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Breast milk exposure influences brain development in preterm infants

Presented at the Neonatal Society 2017 Autumn Meeting.

Blesa M, Sullivan G, Telford EJ, Semple SI, Quigley A, Bastin M, Boardman JP

MRC Centre for Reproductive Health, University of Edinburgh, Edinburgh EH16 4TJ, UK

Background: Preterm infants are at increased risk of brain injury and long term neurocognitive impairment. Breastfeeding is associated with increased IQ and improved brain growth in childhood and adolescence (1,2,3) but study designs leave uncertainty about the dose and timing of exposure required to benefit brain development, and whether preterm birth confounds the benefits observed in infants born at term. We combined early life enteral nutritional information with structural and diffusion brain MRI data, to test the hypothesis that breastmilk exposure influences brain development in preterm infants.

Methods: Participants: 47 Preterm infants (mean GA at birth 29+3 weeks, range 23+2-33+0). MRI: structural and diffusion MRI were acquired at term-equivalent age using a Siemens Magnetom Verio 3T system. After pre-processing, analyses of brain growth, white matter microstructure (fractional anisotropy, FA) and connectivity were carried out using volumetrics, tract-based spatial statistics (TBSS) (4), anatomically-constrained tractography (ACT)5 and network-based statistics (NBS)6. Breast milk exposure: daily nutritional intake was collected from birth until hospital discharge using electronic patient records, and infants were classified as receiving < or ≥ 75% days of exclusive breast milk. Ethical approval was obtained from the UK NRES and parents provided written informed consent. This work was supported by Theirworld.

Results: 27 infants received exclusive breast milk for ≥75% of their neonatal admission and 20 infants received exclusive breast milk feeds for <75% of their stay. There were no significant differences in mean GA at birth, length of neonatal admission, parenteral nutrition days, postnatal somatic growth or exposure to bronchopulmonary dysplasia (BPD) and histological chorioamnionitis (HCA) between groups. Infants in the higher breastmilk group had increased FA in the splenium of the corpus callosum, cingulum cingulate gyri, corticospinal tracts and the left posterior limb of the internal capsule when compared to those who received less breast milk. Voxels demonstrating significantly higher FA (TEFC corrected p<0.05) are highlighted (Figure 1). These findings are supported by NBS, which showed higher FA-based connectivity in infants in the higher breastmilk group (p=0.04) (Figure 2). Analyses are adjusted for GA at birth, age at scan, BPD and HCA. There were no statistically significant differences in brain volumes between groups.

Breast milk exposure influences brain development in preterm infants


Figure 1: (left) NBS demonstrating edges with higher FA in infants who received ≥75% days exclusive breastmilk feeds. Interhemispheric connections are highlighted in red and intrahemispheric connections in blue.
Figure 2: (right) TBSS: Highlighted voxels show higher FA in infants who received ≥75% days exclusive breastmilk feeds.

Conclusion: These data suggest that the quantity of breast milk given to preterm infants during Neonatal Unit care influences brain development.

Corresponding author: james.boardman@ed.ac.uk

References
1. Horta, B.L. et al. (2015). Breastfeeding and intelligence: a systematic review and meta-analysis. Acta Paediatr 104(467): 14-192
2. Isaacs.E.B. (2010) Impact of breast milk on intelligence quotient, brain size, and white matter development. Pediatr Res 67:357-62
3. Deoni S.C.L. (2013) Breastfeeding and early white matter development. Neuroimage 82:77-82
4. Smith, S.M. et al. (2006) Tract-based spatial statistics: Voxelwise analysis of multi-subject diffusion data. NeuroImage 31:1487
5. Smith R.E. et al.(2012) Anatomicallyconstrained tractography NeuroImage
6. Zalesky, A., Fornito A. & Bullmore, E.T. (2010) Network-based statistic: identifying differences in brain networks. NeuroImage.

Acknowledgement
We thank Thorsten Feiweier at Siemens Healthcare for collaborating with dMRI acquisitions (Works-in-Progress Package for Advanced EPI Diffusion Imaging).

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