Search

"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., Competing Interests: Declaration of competing interest The authors have no conflict of interest to disclose., (Copyright © 2021. Published by Elsevier B.V.)

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., (Copyright © 2020. Published by Elsevier Inc.)

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 statement What 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 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.

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 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.

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.

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., (Georg Thieme Verlag KG Stuttgart · New York.)

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.

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., (Georg Thieme Verlag KG Stuttgart · New York.)

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., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Congenital adrenal hyperplasia causes genital ambiguity in females affected with the severe form of the disease; yet the abnormality is preventable with prenatal dexamethasone treatment that must be given to the mother before the ninth week of gestation. In the period from 1978 to March 2011 we have made prenatal diagnosis in 719 pregnancies. Our results indicate that the average Prader score of those fetuses treated with dexamethasone was 1.7, which is much lower than the average Prader score of 3.73 in those not treated. While our data demonstrate no significant abnormalities in the long-range medical and cognitive outcomes in patients prenatally treated with dexamethasone, the current protocol involves invasive procedures such as chorionic villus sampling or amniocentesis, and all fetuses are treated unnecessarily for several weeks before the sex and the affection status of the fetus is known. We are collaborating with Dr. Dennis Lo in Hong Kong to develop a noninvasive protocol, whereby at the sixth to seventh week of gestation we can determine the sex and the affection status of the fetus by harvesting fetal DNA from the maternal plasma. The method will eliminate invasive procedures and unnecessary prenatal treatment and bring noninvasive prenatal diagnosis to underdeveloped areas where amniocentesis and chorionic villus sampling are not available., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

During the latter part of the 20(th) century, the fetus became recognized as a patient separate from the mother. Powerful imaging and sampling techniques provided insight into normal fetal development and the opportunity to detect anomalies. In this overview of the rapidly evolving fetal surgery field, we describe the evolution of surgical techniques, clinical trials, and emerging research. We hope to ignite interest among professionals in this growing area of patient care., (© 2012 AWHONN, the Association of Women's Health, Obstetric and Neonatal Nurses.)

Introduction: Fetal gene therapy (FGT) can potentially be applied to perinatally lethal monogenic diseases for rescuing clinically severe phenotypes, increasing the probability of intact neurological and other key functions at birth, or inducing immune tolerance to a transgenic protein to facilitate readministration of the vector/protein postnatally. As the field is still at an experimental stage, there are several important considerations regarding the practicality and the ethics of FGT., Areas Covered: Here, through a review of FGT studies, the authors discuss the role and applications of FGT, the progress made with animal models that simulate human development, possible adverse effects in the recipient fetus and the mother and factors that affect clinical translation., Expert Opinion: Although there are valid safety and ethical concerns, the authors argue that there may soon be enough convincing evidence from non-human primate models to take the next step towards clinical trials in the near future., (© 2011 Informa UK, Ltd.)

Prenatal gene therapy aims to deliver genes to cells and tissues early in prenatal life, allowing correction of a genetic defect, before long-term tissue damage has occurred. In contrast to postnatal gene therapy, prenatal application can target genes to a large population of dividing stem cells, and the smaller fetal size allows a higher vector-to-target cell ratio to be achieved. Early-gestation delivery may allow the development of immune tolerance to the transgenic protein which would facilitate postnatal repeat vector administration if needed. Targeting particular organs will depend on manipulating the vector to achieve selective tropism and on choosing the most appropriate gestational age and injection method for fetal delivery. Intra-amniotic injection reaches the skin, and other organs that are bathed in the fluid however since gene transfer to the lung and gut is usually poor more direct injection methods will be needed. Delivery to the liver and blood can be achieved by systemic delivery via the umbilical vein or peritoneal cavity. Gene transfer to the central nervous system in the fetus is difficult but newer vectors are available that transduce neuronal tissue even after systemic delivery., (Copyright © 2011 John Wiley & Sons, Ltd.)

Progress in prenatal diagnosis can lead to the diagnosis of severe fetal abnormalities for which natural history anticipates a fatal outcome or the development of severe disability despite optimal postnatal care. Intrauterine therapy can be offered in these selected cases. Prenatal diagnosis is the only field of medicine in which termination is an option in the management of severe diseases. Fetal therapy has therefore developed as an alternative to fatalist expectant prenatal management as well as to termination of pregnancy (TOP). There are few standards of fetal care that have gone beyond the stage of equipoise and even fewer have been established based on appropriate studies comparing pre- and postnatal care. Several ethical questions are being raised as fetal surgery develops, including basic Hippocratic principles of patients' autonomy and doctors' duty of competence moving the boundaries between experimental surgery, therapeutic innovation and standard care. In addition, the technical success of a fetal intervention can only rarely fully predict the postnatal outcome. Managing uncertainty regarding long-term morbidity and the possibility for fetal therapy to change the risk of perinatal death into that of severe handicap remains a critical factor affecting women's choice for TOP as an alternative to fetal therapy., (Copyright © 2011 John Wiley & Sons, Ltd.)

The field of neonatal surgery is now inextricably linked to the field of obstetrics. Neonatologists and surgical specialists experienced with the postnatal management and outcomes of infants with various disorders now look in utero along with obstetricians and fetal medicine specialists to characterize the development and well-being of fetuses with congenital anomalies with a goal to optimize fetal, perinatal and postnatal management. The purpose of this article is to examine how prenatal diagnosis and therapy has influenced neonatal surgery. An overview of prenatal diagnosis and the evolution of fetal therapy are provided. In addition, we review the impact of prenatal diagnosis and therapy on the management and outcomes of infants with specific anomalies, including congenital lung malformations, sacrococcygeal teratoma, myelomeningocele, giant fetal neck masses, diaphragmatic hernia and congenital heart defects., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Interventional paediatric and congenital cardiology is expanding at a rapid pace. Validated techniques (such as aortic or pulmonary valve dilatations and occlusion of persistent ductus arteriosus and atrial septal defects) are improving thanks to the use of smaller introducers and sheaths, low-profile balloons and novel devices. Moreover, catheter-based interventions have emerged as an attractive alternative to surgery in other fields: pulmonary valve replacement, balloon and stent implantation for native and recurrent coarctation, and percutaneous closure of ventricular septal defects. On the other hand, percutaneous interventions in the paediatric population may be limited by patient size or the anatomy of the defect. Hybrid approaches involving both cardiac interventionists and surgeons are being developed to overcome these limitations. Based on a better understanding of cardiac development, fetal cardiac interventions are being attempted in order to alter the history of severe obstructive lesions. Finally, some interventional procedures still carry a low success rate-for example, pulmonary vein stenosis, even with the use of conventional stents. Biodegradable stents and devices are being developed and may find an application in this setting as well as in others. The purpose of this review is to highlight the advances in paediatric interventional cardiology since the beginning of the third millennium.

Progress in prenatal diagnosis has led to more frequent detection of fetal abnormalities which, if left untreated, would be fatal or cause severe disabilities despite optimal postnatal care. Intrauterine surgery is possible in selected cases. Most procedures involve microendoscopy with local or regional analgesia. Fetal analgesia is indicated for procedures that are directly invasive for the fetus. Surgical treatment of twin-to-twin transfusion is so far the only example of successful fetal therapy, as demonstrated in a randomized controlled trial. The most severe forms of congenital diaphragmatic hernia may also benefit from temporary occlusion of the fetal trachea in order to allow lung growth and prevent pulmonary hypoplasia. The future of open fetal surgery will depend partly on the results of the ongoing MOM study of intrauterine coverage of myelomeningocele. These developments also raise ethical questions, including the competence of the surgical team, and the borderline between therapeutic innovation, experimental surgery, and standard of care. The possibility of therapeutic termination should not be overlooked.

Gene therapy uses the intracellular delivery of genetic material for the treatment of disease. A wide range of diseases - including cancer, vascular and neurodegenerative disorders and inherited genetic diseases - are being considered as targets for this therapy in adults. There are particular reasons why fetal application might prove better than application in the adult for treatment, or even prevention of early-onset genetic disorders such as cystic fibrosis and Duchenne muscular dystrophy. Research shows that gene transfer to the developing fetus targets rapidly expanding populations of stem cells, which are inaccessible after birth, and indicates that the use of integrating vector systems results in permanent gene transfer. In animal models of congenital disease such as haemophilia, studies show that the functionally immature fetal immune system does not respond to the product of the introduced gene, and therefore immune tolerance can be induced. This means that treatment could be repeated after birth, if that was necessary to continue to correct the disease. For clinicians and parents, fetal gene therapy would give a third choice following prenatal diagnosis of inherited disease, where termination of pregnancy or acceptance of an affected child are currently the only options. Application of this therapy in the fetus must be safe, reliable and cost-effective. Recent developments in the understanding of genetic disease, vector design, and minimally invasive delivery techniques have brought fetal gene therapy closer to clinical practice. However more research needs to be done in before it can be introduced as a therapy.