Retinopathy of prematurity, often abbreviated as ROP, remains one of the leading causes of childhood visual impairment worldwide. Despite advances in neonatal intensive care and early ophthalmologic screening, extremely preterm infants continue to face a significant risk of developing severe forms of this disease. New research published in JAMA Ophthalmology brings renewed attention to a promising nutritional intervention that may substantially reduce this risk.
A secondary analysis of the Mega Donna Mega randomized clinical trial reports that enteral supplementation with the fatty acids arachidonic acid and docosahexaenoic acid reduced the risk of severe retinopathy of prematurity by nearly half. Even more compelling is the finding that this protective effect persisted regardless of the presence or absence of known clinical risk factors.
This article explores the study findings, explains why arachidonic acid and docosahexaenoic acid matter for retinal development, and discusses what these results may mean for the future of neonatal care.
Retinopathy of prematurity is a disorder of abnormal retinal blood vessel development that primarily affects infants born before 28 weeks of gestation. The retina is not fully vascularized at birth in extremely preterm infants, and postnatal factors can disrupt normal vessel growth.
Mild cases of ROP may resolve spontaneously. Severe ROP, defined as stage 3 disease or worse or disease requiring treatment, can lead to retinal detachment, permanent vision loss, or blindness.
Despite careful monitoring and timely interventions such as laser therapy or intravitreal injections, outcomes are not always optimal. As a result, researchers have increasingly focused on preventive strategies that support healthy retinal vascular development from birth.
Arachidonic acid and docosahexaenoic acid are long chain polyunsaturated fatty acids that play essential roles in neural and retinal development.
Both fatty acids are major structural components of retinal cell membranes. During the third trimester of pregnancy, large amounts of arachidonic acid and docosahexaenoic acid are transferred from mother to fetus. Extremely preterm birth interrupts this process, leaving infants with significantly lower circulating levels of these nutrients.
Previous observational and interventional studies have suggested that low levels of these fatty acids may contribute to inflammation, impaired vascular development, and increased susceptibility to retinopathy of prematurity. The Mega Donna Mega trial was designed to rigorously test whether supplementation could improve clinical outcomes.
The Mega Donna Mega trial was a randomized clinical trial conducted in Sweden involving extremely preterm infants born before 28 weeks of gestation. Infants were enrolled between December 2016 and August 2019.
Half of the infants received enteral supplementation with arachidonic acid at 100 mg per kilogram per day and docosahexaenoic acid at 50 mg per kilogram per day, in addition to standard neonatal care. Supplementation began shortly after birth and continued until term equivalent age.
The original trial demonstrated a 50 percent reduction in severe retinopathy of prematurity among infants receiving supplementation. The newly published secondary analysis focused on understanding whether this benefit was influenced by established clinical risk factors.
This secondary analysis included 177 extremely preterm infants. Severe retinopathy of prematurity was defined as stage 3 disease or higher or retinopathy requiring treatment.
Researchers evaluated several known risk factors for severe ROP, including:
Statistical analyses compared the risk of severe ROP between infants who received fatty acid supplementation and those who received standard care, both overall and within each risk factor category.
The findings were striking. Severe retinopathy of prematurity developed in 37 percent of infants receiving standard care compared with only 19 percent of infants who received arachidonic acid and docosahexaenoic acid supplementation.
This corresponds to a relative risk reduction of approximately 48 percent.
Importantly, the reduction in severe ROP was consistent across all evaluated risk factors. Whether infants had thrombocytopenia, hyperglycemia, necrotizing enterocolitis, or prolonged exposure to parenteral nutrition, supplementation was associated with a similar protective effect.
No safety concerns related to fatty acid supplementation were identified, and rates of other neonatal morbidities were comparable between the two groups.
The analysis also reinforced the importance of several established risk factors for severe retinopathy of prematurity. The strongest associations were observed for:
Some of these risk factors were associated with an eightfold increase in severe ROP risk. Yet even in these high risk groups, supplementation with arachidonic acid and docosahexaenoic acid significantly lowered the likelihood of severe disease.
What makes this study particularly compelling is that the protective effect of supplementation did not depend on modifying individual risk factors. Instead, arachidonic acid and docosahexaenoic acid appeared to support retinal vascularization directly.
This suggests that fatty acid supplementation may act through fundamental biological mechanisms such as:
The consistency of benefit across diverse clinical scenarios increases confidence in the robustness of the findings.
Beyond reducing severe retinopathy of prematurity, earlier reports from the Mega Donna Mega trial demonstrated meaningful functional benefits. A higher proportion of infants who received supplementation achieved visual acuity of at least 20/62 by 2.5 years of age.
This highlights that the benefits of fatty acid supplementation may extend beyond disease prevention to improved long term visual development.
While the results are promising, several limitations should be acknowledged.
The trial was conducted in a single country, and neonatal care practices may vary internationally. This could influence how generalizable the findings are to other healthcare settings.
Baseline serum vitamin and fatty acid levels were not measured, which may have provided additional insight into individual variability in response.
Finally, while the sample size was sufficient to demonstrate significant effects, larger multicenter trials would help confirm these findings and support changes to clinical guidelines.
The results of this study suggest that targeted nutritional supplementation may become an important tool in preventing severe retinopathy of prematurity.
For clinicians caring for extremely preterm infants, arachidonic acid and docosahexaenoic acid supplementation offers a low risk intervention with substantial potential benefit. For researchers, these findings open new avenues to explore how nutrition influences retinal and neurodevelopment in vulnerable populations.
As evidence continues to accumulate, fatty acid supplementation may eventually become a standard component of care for extremely preterm infants.
Severe retinopathy of prematurity remains a major cause of lifelong visual impairment, even with modern neonatal care. The secondary analysis of the Mega Donna Mega randomized clinical trial provides strong evidence that supplementation with arachidonic acid and docosahexaenoic acid can reduce the risk of severe disease by nearly half.
Most notably, this protective effect appears consistent regardless of traditional clinical risk factors. These findings highlight the critical role of nutrition in early retinal development and suggest a promising path forward in the prevention of vision loss among extremely preterm infants.
Lundgren P, Nilsson S, Pivodic A, et al.
Fatty Acid Supplementation and Retinopathy of Prematurity: Secondary Analysis of a Randomized Clinical Trial.
JAMA Ophthalmology. Published online January 29, 2026.
doi:10.1001/jamaophthalmol.2025.5994
This article is for informational and educational purposes only and does not constitute medical advice. Clinical decisions should always be made by qualified healthcare professionals based on individual patient circumstances and current clinical guidelines. The information presented here should not be used as a substitute for professional medical consultation, diagnosis, or treatment.
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