<strong>16</strong> INTRAUTERINE PROGRAMMING OF NCDIntrauterine Programming<strong>of</strong> Non-Communicable Disease:Role <strong>of</strong> MaternalMicronutrientsUrmila S Deshmukh,Himangi G Lubree,Chittaranjan S YajnikKamalnayan Bajaj Diabetology Research Centre,King Edward Memorial Hospitaland Research Centre,Pune, IndiaIntroductionTwo thirds <strong>of</strong> all deaths in the world are due to non-communicablediseases (NCDs), and 80% <strong>of</strong> NCD deaths occur in low- andmiddle-income countries. 1 Cardiovascular diseases, obesity andtype 2 diabetes (T2D) are the major contributors to the globalburden <strong>of</strong> NCDs. Studies in the life course evolution <strong>of</strong> thesechronic diseases have highlighted an etiological role for factorswhich govern <strong>intrauterine</strong> and post-natal growth. Research inthis field could <strong>of</strong>fer a novel solution to the “primordial” prevention<strong>of</strong> conditions which are the most prominent killers intoday’s world.These novel ideas arose from a series <strong>of</strong> studies by DavidBarker and his colleagues in the UK. They proposed that <strong>intrauterine</strong>undernutrition initiated a number <strong>of</strong> adaptations in thefetus which increased disease susceptibility in later life, especiallywhen post-natal nutrition tended to be “excessive”. 2 A developingfetus has the ability to grow in different ways dependingon the surrounding (<strong>intrauterine</strong>) environment; this abilityis called the “plasticity”. 3 An unfavorable environment restrictsthe ability <strong>of</strong> the fetus to grow “wildly” and causes a permanentstructural or functional change, known as “<strong>programming</strong>”. 4 Indiais the world’s capital <strong>of</strong> low birth weight (LBW) babies, while atthe same time it is evolving into one <strong>of</strong> the economic powers <strong>of</strong>the world. It was clear that research in India would shed importantlight on these new and exciting ideas.Fetal nutrition, growth, birth size and <strong>programming</strong>The original ideas in this field were based on birth weight, forwhich there is a large database. However, it was clear from thebeginning that birth size was only a proxy for factors which affectfetal growth. These include genetic factors, maternal size,and <strong>intrauterine</strong> environment. Birth weight is not a sensitive indicator<strong>of</strong> <strong>intrauterine</strong> nutrition, nor is it specific for nutrition. 5Animal experiments show that a brief nutritional disturbancein early pregnancy permanently alters fetal physiology withoutany effect on birth size. 6 Thus, birth weight studies helped focusattention on <strong>intrauterine</strong> life as an important determinant<strong>of</strong> future health, but the excitement will focus on defining theenvironmental factors which are the “true exposures” in this association.This is where the current research is being directed.Possible mechanisms <strong>of</strong> <strong>programming</strong>Fetal growth and development are influenced by an interactionbetween genetic factors and the <strong>intrauterine</strong> environment. Thiswas beautifully shown with reference to the interaction betweenthe glucokinase gene and maternal hyperglycemia. 7 The birthsize <strong>of</strong> the newborn is influenced not only by inheritance <strong>of</strong> thegene, but also by maternal glycemia.Fetal <strong>programming</strong> can be manifested in various ways. Itmight affect size, body composition, systems, organs and cells.It also affects physiology, sometimes without affecting size.Changes include altered setting <strong>of</strong> different enzyme systemsand resetting <strong>of</strong> the endocrine axes. Endocrine mechanisms aremajor contributors to <strong>programming</strong>. Insulin-IGF (insulin-likegrowth factor) and the hypothalamic-pituitary-adrenal axis havebeen shown to be prominently affected. 6It is increasingly being appreciated that epigenetic changesare at the center <strong>of</strong> <strong>programming</strong>. These changes may be mediatedby methylation <strong>of</strong> DNA, acetylation <strong>of</strong> histones and throughthe role <strong>of</strong> micro RNAs, all <strong>of</strong> which modify gene expression. 8,9
SIGHT AND LIFE | VOL. 25 (2) | 2011 17“Epigenetic changes areat the center <strong>of</strong> <strong>programming</strong>”
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