13. Intrauterine programming adult disease

Question 1

What are the complications of human pregnancies?

Answer 1

• Bleeding - Anemia; coagulation - Maternal diseases - Heart & renal disease - Diabetes mellitus - Convulsions - Breech - Intrauterine fetal death

Question 2

What is the definition of preterm labour?

Answer 2

Term is 40 weeks from the last period - Preterm is

Question 3

What is the definition/characteristics of Pre-Eclampsia?

Answer 3

• Most common serious disorder of pregnancy - High maternal blood pressure - Proteunuria; generalised edema - Placental dysfunction & intrauterine growth restriction - Common in first pregnancy - May progress to eclampsia

Question 4

What is the incidence and mortality ?

Answer 4

• Mild 5-10%, severe 1-2% - 15% direct maternal mortality - 10% perinatal mortality

Question 5

What is the aetiology of pre-eclampsia?

Answer 5

• Unknown - Pregnancy specific - Dependent on trophoblast - Genetic basis

Question 6

What is the treatment Pre-Eclampsia?

Answer 6

• Irrespective of stage of pregnancy - delivery

Question 7

What is the definition/characteristics of Interauterine growth restriction?

Answer 7

• Low birth weight (

Question 8

What is the incidence and mortality of Intrauterine growth restriction?

Answer 8

• 2-10% of babies - 2-3 times normal perinatal mortality

Question 9

What is the Etiology of Intrauterine growth restriction?

Answer 9

• Unknown - Multiple pregnancy - Malfomations; Oligohydramnios - Fetal infection - Material disease; pre-eclampsia - Exercise; oxygen deprivation - Maternal smoking - Malnutrition - Placental insufficiency

Question 10

What is the control of fetal growth?

Answer 10

Question 11

What is the genetic factos that control fetal growth?

Answer 11

• About 15% of size of birth is dependent on genotype
• 2% depends on sex

Question 12

What are the hormonal factors that control fetal growth?

Answer 12

• Not GH dependent
• IGFs, thyroid hormones and insulin promote fetal growth
• GCS inhibit fetal growth

Question 13

Are drugs and alcohol bad for fetal growth?

Answer 13

• Fetal organs systems are not fitted in dealing and processing of drugs and alcohol
  Women who exposed to various substance abuse babies are also exposed. There is also buildup of toxins because fetus can’t clear it out

Question 14

What is oligohydraminos?

Answer 14

• Oligohydramnios is when there isn’t enough amniotic fluid because fetus isn’t producing a lot of dilute urine or liquid is not being produced at sufficient levels or if the fluid across the membrane is excessive.
  Associated with slowed fetal growth and development

Question 15

Why is excessive exercise bad for fetal growth?

Answer 15

Excess maternal exercise will restrict blood flow into the fetus

Question 16

What are the causes of fetal growth restriction in Western society?

Answer 16

• Placental insufficiency
  
  • Nothing wrong with the mother but placenta not functioning sufficiently and can’t provide enough oxygen and nutrition
  • No known cause

Question 17

What is the cause of fetal growth restriction in the third world?

Answer 17

• Maternal undernutrition
  
  • Severe malnutrition during pregnancy may result in low birth weight babies
  • Due to reduced nutrient delivery across the placenta

Question 18

What is fetal programming?

Answer 18

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

Question 19

Why is breast milk so important for children born with low birth weight?

Answer 19

Lactation and breast milk is matched for that baby whether that is born small or bigger. So breast feeding fixes that change appropriately so that babies don’t get too fat.

Question 20

What are the sex specific differences in the risks associated with fetal programming?

Answer 20

males who are born small are more at risk at CVD. But women are not at risk of CVD

Question 21

What are the diseases associated with suboptimal intrauterina conditions?

Answer 21

Question 22

What is accelerated postnatal growth? Is it a good thing?

Answer 22

90% of small babies have some accelerated growth in the first 6 months.

It is not a good thing!

Accelerated growth independently associated with increased risk of adult diseases

Question 23

What is the critical period for accelerated postnatal growth?

Answer 23

• Lactaton/postnatal/infancy
• After weaning/childhood
• After puberty/adolesence

Basically from baby to adult

Question 24

What is a developmental deficit?

Answer 24

• Premature loss of structural/functional capacity for life
  If kidney are forming the nephron for example and growth is impacted you can never recover those.

Question 25

What is the immidiate survival advantage?

Answer 25

Enhanced probability of perinatal survival

Immdiate survival advantage can cause mismatch and adverse effects after birth. Born small with fewer organs and you get a mismatch because postnatally you get a lot of nutrition and you grow excessively.

Question 26

What is predictive adaptive response?

Answer 26

○ Mother says “No nutrition”
○ Baby know mother doesn’t have nutrition
○ Baby slow down growth because it’ll be born knowning that there will be less nutrition, so baby has predictive adativ response to survive.
○ Adverse consequences: when it doesn’t match up when baby gets adequate nutrition later in life
○ They get FAT!

Question 27

What can we learn from the Wlodek F1 growth restricted offspring experiment?

Answer 27

When mice born from intrauterine growth restriction gets pregnant, the extra load will cause dysfunctions

Question 28

What happens if fetuses are exposed to suboptimal environment?

Answer 28

If fetuses are exposed to suboptimal enribonment you get growth restriction and program organ deficits in all key organs.

Organ deicits predispose you to organ dysfunction and disease. If you are exposed to a second hit you get argreater risk of getting diseases.

If you get fat/sedentary NOT good!
As you get older/pregnant disease risk emerges

Question 29

What happens to the F2 generation of mice born from restricted uterine growth

Answer 29

F2 generation
- Mothers have an added problem because they have their own consequences
○ Glucose intolerance
○ Kidney dysfunction
○ etc
- These program the next generation
○ If mother was born small she gets pregnant and she passes on deficits and disfunction to the next generation
If fathers are born small and he give sperm to a normal girl the next generation has an impact.