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

BackgroundAdequate nutrient intake during the first few months of life plays a critical role on brain structure and function development.ObjectivesTo 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.MethodsThe 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.ResultsExperimental 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.ConclusionsSupplemented 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 Registrationhttps://www.clinicaltrials.gov/, identifier: NCT02094547.

Joint analyses of human milk fatty acids, phospholipids, and choline in association with cognition and temperament traits during the first 6 months of life

“…However, thus far the results are inconsistent and sometimes controversial. Although the effect of PE on language abilities has not been specifically reported in the literature, the milk fat globule membrane (MFGM), which is a diverse mixture of bioactive components including phospholipids, has been shown to improve visual function, language, and motor domains in both term and preterm infants ( 16 , 54 , 55 ). In contrast, DHA has been reported to improve language ability.…”

Association study between hypothalamic functional connectivity, early nutrition, and glucose levels in healthy children aged 6 years: The COGNIS study follow-up

“…MFGM components positively influence brain development ( 60 ). Recent results from the COGNIS study suggest that the supplementation of infant formulas with MFGM components, LC-PUFAs, and synbiotics could be associated with beneficial long-term effects on neurocognitive development and brain structure at 6 years old ( 61 ). Gangliosides have important functions in neurogenesis and neural repair, being in great abundance during development in the hippocampal region of the brain, which is responsible for memory and higher cognitive function ( 62 ).…”

In vitro Digestion Characteristics of Hydrolyzed Infant Formula and Its Effects on the Growth and Development in Mice

“…During SIF digestion, the fatty acid contents in eHIF were also higher than that in sIF and pHIF, especially LCPUFAs (Figures 3C,F,I). Numerous studies have shown that LCPUFAs containing n-3 and n-6 fatty acids (e.g., α-linoleic acid C18:3, n-3; linoleic acid C18:2, n-6) contribute to the infant nervous system and retina development (38,39), suggesting that eHIF had a better nutrient composition and promoted brain development after digestion. However, the contents of most fatty acids were not significantly different between sIF and pHIF samples.…”

“…For the pHIF group, the number of arm entries and turns were significantly lower than those of the other three groups (p < 0.05). A possible reason for this result was that the abundant fatty acid content in eHIF, especially LCPUFAs (Figure 3), promoted the development of mouse brain (39), thereby improving maze test performance. Fewer LCPUFAs in pHIF (Figure 3) might be responsible for the lower total number of arm entries and turns observed for this group of mice.…”