Long-chain polyunsaturated fatty acid supplementation in the first year of life affects brain function, structure, and metabolism at age nine years

Abstract

The present study sought to determine whether supplementation of long-chain polyunsaturated fatty acids (LCPUFA) during the first year of life influenced brain function, structure, and metabolism at 9 years of age. Newborns were randomly assigned to consume formula containing either no LCPUFA (control) or formula with 0.64% of total fatty acids as arachidonic acid (ARA; 20:4n6) and variable amounts of docosahexaenoic acid (DHA; 22:6n3) (0.32%, 0.64%, or 0.96% of total fatty acids) from birth to 12 months. At age 9 years (±0.6), 42 children enrolled in a follow-up multimodal magnetic resonance imaging (MRI) study including functional (fMRI, Flanker task), resting state (rsMRI), anatomic, and proton magnetic resonance spectroscopy (1 H MRS). fMRI analysis using the Flanker task found that trials requiring greater inhibition elicited greater brain activation in LCPUFA-supplemented children in anterior cingulate cortex (ACC) and parietal regions. rsMRI analysis showed that children in the 0.64% group exhibited greater connectivity between prefrontal and parietal regions compared to all other groups. In addition, voxel-based analysis (VBM) revealed that the 0.32% and 0.64% groups had greater white matter volume in ACC and parietal regions compared to controls and the 0.96% group. Finally, 1 H MRS data analysis identified that N-acetylaspartate (NAA) and myo-inositol (mI) were higher in LCPUFA groups compared to the control group. LCPUFA supplementation during infancy has lasting effects on brain structure, function, and neurochemical concentrations in regions associated with attention (parietal) and inhibition (ACC), as well as neurochemicals associated with neuronal integrity (NAA) and brain cell signaling (mI).

Trial registration: ClinicalTrials.gov NCT02076048 NCT00266825.

Keywords: attention; brain imaging; early life programming; long-chain polyunsaturated fatty acids.

© 2018 Wiley Periodicals, Inc.

Figures

Figure 1:. Attention System: Long-term effects of LCPUFA supplementation as observed by multi-modality imaging in brain structure (A), connectivity (B), and function (C).

(A)Structural: There was a trend for greater white matter volume in the 0.32% group and the 0.64% group compared to control in the right posterior parietal cortex. (B)Functional: Connections between the inferior parietal cortex and distant regions of the left DLPFC were stronger in the 0.64% group. Connectivity between the IPL and insula was stronger in the control group compared to the 0.32% group and the 0.96% group, and stronger in the 0.64% group compared to the 0.32% group and the 0.96% group. (C)Functional: Activation maps showing a group effect for incongruent compared to congruent trials. The parietal regions in the LCPUFA-supplemented groups show greater activation to incongruent trials compared to congruent trials compared to control. (D) Example of the Flanker task.

Figure 2:. Inhibition System: Long-term effects of LCPUFA supplementation as observed by multi-modality imaging in brain structure (A), metabolism (B) and function (C).

(A)Structural: The 0.32% and 0.64% groups had more white matter volume in the left ACC (B)Metabolic: The NAA:creatine ratio was greater in the 0.64% group compared to control. The mI:creatine ratio was greater in the 0.96 group compared to control. (C)Functional: There was greater activation for the LCPUFA-supplemented groups to incongruent compared to congruent trials in the ACC. The control group showed less activation to incongruent compared to congruent trials.