Why Some Babies Who Are Cooled After Birth Turn Out to Have a Different Condition

What a study of 92 cooled newborns in Türkiye by Donmez, Serce Pehlevan and Gunlemez tells families about diagnosis, uncertainty and good care

Doctors cool some newborn babies who show signs of brain injury after a difficult birth, because lowering the body temperature for three days protects the brain. A study from Türkiye found that about one in ten cooled babies turned out to have a different underlying condition — a tumour, a genetic condition or a metabolic disorder. The researchers are clear that cooling should still start straight away; what matters is that doctors keep asking questions alongside it.

How Cooling Became Standard Care

The study behind this article was carried out at a large neonatal unit in Türkiye and published in 2026 [1]. To understand it, it helps to know how cooling came to exist at all. Some babies are born unwell in a particular way: floppy, unresponsive, not feeding, sometimes having seizures in the first hours or days. Doctors call this picture neonatal encephalopathy, which simply means "the newborn brain is not working normally". It is a description of what is seen, not an explanation of why [2].

For a long time, the assumption was that the cause was nearly always the same: the baby had been short of oxygen and blood flow around the time of birth. That specific cause has its own name — hypoxic–ischaemic encephalopathy, usually shortened to HIE. But careful counting across whole populations showed something more complicated. When researchers looked at every baby in a region born with this picture, only a proportion had clear evidence of oxygen deprivation during labour; infections, congenital conditions and problems that began long before labour accounted for a meaningful share [3].

Meanwhile, laboratory research had found something remarkable. After the brain is deprived of oxygen, much of the damage does not happen immediately. It unfolds over the following hours and days, as injured cells run out of energy in a second wave. Cooling the body slows that second wave down, and several large trials tested whether this worked in real babies. The CoolCap trial, an international study across multiple hospitals, cooled the head with mild whole-body cooling in 234 babies born at or near term [4]. The NICHD Whole-Body Hypothermia trial, run by the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network in the United States, cooled the whole body in babies born at 36 weeks or later who arrived within six hours of birth [5]. The TOBY trial, coordinated from the United Kingdom with hospitals in other countries taking part, cooled babies to 33.5°C for 72 hours [6]. Later trials tested the edges: the HELIX trial (Hypothermia for Encephalopathy in Low and Middle-Income Countries) in India, Sri Lanka and Bangladesh, and the Preemie Hypothermia trial in the same United States research network, which studied babies born at 33 to 35 weeks [7],[8]. Together these made cooling the standard treatment it is today, recommended by the American Academy of Pediatrics in 2026 [9] and supported by international reviews of the evidence [10].

Here is the catch, and it is the reason this study exists. Cooling only works if it starts within about six hours of birth — far too soon for anyone to know the true cause of a baby's condition. Genetic tests take weeks. Metabolic tests take days. A brain scan usually waits until the baby is stable. So the decision to cool has to be made using signs available immediately: how acidic the baby's cord blood was, the Apgar scores, how much resuscitation was needed, how the nervous system behaves on examination, and a simplified brain-wave monitor at the cot side.

Those signs were chosen to catch babies who had been short of oxygen, but they are not exclusive to oxygen deprivation. A baby with a tumour pressing on the windpipe, a genetic muscle condition, or an inherited disorder of how the body makes energy can each be born floppy, need resuscitation, and have a low Apgar score and an abnormal brain-wave trace. In that first hour they can look identical. Doctors have known for years that this happens [11], and expert reports have long warned against assuming that "brain not working normally" automatically means "oxygen deprivation at birth" [12]. Harder to answer is a practical question: among the babies a real hospital actually cools, how often does this happen, and does anything at the bedside give it away?

What the Researchers Did

Three doctors in Türkiye set out to answer that [1]. They looked back through the records of every baby cooled at their hospital — a large regional centre that receives babies transferred in from elsewhere — over four years, from January 2019 to January 2023. Ninety-two babies had been cooled. For each, the researchers asked what the final diagnosis turned out to be once all the tests, scans and specialist opinions were in.

Eighty-three of the 92 babies (90%) did have brain injury from lack of oxygen and blood flow, as originally suspected. Nine — about one in ten — turned out to have something else as the main underlying problem. Two had neuroblastoma, a tumour arising from developing nerve tissue; in one baby it was in the abdomen, in the other in the chest, pressing on the airway. Two had chromosomal or syndromic conditions: one had Down syndrome with a heart defect, and one had trisomy 13 with a heart malformation and an abdominal wall defect. Two had inherited metabolic disorders — conditions in which the body cannot process certain chemicals normally. One had congenital myotonic dystrophy, an inherited muscle condition. One had osteogenesis imperfecta, sometimes called brittle bone disease, with multiple fractures and bleeding inside the head. And one had a complex congenital condition affecting the automatic drive to breathe.

One of those nine deserves a special mention, because it shows what finding the right answer can achieve. That baby had pyridoxine-dependent epilepsy — a rare condition in which seizures do not respond to normal seizure medicines but do respond to vitamin B6. When the baby was given pyridoxine, the seizures and the brain-wave trace improved markedly. Without asking the question, that treatment would never have been given.

What the Study Found

The central finding is a difficult one. At the moment the cooling decision had to be made, these nine babies were indistinguishable from the other 83. Their gestational age, birth weight, Apgar scores, cord blood acid levels, neurological examination grades and brain-wave patterns showed no meaningful differences. Whatever made them different was not visible in the things doctors look at first. The researchers also tested four calculations based on ordinary blood tests, hoping one might act as a warning flag. None worked.

What did differ was everything happening outside the brain. Seven of the nine babies with alternative diagnoses (77%) showed signs of heart muscle injury on blood tests, compared with 19 of the 83 (22%). Six of the nine (66%) had a severely low platelet count — platelets are the blood cells that help clotting — compared with 21 of 83 (25%). Eight of the nine (88%) had been born by caesarean section, compared with 34 of 83 (41%).

The differences afterwards were larger still, and sobering. Babies in the alternative-diagnosis group stayed in the neonatal unit for a median of 28 days, compared with 7. Five of the nine died, compared with five of the 83. These are small numbers carrying heavy meaning; they reflect how serious the underlying conditions were, not a failure of the cooling treatment.

What This Means for Families

The most important message, and the one the researchers themselves emphasise most strongly, is this: cooling should not be delayed while doctors work out the cause. Waiting to be certain would mean some babies who genuinely need cooling would miss the narrow window in which it helps. The risk of withholding it from a baby who needs it is greater than the risk of cooling a small number of babies who turn out to have another condition. If your baby was cooled, that was the right decision on the information available at the time.

The second message is about how diagnosis works in a neonatal unit. It is a process, not a single moment. The first days are about supporting a very sick baby and starting a time-critical treatment; the weeks that follow are about answering why. If a diagnosis changes later, that is not a mistake being corrected — it is medicine doing what it is supposed to do. Knowing that in advance can make a later conversation far less bewildering.

The third is that you can ask. If something about your baby's course does not seem to fit — if problems in the heart, the blood, the breathing or the muscles seem out of proportion to the brain picture, or if recovery is not following the path you were told to expect — it is entirely reasonable to ask whether other causes have been considered. Good neonatal teams welcome that question, and this study is a reminder to clinicians to keep asking it themselves.

What Researchers Are Working On Next

This was a single hospital looking back at its own records, and only nine babies had alternative diagnoses — enough to raise a question but not to settle it, and the researchers are careful to say so. Because the tests each baby received were not identical, and because brain scans were not available for four of the nine — some too unwell, some dying too soon — the true figure may be higher than one in ten rather than lower.

Three lines of work follow. The first is larger studies across many hospitals, where every baby receives the same investigations, so a reliable figure can be established. The second is better and more standardised use of brain imaging: scans done at agreed times and scored in a consistent way, since early scans can look misleading in babies whose problem is genetic or metabolic rather than oxygen-related [13]. The third, and probably the most important, is speed in genetic testing. Studies have found genetic diagnoses in roughly a quarter of babies who were initially labelled as having oxygen-related brain injury and who went on to have their genes sequenced [14]. In this Turkish hospital, genetic confirmation required sending samples to outside laboratories, with results arriving long after the treatment decisions had been made. Rapid sequencing that returns an answer in days rather than weeks would change that entirely — turning an explanation that arrives too late into one that can guide care while the baby is still in the unit.

Expert groups are also working to standardise how and when babies with encephalopathy are scanned and assessed, so findings from one hospital can be compared meaningfully with another [15]. The direction of the field is towards precision: not abandoning cooling, which works, but getting better at knowing quickly which baby is in front of you [16]. For families, that means fewer weeks of uncertainty, earlier access to condition-specific treatments where they exist, and more accurate answers to the question every parent asks first — what happened to my baby, and why.

References

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