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Early Metabolic Programming - 1 InfantNutrition B.koletzko
Early Metabolic Programming - 1 InfantNutrition B.koletzko
Topics:
Infant Nutrition and Lifelong Health: z Metabolic Programming of Lifelong
The Power of Metabolic Programming Health: Concept and Examples
z Early Nutrition Programming Project
Berthold Koletzko, MD PhD
Professor of Paediatrics, Dr von Hauner Children‘s Hospital,
University of Munich Medical Centre, Munich, Germany z Infant feeding and later obesity
for the Early Nutrition Programming Project
www.metabolic-programming.org
office.koletzko@med.uni-muenchen.de
Early programming:
Metabolic programming an established concept in biology
Metabolic and nutritional Behavioural programming
factors acting during limited, Hatching geese accept first moving object as „parent“.
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
1
Suboptimal folate during pregnancy Perinatal omega-3 fatty acids
improve verbal IQ @school age
Good folate status
prior to and after
conception prevents
neural tube defects, Ï Seafood intake
and likely orofacial in pregnancy ⇒
clefts and congenital less low verbal IQ
adj. for 28 pot. confounders
heart defects Hibbeln et al, Lancet 2007
2
Programming Infant feeding programmes
by Infant Feeding long-term health: evidence
Increasing evidence z Infection & allergy risk
Epidemiologic & experimental z Autoimmune diseases
studies; first controlled e.g. diabetes T1, inflammatory
intervention studies in infants
bowel disease, coeliac disease
Physiological basis
Rapid growth & differentiation z Cardiovascular risk
z Neural & brain function
Neonatal weight doubled in only 21 wks.
Preventive potential
Potential to modulate z Bone health Koletzko et al (ed.) Adv Exp
Med Biol 2005;569:1-237
substrate supply and growth z Obesity & 2009;646:1-196
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
Birth in the
hungry season
July-October
(hungry season)
3
Ð Birth weight ⇒ Ï mortality ratios at 20-74 y. Fasting insulin in 426 elderly Finish people:
in 10,141 men born in Hertfordshire 1911-1930 birthweight and PPAR-γ SNPs matter
Coronary Heart All Cardiovascular All Dauses
<3000 g 3000-3500 g >3500 g
Disease Disease of Death
110 110 110
80
Insulin (pmol/L)
100 100 100 P=0.00 P=0.02 n.s.
70 8
90 90 90 60
80 80 80 50
70 70 70 40
60 60 60 30
50 50 50 20
40 40 40 10
<5.5 -6.5 -7.5 -8.5 -9.5 >9.5 <5.5 -6.5 -7.5 -8.5 -9.5 >9.5 <5.5 -6.5 -7.5 -8.5 -9.5 >9.5
0
Birthweight (Brit. Pounds ≅ 454 g) Barker 1994 Pro12Pro Pro12Ala/Ala12Ala Pro12Pro Pro12Ala/Ala12Ala Pro12Pro Pro12Ala/Ala12Ala
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de Eriksson et al 2002
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ADULT HEALTH
CHILD
INFANT
Early nutrition and
FETUS
genes interact Prosp. Observat.
GENES
Lifetime Animal
Follow
programming is up of
rando-
where nature and mised
trials
nurture overlap
www.metabolic-programming.org
office.koletzko@med.uni-muenchen.de www.metabolic-programming.org
office.koletzko@med.uni-muenchen.de
z endocrine regulation
24
Obesity risk 23
Metabolic programming 22
z intrauterine metabolism <2.5 2.5-3.0 3.0-3.5 3.5-4.0 4.0-4.5 >4.5
z postnatal diet/growth Birthweight (kg)
z endocrine regulation Adjusted for gest age, birth length, maternal factors
Sorensen et al., BMJ 1997.
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
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Exposure to diabetes in pregnancy ÖÏ later BMI Diabetes in pregnancy and obesity
(58 children from 19 Pima families)
in the offspring: a vicious cycle?
Diabetes Obesity
in pregnancy Ö Diabetes
Dabelea et al 2000
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
Undernutrition Undernutrition
from 3 to 6 weeks from 9 to 12 weeks
=> permanently smaller => no permanent effect
Breast feeding: Ð Odds Ratio for obesity Breastfeeding and obesity: Meta-analysis
@school age, adjusted for confounders Covariate adjusted odds ratios, pooled odds ratio
Arenz, Rückerl, Koletzko, von Kries. Int J Obesity 2004
9206 Bavarian children at school entry; Brit Med J 1999,319:147-50
Adj. Odds Ratios Odds Ratio for
Breast fed Overwt. Obesity
Overweight & Obesity
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Meta-analysis: Ï duration of Probit Study, Belarus: duration of breast
breastfeeding ⇒ Ð later obesity risk feeding not related to obesity @ 6.5 y
OR
AJCN 2007
7
Growth of breast- High weight gain
birth to 2 yrs
and bottle fed infants Î high risk of 30
overweight at
z 19 growth studies in infants from
affluent populations (Australia, Canada,
school age 20
Denmark, Finland, Italy, Japan, South Africa, Sweden, USA) Height and weight in 4,235 children
at birth, 6, 12 & 24 mon. (preventive
z Lower weight gain in the 1st. year health checks by paediatricians/ 10
GPs) & at 5-6 years (school entry)
of life in breastfed infants
if 9 / 12 mon. breastfed, @1 yr. Ð 400 / 600 g 0
10 20 30 40 50 60 70 80 90 100
Dewey, Biol Neonate 1998;74:94-105 Arch Pediatr Adolesc Med 2004;158:449-452 Centile weight gain 0 – 2 yrs
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
3,5
g protein/kg&d
Formula Protein
90th Perc.
3
90th perc.
10th perc. Insulin, IGF1
2-3fold risk of obesity in
2
50th perc.
1,5
8
Randomisation
Not allocated n= 24 Not allocated n= 24
Allocation
unknown n= 10 unknown n= 12
z lack of compliance n= 65
months lack of compliance n= 82
medication/illness n= 3
Low protein High protein
Lost to follow-up: n= 31 Lost to follow-up: n= 30
n = 428 n = 423
Single mothers
parental refusal n= 20 parental refusal n= 23
z other reasons/
unknown
Exclusion
n= 11
n= 13
Follow-up 12
months
other reasons/
unknown
Exclusion
n= 7
n= 10
lack of compliance n= 12 lack of compliance n= 10
medication/illness n= 1
Smoking
Low protein High protein
z Lost to follow-up: n= 45
parental refusal n= 20
n = 384 n = 383 Lost to follow-up: n= 34
parental refusal n= 21
other reasons/ other reasons/
unknown n= 25 Follow-up 24 unknown n= 13
Birth order
Exclusion n= 1 months Exclusion n= 0
z medication/illness n= 1
Low protein High protein
n = 338 n = 349
z
measured
Low protein High protein
n = 313 n = 322
office.koletzko@med.uni-muenchen.de Koletzko et al, Am J Clin Nutr 2009 office.koletzko@med.uni-muenchen.de Koletzko et al, Am J Clin Nutr 2009
higher protein
lower protein
Protein Intake higher protein
Intervention period
Energy Intake 1200
4 Ï protein (kcal/day)
3 Ð protein
800
2
FAO/WHO/UNU **
Reference Intakes 2008
1 600
0 400
3 6 12 24 months
3 6 12 24
office.koletzko@med.uni-muenchen.de Koletzko et al, Am J Clin Nutr 2009 Koletzko et al, Am J Clin Nutr 2009 office.koletzko@med.uni-muenchen.de Age in months
SDS length for age not different SDS weight for length: Ï @high protein
z-scores, mean, 95 % CI, relative to WHO growth charts. z-scores, mean, 95 % CI, relative to WHO growth charts. p-values from Anova adjusted
for baseline value comparing higher and lower protein group: * <0.05, **<0.01, ***<0.001
0.4 ***
0.5 **
0.2 **
z -s c o re
0.0
z-score
0.0
-0.5
-0.2
office.koletzko@med.uni-muenchen.de Koletzko et al, Am J Clin Nutr 2009 office.koletzko@med.uni-muenchen.de Koletzko et al, Am J Clin Nutr 2009
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BMI Ï @high protein Predicted effect on later overweight
z-scores, mean, 95 % CI, relative to WHO growth charts. p-values from Anova adjusted
for baseline value comparing higher and lower protein group: * <0.05, **<0.01, ***<0.001
z Δ 1 SD in weight-for-length gain birth
*** BMI at 2 years to 2 yrs = OR 1.87 (95%CI 1.10-3.18) for
0.5 ** p < 0.01*
obesity @14-16 yrs (Monteiro et al 2003; Ong & Loos
2006)
0.40 ± 0.95
0.4
z -s c o re
z score ± SD
z
**
⇒ 13 % reduction
0.3
0.0
0.25 ± 0.95
1 33 6
6 12
12 24
24 Age (months)
Breast-
fed
Lower
protein
Higher
protein
due to lower protein supply
Koletzko et al, Am J Clin Nutr 2009 *ANOVA adjusted for baseline value
office.koletzko@med.uni-muenchen.de office.koletzko@med.uni-muenchen.de
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