Early Infant Nutrition : short & Long term effects

Dr. Mohamed R. Cheickali

Agenda
To understand:

1. Growth of breastfed and formula fed infants

2. Protein is one mechanism for growth differences 3. Difference between Breast Milk and Infant formula in Protein Quality and Quantity 4.New Technique to improve protein quality and reduce quantity

Recent trends in infant nutrition

Early infant feeding not only influences physical growth and development, but also the incidence of gastro-intestinal, respiratory, and allergic disease in early childhood, as well as possibly metabolism and health in later childhood and adulthood

ESPGHAN Committee on Nutrition

JPGN 2001;32:256

Is Chubby . Cute Baby .Healthy ?

Obesity in the world

300 million obese 15-30% obese in industrialized nations WHO: at least 20 million children under age 5 yrs overweight globally in 2005
(Factsheet 311, Sep. 2006)

Childhood Obesity is Complex

early nutrition (i.e.) from fetal time to 2 years may impact long-term body composition

Human milk is the Gold Standard for Infant Nutrition

Composition of Breast Milk Protein Carbohydrates Fats Vitamins Minerals Bioactive Substances Immunoglobulins

If a mother cannot or chooses not to breast feed, infant formula is the next best alternative

Growth of the Breastfed Infant is the Gold Standard for infant Growth
Several studies have shown that formula fed infants are larger than breastfed infants by the end of the first year of life Kramer et al (2004) Republic of Belarus 16,755 infants Agostoni et al (1990) Italy 119 infants Dewey et al (1993) United States 80 infants

The WHO Multicentre Growth Reference Study

The World Health Organization recognized breastfed and formula fed infants grow differently
Conducted extensive research in 6 countries : Brazil, Oman, India, Ghana, Norway, US Longitudinal- 800 children total (140 per site) Followed monthly from birth to 24 months Cross sectional-7560 total (1260 per site) Children 18 to 71 months measured once Based on these 8360 infants exclusively fed human milk for at least 3 months, New Growth Reference Standards were developed for global usage

Researchers use Growth Z-scores to communicate growth differences among subjects Used to compare the growth of study group to the growth of a reference group

Represents the deviation of the group from the mean value of a reference population

95% of data

Nearly all infants (95%) in a population will be within -2.0 and +2.0 Z-scores

Z-score

-3

-2

-1

Pediatricians use Percentiles on Growth Charts

The DARLING Study showed Growth Differences between Breastfed and Formula fed Infants During 1st Year of Life
Z-SCORE (Weight for length)

*FF significantly greater weight for length compared to BF infants

The DARLING Study, Dewey et al AJCN, 1993

13

Protein requirements in infants

Fomon et al. Growth. Inev. Loss
(g/kg/d)

Age (m) 0-1 1-2 2-3 3-4 4-5 5-6 6-9 9-12

Dewey et al. Total Total

(g/kg/d)

1.03 0.78 0.56 0.38 0.30 0.29 0.26 0.20

0.95 0.93 0.90 0.89 0.88 0.89 0.91 0.94

1.98 1.71 1.46 1.27 1.18 1.18 1.17 1.19

1.99 1.59 1.19 1.06 0.92 0.92 0.85 0.78

Protein requirements for growth represent more than half of the protein needs during the first months of life. The growth rate slows down rapidly with age, and thus the requirements for protein

2.40 2.20 2.00 1.80 1.60 1.40 1.20 1.00 0.80 0.60 0.40 0.20 0.00

Starter Formula

Follow-up Formula

Protein (g/100 kcal)

New Starter Formula

Requirement

0-1

1-2

2-3

3-4

4-5

5-6

6-9
Ziegler 2010

9-12

Age Interval (mo)

15

Excessive protein intake has been hypothesized as one potential risk factor for later development of obesity
The early protein hypothesis
Koletzko et al, 2005

Dietary proteins by influencing secretion of hormones such as insulin and insulin growth factors (IGFs) may influence growth and adiposity in infants and children

16

Effect of feeding type on insulin secretion in infants

Urinary C-peptide/creatinine (nmol/mmol)
7

p < 0.01
6 5 4 3 2 1 0

BF

F 1.9 g protein/ 100 kcal

F 2.6 protein/ 100 kcal

Lucas et al, 1981

Axelsson et al, 1989

Insulin secretion is higher in FF vs BF infants. This effect is prevented when formula contains lower amount of proteins

17

Insulin-secretagogue amino-acids
Plasma concentrations (mol/l) of insulin-secretagogue amino acids of 112 day -old infants fed either a whey predominant formula (WP F) or a modified sweet whey formula (MSWF)
F 2.4 Arginine Isoleucine Leucine Phenylalanine Valine 81 97 140 47 208 F 1.9 95* 74* 131* 47 146*

Protein/energy ratio of 2.4 and 1.9 g prot/100 kcal for WPF and MSW F, respectively *p value < 0.05
Adapted from Ziegler et al, 2003

18

Feeding type and IGF-1 levels in infants

Savino et al, 2005 Savino et al, 2005

FF infants have greater serum IGF-1 levels than BF infants. Plasma IGF-1 levels are directly correlated with the Z score for weight, BMI and tricipital skin-fold thickness in 2 months-old infants

19

presented by Prof Koletzko, Univ. of Munich, at the European Congress on Obesity, Budapest, April 2007. A low protein content infant formula fed during first year of life (starter infant at 1.8 g protein/ 100 kcal and follow up formula at 2.25g protein / 100 kcal) Metabolic and endocrine benefits as well as a body growth rate during the first 2 years close to that of breastfed infants, compared to the feeding of high protein formulae during the first year of life. contributes to the growing body of scientific evidence that early nutrition can exert important long term programming effects on early development and later health.

20

Why did infant formulas contain higher protein levels than breast milk?
In the middle of the 20th century, it was considered that infant formula should deliver more proteins than breast milk. The protein content of a number of widely used formulas ranged from 3 to 4 g/100 kcal This recommendation was based on: An overestimation of the
nutritionally available protein content of human milk protein requirements of the infants

The superiority of human milk compared to cows milk for satisfying the amino-acid needs of infants

21

Comparison of protein fractions from human and cows milk

100
90 80

Whey 20% Whey Whey 60%

lactoferrin immunoglobulins serum albumin -lactoglobulin -lactalbumin

Total proteins (g/dl):

Human milk: 0.89 Cow milk: 3.30

Protein fractions (%)

70

60
50 40 30 20 10 0

Casein 80%

Casein
-casein -casein -casein -casein

Casein 40%

Human Milk

Cows Milk

It is virtually impossible to obtain an aminoacid profile that is similar to human milk with the usual ingredients (skim milk and whey)

22

Tryptophan the limiting AA in reducing protein content in infant formulas

250.0

Human milk (1.5 g prot/100 kcal) Casein predominant formula (2.5 g prot/100 kcal)
200.0

Whey predominant formula (2.5 g prot/100 kcal)

mg aa/100 kcal

150.0

100.0

50.0

0.0

Phenylalanine

Isoleucine

Threonine

Leucine

Methionine

Lysine

Tryptophan

Valine

23

New fractionation process*: CGMP elimination

Others Serum-albumin Immunoglobulins
3.2%
6.4% 9.5%

-lactoglobulin

32%
Remove CGMP... (over-rich in threonine but poor in tryptophan)

12.8% 13%

23.4%
Non-Protein Nitrogen

...thus increasing -lactalbumin (rich in tryptophan) * Nestl Patent : EP 0 880 902 A1

24

New formula with low protein content

Protein Content
g/100kcal

2.0 1.5 1.0

0.5
0 standard New Human Formula* Formula Milk * current whey adapted formula

25

-lactalbumin enriched formula

Tryptophan levels in different formula and human milk Serum tryprophan levels in FF and BF infants

-Lactalbumin Enriched whey formula

-Lactalbumin enriched whey formula (2.0 g prot/100 kcal) Classical Whey formula (2.5 g prot/100 kcal)

Classical Whey formula

NS

Casein predominant formula Breastfed Human milk 0 0 0.5 1 1.5 2 2.5 5 10 15 20

mg/L

g/16 g N

Heine et al Acta Peaediatr 85: 1996

Growth study show similar growth than breast fed infants

Controlled, blind, parallel and prospective feeding study 28 babies/group, 3 groups
Breastfed (BF) Classical Whey Formula (WF): 2.2 g protein / 100 kcal Modified Sweet Whey Formula (MSWF): 1.8 g protein / 100 kcal
Growth (mm/month)
35

26

25

15

BF

MSWF 1.8

WF 2.2

No differences in energy intakes between the formula fed groups whereas protein intakes were less in infants fed the MSWF1.8 No differences were found between the feeding groups for weight- and length gain nor for BMI

30-120 days

Raiha et JPGN, 2002

27

Indispensable amino acids and urea levels in plasma HM

F 1.8

ILE
mM/ml 200

F 2.2
Plasma Urea (mmol/l)

PHE

160 120

LEU

4 3 2 1 0 30 d

* *

80

LYS
0

VAL

60 d

120 d

HIS

THR

MET

TRP

Infants fed the F1.8 formula showed both plasma amino acid and urea levels closer to BF infants than those fed the classical WF

28

Metabolic balance study showed similar nitrogen retention

Crossover, randomized, double blind 8 babies (1-4 months):
Classical Whey Formula (WF): 2.2 g protein / 100 kcal Modified Sweet Whey Formula (MSWF): 1.8 g protein / 100 kcal
WF2.2 MSWF1.8

400 350 300 250 200 150 100 50 0

*
Intake Urinary excretion Retention

Nitrogen intake and excretion were lower in MSWF fed infants but nitrogen retention was identical in both groups Absorption and retention of calcium, magnesium and phosphorus were similar with the 2 formulas

*p < 0.01

Ziegler et al, 2002

Adequate Growth rate

Weight Gain
(g/day, 0-90 days)

Body Mass Index

(kg/m2, at 90 days)

Head Circumference
(mm, 0-90 days)

Growth parameters within the range of breastfed infants

9. Raiha et al. Protein Nutrition During Infancy.: effects on growth and metabolism. In: Martorell R, eds Nutrition and Growth. Nestl Nutrition Workshop Series, vol. 47, New York: Raven Press 2000.

30

Protein intake and IGF-1 levels

100
90 IGF-1 (ng/ml) P < 0.05

80

Whey predominant formula (2.4 g protein/100 kcal)

70

60

MSW formula (1.9 g protein/100 kcal)

0 25 50 Days after birth 75 100 125

50

Steenhout et al, 2005

Infants fed a low protein formula show lower IGF-1 levels than those fed a classical formula

calculated risk for obesity during adolenscence (based on early weight gain) for infants fed low protein formula - 13% vs. infants fed high protein formula

32

Conclusions
Reducing the protein content in the starter formulas may attenuate the metabolic and renal overloads in the immature baby.

Targeted fractionation of the sweet whey proteins allowed the elaboration of a new formula: With low protein content and better amino acid profile Safe and able to support growth rates similar to those obtained by breast feeding Resulting in plasma AA profile closer to breast feeding Resulting in reduced plasma urea and urinary nitrogen excretion than standard, whey adapted formulas: smaller renal overload
OBESITY PREVENTION : early (fetal, 0-2 years) nutrition is important in prevention

33

THANK YOU