bone health - nutrition foundation of...
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Dr. C.S. Yajnik MD,FRCP
Director, Diabetes Unit
KEM Hospital and Research Centre
Rasta Peth, Pune-411011
Maternal Nutrition and Child’s Bone Health
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Maternal Nutrition & Offspring Bone Mass
• Osteoporosis and age-related fractures
• Bone mass (size x density) aquired during skeletal
growth (in utero, childhood and puberty)
• Heritability <80%, a few genetic markers
• Environmental factors influence mineral accrual
• Rapid rate of mineral gain in utero
• Plasticity of skeletal development
• Possibility of programming effects
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Maternal Nutrition & Offspring Bone Mass
• Offspring BMD (Europe and US): parental BW,
paternal height, parental size and BMD,
maternal smoking, vit D, calcium & folate..,
supplements
• Sachan (AJCN 2005) high proportion of
both urban and rural pregnant Indian
women with vit D deficiency ? Role of
chronic low calcium intake
• Maternal vit D a strong determinant of fetal
vit D
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Barker’s Hypothesis
Fetal Undernutrition
Metabolic
Endocrine
Vascular
Growth
Small size
Dys-proportion
Organs, Tissues, Cells
Fetal programmingWindows of opportunity
?Specificity
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Birth Size DevelopmentRisk factors
+Disease
+Mortality
Fetal Nutrition
& Growth
Maternal
Nutrition
Developmental Origins of
Health and Disease (DOHaD)
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Pune MaternalNutrition Study
Preconception Intrauterine Birth Postnatal 6y, 12, 18
Maternal
size
hemoglobin
2675
1993-94
Maternalnutrition
metabolismclinical
Paternal size & IRS
Fetal growth(USG)
8141994-97
Size Phenotype
7701996-97
Growth
every
6 months
743
Child& parents
sizeFat mass
IRSCV risk
698/723(95%)
2000-01
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Bone Programming
Mother(1993-96) Child
(2001-03)
Nutrition, Activity
Metabolism
Size & composition BMD at 6 y
Newborn
(1994-97)
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Nutrition During Pregnancy
• Diet tools specific for community
• Macronutrients from 24 h recall
• FFQ (3 month recall), less frequently eaten foods
• Triangulation of data base using weighment and laboratory estimations
• Micronutrient intake of calcium estimated from FFQ and Ca content in ‘Nutritional values of Indian foods’
• Vitamin D: Enzyme Immuno Assay Kit (IDS) Sensitivity 2 ng/ml
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• 42 kg, 1.52m, 18.1 kg/m2
• Smoking-0, alcohol-0
• 1700 cals, 45g pro, 35g fats
• 320g CHOs (73% cals)
• 1 pre-GDM, 3 IGT, 5 PIH
• <1% folate, 70% B-12 deficient
• Physically fit, active Fall CHD et al, 1999
Rao S et al, J Nutr 2001
Yajnik CS et al, Int J Ob 2003
Mothers
• Gestation 39.5 wks
• 2.65kg, 47.5cm, 24.1kg/m3
• Exclusively breast fed
• Perinatal mortality 21/1000
Babies
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mg/day
Calcium
Magnesium
Phosphorus
268 (RDA1000)
477 477
1016
Nutrient Intake at 28 wks
Micronutrient intake =
portion size (24 hr recall) *frequency (FFQ)*Levels from NIN
• Average portion size, cooked food
• Assumptions of raw weights, NIN ref for raw foods
• Ca-rich: milk & products, pulses, legumes, non-veg,
GLVs, fruits, seasame seeds, coconut
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Boys (369) Girls (326)
Age (y) 6.2 6.2
Weight (kg) 16.4 15.7 ***
Height (cm) 109.9 109.4 **
Total BMC (g) 655.0 615.3 ***
Total BMD (g/cm2) 0.79 0.77 ***
Spine BMD (g/cm2) 0.87 0.87
Lean mass (kg) 13.0 12.1 ***
Fat mass (kg) 2.9 3.3 ***
Characteristics of children at 6 y
Median IQR Different from girls * p< 0.05, **,p< 0.01, *** p<0.001
• No intake and activity measurements at 6y
• Technical issues of DXA
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Maternal Predictors of Bone Outcomes
at 6 y (n=698)
TOTAL
BMD
SPINE
BMD
Pre-pregnant fat mass (kg) 0.15*** 0.15***
Parity (0, 1, >1) -0.08* -0.12**
Red cell folate 28 wks (µg/l) 0.13** 0.17***
Workload score 28 wks -0.11** -0.11**
Tobacco chewing - 0.07 -0.08*
Exclusive breastfeeding -0.04 -0.08*
* p< 0.05, **,p< 0.01, *** p<0.001Values are Partial correlation coefficients
adjusted for child’s age, SES and gender
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0.700
0.710
0.720
0.730
0.740
0.750
0.760
0.770
0.780
0.790
0.800
Frequency 28wks gestation
Wh
ole
bod
y B
MD
M
ean
(S
E)
Milk prMilk Calcium-rich foods
r=0.11
***
r=0.09
**
r=0.12
***
Maternal Calcium Rich Food Intake & Child BMD 6 y
* p< 0.05, **,p< 0.01, *** p<0.001
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0.6
0.5
0.4
0.3
0.2
0.1
0
Mother
Father
Ch
ild
's e
qu
iva
len
t m
easu
rem
ent
GirlsBoys
Parental Bone Measurements & Child BMD at 6y
Correlation coefficient (95% CI)
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Outcome BMD
P
C age (yr) 0.20 ***
C sex (boys 0, girls 1) -0.12 **
C current height (cm) 0.15 **
C birth length (cm) 0.05 -
M height (cm) -0.03 -
M parity (0, 1, - 1) -0.06 -
M milk intake @ 28 wk 0.11 *
M equiv bone outcome 0.23 ***
Father’s equiv bone outcome 0.37 ***
Gestation at birth (wk) 0.01 -
Folate 28 wk (nmol/liter) 0.10 *
Predictors of Child’s Bone Measurements
Adjustments: SES, paternal height, mat energy and protein intakes 28 wk, workload,
tobacco, prepregnant fat mass, duration of breast-feeding
*p<0.05, **p<0.01, ***p<0.001
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Predictors of Child BMD
Total 27% variance explained
Modifiable 22%
Non modifiable
5%Unexplained
73%
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Maternal BMD
44%
Intersept
4%
Age
7%
Paternal BMD
19%
Sex
7%
Others
15%
Maternal milk
consumption
4%
Predictors of Child BMD
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Maternal circulating vit D3
28 wks Gestation
0 1.5
20.4
78.1
0
25
50
75
100
Vitamin D-
Mean 26.9+9.5 ng/ml
%
<5ng/ml
5-10 ng/ml
10-20ng/ml
>20ng/ml
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• Weak association (r2 <2%) macronutrient intake
• No direct measurement of sunlight exposure
– Outdoor physical activity as a surrogate: farming,
fetching water & wood
– Strong association (<0.001) with activity
– No season effect
Maternal circulating vit D3
28 wks Gestation
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0
10
20
30
40
Farming Fetching
Water
Fetching
Wood
% V
itam
in D
Defi
cie
nt
( <
20 n
g/m
l) Involved in activity
Not Involved in activity
Physical Activity & vit D deficiency 28 wks
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363227253246636193787138N =
Month of the visit at 28 wks
121110987654321
VIT
AM
IN D
ng
/ml
100
80
60
40
20
0
Seasonal distribution of Maternal vit D levels
Month
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Maternal vit D in Pregnancy and Offspring Size
• Inverse association with birth size (all measurements)
as well as 6y size, BMD and lean mass
• Persisted on adjusting for maternal intake and
physical activity
• Counterintuitive
• At variance with results in Europe (S’ton)
• Vit D deficiency was rare in Pune, common (~50%)
in S’ton
• Calcium intake poor in Pune, good in S’ton
• other factors: vit B12 and folate story, 1C (-CH3)
metabolism, thin-fat concept
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Summary
• Osteoporosis may be a major problem in India
• A life-course approach for prevention
• Paternal influence on offspring BMD suggest genetic factors, need investigation
• Maternal factors (BMD, intake of Ca, vit D status, folate status, tobacco, activity) make a ‘small’ but significant contribution
• Exclusive breast feeding predisposes
• Maternal vit D had unexpected associations, confounded by outdoor activities
• Future investigations: Genetic and epigenetic mechanisms, novel determinants, interaction with other nutrients (B12, folate), association with other NCD……
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AcknowledgementsMRC EEU
DJP Barker
CHD Fall
Alan Jackson
Barry Margetts
Cyrus Cooper
ARI
Shobha Rao
Sandhya Kanade
NIC
Punam Gupta
St John’s
Anura Kurpad
CCMB
Giriraj Chandak
TDR Hockaday
KGMM Alberti
P Dandona
John Yudkin
Prakash Shetty
Helga Refsum
Andrew Hattersley
Tim Frayling
K.M. Shelgikar
A.N. Pandit
Anoop Misra
FundingThe Wellcome TrustNestle FoundationIAEA, DBTFirodiya familyBajaj family
KEM Hospital Research Centre
Mrs Banoo Coyaji
V.N. Rao
Kurus Coyaji
Siddhi Hirve
Arun Kinare, Manoj, Otiv
S.S. Naik, Bhat, Jyoti
Khadilkar, Niranjan, Meena
Shaila, Anjali
Sonali, Himangi, Vaishali
Charu, Sayyad, Swapna, Smita
Raut, Deokar, Bhalerao, Chougule
Solat, Yenge, Adesh
Pallavi Yajnik