Dr. C.S. Yajnik MD,FRCP

Director, Diabetes Unit

KEM Hospital and Research Centre

Rasta Peth, Pune-411011

diabetes@vsnl.com

Maternal Nutrition and Child’s Bone Health

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

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

Barker’s Hypothesis

Fetal Undernutrition

Metabolic

Endocrine

Vascular

Growth

Small size

Dys-proportion

Organs, Tissues, Cells

Fetal programmingWindows of opportunity

?Specificity

Birth Size DevelopmentRisk factors

+Disease

+Mortality

Fetal Nutrition

& Growth

Maternal

Nutrition

Developmental Origins of

Health and Disease (DOHaD)

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

Bone Programming

Mother(1993-96) Child

(2001-03)

Nutrition, Activity

Metabolism

Size & composition BMD at 6 y

Newborn

(1994-97)

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

• 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

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

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

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

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

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)

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

Predictors of Child BMD

Total 27% variance explained

Modifiable 22%

Non modifiable

5%Unexplained

73%

Maternal BMD

44%

Intersept

4%

Age

7%

Paternal BMD

19%

Sex

7%

Others

15%

Maternal milk

consumption

4%

Predictors of Child BMD

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

• 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

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

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

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

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……

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