Foetal origins of adult disease Flashcards

1
Q

What is meant by foetal origins of adult disease?

A

‘Prenatal events establish lifelong physiological patterns that may manifest as disease processes in later life’ (David Barker)

Nutritional status at birth will determine susceptibility to disease in later life.
Improving the nutritional status of a foetus will improve health throughout its life.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

What is intrauterine programming?

A

A concept that suggests events during pregnancy and critical period may cause permanent effects

  • Growth restriction in utero
  • Increased risk of CVD, type 2 diabetes, and hypertension
  • Predisposition to adult chronic disease

A stimulus or insult at a critical period of development has a lasting or lifelong significance
- Not necessarily low birth weight (<2.5kg)
- Growth restricted - not grown to full potential
- Could be thin but weighs more than 2.5kg
- Could be short and fat or long and thin –> Undernutrition could have come at different times during gestation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

What is the ponderal index?

A

Similar to BMI

weight/ length3

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What can cause restricted growth in utero?

A
  • Lack of nutrients –> baby changes its metabolism and physiology in response
  • Lack of oxygen at a particular stage of gestation
    • Maternal smoking
    • Hypotension
    • Underweight mothers
    • Maternal anaemia
    • Lack of placenta development

Reflects adaptations that foetus makes to sustain its development

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What does foetal nutrient supply depend on?

A

Nutrients in mothers blood
- Associated with low maternal weight/ weight gain
- Density of micronutrients in diet/ stores
- Confounded by deprivation/ smoking

Effectiveness of placenta
- Need adequately grown placenta/ perfusion
- Could be damaged by pre-eclampsia, high blood pressure
- Blood flow decreased by smoking
- Defective transfer of nutrients

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What is the Barker experiment?
What did it find out?

Maternal effects?
Death rates?
Blood pressure?
Glucose tolerance?

A

Archived medical records were researched and noticed links between birth weight and disease later in life

  • Adult deaths from coronary heart disease were found to correlate best with neonatal deaths e.g small size, suggesting common prenatal influences

The standardized mortality rate goes down as birthweight goes up, to 9.5 lbs, then a slight increase. Those with the lowest birth weight are at the highest risk of CHD.

The highest systolic blood pressure in those at the lowest birthweight decreases with increasing bw to 9.5lbs, then a small increase

The odds ratio for impaired glucose tolerance or type 2 diabetes shows that those at a low birth weight have over 7.5x the risk of type 2 diabetes/ poor glucose tolerance than heavier babies.
Same is shown for metabolic syndrome.

A strong correlation also found between offspring CVD deaths and past maternal mortality rates
- could be poor nutrition
- health and development amongst girls and young women contribute to CVD in the next generation
- could be liked to socioeconomic factors

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What happened in the 1944 dutch famine?
What has been learned from it?

A

During the war, there was an occupation of western holland that was for 6 months. Well-nourished to hugely undernourished. Went from 1800kcal a day to 600kcal a day. After that period it went back to 1700kcal

Babies examined in utero were experienced at different points of gestation during the famine. Most babies went on to go into the military so had adult values for birth and adulthood

Those exposed to famine in utero had
- higher plasma glucose 2 hours after glucose load
- higher fasting plasma insulin
Suggests poor glucose tolerance was partly determined by insulin resistance.
These effects were seen in LBW and those of normal birth weight.

Birth weight feel when foetal gestational adaptation to lack of nutrients and oxygen failed.

Obesity was also studied in those (19-year-old - military)
- those who were affected in the first 2 trimesters had a higher prevalence of obesity
- those affected in the final trimester had a lower rate of obesity than the controls

Possible mechanisms (pathophysiology)
- Appetite regulation (hypothalamic appetite control systems effected)
- Adipocyte numbers (late exposure, less adipose lay down due to undernutrition during time of adiposity)
- Sensitivity to insulin and other hormones
No firm evidence

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

What is the Indian baby study?
What was found out?

A

Comparison of Indian babies and mothers in Pune compared with white caucasian mothers and babies in London.

Weight and BMI in Pune much lower than London
Indian baby’s anthropometry is much lower than London, besides subscapular –> preserved fat mass around trunk
Triglycerides and cholesterol are lower in Indian babies
HDL is higher in Pune babies
Leptin, glucose, and insulin (G and I significantly higher) are higher in Indian babies than in white babies.
This could be due to insulin resistance

Visceral adiposity and raised insulin traced back to neonate
Later in childhood - impaired insulin sensitivity inversely correlated to BW
Worse IR with faster postnatal growth, weight and height.

Indian babies were small in all respects but subscapular fat was best preserved
- high prevalence of underweight and small mothers
- large babies would be high risk childbirth for a small mothers

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

What parent affects birthweight?

A

Mother
Indicating its more environmental in mother for the infant than genetic

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

What did the 2008 intervention study show?

A

15 intervention villages and 14 control villages in India
- energy and protein supplements given to pregnant women, carrying on throughout pregnancy and preschool
- showed more favourable CVD risk factors in adolescents of control villages
- 14mm taller
- reduced insulin resistance and arterial stiffness

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does the fetus respond to undernutrition?

A

Permanent changes in physiology and metabolism
- decrease cell numbers in organ production
- altered organ structure
- changes to hormone levels and responses
- insulin and growth

Different effects at different times of development and organ

Liver development timing
- larger but fewer lobules
- different number of cells and cell types
- effect liver function

Plasticity –> foetus will change its structure and development according to the environment it is in.

Other responses
- slowing growth rate
- reduce basic metabolic rate and substrate use
- re-distribute blood flow to vital organs e.g. brain at the expense of muscles
- alters hormone production/ sensitivity of tissues

Ensures immediate survival at the expense of future health

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

How does undernutrition link to hypotension

A

Undernutrition can lead to increased blood flow to the brain, which can be seen by the baby having a large head and small body.
This then leads to reduced blood flow to the trunk which leads to less stress on blood vessels. The lack of stress causes a decrease in the development of elastic tissue meaning the blood vessel is not able to expand as much as it should.
The less elastic blood vessel cannot cope with environmental stress which over time can lead to hypotension

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

How does undernutrition link to placental growth

A

Undernutrition causes the placenta to increase in size as it is trying to provide more nutrition to the foetus to compensate for the lack of maternal nutrition.
In turn this leads to altered placental:foetal weight ratio where the placenta is much larger than expected.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

What are the hormonal effects of undernutrition?

A

Set point of hormonal axes that control are altered or threshold response of tissues is changed
At what level do tissues response?

In response to malnutrition the foetus reduces insulin secretion and increases other activity e.g HPA/ increase cortisol to increase fuel availability.
In long term can increase bp

HPA hypothalamus, pituitary axes –> helps control some hormone systems

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

How does cortisol effect the foetus and influence adult disease?

A

High levels of foetal glucocorticoid (cortisol) comes from high levels of maternal stress which could be from a number of environmental factors
- undernutrition
- stress - psychological/ physical
- infection

It causes a increase release of stress hormones and a decrease in 11beta HSD2 expression (placental enzyme that inactive foetal glucocorticoids –> if inactivated then more will effect foetus) which causes the high foetal cortisol load

This can then induce changes in
- growth
- organ structure
- gene expression
- neuro/endocrinal function (HPA)
- metabolism
which can then go on to cause adult disease

High exposure to exogenous glucocorticoids can also cause the same changes which in turn can lead to adult disease.
Found in animal experiment when given to mother.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What could happen in undernutrition in the later stages of pregnancy

A

The critical period for kidneys
- may lead to reduced kidney growth
- permanently reduce cell numbers
- no catch-up later
- kidneys may have impaired function later in life, especially under stress e.g. high salt diet

Could have an effect on hypertension

17
Q

What is the Thrifty Phenotype?

A

Developing baby is ‘thrifty’, adapting to poor environment. When it comes to increased food intake and low energy expenditure and obesity it can lead to diabetes due to not being developed enough for these conditions.

Prenatal and early infant life:

Maternal malnutrition during pregnancy (or other maternal/ placental abnormalites) –>
Foetal malnutrition –>
Thrifty phenotype
- decrease growth of foetus/infant
- decreased islets function and impaired beta cell growth
- in utero hormonal and metabolic adaptation to maternal malnutrition

Adult life (good or over-nutrition)
- decreased b-cell function +
Obesity +/or Age –>
Type 2 diabetes and metabolic syndrome

18
Q

What is epigentics?
Relation to in utero undernutrition

A

Gene-environment interaction

Environment will induce changes to gene expression (not the gene itself, or base pairs)
These changes in foetal environment can lead to methylation of gene which can have some effects later on. Methyl group on various genes causing a change in how they are expressed
Can cause changes in somatic cells

19
Q

What is some advice to mothers?

A

Healthy lifestyle:
- Stop smoking
- Physical activity
- Good quality diet
- Supplements if required –> formulated for pregnancy/ pre-pregnancy
- Low stress

Weight:
- Not too much emphasis
- Depends on individual

Infants:
- Growth monitoring
- Breastfeeding?
- Educate on some warning signs, what to look out for

Reassurance
- Don’t add burden
- Promote motivation
- Focus on the positive and how to keep the whole situation positive
- No one is perfect
- Do not feel guilty if problems occur