A Possible New Way to Protect the Brains of Newborns Who Suffer Oxygen Loss at Birth

A closer look at a clinical trial of citicoline in babies with hypoxic-ischaemic encephalopathy who could not receive cooling treatment (Salamah et al., Italian Journal of Pediatrics, 2023)

When a baby's brain is briefly starved of oxygen and blood flow around the time of birth, the result can be a serious condition called hypoxic-ischaemic encephalopathy, or HIE. The one proven treatment — cooling the baby's body for three days — only works for certain infants and must start within six hours of birth, leaving many babies with no protective option. In a trial of 80 newborns who could not be cooled, doctors in Egypt gave half of them a medicine called citicoline and the other half a placebo. The babies who received citicoline had fewer seizures, spent fewer days on a breathing machine and in intensive care, had clearer brain scans, and scored better on developmental tests by their first birthday. The medicine appeared safe. It is an early and promising result, though it needs to be confirmed by larger studies before it becomes standard care.

Why This Research Matters

Birth is safe for the vast majority of babies, but occasionally something interrupts the flow of oxygen and blood to a baby's brain — a problem with the placenta, the umbilical cord, or the delivery itself. When that happens, brain cells can be injured, and the baby may be born floppy, not breathing well, and at risk of seizures. This injury, HIE, is one of the more common causes of death and long-term disability in newborns. It affects roughly 1 to 2 in every 1,000 babies in wealthy countries, but many more — up to about 26 in 1,000 — in parts of the world with fewer medical resources [1], [2]. How badly a baby is affected depends on how severe the injury was: some recover fully, while others face lifelong challenges with movement, learning or seizures [3].

How Families and Doctors Used to Face This

For a long time, there was very little doctors could actively do for a baby with HIE beyond supportive care — helping the baby breathe, supporting blood pressure, and treating seizures — and then waiting to see how the brain recovered. Families were often left with agonising uncertainty and no treatment aimed at the injury itself. That changed about two decades ago, when large studies showed that gently lowering a baby's body temperature by a few degrees for three days, a treatment called therapeutic hypothermia or "cooling," could reduce the chance of death or serious disability [4], [5]. Cooling became the standard treatment and remains the only proven one. But it comes with strict rules: the baby usually has to be born close to full term, weigh at least about 2 kilograms, and start cooling within six hours of birth, in a specialised intensive care unit. Babies born too early, too small, too far from such a unit, or recognised too late simply cannot receive it. And a major study in South Asia found that cooling did not help — and might even have caused harm — in lower-resource hospitals, meaning it cannot simply be copied everywhere [6]. This left a real gap: a large group of vulnerable babies with no treatment for their brain injury. Researchers have tested several medicines to fill it, but none has yet proven reliably effective [7].

What the Researchers Studied

The medicine in this trial, citicoline, is a substance the body naturally uses to build and repair the outer membranes of nerve cells. It has been used for years in adults recovering from strokes and head injuries, where it appears to help protect and heal brain tissue, and it has a good safety record [8], [9]. The researchers wondered whether it could also protect newborn brains after oxygen loss.

To find out, they enrolled 80 newborns with moderate or severe HIE at two university hospitals in Egypt between 2019 and 2021 [10]. Importantly, every baby in the study was one who could not be cooled — so the choice was not between citicoline and cooling, but between citicoline and no active brain treatment. By the toss of a computer-generated coin, half the babies were given citicoline through a vein twice a day for four weeks, and half were given a placebo (an inactive substitute). Neither the families nor the doctors assessing the babies knew which treatment each baby had received, which keeps the results fair. All the babies received the same standard care otherwise. The doctors then followed the children for a year, checking their development at 3, 6, 9 and 12 months using a standard test, and performing brain scans at four weeks [11].

What They Found

The two groups of babies were very similar to begin with, so any differences afterward could reasonably be linked to the medicine [10]. The developmental test scores started out similar in both groups but pulled apart as the babies grew: by 9 months and again at 12 months, the citicoline babies scored significantly higher, closer to the normal range. This gradual improvement fits the idea that the medicine helps the brain repair itself over time rather than working instantly.

The other results pointed the same way. Among babies given citicoline, seizures were less common during treatment, and after going home only 2 of 40 (5%) still had seizures, compared with 11 of 40 (about 28%) in the placebo group. Citicoline babies also needed a breathing machine for about half as long (roughly 11 days versus 21), left intensive care sooner (about 26 days versus 34), and were less likely to need blood-pressure medications. Their brain ultrasound and MRI scans were more often normal — MRI was clear in 75% of citicoline babies versus about 48% of the others. The medicine was well tolerated; the only side effect was mild, temporary diarrhoea in four babies, which went away on its own [10].

What This Means for Families

For a parent whose baby has HIE, the most important thing to know is that this is genuinely encouraging news, but it is early news. Cooling is still the proven, recommended treatment for babies who qualify, and nothing here changes that [5]. What this study adds is the first careful, fair test suggesting that a safe and inexpensive medicine might help the babies who cannot be cooled — a group that until now had no treatment aimed at the brain injury. It is worth being clear-eyed, too: this was a single, fairly small study that followed babies for only one year. A good result at twelve months is reassuring but does not tell the whole story, because some difficulties with movement, learning or attention only become clear as a child grows and starts school. That is why children who have had HIE continue to have their development checked for years [12].

If your baby has been affected by HIE, the practical takeaways are to make sure your baby is assessed quickly for cooling if eligible, to expect close monitoring for seizures, and to stay engaged with the long-term follow-up appointments that track your child's development. Citicoline is not yet something to ask for as a standard treatment, but it is a real and hopeful avenue that researchers are actively pursuing.

What Researchers Are Working On Next

The scientists behind this study are careful to call citicoline "promising," not "proven." The natural next step is a much larger study, run across many hospitals, testing different doses and following the children for at least two years to see whether the early developmental gains hold up [3]. Researchers are especially interested in whether citicoline could help in lower-resource parts of the world, where cooling is often unavailable or does not work as well, and where a cheap, easy-to-store medicine could reach many more babies [6]. They also want to learn whether citicoline might add benefit even for babies who do receive cooling. For now, it stands as one of the more hopeful leads in the long effort to give every newborn with a brain injury a real chance at a healthy future [10].

References

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