Artificial uterus: How close is the reality?

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The uterus is just another organ that biomedicine will eventually replace, right? Possibly. Medicine does seem to be going in that direction. In recent years, the media have presented stories, including from this writer, that the era of motherless birth beckons, so we should begin pondering the social-political-economic consequences, as we do with all emerging biotechnologies.

Not so fast — some critics say the debate is getting ahead of itself, that there is no need to even discuss artificial wombs yet for several reasons. The main one is that nobody is currently working to develop one, in part because we don’t understand enough about the placenta.

The first point is true; nobody is working on ectogenesis — the term coined by J.B.S. Haldane in 1924, referring to human development outside the mother, through the entire 40-week process, from conception to birth. However, medical science is moving incrementally toward 40-week ectogenesis by gradually pushing back the age that a fetus can be extracted from a womb and survive.

As for the second point, there have been major advances in the realm of artificial placentas; in fact, that developing technology is why new records for fetal prematurity may be just around the corner. Moreover, a true artificial uterus would not need an artificial placenta. The placenta is part of the conceptus package that develops from a fertilized egg. The interface between machine and biology would be in the tissues on the maternal side of the placenta, not the fetal side, and there’s a driver for advances in this area short of the goal of motherless birth: The need for alternatives to advanced lung support for keeping extremely premature infants alive.

Survival of preterm infants with current technology

The closest phenomenon to motherless human birth is preterm birth slightly later than halfway through pregnancy. Capability for rescuing pre-term infants has been increasing dramatically since the 1970s. This has resulted in an increasing number of premature infants surviving when born at gestational ages down to 23 weeks. At that level of prematurity, survival is still only around 20 percent, but it’s increasing in parallel with technology advances. When it comes to the theoretical minimum survivable gestational age, however, not much has changed for almost 30 years. The record is 21 weeks and five days, set back in 1987, and since then no survival has been reported for anyone born younger than 22 weeks gestation. The situation can be compared with old age, where today, due to improving medical knowledge, an increasing number of people live into their hundreds, but the longest verified life-span of any human is 122 years, 164 days.

Just as the ability for humans to live beyond their early 120s will depend on the advent of new approaches such as gene therapy and stem cell-based treatments, fetuses will begin surviving extraction from the womb at gestational ages below 22 weeks, only when neonatologists implement strategies completely different from those used today. But very different strategies are around the corner.

The reason why fetuses can’t be kept alive outside the mother at gestational ages below 22 weeks has a lot to do with the lungs. Before premature birth, mothers can be given corticosteroid treatment to advance fetal lung maturation. Immature lungs do not produce functional surfactant, a substance that lowers the tension in lungs, but surfactant can be administered into the premature newborn’s lungs so they can stretch better, and the newborn can be mechanically ventilated. These treatments work pretty well for low birth-weight infants born at gestational age of 30 weeks or so, but employing them in infants born at 28, 26, or 24 weeks or lower gets progressively trickier. At 21 weeks gestation, the lungs simply are too premature to work with, so if a fetus is to remain alive, it must receive oxygen, and dispose of carbon dioxide, through a pathway that bypasses the lungs.

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OLYMPUS DIGITAL CAMERA

Of course, there is a pathway for exchanging oxygen and carbon dioxide that bypasses the fetal lungs. It’s the umbilical cord and it connects the fetal circulation to the placenta, which connects with the maternal circulation, while the fetus floats in amniotic fluid inside the uterus. Prior to birth, oxygenated blood from the mother moves through the placenta and umbilical cord and enters the right side of the fetal heart, but most of it does not go to the lungs. That’s because pressure in the fetal lungs is high, plus there are two connections between the right and left circulation, one inside the heart (called the foramen ovale), the other between the pulmonary artery and aorta (called the ductus arteriosus), This anatomy is very different from the arrangement after birth and it allows the oxygen-rich blood from the mother to move directly to fetal body tissues.

Because the lung-supportive treatments used in premature infants today are a delicate balancing act to the point that they become useless below 22 weeks (or in that one case 21 weeks, 5 days), there have been proposals over the last half century to create life-support systems for premature infants that bypass the lungs, similar to how they are bypassed in utero. Now, 50 years ago, the idea was complete science fiction, but the intervening decades saw development of technology called extracorporeal membrane oxygenation (ECMO), which has seen increasing use as a kind of supplemental lung device for people with problems in their pulmonary circulation. Development of ECMO went along with advancing technology used in heart-lung machines, which replaces lungs completely for people going through heart or lung surgery in which the circulation needs to be stopped during the operation. The key technological development has to do with the exchange of gases and precise pumping between blood and air through synthetic membrane-like surfaces. The technology is now so complex that there are ECMO devices that are being called artificial placenta models. These are being studied as an alternative to mechanical ventilation and other lung-based treatments that today are standard for premature infants.

Using an artificial placenta type of device to oxygenate a premature infant’s blood would entail a need to preserve the fetal arrangement of circulation. That means keeping the foramen ovale and ductus arteriosus patent, but that can be done by giving certain treatments and by keeping pressure in the lungs high, which it will be in an infant who is extremely premature and is not given treatments to mature the lungs and make them more elastic.

A complex pathway forward

The process of using an artificial placenta to support a premature infant would involve accessing the umbilical blood vessels and connecting them to the device while inhibiting the process that shifts the anatomy away from fetal circulation. Alternatively, it might make more sense to preserve the fetus’ own placenta, which still would need to integrate with an ECMO system, but this way all of the subtle things that the placenta does that we don’t completely understand will be done.

In either case, the fetus would end up outside of the mother and alive, but it would not be breathing. That potential scenario would change the paradigm regarding fetal viability that underlies current legislative and judicial debates connected with abortion, and raise the question of whether a human developing outside the womb but not yet breathing should be called a premature infant, or an ectogenous fetus.

That would be a qualitative milestone possibly more significant than a quantitative milestone related to pushing back viable gestational age another week or two. Furthermore, depending on it’s gestational age, the fetus/infant might drink formula, but, if removal from the mother is pushed back more, the gastrointestinal tract won’t be any more functional than the lungs. In this case, nutrients would have to be put into the blood along with oxygen, and if the kidneys are not yet working well enough, the placenta will have to be connected  to a dialysis machine to clean the blood.

It’s getting rather complex and becomes more so as we add body systems that may not be functional at earlier and earlier gestational ages, but it’s clear that there is a pathway to ectogenesis. The uncertainly surrounds how many decades it will take to get there, but on the way we also could consider another objection that has been cited against motherless birth, namely that there are other important factors that the mother contributes to fetal development outside the physical and biochemical support that an artificial uterus would replace. The basic argument is that an artificial womb would not be a perfect replace a natural mother no matter how much we learn about the biology, but that could be good or bad. Sure, an artificial womb might be inferior to a healthy mother, but what about a mother who smokes, drinks, is folate deficient, or has any other issue that makes the intrauterine environment less projective than it should be? (No this does not include eating GMO foods, but it could also include mothers who regularly subject their bodies to unproven, untested, unregulated herbal remedies promoted as being healthy on the basis of zero evidence.) Surely, in those cases, the fetus would be better off starting life with no physical connection to the blood stream of such a mother.

David Warmflash is an astrobiologist, physician and science writer. Follow @CosmicEvolution to read what he is saying on Twitter.