The news has been all over a study on premature fetal lambs being maintained in a Biobag (i.e. outside of the uterus) and growing and developing normally. This technology is specifically being developed with extremely premature infants in mind, the kind of babies who are just a week or two away from survival. Babies who are just like my son Aidan who was born at 22 weeks and 3 days and succumbed to prematurity.
Because of my personal connection with prematurity, one son who died and two born at 26 weeks, I am very curious about advances for extremely premature infants. As I started reading the various posts about the study and then the study itself I began to get pretty deflated because it seemed once again we had an example of some interesting basic science being presented and practically promoted as if it were ready for prime time. In almost every article I read the researchers seemed to feel they are just a few years from petitioning the FDA for human trials. This quote is from the Washington Post,
To recap, investigators at CHOP developed an extra-uterine device that was capable of sustaining fetal lambs for up to 4 weeks. The lambs grew appropriately and when sacrificed under the microscope the brain and lung development was appropriate. The full article is here. I also contacted a couple of neonatologists to get their takes.
This is cool and a definite advancement, but to say this will be tested on premature infants in 1-2 years seems awfully hopeful. I just can’t wrap my head around how this interesting piece of basic science that seems quite far from human trials is everywhere. The idealist in me says this was just super cool and everyone got excited (and the photos are fascinating), but the cynic in me says this is a play for press from CHOP to raise funds. The accompanying video very much tugs at the heart-strings (BTW this was a first for me, a promotional video for basic science research). You can see the video if you go to the Washington Post’s piece I linked to above.
The press release does gloss over the major issues with the study. This is what the press release says, “The researchers will continue to evaluate and refine the system, and will need to downsize it for human infants, who are one-third the size of the infant lambs used in the current study.” Here is what actually happened, when tested on lambs of appropriate size the system failed. Dr. Emily Hahn, a neonatology and bioethics fellow, pointed out researchers would need to prove this model works on a 500 g fetal sheep for starters. This is from the publication:
In addition to failing on an appropriately sized fetus the ovine brain develops differently than the human brain. One of the biggest issues for premature infants is bleeding into the brain, specifically an area called the germinal matrix. The ovine germinal matrix is already developed long before the lambs were delivered into the Biobag, but that would not be the case for a 23-week human infant. The authors rightfully point that they cannot assess the risk of brain bleeds, which is probably the biggest cause of serious long term morbidity for extremely premature infants. Lung disease does improve slowly over time for most preemies, brains don’t repair themselves so this is a major hurdle that would need to be addressed before it would be ethical to study on humans.
The system requires a low dose of heparin (blood thinner) to stop clotting and this need for heparin and the vulnerability of the premature infant brain to bleeding are major reasons that have limited the use of a similar type of technology called ECMO to infants over 34 weeks and more than 2,000 grams. ECMO is basically a very high tech way to get oxygen into the blood when the lungs have to be bypassed, it is temporary advanced life support when the lungs have failed. This Biobag model is more advanced than ECMO as it is simulating the placenta, but I think you have to prove that the issues with ECMO will not be the issues here. Heparin doses are likely lower with the Biobag, but brain bleeds are a big deal. Testing the technology of primates might be one way to get a better idea of how premature human infants might respond, but chimps are no longer being used in human research and primate research is harder and harder to do.
Other issues are this technology likely requires a c-section so the umbilical cord can be hooked up immediately. These kinds of early c-sections at 22-23 weeks can damage the uterus potentially affecting future child-bearing. There is also the issue of screening for infection, which commonly associated with premature delivery. And then a fetus delivered via c-section under real world premature delivery situations is not at all similar to a planned c-section in a lab under controlled circumstances.
I feel like I am coming off as a big Debbie Downer here, but I just can’t see how based on the published data this is anywhere close to human trials. This is cool technology, but there are huge hurdles to overcome and it would be unethical to consider human trials until this technology can be shown to work for a 500 g fetus that has brain development that more closely matches a human in a delivery situation that could be realistically approximated. It just seems like a lot of hype for something that based on the publication still seems to be in very early stages. Perhaps I got so hopeful reading the headlines thinking that soon other parents might not have to go through what I did and then I quickly realized that it still seems very far from reality and that, well, hurt.