1. Child Health And Development Opportunities And Challenges In Next Decade

2. Leadership is about imagining the future and preparing for it. Characteristics of Sustained Program and Institutional excellence -Core values -Adaptability -Collaborative culture

3. Loss in translation from policy to programs. We must learn to deliver better what we know. The coverage of child survival interventions is still an issue. Challenges In Health Care Delivery

4. Policy Strategy Plans - Quantitative measures of process and outcome - Continuing innovation in design and delivery of programs - Effective use of technology - Simple innovation in useful product design for easier delivery

5. Underused life securing commodities for maternal Child health; UN Commission, 2012 Oxytocin for prevention of PPH Misoprostol for prevention of PPH Injectable antibiotics for neonatal sepsis Antenatal steroids for fetal living development Chlorhexidine for cord care Resuscitation devices for new born care Amoxicillin for pneumonia ORS, Zinc Female condoms Contraceptives implants Emergency contraceptives

6. Innovation in delivering services Neonatal Home care, District Neonatal units Conditional Cash transfer ICT in health system Novel Human resource strategies Decentralization and local ownership Affordable product innovation and diffusion Outsourcing services by Government in a competitive framework Public-Private partnership

7. Challenges In Next Decade Sustaining Survival, Moving to Child Development

8. Issues In Child Development Early Nutrition Origin of Disease Nutrition insults during fetal life have surprising, long lasting ramifications for health and development

9. Cohort Studies in Brazil, Ghana, India, P, South Africa show- Size and birth and accelerated weight gain after 48 months of life is related to Insulin resistance Greater weight gain during first five years of life is associated with elevated blood pressure

10. Disturbed energy balance; a combination of Genetics, Epigenetics and Environmental Factors Epigenetic Mechanism and Regulation of Transcription Heritable changes in gene expression without altering gene sequence. DNA Methylation Histone Modification Micro RNA Hypo Transcriptional activation Hypo Transcriptional suppression

11. Maternal Diet And Altered Genetic Regulation A nutritional challenge in early pregnancy or early post natal life can result in DNA methylation which is detectable 60 years later. Overfeeding in post natal life can alter methylation of genes critical for appetite control.

12. Reversibility of Altered Phenotype And Epigenotype Nutrition, Stress Pre and Peri-conceptual Later Pregnancy Postnatal Life Design of Complementary feeding; Child feeding Physical activity Pharmacology

13. Depression in Pregnancy, Low Birth Weight and DNA methylation of Imprinted Regulatory Genes Methylation at MEG3 for infants of women with severe and no depressed mood

14. An impoverished environment and early brain development Functional magnetic resonance Imaging reveals important impact of- Cognitive Nurturing Toxic stress operating through lack of engagement and through hormonal and Neural responses. Prefrontal cortex; Most affected language, problem solving, self regulation and social bonding

15. INCREASING LINEAR GROWTH WITHOUT EXCESSIVE WEIGHT GAIN Wasting is an individual disorder Stunting reflects population Inequalities Linear growth faltering -9months to 24 months age Timing of Nutritional Insults a key issue

16. PROPORTION STUNTED, WASTED, UNDER WEIGHT AT VARIOUS AGES 6 weeks6 months9 months12 months n3866354634882987 Stunted28.5%36.2%43.5%51.2% Wasted15.6%14.3%15.2%18.0% Under weight39.4%38.5%40.7%40.5% Severely Stunted10.0%11.2%14.9%19.8% Severely Wasted4.5%3.8%3.3%3.9% Severely Under weight15.2%13.9%14.7%13.7% Data from a birth cohort from Faridabad, Haryana

17. CONTRIBUTION OF LBW TO MALNUTRITION AT 6 MONTHS LBWNormal Birth Weight Stunted38.7%61.3% Wasted38%62% Under weight41.3%58.7% Data from a birth cohort from Faridabad, Haryana

18. GUT HEALTH AND LINEAR GROWTH Microbial Population that triggers inflammation and or gut dysfunction Persistent Gastroenteropathy associated with an active inflammatory response than immune suppression Stunted not underweight children have higher anti-endotoxin levels Children spend roughly 10 times more days with subclinical inflammation than with diarrhea itself.

19. Reduction in stunting Brazil 37% to 7% in 33 years Mexico 27% to 16% in 18 years Ghana 35% to 29% in 20 years India 54% to 45% in 13 years (1993-2006)

20. SUCCESS FACTORS IN STUNTING REDUCTION Increase income through conditional cash transfer (B,M) Maternal schooling (B) Increased use of health care (B,M) Improved water and sanitation services (B)

21. Scientific evidence must drive policy for Individual, family and community behaviors in 21 st century. Current strategies lack research basis. Behavior Change Is Key Challenge

22. Preventing Preterm Birth Is A Key Challenge WHO 1997

23. Regional causes of U5 deaths in 2010 Adapted from Liu et al., 2012 Southeast Asia (N=2.096m)

24. LMICDeveloped Countries Spontaneous PTB (with intact membranes) 70%,40-45% pPROM Spontaneous with premature rupture of membranes 16-21%20-40% Provider initiated11-15%30-35% Clinical types of preterm birth in LMIC and Developed Countries

25. Possible causes of preterm birth Implantation Phase 0 Quiescence Phase 1 Activation Phase 2 Stimulation Phase 3 Involution Intra uterine infections Extreme & very premature/ Still birth Extreme & very premature/ Still birth Uterine over distension, stress Preterm births from 32- 36 weeks Almost 90% mid-trimester spontaneous PTB have intrauterine infection vs 15% at 34–36 w; Culture positive amniotic fluid associated with almost 50% PTB at 23-26 w, 16% at 27-30 w & 11% at 31-34 w Adapted from Gravett et al, BMC Pregnancy and Childbirth 2010

26. Preterm Birth Long term translational research goals Appropriate risk stratification of women Better prediction tools Optimal time of prediction & clinical intervention Unusual/novel microbes that could serve as biomarkers; Gut, Reproductive tract, blood,urine Identify focused remedies targeting one or more mechanistic pathways –infection, inflammation Application of currently available interventions (tocolytic agents) based on better understanding of biological mechanisms

27. Exploring Our Microbiome Through Metagenomics (DNA, RNA, Protein, Metabolites) New concept about- Post natal development Systems physiology Individuality DISEASE ASSOCIATION OF GUT MICROBIOME Prematurity, low birth weight, resistance to infection/Immunity and inflammation Asthma, Auto immune disease, risk of obesity/chronic disease

28. Metagenome of Human Microbiome Elizabeth et al., 2009, Science No. of people participated: 9 No. of sites screened: 27 No. of people participated: 9 No. of sites screened: 27 Total no. of bacterial phyla identified: 22 Total no. of bacterial phyla identified: 22

29. Reid et al., 2011, Nat. Revw. Microb. Skin Vaginal birth canal Envn. sources GI tract Dietary source Envn. sources Oronasopharyngeal cavity Dietary sources Skin Envn. sources Urogenital tract Skin, GI tract Vaginal birth canal Envn. sources Where Do They Come From? Where Are They? O’Hara and Shanahan, 2006, EMBO rep. Who Are They? Backhed et al.,2005, Science Human Gut Microbiota How Are They Selected?

30. Nicholson et al, Science, 2012, Bad digestion is the root of all evil

32. INNOVATION LANDSCAPING FOR AFFORDABLE TECHNOLGY Physicians are conceptual innovators Physicians must define technology and product needs and product profiles

33. Medical Innovation Stanford-India Biodesign (Alumni Fellows) Focus: Pedatrics (2011-2012) Avijit BansalAvijit Bansal Ayesha ChaudharyAyesha Chaudhary Mridusmita ChoudhuryMridusmita Choudhury Chinmay DeodharChinmay Deodhar

34. Status 5. Neonatal Resuscitation Device Working prototype developed and bench- tested Positive feedback from physicians during preliminary mannequin trial 6. Patient Transfer System Working prototype developed and tested Positive reviews from local med-tech firms 7. Surgical Sharps Management Working prototype developed and tested Talks in progress to identify commercialization partners 8. Trans-illumination device Working prototype developed and tested Positive feedback from physicians Device Stanford-India Biodesign Program : Projects Project NeoBreathe

35. Status 1. Fecal Incontinence Device First-in-man safety trial completed Start-up launched Series A funding obtained, 2012 2. Limb Immobilization Device Field-tested in Trauma Center at A.I.I. M.S Talks in progress with industry partners for commercialization 3. Emergency Intra-osseous Access Device Cadaveric trials successfully completed Talks in progress with industry partners for commercialization 4. Newborn Hearing Screening Device Safety and efficacy trials completed Seed funding obtained for further development and commercialization Device Screening for all Stanford-India Biodesign Program : Projects from Clinical Immersion

36. Diversity of target product profiles, users, and selling of POC testing Point of Care Diagnostics Physicians to design the strategy

37. The Riddle of Protein Biomarkers FUTURE BRIGHT OR BLEAK <1.5 near test per year cleared by FDA 53% of tests cleared by the FDA since 1993 used in <10% labs, 60% in <25% FDA clearance does not translate into clinical acceptance

38. Challenges and Opportunities Culture change – Gender perception Promote a culture were a female fetus, infant, child, adolescent and adult women are perceived as critical to development process and their inate abilities are nurtured.

39. Pediatrics education, training and carrier paths in future Pediatrics Institutional design Pediatricians should show the path to others