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.

Ana Nieto-Ruiz,Cristina Campoy,Estefanía Diéguez,Jesús Jiménez,Juan Verdejo-Román,José A García-Santos,M Carmen López-Sabater,Florian Herrmann,Tomás Cerdó,Roser De-Castellar,M Teresa Miranda,Natalia Sepúlveda-Valbuena,Miguel Pérez-García,Mercedes G Bermúdez,Andrés Catena

doi:10.3389/fnut.2022.820224

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.

Highlights

Proteins, long–chain polyunsaturated fatty acids (LC-PUFAs), iron, zinc, iodine, and B vitamins play a critical role on brain function and structure development [1–3]
No significant differences were found between study groups in other maternal baseline characteristics related to child neurocognitive function and brain structure, including pre-conceptional body mass index (BMI), gestational weight gain (GWG), and smoking during pregnancy
While long-term effects of early nutrition on neurocognitive development resulted to be lesser than expected, major changes were observed on the brain structure at 6 years old, mainly in children fed with the supplemented infant formula compared to those who received the standard one, and similar to those found in breastfed children

Summary

Introduction

Long–chain polyunsaturated fatty acids (LC-PUFAs), iron, zinc, iodine, and B vitamins play a critical role on brain function and structure development [1–3]. Given that the infant brain evolves from early childhood to adolescence, early-life nutritional deficiencies may have negative long-lasting or permanent effects on later cognitive function [4], including impairment on visuo-perceptual functions [5], working memory [6, 7], language [8], and executive functions [9]. It is well-established that breastfeeding is related to optimal brain maturation [10, 11] and neurodevelopment [12] in life. When breastfeeding is not possible, infant formulas are available to satisfy infant’s nutritional and energy requirements Their functional and nutritional properties vary considerably from breast milk, and new bioactive compounds are being added to narrow the functional and nutritional gap with breast milk [13]. Adequate nutrient intake during the first few months of life plays a critical role on brain structure and function development

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Conclusion