Early life events
HC1: DOHAD: Developmental origins of Health and Disease
Developmental programming is the foetal or neonatal response to a specific challenge during a
critical developmental time window that alters organ development with resulting effects on offspring
function and health that can persist through life.
Challenges that result in programming are e.g.: maternal under- and overnutrition, paternal under
or over nutrition, environmental pollution and stress
IUGR: Intrauterine growth restriction kan voorkomen door genetische, placentele, foetale en
maternale factoren.
Short term effect of Fetal Growth Restriction (FGR)
1. Pulmonaire hypertensie
2. Hypothermia
3. Fetal death
4. Low serum feritinin
5. Immunodeficiency
6. Renal dysfunction
Long term effect of Fetal Growth Restriction (FGR)
7. Lage cognitieve scores
8. Growth retardation
9. Lage intiligentie
,10. Lage sociale competentie
Diermodellen:
11. Placental insufficiency and maternal undernutrition leidt tot kleinere baby
12. Maternal overnutrition leidt tot kleinere/normale baby
13. Maternal obesity leidt tot kleine/normale baby
14. Maternal diabetes leid tot grotere baby
Moeilijk om een conclusie te trekken uit dierlijke trials aangezien:
15. Verschillende dieren gebruikt zijn
16. Verschillende soorten zijn
17. Verschillende leeftijdscategorieën
18. Verschillende human cohorts met verschillende eigenschappen
FGR animal models
19. Dahl SS
20. RUPP
21. Protein/diet restricted
22. L-NAME treated
23. sFlt1-overexpression
24. Clamped umbilical cord
25. Clamped utero-overian arteries
26. Embolization of the uterine arteries with polystyrene microspheres (sheep; bigger animal)
27. COMT -/-
28. eNOS +/-
29. IGF2 -/-
30. LPS
31. Hypoxic chambers
FGR results in bloodpressure increase of ~10 mmHg in dierstudies:
32. Mannen vooral effect
33. Toename met leeftijd
34. Early-onset FGR results in more severe hypertension
No BP difference in human studies
, 35. Too much heterogeneity?
36. Less severe FGR?
37. Prematurity bigger influencer than FGR itself?
Sildenafil: PDE5 remmer – working mechanism
Sildenafil verbetert het geboortegewicht in een aantal diermodellen voor FGR. Prenatal sildenafil
dampens blood pressure progression and improves endothelial dependent relaxation of mesenteric
arteries in male FGR offspring.
HC1: DOHAD: Developmental origins of Health and Disease
Developmental programming is the foetal or neonatal response to a specific challenge during a
critical developmental time window that alters organ development with resulting effects on offspring
function and health that can persist through life.
Challenges that result in programming are e.g.: maternal under- and overnutrition, paternal under
or over nutrition, environmental pollution and stress
IUGR: Intrauterine growth restriction kan voorkomen door genetische, placentele, foetale en
maternale factoren.
Short term effect of Fetal Growth Restriction (FGR)
1. Pulmonaire hypertensie
2. Hypothermia
3. Fetal death
4. Low serum feritinin
5. Immunodeficiency
6. Renal dysfunction
Long term effect of Fetal Growth Restriction (FGR)
7. Lage cognitieve scores
8. Growth retardation
9. Lage intiligentie
,10. Lage sociale competentie
Diermodellen:
11. Placental insufficiency and maternal undernutrition leidt tot kleinere baby
12. Maternal overnutrition leidt tot kleinere/normale baby
13. Maternal obesity leidt tot kleine/normale baby
14. Maternal diabetes leid tot grotere baby
Moeilijk om een conclusie te trekken uit dierlijke trials aangezien:
15. Verschillende dieren gebruikt zijn
16. Verschillende soorten zijn
17. Verschillende leeftijdscategorieën
18. Verschillende human cohorts met verschillende eigenschappen
FGR animal models
19. Dahl SS
20. RUPP
21. Protein/diet restricted
22. L-NAME treated
23. sFlt1-overexpression
24. Clamped umbilical cord
25. Clamped utero-overian arteries
26. Embolization of the uterine arteries with polystyrene microspheres (sheep; bigger animal)
27. COMT -/-
28. eNOS +/-
29. IGF2 -/-
30. LPS
31. Hypoxic chambers
FGR results in bloodpressure increase of ~10 mmHg in dierstudies:
32. Mannen vooral effect
33. Toename met leeftijd
34. Early-onset FGR results in more severe hypertension
No BP difference in human studies
, 35. Too much heterogeneity?
36. Less severe FGR?
37. Prematurity bigger influencer than FGR itself?
Sildenafil: PDE5 remmer – working mechanism
Sildenafil verbetert het geboortegewicht in een aantal diermodellen voor FGR. Prenatal sildenafil
dampens blood pressure progression and improves endothelial dependent relaxation of mesenteric
arteries in male FGR offspring.
