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
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