'Development and evaluation of biomarkers of infant nutrition, growth and body composition'

Lead Research Organisation: University of Cambridge
Department Name: Paediatrics

Abstract

We know that not only the conditions babies experience in the womb (in-utero) but also their nutrition in early life affects their growth and influences later childhood and adult weight gain. We aim to look for early markers of different babies‘ growth and body composition, reflecting in-utero exposures and nutrition after birth. Our project aims to identify these markers in blood. We will use different methods to look for these markers, including standard hormonal assay techniques, and newer methods looking at metabolic pathways.

The project will use data from babies in the Cambridge Baby Growth Study cohort, (2001-2008). These babies have had several growth measurements taken, including weight, height and skinfold thicknesses, up until 2 years of age. Many of them have had blood taken, which we can use and match to different growth patterns. We will also aim to recruit new babies, focussing on those born to mothers with Diabetes.

Understanding the markers of babies‘ growth will have great scientific and public implications, focussing on improving the health outcomes for the population. It will identify and predict how babies grow, risks for later obesity and the possibility of adapting early nutrition and feeding patterns in those at high risk.

Technical Summary

This project aims to identify, validate and use novel and emerging biomarkers of early infant nutrition, growth and body composition. The objectives are to develop and evaluate biomarker assays, identify relationships between these potential biomarkers and patterns of infant growth and nutritional intake, and to recruit a new cohort subset with high-risk patterns of infant growth.

It is known that the intrauterine environment but also early nutritional factors influence infant growth and predispose to later obesity and metabolic risk. It is hypothesised that biomarkers exist, which reflect infant growth and nutrition, for example Ong et al (2009) found that higher IGF-1 levels in formula-fed babies correlated with greater statural growth. However, they concluded that other hormones were likely to be implicated in the development of increased adiposity.

We will begin by using data from the prospective Cambridge Baby Growth Study (CBGS) cohort, focussing on those showing rapid ‘catch up‘ and ‘catch down‘ growth. This large, population based cohort, recruiting newborns between 2001 and 2008, examines the prenatal and postnatal determinants of early growth, with anthropometric measurements, including body weight, length and skinfold thicknesses. Many of the babies have also had blood-spot samples taken. Blood will be analysed for novel biomarkers. We will develop assays, focussing on hormonal biomarkers, such as leptin, adiponectin and C-peptide. This will predominately be carried out in the Department of Clinical Biochemistry, Cambridge. Work will also be done at the WellChild Laboratory (St Thomas‘ Hospital, London), using mass spectrometry to pilot whether a specific metabolite/metabolomic or protein/proteomic profile can discriminate between different extremes of body composition.

We will enhance the CBGS, with recruitment of babies born to mothers with Type 2 Diabetes Mellitus and Gestational Diabetes Mellitus, collecting the same comprehensiveic, anthropometric and nutritional data, and blood spot samples.

Understanding biomarkers of infant nutrition and body composition will have great scientific value, identifying and predicting risk factors for later adiposity and adult disease. This will then allow us to develop early targeted dietary or other interventions to high risk infants. There are large public health implications, for the health outcomes of the population, and this research fits in with MRC research priorities: living a long and healthy life, and obesity research and methodology development.

Publications

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Acharjee A (2017) The translation of lipid profiles to nutritional biomarkers in the study of infant metabolism. in Metabolomics : Official journal of the Metabolomic Society

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Prentice P (2016) Cohort Profile: the Cambridge Baby Growth Study (CBGS). in International journal of epidemiology

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Prentice P (2015) Lipidomic Analyses, Breast- and Formula-Feeding, and Growth in Infants in The Journal of Pediatrics

 
Description BBSRC Diet and Health Research Industry Club
Amount £686,533 (GBP)
Organisation Biotechnology and Biological Sciences Research Council (BBSRC) 
Sector Public
Country United Kingdom
Start 07/2015 
End 07/2017
 
Description Cambridge-Africa Alborada Research Fund
Amount £7,250 (GBP)
Organisation University of Cambridge 
Department Alborada Research Fund
Sector Charity/Non Profit
Country United Kingdom
Start 03/2015 
End 09/2015
 
Description Collaborative grant, Mead Johnson Nutrition
Amount £119,560 (GBP)
Organisation Mead Johnson Nutrition 
Sector Public
Country United States
Start 10/2013 
End 10/2016
 
Description Collaborative grant, Mead Johnson Nutrition
Amount $530,733 (USD)
Organisation Mead Johnson Nutrition 
Sector Public
Country United States
Start 10/2015 
End 10/2017
 
Description ERA-HDHL Biomarkers in Nutrition and Health
Amount € 1,034,440 (EUR)
Organisation European Research Area 
Sector Public
Country Belgium
Start 03/2017 
End 03/2020
 
Description MRC Centenary Award (University of Cambridge)
Amount £7,500 (GBP)
Organisation Medical Research Council (MRC) 
Sector Academic/University
Country United Kingdom
Start 09/2012 
End 09/2013
 
Description Thomas Eden Watt fellowship
Amount £9,700 (GBP)
Organisation Royal College of Physicians of Edinburgh 
Sector Academic/University
Country United Kingdom
Start 03/2015 
End 09/2015
 
Title Dried blood spot lipidomics 
Description Collaboration to adapt lipidomic profiling with a 3.2mm DBS 
Type Of Material Biological samples 
Provided To Others? No  
Impact Now in a proposal for an international grant proposal. 
 
Title Research data supporting "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations" 
Description Phenotypic dataset and genotype meta-data for the publication by Petry et al. "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations" published in Diabetes & Metabolism (doi 10.1016/DIABET-D-16-00606). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
 
Title Research data supporting "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations" 
Description Phenotypic dataset and genotype meta-data for the publication by Petry et al. "Associations between a Fetal Imprinted Gene Allele Score and Late Pregnancy Maternal Glucose Concentrations" published in Diabetes & Metabolism (doi 10.1016/DIABET-D-16-00606). 
Type Of Material Database/Collection of data 
Year Produced 2017 
Provided To Others? Yes  
 
Description Breast milk analysis 
Organisation University of Wageningen
Country Netherlands 
Sector Academic/University 
PI Contribution Provision of breast milk samples
Collaborator Contribution Analysis of breast milk analytes
Impact In progress. Abstracts at scientific meetings, paper in draft
Start Year 2011
 
Description Collaboration with Prof Norris, University of Witwatersrand 
Organisation University of the Witwatersrand
Country South Africa 
Sector Academic/University 
PI Contribution Working with S African team to align data collection, follow up time points and sample collection, to allow blood spot and breast milk spot analysis in both cohorts. We provide laboratory analysis
Collaborator Contribution Joint learning, provide infancy samples
Impact Ongoing
Start Year 2015
 
Description Hormonal assays 
Organisation Cambridge University Hospitals NHS Foundation Trust
Department Core Biochemical Assay Laboratory (CBAL)
Country United Kingdom 
Sector Academic/University 
PI Contribution Collaboration for the methodology and analysis of hormones on dried blood spot samples
Collaborator Contribution Collaboration for the methodology and analysis of hormones on dried blood spot samples
Impact In progress. Abstracts at scientific meetings
Start Year 2010
 
Description Lipidomics in dried blood spots 
Organisation Medical Research Council (MRC)
Department MRC Mitochondrial Biology Unit
Country United Kingdom 
Sector Public 
PI Contribution Provision of biological material, and involvement in data analysis.
Collaborator Contribution Development of a lipidomic method for dried blood spots, with measurement of our samples. Paper submitted for publication.
Impact Anticipated publications
Start Year 2012
 
Description Metabolomics 
Organisation King's College London
Department WellChild Laboratory
Country United Kingdom 
Sector Academic/University 
PI Contribution Provision of samples for metabolomic analysis
Collaborator Contribution Dried blood spot methodology and analysis
Impact In progress Publication, abstracts in scientific meetings
Start Year 2010