Table 1.
Summary of included studies
| Study | Type | Population | Nutritional intervention | MRI outcome | Results |
|---|---|---|---|---|---|
| Breast milk | |||||
| Belfort et al.23 | Cohort | GA <30 weeks, BW < 1250 g, no congenital anomalies (n= 180) | BM intake in first 28 days of life (days >50% BM, mean daily intake) | Total and regional brain volumes at TEA and 7 years (n = 160 at TEA, n = 108 at 7 years) |
TEA and BM: ↑ deep nuclear GM and hippocampal volumes 7 years and BM: No associations |
| Deoni et al.18 | Cross-sectional | GA 37–42 weeks, healthy and typically developing (n = 133) |
Feed type: Breastfed (≥3 months) vs. formula or both Breastfeeding duration: <12 months vs. >15 months |
WM microstructure using mcDESPOT myelin water fraction (VFM) at age 10 months-4 years |
Breastfed vs. formula (2.2–4 years): ↑ VFM (BM vs. formula: right premotor cortex and frontal lobe, CST; BM vs. both: premotor cortices, left optic radiation, right prefontal cortex and parietal lobe) Breastfeeding duration: ↑VFM (Broca’s area, parietal lobe, secondary somatosensory cortex; right auditory cortex and frontal lobe; left optic radiation, premotor, and primary somatosensory cortex) |
| Isaacs et al.24 | Cohort | GA ≤30 weeks, neurologically normal (n = 50) | %BM (of total dietary intake) | Total and regional brain volumes at 13–19 years | %>BM: ↑ Total and WM volume Sex-specific: ↑ Total and WM volume in males |
| Lu by et al.22 | Cohort | Full-term, IQ >75 (n = 148) | Breastfed (for >30) days vs. non-breastfed | Total regional brain volumes at 9–14 years | ↑ GM (both cortical and subcortical) and total brain volume |
| Kafouri et al.20 | Cohort | Full-term, no cardiac, neurologic, or psychiatric disease (n = 571) | Duration of exclusive breast feeding | Regional cortical thickness at 12–18 years | ↑ Cortical thickness in superior and inferior parietal lobe |
| Ou et al.21 | Cohort | Full-term, BW 5–95%ile, no neurologic/psychiatric history (n = 56) | Breastfed vs. formula-fed in first 12 months | WM microstructure using DTI (FA) at 8 years |
Predominant breastfeeding vs. formula (sex-specific): ↑ FA in males (left SLF, cingulum, corpus callosum, and posterior crossing fibers) Excusive breastfeeding vs. formula (sex-specific): ↑ FA in males (left SLF, corona radiata, external capsule, PLIC, posterior crossing fibers, and 8/9 regions of interest) |
| Ou et al.19 | Cohort | Full-term, BW 5–95%ile, no medical/psychiatric history (n = 42) | Breastfed vs. formula-fed in first 12 months | GM Volume using VBM and fMRI at 8 years |
BM and GM volume: ↑ Left parietal and temporal lobe volumes BM and fMRI: ↑ Activation for perception (temporal right frontal lobe) and language (left temporal and occipital lobes) |
| Pogribna et al.25 | Cohort | G A ≤29 weeks, BW ≤ 1000 g, no congenital CNS anomalies (n = 75) | Duration of BM intake | WM microstructure using DTI (FA and MD) at TEA | ↑ FA in corpus callosum |
| Vasu et al.26 | Cohort | G A <32 weeks (control GA 37–42 weeks), clinically well (n = 61) |
BM (EBM/DBM) and macronutrient intake until 34 weeks PMA | Total brain volume and cerebral arterial vessel tortuosity (CAVT) score (via MR angiography) at TEA | BM and total brain volume: No association BM and CAVT: Borderline ↑ overall CAVT (p = 0.05) Macronutrient and total brain volume, CAVT score: No association |
| LCPUFA supplementation | |||||
| Almaas et al.30 | RCT | BW <1500 g, no congenital anomalies or severe IVH (n = 81) | BM (EBM/DBM) ± high-dose LCPUFA (DHA 32 mg/AA 31 mg total) | Total and regional brain volumes and cortical surface reconstruction (volume, surface area, thickness) at 8 years |
Volumes: No difference between groups Cortical surface: No difference between groups |
| Almaas et al.29 | RCT | BW <1500 g, no congenital anomalies or severe IVH (n = 82) | BM (EBM/DBM) ± high-dose LCPUFA (DHA 32 mg/AA 31 mg total) | WM microstructure using DTI (FA, MD, AD, RD) at 8 years | Borderline ↑ FA in corpus callosum (p = 0.08) |
| Lepping et al.31 | RCT | GA 37–42 weeks, healthy (n = 42) | Formula ± LCPUFA (DHA/AA) in 4 DHA groups: control, 0.32%, 0.64%, 0.96% | GM and WM volume using VBM, fMRI, rsMRI, and 1H MRS at 9 years |
fMRI and LCPUFA: ↑ Activation parietal lobe, anterior cingulate cortex, and cerebellum rsMRI and LCPUFA: ↑ Prefrontal-parietal cortex connectivity (dorsal attention network) VBM and LCPUFA: ↑ WM volume anterior cingulate cortex and R parietal lobe 1H MRS and LCPUFA: ↑ N-acetylaspartate and myo-inositol |
| Tarn et al.33 | Cohort | G A <32 weeks, no congenital anomalies, syndromes, or infections | Early and near-term red blood cell DHA, AA, EPA, and LA levels | WM microstructure using DTI (FA, MD, AD, RD) and brain injury (IVH, WM injury, cerebellar hemorrhage) on early and near-term MRI |
Early DHA and brain injury: |IVH incidence/severity Early DHA and DTI: ↓MD in PLIC and optic radiations Early LA and DTI: ↑ MD in optic radiations |
| van Wezel-Meijler et al32 | RCT | GA <34 weeks, BW < 1750 g, no CNS abnormalities or severe ROP (n = 42) | Formula ± LCPUFA supplementation (DHA 15 mg/AA 31 mg per 100 mL) until 6 months | Global and visual myelination score using T1/T2 images at 3 and 12 months |
3 months and LCPUFA: No difference between groups 12 months and LCPUFA: No difference between groups |
| Macronutrient and energy | |||||
| Beauport et al.34 | Cohort | G A <30 weeks, no congenital anomalies or severe IVH (n = 51) | Cumulative macronutrient and energy intake in first 2 weeks of life | Brain maturation and injury using semi-quantitative |
Total score: ↓ Severity with ↑ fat and energy intake Kidokoro score (grouped by severity) at TEA GM score: ↓ Severity with ↑ fat, carbohydrate, protein, and energy intake |
| Coviello et al.28 | Cohort | GA <31 weeks, no congenital anomalies or CNS infection (n = 131) | Cumulative macronutrient, energy, and BM intake in first 28 days of life | Total and regional brain volumes and WM microstructure using DTI (FA) at TEA |
Cumulative (fat/energy) and enteral (protein/fat/energy) intake and volume: ↑ Total and regional brain volumes (cerebellum, BG/thalamus) PN and volume: ↓ Cerebellum, BG/thalamus, cortical GM, and total brain volumes Cumulative (fat/energy) and enteral (protein/fat/energy) intake and DTI: ↑ FA in PLIC PN and DTI: ↑ FA in PLIC BM andDTI (sex-specific): ↑ FA in left PLIC in males |
| Hansen-Pupp et al.35 | Cohort | GA <31 weeks, no major anomalies (n = 51) | Daily protein and energy intake until 35 weeks PMA | Total and regional brain volumes at TEA | No association with any volume |
| Isaacs et al.36 | Cohort | GA ≤30 weeks, neurologically normal (n = 76) | Standard feeds (donor BM or term formula) vs. high-nutrient (↑ protein/energy) formula | Total and regional brain volumes at 13–19 years | High-nutrient (vs. standard): t caudate volume Sex-specific: t caudate volume in males |
| Paviotti et al.37 | Cohort | BW <1500 g, no congenital anomalies or severe IVH (n = 42) | Mean macronutrient and energy intake until discharge | Total brain and cerebellar volume at TEA | No association with total brain or cerebellar volume |
| Schneider et al.27 | Cohort | GA <30 weeks, no congenital anomalies or severe IVH (n = 49) | Cumulative macronutrient, energy, and BM intake in first 2 weeks of life | Total and regional brain volume and WM microstructure using DTI (FA) at 3 time-points (1st week of life, 3 weeks of life or 34–35 weeks, TEA) |
Lipid/energy and volume: ↑ BG and total brain volume (greater enteral effect) Lipid/energy and DTI: ↑ FA (corona radiata, thalamic radiations, SLF, CST) Protein and volume: ↑Total brain volume Enteral protein and DTI: ↑ FA (corona radiata, thalamic radiations, CST) BM and DTI: ↑ FA (corona radiata, thalamic radiations, SLF) |
| Strom men et a I.38 | RCT | BW <1500 g, no congenital anomalies (n = 50) | High-nutrient (↑ protein, fat, LCPUFA, vitamin A) vs. control until 52 weeks PMA or 5.5 kg | WM microstructure using DTI (MD) at TEA (n = 25 with DTI) | ↓ MD in SLF, borderline for CST (p = 0.05) |
| Tan et al. (2008)39 | RCT | GA ≤29 weeks, <7 days of life, no congenital anomalies (n = 65) |
Hyperalimentation: Enteral and parenteral (↑ macronutrient and calories) vs. standard nutrition until 34 weeks PMA Intake/deficit: Energy and protein for first 28 days of life |
Total and regional brain volumes and WM maturation using T2 relaxation times at TEA |
Hyperalimentation and olumes: No significant difference between group WM maturation (fronto-parietal): No significant difference between groups Energy intake in first 28 days: ↑Total brain volume Energy deficit in first 28 days: ↓Total brain volume |
BW birth weight, GA gestational age, PMA postmenstrual age, TEA term-equivalent age, IVH intraventricular hemorrhage, DTI diffusion tensor imaging, FA fractional anisotropy, MD mean diffusivity, AD axial diffusivity, RD radial diffusivity, fMRI functional MRI, rsMRI resting-state MRI, 1H MRS proton magnetic resonance spectroscopy, VBM voxel-based morphometry, WM white matter, GM gray matter, CST corticospinal tract, SLF superior longitudinal fasciculus, PLIC posterior limb of internal capsule, BG basal ganglia, BM breast milk, LCPUFA long-chain polyunsaturated fatty acids, DHA docosahexanoic acid, AA arachidonic acid, LA linoleic acid, EPA eicosapentaenoic acid, PN parenteral nutrition, RCT randomized controlled trial