C1 Programming developmental disease risk

Question 1

Intrauterine growth restrictions (IUGR)

Answer 1

• Defined:
  
  • <2.5kg (2% of babies),
  • Small for gestational age (10%)
    
    • Mainly from placental insufficiency
    • <2SD below population means
• Increases perinatal mortality risk by 2-3x

Question 2

Z-score of babies born small

Answer 2

• Below 0 z-score

Question 3

Placental insufficiency

Answer 3

• Due to ↓ placental nutrition, not from being born pre-maturely

1. Uteroplacental insufficiency (placenta not working)
   
   • Mostly in the western world
2. Maternal undernutrition
   
   • Mostly in 3rd world
3. Maternal diseases
4. Genetic

Question 4

Fetal programming

Answer 4

• Babies born small → ↑risk of developing adult diseases
  
  • Independent of levels of obesity & exercise
• Boy > girls risk of developing diseases
• 90% of babies have accelerated growth in 1st 6 months
  
  • Early catch-up growth = protective
  • Late = adverse (↑fat → ↑risk)

Question 5

Lactation environment for babies born small

Answer 5

• Lactation env critical feature for babies born small
• ↓milk quality & quantity during lactation (wants to match baby who is small) → further compromises baby growth

Question 6

Features of restricted MALES

Answer 6

• ↓nephron # at 6 months (↓30%)
• Glomerular hypertrophy to compensate → ↑BP

Question 7

Features of restricted FEMALES

Answer 7

• Same nephron deficit + glomerular hypertrophy
  
  • No ↑in BP (protected)
  • Risk of developing renal diseases

Question 8

Rat uteroplacental insufficiency experiments

Answer 8

• Mimics intrauterine growth restriction → born small offsprings
  
  • Alters maternal endocrine env
  • Impairs mammary dev during pregnancy
  • Triggers early lactogenesis
  • ↓Milk quality & quantity during lactation

Question 9

Treatment: Effects of exercise

Answer 9

• Effects of Exercise
• Early exercise → 5-9wks → prevents β-cells deficit
• By 24 wks → full restoration of β-cells
• Ex → prevents metabolic dysfunction

Question 10

Treatment: Effects of nutrition

Answer 10

• Effects of nutrition
• Cross-fostering & improved post-natal nutrition → prevents deficits
  
  • Cross-fostering = removed from biological parents & raised by surrogates

Question 11

Transgenerational programming

Answer 11

• Programmed effects can be transmitted to subsequent generation
• Maternal line transmission more dominant

Question 12

Adverse pregnancy adaptations

Answer 12

• Females born small & pregnant leads to:
  
  • Glucose intolerance
  • Glomerular hypertrophy
  • ↓Vascular compliance
• Affects other generations

Question 13

Implications of doing physiological tests

Answer 13

• Physiological measures causing maternal stress:
  
  • Measuring BP → tail cuff and restraint
  • GTT → tail vein sample & heat
  • Renal function → separate in metabolic cage
• Puts stress on pregnant mothers → maternal stress during pregnancy causes fetal growth restrictions

Question 14

Kidney effects

Answer 14

• 2nd generation nephron #F2 nephrons #
  
  • ↓ (15-22%) at E20 but restored at PN35
    
    • Shows nephrogenesis was delayed

Question 15

Consequences of maternal obesity

Answer 15

• ↑Risk of:
  
  • Gestational hypertension
  • Diabetes
  • Pre-eclampsia

Question 16

Consequences of an increased fat diet

Answer 16

• Exacerbated pre-existing glucose intolerance in females born small
• Exercise before & during pregnancy → prevents development & exacerabation of glucose intolerance

Question 17

2nd hits

Answer 17

• Gender
• Diet
• Lifestyle
• Age
• Pregnancy

Question 18

Paternal line transmission

Answer 18

• Born normal birthweight
• Have period of slow growth → leads to:
  
  • Glucose intolerance/↓1st phase insulin
  • ↑WT of heart