Cooling Babies After a Difficult Birth: Why the Same Treatment Works Differently in Different Parts of the World

A plain-language guide to a new review of eleven trials in India, Uganda, Bangladesh and Sri Lanka, and what it means for families

Cooling a newborn's body for three days after oxygen loss at birth is standard treatment in wealthy countries, but researchers have long questioned whether it helps in places with fewer intensive care resources. A new review of eleven trials involving 1,324 babies found that cooling did not clearly change survival, but that among babies who did survive, far fewer were left with lasting disability. The findings reopen a question many had considered closed.

What Happens When a Baby Loses Oxygen at Birth

Most births go well. Occasionally something interrupts a baby's oxygen supply during labour or delivery — the placenta separates early, the umbilical cord is compressed, or labour becomes obstructed. When the interruption is severe enough, the baby's brain can be injured. Doctors call the resulting condition hypoxic-ischaemic encephalopathy, usually shortened to HIE. "Hypoxic" means low oxygen, "ischaemic" means reduced blood flow, and "encephalopathy" simply means the brain is not working normally. Babies with HIE may be floppy or stiff, feed poorly, have seizures, or be difficult to rouse.

HIE is not rare, and it is not evenly distributed. Around 2.4 million newborn babies die worldwide each year, and the great majority of those deaths happen in the world's poorest countries. Problems during labour and delivery account for roughly a quarter of deaths linked to birth itself [1]. Careful international studies of why children under five die have consistently found that these birth-related complications remain one of the largest causes, concentrated in South Asia and sub-Saharan Africa [2]. In other words, the babies most likely to be affected live in exactly the places where hospitals have the least equipment.

How Cooling Became the Standard Treatment — and Where

The idea behind cooling is that brain injury after oxygen loss does not happen all at once. There is an initial injury, and then, over the following hours and days, a second wave of damage as injured cells release harmful chemicals. Lowering the baby's body temperature by about three and a half degrees Celsius slows that chemical cascade and gives the brain a chance to recover.

Between 2005 and 2009, three large studies established that this works. A study run by the United States National Institute of Child Health and Human Development across fifteen hospitals cooled 208 babies and found that fewer of them died or were seriously disabled by around eighteen months of age [3]. The Cooling Cap trial (known as CoolCap), carried out in twenty-five hospitals in the United Kingdom, United States and New Zealand, cooled babies' heads rather than their whole bodies and found the benefit was greatest for babies whose brain-activity recordings were less severely abnormal [4]. The Total Body Hypothermia trial (TOBY), run in forty-two units across the United Kingdom, Hungary, Israel, Finland and Sweden, found that babies who survived had better neurological outcomes, although the same number died [5]. In 2013, researchers combined eleven such studies covering 1,505 babies and concluded the treatment was effective [6]. Cooling became routine — in hospitals that could provide it.

That last phrase matters. All of these studies were done in well-equipped intensive care units, with machines that hold a baby's temperature to within a fraction of a degree, ventilators, blood tests available around the clock and blood products on hand. Whether cooling would help a baby in a hospital without those things was never tested by those trials.

Why the Question Became So Difficult

Researchers tried to answer it, and the answers conflicted. An early 2013 attempt to combine studies from poorer countries found no clear survival benefit, but the studies were small and came from countries at very different levels of development [7]. A small trial at Mulago Hospital in Kampala, Uganda, cooled babies using a mattress made from three ordinary water bottles filled with cool tap water — and showed that the right temperature could be reached and held without expensive machinery. With only 36 babies, though, it could not say whether the treatment helped [8].

Then, in 2021, a large study changed the conversation. The HELIX trial — the name stands for Hypothermia for Encephalopathy in Low- and middle-Income countries — was run in seven specialist newborn intensive care units in India, Sri Lanka and Bangladesh. It found no benefit at eighteen months, and, more alarmingly, that more of the cooled babies died. Its researchers recommended that cooling not be offered in these settings at all [9]. A further combined analysis published in 2022 came to similarly cautious conclusions, though it included studies from wealthier middle-income countries such as China and Turkey [10].

What the New Review Did

The team behind the new review argued that lumping all "lower-income" countries together hid something important, because a hospital in China or Turkey may have far more resources than one in Uganda or rural India. So they repeated the analysis using only trials carried out in the poorest group of countries, as classified by the World Bank. They registered their plan publicly in advance and followed international reporting standards for this kind of review, so their methods could be checked [11].

They searched six research databases and found 3,237 possible studies. After careful screening, eleven trials involving 1,324 babies qualified. Nine were from single hospitals in India, one was the Ugandan water-bottle study [8], and one was HELIX [9]. Every trial cooled babies within six hours of birth and held their temperature between 33°C and 34°C for 72 hours. Some used cool gel packs, some used special heat-absorbing material, one used the water bottles, and one used a machine. The studies measured very different things — one Indian study of 50 babies used a detailed brain scan measurement as its main result rather than how the children were doing later [12].

What They Found

Among the four trials that followed children to six months of age or beyond, 34.6% of cooled babies had died or had a significant disability, compared with 44.7% of babies who were not cooled. Put in everyday terms, that is about 98 fewer children affected for every 1,000 treated. The researchers rated their confidence in this result as low, because the studies disagreed with each other considerably.

Looking at survival on its own — across all eleven trials — 21.6% of cooled babies died compared with 23.4% who were not cooled. That difference is small enough that it could easily be chance, and the researchers rated their confidence in it as very low. This is an honest way of saying: we cannot tell whether cooling helps or harms survival in these settings.

The clearest result was about disability among children who survived. Here, 6.5% of cooled children had a moderate or severe disability compared with 18.9% of those not cooled — roughly 125 fewer affected children per 1,000. The studies agreed closely with one another on this point, and the researchers rated their confidence as moderate, their highest rating in the review.

Cooling also carried costs. Low platelet counts, which affect the blood's ability to clot, occurred in 15.6% of cooled babies compared with 7.5%. Significant bleeding occurred in 32.9% compared with 21.7%. Infection was slightly more common but not clearly so.

What This Means for Families

If your baby has been affected by oxygen loss at birth, the honest summary is this: in a hospital with the staff, monitoring and blood-testing facilities to do it safely, cooling appears to offer a meaningful chance of a better neurological future for a child who survives. It has not been shown to improve the chance of survival itself in these settings, and it does carry real risks of bleeding problems that need close monitoring.

It is also fair to say that this review does not settle the question. Nine of its eleven studies came from India, so it says very little about African hospitals — the only African evidence is that one small Ugandan study [8]. And the largest, most carefully run study in the group, HELIX, pointed in the opposite direction from the smaller ones [9]. Reasonable doctors currently disagree, and if your hospital does not offer cooling, that decision reflects genuine scientific uncertainty rather than neglect.

One broader point is worth holding onto: a treatment that works in one group of babies does not automatically work in another. Researchers recently tested cooling in babies born a few weeks early, at 33 to 35 weeks, in well-resourced American hospitals, and it did not produce the same benefit seen in full-term babies [13]. Medicine has to test each new situation rather than assume.

What Researchers Are Working On Next

Three things would help most. First, well-designed trials in Africa, where almost no evidence currently exists. Second, studies in which the people assessing children's development do not know which treatment the child received, which removes an important source of unconscious bias. Third — and perhaps most promising — researchers want to pool the individual records of all the babies in these eleven trials, rather than just the summary numbers, so they can ask whether the babies who did badly in HELIX had a different kind of brain injury, one that began before labour started rather than during it [1]. If that turns out to be true, it may become possible to identify in advance which babies cooling will help and which it will not — which would be a far better answer than a single yes or no for an entire half of the world.

References

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  2. Perin J, Mulick A, Yeung D, et al. Global, regional, and national causes of under-5 mortality in 2000–19: an updated systematic analysis with implications for the Sustainable Development Goals. Lancet Child & Adolescent Health. 2022;6(2):106–115. doi:10.1016/S2352-4642(21)00311-400311-4) ↩
  3. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic–ischemic encephalopathy. New England Journal of Medicine. 2005;353(15):1574–1584. doi:10.1056/NEJMoa053391 ↩
  4. Gluckman PD, Wyatt JS, Azzopardi D, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365(9460):663–670. doi:10.1016/S0140-6736(05)17946-X17946-X) ↩
  5. Azzopardi DV, Strohm B, Edwards AD, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. New England Journal of Medicine. 2009;361(14):1349–1358. doi:10.1056/NEJMoa0900854 ↩
  6. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database of Systematic Reviews. 2013;2013(1):CD003311. doi:10.1002/14651858.CD003311.pub3 ↩
  7. Pauliah SS, Shankaran S, Wade A, Cady EB, Thayyil S. Therapeutic hypothermia for neonatal encephalopathy in low- and middle-income countries: a systematic review and meta-analysis. PLoS ONE. 2013;8(3):e58834. doi:10.1371/journal.pone.0058834 ↩
  8. Robertson NJ, Nakakeeto M, Hagmann C, et al. Therapeutic hypothermia for birth asphyxia in low-resource settings: a pilot randomised controlled trial. Lancet. 2008;372(9641):801–803. doi:10.1016/S0140-6736(08)61329-X61329-X) ↩
  9. Thayyil S, Pant S, Montaldo P, et al. Hypothermia for moderate or severe neonatal encephalopathy in low-income and middle-income countries (HELIX): a randomised controlled trial in India, Sri Lanka, and Bangladesh. Lancet Global Health. 2021;9(9):e1273–e1285. doi:10.1016/S2214-109X(21)00264-300264-3) ↩
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  11. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71 ↩
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  13. Faix RG, Laptook AR, Shankaran S, et al. Whole-body hypothermia for neonatal encephalopathy in preterm infants 33 to 35 weeks' gestation: a randomized clinical trial. JAMA Pediatrics. 2025;179(4):396–406. doi:10.1001/jamapediatrics.2024.6613 ↩