Developmental Origins of Health and Disease (DOHaD)

Question 1

What is the relationship between birthweight and prenatal malnutrition to non-communicable diseases?

Answer 1

prenatal malnutrition and low birth weight create a predisposition to obesity, high blood pressure, heart disease and diabetes (non-communicable diseases) later in life.

Studies how that low or excessive birthweight both show predisposing for non-communicable disease later in life

Question 2

What is the DOHaD concept?

Answer 2

Essentially that there is a link between fetal development and metabolic disease later in life. By being exposed to certain negative environments you are predisposed to developing chronic diseases

Question 3

What are considered the potential mechanisms by which fetal development may dispose the risk of non-communicable diseases later in life?

Answer 3

1. effects on tissue or organ structure
   studies have shown:
   - particular diet has caused different different muscle fibres to be more prevalent in offspring
   - glomerular number and size is affected by low birth weight
2. alterations in cellular function
   - low birth weight is associated with changes in protein expression

Question 4

How do changing situations for the fetus in utero affect functional phenotypes?

Answer 4

adaptive responses to stressful situation for a fetus like:
- hypoxia
multiple pregnancy
- stress
- small stature in mum

operate at multilevel in organisms to produce an integrated phenotypes

Occurs by challenges in normal range during pregnancy leading to different hormones/ effectors which lead to different phenotypic effects on structural and functional phenotypes of tissue and organs. This is through epigenetics

Question 5

what is epigenetics?

Answer 5

It is how DNA interacts with smaller molecules found within cells which can activate or deactivate genes based on the cellular environment and exposure to diet, chemicals, pollution, medication etc.

Epigenetic changes can interfere with transcriptional activity of particular genes

Epigenetic changes survive through cell division and therefore can affect an individual for their entire life.

Question 6

How are epigenetic changes made?

Answer 6

the histones that DNA coil around get tagged with different chemical markers.

Methyl groups are one of these chemical markers which inhibit gene expression by causing DNA to coil more tightly preventing transcription from occurring.

Some chemical tags will unwind DNA to boost transcription

Question 7

What are the two most common types of epigenetic changes?

Answer 7

1. DNA methylation
   - Methyl groups can tag DNA and activate or repress genes
2. Histone modification
   - the bindings of epigenetic factors to histone tails alters the extend to which the DNA is wrapped around the histones and the availability of genes in the DNA to be activated

Question 8

What does timing of the stress have to do when different phenotypic expression?

Answer 8

In nature voles that are born in the summer months have a shorter coat whereas those born in winter have longer thicker coats

Question 9

Gestation timing of malnutrition determines the effect on postnatal health, explain what studies show?

Answer 9

higher prevalence of coronary heart disease when there is exposure to famine early in gestation

high prevalence of chronic obstructive pulmonary disease when exposed to famine during the middle of gestation

High prevalence of glucose clearance when exposed to famine around birth.

Question 10

What have studies shown about the health of adult after fetal malnutrition during the Nigerian Civil War?

Answer 10

Blood pressure was checked 40 years after the Nigerian civil war. Children who were born during the civil war showed a much high blood pressure than those born before and after the war

Question 11

What are the 4 corner of the mis match environment and what do they mean?

Answer 11

1. optimal developmental enviro + plentiful adult enviro
   - healthy range and less likely to develop disease
2. optimal developmental and sparse adult
3. impaired development and plentiful adult enviro
   - limited resources with plentiful amount
4. impaired developmental and sparse adult

Question 12

What is the thrift phenotype hypothesis?

Answer 12

during gestation and early post natal life an individual becomes programmed for nutritional thrift in order to adapt and survive in an environment of limited resources

e.g. prenatal undernutrition leads to low birth weight. The low birth weight is an adaption that is good as if the fetus was normal weight it would always be undernourished.

Question 13

How is DOHaD changing the way healthcare is delivered

Answer 13

shifting focus to health optimization and with high important of paternal and child health

Question 14

When is the best point to intervene in regard to life course model

Answer 14

mother and infant stage and child/adolescent stage
also preconception period in both men and women

In adulthood screening may be too late to reduce risk and at affected adult status interventions have limited affect

Question 15

Awareness of associated risk during fetal development to non0communicable disease later in life is not enough what else needs to change?

Answer 15

needs to be a behavioural change to help improve pre-conception health

Question 16

Mismatch theory suggests what?

Answer 16

That the risk for non-communicable diseases established during fetal development is amplified during mismatch

Question 17

Risk for non-communicable disease is passed across generation but is not simply genetic. When is risk established

Answer 17

Partly established during early development