maternal and fetal nutrition petrenko n.v., md, phd
TRANSCRIPT
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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
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“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, long-term health and psychosocial development.” - UNICEF
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Definition: birthweight <2500 g (5.5 lbs)
Low birthweight babies are more than 20 times likely to die during infancy than heavier babies.
http://thebumpoc.com/?p=320
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UNICEF/WHO 2004
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Maternal malnutrition is the leading cause of low birth weight in developing countries
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
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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In adulthood, LBW rats developed obesity and had increased expression of lipogenic “obesity” genes Magee et al., Am J Obstet Gynecol 2008
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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Abdominal obesity
High serum triglycerides
Low HDL (high-density lipoprotein)
Insulin resistance
HypertensionINCREASED RISK OF CARDIOVASCULARDISEASE AND TYPE II DIABETES
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Stimulus
Adaptation
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Maternal Malnutrition
?
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Poor fetal and infant growth increase susceptibility to metabolic syndrome later in
life
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Maternal Malnutrition
Metabolic Syndrome
beta-cell mass or islet dysfunction
adult beta-cell function
insulin resistance
fetal malnutrition
hypertension
obesity age
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Adequate Nutrition
Poor Nutrition
FETALENVIRONMENT
POSTNATALENVIRONMENT
ADULTHEALTH
Adequate Nutrition
Poor Nutrition
Adequate Nutrition
Poor Nutrition
METABOLICSYNDROME
HEALTHY
MALNOURISHED
MALNOURISHED
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Published in early 1990s (Hales, Barker et al.)
468 men born in Hertfordshire 1920-1930 and still living there
Birthweights recordedTests for insulin resistance performed: fasting glucose and insulin before and after glucose drink
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Birth Weight (lbs)Odds Ratio Insulin Resistance
Hales CN et al. BMJ 1991; 303:1019-22
Low Birthweight Increases Risk of Insulin Resistance in Adulthood
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Osmond et al. BMJ 1993
Standardized Mortality Ratio
Birthweight
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Effects of strict food rationing at end of WWII in Holland: Nov 1944 – May 1945
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
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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
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Waterland RA et al. Int J Obes 2008
food + methyl donorfood only
maternal weight
3rd generation offspringweight
Obese mouse dams produce obese offspring, but methyl donor supplementation prevents this effect
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METABOLIC SYNDROME RISK
BIRTH WEIGHT
“U” – Shaped Curve
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Continue to treat maternal undernutrition via programs in resource-poor areas as IMHO currently does.
Address overnutrition/obesity in all areas: Education Promote availability of healthy, affordable unprocessed foods