Death rates from Coronary Heart Disease

in men 1968-78

Gardner MJ et al. 1984 Atlas of mortality from selected diseases in England and Wales, 1968-78. John Wiley, Chichester.

Mortality from coronary heart disease in15726 men and women in Hertfordshire

Hazard ratios for coronary heart disease in men

16 17 18 19 20 21 22 23 24 25 26 27>27

Weight at one year (pounds)

0

0.5

1

1.5

2

2.5

3

Ha

za

rd r

ati

o

Developmental plasticity

“The ability of a single genotype to produce more than one alternative form of structure, physiological state and behaviour in response to environmental conditions”

Developmental plasticityAdaptation

Constraint

The fetal origins theory

Coronary heart disease, stroke, type 2 diabetes, hypertension and osteoporosis, originate through developmental plasticity, in response to malnutrition during fetal life and infancy.

Certain cancers,including breast cancer,also originate in fetal life.

Before I got married I had six theories about bringing up children: now I have six children and no theories.

John Wilmot, Earl of Rochester

Undernutrition,stress, hypoxia

Critical windowof development

Altered gene expression

Adaptation

Gene defect

Fewer cells,altered structure

DISEASE

Phenotypic plasticity and the adult environment

Gene-environment interactions during development alter responses to the environment in adult life

Hazard ratios for coronary heart disease(hospital admission or death) in 3676 men

p for interaction=0.005

3.0

0.5

1.0

1.5

2.0

2.5

Ponderal index<26 kg/m3

Ponderal index>26 kg/m3

>15,70

0

-15,7

00

-12,4

00

-10,7

00

-8,40

0

>15,70

0

-15,7

00

-12,4

00

-10,7

00

-8,40

0

Household income (pounds sterling,1980)

Hazardratio

Weight gain in childhood and later disease

Severe hypertensionor CHD

Mild hypertension or stroke

Normotensive

z score

Prevalence of hypertension

Birth-weight

(kg)

%

Fifths of current weight (kg)

-74.8-62.6

-81.5-68.7

-88.0-75.2

-96.5-83.9

>96.5>83.9

MF

MF

0

20

40

60

80

>4.0

-4.0

-3.5

-3.0

Associations between early growth and later disease extend across the range of fetal and infant growth. This implies that what are regarded as normal variations in the supply of nutrients to the baby have important long–term effects.

Pelvic diameters

The external conjugate diameter is the distance between the spine of the fifth lumbar vertebra and the front of the pubic bone. A

diameter of less than 18 centimetres (7 inches) was used as a marker of a “flat” pelvis, the

result of rickets or lesser degrees of malnutrition in early childhood.

Odds ratios (95% confidence intervals) for stroke and hypertension

Stroke Hypertension

Mother’s pelvic

external conjugate diameter

(cm)

-181.62

(1.30 to 2.02)

1.89

(1.30 to 2.76)

>19 1.0 1.0

In a simultaneous regression of the effects of height and external conjugate on newly diagnosed hypertension, only the trend with external conjugate remained statistically significant (p=0.009)

32 percent of mothers born during December and January had external conjugate diameters of less than 18 centimetres compared with 20 percent among mothers born in the remaining months (p=0.0005)

Conclusion

Malnutrition during infancy, including lack of Vitamin D, leads to persisting changes in protein metabolism which prejudice the early nutrition and growth of the next generation and lead, in adult life, to an atherogenic lipid profile, hypertension and stroke.

The intercristal diameter is the maximal distance between the iliac crests, while the interspinous diameter is the distance between the anterior superior iliac spines. The intercristal is usually 2.5 cm (one inch) longer than the interspinous. The more the intercristal diameter exceeds the interspinous, the rounder the iliac crest.

The pubertal growth of girls is characterized by a disproportionate increase in the intercristal diameter and rounding of the iliac crests. This female pattern of hip growth is under the control of estrogens, though other hormones including growth hormone also play a role.

Hazard ratios for breast cancer

All mothers Multiparous mothers

Haz

ard

rati

o

Length of gestation (weeks)

Mothers’ intercristal diameter (cm) -28 -30 >30

40<40 40<40

Conclusion

Breast cancer is initiated by hormonal events during the mother’s puberty which lead to round, wide hips. The daughters of mothers with such hips are at increased risk of breast cancer because their mothers have an estrogen profile that adversely affects early mammary development.

Ovarian Cancer The hazard ratio for ovarian cancer was 3.3 (95% CI 1.6 to 7.0, p=0.004) in the daughters of mothers whose interspinous diameter was greater than 27 cm 

Hazard ratios for ovarian cancer according to mothers’ interspinous diameter and age at menarche

0

2

4

6

8

10

25 25.1-26.0 26.1-27.0 >27.0

Menarche at age 14 years or lessp for trend 0.002

Menarche at age 15 years or morep for trend 0.63

Interspinous diameter (cm)

Haz

ard

rati

o

 Hazard ratios (95% CI) for ovarian cancer among women whose mother’s age at menarche was 14

years or less

Mother’s height (cm)

Interspinous diameter 160 >160

>26cm9.7

(1.9 to 49)

1.5

(0.3 to 6.8)

p = 0.001 p = 0.25

www. Barker.org

Mother

Adult

Infant

Child

EmbryoFetus

Men Women

slow growthfunctional incapacity

metabolic incompetence

fat accumulation

cardiovascular diseasetype 2 diabetes

osteoporosis

slow growthpoor cognitive development

metabolic incompetence

poor livingconditions

excess caloriesunbalanced/unvaried diet

TheCycle of

Inequality

unbalanced/unvaried dietmetabolic incompetence