Improved Neurodevelopmental Outcomes at 5.5 Years of Age in Children Who Received Bovine Milk Fat Globule Membrane and Lactoferrin in Infant Formula Through 12 Months: A Randomized Controlled Trial

Abstract

To evaluate neurodevelopmental outcomes at 5.5 years of age in children who were previously randomized to cow milk-based infant formula (control) or similar formula (milk fat globule membrane plus lactoferrin [MFGM+LF]) with added sources of bovine MFGM and bovine LF (bLF) through 12 months of age. Children who completed study feeding were invited to participate in follow-up assessments: cognitive development across multiple domains (primary outcome; Wechsler Preschool & Primary Scale of Intelligence™, 4th Edition; WPPSI™-IV), inhibitory control/rule learning (Stroop Task), flexibility/rule learning (Dimensional Change Card Sort; DCCS), and behavior/emotion (Child Behavior Checklist; CBCL). Of 292 eligible participants (Control: 148, MFGM+LF: 144), 116 enrolled and completed assessments (Control: 59, MFGM+LF: 57). There were no group demographic differences except family income (MFGM+LF significantly higher). WPPSI-IV composite scores (mean±SE) for Visual Spatial (100.6±1.7 vs 95.3±1.7; P=0.027), Processing Speed (107.1±1.4 vs 100.0±1.4; P<0.001), and Full Scale IQ (98.7±1.4 vs 93.5±1.5; P=0.012) were significantly higher for MFGM+LF vs Control, even after controlling for demographic/socioeconomic factors. Stroop Task scores were significantly higher in MFGM+LF vs control (P<0.001). Higher DCCS scores (P=0.013) in the border phase (most complex/challenging) were detected and more children passed the border phase (32% vs 12%; P=0.039) for MFGM vs control. No group differences in CBCL score were detected. Children who received infant formula to 12 months of age with added bMFGM and bLF vs standard formula demonstrated improved cognitive outcomes in multiple domains at 5.5 years of age, including measures of intelligence and executive function.