Fetal origins of adult disease

Anne Wallis

MCH – Cluj

27 October 2010

Development of an idea

• Early geographic associations showed that contemporary mortality rates from CVD were associated with IMRs >50 years prior, by area, in England and Wales

• Was this evidence of fetal disease origins, or confounding of socioeconomic variables?

BP and birthweight

• Law & Shiell conducted a meta-analysis that showed persistent relationship between increased BP at all ages and lower birthweight

• Koupilova, et al, showed in a Swedish study that socioeconomic factors did not account for this association

• Similar evidence for non-insulin dependent diabetes

Hertfordshire study

BW (pounds) Men (born 1911-30) RRs for CHD

5.5 1.00

6 0.81

7 0.80

8 0.74

9 0.55

10 0.65

P-value for trend P<0.0005

(Osmond, et al., 1993)

Possible mechanisms• Genetic factors

• Maternal nutrition, including placental function in transfer of nutrients

• “Programming” (Lucas, 1991)

• Induction, deletion, or impaired development of a permanent somatic structure as a result of a stimulus or insult operating at a critical period

• Physiological 'setting' by cm early stimulus or insult at a 'sensitive' period, resulting in long-term consequences for function.

What does this mean?• Forces us to reorient how we think about

fetal growth and fetal growth restriction

• Perinatal epi has been mostly concerned with studying the immediate or short-term pathologic consequences of variations in fetal growth

• This hypothesis suggests that insults to fetal growth carry lifetime implications

Implications for theory?

• Socioeconomic origins?

• Place of residence?

• Birth health of parents?

• Global health

• Implications for research

community health centers

0.0

12.5

25.0

37.5

50.0

62.5

75.0

87.5

100.0

112.5

125.0

Coted’Ivoire

Haiti India Georgia Mexico Columbia US Japan

IMR

hygiene

antibiotics

warming

trained birthattendants

improved standardof living social

medicine

surfactant

NICU tech

food

antimalarial Rx

cord care

breastfeeding

education of women

equalityemergency transport

in-hospitalbirths

Resources/NMR 50-70/1000 NMR 20-50/1000 NMR 10-20/1000 NMR <10/1000 NMR

Low

hygiene; breastfeeding; nutritional suppl;

warming; cord care; tetanus toxoid vax

home visit; surveillance; trained

attendants; kangaroo mom care

community interventions

community interventions; SIDs

campaigns; smoking cessation

Med

Vaccinations; monitoring; skilled

attendant; oral antibs; resuscitation;

assessment w/low-cost eqpt (e.g., scales)

scaling-up health system; political

commitment; birth registration;

housing/sanitation

environmental improvements;

working conditions

political commitment to

ending racism/classism;

education/empowerment of highest risk

High

parenteral antibs; education/empowermen

t of women; birth registration; accurate

measurement/dx; clean water; redistribution of

wealth/reduction of poverty

education of women; hospital-

based births; universal access

NICU technology; transport

emergency transport increased

income redistribution;

universal h/c; NICU tech

Cross-cuttingcommitment to ending war; reduction in expenditures on military; universal rights;

equitable distribution of wealth

Proposed decision-making matrix for antenatal, OB, and neonatal care