Theme C lecture 2

Question 1

What controls fetal growth during development?

Answer 1

Genetic factors: 15% on genotype and 2% on sex.

Hormonal factors: IGFs, thyroid hormones, insulin promote fetal growth whereas glucocorticoids inhibit fetal growth.

*Growth Hormone is not a main contributor to fetal growth.

Question 2

What life factors control fetal growth?

Answer 2

High altitude/hypoxia/oxygen deprivation (decreases fetal body weight)

Hyperthermia (reduce fetal growth

Maternal Exercise (reduce fetal growth)

Substance abuse/alcohol/drugs/smoking/toxins (reduce fetal growth)

Maternal disease (some decrease some increase)

Olihydramnios/multiple pregnancy/ fetal malformations (decrease fetal growth)

stress/hormones/fetal infection (decrease fetal growth)

Question 3

What are some examples of intrauterine growth restricting conditions?

Answer 3

Pre eclampsia

Bleeding; anemia

Renal and heart diseases

Convulsions

Diabetes mellitus

coagulation

Intrauterine fetal death

Question 4

What are the definitions of Intrauterine growth restriction (IUGR)?

Answer 4

low term birth weight (2.5 kgs): 2% of term babies.

Small-for-gestational age (IUGR):

Question 5

What is the incidence of Intrauterine growth restriction (IUGR)?

Answer 5

2 - 10% of babies

Question 6

What is the problem with a small birth weight?

Answer 6

it causes 2 - 3 times more perinatal mortality

Question 7

What are the main causes of Intrauterine growth restriction (IUGR) in developed and developing countries?

Answer 7

Developed: Uteroplacental insufficiency (Western Society)

Developing: Maternal undernutrition

Other causes include maternal disease and genetic problem

Question 8

What is fetal programming?

Answer 8

Exposure to suboptimal environment causes adaptations that may help the fetus survive in the short term but leads to increased susceptibility of deceloping some diseases in adulthood.

Question 9

What are the critical developmental periods which influence fetal programming?

Answer 9

Perincoception / preimplantation

Implantation / placental development

Organogenesis / maximal fetal growth

prepartum maturation (maturation after organogenesis and before birth)

suckling / postanatal / infancy

after weaning / childhood

After puberty / adolscence

Question 10

What are the problems that are more prominent in smaller fetuses and are influenced by fetal programming?

Answer 10

Hypertension

Coronary heart disease

Stroke

Atherosclerosis

Coagulation disorders

Question 11

What mechanisms are involved in programming cardiovascular diseases?

Answer 11

Organs: Heart; vasculature; kidney; brain

Systems: Renin-angiotensin system; HPA axis

Alterations: Reduced cell numbers, altered organ structure, altered set points, altered hormone sensitivity

Question 12

What heart problems are seen in adults born small?

Answer 12

Cardiac hypertrophy

Hypertension

Coronary heart disease

Altered cardiac genes

Question 13

What are the hypothalamic HPA axis differences seen more often in adults of small birth weight?

Answer 13

Higher plasma cortisol levels

Altered mineralo and glucocorticoid receptors

Greater hypothalamic pituitary adrenal axis responsiveness to ‘stress’

Altered renal function

hypertension

Question 14

What are the differences in vasculature seen in adults born small?

Answer 14

Altered vascular/endothelial reactivity to vasoconstrictors and vasodilators. (reduced responsiveness)

Increased vessel stiffness

Predisposition to atherosclerosis (hypertension)

Question 15

What are the differences in kidneys seen in adults born small?

Answer 15

Human and animal models have shown to have a smaller nephron number and higher blood pressure

Question 16

What happens to heart size of smaller fetuses?

Answer 16

hearts are smaller in smaller fetuses relative to their body weight compared to normal babies.

Question 17

What is the difference in this effect between males and females?

Answer 17

Males are more prone to heart problems than females due to low birth weight. Females develop hypertension 18 months

Question 18

What is the result of uteroplacental insufficiency?

Answer 18

Offspring are born small

maternal endocrine environment is altered

mammary development is impaired

Early lactogenesis

poor milk quality and quantity

Question 19

What is the problem of impaired lactation nutrition?

Answer 19

impaired lactation nutrition compromises postnatal growth with consequences for adult disease development.

Question 20

What happens to glomerular volume in males during adulthood?

Answer 20

They become larger while staying at a low number. This results in an increase in hypertension.

*This does NOT happen in females.

Question 21

What happens to glomerular volume in females during adulthood?

Answer 21

In females there is a decrease in glomerular number but no change in glomerular volume. No hypertension in females. (even at 18 months)

Question 22

What happens to cardiomyocyte numbers in mice?

Answer 22

Males develop less cardiomyocytes

Females don’t develop less cardiomyocytes

Question 23

What is the effect of early and late accelerated growth on disease?

Answer 23

early accelerated growth is protective against disease whereas late accelerated growth is detrimental.

Question 24

What is the function of leptin?

Answer 24

leptin regulates adiposity and appetite and acts to reduce food intake and increase activity

Question 25

Where does leptin act?

Answer 25

hypothalamus

Question 26

What leptin levels cause obesity?

Answer 26

very low or very high leptin levels

Question 27

What is the mechanism of leptin’s action?

Answer 27

leptin binds to receptor on cell membrane. Other proteins get turned on and in turn gene transcription is increased.

Question 28

What is the function of leptin in human babies?

Answer 28

Human babies have a leptin surge prior to birth. Leptin goes to human levels after 35 days.

Leptin is critical in the development of the kidneys

Question 29

What happens to leptin levels in growth restricted rats?

Answer 29

growth restricted rats have low protein and as a result a low leptin surge

Question 30

What are the consequences of the reduced leptin surge?

Answer 30

Growth restricted offspring

Reduced nephron endowment

Increased BP in males and cardiovascular disease risk

Question 31

Does restoring leptin surge restore nephron endowment?

Answer 31

Yes, cross fostering improves nephron endowment

Question 32

What is the effect of cross-fostering on leptin signalling?

Answer 32

Cross-fostering does restore altered kidney development but signalling does not assist in restoring leptin signalling.