From non-invasive to invasive fetal therapy: A comprehensive review and current update.

"Fetus as patient" indicates fundamental concept of fetal therapy. With advance in maternal serum analysis and fetal imaging, prenatal screening has become standard of care. Accurate diagnosis in early gestation allows intervention to reverse pathophysiology and delay progression immediately. Non-invasive, minimally invasive and invasive therapies demonstrate their therapeutic potential in certain diseases. Recently, stem cell and gene therapies have been developed to avoid irreversible impairment. To elevate efficacy of treatment modality, extensive studies should be conducted according to regulatory authority. Striking a balance between scientific and ethical integrity is essential, so long-term follow up should be arranged for protecting mother and fetus.

Integrative Review of Nursing Practices in Fetal Therapy.

OBJECTIVE: To synthesize nursing practices related to fetal therapy (intervention to correct or treat a fetal anomaly). DATA SOURCES: We searched electronic databases, including PubMed, Embase, OvidSP, and CINAHL, for all relevant published work. We identified additional resources through discussion with experts in the field, hand searches of relevant resources, and examination of the reference lists of articles in our search results. STUDY SELECTION: Any published literature about fetal therapy in which nursing practices were discussed by nurses. DATA EXTRACTION: We used Whittemore and Knafl's methodology to guide this integrative review (2005). We completed data extraction using an analytic review template organized to compare results to Kim's (2015) theoretical framework for nursing practice. DATA SYNTHESIS: We used qualitative techniques described by Miles, Huberman, and Saldaña (2014) to code and thematically interpret the data. Nurses described their contributions to the establishment of fetal therapy programs through the development of entirely new technical and caring skills and their work in relation to care quality, clinician education, ethics, research, and health policy. Data were synthesized under three philosophies of nursing practice: therapy, care, and professional work. CONCLUSION: Nurses have made important contributions to the evolving practice of fetal therapy, a nuanced practice that is critical to the development and provision of comprehensive patient- and family-centered care. Clinical implications of this review include practical recommendations for enhanced support of nursing practice in fetal therapy, which includes the provision of reliable forums to learn and share feedback about nursing practice in this field. Future work should focus on increasing understanding and visibility of nursing in fetal therapy through interdisciplinary evidence-based practice development.

A study to assess knowledge and acceptability of foetal surgery for spina bifida amongst healthcare professionals in the UK.

Foetal surgery to repair open spina bifida before birth improves infant motor function and reduces ventriculoperitoneal shunt requirement. Alongside the development of the first UK foetal surgery service, we surveyed the knowledge and acceptability of this treatment to healthcare professionals in the UK and Ireland via an electronic questionnaire. Ninety-eight (98) responses were received: MFM clinicians (21), midwives (20), paediatric neurosurgeons (17), obstetricians (15), neonatologists (13), theatre nurses (11) and commissioners (1). Overall 70% of responders agreed with the concept that foetal surgery improved neonatal outcome in selected cases; although, only 41% of paediatric neurosurgeons agreed. A variety of concerns were expressed, the most common being the lack information regarding mid- to long-term effects on the child and mother.In offering this new service, it is important that we are cognisant of healthcare professional concerns and address them by applying internationally accepted criteria for foetal surgery, emphasising patient choice and collecting long-term data.Impact statementWhat is already known on this subject? Foetal surgery is a potentially controversial intervention, which is increasing in availability globally. Foetal surgery is now available in the UK on a charitable-funding basis. Prior to starting a UK foetal surgery service, we assessed the attitudes and knowledge of healthcare professionals in the UK towards this new surgery.What the results of this study add? Overall the majority of healthcare professionals agree with the concept that foetal surgery improves neonatal outcome in selected cases, but a variety of concerns exist, the most common being the lack of information regarding mid- to long-term effects on the child and mother. Other concerns included a lack of education, training and research; the specific risk of preterm birth following surgery; the evidence base for this procedure; effects on maternal choice and financial implications.What the implications are of these findings for clinical practice and/or further research? Those developing this new service should be mindful of the concerns expressed and address them by applying internationally accepted criteria for foetal surgery, emphasising patient choice and collecting long-term data.

[Advances in fetal surgery]. / Fosterkirurgi är en växande multidisciplinär subspecialitet - Etablerad behandling vid ryggmärgsbråck ­ i framtiden skymtar artificiell placenta och stamcellsterapi.

Advances in fetal surgery Fetal surgery is a subspeciality that is evolving rapidly with focus on improving the natural history of congenital malformations and conditions that are either life threatening or cause severe disability. Fetal surgery for myelomeningocele has been shown to improve neurologic outcome, motor function and to reduce the need of ventriculo-peritoneal shunting after birth compared to postnatal care. However, it conveys an increased risk of preterm birth and maternal morbidity. The role of prenatal intervention with endoscopic tracheal occlusion in congenital diaphragmatic hernia is currently the focus of an ongoing multicenter randomized controlled trial. The trial is comparing the effect of fetal surgery as an alternative to standard postnatal management. The main, but not sole, indication for an Ex-utero intrapartum treatment (EXIT) is airway obstruction due to laryngeal atresia and tumors in the head and neck region. It is a complex procedure that should be performed only in experienced centers with a multidisciplinary team.

New directions in fetal surgery for myelomeningocele.

The treatment of children with myelomeningocele (MMC) has improved over time, from supportive management to early postnatal closure to prenatal repair of the defect. The Management of Myelomeningocele Study (MOMS) showed that prenatal repair of MMC resulted in improved neurological outcomes compared to postnatal closure. Follow-up studies showed that prenatal repair was, as with any other fetal intervention, associated with higher rates of obstetrical complications. There was no significant difference in urological outcomes. Long-term follow-up of ambulatory status, executive functioning, and urological outcomes is needed to determine the durable effects of fetal MMC repair on mobility, functional independence, and the prevalence of renal insufficiency in patients with MMC who survive to adulthood. The future of fetal MMC repair consists of developing strategies to reduce maternal morbidity and improve infant outcomes. Fetoscopic MMC repair has been suggested as an alternative to open repair that may reduce obstetrical complications and the need for cesarean delivery in subsequent pregnancies. Translational research using mesenchymal stromal cells to augment fetal repair of ovine MMC has shown improvement in motor function.

The North American Fetal Therapy Network Consensus Statement: Management of Complicated Monochorionic Gestations.

The North American Fetal Therapy Network is a consortium of 30 medical institutions in the United States and Canada with established expertise in fetal therapy and other forms of multidisciplinary care for complex fetal disorders. This publication is the third in a series of articles written by NAFTNet about monochorionic pregnancies. In this article, we provide the general obstetric practitioner with information regarding management options available for complications of monochorionic gestations. This information may be useful for a better understanding of the pathophysiology of the various conditions, for better patient counseling, for timely referral to a regional treatment center, and for ongoing comanagement after treatment.

Fetal Therapy for Isolated Aqueductal Stenosis.

Aqueductal stenosis (AS) is a form of noncommunicating hydrocephalus, which causes increased intracranial pressure secondary to obstruction of the aqueduct of Sylvius. Relief of intracranial pressure in the fetus by ventriculoamniotic shunting may diminish or even prevent permanent neurologic injury. Shunting was attempted in the 1980s but was abandoned due to technical difficulties. Given the advances in prenatal diagnosis and fetal intervention over the last 3 decades, we believe that an evidence-based reevaluation of the option is timely and appropriate. The aim of this review article is to discuss the clinical significance of the diagnosis of AS, current management strategies, current diagnostic capabilities, new shunt technology, and barriers to progress. Finally, we will advance a research agenda that will provide evidence-based management recommendations.

In utero stem cell and gene therapy: current status and future perspectives.

Advances in prenatal diagnosis have led to the development of fetal therapies for congenital disorders. Although in utero surgical intervention has been used successfully for correction of anatomical defects that cause fetal demise or long-term disability, its clinical indications remain limited. In contrast, prenatal stem cell and gene therapy might have tremendous potential to treat multiple inherited disorders, and could dramatically expand the use of fetal intervention to a wide range of anticipated pediatric and adult diseases. Despite encouraging results from studies in animal models of disease, the clinical utility of such therapies has been restricted by poor efficacy and concerns about safety. The aim of this review is to summarize experimental progress toward clinical application of in utero stem cell transplantation and gene transfer for the treatment of congenital disease.

[Fetal therapy of skeletal dysplasias].

Three types of fetal therapy of skeletal dysplasias, as enzyme replacement, in utero stem cell transplantation, and gene therapy, are reviewed. Clinical trial of recombinant ALP for infantile hypophosphatasia has already started in Japan. In future, such enzyme replacement therapy is expected to be adapted to fetus. There are several reports of mesenchymal stem cell transplantation for osteogenesis imperfecta fetus. These case reports have showed that stem cell transplantation is safe and to some extent works in patients. No clinical trial for gene therapy has been reported. Recently, the study of gene therapy of using HPP fetal mouse showed an excellent therapeutic effect. Fetal therapy of skeletal dysplasias is still the stage of research because of the safety and the ethical issues. However, in order to treat severe cases of skeletal dysplasias which abnormal development has been already completed at birth, fetal therapy at an early stage would be demanded.

Fetal surgery for myelomeningocele: a critical appraisal.

This article narrates the thrilling story of how the pathogenetic understanding of myelomeningocele was fundamentally revised during the last decades and how these new insights, in particular the "two-hit hypothesis," have prepared the terrain for human fetal surgery. Formerly, the devastating cluster of neurologic and neurogenic problems was mainly attributed to the primary malformation, that is, failure of neurulation. At present, there is solid evidence that in early gestation the nonneurulated spinal cord functions well, but suffers from progressive traumatic and degenerative damage in later gestation because it is openly exposed to the amniotic cavity. There is no doubt that the secondary, in utero acquired spinal cord destruction is mainly responsible for the disastrous and irreversible peripheral neurologic deficit present at birth, and there is no doubt either that timely prenatal protective coverage can potentially arrest these deleterious dynamics and preserve neurologic function. Also, tethering of the cord within and constant outflow of cerebrospinal fluid from the lesion are seen as the driving forces behind the Chiari II malformation and consequent ventriculomegaly. Untethering and watertight sealing of the lesion reverses hindbrain herniation and lowers the risk for a relevant hydrocephalus. This article then details how human fetal surgery started in the late 1990s and follows the evolution from the pioneer case studies via the first case series providing encouraging results to the ground breaking Management of Myelomeningocele Study Trial, published in The New England Journal of Medicine in February 2011 by Adzick et al, that has, for the first time, generated unequivocal evidence that patients with prenatal repair do significantly better than those with postnatal care only. Finally, this review looks at several other critical issues, including the hitherto immature endoscopic approach to fetal repair, some future directions of research and clinical practice, and also utters a plea for concentration of these equally rare and complex cases to a few truly qualified centers worldwide. The conclusion derived from all data existing today is that maternal-fetal surgery, although not a cure and not free of risks, represents a novel standard of care for select mothers and their fetuses suffering from one of the most ruinous nonlethal congenital malformations.

Fetal surgery for spina bifida: past, present, future.

Open spina bifida or myelomeningocele (MMC) is a common birth defect that is associated with significant lifelong morbidity. Little progress has been made in the postnatal surgical management of the child with spina bifida. Postnatal surgery is aimed at covering the exposed spinal cord, preventing infection, and treating hydrocephalus with a ventricular shunt. Experimental and clinical evidence suggest that the primary cause of the neurologic defects associated with MMC is not simply incomplete neurulation, but rather chronic, mechanical and amniotic-fluid induced chemical trauma that progressively damages the exposed neural tissue during gestation. The cerebrospinal fluid leak through the MMC leads to hindbrain herniation and hydrocephalus. In utero repair of open spina bifida is now performed in selected patients and presents an additional therapeutic alternative for expectant mothers carrying a fetus with MMC. In the past, studies in animal models and clinical case series laid the groundwork for a clinical trial to test the safety and efficacy of fetal MMC repair. In the present, a prospective, randomized study (the MOMS trial) has shown that fetal surgery for MMC before 26 weeks' gestation may preserve neurologic function, reverse the hindbrain herniation of the Chiari II malformation, and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, this study also demonstrates that fetal surgery is associated with significant risks related to the uterine scar and premature birth. In the future, research will expand our understanding of the pathophysiology of MMC, evaluate the long-term impact of in-utero intervention, and to refine timing and technique of fetal MMC surgery using tissue engineering technology.