Poor Fetal and Infant growth: Antecedents of childhood obesity Alan Jackson Institute of Human Nutrition Division for Developmental Origins of Adult Disease University of Southampton
Evidence base for rational interventions in public health 14,000 deaths each day
Activity Initial treatment Rehabilitation Follow-up days1-2 days 3-7 weeks 2-6 weeks 7-26 Treat or prevent: hypoglycaemia hypothermia dehydration Treat infection Correct electrolyte imbalance Correct micronutrient deficiencies Begin feeding Increase feeding to recover lost weight ( catch-up growth ) Stimulate emotional and sensorial development Prepare for discharge without iron with iron
Key to effective treatment: gain metabolic control correct metabolic imbalance provide nutrient rich food intake case mortality 5-10%,from 30-50%
During last two years; three meetings of direct relevance 1. Fetal Origins of Adult Disease International Congress: Brighton broad scientific community: multidisciplinarity 2. USAID/Wellcome Trust: Merton small workshop for experts address focussed considerations 3. USAID/Wellcome Trust: meeting of potential funders of research and implementation to explore potential for collaborative/integrated approach.
International Congress Fetal Origins of Adult Disease: Barker hypothesis: programming of function During early life nutrient exposure sets metabolic behaviour and thereby determines the risk of chronic disease during adult life.
Early Life Origins of Health and Disease Evidence of a relationship between birth weight and risk of non-communicable disease in adult life: - Type II diabetes -Hypertension -CVD -Obesity - Other.
Coronary heart disease: mother < 1.58 m standardised mortality rate Ponderal index of baby BMI of mother < 24-26 -28-30 > 30 All <25 55 106 168 170 224 131-27 55 70 146 113 134 104-29 26 54 31 137 149 75 > 29 0 63 26 55 75 48 All 43 73 88 114 136 90 Forsen et al, BMJ 1997; 315: 837-840
Early Life origins of disease: Birthweight Tertile and Prevalence of Insulin Resistance Syndrome Evidence from wide range of international studies IRS percentage 16 14 12 10 8 6 4 2 0 1 2 3 Birthweight tertile Valdez et al, Diabetologia 1992 Mexican American Non-hispanic American Birthweight Tertile, Adult BMI and Insulin Resistance Syndrome 30 25 20 15 10 5 0 1 2 3 Birthweight Tertile Valdez at al, Diabetologia 1994 IRS Prevalence 3 1 2 BMI Tertile Metabolic changes already evident in childhood by 5 years of age
Fig. 1. Mean Z-scores for height, weight and BMI during childhood in 290 people who later developed Type 2 diabetes within a cohort of 8760 men and women. At any age, the mean Z-score for the cohort is set at 0 while the standard deviation is set at 1
Fig. 2. Mean BMI in 6060 children according to the age of adiposity rebound
Fetal origins of hyperphagia, obesity and hypertension and postnatal amplification by hypercaloric nutrition. Vickers, Breier, Cutfield, Hofman, Gluckman: Am J Physiol Endocrinol Metab 2000; 279: E83-E87
Diet Dietary patterns: national surveys. Carbohydrate: sucrose, glycaemic response Micronutrients: folate vitamin A riboflavin Iron Zinc Iodine
Risk of fetal death by maternal smoking and micronutrient supplementation. Wu et al, 1998 Number smoked per day 0 Regular supplements before pregnancy recognised NO 1.00 YES 0.96 Regular supplements after pregnancy recognised NO 1.00 YES.94 1-9 1.12 1.00 1.04 1.06 10-19 1.36 1.09 1.42 1.21 >20 1.59 0.84 1.77 1.22 trend < 0.05 >0.05 <0.05 <0.05
Nutrition as a Preventive Strategy Against Adverse Pregnancy Outcomes USAID/Wellcome Trust, July, 2002 Overview evidence base and plausibility Infection and inflammation genital tract infection, malaria, HIV Metabolic eclampsia, diabetes, underweight Life and fitness smoking, alcohol, social stress Fetal and infant macronutrients, micronutrients
During early development, plasticity allows fetus/infant to acquire the metabolic capability to deal as best it might with the environment to which it is exposed. Directly, or indirectly through maternally mediated signals. Later exposure to an environment, or environmental signals which are substantially different, likely to generate metabolic stress. Small size at birth, marks environmental limitation and developmental constraint, which is ill-fitted for later environmental which is energy dense. Greater the energy richness/nutrient poverty of diet, the greater the metabolic stress
General phenomenon, Demonstrated human disease outcomes: cardiovascular disease type 2 diabetes mental health cancer Animal models vary in detail, timing and exposure fundamental mechanisms operating in different contexts Outcome unbalanced development neuro-cognitive/obesity
Nature of the problem: - expressed as energy balance (obesity), relationship between activity and energy (food) intake - energy derived from macronutrients, partitioning between lean and adipose tissues - macronutrient partitioning protein, EAA and Non-essential nitrogen CHO: simple sugars, complex carbohydrates Lipids: SFA, monounsaturated, n-3,n-6 FA - capability for partitioning: metabolic capability: mineral, vitamin and trace element status
Quality and quantity of diet: - macronutrient quality AND - micronutrient density per unit energy consumed Nutrient poor energy sources displace nutrient rich foods, Effect most marked at low levels of energy expenditure Leading to: - poor quality pregnancy - low birth weight - increased risk of obesity