Transgenerational programming of disease Flashcards
What us the definition of low birth weight?
What causes low birth weight in developed countries?
Placental insufficiency
What is the incidence of intrauterine growth restriction?
2 - 10% of babies
*This is 2 - 3 times normal perinatal mortality
What causes low birth weight in developing countries?
Maternal undernutrition
What are some other causes of babies being born small?
Maternal disease
Genetic disease
Being born small does not count if born prematurely.
What is a feature that is common among all IUGR babies?
Low nutrient delivery to the baby
What is fetal programming?
Babies born small have an increased risk of developing adult disease. This occurs because they develop adaptations to survive in the short term which causes problems in the long term.
Does obesity and exercise influence programmed conditions?
Fetal programming of adult disease is independent of exercise and level of obesity. (I.e it is a separate risk factor)
What conditions are adults born small at a higher risk of developing?
Diabetes and obesity
Osteoporosis
Cardiovascular disease and hypertension
Renal disease
What are the critical periods of a child’s development?
Pre-conception
Pre-implantation
Implantation and placental development
Organogenesis
Maximal fetal growth
Prepartum maturation
Birth
Suckling
Weaning
What percentage of small babies have accelerated growth in utero?
90% of small babies have some degree of accelerated growth during the first 6 months.
How is heart disease rates influenced by accelerated growth?
Accelerated growth is independently associated with an increased risk of heart disease.
What happens to milk quality after birth of a small baby? How can this be fixed?
Mothers milk loses quality because the nutrition matches the placental delivery of nutrients
Why do these conditions result from impaired development?
Reduced organ development causing deficits and later life dysfunction. (more prone to second hits)
What are the changes in the kidneys during adulthood in IUGR males?
Restricted males get low nephron numbers at 6 months.
Glomerular hypertrophy
Normal glomerular volume
Increase in Blood pressure by 6 weeks
What are the changes in the kidneys during adulthood in IUGR females?
No increase in blood pressure at 18 months.
Low nephron number
Glomerular hypertrophy at 18 months
Increase in plasma creatinine and renal insufficiency at 18 months.
*Girls were better protected
What effects did uteroplacental insufficiency have on male babies of the F1 generation?
Low birth weight
Bone defects
Decrease in beta cell mass
Glucose intolerance
Decrease in skeletal muscle mitochondrial biogenesis
Increase in BP and lower cardiomyocyte number
Lower nephron number and glomerular hypertrophy
Increased mesenteric vessel stiffness and less relaxation
What symptoms did F1 females develop?
Like males:
Low birth weight
Bone defects
Decrease in beta cell mass but didn’t develop glucose intolerance
Decrease in renal nephron number and glomerular hypertrophy.
Unlike Males:
Females did not experience skeletal muscle mitochondrial biogenesis.
Females did not experience higher Blood pressure
Females experienced glomerular hypertrophy at 18 months unlike males who developed it at 6 months
Unlike males females did not develop stiffness in their mesenteric vessels but rather they experienced stiffness in their uterine vessels
What is the general difference between how males and females react to IUGR?
Both males and females exhibit organ deficits but females are protected from the harsh effects of these organ defects.
What happens to the phenotype of small birth weight with age?
With age the phenotype gets worse. Several other phenotypes also make the condition worse.
What effect does exercise have on beta cell mass?
If exercise is done early in life it can increase beta cell number to full and reduce metabolic conditions.
What happens when babies are cross-fostered with other mothers of healthy babies?
Cross-fostering a baby with other mothers completely reduced all the organ deficits and prevented high blood pressure and metabolic dysfunction.
What happens when babies are cross-fostered with other mothers of healthy babies?
Cross-fostering a baby with other mothers completely reduced all the organ deficits and prevented high blood pressure and metabolic dysfunction.
What causes low birth weight in developed countries?
Placental insufficiency
