FETAL INTERVENTIONS: THE HISTORY, MODERN ACHIEVEMENTS, DEVELOPMENT PROSPECTS AND PROBLEMS
Abstract
Fetal surgery is becoming today one of the leading areas in the treatment of congenital malformations of the fetus. More than 60 years have passed since the first documented fetal intervention happened. Despite the obvious prospects, the development of fetal medicine is associated with many medical, technical, legal and ethical problems. The article presents the history of the formation of this field of medicine in the world and in Russia, modern approaches to surgical interventions in the fetus, considers current problems of determining indications for antenatal correction of various pathologies, the need for adequate relief of pain sensitivity in the fetus and eliminating or minimizing risks for the mother. Currently, in world practice, both surgical operations on the fetus and minimally invasive fetoscopic techniques, as well as intrapartum surgical treatment of the fetus (EXIT, Ex Utero Intrapartum Treatment), are used. In addition to surgical methods, therapeutic methods are being actively developed, both using mother’s circulatory system and intrauterine intravascular administration of drugs. Summarizing the opinion of authoritative specialists in medicine and law on the prospects for the development of this field, the authors presented their views and focused on ethical and legal issues. Undoubtedly, fetal surgery is a science-intensive and high-tech field of medicine that requires a high level of funding and staffing, legal regulation, and information transparency. However, the development of this area corresponds to the principles of humanism, the high value of human life, when every member of society can and should count on comprehensive help and support from the entire society.
References
Башмакова Н.В., Косовцова Н.В. Фетальная хирургия: достижения и проблемы. Доктор.Ру. 2017;13(142) — 14(143):31–36.
Ковалев В.В. Пренатальная диагностика состояния плода. Учебное пособие. Екатеринбург: УГМУ; 2019.
Конституция Российской Федерации (принята всенародным голосованием 12.12.1993) (с учетом поправок, внесенных Законами РФ о поправках к Конституции РФ от 30.12.2008 № 6-ФКЗ, от 30.12.2008 № 7-ФКЗ, от 05.02.2014 № 2-ФКЗ, от 21.07.2014 № 11-ФКЗ, от 30.12.2008 № 6-ФКЗ и № 8-ФКЗ)
Миткинов О.Э., Горбачев В.И. Плод как пациент: правовые коллизии критических состояний в акушерстве и неонатологии. Вестник интенсивной терапии имени А.И. Салтанова. 2018;4:26–29.
Морозов Д.А. Проблемы законодательного регулирования детской хирургии и хирургии плода в российской Федерации. Российский вестник детской хирургии, анестезиологии и реаниматологии. 2018;8(2):6–15. DOI:10.30946/2219-4061-2018-8-2-6-15.
Приказ Минздрава России от 20.10.2020 № 1130н «Об утверждении Порядка оказания медицинской помощи по профилю “акушерство и гинекология”» (зарегистрировано в Минюсте России 12.11.2020 № 60869).
Туманова У.Н., Шувалова М.П., Щеголев А.И. Анализ статистических показателей врожденных аномалий как причины ранней неонатальной смерти в Российской Федерации. Российский вестник перинатологии и педиатрии. 2018;63(6):60–67. DOI: 10.21508/1027-4065-2018-63-5-60-67.
American College of Pediatricians — January 2021. Fetal Pain: What is the Scientific Evidence? Issues Law Med. 2021;36(1):113–122.
Basurto D., Russo F.M., Van der Veeken L. et al. Prenatal diagnosis and management of congenital diaphragmatic hernia. Best Pract Res Clin Obstet Gynaecol. 2019;58:93–106. DOI: 10.1016/j.bpobgyn.2018.12.010.
Begović D. Maternal-Fetal Surgery: Does Recognising Fetal Patienthood Pose a Threat to Pregnant Women’s Autonomy? Health Care Anal. 2021;29:301–318. DOI: 10.1007/s10728-021-00440-2.
Bellieni C.V. Analgesia for fetal pain during prenatal surgery: 10 years of progress. Pediatr Res. 2021;89(7):1612–1618. DOI: 10.1038/s41390-020-01170-2.
Bellieni C.V., Vannuccini S., Petraglia F. Is fetal analgesia necessary during prenatal surgery? J Matern Fetal Neonatal Med. 2018;31(9):1241–1245. DOI: 10.1080/14767058.2017.1311860.
Clewell W.H., Johnson M.L., Meier P.R. et al. A surgical approach to the treatment of fetal hydrocephalus. N Engl J Med. 1982;306:1320–5.
Cruz-Martínez R., Chavelas-Ochoa F., Martínez-Rodríguez M. et al. Open Fetal Microneurosurgery for Intrauterine Spina Bifida Repair. Fetal Diagn Ther. 2021;48(3):163–173. DOI: 10.1159/000513311.
Deprest J.A., Nicolaides K.H., Benachi A., Gratacos E. et al. TOTAL Trial for Severe Hypoplasia Investigators. Randomized Trial of Fetal Surgery for Severe Left Diaphragmatic Hernia. N Engl J Med. 2021;385(2):107–118. DOI: 10.1056/NEJMoa2027030.
Deprest J.A., Flake A.W., Gratacos E. et al. The making of fetal surgery. Prenat Diagn. 2010;30:653–67.
Derbyshire S.W., Bockmann J.C. Reconsidering fetal pain. J Med Ethics. 2020;46(1):3–6. DOI: 10.1136/medethics-2019-105701.
DiFiore J.W., Fauza D.O., Slavin R. et al. Experimental fetal tracheal ligation and congenital diaphragmatic hernia: a pulmonary vascular morphometric analysis. J Pediatr Surg. 1995;30:917–923.
Evans L.L., Harrison M.R. Modern fetal surgery — a historical review of the happenings that shaped modern fetal surgery and its practices. Transl Pediatr. 2021;10(5):1401–1417. DOI: 10.21037/tp-20-114.
Harrison M.R. The University of California at San Francisco Fetal Treatment Center: a personal perspective. Fetal Diagn Ther. 2004;19:513–524.
Harrison M.R., Adzick N.S., Bullard K.M. et al. Correction of congenital diaphragmatic hernia in utero VII: a prospective trial. J Pediatr Surg. 1997;32:1637–1642.
Harrison M.R., Filly R.A., Golbus M.S. et al. Fetal treatment 1982. N Engl J Med. 1982;307:1651–1652.
Jaiman S., Romero R., Bhatti G. et al. The role of the placenta in spontaneous preterm labor and delivery with intact membranes. J Perinat Med. 2022;50(5):553–566. DOI: 10.1515/jpm-2021-0681.
Jeanty C., Derderian S.C., Mackenzie T.C. Maternal-fetal cellular trafficking: clinical implications and consequences. Curr Opin Pediatr. 2014;26(3):377–382. DOI: 10.1097/MOP.0000000000000087.
Joshi H., Packiasabapathy S. Anesthetic Management of Ex Utero Intrapartum Treatment (EXIT) and Fetal Surgery. 2023 May 29. In: Stat Pearls [Internet]. Treasure Island (FL): Stat Pearls Publishing; 2024.
Joyeux L., De Bie F., Danzer E. et al. Learning curves of open and endoscopic fetal spina bifida closure: a systematic review and meta-analysis. Ultrasound Obstet Gynecol. 2020;55:730–739.
Kabagambe S.K., Lee C.J., Goodman L.F. et al. Lessons from the Barn to the Operating Suite: A Comprehensive Review of Animal Models for Fetal Surgery. Annu Rev Anim Biosci. 2018;6:99–119. DOI: 10.1146/annurev-animal-030117-014637.
Kelly E.N., Seaward G., Ye X.Y. et al. Short- and long-term outcome following thoracoamniotic shunting for fetal hydrothorax. Ultrasound Obstet. Gynecol. 2021;57:624–630.
Liley A.W. Intrauterine Transfusion of Foetus in Haemolytic Disease. Br. Med. J. 1963;2:1107–1109.
Mallmann M.R., Graham V., Rösing B. et al. Thoracoamniotic shunting for fetal hydrothorax: Predictors of intrauterine course and postnatal outcome. Fetal
Diagn. Ther. 2017;41:58–65.
Meuli M., Meuli-Simmen C., Yingling C.D. et al. In utero repair of experimental myelomeningocele saves neurological function at birth. J Pediatr Surg. 1996;31:397–402.
Moon-Grady A.J., Baschat A., Cass D. et al. Fetal Treatment 2017: The Evolution of Fetal Therapy Centers — A Joint Opinion from the International Fetal Medicine and Surgical Society (IFMSS) and the North American Fetal Therapy Network (NAFTNet). Fetal Diagn Ther. 2017;42:241–248.
Morris R.K., Malin G.L., Quinlan-Jones E. et al. Percutaneous vesicoamniotic shunting in Lower Urinary Tract Obstruction (PLUTO) Collaborative Group. Percutaneous vesicoamniotic shunting versus conservative management for fetal lower urinary tract obstruction (PLUTO): a randomised trial. Lancet. 2013;382(9903):1496–506. DOI: 10.1016/S0140-6736(13)60992-7.
Novoa R.H., Quintana W., Castillo-Urquiaga W. et al. EXIT (ex utero intrapartum treatment) surgery for the management of fetal airway obstruction: A systematic review of the literature. Journal of Pediatric Surgery. 2020;55:1188–1195. DOI: 10.1016/j.jpedsurg.2020.02.011.
Restrepo O.I., Prieto Soler M.P. Dolor fetal y susconsideraciones bioéticas [Fetal pain and its bioethical considerations]. Cuad Bioet. 2022;33(107):55–66. DOI: 10.30444/CB.113. (In Spanish).
Ruano R. Prenatal regenerative fetoscopic interventions for congenital anomalies. BMJ. 2020;370:m1624. DOI: 10.1136/bmj.m1624.
Russo F.M., De Bie F., Hodges R. et al. Sildenafil for antenatal treatment of congenital diaphragmatic hernia: from bench to bedside. Curr Pharm Des. 2019;25:601–608.
Sacco A., Ushakov F., Thompson D. et al. Fetal surgery for open spina bifida. Obstet Gynaecol. 2019;21(4):271–282. DOI: 10.1111/tog.12603.
Sagar R., Götherström C., David A.L. et al. Fetal stem cell transplantation and gene therapy. Best Pract Res. 2019;58:142–153.
Sharma D., Tsibizova V.I. Current perspective and scope of fetal therapy, part 1. J Matern Fetal Neonatal Med. 2022;35(19):3783–3811. DOI: 10.1080/14767058.2020.1839880.
Smajdor A. Ethical challenges in fetal surgery. Journal of Medical Ethics. 2011;37(2):88–91.
Spiers A., Legendre G., Biquard F., Descamps P., Corroenne R. Ex utero intrapartum technique (EXIT): Indications, procedure methods and materno-fetal complications — A literature review, Journal of Gynecology Obstetrics and Human Reproduction. 2022;51(1):102252. DOI: 10.1016/j.jogoh.2021.102252.
Suyama F., Ozawa K., Ogawa K. et al. Fetal lung size after thoracoamniotic shunting reflects survival in primary fetal hydrothorax with hydrops. J Obstet Gynaecol Res. 2018;44:1216–1220.
Vander Wall K.J., Skarsgard E.D., Filly R.A. et al. Fetendo-clip: a fetal endoscopic tracheal clip procedure in a human fetus. J Pediatr Surg.1997;32:970–972.
Van Mieghem T., Al-Ibrahim A., Deprest J. et al. Minimally invasive therapy for fetal sacrococcygealteratoma: case series and systematic review of the literature. Ultrasound Obstet Gynecol. 2014;43:611–619. DOI: 10.1002/uog.13315.
