Molecular and Metabolomic Mechanisms Affecting Growth in Children Born Small

Abstract

Small for gestational age (SGA) is defined as a birth weight or crown to heel length of -2 or more standard deviation scores. It is associated with increased risk of mortality and morbidity in the neonatal period and also has long term effects including an increased risk of developing type II diabetes, high blood pressure and cardiovascular disease later in life. Infants born SGA usually show catch-up growth within the first few years of life. However in the UK, ~1500 SGA children each year remain small and the reason for this is not understood.The aim of this work was to investigate the molecular mechanisms known to contribute to post-natal growth and also to develop a metabolomic profile in children born SGA. Skin biopsies were obtained with local ethical approval from prepubertal healthy children and children born SGA. Cell turnover (proliferation and apoptosis) and growth hormone (GH) and insulin like growth factor-I (IGF-I) signalling in fibroblasts was assessed and the metabolomic profile in these groups was determined. During this study, blood samples and auxological data were also obtained in children born SGA with catch-up growth and children born SGA without catch-up growth. Cell counting and bromodeoxyuridine incorporation demonstrated that proliferation was comparable between SGA cells compared to control cells under basal, GH (200ng/ml) and a combination of GH (20ng/ml) plus IGF-I (10ng/ml) stimulated conditions. However, IGF-I (100ng/ml) stimulated proliferation was significantly reduced in the SGA cells compared to control cells (p

Date of Award	31 Dec 2014
Original language	English
Awarding Institution	The University of Manchester
Supervisor	Peter Clayton (Supervisor) & Melissa Westwood (Supervisor)