Could Donated Cord Blood Help Protect a Premature Baby's Eyes?

What the BORN trial (Teofili and colleagues, Italian Journal of Pediatrics, 2024) found when it gave the smallest babies a gentler kind of blood transfusion

Very premature babies often need blood transfusions, and those transfusions usually use blood donated by adults. A trial in Italy asked a new question: what if the blood came instead from donated umbilical cords, which is naturally richer in the type of hemoglobin a baby is born with? In its first 58 babies, this cord-blood approach was just as safe as standard transfusions, and there were early hints it might help protect against a serious eye disease of prematurity. The findings are promising but preliminary.

Why this question matters for families

The study behind this article, called the BORN trial, set out to test exactly that idea in four large hospitals in Italy [1]. To understand why it matters, it helps to know what these babies are up against. When a baby is born months too early, almost every organ is still under construction — including the eyes. One of the conditions parents in the neonatal intensive care unit (NICU) hear about is retinopathy of prematurity, or ROP, a disease in which the delicate blood vessels at the back of the eye grow abnormally. Most cases are mild and resolve on their own, but severe ROP can threaten a child's sight and remains one of the leading causes of childhood blindness worldwide. Thanks to steady progress in newborn care, more extremely premature babies survive than ever before [2], yet severe ROP has not become rarer in step with those gains [3]. That is why researchers keep looking for new ways to prevent it.

How babies used to face this problem

For decades, the main tools against ROP have been careful control of the oxygen babies breathe, regular eye examinations, and treatments — laser or injections — for eyes that have already developed advanced disease. These approaches help, but they mostly manage the disease once the risk is present rather than removing a cause. It helps to picture what is happening inside the eye. In a baby born close to term, the blood vessels that nourish the retina have nearly finished growing. In a baby born at 24 or 25 weeks, that network is barely started, and the sudden change from the low-oxygen world of the womb to the oxygen-rich world outside can throw its growth off course — first stalling the vessels, then later triggering a burst of abnormal, fragile ones that can scar and pull on the retina. Doctors had long noticed something puzzling: the premature babies who received the most blood transfusions also tended to develop more ROP [4]. The reason seems to lie in the blood itself. Babies are born with "fetal hemoglobin," a form of hemoglobin that holds onto oxygen tightly. Standard transfusions from adult donors replace it with "adult hemoglobin," which releases oxygen more readily. Studies found that babies whose fetal hemoglobin dropped the most were more likely to develop ROP [5][6], which led some doctors to ask whether adult donor blood was really the right choice for the tiniest infants [7]. An early, small study showed that red cells taken from donated umbilical cord blood could raise a baby's blood counts just as well as adult blood while keeping fetal hemoglobin high [8]. That encouraging result set the stage for a proper trial [9].

What the researchers did

BORN is a carefully designed study — randomized, meaning babies were assigned by chance to one of two groups, and double-blinded, meaning neither the parents nor the treating doctors knew which type of blood a baby was receiving [1]. It ran in four large Italian NICUs, with cord blood supplied by six public cord-blood banks. Babies born between 24 and nearly 28 weeks of pregnancy were enrolled. Half were assigned to receive ordinary adult-donor red cells, and half to receive red cells prepared from donated cord blood, from birth until they reached about 32 weeks of adjusted age. To keep the study fair and blinded, both kinds of blood were delivered in identical bags. The main goal of the full trial, which plans to enroll 146 babies, is to compare how many develop severe ROP. Because giving cord blood this way was such a new idea, the team paused after the first 58 babies to check, above all, that it was safe.

What they found in the first 58 babies

The safety news was reassuring. Across the 58 babies — 28 who received adult blood and 30 assigned to cord blood — the number and seriousness of medical complications were very similar in the two groups, and the overall survival rate did not differ [1]. Importantly, none of the complications could be blamed with certainty on a transfusion, and the handful of problems that might possibly have been transfusion-related all followed adult-donor blood, not cord blood. Even though the cord-blood units were older and slightly more dilute, the babies' blood chemistry after transfusion — the salt, acid, and lactate levels doctors watch closely — looked just as stable. This was the single most important thing the researchers wanted to know before going further, because cord-blood units are smaller and stored differently, and there had been a reasonable worry that they might be harder on a tiny, fragile baby. That worry did not materialize.

Then came the more surprising part. Among the 44 babies who could be examined for ROP, 10 developed the severe form. When the researchers looked simply at the group each baby had been assigned to, the two groups looked alike — but that comparison was muddied by a practical problem, described below. When they instead looked at what each baby had actually received in the crucial first weeks, a pattern appeared: not a single baby who received only cord-blood cells in that early window developed severe ROP, whereas babies who received adult blood did. Each adult-blood transfusion in those early weeks was linked to a higher risk of severe ROP [1]. The researchers also measured fetal hemoglobin over time and found that babies who kept it higher, especially in the earliest weeks, were less likely to develop severe eye disease — fitting neatly with earlier work showing that adult blood delivers more oxygen to a baby's tissues than cord blood does [10].

What this means for families right now

It is important to be clear-eyed about what this study does and does not show. This was an early look at a small number of babies, designed mainly to check safety, and the encouraging eye findings come from a secondary analysis rather than the trial's main comparison. A real-world hurdle also complicated the results: cord-blood units are small and must pass extra safety checks, so in nearly 4 in 10 cases a baby assigned to cord blood had to be given adult blood because a matching cord-blood unit was not available. The babies who did worst were simply the sickest, needing the most transfusions of any kind. So the honest summary today is that cord-blood transfusion appears safe and looks promising for protecting vision, but it is not yet a proven treatment or a standard part of NICU care. Families will not need to make any decision about it outside of a research study. What remains true and reassuring is that NICU teams already work hard to reduce the number of transfusions a baby needs and to protect the eyes through oxygen management and regular screening. Because severe ROP is also a signal that a child may need extra developmental follow-up as they grow [11], that ongoing attention matters regardless of which blood a baby received.

What researchers are working on next

The BORN team has already used what they learned to improve the study. Because the earliest weeks appear to matter most, they adjusted the trial so that the limited supply of cord blood is focused on the youngest babies, when it may do the most good and when shortages caused the biggest problems. The next milestone is completing the full trial of 146 babies — more than double the number reported so far — to see whether the early hint of eye protection holds up when tested in the way that gives the most reliable answer. Beyond that, larger studies across more hospitals will be needed, along with a hard look at whether cord-blood banks can reliably supply this kind of blood if it proves to work. There is also something hopeful in where the cord blood comes from. It is donated by families after a healthy full-term birth, from the umbilical cord that would otherwise be discarded, and it is screened, matched, and treated with the same care as any other blood a baby receives. In other words, one baby's healthy start could one day help protect the eyes of another born far too soon. What makes this line of research striking is its simplicity: it does not add a drug or a procedure, but reconsiders something already given every day in the NICU, asking whether a gentler, more natural kind of blood might give the smallest babies a better start — including a clearer view of the world.

References

  1. Teofili L, Papacci P, Dani C, et al. Cord blood transfusions in extremely low gestational age neonates to reduce severe retinopathy of prematurity: results of a prespecified interim analysis of the randomized BORN trial. Italian Journal of Pediatrics. 2024;50(1):142. doi:10.1186/s13052-024-01714-w ↩
  2. Stoll BJ, Hansen NI, Bell EF, et al. Trends in care practices, morbidity, and mortality of extremely preterm neonates, 1993–2012. JAMA. 2015;314(10):1039–51. doi:10.1001/jama.2015.10244 ↩
  3. Good WV. Retinopathy of prematurity incidence in children. Ophthalmology. 2020;127(4S):S82–3. doi:10.1016/j.ophtha.2019.11.026 ↩
  4. Hellström A, Smith LE, Dammann O. Retinopathy of prematurity. Lancet. 2013;382(9902):1445–57. doi:10.1016/S0140-6736(13)60178-660178-6) ↩
  5. Stutchfield CJ, Jain A, Odd D, Williams C, Markham R. Foetal haemoglobin, blood transfusion, and retinopathy of prematurity in very preterm infants: a pilot prospective cohort study. Eye (Lond). 2017;31(10):1451–5. doi:10.1038/eye.2017.76 ↩
  6. Jiramongkolchai K, Repka MX, Tian J, et al. Lower foetal haemoglobin levels at 31- and 34-weeks post menstrual age is associated with the development of retinopathy of prematurity: PacIFiHER Report 1. Eye (Lond). 2021;35(2):659–64. doi:10.1038/s41433-020-0938-5 ↩
  7. Gavulic AE, Dougherty D, Li SH, et al. Fetal hemoglobin levels in premature newborns. Should we reconsider transfusion of adult donor blood? Journal of Pediatric Surgery. 2021;56(11):1944–8. doi:10.1016/j.jpedsurg.2021.04.018 ↩
  8. Teofili L, Papacci P, Orlando N, et al. Allogeneic cord blood transfusions prevent fetal haemoglobin depletion in preterm neonates. Results of the CB-TrIP study. British Journal of Haematology. 2020;191(2):263–8. doi:10.1111/bjh.16851 ↩
  9. Teofili L, Papacci P, Orlando N, et al. BORN study: a multicenter randomized trial investigating cord blood red blood cell transfusions to reduce the severity of retinopathy of prematurity in extremely low gestational age neonates. Trials. 2022;23(1):1010. doi:10.1186/s13063-022-06949-8 ↩
  10. Pellegrino C, Papacci P, Beccia F, et al. Differences in cerebral tissue oxygenation in preterm neonates receiving adult or cord blood red blood cell transfusions. JAMA Network Open. 2023;6(11):e2341643. doi:10.1001/jamanetworkopen.2023.41643 ↩
  11. Blencowe H, Lee AC, Cousens S, et al. Preterm birth-associated neurodevelopmental impairment estimates at regional and global levels for 2010. Pediatric Research. 2013;74(1):17–34. doi:10.1038/pr.2013.204 ↩