Table.

Original research using MRI to investigate brain development in relation to human milk exposure during the preterm period.

First author	Year	Gestational age	N*	Exposure definition	Scanner type	MRI outcomes	Covariates	Summary of key findings
1) Pogribna	2013	≤29 weeks	86	Duration of human milk use, days	Philips Achieva (3T)	DTI Regions of interest: - anterior & posterior limbs of internal capsule - frontal & occipital periventricular zones - centrum semiovale - genu - splenium of corpus callosum - subventricular zone Control regions of interest: - external capsule -middle cerebellar peduncles	- Maternal hypertension - Private insurance - Outborn status - Antenatal steroids - Chorioamnionitis - Rupture of membranes duration - Hypothermia - Birth weight - Caucasian - Sex - White matter injury on ultrasound - NEC - PDA - Duration of caffeine therapy - Duration of mechanical ventilation	- Longer duration of human milk intake associated with greater FA maturation of corpus collosum (3.7 weeks per 10 days, 95% CI 1.9, 5.6)
2) Vasu	2014	<32 weeks	22	1) mL/kg/day, early (first week of life) and total (birth to 34+6 weeks PMA) 2) percent enteral diet as human milk	Philips Achieva (3T)	1) Total brain volume 2) Proximal cerebral arterial vessel tortuosity (CAVT) score	- Age at scan	- Early human milk intake positively correlated with CAVT score (r=0.31, p=0.18) - Total human milk intake positively correlated with CAVT score (r=0.44, p=0.05) - Percent enteral diet as human milk positively correlated with CAVT score (r=0.45, p=0.04)
3) Belfort	2016	<30 weeks	147	In first 28 days: 1) number of days with enteral intake >50% maternal milk 2) mean mL/kg/day maternal milk	General Electric Signa Echospeed (1.5T)	Brain volumes - total - gray matter - white matter (myelinated, unmyelinated) - deep nuclear gray matter - cerebellum - hippocampus	- Sex - Age at scan - Gestational age - Social risk - Neonatal illness	- Positive association of days enteral intake >50% maternal milk with deep nuclear gray matter volume (0.15 cc per day, 95% CI 0.05, 0.25) - Positive association of mean maternal milk intake with hippocampus volume (0.02 cc per 10 mL/kg/day, 95% CI 0.004, 0.03)
4) Blesa	2019	≤33 weeks	47	Percent of days receiving exclusive breast milk ≥75% or ≥90% vs. <75%	Siemens MAGNETOM Verio (3T)	1) Edgewise connectome 2) Network analysis 3) Tract based spatial statistics 4) Brain volumes - total - brainstem - cerebellum - cortical gray matter - deep gray matter - white matter	None	- Increased FA-weighted connectivity in ≥75% and ≥90% vs. <75% (connections involved intra- and inter-hemispheric frontoparietal and limbic system structures); also subcortical networks in ≥90% vs. <75% - Higher FA in major white matter tracts (splenium, centrum semiovale, corticospinal tracts, arcuate fasiculi, posterior limbs of internal capsule) in ≥75% and ≥90% vs. <75%
5) Ottolini	2020	≤32 weeks	68	Primarily breast milk or formula (>50% total enteral intake) Secondary analysis of donor milk vs. formula	General Electric Discovery (3T)	1) Brain volumes - total - cortical gray matter - white matter - deep gray matter - amygdala-hippocampus - cerebellum - brainstem 2) Diffusion tensor imaging	- gestational age - age at scan - average weight gain	- Larger volumes of total brain, amygdala-hippocampus, cerebellum in human milk vs. formula - Larger amygdala-hippocampus in donor milk vs. formula - lower MD in corpus callosum, R & L PLIC, middle cerebellar peduncle; lower FA in cerebellar vermis in human milk vs. formula - lower MD in corpus callosum, L PLIC, middle cerebellar peduncle, lower FA in cerebellar vermis in donor milk vs. formula
6) Niu	2020	≤33 weeks	50	Breastmilk >75% vs. <75%	Siemens Avanto (1.5T)	Resting state functional connectivity	None	Breastmilk positively correlated with - temporal global efficiency (r=0.362, p=0.014) - temporal nodal efficiency of bilateral caudate (r=0.439, p=0.002), right middle temporal gyrus (r=0.421, p=0.004), right inferior temporal gyrus (r=0.319, p=0.031), right insula gyrus (r=0.355, p=0.016), left thalamus (r=0.539, p=0.0001)
7) Parikh	2021	≤32 weeks	377	Exclusive maternal milk at discharge	Philips Ingenia (3T)	Volume of diffuse white matter abnormality (DWMA)	- Pneumothorax - Severe bpd - Severe rop - Dexamethasone - Caffeine - White matter abnormality score - Sex - Age - Center	Exclusive maternal milk associated with lower DWMA score

^*Sample size with neuroimaging data, may be lower than total cohort sample size

DTI is diffusion tensor imaging, FA is fractional anisotropy, MD is mean diffusivity, NEC is necrotizing enterocolitis, PDA is patent ductus arteriosus