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The artificial placenta and EXTEND technologies: one of these things is not like the other

Journal of Perinatology volume 43, pages 1343–1348 (2023)Cite this article

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Abstract

The so called “Artificial Placenta” and “Artificial Womb” (EXTEND) technologies share a common goal of improving outcomes for extreme premature infants. Beyond that goal, they are very dissimilar and, in our view, differ sufficiently in their technology, intervention strategy, demonstrated physiology, and risk profiles that bundling them together for consideration of the ethical challenges in designing first in human trials is misguided. In this response to the commentary by Kukora and colleagues, we will provide our perspective on these differences, and how they impact ethical clinical study design for first-in-human trials of safety/feasibility, and subsequently efficacy of the two technologies.

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References

  1. Gray BW, El-Sabbagh A, Rojas-Pena A, Kim AC, Gadepali S, Koch KL, et al. Development of an artificial placenta IV: 24 h venovenous extracorporeal life support in premature lambs. Asaio J. 2012;58:148–54.

    Article  CAS  PubMed  Google Scholar 

  2. Spencer BL, Mychaliska GB. Milestones for clinical translation of the artificial placenta. Semin Fetal Neonatal Med. 2022;27:101408.

    Article  PubMed  Google Scholar 

  3. De Bie FR, Davey MG, Larson AC, Deprest J, Flake AW. Artificial placenta and womb technology: past, current and future challenges towards clinical translation. Prenat Diagn. 2020;41:145–58.

    Article  PubMed  Google Scholar 

  4. Partridge EA, Davey MG, Hornick MA, McGovern PE, Mejaddam AY, Vrecenak JD, et al. An extra-uterine system to physiologically support the extreme premature lamb. Nat Commun. 2017;8:15112.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Gray BW, El-Sabbagh A, Zakem SJ, Koch KL, Rojas-Pena A, Owens GE, et al. Development of an artificial placenta V: 70 h veno-venous extracorporeal life support after ventilatory failure in premature lambs. J Pediatr Surg. 2013;48:145–53.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gagliardi L, Cavazza A, Brunelli A, Battaglioli M, Merazzi D, Tandoi F, et al. Assessing mortality risk in very low birthweight infants: a comparison of CRIB, CRIB-II, and SNAPPE-II. Arch Dis Child Fetal Neonatal Ed. 2004;89:F419–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hornick MA, Davey MG, Partridge EA, Mejaddam AY, McGovern PE, Olive AM, et al. Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND). J Physiol. 2018;596:1575–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. McGovern PE, Hornick MA, Mejaddam AY, Lawrence K, Schupper AJ, Rossidis AC, et al. Neurologic outcomes of the premature lamb in an extrauterine environment for neonatal development. J Pediatr Surg. 2020;55:2115–23.

    Article  PubMed  Google Scholar 

  9. McGovern PE, Lawrence K, Baumgarten H, Rossidis A, Mejaddam A, Licht DJ, et al. Ex-utero extracorporeal support as a model for fetal hypoxia and brain dysmaturity. Ann Thorac Surg. 2019;109:810–9.

    Article  PubMed  Google Scholar 

  10. Ozawa K, Davey MG, Tian Z, Hornick MA, Mejaddam AY, McGovern PE, et al. Fetal echocardiographic assessment of cardiovascular impact of prolonged support on EXTrauterine Environment for Neonatal Development (EXTEND) system. Ultrasound Obstet Gynecol Off J Int Soc Ultrasound Obstet Gynecol. 2020;55:516–22.

    Article  CAS  Google Scholar 

  11. Bryner B, Gray B, Perkins E, Davis R, Hoffman H, Barks J, et al. An extracorporeal artificial placenta supports extremely premature lambs for 1 week. J Pediatr Surg. 2015;50:44–49.

    Article  PubMed  Google Scholar 

  12. McLeod JS, Church JT, Yerramilli P, Coughlin MA, Perkins EM, Rabah R, et al. Gastrointestinal mucosal development and injury in premature lambs supported by the artificial placenta. J Pediatr Surg. 2018;53:1240–5.

    Article  PubMed  PubMed Central  Google Scholar 

  13. El-Sabbagh AM, Gray BW, Shaffer AW, Bryner BS, Church JT, McLeod JS, et al. Cerebral oxygenation of premature lambs supported by an artificial placenta. ASAIO J. 2018;64:552–6.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Harvey SL, Fallon BP, McLeod JS, Matusko N, Rabah R, Arnold MA, et al. Hepatic function in premature lambs supported by the artificial placenta and total parenteral nutrition. ASAIO J (Am Soc Artif Intern Organs 1992). 2022;68:949–55.

    Article  CAS  Google Scholar 

  15. Church JT, Werner NL, Coughlin MA, Menzel-Smith J, Najjar M, Carr BD, et al. Effects of an artificial placenta on brain development and injury in premature lambs. J Pediatr Surg. 2018;53:1234–9.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Church JT, Coughlin MA, Perkins EM, Hoffman HR, Barks JD, Rabah R, et al. The artificial placenta: continued lung development during extracorporeal support in a preterm lamb model. J Pediatr Surg. 2018;53:1896–903.

    Article  PubMed  PubMed Central  Google Scholar 

  17. McLeod JS, Church JT, Coughlin MA, Carr B, Poling C, Sarosi E, et al. Splenic development and injury in premature lambs supported by the artificial placenta. J Pediatr Surg. 2019;54:1147–52.

    Article  PubMed  PubMed Central  Google Scholar 

  18. McLeod JS, Church JT, Carr B, Poling C, Caceres Quinones M, Hala P, et al. Hepatic effects after support on the artificial placenta. ASAIO J. 2018;64:122.

    Google Scholar 

  19. Bütter A, Piedboeuf B, Flageole H, Meehan B, Laberge JM. Postnatal pulmonary distension for the treatment of pulmonary hypoplasia: pilot study in the neonatal piglet model. J Pediatr Surg. 2005;40:826–31.

    Article  PubMed  Google Scholar 

  20. Muensterer OJ, Flemmer AW, Bergmann F, Hajek KS, Lu HQ, Simbruner G, et al. Postnatal lung mechanics, lung composition, and surfactant synthesis after tracheal occlusion vs prenatal intrapulmonary instillation of perfluorocarbon in fetal rabbits. J Pediatr Surg. 2005;40:26–31.

    Article  PubMed  Google Scholar 

  21. Kotecha S. Lung growth for beginners. Paediatr Respir Rev. 2000;1:308–13.

    CAS  PubMed  Google Scholar 

  22. DiFiore JW, Wilson JM. Lung development. Semin Pediatr Surg. 1994;3:221–32.

    CAS  PubMed  Google Scholar 

  23. Khan PA, Cloutier M, Piedboeuf B. Tracheal occlusion: a review of obstructing fetal lungs to make them grow and mature. Am J Med Genet C Semin Med Genet. 2007;145C:125–38.

    Article  PubMed  Google Scholar 

  24. Carmel JA. Fetal tracheal ligation and lung development. Arch Pediatr Adolesc Med. 1965;109:452.

    Article  CAS  Google Scholar 

  25. Jobe AJ. The new BPD: an arrest of lung development. Pediatr Res. 1999;46:641–3.

    Article  CAS  PubMed  Google Scholar 

  26. Bancalari E, Jain D. Bronchopulmonary dysplasia: 50 years after the original description. Neonatology. 2019;115:384–91.

    Article  PubMed  Google Scholar 

  27. Major TC, Brant DO, Reynolds MM, Bartlett RH, Meyerhoff ME, Handa H, et al. The attenuation of platelet and monocyte activation in a rabbit model of extracorporeal circulation by a nitric oxide releasing polymer. Biomaterials. 2010;31:2736–45.

    Article  CAS  PubMed  Google Scholar 

  28. Fallon BP, Lautner-Csorba O, Major TC, Lautner G, Harvey SL, Langley MW, et al. Extracorporeal life support without systemic anticoagulation: a nitric oxide-based non-thrombogenic circuit for the artificial placenta in an ovine model. Pediatr Res. 2023. https://doi.org/10.1038/s41390-023-02605-2.

  29. Silva ER, Shukla VV, Tindal R, Carlo WA, Travers CP. Association of active postnatal care with infant survival among periviable infants in the US. JAMA Netw Open. 2023;6:e2250593–e2250593.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Antiel RM, Flake AW. Responsible surgical innovation and research in maternal-fetal surgery. Semin Fetal Neonatal Med. 2017;22:423–7.

    Article  PubMed  Google Scholar 

  31. Chervenak FA, McCullough LB. Ethics of maternal-fetal surgery. Semin Fetal Neonatal Med. 2007;12:426–31.

    Article  PubMed  Google Scholar 

  32. Chervenak FA, McCullough LB. The ethics of maternal–fetal surgery. Semin Fetal Neonatal Med. 2018;23:64–67.

    Article  PubMed  Google Scholar 

  33. Raju TN, Mercer BM, Burchfield DJ, Joseph GF. Periviable birth: executive summary of a Joint Workshop by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, Society for Maternal-Fetal Medicine, American Academy of Pediatrics, and American College of Obstetricians and Gynecologists. J Perinatol. 2014;34:333–42.

    Article  CAS  PubMed  Google Scholar 

  34. Khoury MJ, Marks JS, McCarthy BJ, Zaro SM. Factors affecting the sex differential in neonatal mortality: the role of respiratory distress syndrome. Am J Obstet Gynecol. 1985;151:777–82.

    Article  CAS  PubMed  Google Scholar 

  35. Stevenson DK, Verter J, Fanaroff AA, Oh W, Ehrenkranz RA, Shankaran S, et al. Sex differences in outcomes of very low birthweight infants: the newborn male disadvantage. Arch Dis Child Fetal Neonatal Ed. 2000;83:F182–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Flake AW. Artificial Placenta. Artif Organs. 2017;41:A83.

    Google Scholar 

  37. De Bie FR, Kim SD, Bose SK, Nathanson P, Partridge EA, Flake AW, et al. Ethics Considerations Regarding Artificial Womb Technology for the Fetonate. Am J Bioeth. 2023;23:67–78.

  38. Watkins PL, Dagle JM, Bell EF, Colaizy TT. Outcomes at 18 to 22 months of corrected age for infants born at 22 to 25 weeks of gestation in a center practicing active management. J Pediatr. 2020;217:52–8.

    Article  PubMed  Google Scholar 

  39. Bell EF, Hintz SR, Hansen NI, Bann CM, Wyckoff MH, DeMauro SB, et al. Mortality, in-hospital morbidity, care practices, and 2-year outcomes for extremely preterm infants in the US, 2013–2018. Obstet Gynecol Surv. 2022;77:389–91.

    Article  Google Scholar 

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Funding

Funding

AWF has interest in Intellectual Property related to the EXTEND technology and has received consulting fees, grant support, and option rights, related to the EXTEND technology from Vitara Biomedical Inc.

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Authors and Affiliations

  1. Department of Surgery, Center for Fetal Research, Children’s Hospital of Philadelphia, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Alan W. Flake & Felix R. De Bie

  2. Division of Neonatology, Children’s Hospital of Philadelphia, Department of Pediatrics, Perelman School of Medicine, Universityof Pennsylvania, Philadelphia, PA, USA

    David A. Munson

  3. Department of Medical Ethics, Children’s Hospital of Philadelphia, and Departments of Pediatrics and of Medical Ethics and Health Policy, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Chris Feudtner

Authors
  1. Alan W. Flake
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  4. Chris Feudtner
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Contributions

AWF wrote the manuscript, CF helped write the manuscript and helped construct the Tables, FRD reviewed and edited the manuscript, DAM reviewed and edited the manuscript.

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Correspondence to Alan W. Flake.

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As per AWF financial disclosure. There are no other conflicts of interest to disclose.

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Flake, A.W., De Bie, F.R., Munson, D.A. et al. The artificial placenta and EXTEND technologies: one of these things is not like the other. J Perinatol 43, 1343–1348 (2023). https://doi.org/10.1038/s41372-023-01716-2

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