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