BACKGROUND: Myelomeningocele (MMC) is the most serious form of spina bifida, a congenital defect in neural tube development. Defect closure in a patient with an extremely low birth weight presents unique challenges and risks; lower birth weight is associated with multiple organ system concerns, homeostasis is difficult, and local tissue is underdeveloped. To the authors\' knowledge, the present case is the lowest reported weight (490 g) for a neonate with postnatal MMC repair.
METHODS: A preterm male with a prenatally diagnosed lumbosacral MMC and associated Chiari malformation type II was born at 23 weeks 1 day to a 29-year-old mother, gravidity 6 parity 4. The patient was medically stabilized and underwent MMC closure on day of life 5. His weight was 490 g at the time of this repair, and he did not have any surgical complications. At age 16 months, he underwent endoscopic third ventriculostomy with choroid plexus cauterization; he has not required any further hydrocephalus treatments since the last follow-up at 30 months of age.
CONCLUSIONS: To the authors\' knowledge, this case is the lowest birth weight ex utero MMC closure reported in the literature. Challenges of prematurity and size required appropriate preoperative stabilization, careful hemostasis and temperature regulation, and meticulous surgical technique.

Congenital high airway obstruction syndrome is a rare malformation whose prognosis is very poor resulting in foetal or perinatal death if no perinatal intervention is performed. However, ultrasound and magnetic resonance enable an accurate prenatal diagnosis and optimal choice of interventional foetal medicine techniques (transtracheal puncture, fetoscopy). These approaches reduce foetal side effects related to the pathological process, and avoid the mother ex utero intrapartal treatment and its deleterious effects. If it becomes indispensable ex utero intrapartal treatment allows optimal management of the new born by securing the foetal airways while minimizing risk for hypoxic damage through the maintenance of maternal-foetal circulation. We present the story of a couple with a suspected case of CHAOS at 21 weeks of amenorrhea, the diagnostic and the management until the birth of the child.
Le syndrome d’obstruction congénitale des voies respiratoires supérieures est une malformation rare dont le pronostic est très péjoratif sans intervention périnatale, entraînant un décès in utero ou à la naissance. L’échographie et la résonance magnétique nucléaire permettent de poser un diagnostic prénatal précis et de choisir les techniques de médecine fœtale interventionnelle les mieux adaptées (ponction trachéale sous contrôle échographique, reperméabilisation sous fœtoscopie). Ces approches réduisent les effets secondaires fœtaux liés au processus pathologique, et évitent à la mère le traitement intrapartal ex utero et ses effets délétères. S’il devient indispensable, le traitement intrapartal ex utero permet une prise en charge optimale du nouveau-né en sécurisant ses voies respiratoires, tout en minimisant les dommages hypoxiques, grâce au maintien de la circulation materno-foetale. Nous présentons l’histoire d’un couple confronté à une suspicion de CHAOS à 21 semaines d’aménorrhée, le parcours diagnostique et la prise en charge jusqu’à la naissance de l’enfant.

In vitro cultured stem cells with distinct developmental capacities can contribute to embryonic or extraembryonic tissues after microinjection into pre-implantation mammalian embryos. However, whether cultured stem cells can independently give rise to entire gastrulating embryo-like structures with embryonic and extraembryonic compartments remains unknown. Here, we adapt a recently established platform for prolonged ex utero growth of natural embryos to generate mouse post-gastrulation synthetic whole embryo models (sEmbryos), with both embryonic and extraembryonic compartments, starting solely from naive ESCs. This was achieved by co-aggregating non-transduced ESCs, with naive ESCs transiently expressing Cdx2 or Gata4 to promote their priming toward trophectoderm and primitive endoderm lineages, respectively. sEmbryos adequately accomplish gastrulation, advance through key developmental milestones, and develop organ progenitors within complex extraembryonic compartments similar to E8.5 stage mouse embryos. Our findings highlight the plastic potential of naive pluripotent cells to self-organize and functionally reconstitute and model the entire mammalian embryo beyond gastrulation.

The in utero development of mammals drastically reduces the accessibility of the mammalian embryo and therefore limits the range of experimental manipulation that can be done to study functions of genes or signaling pathways during embryo development. Over the past decades, tissue and organ-like culture methods have been developed with the intention of reproducing in vivo situations. Developing accessible and simple techniques to study and manipulate embryos is an everlasting challenge. Herein, we describe a reliable and quick technique to culture mid-gestation explanted mouse embryos on top of a floating membrane filter in a defined medium. Viability of the cultured tissues was assessed by apoptosis and proliferation analysis showing that cell proliferation is normal and there is only a slight increase in apoptosis after 12h of culture compared to embryos developing in utero. Moreover, differentiation and morphogenesis proceed normally as assessed by 3D imaging of the transformation of the myotome into deep back muscles. Not only does muscle cell differentiation occur as expected, but so do extracellular matrix organization and the characteristic splitting of the myotome into the three epaxial muscle groups. Our culture method allows for the culture and manipulation of mammalian embryo explants in a very efficient way, and it permits the manipulation of in vivo developmental events in a controlled environment. Explants grown under these ex utero conditions simulate real developmental events that occur in utero.

Optical projection tomography (OPT) is a technology ideally suited for imaging embryonic organs. We emphasize here recent successes in translating this potential into the field of live imaging. Live OPT (also known as 4D OPT, or time-lapse OPT) is already in position to accumulate good quantitative data on the developmental dynamics of organogenesis, a prerequisite for building realistic computer models and tackling new biological problems. Yet, live OPT is being further developed by merging state-of-the-art mouse embryo culture with the OPT system. We discuss the technological challenges that this entails and the prospects for expansion of this molecular imaging technique into a wider range of applications.