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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
• 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
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 activationHypo 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
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%
Data from a birth cohort from Faridabad, Haryana
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)
• Scientific evidence must drive policy for
Individual, family and community
behaviors in 21st century.
• Current strategies lack research basis.
Behavior Change Is Key Challenge
Preventing Preterm Birth Is A Key Challenge
WHO 1997
Regional causes of U5 deaths in 2010
Childhood infectious diseases
31%
Injury4%
Other childhood disorders13%
Neonatal infec-tious diseases
16%
Preterm birth
compli-cations
19%Intrapartum-related complicaations
10%Other neonatal disorders
2%
Congenital abnormalities
5%
Adapted from Liu et al., 2012
Southeast Asia (N=2.096m)
LMIC Developed Countries
Spontaneous PTB(with intact
membranes)
70%, 40-45%
pPROMSpontaneous with premature rupture
of membranes
16-21% 20-40%
Provider initiated 11-15% 30-35%
Clinical types of preterm birth in LMIC and Developed Countries
Possible causes of preterm birth
Implantation
Phase 0Quiescence
Phase 1Activation
Phase 2Stimulation
Phase 3Involution
Intra uterine infectionsExtreme & 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
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 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
Metagenome of Human Microbiome
Elizabeth et al., 2009, Science
No. of people participated: 9No. of sites screened: 27
Total no. of bacterial phyla identified: 22
Reid et al., 2011, Nat. Revw. Microb.
SkinVaginal birth canalEnvn. sources
GI tractDietary sourceEnvn. sources
Oronasopharyngeal cavityDietary sourcesSkinEnvn. sources
Urogenital tractSkin, GI tractVaginal birth canalEnvn. 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?
Nicholson et al, Science, 2012,
Bad digestion is the root of all evil
INNOVATION LANDSCAPING FOR AFFORDABLE TECHNOLGY
• Physicians are conceptual innovators
• Physicians must define technology and product
needs and product profiles
Medical InnovationStanford-India Biodesign (Alumni
Fellows)
• Focus: Pedatrics (2011-2012)
Avijit Bansal Ayesha Chaudhary
Mridusmita Choudhury Chinmay Deodhar
Status5. Neonatal Resuscitation Device
Working prototype developed and bench-tested
Positive feedback from physicians during preliminary mannequin trial
6. Patient Transfer SystemWorking prototype developed and testedPositive reviews from local med-tech firms
7. Surgical Sharps ManagementWorking prototype developed and testedTalks in progress to identify
commercialization partners
8. Trans-illumination deviceWorking prototype developed and testedPositive feedback from physicians
Device
Stanford-India Biodesign Program : Projects
Project NeoBreathe
Status1. Fecal Incontinence Device
First-in-man safety trial completedStart-up launchedSeries A funding obtained, 2012
2. Limb Immobilization DeviceField-tested in Trauma Center at A.I.I. M.STalks in progress with industry partners for
commercialization
3. Emergency Intra-osseous Access DeviceCadaveric trials successfully completedTalks in progress with industry partners for
commercialization
4. Newborn Hearing Screening DeviceSafety and efficacy trials completedSeed funding obtained for further development
and commercialization
Device
Screening for all
Stanford-India Biodesign Program : Projects from Clinical Immersion
Home Community ClinicPeripheral
lab Hospital ….
SelfHealth worker
Doctor/nurse
Lab technology ER,OR,ICU
Self assessmen
t and referral
Triage and referral
Diagnosis and Rx
Diagnosis and Rx,
monitoring
Diagnosis and Rx,
monitoring
Diversity of target product profiles, users, and selling of POC testing
Point of Care Diagnostics
Physicians to design the strategy
The Riddle of Protein BiomarkersFUTURE 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