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      Prenatal regenerative fetoscopic interventions for congenital anomalies

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      Publication date (Electronic):
      Journal: BMJ
      Publisher: BMJ

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          Abstract

          Fetal intervention has progressed in the past two decades from experimental proof-of-concept to practice-adopted, life saving interventions in human fetuses with congenital anomalies. This progress is informed by advances in innovative research, prenatal diagnosis, and fetal surgical techniques. Invasive open hysterotomy, associated with notable maternal-fetal risks, is steadily replaced by less invasive fetoscopic alternatives. A better understanding of the natural history and pathophysiology of congenital diseases has advanced the prenatal regenerative paradigm. By altering the natural course of disease through regrowth or redevelopment of malformed fetal organs, prenatal regenerative medicine has transformed maternal-fetal care. This review discusses the uses of regenerative medicine in the prenatal diagnosis and management of three congenital diseases: congenital diaphragmatic hernia, lower urinary tract obstruction, and spina bifida.

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          Lung organogenesis.

          David Warburton, Ahmed El-Hashash, Gianni Carraro … (2009)
          Developmental lung biology is a field that has the potential for significant human impact: lung disease at the extremes of age continues to cause major morbidity and mortality worldwide. Understanding how the lung develops holds the promise that investigators can use this knowledge to aid lung repair and regeneration. In the decade since the "molecular embryology" of the lung was first comprehensively reviewed, new challenges have emerged-and it is on these that we focus the current review. Firstly, there is a critical need to understand the progenitor cell biology of the lung in order to exploit the potential of stem cells for the treatment of lung disease. Secondly, the current familiar descriptions of lung morphogenesis governed by growth and transcription factors need to be elaborated upon with the reinclusion and reconsideration of other factors, such as mechanics, in lung growth. Thirdly, efforts to parse the finer detail of lung bud signaling may need to be combined with broader consideration of overarching mechanisms that may be therapeutically easier to target: in this arena, we advance the proposal that looking at the lung in general (and branching in particular) in terms of clocks may yield unexpected benefits. Copyright 2010 Elsevier Inc. All rights reserved.
          Article 0 comments Cited 127 times – based on 0 reviews     Review now
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            Spina bifida.

            Laura Mitchell, N Scott Adzick, Jeanne Melchionne … (2015)
            Spina bifida results from failure of fusion of the caudal neural tube, and is one of the most common malformations of human structure. The causes of this disorder are heterogeneous and include chromosome abnormalities, single gene disorders, and teratogenic exposures. However, the cause is not known in most cases. Up to 70% of spina bifida cases can be prevented by maternal, periconceptional folic acid supplementation. The mechanism underlying this protective effect is unknown, but it is likely to include genes that regulate folate transport and metabolism. Individuals with spina bifida need both surgical and medical management. Although surgical closure of the malformation is generally done in the neonatal period, a randomised clinical trial to assess in utero closure of spina bifida has been initiated in the USA. Medical management is a lifelong necessity for individuals with spina bifida, and should be provided by a multidisciplinary team.
            Article 0 comments Cited 85 times – based on 0 reviews     Review now
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              Severe diaphragmatic hernia treated by fetal endoscopic tracheal occlusion.

              L Gucciardo, C Alexander Valencia, E Done … (2009)
              To examine operative and perinatal aspects of fetal endoscopic tracheal occlusion (FETO) in congenital diaphragmatic hernia (CDH). This was a multicenter study of singleton pregnancies with CDH treated by FETO. The entry criteria for FETO were severe CDH on the basis of sonographic evidence of intrathoracic herniation of the liver and low lung area to head circumference ratio (LHR) defined as the observed to the expected normal mean for gestation (o/e LHR) equivalent to an LHR of 1 or less. FETO was carried out in 210 cases, including 175 cases with left-sided, 34 right-sided and one with bilateral CDH. In 188 cases the CDH was isolated and in 22 there was an associated defect. FETO was performed at a median gestational age of 27.1 (range, 23.0-33.3) weeks. The first eight cases were done under general anesthesia, but subsequently either regional or local anesthesia was used. The median duration of FETO was 10 (range, 3-93) min. Successful placement of the balloon at the first procedure was achieved in 203 (96.7%) cases. Spontaneous preterm prelabor rupture of membranes (PPROM) occurred in 99 (47.1%) cases at 3-83 (median, 30) days after FETO and within 3 weeks of the procedure in 35 (16.7%) cases. Removal of the balloon was prenatal either by fetoscopy or ultrasound-guided puncture, intrapartum by ex-utero intrapartum treatment, or postnatal either by tracheoscopy or percutaneous puncture. Delivery was at 25.7-41.0 (median, 35.3) weeks and before 34 weeks in 65 (30.9%) cases. In 204 (97.1%) cases the babies were live born and 98 (48.0%) were discharged from the hospital alive. There were 10 deaths directly related to difficulties with removal of the balloon. Significant prediction of survival was provided by the o/e LHR and gestational age at delivery. On the basis of the relationship between survival and o/e LHR in expectantly managed fetuses with CDH, as reported in the antenatal CDH registry, we estimated that in fetuses with left CDH treated with FETO the survival rate increased from 24.1% to 49.1%, and in right CDH survival increased from 0% to 35.3% (P < 0.001). FETO in severe CDH is associated with a high incidence of PPROM and preterm delivery but a substantial improvement in survival.
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                Author and article information

                Journal
                Title: BMJ
                Abbreviated Title: BMJ
                Publisher: BMJ
                ISSN (Electronic): 1756-1833
                Publication date (Electronic): July 01 2020
                Page: m1624
                Article
                DOI: 10.1136/bmj.m1624
                SO-VID: 96bc42ba-58d7-4fcb-a1af-2597cd3a3f17
                Copyright © © 2020
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                http://www.bmj.com/company/legal-information/terms-conditions/legal-information/tdm-licencepolicy

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