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Urinary metabolome in ex-preterm adults following postnatal dietary intervention

Presented at the Neonatal Society 2012 Autumn Meeting.

Parkinson JRC1, Hyde MJ1, Wijeyesekera D2, Holmes E2, Singhal A3, Modi N1

1 Section of Neonatal Medicine, Chelsea and Westminster campus, Imperial College London
2 Section of Biomolecular Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London
3 Clinical Trials & Cardiovascular Nutrition Group, MRC Childhood Nutrition Research Centre, ICH, London

Background: Optimising nutrition represents a key therapeutic window for improving outcomes for preterm babies in both infancy and adulthood. We have previously presented data to the Society showing preterm adults demonstrate an altered urinary metabolic profile compared to term born controls; including increased acetylated glycoprotein fragments, associated with inflammation and reduced hippurate, which has an inverse correlation with blood pressure (1). The aim of this study was to determine if postnatal nutritional intervention alters metabonomic profile in ex-preterm adults.

Methods: We analysed urine samples collected during a follow-up of a cohort of ex-preterm adults (aged 19-20 years, gestational age (GA) (mean ± SD: 30.9 ± 2.7 years)) randomised to banked breastmilk (BBM), term formula (TF) or preterm formula (PTF) for an average of one month postnatally (2). 1H NMR spectroscopy was performed on urinary samples. Spectra were analysed by dietary group and by gender. Orthogonal projection to latent structure discriminant analyses (O-PLS-DA) was used to model class differences, and identify metabolites contributing to the differences between groups. Gender specific group comparisons were calculated for 1. higher nutrient (PTF) versus lower nutrient (TF and BBM combined), 2. PTF vs. BBM groups and 3. PTF versus TF. In addition, spectra were correlated with birth weight (bwt), GA and 2 week bwt z scores.

Results: We studied 197 healthy young adults (BBM, n=55 (28 men)), term formula (TF: n=48 (14M)) or preterm formula (PTF, n=94 (40M)). We found no significant differences in urinary spectra between dietary groups when combined or analysed in a gender specific fashion. Correlation analysis revealed a significant correlation between GA and preterm spectra (R2: 0.65, Q2: 0.26). Metabolites significantly correlated with increased GA are listed in Table 1.

Urinary metabolome in ex-preterm adults following postnatal dietary intervention


Table 1: Metabolites significantly associated with gestational age

Conclusion: Despite a number of physiological benefits observed in ex-preterm individuals randomised to BBM (2), we observed no differences in metabolic profile between dietary intervention groups. In line with previous metabonomic data an increased GA was associated with increased hippurate (1) and 4-cresyl sulphate, metabolites associated with reduced blood pressure, improved gut microflora and lower BMI (3). In addition to the established inverse correlation between prematurity and blood pressure, these data suggest that gut health in ex-preterm adults is also dependent on the degree of prematurity.

Corresponding author: jrcp@imperial.ac.uk

References
1. Aberrant adiposity and ectopic lipid deposition characterize the adult phenotype of the preterm infant. Thomas et al. Pediatr Res. (2011) Nov;70(5):507-12.
2. Early diet and peak bone mass: 20 year follow-up of a randomized trial of early diet in infants born preterm. Fewtrell et al. (2009) Bone 45 142–149
3. Quantitative UPLC-MS/MS analysis of the gut microbial co-metabolites phenylacetylglutamine, 4-cresyl sulphate and hippurate in human urine. Wijeyesekera A et al. (2012) Anal. Dyn Meth 2012, 4, 65

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