Introduction

The most recent Center for Disease Control and Prevention Breastfeeding Report Card shows that currently 83.2% born in the US started out breastfeeding, and 46.9% were exclusively breastfed at 3 months. For those who did not start out breastfeeding or ended sooner than recommended, cow’s milk protein-based formula has been the main alternative. In addition, soy protein-based formula currently also accounts for a small percentage of the infant formula market in the US and remains useful for infants allergic to milk formula or for parents wishing to maintain a vegetarian lifestyle. While soy-based formula and milk-based formula sold in the US all meet specific requirements of the FDA for nutrient content, a major difference in soy formula and all other formulas is that the soy protein used in soy-based formula contains isoflavones which can have weak estrogenic activity, and this has led to some health professionals to be concerned about sexual development and reproduction in children fed soy formula. Many studies have observed benefits to children’s health and development associated with breastfeeding. Few studies have evaluated whether there are brain developmental differences associated with soy- vs. milk- based formula, despite recent findings that estrogen may play an important role in neurodevelopment and soy isoflavone may have important implications in cognitive function. In this study, we aim to evaluate whether different types of infant formula feeding (particularly soy vs. milk based formula) during the first year of life would have impact on children’s brain development and neurodevelopmental outcomes such as executive functions.

Methods

Healthy 8-year-old children were recruited for this imaging study. Inclusion criteria for the participants were: age 90-101 months at time of study, parental report of an uncomplicated full-term gestation, birth weight between 5-95th percentile-for-age (5.5-9.25 pounds), and the type of infant diet between birth and age 8 months. They were either predominately breast-fed (BF) or predominately fed commercially available milk formula (MF) or soy formula (SF) during infancy. BF children were breastfed for about 8 months or longer before completely transitioning to formula and/or other diets. MF and SF children were fed the same types of formula (cow’s milk-based or soy-based) since first weeks of life through age ~8 months or above. Exclusion criteria for the participants included: maternal use of alcohol, tobacco, illicit drugs, or psychotropic medications during pregnancy; illnesses and chronic diseases which may affect children’s growth or development; psychological/psychiatric diagnoses; neurological impairment or injury; history or current use of anticonvulsant, stimulant, or mood-stabilizing medications; and history or current use of remedial special education services. The children were scanned on a 1.5T Achieva scanner (Philips Healthcare, Best, the Netherlands) with an 8-channel SENSE head coil. Pulse sequences included a T1-weighted 3D turbo field echo pulse sequence with the following parameters: 7.3 ms TR; 3.4 ms TE; 8° flip angle; 1x1x1 mm acquisition voxel size; 256x232x150 matrix size; and 2 averages. The 3D T1 images were exported to a workstation with FreeSurfer software (developed by the Laboratory for Computational Neuroimaging, Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital) for cortical thickness analysis. Standard preprocessing steps were applied, and thickness for all cortical regions was calculated from distances between gray/white to gray/CSF boundaries. In addition, the parents of the children were asked to complete a Behavior Rating Inventory of Executive Function (BRIEF) assessment, which is an 86-item questionnaire for parents that assesses executive function and behaviors of their children. The MRI parameters and BRIEF scores were then compared between different infant diet groups. In total, 71 children (10 boys / 12 girls for BF, 10/15 for MF, and 11/13 for SF) had valid structural MRI data and completed BRIEF assessment and were included in this study.

Results

A Number of clusters in the brain showed significant differences in cortical thickness between the 3 diet groups. The details are listed in Figure 1. The three groups of children also showed significant differences in the measures of parental reported executive functions using the BRIEF (Figure 2). In general, while the means of each score for each groups are all within normal range, the SF group has lower BRIEF scores (P<0.05) compared to the MF groups, for several subscales including Initiate, Plan/Organize, and Monitor, and for combined measures including the metacognition index (MI) and Global Executive Composite (GEC).

Conclusions

Differences in brain development, particularly, cortical thickness in several regions, were observed in 8-year-old children who were predominately breastfed, cow’s milk formula fed, or soy formula fed during infancy. These children also showed differences in evaluation of parental-reported executive functions. Increasing group sizes and refining our analytical methods are currently ongoing efforts to further assess effects of early diet on brain development.

Acknowledgements

This project was supported by USDA/ARS 6251-51000-006-00D

References

No reference found.