R.D.S.P. is funded by MRC grant number G0800674. M.G.H., J.M.M. and C.D.J.S. are supported by an MRC Centre grant G0601943. S.R. is supported by Great Ormond Street Hospital Children’s Charity. This study was supported by the NIHR UCLH/UCL Comprehensive Biomedical Research Centre and undertaken at University College London Hospitals/University College London, which received a proportion of funding from the Department of Health's National Institute for Health Research Biomedical Research Centres funding scheme. Methodology: prospective, observational, performed at one institution.