Transcript 2_Maternal and fetal nutrition

Petrenko N.V., MD, PhD
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Maternal Undernutrition and Low
Birthweight (LBW)
Overnutrition and Metabolic Syndrome
LBW and Metabolic Syndrome: Is There a
Relationship?
Fetal Programming, “thrifty phenotype”, and
epigenetics
Future Directions
“Birthweight is a strong
indicator not only of a
birth mother's health and
nutritional status but also
a newborn's chances for
survival, growth, longterm health and
psychosocial
development.”
- UNICEF
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Definition: birthweight <2500 g (5.5 lbs)
http://thebumpoc.com/?p=320
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Low birthweight babies are more than 20 times
likely to die during infancy than heavier babies.
UNICEF/WHO 2004
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Maternal malnutrition is the leading cause
of low birth weight in developing countries
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Has varied roots:
 Poor nutritional status prior to pregnancy
 Short stature
 Poor nutrition during pregnancy
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Numerous disorders occur more commonly in
adult former LBW babies.
 COPD, breast CA, osteoporosis, schizophrenia,
metabolic syndrome
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LBW babies are more likely than average
birthweight babies to develop type 2 diabetes
and hypertension in adulthood.
Barker et al. Rev Reprod 1997
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Rats exposed to 50% maternal undernutrition
in the last half of pregnancy had poor
remodeling of vasculature, a contributing
factor to subsequent hypertension.
Khorram O. et al. Repreod Sci 2007
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In adulthood, LBW rats developed obesity
and had increased expression of lipogenic
“obesity” genes
Magee et al., Am J Obstet Gynecol 2008
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Abdominal obesity
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High serum triglycerides
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Low HDL (high-density lipoprotein)
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Insulin resistance
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Hypertension
INCREASED RISK OF CARDIOVASCULAR
DISEASE AND TYPE II DIABETES
Stimulus
Adaptation
Maternal Malnutrition
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Poor fetal and infant growth increase
susceptibility to metabolic syndrome later in
life
Maternal Malnutrition
fetal malnutrition
beta-cell mass or islet dysfunction
adult beta-cell function
obesity
age
insulin resistance
Metabolic Syndrome
hypertension
FETAL
ENVIRONMENT
Adequate Nutrition
POSTNATAL
ENVIRONMENT
ADULT
HEALTH
Adequate Nutrition
HEALTHY
Poor Nutrition
Adequate Nutrition
Poor Nutrition
Poor Nutrition
MALNOURISHED
METABOLIC
SYNDROME
MALNOURISHED
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Published in early 1990s (Hales, Barker et al.)
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468 men born in Hertfordshire 1920-1930 and
still living there
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Birthweights recorded
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Tests for insulin resistance performed:
 fasting glucose and insulin before and after
glucose drink
Odds Ratio Insulin Resistance
Low Birthweight Increases Risk of Insulin Resistance in Adulthood
Birth Weight (lbs)
Hales CN et al. BMJ 1991; 303:1019-22
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5585 men and 10,141 women born in
Sheffield, UK 1911-1930.
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Low birthweight infants had higher risk of
coronary artery disease in adulthood
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Similar trends in risk for hypertension and
type 2 diabetes
Osmond et al. BMJ 1993
Standardized Mortality Ratio
Birthweight
Osmond et al. BMJ 1993
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Effects of strict food rationing at end of WWII
in Holland: Nov 1944 – May 1945
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Men and women exposed to famine while in
utero had increased risk of insulin resistance
and metabolic syndrome as adults
 More obesity and coronary artery disease in those
exposed to famine during early gestation
 Those with low birthweight who became obese
during adulthood had more insulin resistance
Ravelli et al. Lancet 2998
Epigenetics:
“The study of heritable changes in phenotype
(appearance) or gene expression caused by
mechanisms other than changes in the
underlying DNA sequence.”
Wikipedia
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Studies in Avy/a mice:
 Mice vary in expression of agouti gene expression
 Genetically identical but methylation of agouti
gene varies considerably
 Tend to overeat and become obese if allowed to
eat ad libitum
 Good model for human obesity
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Studies in Avy/a mice:
 Allowed mice to eat ad lib and become obese
 Bred for three successive generations
 Some mice given methyl donor supplement,
others not given methyl donor supplement.
food + methyl donor
food only
GROUP 1
GROUP 2
Obese mouse dams produce obese offspring,
but methyl donor supplementation prevents this effect
maternal weight
food + methyl donor
food only
3rd generation offspring
weight
Waterland RA et al. Int J Obes 2008
METABOLIC SYNDROME RISK
“U” – Shaped Curve
BIRTH WEIGHT
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Continue to treat maternal undernutrition via
programs in resource-poor areas as IMHO
currently does.
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Address overnutrition/obesity in all areas:
 Education
 Promote availability of healthy, affordable
unprocessed foods