Hvad kan vi lære af at bruge grise som modeller for tidligt født børn?

Department of Veterinary Clinical and Animal Sciences
Livets svære start efter tidlig fødsel
Thomas Thymann, MSc, DVM, PhD, Lektor
Comparative Pediatrics and Nutrition
Dept of Veterinary Clinical and Animal Sciences
Faculty of Health and Medical Sciences
University of Copenhagen
Komparativ pædiatri og ernæring
Foster Præmatur
Termin
Fravænning
Fejlernæring
Obesitas/ T2D
Immediate postnatal survival, - what are
the challenges and what do we do ?
Oxygen, surfactant,
Respiration
and
caffeine, ventilation
pulmonary
expansion
Circulatory
Adrenalin
changes
Dopamin
Atropin
Steroid
Blood transfusion
Blood pressure
Fluid support
and perfusion
NSAID
Provision
Active thermoregulation
of external heat
Colostrum
intake
Immunization
Germ free
Antimicrobials
Infection/sepsis
Probiotics
resistance
Prebiotics
Mothers
Nutritionmilk
Donor milk
Formula, PN
Whom signals to whom ?
About what ?
And when ?
P.W. Nathanielsz
Development of blood cortisol before birth
Fetal cortisol (ng/ml)
140
Piglet
Lamb
Foal
Calf
120
100
80
(modified from Silver & Fowden, 1995)
60
40
20
0
-30
-20 -18 -16 -14 -12 -10
-8
-6
-4
-2
0
Days before birth (days)
BIRTH
2
6
Vægt af mave-tarmkanalen
relativt til kropsvægten:
Stor øgning omkring fødsel
Stomach
5
4
Birth
3
80
Pancreas
Small
intestine
1,6
60
1,2
40
0,8
20
-30
-20
-10
0
10
20
30
40
-30
-20
-10
Alder før og efter fødsel (dage)
0
10
20
Sangild et al.
30
40
Variation i modenhed og vægt ved fødsel:
Optimal
fødsel:
115d
118d
Store
kuld
115d
116d
116d
113d
114d
115d
Preterm Pig Intensive Care Unit
Why?
Controlled conditions
Multiple interventions
Detailed organ insights
Exploratory treatments
Ethics, economics, time
Translational relevance?
Respiratory support
Temp./moisture control
High sanitary conditions
Ventilation control
Parenteral/enteral nutrition
24 hour camera surveillance
Distal
intestine
Præmatur gris
Colostrum
CaecumColon
Præmatur gris - Formula
NEC
Præmaturitet, formula ernæring og kolonisering er
risikofaktorer for necrotiserende enterocolitis (NEC)
Gut responses
TPN (n=6-14)
Infant Formula (IF, n=8-15)
Bovine Colostrum (BC, n=7-13)
Small volume of formula
→ sub-clinical NEC- 0.20
lesions
15%
0.10
0.05
0%
0.00
NEC
150
300
50
40
0
Gut permeablity
*
60
20
15%
7%
Diarrhea
Colostrum
≈ antimicrobial?
1500
*
1000
[ µmol/L]
[ µmol/L]
100
*
400
*
93%
80
0.15
% of animals
60%
**
Lac/Man-ratio
*
**
100
200
500
100
0
IL-8
0
0
Lactose digestion
Galactose absorbtion
First nutrition after term and preterm birth
- What are the long term consequenses ?
Body
weight (g)
4000
3500
Minimal
Term
litter 1: enteral
MEN-BC for 5d
Totallitter
parenteral
for 5d
Term
1: TPN
Minimal
for 5d
Preterm
litterenteral
1: MEN-BC
Total parenteral
Preterm
litter 1: TPN for 5d
term
preterm
3000
2500
2000
1500
1000
500
0
5
10
15
20
25
Days
of life
Kunstig ”opstart” af svage nyfødte grise
– nytter det noget?
300
Tilvækst før fravænning (g)
200
100
0
100
Overlevelse
(%)
vægt v fød
80
Gns. fødselsvægt 850 g:
n=90, kontrol
n=90, 2 x sondefodring
60
40
20
0
"Skravl"
grise
kontrol
"Skravl"
grise
2xfodring
Immediate postnatal survival, - what are
the challenges and what do we do ?
Oxygen, surfactant,
Respiration
and
Opsummering:
caffeine, ventilation
pulmonary
expansion
Provision
Active thermoregulation
of external heat
- Også de små grise har overlevelsespotentiale
Circulatory
Adrenalin
Colostrum
intake
Immunization
changes
Dopamin
Højest
prioritet
til
minimering
af
varmetab
Atropin
Germ free
Steroid
Antimicrobials
Infection/sepsis
- Bovin
kolostrum ok som støtte
Blood
transfusion
Probiotics
resistance
Blood pressure
Fluid support
Prebiotics
and perfusion
NSAID
Mothers
Nutritionmilk
Donor milk
Formula, PN
www.Neomune.ku.dk
Comparative Pediatrics
and Nutrition,
Univ. of Copenhagen