188b - Fetal Origins of Disease

Question 1

What is developmental plasticity?

How does it affect the fetus?

Answer 1

Developmental plasticity causes the fetus to adapt to an environmental stressor

• No harm to the fetus
• Confers a survival advantage
  
  • However, may affect person later on in life with metabolic issues, etc

Example: Malnutrition in utero -> thrifty phenotype -> obesity later in life

Question 2

What are the risk factors for intrauterine growth restriction? (7)

Answer 2

• Increased maternal age
• High altitude
• Pre-eclampsia (maternal HTN)
• Smoking
• Undernutrition
• 2 vessel cord

Question 3

Describe the develpment of gestational diabetes melitus

Answer 3

• Early in pregnancy mother is insulin sensitive
• At ~24 weeks, insulin resistance increases
  
  • Baby is growing rapidly
  • GDM develops if maternal insulin production cannot keep up

Similar to the development of T2DM, but GDM goes away when baby is born

Question 4

List 4 risk factors for gestational diabetes

Answer 4

• Maternal age >35
• Overweight or obese maternal BMI
• Family hx of diabetes
• Parity 2+

Question 5

Why does maternal GDM increase the risk fo fetal demise?

Answer 5

Maternal excess circulating glucose

• -> Fetal hyperglycemia
• -> Increased fetal insulin production
  
  • Maternal insulin does not cross the placenta
• -> Increaed fetal glucose uptake
  
  • Increased tissue O2 consumption
  • Hypoxia
  • -> increased risk of still birth
  • Also, increased erythropoetin
    
    • Polycythemia, hyperbilirubinemia, jaundice

Question 6

What systems might be affected in a fetus born to a mother with obesity? (4)

Answer 6

• Metabolic
• Allergy/asthma/atopy
• Endocrine disruption
• Neurodevelopment

The key is that in-utero exposures may have a life-ling impact on offspring health

Question 7

Answer 7

B - fetal insulin binds IGF-1 receptors with high affinity

-> Excessive growth of the fetus

Question 8

How will methylation affect gene expression?

Answer 8

Methylation -> decreased gene expression

Question 9

Answer 9

C - placental insufficiency

Question 10

How does maternal gestational diabetes affect RBCs in the fetus?

What is the effect?

Answer 10

• *Hypoxia -> Increased EPO -> increased RBCs -> polycythemia**
• > Jaundice
• Maternal excess circulating glucose
• -> Fetal hyperglycemia
• -> Increased fetal insulin production
  
  • Maternal insulin does not cross the placenta
• -> Increaed fetal glucose uptake
  
  • Increased tissue O2 consumption
  • -> Hypoxia
    
    • -> increased risk of still birth
    • -> increased erythropoetin -> Polycythemia, hyperbilirubinemia, jaundice