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1 Note: for non-commercial purposes only Lunch Buffet Welcome to

2 The Power of Programming conference Focus on early nutrition impact on non-communicable diseases, underlying mechanisms, & related issues Presentation and discussion of current concepts and recent results on developmental programming Brought to you by the research project Early Nutrition

3 The Early Nutrition Project World s largest research project on developmental programming of adult health International multidisciplinary collaboration Explores effects of diet from pre-pregnancy to early childhood on later adiposity (body fat content) and related health outcomes

4 36 research institutions, 16 countries, 3 continents Budget >11 Mio with co-funding by NHMRC & industry partners Co-ordination: Hauner Children s Univ. of Munich

5 First 1000 days: a window of opportunity Nutrition and other influences during pre- and postnatal development and plasticity lasting effects on physiology, function, health & disease risks: developmental programming

6 Metabolic programming Sensitive time windows of pre- and postnatal development Metabolic modulators Cytogenesis <<<<<<<<<<< Organogenesis Early metabolic programming of lifelong health Metabolism Endocrine Gene expression Brands B, Koletzko B. Early nutrition and longterm obesity risk: opportunities for paediatric prevention. Monatsschr Kinderheilkd 2012;160:

7 WHO: obesity & consequences = 5 th. leading cause of global deaths Globally, 44% of diabetes, 23 of ischaemic heart disease, 7-41% of certain cancer burdens due to overweight/ obesity

8 Health economic consequences Europe 33 million diabetics, cost for diabetes T2 15 billion /yr. or 8% of EU total health care costs USA 17% of total health care costs for treatment of diabetes and obesity BMJ 2010;341:c6014

9 Demographic change needs early prevention for increasing healthy & productive life years BMJ 2010;341:c6014

10 Early Nutrition: key hypothesis Fetal overnutrition e.g. maternal obesity, high pregnancy weight gain, diet in pregnancy, gestational diabetes Fuel mediated in utero hypothesis Mismatch hypothesis Fetal undernutrition & postnatal overnutrition e.g. maternal malnutrition, placental dysfunction Environment Lifestyle Genes Adiposity/Diabetes Visceral adiposity & Metabolic syndrome Insulin resistance Hypertension, CHD, Stroke Asthma Postnatal overnutrition e.g. overfeeding, short breastfeeding, excessive protein supply Accelerated postnatal growth hypothesis Koletzko et al, Am J Clin Nutr. 2011;94: S.

11 The EarlyNutrition Project

12 The Early Nutrition project combines 11 observational cohorts: SWS, DNBC, Generation R, HUMIS/MOBA, LISA, PreventCD, Raine, UC Irvine, Project VIVA 9 intervention studies (RCTs): UPBEAT, SCOPE/Baseline, CHOP, ROLO, LIMIT, AMELIE, PROTEUS, NIGO-Health from 13 European countries, the USA and Australia comprising > individuals

13 Evidence for relevant programming effects?

14 Prenatal intervention

15 Prenatal intervention RCT in 2212 pregnant women, BMI>25, South Australia Standard care, or counseling (3 x face to face, 3 x phone) on balanced diet, limiting refined CHO and SAFA, and increased physical activity No significant effect on LGA (primary outcome, RR 0.90) Reduced birthweight <4000 g (RR 0.81, p=0.03, NNT 28)

16 Birthweight >4kg: 2x risk of later obesity Yu et al, Obesity Rev 2011;12:

17 Birthweight >4kg: high risk for later obesity Early Childhood Longitudinal Study, 7738 children, USA Birth- n Obesity (%) at age (yrs) weight <4 kg >4 kg Birthweight >4 kg = 12% of the population, but >36% of the obese children at age 14 yrs Cunningham SA et al, NEJM 2014; 370:

18 Intervention after birth: less protein for infants RCT, childhood obesity project (CHOP study), 1678 healthy term infants enrolled in 5 European countries Fully breastfed for >3 mon. 1.2 g protein/dl Higher protein formula 2.05 g protein/dl IF Double blind randomised Lower protein formula 1.25 g protein/dl IF Intervention No intervention - long term follow-up 0 1yr 2 yrs 6 yrs Koletzko et al, Am J Clin Nutr 2009, Weber et al, Am J Clin Nutr 2014.

19 Intervention after birth: less protein for infants RCT, childhood obesity project (CHOP study), 1678 healthy term infants enrolled in 5 European countries * * * * Intervention Weber et al, Am J Clin Nutr 2014, Koletzko et al, Am J Clin Nutr 2009.

20 Protein for infants obesity at 6 yrs. RCT, childhood obesity project (CHOP study), 1678 healthy term infants enrolled in 5 European countries Low Protein High Protein Relative Risik (OR) Breast fed 4.4% 10% 2.42 (95% CI: ) p= % Promote, protect, support breastfeeding Avoid formula with very high protein content Avoid cows milk as a drink in the 1 st. year of life (if affordable, feasible and safe) Weber et al, Am J Clin Nutr 2014, Koletzko et al, Am J Clin Nutr 2009.

21 Metabolic mechanisms and markers? Amino acids, branched chain Amino acids, urea cycle Amino acids, others Acyl-Carnitines, short-chain Acylcarnitines, medium/long Acylcarnitines, hydroxy- Acylcarnitines, dicarboxy- PC, saturated PC, mono-/bis-unsaturated PC, poly-unsaturated Bonferroni Lyso-PC Sphingomyelins Hydroxy-sphingomyelins Hexose

22 Epigenetic mechanisms? Nutrition genome.ucsc.edu/encode Gene product Phenotype & health

23 Epigenetic mechanisms? % body fat (M+SEM, adj. f. gender&age) Godfrey K et al, Diabetes 2011.

24 Translational application

25 Free e-learning f. Health Care Professionals, CME accredited (EU, USA) In collaboration with Univ. of Munich & ESPGHAN Supported by European Commission FP7 Internationally reknown experts Available modules: Breastfeeding Nutrition & Lifestyle in Pregnancy Complementary Feeding Coming: Infant Formula Feeding (April 2014) Nutrition and Brain Development Nutrition and Epigenetics

26 The Power of Programming Plenary Sessions 18 Parallel Sessions 6 Workshops / Symposia Meet the Professors Sessions Career Building New Investigators Forum 520 pre-registered delegates, 54 countries (plus onsite-reg.) 14 European CME / 15 German CME credits

27 ENA (Early Nutrition Academy) Now on For live information during the Conference #PowerOfProgramming2014

28 Welcome reception Thursday, March 13, h, Old City Hall

29 Conference Dinner Friday, March 14, h, Hofbräukeller

30 Conference Dinner: Special Guests Monsieur Jean-Baptiste Pierre Antoine de Monet, Chevalier de Lamarck Inheritance of acquired characteristics Mister Charles Robert Darwin Natural selection wikimedia

31 Thanks to collaborating societies

32 Thanks for financial support German Research Foundation Ludwigs Maximilians University of Munich

33 Thanks to further sponsors

34 Thanks to a great conference organizing team Brigitte Brands, Team Lead, Scientific Program Simone Cramer, Overall Congress Orga Mirella Gutser, PR Congress & ENeA Rebecca Spörl, Correspond. Scient. Programme, Proofreadings Team Support, Finances & Adminstration Julian Decker, Team Support, CME Certificates, ENeA&PoP Kristin Duvinage, Team Support, Orga, EN Chang Ming, Team Support Steffi Roth, Eurokongress Elisabeth Axthammer, Eurokongress

35 Thank you for your kind attention Have an enjoyable and fruitful conference Return to The Power of Programming, fall 2016