Leveraging Opportunities in Infant Nutrition

Dr. Sanjeev Ganguly Medical Director-South Asia

Nestle Nutrition

Top 10 countries for numbers of stillbirths, neonatal and maternal deaths

Ranking for neonatal

deaths

Ranking for

maternal deaths

Ranking for

stillbirths

India 1 1 1

Nigeria 2 2 3

Pakistan 3 8 2

China 4 13 8

DR Congo 5 3 6

Ethiopia 6 5 5

Bangladesh 7 6 4

Indonesia 8 7 7

Afghanistan 9 4 12

Tanzania 10 9 11

1.5 million neonatal deaths Approx 67% of global total

178,000 maternal deaths Approx 65% of global total

Ref: Lawn JE et al BJOG sept 2009. Data sources: Estimates of maternal (2005) and neonatal (2008) deaths from WHO. Stillbirths from Cousens et al 2010 Updated Aug 2010

1.77 million stillbirths Approx 63% of global total

We live in a World with Large Inequalities

Population

Income

Germany: The Melander family of Bargteheide Food expenditure for one week US $500

Ecuador: The Ayme family of Tingo Food expenditure for one week US $31.55

Chad: The Aboubakar family of Breidjing Camp Food expenditure for one week US $1.23

India

• One of the most malnourished countries in the World.

• > 40% of the World’s under weight children below five years live in India (Global Hunger Index 2007)

• The NFHS 3 - not much progress achieved in improving human resources.

• Poverty is a major, but not the only cause of malnutrition

• Percentage of population suffering from various forms of malnutrition, far exceeds the percentage below poverty line

• After National Nutrition Policy 1993 and National Plan of Action, 1995 no national programs or policies for eradicating malnutrition have appeared.

• Today, no national program specifically to combat malnutrition

Nutrition Interventions

• Coverage of essential nutrition interventions is low ~ 30-40% (Menon2009)

• ICDS: new evidence to show positive impacts, but could be much more efficient (Kandpal2011)

• MMS: good impacts on nutrition (Singh 2008), but wrong age group (4-5 year olds) for early under nutrition

• ASHA: promising (Ved2011) but no impact studies yet and recruitment and support systems need strengthening

Facts :

• More than 4 out of every 10 children in Mumbai, Meerut, and Delhi are stunted.

• Underweight is much more prevalent in slum areas than non-slum areas

• More than half (54 percent) of all deaths before age five years in India are related to malnutrition.

• Because of its extensive prevalence in India, mild to moderate malnutrition contributes to more deaths (43 percent) than severe malnutrition (11 percent).

• Seven out of every 10 children age 6-59 months in India are anaemic.

Trends in Malnutrition Among Children Under Three Years

Poor Nutrition as a Contributing Factor to Under-Five Mortality

N

U

T

R

I

T

I

O

N

Low Birth Weight

Stunted Child

Malnourished Girl

Malnourished Mother

Inter-generational Cycle of Malnutrition and Ill Health

•Early Marriage •Poor Nutrition •Short inter-pregnancy gap •Low BMI •Gender discrimination

•Poverty •Poor Nutrition •Awareness & Education •Infection & Healthcare facility •Gender discrimination

•No excl. BF •Delayed /Poor complementary feeding •Inadequate food •Infection & healthcare •Poor growth catch-up

•Poor fetal nutrition •Poor mother nutrition •No / poor supplementation •Gender discrimination •Infection & healthcare

Courtsey : Veena S Rao

Opportunities

• Preterm Nutrition – In NICU

– Post Discharge

– HMF

• Especialized Nutrition for IUGR babies ?

• 0-6 months – Infant Formula

• 6-24 months – Follow up formula

– Complementary foods

Opportunities – Functional Benefits

• Growth & Development

• Digestion

• Immunity

• Allergy Prevention

• Allergy Management

ROLE OF IMMUNONUTRIENTS

IMPACT OF NUTRITIONAL DEFICIENCY ON IMMUNITY

• Nutritional deficiency is commonly associated with impaired immune responses, especially cell-mediated immunity, cytokine production, secretory antibody response and affinity

• The proper consumption and absorption of micronutrients (e.g. zinc, iron, selenium, vitamin A, pyridoxine, vitamin E) is essential for optimal immune responses

ROLE OF NUTRIENTS ON IMMUNE SYSTEM

• The immune system is undergoing permanent renewal and produces millions of immune cells daily. Immune cell renewal is elevated during infectious disease, and recovery depends on the rate of cell division between the invading microorganism and that of immune cells.

• The immune system uses both macro and micronutrients involved in DNA, RNA and protein synthesis.

• Under-nutrition has a strong influence on the immune system at all ages but mainly in growing and aged humans, i.e. when the body’s nutritional reserves are limited.

FATTY ACIDS AND THE IMMUNE SYSTEM

• Feeding EPA and DHA has been shown to modulate specific functions of innate and acquired immunity.

• Feeding high levels (>10% of total fat) of n-3 PUFA (compared with diets high in n-6 PUFA) to healthy animals or human subjects results in suppression of the ability of lymphocytes to respond to mitogen stimulation, NK cell activity, and delayed-type hypersensitivity (DTH) reactions

MECHANISMS RESPONSIBLE FOR THE ROLE OF LONG CHAIN N-3 PUFA ON IMMUNE FUNCTION

• compared with Formula-fed infants, the Formula+LCP infants had a higher % of CD3+CD44+and CD4+CD28+ cells and cytokine profile (lower production of TNF-a post-stimulation) that did not differ from HM infants.

• “feeding infants formula during the first 10 d of life influenced immune function… infants had a higher percentage of CD3+, CD4+CD28+, and lower percentage of CD14+ cells and produced more TNF-a and interferon-g after PHA stimulation than HM-fed infants (P,0·05).

VITAMIN A AND THE IMMUNE SYSTEM

• The importance of vitamin A in immune function and protection against infections is well-established

• Vitamin A deficiency can affect host defenses directly through its essential functions in metabolism in the various immune cells or indirectly through its role in epithelial cell differentiation and host barrier function

VITAMIN A AND THE IMMUNE SYSTEM

• Vitamin A supplements has been found to improve the antibody titer response to measles vaccines, maintain gut integrity, lower the incidence of respiratory tract infections, and reduce mortality associated with diarrhea and measles

MECHANISMS RESPONSIBLE FOR THE ROLE OF VITAMIN A ON IMMUNE FUNCTION

• “43 randomized trials representing 215,633 children, shows that giving vitamin A capsules to children aged 6 months to 5 years can reduce death and some diseases”

• “death due to measles, respiratory infections or meningitis was not specifically reduced, but vitamin A can reduce new occurrences of diarrhoea and measles”

IRON AND IMMUNE SYSTEM

• Iron regulates the function of T lymphocytes, and in most studies (in vivo and in vitro), a deficiency results in impaired cell-mediated immunity.

• Iron deficiency may also delay the development of cell-mediated immunity

• Neutrophil function (decreased myeloperoxidase activity and bactericidal activity) and NK activity are impaired with iron deficiency

MECHANISMS RESPONSIBLE FOR THE ROLE OF IRON ON IMMUNE FUNCTION

• “Significantly lower levels of T lymphocytes as well as CD4+ cells was observed in the iron deficient children (P<0.01 and 0.002 respectively). The CD4 : CD8 ratio was also significantly lower in this group (P<0.05)”

• “Iron supplementation improved the CD4 counts significantly”

ZINC AND IMMUNE SYSTEM

• Zn deficiency impedes host-defense systems leading to increased susceptibility to a variety of pathogens, and a deficiency of Zn is known to occur in many diseased states that involve the immune system like alcoholism, renal disease, burns, gastrointestinal tract disorders and diarrhea

MECHANISMS RESPONSIBLE FOR THE ROLE OF ZINC ON IMMUNE FUNCTION

• “Children who received a zinc supplement had fewer episodes of diarrhea (rate ratio: 0.86) and respiratory tract infections (rate ratio: 0.92) and significantly fewer attacks of severe diarrhea or dysentery (rate ratio: 0.85), persistent diarrhea (rate ratio: 0.75), and lower respiratory tract infection or pneumonia (rate ratio: 0.80) than did those who received placebo. They also had significantly fewer total days with diarrhea (rate ratio: 0.86)”

• “Zinc supplementation decreased the proportion of diarrhoeal episodes which lasted beyond 7 days, risk of hospitalization, all-cause mortality and diarrhoea mortality”

• “…zinc for the treatment of diarrhoea is estimated to decrease diarrhoea mortality by 23%”

• “six trials and 7850 participants ….analysis showed that zinc supplementation reduced the incidence of pneumonia by 13% and prevalence of pneumonia by 41%”

• “subgroup analysis…zinc reduced the incidence of pneumonia defined by specific clinical criteria by 21%”

NUCLEOTIDES AND IMMUNE SYSTEM

• Nucleotides may become conditionally essential during growth and immunological challenges when demand may exceed de novo synthetic capacity

• The addition of nucleotides to nucleotide-free diets has been shown to reverse or restore many of the changes observed with nucleotide deficiency, such as increasing Th1-type cytokines, increasing antibody production, and increasing spleen cell proliferation.

• Human infants fed breast milk or formula supplemented with nucleotides had higher NK cell activity and IL-2 production compared with infants fed formula without nucleotides.

MECHANISMS RESPONSIBLE FOR THE ROLE OF NUCLEOTIDES ON IMMUNE FUNCTION

• Nucleotides contribute to the pool of nucleotides available to immune cells

• Nucleotides are building blocks for DNA and RNA synthesis and are involved in diverse cellular processes, serving as sources of chemical energy [e.g., 5-triphosphate (ATP)] and intracellular signals (e.g., adenosine cyclic 3,5-adenosine monophosphate and cyclic 35-guanosine monophosphate)

• Systematic review and meta-analysis showed that ribonucleotide-supplemented infant formulae were associated with a better antibody response to immunisation with Haemopillus influenzae vaccine [SMD 1·74 (99 %CI 1·43–2·05), P = 0·001], diphtheria toxoid [SMD 0·94 (0·75–1·12), P = 0·001], oral polio vaccine [SMD 0·73 (0·51–0·95), P =¼ 0·001], and fewer episodes of diarrhoea [RR 0·67 (0·58–0·76),P = 0·02]

PROBIOTICS AND IMMUNE SYSTEM

• Probiotics are live microbial food supplements, which beneficially affect the host by improving its intestinal microbial balance.

• Recent evidence indicates that probiotics (e.g. bifidobacterium and Lactobacillus species) may influence both systemic and gut-associated immune responses.

• “Infants consuming formula with Bb12 produced feces with detectable presence of Bb12 and augmented sIgA concentration”

VITAMIN C AND THE IMMUNE SYSTEM

• Vitamin C is an essential component of every living cell. Vitamin C is highly concentrated in leukocytes and is used rapidly during infection (e.g., to prevent oxidative damage).

• Reduced concentrations of this vitamin in leukocytes is associated with reduced immune function

MECHANISMS RESPONSIBLE FOR THE ROLE OF VITAMIN C ON IMMUNE FUNCTION

VITAMIN E AND SELENIUM AND THE IMMUNE SYSTEM

• Vitamin E and the trace element selenium (Se) function synergistically (by related but independent mechanisms) in tissues to reduce damage to lipid membranes by the formation of reactive oxygen species (ROS) during infections

MECHANISMS RESPONSIBLE FOR THE ROLE OF VITAMIN E AND SELENIUM ON IMMUNE FUNCTION

• Intervention: One year of fortified milk providing additional 7.8 mg zinc, 9.6 mg iron, 4.2 g selenium, 0.27 mg copper, 156 g vitamin A, 40.2 mg vitamin C, 7.5 mg vitamin E per day

• Results: Reduced the odds for days with severe illnesses by 15%, the incidence of diarrhea by 18%, and the incidence of acute lower respiratory illness by 26%

Challenges

• Activism is a major challenge

• Regulations are archaic

– Zn is a contaminant as per Food Laws

– Low levels of protein in Preterms

– IYCF guidelines outdated

• Environmental sanitation & Clean drinking water

• Generating evidence on Nutritional solutions

Thank you