Infant Formula Supplemented With Milk Fat Globule Membrane, Long-Chain Polyunsaturated Fatty Acids, and Synbiotics Is Associated With Neurocognitive Function and Brain Structure of Healthy Children Aged 6 Years: The COGNIS Study

Abstract

Background: Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development.

Objectives: To analyze the long-term effects of an experimental infant formula (EF) on neurocognitive function and brain structure in healthy children aged 6 years compared to those fed with a standard infant formula or breastfed.

Methods: The current study involved 108 healthy children aged 6 years and participating in the COGNIS Study. At 0-2 months, infants were randomized to receive up to 18 months of life a standard infant formula (SF) or EF enriched with milk fat globule membrane (MFGM), long-chain polyunsaturated fatty acids (LC-PUFAs) and synbiotics. Furthermore, a reference group of breastfed (BF) infants were also recruited. Children were assessed using neurocognitive tests and structural Magnetic Resonance Imaging (MRI) at 6 years old.

Results: Experimental infant formula (EF) children showed greater volumes in the left orbital cortex, higher vocabulary scores and IQ, and better performance in an attention task than BF children. EF children also presented greater volumes in parietal regions than SF kids. Additionally, greater cortical thickness in the insular, parietal, and temporal areas were found in children from the EF group than those fed with SF or BF groups. Further correlation analyses suggest that higher volumes and cortical thickness of different parietal and frontal regions are associated with better cognitive development in terms of language (verbal comprehension) and executive function (working memory). Finally, arachidonic acid (ARA), adrenic acid (AdA), docosahexaenoic acid (DHA) levels in cheek cell glycerophospholipids, ARA/DHA ratio, and protein, fatty acid, and mineral intake during the first 18 months of life seem to be associated with changes in the brain structures at 6 years old.

Conclusions: Supplemented infant formula with MFGM components, LC-PUFAs, and synbiotics seems to be associated to long-term effects on neurocognitive development and brain structure in children at 6 years old.

Clinical trial registration: https://www.clinicaltrials.gov/, identifier: NCT02094547.

Keywords: LC-PUFAs; MFGM; breastfeeding; cognition; early nutrition; infant formula; neuroimaging; synbiotics.

Figure 1

Participant flow-chart from baseline visit to 6 years old. BF, Breastfed infants; D, Drop-outs; E, Exclusions; EF, Experimental infant formula; MRI, Magnetic Resonance Imaging; n, Sample size; R, Recovered; SF, Standard infant formula. Fatty acid (FA) status was analyzed from available cheek cell samples of children who attended to 6 years follow-up visit. Incomplete dietary intake data were excluded from the current analysis. At 6 years old: *2 children did not attend to cognitive assessment. Some MRI data from participants (n = 30) were eliminated because the quality of the brain images was not adequate to be analyzed due to excessive movement of children inside the scanner: Unable to analyze the data from 7 children; ^‡Unable to analyze the data from 14 children; ^§Unable to analyze the data from 11 children. ^aBF infants were randomized between 0–6 months of age.

Figure 2

Differences in brain volume (A) and cortical thickness (B) between children participating in the COGNIS study at 6 years of life. Analysis adjusted by smoking during pregnancy, maternal age, familiar socioeconomic status, age, and sex of the children. Brain volume analysis was also corrected for total brain volume. Experimental infant formula (EF) > Standard infant formula (SF) (light blue); EF > BF (dark blue); and EF > SF and EF > BF (purple). SF, Standard infant formula; EF, Experimental infant formula; BF, breastfed infants.