Limitations of neonatal intensive care

The occurrence and severity of complications associated with preterm birth decline markedly with increased gestation.12 Neonates born before 26 weeks gestation remain unlikely to survive common complications.12 Around 50% of surviving preterms at 26 weeks have a severe long-term impairment. This increases to 75% among those born at 23 weeks.10 The biggest issues plaguing preterms include: underdeveloped lungs and respiratory problems, circulatory problems causing low blood pressure and oxygen deprivation and an underdeveloped ability to swallow or suck.12 These complications are almost inevitable before 26 weeks. They can be managed by providing mechanical ventilation, administering oxygen, using external pumps to aid circulation and nasogastric feeding.12 These functions are all interventions facilitated in infant incubators, and they each carry risks and limitations. Mechanical ventilation and the administration of oxygen can hinder further lung development or damage the lungs.13 External aids for circulation can cause heart failure by effecting imbalances in blood flow.13 Nasogastric feeding carries a high risk of necrotising enterocolitis (death and leakage of intestinal tissue)14 and infection.12

Due to the risks and limitations of interventions, some scientists believe the clinical possibilities of NIC have been exhausted.15 There is only so much medicine can do for a neonate born without the capacity for an independent life. This is why between 60% and 80% of NIC deaths occur after withdrawal of interventions.11 Conventional NIC also raises ethical concerns. When treatment is withdrawn, as is often the case, all treatment achieved was the prolonging of the neonate’s physical suffering and the emotional distress of its parent/s. Possible alternative forms of intervention to those used routinely will still harbour risks and similar barriers to success. With this in mind, researchers are seeking an alternative physiological approach to sustaining underdeveloped human beings by better mimicking the uterine environment to effectively prolong gestation.ⁱ ,16 This encompasses a support system closer to an AW, facilitating continuing development as if the neonate had never been born, as opposed to infant incubators assisting preterms with bodily functions they cannot perform adequately for themselves.

The biobag

In early testing, the newly designed AW was able to sufficiently mimic the uterine environment to sustain preterm lamb ‘fetuses’ for 4 weeks.1 These lambs were developmentally equivalent to human preterms at the recognised viability threshold: 24 weeks. After the incubation period, all subjects were ‘delivered’ and survived. News of the Philadelphia-based team’s success made global headlines.17

The biobag consists of a sealed bag to contain the subject, a ‘pump-less oxygenator circuit’ and umbilical cord access. The sealed system prevents outside exposure, minimising the risk of infection. The bag enables constant exchange of amniotic fluid, providing all necessary water and nutrients. Cannulae act as an ‘umbilical cord’ carrying required nutrients and oxygen into the subject’s bloodstream. Circulation is dependent on the subject’s heart working with an oxygenator. This mimics normal placental circulation, ensuring sufficient oxygen and a safe blood pressure.1 The biobag effectively simulates natural gestation in utero. All biobag test subjects had continued normal lung development and circulation without any infection.1 The three most common complications (lung development, circulation, infection) experienced in NIC appear to have been sidestepped. Another research team based in Australia has also developed an AW system with comparable success in animal studies.16 The AW this team has developed, however, is not the focus of this paper because the team are more tentative about the potential clinical application of their technology in humans.16 The enormity of these findings, and their capacity to reduce morbidity among preterms, is hard to overstate.

Further refinement of the biobag as well as scientific and safety validation is necessary before clinical use can be anticipated.1 It seems probable, however, that we are only several years away from testing on human subjects.13 If the results of this animal study are repeated with similar success there will soon be calls for its use from parents trying to overcome troubled pregnancies18 or aid preterm children. The biobag study authors identify their ‘clinical target population’ as preterms between 23 and 25 weeks gestation.1 The researchers comment that if animal testing continues to yield positive results the morbidity rate among human preterms alone justifies use of the technology.1 They are already foreseeing the clinical application of the biobag.ⁱⁱ The team’s brief mention of a justification for experimental use implies they see no meaningful difference between the AW they have designed and NIC relevant to decision-making about its use. It could be argued there is no difference for now, because the objective of the technology’s use will be similar to NIC. However, because of the implications that will be explored the assumption that there is little difference between AWT and current NIC must be critiqued.

The innate features of AWT

When two medical technologies provide the same function they can be treated as interchangeable, unless the process of each markedly distinguishes them. Medical and surgical remedies, for example, are distinguished by comparative invasiveness. AWT and conventional NIC both support underdeveloped humans. Hendricks observes, however, that AWT is different in nature because it provides more comprehensive support.23 Current care is dependent on the preterm ‘tolerating artificial ventilation’, which is limited by a natural threshold of lung development. This threshold does not limit the AW because it better resembles natural gestation,23 and thus does not rely on the lungs for gas exchange. There appears to be no natural limit, at least related to lung development, restricting the AW.

The inherent difference between AWT and NIC is more nuanced than its effect on one aspect of development. AWT has the capacity to entirely replace a human function: it works by replicating and replacing a biological process, rather than attempting a rescue. This makes it, in effect, a move into the realm of automation. The purpose of AWT is to treat a gestateling as if it had never been born, and thus requires the gestateling to exercise, regardless of its capabilities, no independent capacity for life. The traditional infant incubator, in contrast, has the purpose of only supporting what capacity for life the newborn is already exercising or beginning to exercise. Therefore, the neonate shoulders some of the burden of sustaining itself. The gestateling, however, has no such pressure incumbent on them during partial ectogenesis. AWT requires of its subject no exercise of any independent capacity for life. If the AWT were switched off or malfunctioned, an underdeveloped gestateling would die just as a fetus would in utero during a severe placental abruption. The underdeveloped premature neonate in an infant incubator that is then switched off, however, might survive a short time before life functions dwindled. AWT is closer to technologies sustaining individuals with brain stem death, than to forms of artificial support provided to comatose patients with working nervous systems still coordinating some important bodily functions. The latter is more comparable to NIC.

Rieder argues that when physicians, at present and with only current technologies available, engage in the resuscitation and treatment of extremely premature infants they effectively take over the process of creating them.24 He argues that conventional NIC does not rescue when used to aid extremely premature infants, but attempts to uptake the creative process and ‘artificially continue gestation’. He posits this observation needs little defence.24 It is my contention, however, that his observations work when applied to technologies like the biobag, but are misplaced when applied to conventional NIC. Rieder conflates a human being continuing to develop with gestation (the creative process). Gestation, whether in or ex utero, is distinct from ‘continuing to develop after being born’. Human beings continue to develop long after the gestational process is complete, for example as part of development continuing into childhood.25 Gestation, however, is different in that it is a process of formation, which if not completed adequately the human being has no capacity for life independent. The limitations of conventional NIC demonstrate it is not capable of anything other than providing assistance with life functions a preterm is struggling to perform itself. Conventional NIC is not a ‘creative process’, AWT, however, is.

A further distinction between AWT and conventional NIC is in environment. Intensive assistance with life functions is wholly invasive, and yet also leaves the preterm exposed and within an environment where some human interaction (skin-to-skin contact) is possible. The gestateling in the biobag, however, is encased and support is almost entirely non-invasive. Support mechanisms surround rather than aggressively invade the gestateling. One imagines the process of AWT would be less stressful and painful for the developing human. Less is required of, and there is less to disturb, the gestateling. Notably, AWT is so unique in method that outcomes will be different and, outside of one study, are unknown. There is no way of knowing now, or anytime soon, what the long-term implications of artificial gestation might be. Gestatelings may be subjects of a research trial long after removal from the biobag. For some time, the biobag will remain a new experimental treatment, while conventional NIC is business as usual. The unknown implications should encourage some caution.

The subject of partial ectogenesis

AWT could in theory, and possibly in practice, support a gestateling unable to exercise any independent life functions ex utero at all. The marked difference in terms of gestational age, and consequent abilities, of the subject potentially sustained by each support mechanism is striking. Hendricks argues the status of the subject would, therefore, be an important distinguishing factor. We may be inclined to accept that AWT is different because it can sustain something that ‘does not look like a baby’.23 Whether there is any difference in moral status between the gestateling and the premature neonate is beyond the scope of this paper. There is, however, based on their dissimilarities in development and appearance, a huge difference in their capacities. This difference is meaningful in terms of the function technology must serve to sustain them.

Let us assume AWT does not confuse the viability threshold further and it has the same natural limitations as NIC in terms of the subjects it could support.ⁱⁱⁱ There remains a distinction in the way the subjects behave. The significance of the subjects’ contributing, or not, to their own survival has already been highlighted. Additionally, the premature neonate is available for social interaction, can experience the benefits of connection with other human beings and become embedded in social networks. Other individuals can interact directly and physically with it. The gestateling is shut off from the outside world and does not touch, smell or interact with anything other than its artificial gestator. This isolation will influence the perception of and, on occasion, the feeling attached to each entity. These perceptions will impact, in various meaningful ways, on the decision-making of those surrounding the gestateling.

Potential uses of partial ectogenesis

Finally, AWT introduces opportunities beyond more efficacious care for preterms. Partial ectogenesis, once AWs are available, could become a distinct course of action in obstetrics to manage dangerous pregnancies. A dangerous, but wanted, pregnancy is not wholly uncommon and the choices at present seem painfully bleak. When pregnancy threatens a woman’s life, she is usually advised to have an abortion. The alternative is that she continues the pregnancy hoping she survives long enough to deliver a healthy child, but taking the risk that neither she, nor her fetus, will survive. In 2016, Heidi Loughlin faced this decision after being diagnosed with a cancer untreatable during pregnancy. Loughlin refused to accept there was no alternative to choosing between her life and her fetus. She elected for a third choice: remaining pregnant until 28 weeks and opting for premature delivery. Unfortunately, the premature neonate did not survive long after delivery.26 This decision was partial ectogenesis in action, but before AWT was available. An AW, were it accessible, may have changed the odds. AWT might encourage more women with dangerous pregnancies to make Loughlin’s choice. It might even be that, in future, women wish to opt for AWT over continuing pregnancy in situations of less concern, for example to avoid unpleasant symptoms like morning sickness. AWT is, therefore, distinct from rescue technologies because it introduces the possibility of the extraction of gestatelings that would never have existed ex utero otherwise. AWT in these situations performs the function of reliably sustaining gestatelings removed from pregnant women and unable to sustain themselves. However, AWT is then functionally not just about ‘sustaining a fetus/gestateling’ but enabling pregnant women to choose an alternative to pregnancy without risking the loss of the product of reproduction. NIC, because of its risks and limitations, will never be considered a reliable enough alternative to gestation to enable this choice.

If AWT is chosen as an alternative to the ‘dangerous pregnancy-abortion’ dichotomy, an extraction procedure will be part of the therapeutic process and is also experimental. A safe method of extraction, potentially a ‘more complex and intricate’ C-Section must be developed27 28 inevitably involving trial and error. We are considering experimenting on gestatelings and also potentially considering experimenting on the women who carried them.