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Unique ethical considerations of the artificial womb and placenta: the threshold for patient eligibility in clinical trials

Journal of Perinatology volume 43, pages 1335–1336 (2023)Cite this article

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After decades of technological development, fetal lamb studies of the artificial womb (AW) and the artificial placenta (AP) have brought both within sight of an exciting milestone: clinical trials. These technologies aim to support extremely premature neonates during a critical period of pulmonary development, providing oxygen via the umbilical vein while the lungs remain fluid-filled. Although both the AW and the AP have the same goal, the timing of their intended application differs [1]. Previous ethical discussions of AW and AP technologies have considered them together with respect to the patients’ terminology (whether fetus, neonate, or a new term entirely [2, 3]), moral status, legal status, and end-of-life considerations, as well as the rights of their parents [4]. However, key differences between the two will have important implications for patient selection in human trials. AP technology may be applied after a failure of conventional therapy, hours or days after delivery, allowing time for postnatal risk stratification. Encouraging AW technology, known as the Extra-uterine Environment for Newborn Development (EXTEND), involves cannulation immediately after cesarean delivery, necessitating decision making based solely on prenatal risk. With a robust, albeit imperfect, outcomes model [5] at their disposal prior to delivery, what threshold for inclusion should be used for EXTEND?

Two important papers on this topic, by Kukora et al. [6] and Flake et al. [7], are presented in this issue of the Journal of Perinatology, providing diverging opinions on patient selection for initial enrollment in clinical trials. When considering the AW, Kukora et al. assert that it should first be used on patients with 80% or higher predicted mortality. Flake et al. contend that the figure of 80% limits their prospective enrollment to only growth-restricted male neonates at 22 weeks; they do not offer an alternative starting threshold. Historically, the criteria for the first ECMO trials in neonates included severe respiratory distress with a predicted mortality of at least 80% [8]. At that time, no validated prediction models existed, so the “predicted mortality” was highly subjective. Nonetheless, there is a precedent for applying new technology to those with a poorer prognosis and more potential benefits. Initial inclusion criteria should be based on ethical considerations of risk and benefit, not on the need to enroll enough subjects. Kukora et al.’s notion of using The Extremely Preterm Birth Outcomes Tool [5] to determine initial eligibility for EXTEND seems appropriate, although where to delineate a sufficiently poor prognosis to justify inclusion in early human trials of the AW remains uncertain.

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Authors and Affiliations

  1. Department of Pediatrics, Columbia University Vagelos College of Physicians and Surgeons, New York, NY, USA

    Kelly M. Werner

  2. Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA

    Alice C. Baker

  3. Program for Biomedical Ethics and Department of Pediatrics, Yale School of Medicine, New Haven, CT, USA

    Mark R. Mercurio

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  1. Kelly M. Werner
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  2. Alice C. Baker
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KMW, ACB, MRM contributed to the theory, writing, editing, and final approval of this manuscript.

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Correspondence to Kelly M. Werner.

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Werner, K.M., Baker, A.C. & Mercurio, M.R. Unique ethical considerations of the artificial womb and placenta: the threshold for patient eligibility in clinical trials. J Perinatol 43, 1335–1336 (2023). https://doi.org/10.1038/s41372-023-01753-x

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