1. EARLY INFANT FEEDING AND LONG-TERM CONSEQUENCES (OBESITY)

2. Adequate protein intake 0 – 12 (24) months Exclusive breastfeeding until 6 months, continuation of breastfeeding until 2 years >6 months introduction of solids

3. The First 1,000 Days – Programming for Healthy Life
270 days of pregnancy
365 days of baby’s first year
365 days of baby’s second year
The ‘programming’ that takes place during this period has a life-long impact on many aspects of future health
Programming of healthy or non-healthy growth
Metabolic programming
(Obesity, cognitive deficits)
Programming of Immune response
(infections, allergy)
Saavedra JM and Dattilo AM. Elsevier, Oxford 2017:xxxv.

4. Worldwide, the prevalence of overweight and obesity combined rose by 27.5% for adults and 47.1% for children between 1980 and 2013
Ng et al. Lancet 2014;388:

5. Risk factors for later obesity: early nutrition and lifestyle
Maternal overweight/obesity
Rapid weight gain during infancy
High protein intake during infancy and early childhood
Weng SF et al. Arch Dis Child 2012;97:1019–1026; Salsberry PJ et al. Pediatrics. 2005;116(6): Li L et al. J Dev Orig Health Dis 2014;5: ; Rolland-Cachera Mf et al. Int J Obes Relat Metab Disord. 1995;19(8):

6. True protein concentration in breastmilk is rapidly decreasing between 0–12 months
True Protein (g/100mL) 3 2 1 4 6 8 10 12
Time (months)
6 -24 months
1.3 – 1.5 g protein/100 kcal
1 -6 months
1.4 – 1.7 g protein/100 kcal
Lonnerdal B et al. J Nutr Biochem 2017;41:1-11.

7. Protein concentrations (g/100ml) in old infant formulas, old follow-up formulas and cow’s milk are higher than in breast milk
True Protein (g/100mL) 3 2 1 4 6 8 10 12
Time (months)
Old infant formulas
Old Follow-up formulas
Cow´s milk
Lonnerdal B et al. J Nutr Biochem 2017;41:1-11.

8. Protein intake (grams/day)
Average protein intake, g/day, of non-breastfed infants and young children compared to the Recommended Dietary Allowance (FITS 2016)
Protein intake (grams/day)
RDA
RDA
RDA
Cut?
Average energy intake > EER at all time points. Possible that Mother’s overestimated portion sizes consumed – yet, extensive training with 4-pass methodology to accurately represent 24-hr food consumption with FITS methodology.
In 2004: increase over EER was 10% at 4-6 mo, 23% at 7-12 mo and 31% at mo.
In 2008: increase over EER at 0-5 mo = 13.6%; 6-11 mo = 18.4% and mo = 21.8%
In 2008, infants participating in the FITS survey, age birth to 5months, consumed nearly 14% more calories (83 kcal/d) than estimated needs.
Applying the first law of thermodynamics in its simplest form, after 6 weeks, an estimated 0.45 kg weight gain would be possible, and after 6 months, an additional 1.9 kg of weight could be predicted. Utilizing an average weight of 7.9 kg for a 6-month-old infant boy, the weight differential of 1.9 kg corresponds to the difference between a weight for age between the 50th percentile and the 98th percentile.
Computed the mean EER for each age group based on the average weights/heights available on the subset of kids
EER: 0 to 5 6 to to to to 47
Actual intake: Age mo 0 to 5 6 to to to to 47
Energy intake (kcal/d)
Age in Months
Bailey RL et al. J Nutr 2018;148:1557S-1566S; IOM, Washington (DC): National Academies Press; 2005.

9. Increased risk of Childhood Obesity
Protein in early life influence health and metabolic programming, affecting growth and weight gain
High Protein Intake
Accelerated Growth
Increased risk of Childhood Obesity
Haschke F et al. NNI Workshop Series 2016;85:pp

10. Breastfeeding is associated with lower prevalence of obesity at 5–6 years
12.6%
9.2%
Prevalence (%)
4.5%
2.8%
Key message: breastfed infants have a lower risk of overweight and obesity in later childhood, with a stronger effect for those who are breastfed longer
A cross-sectional survey to assess the impact of breastfeeding on the risk of obesity and risk of being overweight in children at the time of entry to school
Subjects were 9,357 children aged 5 and 6 whose height and weight data were collected at an obligatory health examination at the time of school entry; feeding, diet and lifestyle factors were assessed using responses to a questionnaire completed by their parents
The prevalence of obesity in children who had never been breastfed was 4.5%, compared with 2.8% in breastfed children; prevalence of overweight was 12.6% and 9.2%, respectively
A clear dose-­response effect was identified for the duration of breastfeeding on the prevalence of obesity: the prevalence was 3.8% for 2 months of exclusive breastfeeding, 2.3% for 3­5 months, 1.7% for 6­12 months, and 0.8% for more than 12 months
In children who had been breastfed for ≥6 months or more, the risk of being overweight or obese was reduced (>30% and >40%, respectively)
Reference
von Kries R et al. BMJ 1999; 319:147–150.
Overweight = BMI >90th percentile
Obesity = BMI >97th percentile
von Kries R et al. BMJ 1999; 319:147–150.

11. FORMULAS – HIGH PROTEIN BREASTMILK – LOW PROTEIN
Weight/length z-score differences – breastfeeding vs high-protein formula (before 2000)
-0.8
-0.6
0.6
0.8
Age (months) 3 6 9 12 15 18 21
0.4
0.2
-0.4
-0.2
…the problem seems to start at 3 months
FORMULAS – HIGH PROTEIN
BREASTMILK – LOW PROTEIN
SDS weight-for-length
Key message: high protein intake (formula) compared with low protein intake (breast milk) is associated with greater weight-for-length over 2 years
Anthropometric indexes from 1–24 months were compared between matched cohorts of infants either breastfed (n=46) or formula-fed (n=41) until ≥12 months
Neither group received solid foods before 4 months
Weight-for-length was significantly greater among formula fed infants from 7–24 months
Reference
Dewey KG et al. Am J Clin Nutr 1993; 57:140–145.
*Significant difference
Dewey KG et al. Am J Clin Nutr 1993;57:

12. A Longitudinal Cohort Study in France Indicated Higher BMI until Adulthood, if Protein Intake at Months was High

13. High protein intake during the first 2 years is associated with increased BMI later in life14 16 24
Age (year) 2 6 8 10 12 18 20 22
BMI (kg/m2) 4
Early Rebound
Late Rebound
High
protein intake
Higher BMI
High protein intake
Earlier adiposity rebound
Seen in subjects who become overweight
Key message: high versus low protein intake in the first 2 years is associated with a higher BMI at 20 years
Children with high (>16% of calories) or low (<16% of calories) protein intakes during the first 2 years were followed until the age of 20 years
At the endpoint of the study (age 20 years), the group with the higher protein intake during the first 2 years had a BMI that was >2 kg/m2 higher
Reference
Rolland-Cachera MF et al. Int J Environ Res Public Health 2016; 13:E564.
Rolland-Cachera MF et al. Int J Environ Res Public Health 2016;13:2-7.

14. RCTs to Proof Causality: With New Low Protein Children Grow Like Breastfed Infants Breastfed Infants (Reference) Low Protein Formula High Protein Formula

15. Protein – improvement in protein quality allow protein in formulas to be closer to breast milk
True Protein (g/100mL) 3 2 1 4 6 8 10 12
Time (months)
Breast Milk 0 – 12 Months
High Protein Infant/follow up Formula
Low Protein Infant/follow up Formula
Lonnerdal B et al. J Nutr Biochem 2017;41:1-11; Haschke F et al. NNI Workshop Series 2016;85:pp , 2016; Ziegler EE et al, JPGN 2015;6(5):

16. Lower protein infant and FU formula: lower weight gain 0–12 months versus higher protein formula
Three randomised controlled trials comparing LOW PROTEIN and HIGH PROTEIN formula with BREASTFED reference groups (n=456) 10 15 30
Breastfed
Lower protein ( g / 100 kcal)
Higher protein ( g / 100 kcal) 20 25
Weight gain 0–12 months (g/day)
P < 0.05
Key message: lower protein infant formulas followed by lower protein formulas from 4–12 months lower weight gain than high protein formulas
Three recent randomised controlled trials with similar experimental designs compared growth and metabolic outcome of infants who received formulas with higher (HP) and lower protein (LP) contents until 12 months of age, or breast milk
Combined results indicate that low protein formulas slow rapid growth during the first year of life in infants of normal weight and overweight mothers while supporting normal growth1
Biomarkers of protein nutrition reflect the lower protein intake and levels are more like those of breastfed infants1
CHOP – Europe2
The Childhood Obesity Project (CHOP), a multicentre European trial compared outcomes of feeding formulas with 2.9 g and 4.4 g protein/100 kcal from 6 to 12 months of age
Up to 6 months the infants received formula with 1.77 or 2.2 g/ 100 kcal
BMI was significantly higher between 6 and 12 months in the group that received the HP formula
US3 and Chilean4 trials
Tested an experimental whey-based formula (3–12 months) with 1.61 g protein /100 kcal (< minimum protein limit in EU and USA), with a modified whey fraction with amino acid profile close to mature breast milk
Under 3 months the infants received formula with 1.8 g protein/100 kcal
In a multicentre US study, weight gain (g/day) from 3–6 months (1° outcome) was similar in the LP and HP groups3
Longitudinal analysis indicated lower weight from 4–12 months (p=0.031) and a lower % of infants with weight >85th percentile (p=0.015) in the group fed LP formula3
Serum biochemical parameters in the LP group reflected protein intake and were closer to biomarkers in breastfed infants than to those in the HP group3
The Chilean study tested whether a LP formula with slows weight gain in infants of overweight mothers4
Infants fed LP formula gained less weight (–1.77 g/day; p=0.028) from 3–6 months than infants fed HP formula4
The weight of infants fed the LP formula remained below that of infants fed the HP formula until 2 years of age (p=0.031), but was similar to the weight of breastfed infants4
Biomarkers of protein nutrition of infants fed the low protein formula were close to those of breastfed infants4
References
Haschke F et al. NNI Workshop Series; Vol 85, 2016.
Koletzko B et al. Am J Clin Nutr 2009;89:1836–45.
Ziegler EE et al. J Pediatr Gastroenterol Nutr 2015;61(5):596–603.
Inostroza J at el. JPGN 2014;59:70–77.
Haschke F et al. NNI Workshop Series 2016(85):pp , 2016; Ziegler EE et al, JPGN 2015;6(5):

17. BMI: breastfed infants, low-protein and high-protein formula: lower BMI at 6 years
17.5
Low Protein
High Protein
Breastfed
17.0
16.5
Adiposity rebound
Mean BMI kg/m2
16.0
15.5
Key message: in follow-up outcomes to 6 years BMI was similar in children who were breastfed and those who were fed low protein formula, and was increased in infants fed high protein formula
The Childhood Obesity Project (CHOP), a multicentre European trial compared outcomes of feeding high protein formulas, low protein formulas or breastfeeding2
The low protein formula group received formulas containing: 1.77 g protein/100 kcal (0–6 months) and 2.9 g/100 kcal (6–12 months)2
The high protein formula group received formulas with: 2.2 g / 100 kcal (0–6 months) and 4.4 g/100 kcal (6–12 months)2
Follow-up at 6 years: higher protein group (n=221), lower protein group (n=227), breastfed group (n=209)1
BMI at 6 years of age was significantly higher in the high protein than in the low protein group; the estimated difference in BMI was 0.51 (95% CI: 0.13–0.90; p=0.009)1
No significant difference was found between the low protein and breastfed children in mean BMI or obesity risk1
References
Weber M et al. Am J Clin Nutr 2014; 99:1041–1051.
Koletzko B et al. Am J Clin Nutr 2009; 89:1836–1845.
[NOTE TO SPEAKER: PLEASE DELETE FIGURE FROM SLIDE BEFORE PRINTING, DUE TO COPYRIGHT RESTRICTIONS]
15.0 3 6 12 24 30 36 42 48 54 60 66 72
Age (months)
Higher protein formulas – 2.2 g protein/100 kcal then 4.4 g protein/100 kcal
Lower protein formulas – 1.77 g protein/100 kcal then 2.9 g protein/100 kcal
Weber M et al. AJCN 2014;99:

18. Breastfeeding and lower protein formula: lower obesity risk at 6 years
Obesity prevalence (%)
Key message: reduced protein formula (infant and follow-on formula) in the first year reduces weight gain and BMI compared with higher protein formula and produces outcomes closer to that of children who were breastfed
The Childhood Obesity Project (CHOP), a multicentre European trial compared outcomes of feeding high protein formulas, low protein formulas or breastfeeding2
The low protein formula group received formulas containing: 1.77 g protein/100 kcal (0–6 months) and 2.9 g/100 kcal (6–12 months)2
The high protein formula group received formulas with: 2.2 g / 100 kcal (0–6 months) and 4.4 g/100 kcal (6–12 months)2
Follow-up at 6 years: higher protein group (n=221), lower protein group (n=227), breastfed group (n=209)1
Weight, length, weight-for-length and BMI were determined at inclusion and at 3, 6, 12 and 24 months of age, and thereafter every 6 months until 6 years of age
At 6 years the prevalence of obesity was 5.6% (95% CI: 0.9–10.4) higher in the high protein than in the low protein group1
Odds ratio (adjusted for confounders)=2.87 (95% CI: 1.22–6.75; p=0.016) 1
No significant difference was found between the low protein formula and breastfed children in mean obesity risk1
References
Weber M et al. Am J Clin Nutr 2014;99:1041–1051.
Koletzko B et al. Am J Clin Nutr 2009; 89:1836–1845.
Weber M et al. AJCN 2014;99:

19. HIGH PROTEIN INTAKE: BIOMARKERS INDICATE ACCELERATED GROWTH
Insulinogenic Aminoacids (Growth drivers)
Insulin
IGF-1
Koletzko et al. AJCN 2011;94: S

20. High protein intake in early life affect growth and weight gain
SUMMARY:
High protein intake in early life affect growth and weight gain
Slower growth is not so bad
Demand to be breastfed > 6mo
Avoid high protein supply:
If infant not (fully) breastfed: formula with reduced protein (high quality)
No cow‘s milk as a drink in infancy
   

21. For more information Visit:
childhood-obesity-outcomes-of-clinical-studies-