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Altered urinary metabolome in young adults born below 33 weeks gestation

Presented at the Neonatal Society 2010 Spring Meeting.

Parkinson JR1, Hyde MJ1, Beckonert OP3, Yap I3, Thomas EL2, Doré C, Bell JD2, Holmes E3, Modi N1

1 Section of Neonatal Medicine, Chelsea and Westminster Campus, Imperial College, London, UK
2 Metabolic and Molecular Imaging Group, MRC Clinical Sciences Centre, Imperial College, London, UK
3 Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Imperial College, London, UK

Background: We have previously presented data to the Society showing preterm adults have increased blood pressure and altered body composition; notably an increase in intra-hepatocellular lipid and total adiposity, and in men, an increase in internal-abdominal adipose tissue (1).

Aims and Methods: In this study we compared blood plasma and urinary metabolites in ex-preterm young adults and term controls. Glucose, total cholesterol, triglycerides, high-density lipoprotein, low density lipoprotein and insulin were measured by standard clinical methods. Insulin sensitivity was assessed from fasting concentrations of glucose (G0) and insulin (I0) using the Quantitative Insulin Sensitivity Check Index (QUICKI = 1/[log10 G0 (mg/dl) + log10 I0 (μU/ml)]). 1H NMR spectroscopy was performed on urine and blood serum samples (2). Spectra were analysed by gender for differences in metabolomic profile between term and preterm groups. The study received National Ethics Service approval (REC 07/HO11/118).

Results: We have studied 48 healthy young adults, aged 19-27y, born term (controls; 10M, 15F) or preterm (<33 weeks gestation; 13M, 10F). We detected no difference in blood biochemistry or serum metabolome between term and preterm individuals. There were significant differences in the urinary metabolome of term and preterm individuals. The most marked differences were observed in preterm males, who demonstrated significant elevation in methylamines and acetyl-glycoproteins and lower hippurate compared to term born controls (p<0.01). Female preterm subjects also demonstrated significantly increased acetylated glycoproteins and a trend towards lower hippurate.

Conclusion: Acetylated glycoprotein fragments are associated with inflammation; a prime candidate cause of hypertension and abdominal obesity (3). Hippurate has been show in large population studies to show an inverse correlation with blood pressure (4). The lower urinary hippurate observed in preterm males is in keeping with the higher blood pressure we have noted in these subjects and in reports from the around the world indicating that ex-preterms are at greater risk of elevated blood pressure. Our data indicate a role for metabolomic technologies in the identification of biomarkers for follow up of preterm infants.

1. Doolan A, Thomas EL, Uthaya S, Fitzpatrick J, Durighel G, McCarthy J, Bell J, Modi N. Intramyocellular lipid deposition in young adults born <33 weeks gestation. Neonatal Society; 2009.
2. Beckonert O, Keun HC, Ebbels TM et al. Metabolic profiling, metabolomic and metabonomic procedures for NMR spectroscopy of urine, plasma, serum and tissue extracts. Nat Protocols 2007; 2(11):2692-2703.
3. Cartier A, Cote M, Lemieux I et al. Age-related differences in inflammatory markers in men: contribution of visceral adiposity. Metabolism 2009; 58(10):1452-1458.
4. Trump S, Laudi S, Unruh N, Goelz R, Leibfritz D. 1H-NMR metabolic profiling of human neonatal urine. MAGMA 2006; 19(6):305-312

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