Two Building-Block Fats for Very Premature Babies: What New Research Says About the Lungs, Eyes and Brain

A family guide to a review of 11 trials and two new studies from the Swedish Mega Donna Mega trial on giving arachidonic acid together with docosahexaenoic acid

Babies born very early miss months of the special fats that the placenta normally delivers to build the brain and eyes. New research suggests that giving two of these fats together, rather than one on its own, may be gentler on the lungs and may help protect the eyes and the brain's wiring. The results are encouraging, but they still need to be confirmed before this becomes routine care.

Why Doctors Have Been Thinking About Fats

If your baby was born before about 28 weeks of pregnancy, you will have heard a lot about breathing, feeding and growth. Fats are part of that story. Two particular fats are important building materials for the brain and the back of the eye. One is docosahexaenoic acid, usually shortened to DHA, an omega-3 fat. The other is arachidonic acid, shortened to AA or ARA, an omega-6 fat. Before birth, the placenta (the organ that feeds the baby in the womb) passes large amounts of both to the baby, especially in the last three months of pregnancy. Researchers estimate this at about 212 milligrams of AA and 43 milligrams of DHA per kilogram of the baby's weight every day, so roughly five times more AA than DHA [1]. Neither the fats in intravenous (drip) nutrition nor breast milk alone can fully replace this supply after a very early birth.

This article brings together three recent research papers that ask whether giving these two fats together helps: a review that combined the results of 11 earlier trials [2], and two new studies from a Swedish trial that looked at babies' brain scans [1] and at proteins in their blood [3].

What Happened When Doctors First Tried to Fill the Gap

For around twenty years, researchers tested whether extra DHA could help premature babies. Experts calculated that babies fed by tube or bottle fall well short of the DHA they would have received in the womb, missing nearly half of it [4]. The early results were mixed. In one Australian trial of 657 premature babies, extra DHA did not improve overall scores on a standard infant development test [5]. Another study that added DHA and AA to breast milk found better problem-solving at 6 months [6], but by 8 years old the children's thinking skills and brain scans looked no different [7].

Then came a worry. In a large trial of 1,273 very premature babies in Australia, New Zealand and Singapore, DHA given on its own was linked to slightly more bronchopulmonary dysplasia, or BPD, a long-lasting lung condition in premature babies: about 49 in every 100 babies on DHA developed it, compared with about 44 in every 100 without [8]. A Canadian trial, in which breastfeeding mothers took DHA capsules, was stopped early because of similar concerns [9]. Experts then advised against high doses of DHA to prevent lung disease [10]. Families and doctors were left unsure whether these fats help or harm. For parents, this meant that a supplement that sounded simple and natural came with an honest "we don't know yet", while breast milk and careful nutrition remained the foundation of care.

A Different Idea: Give Both Fats Together

Because the placenta supplies far more AA than DHA, a team in Sweden wondered whether DHA might work better, and more safely, alongside its partner. They ran the Mega Donna Mega (MDM) trial (giving AA and DHA to prevent the eye disease retinopathy of prematurity) in three university hospitals in Gothenburg, Stockholm and Lund [1]. The trial included 206 babies born before 28 weeks between December 2016 and August 2019. Half were chosen at random to receive a small daily dose of oil (between 0.1 and 1 millilitre, depending on weight), with twice as much AA as DHA, mixed into their milk or placed inside the cheek, from the first days of life until their original due date. The other half received usual care. There was no dummy oil, but the eye doctors who checked the babies did not know which group each baby was in [11].

The main result concerned retinopathy of prematurity, or ROP, a condition in which blood vessels at the back of a premature baby's eye grow abnormally and can threaten sight. Severe ROP affected 16 of 101 babies who had the oil (about 16 in 100) compared with 35 of 105 babies who did not (about 33 in 100), roughly halving the risk [11]. Importantly, BPD was about equally common in both groups, and a later analysis found that the oil did not make lung disease more severe [12]. Blood tests from the same babies added an intriguing clue: higher DHA levels went along with less severe eye disease only in babies who also had enough AA in their blood [13]. In other words, the two fats may need each other.

What Happens When All the Trials Are Combined

One trial, however well run, can be a matter of chance. That is why researchers also pool the results of many trials, an approach called a meta-analysis, to see which patterns hold up. A team at Jilin University in China combined 11 trials involving 2,567 premature babies from 10 countries [2]. Overall, the supplements did not reduce eye disease, bowel inflammation (necrotising enterocolitis), infection, brain bleeding or deaths, and BPD was slightly more common. But that extra lung risk came from the trials that gave DHA alone. In the four trials that gave DHA together with AA, there was no increase in BPD. Those combined-fat trials were few and small, though, and one of them was the Swedish trial itself, so this is not fully independent proof. The authors concluded that more research is needed.

A Closer Look at the Brain

Scans taken around the due date often show that very premature babies have smaller volumes in some parts of the brain than babies born at full term [14]. White matter is the brain's wiring, the bundles of nerve fibres that connect different areas, and in teenagers born early it is closely linked with thinking skills [15]. The Swedish team looked at brain scans taken around each baby's due date, using magnetic resonance imaging (MRI), a scan that uses magnets rather than X-rays. Clear enough images were available for 117 babies [1]. After accounting for differences in maturity, sex, hospital and timing of the scan, babies who had received the oil had about 6.8 cubic centimetres more white matter. The researchers estimate this is similar to the white-matter growth of roughly 10 extra days in the womb. Overall brain size and the other brain areas did not differ clearly. A separate trial in Norway, using the same fat mixture, found signs that the brain's wiring was more mature [16].

These are encouraging hints, not proof. Many scans could not be used, the babies who received the oil also had less severe eye disease (which itself is linked with slower white-matter development [17]), and the researchers describe their result as a first signal that needs testing. We do not yet know whether more white matter at term means better learning in later childhood. A follow-up of the Swedish children at 2.5 years did not find a clear difference in eyesight [18].

Clues From the Blood

In the third paper, researchers measured 538 proteins in small blood samples from 177 babies in the same trial, looking for early warning signs of severe ROP [3]. Babies who later developed severe ROP showed a faster rise, in their first four days, in a stress hormone called FGF-21 (fibroblast growth factor 21) and in a clot-dissolving protein. This rise was linked to being born earlier and smaller, receiving less milk in the first week, and needing a breathing machine for longer. In mice, FGF-21 seems to help healthy blood vessels grow in the eye [19]. Interestingly, the AA and DHA oil did not change these blood proteins, so how it protects the eye is still a mystery. The authors note it might act locally, inside the eye itself.

What This Means for Your Baby

At present, giving AA and DHA together is not yet established as standard care, and the evidence comes mainly from one Swedish trial. Your baby's team may follow different feeding plans for good reasons, and it is always fine to ask how they think about fats and nutrition. Useful questions might include whether your unit gives any fat supplements, whether your baby is part of a research study, and how your baby's eyes will be checked for ROP. The research also points in a hopeful direction: the Swedish researchers suggest that steady nutrition in the first days of life, including mother's own milk, may help protect the eyes, although this still needs to be tested [3]. If your baby does develop ROP, the treatment options are explained in our article on treating retinopathy of prematurity.

What Researchers Are Working on Next

Researchers want larger trials that compare the AA and DHA oil with a dummy oil, so that nobody knows which babies are receiving it, and that follow children into school age to see whether more white matter means better learning. They also want to find the best balance of the two fats, and to test whether giving very premature babies more energy in their first week could lower the chance of severe ROP.

The Bottom Line

Giving DHA on its own to very premature babies has not clearly helped and may slightly raise the risk of lung disease. Giving it together with AA, in the way the Swedish trial did, appears safer for the lungs and was linked with less severe eye disease and a little more brain white matter. These findings are hopeful, but they come from a small number of babies and still need confirming.

References

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  2. Dang D, Gao Z, Zhang C, Mu X, Lv X, Wu H. Effect of enteral supplementation of DHA with or without ARA in preterm infants: a meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2025;111(1):F27-F33. doi:10.1136/archdischild-2024-327606 ↩
  3. Lundgren P, Danielsson H, Panwar MB, et al. Proteomic Profile in Retinopathy of Prematurity: A Secondary Analysis of the Mega Donna Mega Randomized Clinical Trial. JAMA Ophthalmol. 2026;144(2):174-184. doi:10.1001/jamaophthalmol.2025.5594 ↩
  4. Lapillonne A, Jensen CL. Reevaluation of the DHA requirement for the premature infant. Prostaglandins Leukot Essent Fatty Acids. 2009;81(2-3):143-150. doi:10.1016/j.plefa.2009.05.014 ↩
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