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Arachidonic and docosahexaenoic acid supplementation affects white matter microstructure in preterm infants

In brief

Supplements raised white matter anisotropy in several regions of preterm infants

In a randomized trial of 64 infants born before 29 weeks, arachidonic and docosahexaenoic acid supplements were linked at term-equivalent age to higher fractional anisotropy and lower radial diffusivity in several white matter regions, especially those that myelinate early. Other imaging measures showed mixed results, and whether these differences reflect better brain development or affect later outcomes remains unknown.

Journal
Brain communications (Q1)
Published
11 October 2026
Study design
Randomized controlled trial
Evidence level
Level 1, High (CEBM 1b)
Authors
Gunnthorunn Gunnarsdottir, Ivan I Maximov, Oliver Marcel Geier, Tone Nordvik, Anette Ramm-Pettersen, Tom Stiris, et al.
PMID
42877701
DOI
10.1093/braincomms/fcag362

Why clinicians should know about it

  • Picked for Neonatology (top studies of the week, 18 October 2026): AA/DHA supplementation increased fractional anisotropy in preterm white matter

Abstract

Arachidonic acid and docosahexaenoic acid are long-chain polyunsaturated fatty acids that serve as key structural components of neuronal cell membranes and exhibit anti-inflammatory properties. They accumulate most rapidly during the third trimester of pregnancy, leaving very preterm infants deprived at birth. We conducted a double-blind randomized controlled trial comparing arachidonic and docosahexaenoic acid supplementation to medium chain triglycerides oil and assessed effects on white matter maturation using advanced diffusion imaging techniques. We used tract-based spatial statistics to localize significant changes across major tracts. Diffusion kurtosis imaging and Bayesian rotation invariant approach were applied to describe white matter microstructure within the intra- and extra-axonal water compartments enabling a more detailed characterization of tissue changes. These advanced diffusion MRI data were acquired at term-equivalent age for 64 infants born before 29 weeks of gestation, including 33 in the supplemented group and 31 in the control group. We identified significantly higher fractional anisotropy and lower radial diffusivity in several white matter regions in the supplemented group, mostly pronounced in areas that myelinate early. There were no significant differences in diffusion kurtosis imaging metrics between the two groups, but the Bayesian rotational invariant approach revealed several significant differences. This might illustrate a different developmental trajectory in the supplemented group compared to the control group. Applying advanced diffusion models can potentially provide a deeper understanding of early brain development and facilitate opportunities for early detection and intervention for preterm children.

Abstract as published, via PubMed.

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For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.