MFGM-enriched infant formula: Effects on neurodevelopmental, immune, and gastrointestinal health

One of the leading manufacturers of infant formula, Mead Johnson Nutrition (MJN), strives to nourish the best start in life for children. A child’s first 1,000 days is a critical time for their overall development and proper nutrition plays a crucial role. [Pediatrics 2018;141(2):e20173716] During this period, growth is rapid; the brain forms about over 1 million new connections per second and achieves about 80% of its adult size, the immune system starts fighting off viruses and infections, and the digestive system develops the right balance of beneficial bacteria. [https://developingchild.harvard.edu/science/key-concepts/brain-architecture/]

Hence, researchers at MJN constantly work to gain a deeper understanding of human milk and its benefits to infants. They were the first to add the brain-building nutrient DHA into infant formula, and now they are continuing to innovate by incorporating milk fat globule membrane (MFGM) – a component recently discovered in human milk. Randomized, controlled clinical trials in infants have shown the difference that MFGM can make in improving neurodevelopmental outcomes (IQ and EQ), immunity, and gut health.

What is MFGM?
Milk fat globules consist of a core rich in non-polar lipids, surrounded by a trilayer membrane – the MFGM – which is mainly composed of polar lipids. The molecules present in the membrane, such as phospholipids, cholesterol, and membrane proteins are shown to have important bioactivities (Figure 1). [International Dairy Journal 2008;18:436-457; J Agric Food Chem 2008;56:5226-5236] Studies suggest that MFGM supports digestive health, as well as immune and central nervous system development and function. [Nutrients 2017;9:817]

Effects on neurodevelopment
Several prospective randomized, controlled trials (RCTs) have demonstrated neurodevelopmental benefits of adding MFGM to infant formula, compared to a standard formula. [J Pediatr 2019;215:24-31; Am J Clin Nutr 2014;99(4):860-868; Nutrition 2012;28:749-752]

In a double-blinded RCT, healthy full-term infants whose mothers were unable to breastfeed were randomized to receive either a standard formula (control), or a similar formula enriched with bovine MFGM and lactoferrin (MFGM+LF) through 365 days of age. A total of 291 infants completed the study (control, 148; MFGM+LF, 143) and neurodevelopment was assessed according to the Bayley Scales of Infant Development, 3rd Edition (primary endpoint), ASQ, MacArthur-Bastes CDI, and Single Object Free Play. Infants in the MFGM+LF arm had significantly higher mean cognitive, language, and motor scores than the control arm at 365 days (p<0.001), thus meeting the primary endpoint. In addition, global development scores from day 120 to day 275, attention at day 365, as well as language subcategories at day 545, were significantly improved in the MFGM+LF group (Figure 2). [J Pediatr 2019;215:24-31]

These findings were similar to that published in earlier trials, where infants fed a formula supplemented with MFGM reaped benefits in cognitive development and early growth at 12 months compared with those fed a standard formula; the cognitive scores of the MFGM group were similar to those of the breastfed reference group. [Am J Clin Nutr 2014;99(4):860-868]

Healthy brain development implies not only progress in cognitive abilities but also proficiency in emotional regulation. [Soc Neurosci 2010;5(5-6):533-542] These are critical aspects of early development, which comprises various domains including physical, emotional, behavioural, cognitive, language, and general learning competencies. Research has shown that development in the first 8 years of life is foundational for future health and life success. [MMWR Morb Mortal Wkly Rep 2017;66:769-772]

Interestingly, MFGM has shown to have effects on behavioural development as well. A study conducted in preschoolers (mean age 4.4 years) showed that regular consumption of a formula enriched with MFGM over 4 months led to improved behavioural regulation, as measured using the Achenbach System of Empirically Based Assessment, compared with consuming a standard formula without MFGM. The MFGM group had demonstrated significant improvements in internal (p<0.003), external (p<0.004), and total (p<0.002) problem scores. [Nutrition 2012;28:749-752]

Effects on immunity
MFGM activates and modulates the immune system. It protects against pathogenic bacteria through both direct and indirect bactericidal activity, with fragments containing glycans acting as decoys to prevent pathogens from infecting enterocytes via glycan binding. Some glycosylated membrane-bound proteins and polar lipids modulate the immune system via actions on B cells, T cells, mast cells, macrophages, and dendritic cells, whereas some MFGM components may act as prebiotics to feed enteric microbiota, indirectly stimulating the immune system. [Front Pediatr 2018;6:313; J Anim Sci 2009;87(13 Suppl):26-34; J Pediatr Gastroenterol Nutr 2015;60:384-389]

Clinical data have shown that babies fed with MFGM-supplemented formula have similar rates of upper respiratory tract infections as breastfed infants until 12 months [Front Pediatr 2019;7:347] and the rate of respiratory events was 13% lower when compared with a control formula (Figure 3). [J Pediatr 2019;215:24-31]

Another double-blinded RCT showed that MFGM-supplementation was associated with a lower incidence of acute otitis media (AOM) and less frequent use of antipyretics at 6 months of age. The cumulative incidence of AOM was 1% vs 9% in the MFGM-enriched formula and standard formula, respectively, translating to a relative reduction of 89% (p=0.034). [J Pediatr Gastroenterol Nutr 2015;60:384-389]

The immune-enhancing benefits extend to children of preschool age. MFGM-supplementation was linked to fewer days with fever (>38.5°C) and fewer short febrile episodes (1.7 ± 2.5 vs 2.6 ± 3.1 d), translating to a 39% reduction (p<0.002). [Nutrition 2012; 28:749-752]

Effects on gut health
Evidence indicate that proteins in the bovine MFGM have been demonstrated to possess broad activities against pathogens, thus it was suggested that MFGM may help to prevent diarrhoea of bacterial and viral origin. Bioactive components in MFGM include mucin, lactadherin, folate-binding protein, lactoferrin, Immunoglobulin (Ig) G, sialic acid, sphingomyelin, and gangliosides, which have been shown to inhibit various pathogenic bacteria (eg, Vibrio cholerae, Escherichia coli), as well as viruses (eg, rotavirus). [J Pediatr Gastroenterol Nutr 2011;53:561-568]

One study evaluated the efficacy of MFGM supplementation on diarrhoea, anaemia, and micronutrient status in infants aged 6 to 11 months old. After 6 months of supplementation, the overall prevalence of diarrhoea was significantly lower in the MFGM group vs the control group (3.84% vs 4.37%; p<0.05). The study found a 46% reduction in the incidence of bloody diarrhoea in the MFGM group vs the control group (odds ratio, 0.54, 95% confidence interval, 0.31-0.93; p=0.025). [J Pediatr Gastroenterol Nutr 2011;53:561-568]

Similarly, a study by Li et al also found that infants in the MFGM group had a lower incidence of gastrointestinal (GI) events including diarrhoea, when compared with the control group (Figure 4). [J Pediatr 2019;215:24-31]

Conclusion
MFGM, a complex protein-phospholipid trilayer surrounding fat droplets, is a natural bioactive milk constituent. RCTs have indicated that supplementation with MFGM confers clinically relevant immune, gut, and neurodevelopmental effects. The benefits of MFGM-enriched formula can help to fuel kids’ smartness with heart (IQ & EQ), and promote holistic healthy development with stronger immunity and enhanced gut health.