[The ethics of fetal myelomeningocele surgery]. / Réflexions éthiques concernant la chirurgie fœtale de réparation des myéloméningocèles.

Fetal myelomeningocele surgery was introduced in France in 2014. Developments in prenatal diagnosis of neural tube defects have accompanied the development of prenatal diagnosis. This fetal surgery represents one of the three possible care paths for pregnant women faced with this prenatal diagnosis. The ethical issues of this fetal surgery are discussed and in particular regarding prenatal counselling and patient autonomy of choice.

Prevalence of COL4A1 and COL4A2 mutations in severe fetal multifocal hemorrhagic and/or ischemic cerebral lesions.

OBJECTIVE: To establish the prevalence of COL4A1 and COL4A2 gene mutations in fetuses presenting with a phenotype suggestive of cerebral injury. METHODS: This was a single-center retrospective analysis of all cases of fetal cerebral anomalies suggestive of COL4A1 or COL4A2 gene mutation over the period 2009-2018. Inclusion criteria were: (1) severe and/or multifocal hemorrhagic cerebral lesions; (2) multifocal ischemic-hemorrhagic cerebral lesions. These anomalies could be of different ages and associated with schizencephaly or porencephaly. Between fetuses with and those without a mutation, we compared gestational age at the time of diagnosis, parity and fetal gender. RESULTS: Among the 956 cases of cerebral anomaly diagnosed in our center during the 10-year study period, 18 fetuses were identified for inclusion. A pathogenic COL4A1 gene mutation was found in five of these cases, among which four were de-novo mutations. A variant of unknown significance was found in four fetuses: in the COL4A1 gene in one case and in the COL4A2 gene in three cases. No COL4A1 or COL4A2 mutation was found in the remaining nine fetuses. The median (interquartile range) gestational age at diagnosis was significantly lower in cases with a mutation (24 (22-26) weeks) than in cases without a mutation (32 (29.5-34.5) weeks) (P = 0.03). CONCLUSIONS: A phenotype suggestive of cerebral injury was found in 18 of the 956 (1.9%) cases in our population, in 28% of which there was an associated COL4A1 or COL4A2 mutation. COL4A1 and COL4A2 gene mutations should be sought systematically in cases of severe and/or multifocal hemorrhagic or ischemic-hemorrhagic cerebral lesions, with or without schizencephaly or porencephaly. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

New insights in cerebral findings associated with fetal myelomeningocele: a retrospective cohort study in a single tertiary centre.

OBJECTIVE: To investigate cerebral anomalies other than Chiari type 2 malformation in fetuses with myelomeningocele (MMC). DESIGN: A retrospective cohort study in a single tertiary centre. SETTING: A review of associated cerebral anomalies in cases with prenatal diagnosis of myelomeningocele. POPULATION: Seventy cases of fetal myelomeningocele. METHODS: Ultrasound and MRI images were blindly reviewed. Postnatal imaging and results of the postmortem results were also reviewed. The association between cerebral anomalies and the following ultrasound findings was measured: level of the defect, ventriculomegaly, microcephaly and fetal talipes. MAIN OUTCOME MEASURES: A microcephaly was observed in 32/70 cases (46%) and a ventriculomegaly was observed in 39/70 cases (56%). Other cerebral anomalies were diagnosed in 47/70 (67%). RESULTS: Other cerebral anomalies were represented by 42/70 cases with abnormal CC (60%), 8/70 cases with perinodular heterotopia (PNH; 11%), 2/70 cases with abnormal gyration (3%). MRI performed only in fetal surgery cases confirmed the ulltrasound findings in all cases and provided additional findings in two cases (PNH). Risk ratios of fetal cerebral anomalies associated with MMC did not reach significance for microcephaly, ventriculomegaly, talipes or the level of the defect There was an overall good correlation between pre- and postnatal findings with a Kappa value of 0.79 [95% CI 0.57-1] and 82% agreement. CONCLUSION: Fetal brain anomalies other than Chiari type 2 malformation are frequently observed in fetuses with myelomeningocele, predominantly represented by CC anomalies. Whether these associated cerebral anomalies have an impact on selecting cases eligible for fetal surgery needs further evaluation. TWEETABLE ABSTRACT: Fetal cerebral anomalies other than Chiari type 2 malformation, microcephaly, and ventriculomegaly may be associated with MMC in up to 67% of the cases.

Cell therapy for prenatal repair of myelomeningocele: A systematic review.

Myelomeningocele (MMC) is a spinal cord congenital defect that leads to paraplegia, bladder incontinence and bowel dysfunction. A randomized human trial demonstrated that in utero surgical repair of the MMC defect improves lower limb motor function. However, functional recovery remains incomplete. Stem cell therapy has recently generated great interest in the field of prenatal repair of MMC. In this systematic review we attempt to provide an overview of the current application of stem cells in different animal models of MMC. Publications were retrieved from PubMed and Cochrane Library databases. This process yielded twenty-two studies for inclusion in this review, experimenting five different types of stem cells: human embryonic stem cells, neural stem cells, induced pluripotent stem cells, human amniotic fluid stem cells, and mesenchymal stem cells (MSCs). Rodents and ovine were the two major species used for animal model studies. The source, the aims, and the main results were analyzed. Stem cell therapy appears to be a promising candidate for prenatal repair of MMC, especially MSCs. Further explorations in ovine and rodent models, reporting clinical and functional results, are necessary before an application in humans.

[Feticide procedures in second and third trimesters terminations of pregnancy]. / Geste d'arrêt de vie fœtale : techniques pour les interruptions médicales de grossesse des deuxième et troisième trimestres.

Performing a feticide as part of termination of late pregnancy is recommended in many countries. Feticide avoids a live birth of a severely affected premature newborn and prevents fetal pain. There are limited data on feticide procedures since only a few countries in the world authorize late termination of pregnancy. The objective of this review was to assess the most appropriate feticide procedure based on published data during the last thirty years. Administration of an initial fetal analgesia followed by a lethal lidocaine injection through the umbilical cord, under ultrasound guidance, appears to be the most effective, safe and ethical way to perform feticide. According to the current knowledge regarding the risk of fetal pain and survival of extremely preterm infants, a feticide should be discussed as early as 20-22 weeks of gestation.

Towards ontology-based decision support systems for complex ultrasound diagnosis in obstetrics and gynecology.

INTRODUCTION: We have developed a new knowledge base intelligent system for obstetrics and gynecology ultrasound imaging, based on an ontology and a reference image collection. This study evaluates the new system to support accurate annotations of ultrasound images. We have used the early ultrasound diagnosis of ectopic pregnancies as a model clinical issue. MATERIAL AND METHODS: The ectopic pregnancy ontology was derived from medical texts (4260 ultrasound reports of ectopic pregnancy from a specialist center in the UK and 2795 Pubmed abstracts indexed with the MeSH term "Pregnancy, Ectopic") and the reference image collection was built on a selection from 106 publications. We conducted a retrospective analysis of the signs in 35 scans of ectopic pregnancy by six observers using the new system. RESULTS: The resulting ectopic pregnancy ontology consisted of 1395 terms, and 80 images were collected for the reference collection. The observers used the knowledge base intelligent system to provide a total of 1486 sign annotations. The precision, recall and F-measure for the annotations were 0.83, 0.62 and 0.71, respectively. The global proportion of agreement was 40.35% 95% CI [38.64-42.05]. DISCUSSION: The ontology-based intelligent system provides accurate annotations of ultrasound images and suggests that it may benefit non-expert operators. The precision rate is appropriate for accurate input of a computer-based clinical decision support and could be used to support medical imaging diagnosis of complex conditions in obstetrics and gynecology.

[Ultrasound screening for birth defects: A medico-economic review]. / Aspects médico-économiques du dépistage échographique des malformations fœtales : revue de la littérature.

OBJECTIVES: The systematic use of ultrasound during pregnancy aims at birth defect detection. Our objective was to assess the economic efficiency of prenatal ultrasound screening for fetal malformations. METHODS: We carried out a literature review on Medline via PubMed between 1985 and 2015, from the economic perspective of the prenatal ultrasound screening for fetal malformations. RESULTS: The literature on this subject was sparse and we selected only twelve articles presenting relevant economic data, of which only eight were proper medico-economic studies. We found arguments for the economic effectiveness of ultrasound screening for fetal malformation detection, which is largely linked to the terminations of pregnancies and to the cost of the handicaps "avoided". However, none of the reviewed articles could reach medico-economic conclusions. Additionally, we highlighted various elements making economic analyses more complex in this field: the choice of the method, the uncertainty around two essential parameters (the efficiency of ultrasound and the costs of procedures) and the difficulties to compare or to generalize results. We also noticed important methodological heterogeneity among the studies and the absence of French study. CONCLUSIONS: Previously published data are insufficient to assess the economic efficiency of prenatal ultrasound screening for fetal malformations.

[Intrauterine blood transfusion: Status report of 4years of practice in France (2011-2014)]. / Transfusions fœtales érythrocytaires : état des lieux sur 4 ans en France (2011­2014).

OBJECTIVES: The aim of our study was to evaluate in utero blood transfusion's (IUT) performed in France, among the French prenatal diagnosis centers in order to study the etiology of severe anemia requiring IUT. METHODS: We conducted a national retrospective descriptive study between 2011 and 2014. The data were collected using a survey sent by email to all French prenatal diagnosis centers. RESULTS: Among the 49 centers, 18 (38 %) had performed at least one IUT during the study period. The geographical repartition of these centers was appropriate for the "Aquitaine Pyrénées" region. Five centers performed 68 % of the national activity and one center performed 40 % the national activity. Each year, a mean of 204 IUTs were performed in 113 pregnancies. The principal etiology of severe fetal anemia requiring IUT was hemolytic disease of the fetus (69 % of the etiologies) with anti-RhD being the most prevalent antibody. The second etiology was represented by parvovirus B19 infection (17 % of IUTs). CONCLUSION: The French IUT activity was stable in numbers and indications during the study period. A national register could be set up in order to better evaluate prospectively the number of pregnancies concerned by IUT and to study the prevalence of hemolytic disease of the fetus due to anti-RhD antibodies.

[Preliminary results from the French study on prenatal repair for fetal myelomeningoceles (the PRIUM study)]. / Résultats préliminaires de l'étude PRIUM : programme de réparation in utero des myéloméningocèles.

OBJECTIVES: To present the preliminary results of the PRIUM study, a French pilot study of prenatal repair for myelomeningoceles (MMC). MATERIAL AND METHODS: The fetal surgery for MMC is offered in cases of patients that did not opt for termination of pregnancy. RESULTS: Thirty-six patients were referred in an 18-month period. Eight patients were not eligible for prenatal repair. Another type of dysraphism was made in 6 cases (one spina-lipoma, 5 cases of limited dorsal myeloschisis). Twenty-two patients were eligible to fetal surgery. A prenatal repair was performed in three cases (14%). Four patients opted for a conventional postnatal treatment. Fifteen patients opted for termination of the pregnancy. CONCLUSION: The establishment of a prenatal repair of MMC protocol in France was justified. The experience of the first 18months of this study however suggests that only a limited number of couples will choose this procedure after specialized counseling in a reference center.

Limits of the surgically induced model of myelomeningocele in the fetal sheep.

PURPOSE: The prevention of Chiari type II malformation (CM) is commonly used as a primary outcome for the evaluation of techniques of fetal myelomeningocele (MMC) surgery in the fetal lamb. The aim of our study was to investigate the frequency of the associated CM in the MMC fetal sheep model and to investigate the contribution of prenatal ultrasound evaluation of CM at the time of prenatal repair. METHODS: A MMC-like lesion was surgically created at 75 days of gestation in 21 fetuses performing a L1-L5 laminectomy followed by an excision of the exposed dura and a midline myelotomy. At a 90-day gestation, among the 19 alived fetuses, a conventional repair of the MMC-like lesion was performed in seven, four of whom underwent cerebral ultrasound (US) examination before the repair. Twelve fetuses remained untreated (control group). All fetuses underwent post-mortem examination (PM) at 138 days. RESULTS: At a 90-day gestation, CM was demonstrated by US examination in all four evaluated fetuses. At birth, CM was found in 3/6 control whether CM was absent in all alived fetuses in the prenatal repair group (n = 4). CONCLUSIONS: Creation of a MMC-like lesion with an additional myelotomy does not always lead to hindbrain herniation. Our study suggests that CM should be assessed by ultrasound examination at the time of the prenatal repair to demonstrate the effectiveness of new techniques for the prenatal repair of MMC.

[Severe neonatal acidosis: comparison and analysis of obstetrical practices in two French perinatal centers]. / Comparaison des taux d'acidose néonatale sévère et analyse des pratiques obstétricales dans deux maternités françaises.

OBJECTIVES: To identify and compare risk factors for severe neonatal acidosis, defined by an umbilical artery pH inferior to 7.00, and clinical practices in two different perinatal centers. PATIENTS AND METHODS: In a retrospective study, from 2003 to 2008, in two university perinatal centers (Poitiers and Saint-Antoine in Paris) on all term pregnancies complicated by severe neonatal acidosis (umbilical artery pH<7.00), we elected to compare the following risk factors: maternal characteristics, medical and obstetrical histories, progress of pregnancy, labour and delivery as well as the neonatal status. RESULTS: Among 23,508 births, 177 term newborns had severe neonatal acidosis. The rate was similar for both perinatal centers of Poitiers and Saint-Antoine (0.92% and 0.77% respectively). Factors associated with severe neonatal acidosis were similar in both centers: maternal age, thick meconium, prior cesarean section. There were differences in obstetrical practices between the two centers: there were more caesarean sections and assisted vaginal deliveries in Paris and more inductions of labour in Poitiers. CONCLUSION: Severe neonatal acidosis is associated with the geographical origin, the progress of labour and the mode of delivery. It seems that severe neonatal acidosis is unrelated to cesarean delivery.

Mycobacterium tuberculosis infection in a dog from Africa.

A 4-year-old male Boxer dog with a history of vomiting, diarrhea, and weight loss moved from West Africa to Lyon, France, where it was further evaluated. Radiographs revealed pleural effusion and enlargement of tracheobronchial lymph nodes and liver. Cytologic examination of the pleural effusion and a fine needle aspirate specimen of the liver showed mixed mononuclear inflammation with nonstaining rod structures within epithelioid histiocytes. At necropsy, the main gross pathologic findings were exudative pleuritis, nodular hepatitis, and infarcts and caseous nodules in the kidneys. The main histologic lesions were granulomatous hepatitis, granulomatous pneumonia, fibrinous leukocytic pleuritis, necrotic and fibro-calcified granulomatous lymphadenitis, and granulomatous nephritis. A Ziehl-Neelsen stain applied to both cytologic and histologic samples was positive for acid-fast bacilli. Bacterial culture of the pleural fluid was positive for Mycobacterium tuberculosis. Cytology is a valuable tool in the diagnosis of this important zoonotic disease.

Genetic diversity of old french six-rowed winter barley varieties assessed with molecular, biochemical and morphological markers and its relation to BaMMV resistance

Twenty-six old French six-rowed winter barley (Hordeum vulgare L.) varieties were characterized for their reaction against barley mild mosaic virus (BaMMV). The genetic diversity of these varieties and two recent barley varieties was assessed using molecular, biochemical and morphological data. Seven old varieties were fully resistant to BaMMV. A higher differentiation level between varieties was observed by using DNA molecular markers compared to biochemical and morphological ones. Correspondence analysis using all markers showed that DNA molecular data could fully discriminate between all varieties, whereas biochemical and morphological markers were not able to achieve a complete discrimination. The dendrogram clustering computed with the DNA marker dissimilarity index showed two main groups. The first group included the seven varieties resistant to the BaMMV, whereas the second contained susceptible varieties. The relationships between these varieties, their diversity level, and their characterization are discussed. We infer that the seven BaMMV-resistant varieties have a common origin.