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

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 randomised 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 localise 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 characterisation 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. Trial registration: ClinicalTrials.gov NCT03555019