Cognitive health study finds formula mimicking human milk structure gets closer to health benefits of breastmilk

As breastfeeding has been positively associated with infant and child neurocognitive development and function, the authors from the Netherlands and Belgium hypothesised that it may be differences in the milk lipid composition and milk fat globule structure that contribute to this effect. 

The current study, conducted by Danone Nutricia Research and published in ‘Frontiers in Nutrition’ evaluated the effects of an infant formula mimicking human milk (HM) lipid composition and milk fat globule structure on childhood cognitive performance. 

They found that the infants fed HM mimicking formula had fatty acid ratios more similar to HM fed infants and higher cognitive health scores compared to those fed standard formula.  

The report states: “These outcomes suggest that exposure to an infant formula mimicking human milk lipid composition and milk fat globule structure positively affects child neurocognitive development. Underlying mechanisms may include a different omega-3 fatty acid status during the first months of life.”

Significance​

The connection between breastfeeding and improved neurocognitive development is thought to be influenced by the differences between human milk (HM) and infant formula (IF), particularly in terms of the quality of dietary lipids, such as omega-3 and omega-6 fatty acids.

HM contains specific fatty acids like docosahexaenoic acid (DHA) that are crucial for neuronal development​, and child neurocognitive outcomes have been associated​ with dietary long-chain polyunsaturated fatty acids (LCPUFA) supply in the first year of life.

The composition and structure of lipids in HM differ from those in IF​, with HM comprising of large lipid globules (mode diameter of ∼4 μm) that are encapsulated by the milk fat globule membrane (MFGM), a 3-layered membrane composed of phospholipids (PL), sphingolipids, glycolipids, proteins, and other components.

In contrast, IF is produced in factories and often relies on bovine milk-based proteins and vegetable oils for the lipid fraction.

While lipid globules in raw bovine milk are also large and encapsulated by a similar MFGM, the membrane structure is disrupted during common manufacturing processes​ such as homogenisation and emulsification. 

Recent advancements​ have attempted to make IF more like HM by incorporating dairy lipids and MFGM-derived ingredients, resulting in larger lipid droplets coated by phospholipids, resembling the structural properties of HM.

According to the authors, these structural features can affect lipid digestion and absorption, potentially influencing infant neurocognitive development​.

One randomised controlled trial​ previously demonstrated that one IF called Concept, which incorporated dairy lipids and large lipid droplets coated with bovine MFGM-derived phospholipids, supported growth and was well-tolerated in healthy-term infants.

The authors of the current study therefore hypothesised that infants exposed to Concept IF would exhibit improved neurocognitive outcomes in early childhood compared to those exposed to standard IF.

The study ​

The randomised, controlled trial included 311 healthy term infants up to four months old, who received either a standard infant formula (n = 108), Concept infant formula (n = 115) with large, milk phospholipid coated lipid droplets and containing dairy lipids, or were breastfed (n = 88). 

Erythrocyte fatty acid composition was determined at 3 months of age, and neurocognitive function was assessed at 3, 4, and 5 years of age, using the Flanker test, Dimensional Change Card Sort (DCCS) test, and Picture Sequence Memory test from the National Institutes of Health Toolbox Cognition Battery.  

Results showed that the erythrocyte omega-6 to -3 long-chain polyunsaturated fatty acid ratio appeared to be lower in the Concept compared to the Standard group (P = 0.025).

At age 5, only the Concept group was comparable to the Breastfed group in the highest reached levels on the Flanker test, and the DCCS score was higher in the Concept group, compared to the Standard group (P = 0.021).

The study concludes that infants exposed to infant formula (IF) closely resembling human milk (HM) in both lipid composition and lipid droplet structure  may experience improved cognitive function during childhood, approaching the levels seen in breastfed children​. 

At age 5, children exposed to specialised IF demonstrated higher scores in tests measuring executive function. 

The authors of the study note that the potential mechanisms behind cognitive improvements include better accumulation of essential fatty acids in the brain during the first year of life, influenced by the unique lipid composition of the IF.

The authors observe improved n-3 LCPUFA accumulation in the brain during the first year of life, and a lower n-6 to n-3 LCPUFA ratio in erythrocyte membranes of infants exposed to Concept IF compared to Standard IF at 13 weeks of age. 

Erythrocyte n-6 and -3 LCPUFA composition is considered an indirect biomarker for LCPUFA composition in neuronal tissue​.

The authors summarise that IFs closely mimicking HM in lipid composition and structure may support better cognitive development in formula-fed infants, bridging the gap between breastfed and formula-fed children.

They conclude that while the study has strengths, such as long-term follow-up and repeated cognitive assessments, it also has limitations, including a relatively small sample size and the exploratory nature of the investigation. 

Journal: Frontiers in Nutrition 

https://www.frontiersin.org/articles/10.3389/fnut.2023.1215199/full​

“Infant formula containing large, milk phospholipid-coated lipid droplets and dairy lipids affects cognitive performance at school age.”

Authors: Lidewij Schipper, Nana Bartke, Maya Marintcheva-Petrova, Stefanie Schoen, Yvan Vandenplas, and Anita