The fetal origins of adult disease

by

ACKNOWLEDGEMENT

There is an immense role of my supervisor, family and associations for the completion of this research study. I would be gratitude to them for supporting me and assisting me.

DECLARATION

I take oath that the entire dissertation has been completed by me and the entire work has been done by writing and no copy pasting material has been added in this dissertation.

Signed __________________ Date _________________

ABSTRACT

The concept of “fetal origins” of adult disease was first hypothesized by David Barker and colleagues at the University of Southampton. They hypothesized that factors in utero influence the development of disease later in life. This hypothesis was based on the positive relationship observed in England and Wales between cardiovascular and stroke death in the early 1970's and neonatal mortality some fifty years earlier. High infant mortality was taken to reflect poor nutrition across the whole study population, and this was linked to high cardiovascular and stroke death later in life in adults who survived. From this relationship they concluded that poor health of mothers was important in stroke risk of the children later in life. Early in the genesis of the area of fetal programming Barker, et al observed a correlation between low birth weights and the incidents of Hypertension. Since then numerous studies, either following human subjects or utilizing animal models, have observed the effect of intra-uterine growth restriction (IUGR) or fetal malnutrition on the development of chronic diseases later in life. The onset of these diseases has been associated with rapid postnatal catch up growth. The Fetal Origins of Adult Diseases new emphasis on the fetal environment has led to the hypothesis that exposure to environmentally relevant levels of xenoestrogens may cause alterations in the endocrine status of the developing fetus that could contribute to the development of pathologies in adulthood. Barker suggested that poor nutrition during early development led to an increased susceptibility to nutritional problems as a result of a more affluent diet later in life. The poorly nourished mother essentially gives the fetus a forecast of the nutritional environment into which it will be born. Reduced fetal growth was associated with hypertension, insulin resistance, glucose intolerance and diabetes, coronary heart disease, stroke and other vascular heart disease in adulthood; these are very strong and consistent results.

TABLE OF CONTENTS

ACKNOWLEDGEMENTII

DECLARATIONIII

ABSTRACTIV

CHAPTER # 1: INTRODUCTION1

Background of the Study1

The Problem2

Purpose of the Study2

Aims and Objectives of the Study3

Research Question3

Structure of Dissertation3

CHAPTER # 2: METHODS5

Methodology5

Data Collection5

Systematic Review5

CHAPTER # 3: LITERATURE REVIEW7

Hypotheses8

Statistical Analysis9

Results11

CHAPTER # 4: DISCUSSION13

Pre- and post-natal growth and adult disease16

Plasticity in early development18

Linking fetal environments with adult phenotypes in humans19

Fetal Programming by Nutrient Restriction23

CHAPTER # 5: CONCLUSION27

REFERENCES29

APPENDIX40

CHAPTER # 1: INTRODUCTION

Background of the Study

The Barker et al. study demonstrating that low birth weight increases the risk of adult mortality due to ischemic heart disease (Barker, et al., 1989 575). Additional studies by Barker et.al. lead to the development of Barker's Hypothesis; which states that the need for fetal adaptation to limited nutrient supply permanently alters offspring physiology and ...