical masses. Detection of associated lesions seems to help in the final lymphangioma diagnosis. Most of the time, lymphangiomas seem to be stable lesion during pregnancy and a good prognosis in cases of uncomplicated cervical lymphatic mass and without pejorative extension. [ABSTRACT FROM AUTHOR]

Résumé Objectif Les anomalies du développement maxillofacial concernent 1 pour 700 naissances. Environ 30 % des diagnostics anténatals (fentes du palais primaire isolée associée ou non à une atteinte du palais secondaire) sont corrigés en postnatal. Cette étude observationnelle rétrospective a pour but d’analyser la corrélation entre le dépistage échographique et l’aspect postnatal dans le cadre des fentes toutes confondues, en comparant les données anté- et postnatales. Méthodes Tous les enfants nés entre le 1er décembre 2009 et le 31 janvier 2014 dans un centre de référence de diagnostic anténatal et présentant une fente du palais primaire et/ou secondaire ont été inclus. Les malformations associées à une fente ont été exclus. Une comparaison a été réalisée entre les données anténatales selon les comptes rendus d’échographie et celles postnatales décrites par le chirurgien maxillofacial lors de la chirurgie. Résultats Quarante-quatre enfants ont été inclus et 3 exclus en raison d’une anomalie associée. Parmi ces 41 enfants, 27 enfants ont bénéficié d’un dépistage. Le diagnostic échographique et clinique était identique pour 23 cas (85,2 %) et inexact pour 4 patientes (14,8 %). En cas d’atteinte du palais primaire un diagnostic anténatal a été réalisé pour 19 cas sur 21 (90,5 %), mais seulement 8 sur 20 si l’atteinte concernait uniquement le palais secondaire (42,1 %) dont 7 avec une séquence de Pierre-Robin. Discussion La sensibilité du dépistage anténatal des fentes du palais primaire et secondaire augmente ces dernières années avec un taux de 85,2 % dans notre série. Par contre, pour les fentes du palais secondaire seules, la caractérisation semble être plus difficile et l’échographie 3D n’améliore pas toujours la performance du dépistage. Conclusion L’échographie 2D semblerait suffisante pour le dépistage de la fente du palais primaire et secondaire. L’échographie 3D pourrait être utile pour une meilleure représentation de la fente pour les futurs parents. Un même langage concernant la classification des fentes, faciliteraient l’harmonisation des comptes rendus et une meilleure compréhension entre les professionnels. La présence du chirurgien maxillofacial en salle d’échographie, permettrait à l’échographiste d’orienter son échographie de façon précise, voire d’améliorer sa courbe d’apprentissage. Objectives Anomalies of the maxillofacial development concern 1 for 700 births. About 30 % of prenatal diagnoses of isolated primary cleft palate or associated with a cleft of secondary palate will be corrected in postnatal. This retrospective observational study was designed to compare the antenatal data and postnatal diagnosis regarding a series of clefts. Materials and methods All children born between 1 December 2009 and 31 January 2014 in a prenatal diagnostic reference center and having a cleft palate were included. Newborns with an abnormality associated with the cleft were excluded. A comparison was made between the data in the antenatal ultrasound reports and postnatal those described by the surgeon during surgery. Results Forty-four children were included and three infants were excluded due to associated anomalies. Of those 41 children, 27 children have been screened. Ultrasound and clinical diagnosis was the same for 23 cases (85.2 %) and inaccurate for 4 patients (14.8 %). In case of primary cleft palate prenatal diagnosis was performed to 19 cases of 21 (90.5 %), but only 8 of 20 if only secondary cleft palate (42.1 %) including 7 with a Pierre-Robin sequence. Discussion Antenatal screening sensitivity of primary and secondary cleft palate increase in recent years with a rate of 85.2 % in our series. By contrast, diagnosis of isolated secondary cleft palate seems to be more difficult and 3D ultrasound does not always improve screening performance. Conclusion Ultrasound 2D seem sufficient for screening of primary and secondary cleft palate. The 3D ultrasound may be useful for a better representation of the cleft for future parents. The same language concerning the classification of the clefts facilitates harmonization of reporting and understanding between professionals. The presence of the maxillofacial surgeon ultrasound room would allow the sonographer to direct its ultrasound accurately or improve its learning curve. [ABSTRACT FROM AUTHOR]

Résumé Objectif Le syndrome de Beckwith-Wiedemann (SBW) est le syndrome d’excès de croissance congénitale le plus fréquent avec une incidence de 1/13 700 naissances. Son diagnostic est le plus souvent réalisé après la naissance. Il prédispose à un risque élevé d’hypoglycémie en postnatal immédiat et de tumeurs embryonnaires. Le but de ce travail est d’identifier les signes d’appel échographique en anténatal devant alerter tout échographiste afin de permettre une meilleure prise en charge périnatale. Méthodes Il s’agit d’une étude rétrospective concernant une série de 14 cas de SBW de diagnostic périnatal dont 4 diagnostics évoqués en anténatal. Les signes échographiques décrits en anténatal ont été analysés et comparés aux signes cliniques de la période postnatale. Résultats Les signes majeurs le plus souvent rapportés étaient représentés par la macrosomie pour 71,4 % des enfants avec une augmentation du périmètre abdominal et la macroglossie pour 78,6 %. Les signes mineurs étaient divers mais avec 64 % de viscéromégalie (néphromégalie et/ou hépatomégalie), 50 % d’hydramnios et pour 80 % d’enfants de sexe masculin une anomalie génitale (cryptorchidie et/ou hypospade). Conclusion Cette étude a permis d’identifier certains signes échographiques anténataux devant alerter le clinicien vers un diagnostic de SBW. Un conseil génétique, après confirmation par biologie moléculaire, pourrait être proposé dans un avenir plus au moins proche en prénatal, et cela afin d’améliorer la prise en charge de ces enfants à risque néonatal. Objectives Beckwith-Wiedemann syndrome (BWS) is the most common overgrowth syndrome and has an incidence of 1/13,700. The majority of the cases are diagnosed after birth. Patients with BWS have an increased risk of neonatal hypoglycemia and embryonal tumors development in childhood. We wanted to identify the ultrasound signs that must alert physicians to prepare best perinatal management strategies. Methods We conducted a retrospective study of a population of 14 cases of BWS diagnosed in perinatal period; four of them were detected prenatally by ultrasound. The anomalies signs described in prenatal were analyzed and compared with the clinical features of the postnatal period. Results The major features reported were represented by macrosomia for 71.4% with an increase of abdominal circumference, and macroglossia for 78.6%. The minor features were various with 64% of visceromegaly (nephromegaly and/or hepatomegaly), 50% of hydramnios and for 80% of male children a genital anomaly (crytorchidism and/or hypospadias). Conclusion This study identified some prenatal ultrasound signs that should alert the clinician to the possibility of BWS. A genetic conseling, after confirmation by molecular diagnosis, could be proposed in a near future in prenatal, and could improve postnatal management strategies for these affected children at high postnatal risk. [ABSTRACT FROM AUTHOR]

Résumé Objectifs Les images kystiques abdominales du premier trimestre de la grossesse sont rares et de pronostic indéterminé. Le but de cette étude est d’en évaluer le devenir. Méthodes Le collège français d’échographie fœtale a mené une étude prospective observationnelle de 24 mois, avec un recueil de tous les cas d’images kystiques abdominales découvertes à l’échographie de dépistage du premier trimestre, à l’exclusion des cas de méga-vessie. L’imagerie initiale, le suivi par les centres pluridisciplinaires de diagnostic prénatal et les issues des grossesses ont été recueillis par les échographistes après consentement des patientes. Résultats Dix cas d’images abdominales kystiques ont été recensés. Ces images avaient un diamètre moyen de 15 mm. Elles étaient anéchogènes dans 5 cas, hyperéchogènes dans 2 cas et mixtes dans 3 cas. Dans 6 cas sur 10, une régression complète a été observée à 18 SA et le pronostic post-natal était alors excellent : dans les 5 cas d’images anéchogènes, l’examen pédiatrique était normal à la naissance et dans un des cas d’image hyperéchogène, une imperforation anale simple a été observée. Dans les quatre cas d’images hyperéchogènes ou mixtes qui n’avaient pas régressé, le devenir était défavorable avec quatre interruptions médicales de grossesse, dont deux cas de dysgénésie cloacale. Conclusions Les images kystiques abdominales sont rares au premier trimestre de la grossesse. Elles disparaissent dans deux tiers des cas et sont alors de bon pronostic. Lorsqu’elles persistent ou que leur contenu n’est pas strictement anéchogène, elles nécessitent un suivi échographique spécialisé à 18 et 22 SA. Objectives Abdominal cysts are seldom detected at the first trimester scan. The aim of this study is to ascertain their outcome, which is currently not established. Methods The French College of Fetal Ultrasound conducted a prospective observational study of 24 months, collecting all cases of abdominal cysts discovered during the first trimester ultrasound. Cases of megacystis were excluded from the study. Ultrasound images, prenatal diagnosis expert reports and pregnancy outcomes were collected by sonographers after patient consent. Results Ten cases of abdominal cysts were collected. The cysts had a mean diameter of 15 mm. They were anechoic in 5 cases, hyperechoic in 2 cases and mixed in 3 cases. In 6 of 10 cases, complete resolution was observed at 18 WG with a good post-natal outcome; the five cases with anechoic images were associated with normal pediatric examination at birth and in the case of the resolved hyperechoic image, an isolated imperforate anus was observed. In the four cases of hyperechoic or mixed images that had not resolved, the outcome was poor with four termination of pregnancies, including two cases of cloacal dysgenesis. Conclusions Abdominal cysts are rare at the first trimester scan. They resolve in two thirds of cases and are then associated with good outcome. When they do not resolve or when they are not strictly anechoic, they require a referral ultrasound examination at 18 and 22 WG. [ABSTRACT FROM AUTHOR]

Résumé Objectif Déterminer l’incidence des anomalies chromosomiques, des associations syndromiques et des malformations fœtales en cas de retard de croissance intra-utérin (RCIU) dans un centre de référence en diagnostic prénatal. Patientes et méthodes Il s’agit d’une revue rétrospective de tous les cas vus entre 14 et 27 SA avec un périmètre abdominal (PA) < 5 e percentile entre 2008 et 2012. Les aneuploïdies et malformations associées étaient recherchées. Les grossesses multiples étaient exclues. Résultats Un total de 8626 fœtus a bénéficié d’un examen échographique entre 14 et 27 SA. Deux cent trente-neuf fœtus (2,8 %) présentaient un RCIU défini par un PA < 5 e percentile. Parmi eux, 37 fœtus avaient un caryotype anormal ou un syndrome identifié (15 %). L’anomalie chromosomique la plus fréquente était la trisomie 18 (10 cas, 4,2 %). Soixante-sept fœtus avaient au moins une anomalie morphologique sans aneuploïdie ou association syndromique (28 %), 135 cas étaient isolés (57 %). Les anomalies associées les plus courantes étaient le fémur court (5 %), l’omphalocèle (5 %) et le laparoschisis (4 %). L’âge maternel était plus élevé (33 ans ± 5 ans versus 31 ans ± 5,6 ans, p < 0,01) et le z-score pour le PA plus bas (2,5 ± 1 versus 2,15 ± 0,6) dans le groupe à caryotype anormal ou association syndromique que dans le groupe sans malformation. Le liquide amniotique était plus souvent augmenté dans le groupe à anomalie du caryotype ou avec malformations associées (14 % et 17 %) que dans le groupe sans malformation (0 %, p < 0,01). Discussion et conclusion Cette étude décrit les anomalies et issues associées au diagnostic de RCIU au 2 e trimestre dans une large population de patientes. Nos résultats suggèrent que l’absence de malformation associée, le degré de retard de croissance, l’âge maternel et la quantité de liquide amniotique peuvent orienter le diagnostic et le conseil anténatal de cette population à haut risque. Objectives To determine the incidence of chromosomal abnormalities, syndromic association and fetal defects associated with second trimester fetal growth restriction (FGR) in a tertiary referral center. Patients and methods Retrospective review of all cases referred between 14 and 27 weeks with an abdominal circumference (AC) < 5 th centile between 2008 and 2012. Multiple pregnancies were excluded. Medical records were retrieved to look for the presence of associated malformations, aneuploidy and outcomes. Results A total of 8626 fetuses had ultrasonographic examination between 14 and 27 weeks. Of these, there were 239 cases (2.8%) with evidence of FGR as based on AC measurement. Thirty-seven fetuses had an abnormal karyotype or an identified syndromic association (15%). The most common chromosomal defect was Trisomy 18 (10 cases, 4.2%), 67 had at least one associated morphological abnormality without aneuploidy or syndromic association (28%). Most common associated abnormalities were relative short femur (5%), omphalocele (5%) and gastroschisis (4%). Last 135 cases were isolated fetal growth retardation (5%). Maternal age was higher (33 yr ± 5 yr versus 31 yr ± 5.6 yr, P < 0.01) and the z-score for the AC lower (2.5 ± 1 versus 2.15 ± 0.6) in the group with abnormal karyotype or syndromic association than in the group without associated malformation. Amniotic fluid was more often increased in the group with an abnormal karyotype or associated malformation (14% and 17%) than in the group without malformations (0%, P < 0.01). Discussion and conclusion This study describes abnormalities and outcomes associated with second trimester fetal growth retardation in a large population of patients. Our results suggest that the absence of associated malformation, degree of growth restriction, maternal age and the amniotic fluid index may help in the prenatal management and counseling of this high risk population. [ABSTRACT FROM AUTHOR]

Résumé: Objectifs: Répertorier les signes échographiques mis en évidence lors de la suspicion d’un placenta accreta. Les objectifs secondaires sont d’analyser la pertinence du diagnostic en échographie et en imagerie par résonance magnétique (IRM), et de connaître les circonstances diagnostiques afin d’identifier une population à risque. Patientes et méthodes: Il s’agit d’une étude rétrospective monocentrique. Les cas de placentas accreta pris en charge au centre hospitalo-universitaire de Lille entre 2005 et 2010, suspectés en anténatal ou découverts per-partum, ont été recensés. Résultats: Vingt-sept patientes ont présenté un placenta accreta sur cette période. 22 cas étaient suspectés en anténatal, dont 21 confirmés à la naissance. Six cas étaient découverts per-partum. Le diagnostic était suspecté dans 41 % des cas suite à un épisode de métrorragies. Cent pourcent des patientes suivies au diagnostic anténatal avaient un utérus au moins unicicatriciel et un placenta antérieur inséré bas. Cinquante pourcent des patientes non dépistées avaient un placenta postérieur non inséré bas. Les signes échographiques les plus fréquents étaient ű lacune placentaire Ƈ (85,7 %), ű vascularisation anormale Ƈ (71,4 %), ű perte du liseré hypoéchogène du myomètre Ƈ (66,7 %), ű irrégularité de la paroi vésicale Ƈ (57,1 %). La sensibilité de l’échographie de dépistage est de 78 %. Vingt et une IRM, réalisées en deuxième intention confirmaient le diagnostic dans 66,7 % des cas. Discussion et conclusion: L’échographie est un examen pertinent pour le diagnostic de placenta accreta. Les placentas postérieurs, plus difficiles d’accès, ne doivent pas être négligés. Les placentas antérieurs praevia chez les patientes multipares ayant un utérus cicatriciel doivent requérir toute l’attention de l’examinateur. [ABSTRACT FROM AUTHOR]

Résumé: Le génotypage RHD fœtal sur plasma maternel est une méthode novatrice et non invasive pour évaluer le risque de maladie hémolytique fœtale chez les femmes allo-immunisées anti-RH1. Après revue bibliographique, la méthodologie décrite par J.M. Minon (J Gynecol Obstet Biol Reprod 2005) a été choisie au laboratoire : les exons 4, 5 et 10 du gène RHD sont amplifiés par PCR en temps réel. Lors de la mise au point du test au laboratoire, 200 résultats de génotypage ont été comparés au phénotype RH1 à la naissance. La validation de méthode a permis de vérifier notamment la sensibilité et spécificité de la méthode, la valeur prédictive négative ; l’étude de corrélation a permis d’établir les critères d’interprétation des résultats. L’analyse de risques résiduels a permis de mesurer les limites réelles de la méthode, notamment liés à la faible concentration d’ADN dans le plasma et aux variants de ce gène. En conclusion, le génotypage RHD fœtal permet d’optimiser la prise en charge obstétricale des femmes RH:-1 allo-immunisées, par une méthode simple, fiable et peu invasive. Le laboratoire a obtenu en 2013 l’accréditation pour cet examen. [ABSTRACT FROM AUTHOR]

Résumé: Les prélèvements fœtaux concernent encore 6 à 7 % des grossesses en France. Si dans la majorité des cas, le prélèvement ne présente pas de difficulté pour un opérateur entraîné, il peut arriver que des circonstances particulières liées au terrain maternel (traitements anticoagulants, métrorragies, fièvre, etc.) rendent le geste plus difficile à réaliser. À partir d’un questionnaire adressé aux centres pluridisciplinaires de diagnostic prénatal français et d’une revue de la littérature, nous établissons une conduite à tenir pour des prélèvements fœtaux dans ces différentes circonstances. [ABSTRACT FROM AUTHOR]

Résumé: Lorsqu’une pathologie fœtale incurable est découverte, certains couples choisissent de poursuivre la grossesse, ne pouvant se résoudre à une interruption de grossesse pour motif médical. De telles situations apparaissent, depuis quelques années, en médecine néonatale et peuvent déboucher sur une prise en charge palliative néonatale. Devant l’imprécision du diagnostic anténatal et face aux incertitudes pronostiques, l’équipe médicale se doit d’informer le couple des différentes évolutions possibles, étape après étape. La prise en charge palliative de l’enfant à naître doit alors avoir une cohérence d’intention à la fois dans la réflexion qui la porte, le discours qui est livré aux parents et les actions qui sont menées, tout en faisant participer l’ensemble des intervenants d’une équipe de santé. L’un des enjeux est d’explorer comment il est possible de contribuer à la construction de la parentalité dans le contexte d’un projet de naissance en soins palliatifs. [ABSTRACT FROM AUTHOR]

Abstract: Gyration abnormalities often reflect severe neurological diseases. Their diagnosis is impeded by our limited knowledge about normal sulci anatomy throughout fetal brain development. Primary sulci appears in a specific chronology which is unchanged among all fetuses. We think it is interesting to remind of sulci anatomy and then to depict sulci MRI and ultrasonography appearance at 22, 27 and 32 weeks of gestation. We pay particular attention to the lateral sulcus, also called Sylvian fissure. [Copyright &y& Elsevier]

Summary: Objectives: To review clinical and epidemiologic data of orofacial clefts and to evaluate the efficacy and the impact of prenatal diagnosis. Material and methods: A population-based retrospective study was carried out on data from the Congenital Malformations of Alsace Registry (France) between 1995 and 2006. Results: A total of 321 orofacial clefts were recorded (overall prevalence, 2.1 per 1000), divided into cleft lip (CL) or cleft lip palate (CLP) (204 cases) and cleft palate (117 cases). The cleft lip and cleft lip palate CL±P sex-ratio was 1.87, whereas the CP sex-ratio was 1. CLs were more often unilateral than CLPs (79% versus 59%). CLs were unilateral in 79% of the cases (60/76), bilateral in 20% of the cases (15/76), and median in 1% (1/76); 55% of the unilateral CLs were right and 45% were left. CLPs were unilateral in 59% of the cases (76/128), bilateral in 39% of the cases (50/128), and median in 2% (2/128); 45% of the unilateral CLPs were right and 55% were left. The 117 CPs were divided into 50 clefts of the total palate (43%) and 67 clefts of the posterior palate (57%); 25 cases (21%) of Pierre Robin sequence were collected. Sixty-six percent of CL±P (134/204) were associated with other congenital anomalies, including chromosome abnormality in 31 cases and identified monogenic syndrome or association in 12 cases. The most frequent chromosome abnormalities were 16 cases of trisomy 13 and 7 cases of trisomy 18. No cases of 22q11.2 microdeletion or duplication were detected among CL±P. Monogenic syndromes were identified in 6% (12/204) of CL±P cases: Van der Woude syndrome (2 cases); CHARGE syndrome (2 cases); ectrodactyly, ectodermal dysplasia, and cleft/lip palate (EEC) syndrome (2 cases); branchiooculofacial (BOF) syndrome (1 case); Treacher-Collins syndrome (1 case); Nager syndrome (1 case); Goldenhar syndrome (1 case); holoprosencephaly spectrum (1 case); and Meckel syndrome (1 case). Forty-two percent of CPs (49/117) were associated with other congenital anomalies; chromosome abnormality was identified in 12 cases and monogenic syndrome was diagnosed in 14 cases. The most frequent chromosome abnormality was 22q11 microdeletion (5 cases). Monogenic syndromes were recognized in 12% of the CP cases (14/117): fragile X syndrome (2 cases), Meckel syndrome (2 cases), Orofaciodigital syndrome type I (OFD1) (1 case), Stickler syndrome (1 case), Larsen syndrome (1 case), Kniest syndrome (1 case), Cornelia de Lange syndrome (1 case), thanatophoric dysplasia (1 case), other unknown bone chondrodysplasia (1 case), Fryns syndrome (1 case), fetal akinesia sequence (1 case), and Silver-Russel syndrome (1 case). Fifty-two percent of CL cases (106/204) were prenatally diagnosed. An increasing tendency was observed between the 1995–2000 and 2001–2006 periods with a detection rate increasing from 47% to 56%. During the whole period, only 1 case of CP was prenatally diagnosed. Eighty-two percent of all cases (263/321) were livebirths; 8 stillbirths were reported (2%); 50 syndromic or associated cases (16%) led to medical abortion (no termination of pregnancy was performed for isolated cleft). Conclusion: Orofacial clefts are a frequent malformation with a total prevalence of 2.1 per 1000 total births. Sonbographic prenatal diagnosis of orofacial clefts remains difficult with a mean detection rate about 50% for CL±P and is extremely rare for CP. Associated malformations and genetic syndromes are frequent and require a systematic survey. This study also highlights the different pathogenic background of CL±P compared to CP, regarding the sex-ratio and the proportion and type of associated malformations. [Copyright &y& Elsevier]

Summary: Objectives: To assess overall and malformation-specific trends in the prevalence and prenatal diagnosis of congenital anomalies in the Parisian population. Methods: The Paris Registry of Congenital Malformations is population-based and since 1981 has registered all cases with structural birth defects or chromosomal anomalies in the Parisian population. The total and livebirth prevalence and the proportion of cases with prenatal diagnosis were calculated for all anomalies and 20 malformations selected based on their higher frequency and their impact on health outcomes. Results: The overall prevalence was 3.30% (95% CI 3.27–3.33), and the livebirth prevalence 2.42% (95% CI 2.39–2.45). The proportion of cases diagnosed prenatally increased from 16.5% (95% CI 14.1–19.1) in 1983 to 70.7% (95% CI 68.3–73.1) in 2007. Terminations of pregnancy for fetal anomaly (TOPFA) increased from 8.8% (95% CI 7.0–10.8) in 1983 to 35.6% (95% CI 33.1–38.1) in 2007. These results varied substantially for the 20 congenital anomalies studied. Conclusion: We found an increase in the overall prevalence of all anomalies, especially for chromosomal abnormalities. The observed increase is at least to a large extent due to trends in delayed childbearing and an increase in both pre- and postnatal diagnosis of congenital anomalies in our population. [Copyright &y& Elsevier]

Abstract: In France, screening for toxoplasmosis is mandatory during pregnancy, whereas it is not performed in most other countries. The rationale for prenatal screening is to allow for several levels of intervention: primary prevention by health education; in case of seroconversion, prophylactic therapy; prenatal diagnosis using amniocentesis; the possibility of termination of pregnancy (TOP) in case of severe cerebral lesions at ultrasound; in most cases of fetal infection, antiparasitic therapy prenatally as well as postnatally. The French Health Authority (Haute Autorité de santé [HAS]) called into question the screening policy, but maintained it for 5 years pending randomized clinical trials. Recent data is available to answer some of the questions, but not the place of prenatal therapy. The sensitivity of prenatal diagnosis has progressed, while the place of TOP has decreased. The incidence of toxoplasmosis in the French population has fallen. Some studies have shown evidence in favor of prenatal therapy for infected fetuses. However, studies of prophylactic therapy are disappointing. These studies are purely observational and concern mostly spiramycine. For the first time, a multicenter randomized clinical trial of prevention of mother-to-child transmission of Toxoplasma gondii is underway (the TOXOGEST study). The HAS guidelines are that any suspected toxoplasmosis seroconversion should be confirmed in a reference laboratory, and that patients should be referred to expert centers without delay. It is not recommeded to start therapy before such expert consultation. The reference centers should provide counseling and access to prenatal diagnosis and therapy options. [Copyright &y& Elsevier]

Summary: Inherited metabolic diseases are mostly due to enzyme deficiency in one of numerous metabolic pathways, leading to absence of a compound downstream from and the accumulation of a compound upstream from the deficient metabolite(s). Diseases of intoxication by proteins (aminoacidopathies, organic acidurias, urea cycle defects) and by sugars (galactosemia, fructosemia) usually do not give prenatal symptoms since mothers protect their fetuses from pathological metabolite accumulation. A well-known exception is hypoplasia of corpus callosum, as is sometimes observed in nonketotic hyperglycinemia and sulfite oxidase deficiency. Conversely, women with phenylketonuria “poison” their fetus if they are not treated (spontaneous abortions, intrauterine growth restriction [IUGR], cardiac malformations, and brain disease). Amino acid synthesis defects can lead to prenatal symptoms: microcephaly in serine deficiency (detectable by amino acid analysis in fetal cord blood), and brain malformations in glutamine synthetase deficiency. Impaired folate metabolism is involved in a large fraction of neurodevelopmental defects referred to as spina bifida, yet the underlying genetic component(s) are largely unknown. Energy metabolism diseases caused by defects in the synthesis or utilization of relevant metabolites lead to organ dysfunctions or malformations, but prenatal diagnosis is usually impossible unless genetic analysis can rely on a previously affected child in the family. A somewhat intermediate condition is defects of mitochondrial beta-oxidation of fatty acids, as they may sometimes be symptomatic prenatally (notably the HELLP syndrome or other presentations), and in this case, organic acid and acylcarnitine analysis in amniotic fluid can be informative in the absence of an index case. In contrast, complex molecule diseases commonly give prenatal symptoms that may permit the diagnosis even in the absence of index cases: hydrops fetalis and skeletal anomalies in lysosomal storage diseases, hydrops fetalis in congenital disorders of glycosylation (CDG) and transaldolase deficiency, brain malformations in O-glycosylation defects, brain malformations, kidney cysts and skeletal anomalies in peroxysomal diseases (Zellweger syndrome), syndactyly, genitalia malformations, and IUGR in Smith-Lemli-Opitz (SLO) syndrome. Although many metabolic disorders show biochemical abnormalities during fetal development that are informative for prenatal diagnosis, only a fraction of them are clinically/sonographically symptomatic before birth, thus allowing for prenatal diagnosis in the absence of an index case, i.e., serine deficiency, some fatty acid beta-oxidation defects, transaldolase deficiency, lysosomal diseases, CDG, Zellweger syndrome, and SLO syndrome. [Copyright &y& Elsevier]

Summary: Tumor predisposition in children is rare, accounting for approximately 10% of all cancers in childhood. Tumor predisposition involves very rare tumors such as pleuropulmonary blastoma, adrenocortical carcinoma, hepatoblastoma, rhabdoid tumors, optic pathway glioma, as well as rare tumors such as retinoblastoma, medulloblastoma, nephroblastoma, or more frequent tumors such as sarcomas, neuroblastoma, and leukemias. The identification of these predispositions is important for improved management for both the child and relatives. Prenatal and preimplantation genetic diagnosis are options that could be considered for young parents in a perspective of future pregnancies. This manuscript describes the main tumor predispositions in childhood. From each histological subtype, the different diagnosis directions are discussed in view of these main tumor predispositions. [ABSTRACT FROM AUTHOR]

Abstract: Cleft lips and palates (CLP) are the most common human facial malformations. Depending on the ethnic and/or geographical origin of the studied populations, they can affect up to 1/500 newborns. The treatment of these patients is multidisciplinary because these malformations have not only aesthetic consequences but also functional consequences as the phonation, hearing, deglutition, mastication and ventilation are altered. These consequences can also be psychological since the building of the body image, the way others perceive it, is likely to be seriously altered. Patients presenting with CLP don’t usually seem to present with any serious psychological or psychiatric pathology. Yet a close review of the related literature shows that disorders are actually described: behavioural troubles, anxiety, depression and esthetical dissatisfaction with one''s face in children as well as in adults. The difficulty in interpreting these disorders lies in the various factors that are likely to impact this condition (family setting, importance and type of the cleft, surgery protocol, growth, social environment…). A careful consideration of concerned families show the importance of the psychological context and the risks of a disharmonious structuring of the parents–child relationships on the child''s development. The identification of the difficulties faced by these families, depending on the child''s age, can be easily identified. They can be identified more particularly at birth when the family first sees the child. [Copyright &y& Elsevier]

Abstract: By way of this round table''s introduction about “transmission and genetics” and before the conference of professor J.-M. Mandel, we propose some thoughts round fundamentals questions of innate and acquired, risks of predetermination, dangers of some predictions. A clinical illustration supports our questioning about stakes of prenatal diagnosis, hazards of genetics’ diagnosis and effects of a predictive diagnosis. In fact, our experience as consultation-liaison child psychiatrist in paediatrics allows us to observe the different viewpoints applied to children: those of science, of genetics, those of neonatology, of paediatrics, of psychoanalysis. If tendency has long been to pit the science''s child against the psychoanalysis one, it appears to us that this opposition is becoming obsolete; clinical medicine itself imposes such a correction. The matter is no more to pit but to make up. Besides, it is probably no accident that psychoanalysis is more than ever topical. The more science progresses, the more the question of singularity is obvious. Neurosciences and genetics seek universal mechanisms that finally produce something singular, making still relevant what is peculiar to psychoanalysis. But the confusion is frequent between history and destiny of the child, between anamnesis and destiny, between prevention and prediction, between knowledge and certitude. We insist on the trap of causalities and determinisms (genetic, epidemiological, paediatric, sociologic and even child psychiatric determinisms) specifying that “future is not written”. Always, there is a radical hiatus between a state of the brain and the subject, which is going to deduct (brain plasticity and unconscious), a distance between IRM and the subject, between the disease and the subject who suffers, between genotype and phenotype… And it is in this distance that it''s possible to offer a space of freedom, to leave opened the question of the subject, including in the extreme situations. In this debate about the transmission and the predictive diagnosis, the child psychiatrist''s has a place. We discuss this place, specifying why the child psychiatrist''s is a practitioner of the unexpected, an artisan of the meeting. [Copyright &y& Elsevier]

Summary: We analyzed 16 cases of hypoplastic left heart syndrome (HLHS) submitted to the multidisciplinary center at Rennes Teaching Hospital from 2006 to 2010 for prenatal diagnosis. The information given to parents at the moment of choice is capital for them to make their own decision: in our team the real choice for parents stands between termination of pregnancy (TOP) and palliative care (PC). The Norwood procedure is rarely proposed to parents in France and it is performed in very few centers. Heart transplant is never proposed nor done at this age. The objectives of our study were to understand the reasons for the choice of PC, take stock of our experience of PC, and relate the benefits but also the disadvantages of PC. Over the 16 patients whose fetus had HLHS, 9 requested TOP, while 7 others wanted to live their pregnancy and meet their child at birth, therefore requesting neonatal PC. No family asked for the Norwood procedure. Four children died within the first days (D1, D2, D4, D9), 2 others died at 5 and 7 months, 1 child was operated on for coarctation of the aorta (unknown before birth) and is still alive 1.5 years later. Maternal motivations to continue the pregnancy were clearly described for 2 of the 7 cases: religious prohibition of TOP in 1 case, negative experiences of previous abortions in the second case. In another case, the parents hesitated between PC and Norwood surgery. For the other women, the reasons were less clearly expressed. In our series, HLHS is the first indication for PC from prenatal diagnosis (7/16 cases in the same period) while in the literature, heart diseases are the second cause of TOP after the neurological causes. The overrepresentation of this pathology in the families who opt for PC may be due to the unconscious image that both professionals and families have of HLHS: severity of an inevitably fatal disease, rapid postnatal death, and no suffering. Our study may change this view: a child was in fact carrying a curable defect which was discovered 12 days after birth, 2 children died at 5 and 7 months, and 5 of 6 children had major analgesics at the end of life. Nevertheless, the families were supported and followed by the PC network, except 1 who ruptured all contacts in a context of presumed intense suffering, but the other 6 do not regret their choice despite the difficulties. [Copyright &y& Elsevier]

Summary: The ureteric-pelvic junction (UPJ) is an uropathy that his management had profoundly evolved during these last thirty years, both from the point of view of the care and diagnosis. Purpose: The purpose of this study is to discuss a diagnostic and therapeutic strategy of this uropathy. Patients and methods: This study concerning 53 children (59 UPJ with antenatal diagnosis) brought together in the unity of paediatric surgery of 1999 in 2008. We classified the patients according to their care: group I: surgical at once; group II: medical then secondarily surgical; group III: purely medical. Results: This study was about 34 boys and 19 girls with a sex ratio of 1.8. The UPJ was noticed in 26 cases to the left. The vesico-ureteral reflux was the most frequent associated abnormality (five cases). The majority are a part of the group I (42%). The anteroposterieur diameter in the ultrasound was on average 32.65mm for the group I while it was respectively 25.86 and 14mm for the group II and III. The differential renal average function in the scintigraphy (DTPA or MAG III) was normal (46%) in the group III while was 35 and 38% respectively in the group I and II. The nephrogram was obstructive in 72 and 75 % of the cases respectively in the group I and II and only in 16 % of the cases in the group I. The final comparison of the differential renal function between the group I, and the group II, does not show a significant difference (P <0.005). Thirty-three patients benefited from an initial medical supervision. Only sixteen children (48%) had pyeloplasty. Conclusion: The big frequency of the spontaneous improvements at the infant by simple tissular maturation (30% in this series), and the low incidence of the postoperative complications of the patients operated late do not authorize any more the premature pyeloplasty in front of an antenatal diagnosis UPJ. [Copyright &y& Elsevier]

Summary: Introduction: The orofacial clefts include 30 variant according to Tessier classification: the number 30 contain mandibular arc damage isolated or associated with damage of surrounding soft tissue. Case report: Our patient was a newborn with median mandibular cleft associated with ankyloglossia, bifid tongue and a top cervical fistula. We have not found polymalformative syndrome. The early surgical management included one time and after-effect were simple within 11months. Discussion: We point up difficulties for antenatal diagnosis and controversy about appropriate time for management of bone defect. The last physiopathologic hypotheses were explicated. [ABSTRACT FROM AUTHOR]

Abstract: Coarctations of the aorta can be associated with severe neonatal consequences. Screening for and diagnosis of this prenatal malformation remain difficult. We review the various tools currently available to us, and their respective limits, to minimize the rate of false negatives and false positives associated with prenatal screening for this situation. [Copyright &y& Elsevier]

Summary: The value of prenatal diagnosis of major congenital heart diseases (CHDs) has already been proved. In this study, we observed the evolution of the detection rate of CHDs and the quality of the diagnoses over a 15-year period in the Indre-et-Loire department of France. Method: Retrospective analysis of the quantitative and qualitative data of prenatal diagnosis between 2000 and 2005 (period 3) and comparison with studies conducted from 1991 to 1994 (period 1) and from 1995 to 1999 (period 2). The CHDs considered to be detectable are the major CHDs with neonatal symptoms. In order to analyze the quality of prenatal diagnosis, each diagnosis was classified as correct, false, or incomplete during period 3. Results: Period 3: 65.7% detectable CHDs were screened. Using period 1 criteria for prenatal diagnosis, the percentage of CHDs detected for periods 1, 2, and 3 was 43.2, 66.7, and 78%, respectively. Between periods 2 and 3, the detection rate increased from 52 to 74% for CHDs diagnosed with the visualization of the outflow tract. It increased from 63 to 71% for CHDs diagnosed with a four-chamber view. During period 3, diagnoses made by a pediatric cardiologist were correct and complete in 80% of cases. It was less than 25% otherwise. Conclusion: The improvement of prenatal diagnosis over time results from technological progress, the greater experience of ultrasonographers, and the systematic visualization of the outflow tract in addition to the four-chamber view. Despite the improvement in prenatal diagnosis, one-third of major CHDs were not screened before birth. Pediatricians still need to diagnose CHDs after birth. [ABSTRACT FROM AUTHOR]

Abstract: Objective: To evaluate the caregivers’ opinions regarding decision-making in termination of pregnancy (TOP) for fetal anomaly. Material and methods: Questionnaire survey using a semi-structured survey based on visual analogue scales, sent to all multidisciplinary centres for prenatal diagnosis in France. Answers were received from 26 centres nation-wide. Results: Response rate was 39% (213 responses received over 550 questionnaires sent). Fifty-five percent of respondents were women, 90% physicians, 7,5% midwives. A vast majority (69.8%) believes that their own convictions play a bigger role in decision in real practice than in their ideal. The major decisional factors in decision-making for TOP are: the long-term prognosis of the anomaly, a specialized opinion on its curability, the quality of the information given to the future parents, their expressed opinion, the existence of a multidisciplinary decision, the ability of the future parents to understand the medical data, the obtention of a medical consensus, the proof level of the medical information. For only 55% of the respondents, the current legal framework is adequate to manage the situations that result from prenatal diagnostic practices today. The question of late third-trimester TOP raises ethical debate: over a third (37%) see no ethical difference between TOP and withdrawal of care during the neonatal period; the majority (48% versus 43%) feel that ethically speaking a neonate and a foetus at 39weeks gestational age (GA) should not be treated differently; 37% of the respondents feel that current practice is likely to lead to eugenism. Discussion and conclusion: As far as TOP is concerned, the huge discrepancies in responses from the professionals highlight the ongoing ethical debate, especially concerning the concept of informed choice in TOP, which we believe should be entirely revisited. [Copyright &y& Elsevier]

Summary: Netherton syndrome is a rare autosomal recessive disorder characterized by the triad of ichthyosiform erythrodermia, typical hair dysplasia, and severe atopic features. The broad range of variable expression of this disease is well described and 20% of complications occur during the neonatal period such as hypernatremic dehydration, electrolyte imbalances, recurrent or severe infections, and failure to thrive. Mutation of the SPINK5 gene has been identified as disease-causing in Netherton syndrome, but the pathophysiology still remains unclear. Almost all SPINK5 mutations result in the absence of the serine-protease inhibitor LEKTI protein in both keratinocytes and lymphocytes. In this study, we report on a severe form of Netherton syndrome observed in three patients within a large inbred Rom family. All of them died in the first months of life despite early treatment. They were found to be homozygous for the c.1431-12G>A SPINK5 gene mutation, which has not been associated with a lethal form of the disease thus far. This family illustrates the extreme phenotype of Netherton disease of neonatal onset. Molecular diagnosis allowed further genetic counseling and prenatal testing during other pregnancies. [Copyright &y& Elsevier]

Abstract: Cystic fibrosis (CF) is a frequently fatal autosomal recessive inherited disease affecting around one in 3000 newborns in France, the carrier frequency varying from one in 20 to one in 40 subjects depending on the geographical area. The disease is caused by a chloride channel defect that is attributable to mutations in the gene that encodes the CF transmembrane conductance regulator (CFTR). Approximately, 1200 different mutations have been discovered. Among them, the F508del mutation accounts for 70% of mutated alleles worldwide. Prenatal diagnosis (PND) of inherited monogenic disorders such as CF currently relies on invasive procedures-amniocentesis, chorionic villus sampling (CVS) – which carry a significant risk of miscarriage (from 0.5 to 3%). Several methods have been proposed to enrich circulating fetal cells (CFCs) from blood and use them in PND. However, up to now, no assay has been shown to be reliable enough for routine application in place of the invasive protocols. When combined with laser microdissection, isolation by size of epithelial tumor/trophoblastic cells (ISET) allows mutation analysis of DNA from single cells demonstrated to be fetal (circulating fetal trophoblastic cells [CFTC]) by short tandem repeat (STR) genotyping and uncontaminated with maternal DNA. Application of this protocol to 12 couples at risk of having a child affected by CF has shown, in a blind study, that the new method affords a reliable and safe PND of affected fetus, healthy carrier or normal non carrier fetus. A following prospective blind study has then been performed on 32 couples at risk of having an affected child. For each mother, five or 10 CFTCs have been analyzed with an individual genetic diagnosis performed per CFTC. Results have been obtained in 240 CFTC showing that seven mothers were carrying an affected foetus, with 100% sensitivity and 100% specificity. These results open the way to a multicenter clinical validation trial and to the potential future application of the ISET non invasive approach as a reliable alternative to the invasive PND procedures. [Copyright &y& Elsevier]

Abstract: Array-CGH emergence allowed important diagnosis progress, and a better care of patients in postnatal. So, there is a great temptation to use it also in prenatal diagnosis. The point of view objective is to make a rapid overview of cytogenetic diagnosis evolution during the last 50 years, and to show all questions raised by the use of array-CGH, and problems that could arise in prenatal diagnosis. While array-CGH just comes in genetic laboratories, new diagnosis approaches emerged like whole genome sequencing or non-invasive prenatal diagnosis. The 2nd objective will be to review all these techniques for a probably close future. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this work is to compare pregnancy for primiparous and secondiparous women, an unusual approach since most of the scientific literature focuses on primiparous women only. Our main results are: (i) sibling rivalry is strongly revived for secondiparous women, and (ii) although they manage to distanciate themselves from oedipean conflict, it is somehow reactivated, but with respect to the first child, with whom they create the second one. [ABSTRACT FROM AUTHOR]

Abstract: Dysmorphology is the study of congenital malformations and anatomic variations of the individuals. Up to 2500 dysmorphic or malformative syndromes are described, most of them being characterized by mental retardation. Craniofacial dysmorphology may be the keystone of syndrome identification, although limb anomalies are sometimes important diagnostic clues. The advances of fetal imaging, particularly the development of 3D ultrasound techniques, allow a detailed analysis of the fetal face. Dysmorphology requires experience of rare syndromes and a perfect knowledge of normal facial appearance and variations. In utero, this approach must combine the skills of both a practitioner with expertise in fetal ultrasound and a pediatric dysmorphologist. Furthermore, facial changes have to be analyzed according to the context of the pregnancy and family history. Identification of patent facial anomalies may be a clue for the diagnosis of severe fetal syndromes and diseases. Conversely, when fetal malformations or abnomalities of the fetal growth are identified, a careful facial analysis can be proposed in order to rule out well-known syndromes with a poor prognosis. However, from an ethical point of view, parents should not be aware of a possible facial dysmorphism unless there is a precise diagnosis and options concerning the pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: The purpose of this study is to describe the diagnosis, the care and the prognosis of the fetuses with an antenataly diagnosed megacystis. Patients and methods: Six year retrospective study about 46 cases of megacystis (26 diagnosed during 1st trimester; 14 during 2nd trimester; 9 during 3rd trimester) referred in the prenatal fetal medicine unit of the Femme–Mère-Enfant hospital in Lyon (France). Results: The main aetiology is urethral occlusion, particularly for megacystis discovered during the 1st and the 2nd trimesters. Twenty-two terminations of pregnancy were performed (47.8%) and 6 pregnancies arrested spontaneously (13%). Eighteen children were born alive, but 2 died in neonatal period. Finally, 16 children survived (34.8%). Chromosomal abnormalities are frequent (22%). Discussion and conclusion: Antenatal discovery of a megacystis is a complex situation, and often of poor fetal prognosis. It requires a multidisciplinary approach to allow the concerned couple to be determined on the best care of this pregnancy. [ABSTRACT FROM AUTHOR]

Abstract: This article focuses on six questions raised by genetic testing in human: (1) the use of genetic tests, (2) information given to relatives of patients affected with genetic disorders, (3) prenatal and preimplantatory diagnosis for late onset genetic diseases and the use of pangenomic tests in prenatal diagnosis, (4) direct-to-consumer genetic testing, (5) population screening in the age of genomic medicine and (6) incidental findings when genetic testing are used. [ABSTRACT FROM AUTHOR]

Abstract: Cleft lips and palates (CLPs) are the most common human facial malformations. Depending on the ethnic and/or geographical origin of the studied populations, they can affect up to 1/500 newborns. The treatment of these patients is multidisciplinary because these malformations have not only aesthetic consequences but also functional consequences as the phonation, hearing, deglutition, mastication and ventilation are altered. These consequences can also be psychological since the building of the body image, the way others perceive it, is likely to be seriously altered. In Europe there are over 210 reference hospitals for children affected by CLP. Besides, about 190 different protocols were identified. So far no generic protocol was recognized by the medical community as a whole. This discrepancy can be explained by the fact that the aesthetic and functional result of a protocol cannot be accurately assessed before adulthood when the child''s growth is complete. Patients presenting with CLP don’t usually seem to present with any serious psychological or psychiatric pathology. Yet a close review of the related literature shows that disorders are actually described: behavioural troubles, anxiety, depression and esthetical dissatisfaction with one''s face in children as well as in adults. The difficulty in interpreting these disorders lies in the various factors that are likely to impact this condition (family setting, importance and type of the cleft, surgery protocol, growth, social environment…). A multidisciplinary examination of the face and a careful consideration of concerned families show the importance of the psychological context and the risks of a disharmonious structuring of the parents-child relationships on the child''s development. The identification of the difficulties faced by these families, depending on the child''s age, can be easily identified. Of course they can be identified at birth when the family first sees the child and later on at each stage of the child''s life cycle (when starting at kindergarten where the child socialises for the very first time, at the start of the first year in primary school where pupils learn how to read and then at the start of secondary school which is yet another crucial step for the child due to the adolescence period). It is also obvious that an adult affected by CLP has a particularly heavy medical history as the patient had to go through various treatments and surgical interventions during his childhood and adolescence, which is even sometimes maintained at adulthood. Repeated appointments with the different specialists involved in their treatment punctuate their life as well as their parents’. This medico-surgical setting for facial malformations i.e. the features of the patient''s face which are largely involved in their interpersonal relationships and the expression of emotions can have serious consequences. Most children presenting with CLPs and living in France benefit from regular follow-up schemes carried out in competent reference centres by a multidisciplinary team whose members represent each of the fields of expertise involved in the correction of this malformation: infantile and maxillofacial surgery, otorhinolaryngology (or ENT), orthophony and dentofacial orthopedics. Only the two French reference centres benefit from the permanent presence of a psychologist. This raises the question whether every care centre should take into care these children and their parents’ mental health by offering psychological support during the course of the therapeutic follow-up scheme for these children, and this from an early age on as is recommended by the American Cleft Palate Craniofacial Association. [Copyright &y& Elsevier]

Abstract: Microarray-based comparative genomic hybridization (aCGH) is becoming an efficient clinical diagnostic tool enabling genome-wide screening of segmental copy number variations (CNVs). Regarding its ability to detect segmental genomic CNVs in individuals with mental retardation, autism and multiple congenital anomalies, aCGH is gradually replacing cytogenetic methods. Using this tool as a prenatal test for foetal genomic imbalance offers the promise of detecting pathogenic gain or loss of genomic material more quickly and much more frequently than current methods. However, there is a concern about CNVs of uncertain significance (for example, predisposition to adult occurring disease with incomplete penetrance) which might lead to termination of normal pregnancies. We report in this article recent data using aCGH in foetuses from spontaneous or medically terminated pregnancies associated with multiple malformations. aCGH should be considered as a diagnostic tool to improve genetic counselling in fetopathology. We also report recent data on aCGH as a prenatal test. Larger studies with targeted arrays are mandatory to determine whether the improved overall detection rates of clinically chromosomal abnormalities will justify offering aCGH in a prenatal diagnosis setting. [Copyright &y& Elsevier]