text: Several studies of diets supplemented with MFGM and its components, including gangliosides and sphingomyelin, have aimed to address measures of cognitive development in pediatric populations. In some of the studies, MFGM supplementation to infant formula was shown to narrow the gap in cognitive development between breastfed and formula-fed infants.
  Tanaka et al. (2013) studied the neurobehavioral effects of feeding formula supplemented with sphingomyelin-enriched phospholipid in 24 very low birth weight preterm infants (birth weight <1500 g).
  In this double-blind RCT, the preterm infants were fed either control formula containing phospholipids derived from egg yolk lecithin with sphingomyelin at 13% of total phospholipid or a supplemented formula with milk-derived phospholipids containing 20% sphingomyelin. Infants fed the supplemented formula had significantly higher percentages of sphingomyelin in total plasma phospholipids after 4, 6, and 8 weeks of feeding compared to those fed the control formula. The infants fed the supplemented formula also showed improvements across multiple developmental measures at 18 months, with significantly better scores on the Behavior Rating Scale of the Bayley Scales of Infant Development II (BSID-II), the Fagan test (novelty preference rate), the latency of visual evoked potentials (VEP), and sustained attention test than in the control group.
  Gurnida et al. (2012) assessed the cognitive effects of formula supplemented with a ganglioside-enriched, MFGM-derived complex milk lipid in term infants. In this double-blind RCT, healthy infants (2–8 weeks of age) were fed until 6 months of age, either control infant formula (n=30), or a supplemented infant formula (n=29) with added complex milk lipids to increase ganglioside concentration to approximately 11-12 μg/mL to be within the human milk range. A breastfed reference group (n=32) was also included. Results showed that serum ganglioside levels in the supplemented group were significantly higher compared to the control group at 6 months, but did not significantly differ from levels in the breastfed group. The cognitive outcomes measured using the Griffiths Mental Development Scale showed that the supplemented group had significantly increased scores for Hand and Eye Coordination, Performance, and Total Score (General Quotient) at 6 months compared to the control group, and there were no significant differences in cognitive performance compared to the breastfed reference group.
  Timby et al. (2014) also assessed the potential impact of MFGM supplementation on cognitive development in term infants. In this double-blind RCT, term infants (<2 months old) were fed until 6 months of age either a control formula (n=64) or an MFGM-supplemented formula (n=71). A breastfed reference group (n=70) was also included. Cognitive assessment done using the BSID-III at 12 months of age showed that the MFGM-fed infants exhibited significantly higher mean cognitive scores than the control group (105.8 vs 101.8; P<0.008), and not significantly different from the breastfed reference group. In contrast, there were no significant differences in motor domain scores between the three groups, and both experimental and control formula groups scored lower than the reference group in the verbal domain.
  Veereman-Wauters et al. (2012) assessed the potential behavioral benefits of MFGM supplementation in young children. In this double-blind RCT, healthy preschool children (2.5 to 6 years of age) consumed for 4 months, either a control formula (n=97) providing 60 mg/day of endogenous phospholipid, or an MFGM-supplemented formula (n=85) providing a total of 500 mg/day of dairy-derived phospholipids. At the end of the trial, parents and teachers completed the Achenbach System of Empirically Based Assessment (ASEBA), a validated questionnaire considered to be a gold standard for assessing emotion and behavior in preschool children. Significant differences in internal, external, and total behavioral problem scores were observed in favor of the supplemented formula group, as reported by parents (but not by teachers).