Lecture 2: Developmental Origins of Cardiovascular Disease Flashcards
What is the placenta responsible for?
Transport of nutrients and waste exchange from the foetus
What hormones promote fetal growth?
IGFs, thyroid hormones and insulin
What effect do glucocorticoids have?
Inhibit fetal growth
When are glucocorticoids released?
In stressful situations
What is the figure for small for gestational age and what % of babies is this?
Less than 2500g - 2%
What % of birth size is dependent on genotype and sex?
15%
2%
What is low term birth weight and what % of babies have this?
2SD below population mens - 10%
What % of babies die due to being born small?
2-10%
What is intrauterine growth restriction caused by in western and 3rd world societies?
Placental insufficiency
Maternal undernutrition
What is the common feature of the causes of IUGR?
Reduced nutrient delivery across the placenta
What is fetal programming?
Exposure of the fetus to a suboptimal environment causes adaptations that may help the fetus to survive in the short term but leads to increased susceptibility of developing some diseases in adulthood. If there is a reduction in nutrient transport across the placenta the baby will keep brain developing normal and restrict development of other organs - disease occurrence
What is prepartum maturation?
Maturation after organogenesis but before birth
What are adult disease associated with?
Suboptimal intrauterine conditions in humans
What cardiac conditions are adults born small susceptible to?
Cardiac hypertrophy, hypertension, coronary heart disease and altered cardiac genes
What corticoid changes are present in adults who were born small?
Higher plasma cortisol, altered mineralo and glucocorticoid receptos
What are the changes in nephrons in adults born small?
Reduced nephron endowment, low nephron number, high BP
When do cardiomyocytes transition to binucleate form?
Late development and around birth (reduced binucleate cardiomyocytes when born small)
What does uteroplacental insufficiency lead to?
- Offspring born small (10% reduction in birth weight)
- Altered maternal endocrine environment (reduced progesterone)
- Impaired mammary development during pregnancy
- Triggers early lactogenesis (increases milk protein genes)
- Reduced milk quality and quantity during lactation: impaired lactational nutrition compromises postnatal growth with consequences for adult disease development
What are the sex specific differences associated with being born small?
Males more susceptible to disease development in adulthood, whereas females are relatively protected - even after being subjected to the same in utero restriction. Males develop hypertension at 6 months and females don’t develop hypertension even by 18 months
What % of babies born small have accelerated growth in the first 6 months?
90%
When is accelerated growth good and bad?
Protective if early and detrimental if late
What happens when you cross foster a restricted male with a control mum?
Improved postnatal body weight due to adequate lactational nutrition
