Preterm nutritional intake and MRI phenotype at term age: a prospective observational study

Objective: To describe (1) the relationship between nutrition and the preterm-at-term infant phenotype, (2) phenotypic differences between preterm-at-term infants and healthy term born infants and (3) relationships between somatic and brain MRI outcomes. Design: Prospective observational study. Setting: UK tertiary neonatal unit. Participants: Preterm infants (<32 weeks gestation) (n=22) and healthy term infants (n=39) Main outcome measures: Preterm nutrient intake; total and regional adipose tissue (AT) depot volumes; brain volume and proximal cerebral arterial vessel tortuosity (CAVT) in preterm infants and in term infants. Results: Preterm nutrition was deficient in protein and high in carbohydrate and fat. Preterm nutrition was not related to AT volumes, brain volume or proximal CAVT score; a positive association was noted between human milk intake and proximal CAVT score (r=0.44, p=0.05). In comparison to term infants, preterm infants had increased total adiposity, comparable brain volumes and reduced proximal CAVT scores. There was a significant negative correlation between deep subcutaneous abdominal AT volume and brain volume in preterm infants (r=−0.58, p=0.01). Conclusions: Though there are significant phenotypic differences between preterm infants at term and term infants, preterm macronutrient intake does not appear to be a determinant. Our preliminary data suggest that (1) human milk may exert a beneficial effect on cerebral arterial vessel tortuosity and (2) there is a negative correlation between adiposity and brain volume in preterm infants at term. Further work is warranted to see if our findings can be replicated and to understand the causal mechanisms

Functional cardiac MRI in preterm and term newborns.

Published versio

Population-based studies of myocardial hypertrophy: high resolution cardiovascular magnetic resonance atlases improve statistical power

BACKGROUND: Cardiac phenotypes, such as left ventricular (LV) mass, demonstrate high heritability although most genes associated with these complex traits remain unidentified. Genome-wide association studies (GWAS) have relied on conventional 2D cardiovascular magnetic resonance (CMR) as the gold-standard for phenotyping. However this technique is insensitive to the regional variations in wall thickness which are often associated with left ventricular hypertrophy and require large cohorts to reach significance. Here we test whether automated cardiac phenotyping using high spatial resolution CMR atlases can achieve improved precision for mapping wall thickness in healthy populations and whether smaller sample sizes are required compared to conventional methods. METHODS: LV short-axis cine images were acquired in 138 healthy volunteers using standard 2D imaging and 3D high spatial resolution CMR. A multi-atlas technique was used to segment and co-register each image. The agreement between methods for end-diastolic volume and mass was made using Bland-Altman analysis in 20 subjects. The 3D and 2D segmentations of the LV were compared to manual labeling by the proportion of concordant voxels (Dice coefficient) and the distances separating corresponding points. Parametric and nonparametric data were analysed with paired t-tests and Wilcoxon signed-rank test respectively. Voxelwise power calculations used the interstudy variances of wall thickness. RESULTS: The 3D volumetric measurements showed no bias compared to 2D imaging. The segmented 3D images were more accurate than 2D images for defining the epicardium (Dice: 0.95 vs 0.93, P < 0.001; mean error 1.3 mm vs 2.2 mm, P < 0.001) and endocardium (Dice 0.95 vs 0.93, P < 0.001; mean error 1.1 mm vs 2.0 mm, P < 0.001). The 3D technique resulted in significant differences in wall thickness assessment at the base, septum and apex of the LV compared to 2D (P < 0.001). Fewer subjects were required for 3D imaging to detect a 1 mm difference in wall thickness (72 vs 56, P < 0.001). CONCLUSIONS: High spatial resolution CMR with automated phenotyping provides greater power for mapping wall thickness than conventional 2D imaging and enables a reduction in the sample size required for studies of environmental and genetic determinants of LV wall thickness

Link between increased gut hormones signaling satiety and reduced food reward following gastric bypass surgery for obesity

CONTEXT: Roux-en-Y gastric bypass (RYGB) surgery is an effective long-term intervention for weight loss maintenance, reducing appetite, and also food reward, via unclear mechanisms. OBJECTIVE: To investigate the role of elevated satiety gut hormones after RYGB, we examined food hedonic-reward responses after their acute post-prandial suppression. DESIGN: These were randomized, placebo-controlled, double-blind, crossover experimental medicine studies. PATIENTS: Two groups, more than 5 months after RYGB for obesity (n = 7-11), compared with nonobese controls (n = 10), or patients after gastric banding (BAND) surgery (n = 9) participated in the studies. INTERVENTION: Studies were performed after acute administration of the somatostatin analog octreotide or saline. In one study, patients after RYGB, and nonobese controls, performed a behavioral progressive ratio task for chocolate sweets. In another study, patients after RYGB, and controls after BAND surgery, performed a functional magnetic resonance imaging food picture evaluation task. MAIN OUTCOME MEASURES: Octreotide increased both appetitive food reward (breakpoint) in the progressive ratio task (n = 9), and food appeal (n = 9) and reward system blood oxygen level-dependent signal (n = 7) in the functional magnetic resonance imaging task, in the RYGB group, but not in the control groups. RESULTS: Octreotide suppressed postprandial plasma peptide YY, glucagon-like peptide-1, and fibroblast growth factor-19 after RYGB. The reduction in plasma peptide YY with octreotide positively correlated with the increase in brain reward system blood oxygen level-dependent signal in RYGB/BAND subjects, with a similar trend for glucagon-like peptide-1. CONCLUSIONS: Enhanced satiety gut hormone responses after RYGB may be a causative mechanism by which anatomical alterations of the gut in obesity surgery modify behavioral and brain reward responses to food

Nutritional Evaluation and Optimisation in Neonates (NEON) trial of amino acid regimen and intravenous lipid composition in preterm parenteral nutrition: a randomised double-blind controlled trial

Background Parenteral nutrition (PN) is central to the care of very immature infants. Early intakes of higher amounts of amino acids and the use of lipid emulsions containing fish oils are recommended by current international recommendations. Objective To confirm the safety and demonstrate efficacy of the immediate introduction of the recommended daily intake of amino acids (Imm-RDI) and soya bean oil, medium-chain triglycerides, olive oil and fish oil lipid in PN to increase non-adipose (lean) body mass and decrease intrahepatocellular lipid (IHCL) content. Design Multicentre, double-blind, 2 × 2 factorial and randomised controlled trial (RCT). Setting Neonatal units in London and south-east England, UK. Participants Extremely preterm infants born before 31 weeks of gestation without major congenital or life-threatening abnormalities who could to be randomised to receive PN within 24 hours of birth. Interventions Infants were randomised within 24 hours of birth to receive PN containing either high [RDI of amino acids (Imm-RDI)] or low [incremental amino acids (Inc-AA) control] levels of amino acids. In addition, infants were randomised to receive either 20% SMOFlipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) or 20% Intralipid® (Fresenius Kabi AG, Richmond Hill, ON, Canada) (control). This resulted in four groups: (1) Inc-AA/Intralipid, (2) Inc-AA/SMOFlipid, (3) Imm-RDI/Intralipid and (4) Imm-RDI/SMOFlipid. The intervention was continued until infants were receiving 150 ml/kg/day of enteral feeds for 24 hours. Primary outcome measure For the amino acid intervention, this was non-adipose or lean body mass measured by magnetic resonance imaging. For the lipid composition intervention, this was IHCL content as measured by hepatic magnetic resonance spectroscopy. Primary outcomes were measured at term age equivalent, between 37 and 44 weeks postmenstrual age. Results We randomised 168 infants born before 31 weeks of gestation. We evaluated outcomes, at term, in 133 infants. There were no significant differences in non-adipose mass between the Imm-RDI and Inc-AA groups [adjusted mean difference 1.0 g, 95% confidence interval (CI) –108 to 111 g] or in levels of IHCLs between the SMOFlipid and Intralipid groups (adjusted mean SMOFlipid to Intralipid ratio 1.1, 95% CI 0.8 to 1.6). Infants receiving the Imm-RDI were more likely than Inc-AA infants to have blood urea nitrogen levels > 7 mmol/l [75% vs. 49% (p  10 mmol/l [49% vs. 18% (p < 0.01)]. Furthermore, head circumference at term was smaller in the Imm-RDI group (mean difference –0.8 cm, 95% CI –1.5 to –0.1 cm; p = 0.02). There were no significant differences in any prespecified secondary outcomes, including adiposity, liver function tests, weight, length and mortality. Limitations Not all eligible babies were available for recruitment, as pharmacy staff trained in clinical trial procedures were unavailable at weekends in three of the four centres. We were able to assess brain volumes in only one-third of participants, as imaging was carried out while the participants were sleeping naturally and we measured primary outcomes first and continued to brain imaging only if the infant remained asleep. Conclusions Immediate delivery of the recommended daily intake of parenteral amino acids does not benefit body composition or growth to term and may be harmful; SMOFlipid does not affect IHCL content. Future work The long-term functional outcomes of early administration of RDI of amino acids and the use of SMOFlipid, including neurodevelopment, body composition and metabolic health, should be evaluated. Trial registration Current Controlled Trials ISRCTN29665319 and EudraCT 2009-016731-34. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership

Sexual dimorphism in relation to adipose tissue and intrahepatocellular lipid deposition in early infancy

Sexual dimorphism in adiposity is well described in adults, but the age at which differences first manifest is uncertain. Using a prospective cohort, we describe longitudinal changes in directly measured adiposity and intrahepatocellular lipid (IHCL) in relation to sex in healthy term infants. At median ages of 13 and 63 days, infants underwent quantification of adipose tissue depots by whole-body magnetic resonance imaging and measurement of IHCL by in vivo proton magnetic resonance spectroscopy. Longitudinal data were obtained from 70 infants (40 boys and 30 girls). In the neonatal period girls are more adipose in relation to body size than boys. At follow-up (median age 63 days), girls remained significantly more adipose. The greater relative adiposity that characterises girls is explained by more subcutaneous adipose tissue and this becomes increasingly apparent by follow-up. No significant sex differences were seen in IHCL. Sex-specific differences in infant adipose tissue distribution are in keeping with those described in later life, and suggest that sexual dimorphism in adiposity is established in early infancy

Obese patients after gastric bypass surgery have lower brain-hedonic responses to food than after gastric banding

Objectives Roux-en-Y gastric bypass (RYGB) has greater efficacy for weight loss in obese patients than gastric banding (BAND) surgery. We hypothesise that this may result from different effects on food hedonics via physiological changes secondary to distinct gut anatomy manipulations. Design We used functional MRI, eating behaviour and hormonal phenotyping to compare body mass index (BMI)-matched unoperated controls and patients after RYGB and BAND surgery for obesity. Results Obese patients after RYGB had lower brain-hedonic responses to food than patients after BAND surgery. RYGB patients had lower activation than BAND patients in brain reward systems, particularly to high-calorie foods, including the orbitofrontal cortex, amygdala, caudate nucleus, nucleus accumbens and hippocampus. This was associated with lower palatability and appeal of high-calorie foods and healthier eating behaviour, including less fat intake, in RYGB compared with BAND patients and/or BMI-matched unoperated controls. These differences were not explicable by differences in hunger or psychological traits between the surgical groups, but anorexigenic plasma gut hormones (GLP-1 and PYY), plasma bile acids and symptoms of dumping syndrome were increased in RYGB patients. Conclusions The identification of these differences in food hedonic responses as a result of altered gut anatomy/physiology provides a novel explanation for the more favourable long-term weight loss seen after RYGB than after BAND surgery, highlighting the importance of the gut–brain axis in the control of reward-based eating behaviour

The effect of preterm birth on adiposity and metabolic pathways and the implications for later life

The last few years have seen an increasing number of extremely preterm babies surviving to adulthood. The relationship between low birth weight, insulin resistance and Type 2 diabetes in adulthood is well established, but less is known regarding the effects of preterm birth on body composition and metabolic pathways. In this review, we consider the literature regarding the effects of prematurity on body composition in the neonatal period, infancy, childhood and adulthood. We also discuss prematurity and metabolic related changes including blood pressure and insulin resistance in later life. Although several studies suggest that ‘catch-up’ growth is the main factor influencing the risk of an adverse body composition and metabolic profile, there is growing evidence to indicate an independent effect of gestational age on liver fat content and blood pressure in adulthood. However, more research is needed regarding specific metabolic changes in adults born preterm