Fetal Cardiovascular and Growth response to Undernutrition Flashcards
What is the baby doing within the womb during gestation?
Growing
Metabolism
Breathing and moving
Keeping heart beating
Foetal brain electrical activity (sleep states)
Being a foetus is metabolically demanding, explain the energy requirements for mum, foetus and newborn
Mum –> 26kcal /kg/day
Foetus –> 49kcal/kg/day (roughly 100 including carcass energy)
Newborn –> roughly 120 kcal/kg/day (must maintain body temperature)
Metabolic rate is energy liberated over time e.g., kcal/kg/unit time
In the sheep model, how is the metabolic demand effected by low glucose or undernutrition?
How does the foetus adapt to changes in their environment?
Stay in the womb longer or get out
Change where nutrients are sent
Change what is done with the nutrients
Questions for today
1.Is there a foetal cardiovascular response to nutrients?
2.How does the foetus make this response?
3.What are the short- and long-term implications for the growing baby?
Tell me about the cardiovascular adaptation the foetus has in response to nutrients
We’ll think about this in 2 main ways:
Baseline CV
Responses to the CVS
Timing
Regions of the foetal body
How do you monitor the foetus?
Ultrasound scans
Animal models are successful in discovering how the foetus responds to changes in environment
Sheep is a good model, as high proportion of singletons and twins which grow similar to humans and different to multiple births
How does the foetus respond to low oxygen?
Foetus redistributes blood flow around body in favour of vital organs like heart and adrenal glands when there is low oxygen
Tell me about the baseline cardiovascular changes that occur and some studies to support the findings
Purple= study 1
Shows conflict in literature about this as to whether baseline cardiovascular is changed by undernutrition
Top looked at mild undernutrition from conception –> mid-gestation
Found that in foetal with mild undernutrition (15%) has a reduced BP
More blood going to brain and less going to legs- redistribution
red= study 2
Measured late gestation
Found no effect on foetal blood flow or blood pressure
Timing?
Green= study 3
Slightly different results
Black= study 4
No effect of UN in singletons when measured BP in late gestation
Found rise in BP in twins in early gestation
How are resources redistributed?
Use the human model and the sheep model
Thin mothers and those eating an ‘imprudent’ diet- human model
- Decrease ductus venosus flow
- Increase liver blood flow
Foetal low glucose in sheep
- More blood to adrenal gland, less to liver and less to femoral
Tell me what the altered foetal cardiovascular response is in sheep
Hypoxia test after placental reduction
Shape of response is different in those with placental restriction
Tell me whats seen in the altered foetal cardiovascular response in sheep in the hypoxia test after 0-70dGA 15% maternal undernutrition
Tell me what happens in the altered foetal cardiovascular response in sheep with the hypoxia test in prevailing conditions
If you occlude the umbilical cord foetal blood pressure rises and heart rate drops
These changes are bigger if the foetus had already experienced low glucose conditions (via maternal insulin)
If you make glucose low (via maternal insulin) then blood flow to foetal leg drops
It drops faster if the foetus had experienced moderate maternal undernutrition beforehand
What are some of the outcomes seen from an overabundant nutrients environment
Variable maternal obesity
Weight gain
Associated maternal insulin resistance
Oxidative stress and inflammation
Tell me the changes seen in the foetal heart in the human and sheep model in response to overnutrition
The foetal circulation in overnutrition situations
What are the coordination/ gate keepers in the foetus?
What componenets are involved in the activation of the sympathetic nervous system?
Sympathoexcitatory hyper-responsiveness in juvenile rat offspring from obese mothers (rat)
- Things occur quicker in face of low nutrient environment. Which suggest nutrition acts at levels of carotid body
More rapid ‘chemoreflex’ mechanisms in late gestation foetus after undernutrition in early gestation (sheep)
How is the sympathetic nervous system activated in the sheep?
Take out the carotid body
Late undernutrition model
Greater ewe weight loss in late gestation (proxy for foetal nutrition) =
- Decreased liver weight and
- Increased brain: liver ratio
- Increased adrenal weight
Not in carotid sinus denervated foetuses
Carotid body may sense decrease in nutrients and redistribute resources
How does Hypoxia help with cardiovascular control?
Autonomic nervous system
Endocrine factors
Local hormones
What axis may be activated early in sheep?
Tell me about this axis
How does maternal undernutrition alter the HPA axis?
Describe the renin angiotensin system in sheep
The Foetal vascular endothelial function is also altered in sheep by undernutrition, explain the changes seen
Foetal cardiovascular adaptations –> increased long term legacy on CV health
What does the maternal diet/ body composition have later effects on?
Explain effect of undernutrition with pre-implantation in rats and late gestation in sheep
Timing and severity…
What happens to blood pressure as the foetus grows?
How is this effected if you are a smaller foetus?
Tell me about the IGF axis
IGF= Insulin-like growth factor
What is the consequence in the skeletal muscle of sheep with undernutrition?
What are some effects of foetal cardiovascular adaptations?
Long term legacy on CV health
Help immediate survival- gets nutrients to where most needed
There is a ‘cost’ to some other organs
… and this may be payable for life
IGF interactions with other hormones
IGF, insulin and glucose
IGF-I therapy
