C L9.2 Developmental origins of cardiovascular diseases Flashcards
What is fetal growth determined by?
- Fetal growth is determined by multiple factors including genome and env
- 15% genotype
- 2% sex
What are the hormonal factors controlling growth?
- IGF, thyroids, insulin → promote growth
- Glucocorticoids → inhibits fetal growth
- GH → minimal control
What is intrauterine growth restriction (IUGR)
- Low term birth weight (<2.5g) (2% of term babies)
- Small-for-gestational age
- <2SD below population mean
- 10% of babies
- 2-3 times normal perinatal mortality
Why are babies born small?
- Causes: (↓delivery across placenta → distinct from being born premature)
- Uteroplacental insufficiency (mainly in western society)
- Maternal undernutrition (mainly in third world countries)
- May have trimester specific effects
- Maternal disease states
- Genetic factors
What are the risks associated with babies born small?
- Babies born small have a risk of developing adult disease
Fetal adaptations to improve survivability
- 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
- Independent of level of obesity or exercise
- i.e. obese people can give birth to IUGR babies
What are the critical programming periods and what is the significance of these periods being affected?
- Timing, duration, nature
- Preimplantation/implantation/organogenesis/prepartum maturation/suckling/after weaning/after puberty
- Different stages affected will have different outcomes
In what parameters are adults who were born small susceptible to?
- Organs
- Heart, vasculature, kidney, brain
- Systems
- RAS, HPA (hypothalamis-pituitary-adrenal) axis
- Alterations
- ↓ cell numberes
- Altered organ structure/”set-points”/hormone sensitivity
Characteristics of individuals born small
- Have a higher mortality rates of CV diseases
- Greater risk of non-fatal coronary heart disease & stroke
- Altered HPA Axis
- Higher plasma cortisol levels
- Altered mineralo & glucocorticoid R.
- Greater HPA axis responsiveness to stress
- Altered renal function → hypertension
Difference in cardiomyocytes in fetus of mothers exposed to maternal stress?
- ↓fetal body weight and relative heart weight
- ↑mononucleated cardiomyocytes & ↓binucleated cardiomyocytes → retarded maturation
- Implications in CV functions
How are the features of human IUGR models imitated?
- Bilateral uterine vessel ligation → uteroplacental insufficiency
What are the results in animal models with imitated IUGR?
- Offspring born small
- Alters maternal endocrine env (↓progesterone)
- Impairs mammary dev, early lactogenesis (↑milk protein genes)
- ↓milk quality and quantity during lactation
- Compromise postnantal growth with consequence for adult disease devlopment
Are there gender specific differences?
- Dev hypertension:
- Males at 6 months; Female don’t dev even by 18months
- Males have reduced cardiomyocytes numbers → causes hypertension
What is accelerated growth?
- 90% small babies have accelerated growth in first 6 months
- Independently associated with increased risk of adult diseases
- Early accelerated growth → protective against disease
- Late accelerated growth → detrimental (after 1 year)
Results of the intervention study on the effect of nutrition on babies born from IUGR
- Cross-fostering → restricted males onto control mothers
- Improves postnatal body weight due to early accelerated growth
- Cardiomyocyte numbers restored (prevents development of hypertension)
