Lecture 2: Developmental Origins of Cardiovascular Disease

Question 1

What is the placenta responsible for?

Answer 1

Transport of nutrients and waste exchange from the foetus

Question 2

What hormones promote fetal growth?

Answer 2

IGFs, thyroid hormones and insulin

Question 3

What effect do glucocorticoids have?

Answer 3

Inhibit fetal growth

Question 4

When are glucocorticoids released?

Answer 4

In stressful situations

Question 5

What is the figure for small for gestational age and what % of babies is this?

Answer 5

Less than 2500g - 2%

Question 6

What % of birth size is dependent on genotype and sex?

Answer 6

15%

2%

Question 7

What is low term birth weight and what % of babies have this?

Answer 7

2SD below population mens - 10%

Question 8

What % of babies die due to being born small?

Answer 8

2-10%

Question 9

What is intrauterine growth restriction caused by in western and 3rd world societies?

Answer 9

Placental insufficiency

Maternal undernutrition

Question 10

What is the common feature of the causes of IUGR?

Answer 10

Reduced nutrient delivery across the placenta

Question 11

What is fetal programming?

Answer 11

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

Question 12

What is prepartum maturation?

Answer 12

Maturation after organogenesis but before birth

Question 13

What are adult disease associated with?

Answer 13

Suboptimal intrauterine conditions in humans

Question 14

What cardiac conditions are adults born small susceptible to?

Answer 14

Cardiac hypertrophy, hypertension, coronary heart disease and altered cardiac genes

Question 15

What corticoid changes are present in adults who were born small?

Answer 15

Higher plasma cortisol, altered mineralo and glucocorticoid receptos

Question 16

What are the changes in nephrons in adults born small?

Answer 16

Reduced nephron endowment, low nephron number, high BP

Question 17

When do cardiomyocytes transition to binucleate form?

Answer 17

Late development and around birth (reduced binucleate cardiomyocytes when born small)

Question 18

What does uteroplacental insufficiency lead to?

Answer 18

• 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

Question 19

What are the sex specific differences associated with being born small?

Answer 19

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

Question 20

What % of babies born small have accelerated growth in the first 6 months?

Answer 20

90%

Question 21

When is accelerated growth good and bad?

Answer 21

Protective if early and detrimental if late

Question 22

What happens when you cross foster a restricted male with a control mum?

Answer 22

Improved postnatal body weight due to adequate lactational nutrition