Child Health And Development Opportunities And Challenges In Next Decade • Leadership is about imagining the future and preparing for it. • Characteristics of Sustained Program and Institutional excellence -Core values -Adaptability -Collaborative culture Challenges In Health Care Delivery • 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. 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 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 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 Challenges In Next Decade Sustaining Survival, Moving to Child Development Issues In Child Development Early Nutrition Origin of Disease • Nutrition insults during fetal life have surprising, long lasting ramifications for health and development 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 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 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. 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 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 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 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 Data from a birth cohort from Faridabad, Haryana PROPORTION STUNTED, WASTED, UNDER WEIGHT AT VARIOUS AGES 6 weeks 6 months 9 months 12 months n 3866 3546 3488 2987 Stunted 28.5% 36.2% 43.5% 51.2% Wasted 15.6% 14.3% 15.2% 18.0% Under weight 39.4% 38.5% 40.7% 40.5% Severely Stunted 10.0% 11.2% 14.9% 19.8% Severely Wasted 4.5% 3.8% 3.3% 3.9% Severely Under weight 15.2% 13.9% 14.7% 13.7% Data from a birth cohort from Faridabad, Haryana CONTRIBUTION OF LBW TO MALNUTRITION AT 6 MONTHS LBW Normal Birth Weight Stunted 38.7% 61.3% Wasted 38% 62% Under weight 41.3% 58.7% 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. 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) 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) Behavior Change Is Key Challenge • Scientific evidence must drive policy for Individual, family and community behaviors in 21st century. • Current strategies lack research basis. Preventing Preterm Birth Is A Key Challenge WHO 1997 Regional causes of U5 deaths in 2010 Southeast Asia (N=2.096m) Injury 4% Other childhood disorders 13% Neonatal infectious diseases 16% Childhood infectious diseases 31% Congenital abnormalities 5% Adapted from Liu et al., 2012 Preterm birth complications 19% Other neonatal disorders 2% Intrapartum-related complicaations 10% Clinical types of preterm birth in LMIC and Developed Countries LMIC Developed Countries Spontaneous PTB (with intact membranes) 70%, 40-45% pPROM Spontaneous with premature rupture of membranes Provider initiated 16-21% 20-40% 11-15% 30-35% Possible causes of preterm birth Intra uterine infections 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 Implantation Extreme & very premature/ Still birth Phase 0 Phase 1 Phase 2 Quiescence Activation Stimulation Uterine over distension, stress Phase 3 Involution Preterm births from 32- 36 weeks Adapted from Gravett et al, BMC Pregnancy and Childbirth 2010 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 Exploring Our Microbiome Through Metagenomics (DNA, RNA, Protein, Metabolites) • New concept aboutPost 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 Metagenome of Human Microbiome No. of people participated: 9 No. of sites screened: 27 Total no. of bacterial phyla identified: 22 Elizabeth et al., 2009, Science Human Gut Microbiota Where Do They Come From? Urogenital tract How Are They Selected? GI tract Dietary source Envn. sources Skin, GI tract Vaginal birth canal Envn. sources Oronasopharyngeal cavity Dietary sources Skin Envn. sources Skin Vaginal birth canal Envn. sources Reid et al., 2011, Nat. Revw. Microb. Who Are They? Where Are They? O’Hara and Shanahan, 2006, EMBO rep. Backhed et al.,2005, Science Bad digestion is the root of all evil Nicholson et al, Science, 2012, INNOVATION LANDSCAPING FOR AFFORDABLE TECHNOLGY • Physicians are conceptual innovators • Physicians must define technology and product needs and product profiles Medical Innovation Stanford-India Biodesign (Alumni Fellows) • Focus: Pedatrics (2011-2012) Avijit Bansal Mridusmita Choudhury Ayesha Chaudhary Chinmay Deodhar Stanford-India Biodesign Program : Projects Device 5. Project NeoBreathe 6. 7. Status Neonatal Resuscitation Device Working prototype developed and benchtested Positive feedback from physicians during preliminary mannequin trial Patient Transfer System Working prototype developed and tested Positive reviews from local med-tech firms 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 Stanford-India Biodesign Program : Projects from Clinical Immersion Device 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. Screening for all Newborn Hearing Screening Device Safety and efficacy trials completed Seed funding obtained for further development and commercialization Point of Care Diagnostics Physicians to design the strategy Diversity of target product profiles, users, and selling of POC testing 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 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. • Pediatrics education, training and carrier paths in future • Pediatrics Institutional design Pediatricians should show the path to others