In Switzerland, TH has been offered since 2005 according to a TH protocol4). A retrospective analysis of all cooled infants showed that passive cooling is the most common cooling method in Switzerland and that neuromonitoring with cerebral MRI and amplitude EEG during cooling and thereafter is not applied uniformly and thus could be improved4). Furthermore, passive cooling showed the highest variability in temperature compared to active cooling. So far, no prospective systematic data recording or follow-up assessment has been undertaken for cooled infants born in Switzerland. Therefore, to improve clinical management and provide standardized long-term follow-up assessments of children with HIE, a National Asphyxia and Cooling register was established in 2011. This register enables the evaluation of the efficacy of TH in Switzerland, ensures a safety control of applied cooling methods, allows comparing neurodevelopmental outcome depending on different cooling methods and in comparison with published outcome data.
11
Therapeutic ahyp othermia a(TH ) aimpr oves athe a
sur
vival
aand aneu
rodevelopmental
aoutc
ome
aa
of
ainf
ants
awit
h
amod
erate
atoasev
ere
ahypo
xic
a
ischae
mic
aenc
ephalopathy
a(HI
E)
1–3 )aand ahas a
beacom
e
asta
ndard
acar
e
ainathe adev
eloped
a
worl
d.
In
aSwi
tzerland,
aTHahas abee
n
aoff
ered
asin
ce
a
200
5
aacc
ording
atoaaaTHapro
tocol
4).aAaretros-
pe
ctive
aana
lysis
aofaallacoo
led
ainf
ants
asho
wed
a
tha
t
apas
sive
acoo
ling
aisathe amos
t
acom
mon
a
coo
ling
amet
hod
ainaSwi
tzerland
aand atha
t
aneu
–
romonitoring
awith acer
ebral
aMRI aand aamp
litude
a
EEG adur
ing
acoo
ling
aand athe
reafter
aisanot aap-
p
lied
aun
ifor mly
aan
d
ath
us
aco
uld
abeaim
proved
4).a
Fur
thermore,
apas
sive
acoo
ling
asho
wed
athe a
hig
hest
avaria
bility
ainatem
perature
acom
pared
a
toaact
ive
acoo
ling.
aSoafar
,
anoapro
spective
asys
–
tematic
adata arec
ording
aorafoll
ow-up
aass
ess –
ment
ahas abeen aunder
taken
afor acoo
led
ainfa
nts
a
bor
n
ainaSwi
tzerland.
aThe
refore,
atoaimp
rove
a
clin
ical
amana
gement
aand apro
vide
asta
ndar –
dized
along-
term
afol
low-up
aass
essments
aofa
chi
ldren
awit
h
aHIE
,
aaaNat
ional
aAsp
hyxia
aand a
Coo
ling
areg
ister
awas aestab
lished
aina201
1.
aThis a
reg
ister
aenab
les
athe aeva
luation
aofathe aeffi
cacy
a
ofaTHainaSwi
tzerland,
aens
ures
aaasaf
ety
acon
trol
a
ofaap
plie d
aco
oling
ame
tho ds ,
aal
lows
aco
mpar ing
a
neu
rodevelopmental
aoutc
ome
adepen
ding
aona
dif
ferent
acoo
ling
amet
hods
aand ainacompar
ison
a
wit
h
apu
blished
aou
tcome
ada
ta.
a
THaisaoff
ered
ainanin
e
aneo
natal
aint
ensive
acar
e
a
uni
ts
aand ainatwo apae
diatric
aint
ensive
acar
e
a
uni
ts
ainaSwi
tzerland
a( F i
g .1) .
aThe aaim aofathe a
reg
ister
aisatoasys
tematically
arec
ord
aper
inatal
a
data
,
ade
tails
aonare
suscitation,
aonaco
oling
acri –
t
eria,
atempe
rature
aman
agement
aand aneu
ro –
monitoring
ainaorde
r
atoaimpr
ove
aclin
ical
aman
a –
gement
aofath
ese
ain
fants.
aEn
try
acr
iteria
afo
r
aTHa
wer
e
aset aacc
ording
atoathe aran
domized
atri
al
a
( Tab
l e 1)
1).aAaTHaprotocol aonaman agement aofa
inf
ants
aund
er
aTHahas abee
n
aagr
eed
aonabyaalla
participating acent ers. aEle ctronic acas e arep ort a
for
ms
a(eC
RF)
aare afill
ed
ainafor aeac
h
ainf
ant
awho a
und
erwent
acoo
ling
aand athi
s
adat
a
aisaent
ered
a
into athe areg
ister
adat
abase
abyaaaclin
ic
arepr
esen-
tative.
aSin
ce
a201
4,
aaamin
imal
aeCR
F
afor aallaa
inf
ants
awit
h
aHIE awho awer
e
anot acoo
led
aisaa
als
o
arec
orded.
aThe aeCR
F
aisaava
ilable
aonl
ine
aa
( www
.neonet.unibe.ch/php/manuel.php ) .
a
The adat
abase
aisaman
aged
abyaaadat
a
aman
ager.
a
Inaaddi
tion,
aaareg
ister
acoo
rdinator/nurse
a
con
ducts
areg
ular
adat
a
amon
itoring
avis
its
aina
eac
h
acen
ter
atoaens
ure
acor
rect
adat
a
arec
ording.
a
The areg
ister
aisasup
ervised
abyatwo aneo
natal
a
con
sultants,
areg
ular
areg
ister
amee
tings
aare a
hel
d
awith athe aclin
ic
arepr
esentatives
aand anew
s-
let ter s
aar
e
ap o
sted
afo
ur
ati
mes
aaaye
ar.
aFo
llow – up
a
isaper
formed
aatathe aNeo
natal
aFol
low-up
acen
–
ters
awit
hin
athe aNeo
natal
aNet
work
a(se
e
aart
icle
a
inathis aeditio
n).
Since
athe aint
roduction
aofathe areg
ister,
a257 a
inf
ants
ahav
e
abee
n
areg
istered
aofawho
m
a193 a
wer
e
acoo
led
aand a64anot
.
aFro
m
a201
5
aonw
ards,
a
inf
ants
awho aare abor
n
awit
h
aaamil
d
aenc
ephalo
–
pathy
aataaasec
ondary
aneo
natal
acar
e
auni
t
anot a
off
ering
aTH a(e.
g.
aSion
,
aBiel
,
aMünst
erlingen,
a
Bad
en,
aZur
ich
a(Zo
llikerberg,
aTrie
mli)
aand a
Sch
affhausen)
awi
ll
aal
so
abeare
gistered.
a
Ano
ther
aimp
ortant
aaim aofathe areg
ister
aisatoa
org
anize aand aensu re ashor t-and along- term afol
–
l ow-up
aass
essments.
aCon
sistent
adat
a
aare a
lac
king
awit
h
ares
pect
atoasch
ool
aout
comes
aina
coole
d
achi
ldren:
athe aCool
Cap
astud
y
aeva
luated
a
the aef
ficacy
aofase
lective
ahea
d
aco
oling
aofa46a%a
ofathe achi
ldren
aata7atoa8ayea
rs
aonathe abas
is
aofa
par
ental
aques
tionnaires
aand adem
onstrated
aaa
mod
erate
acor
relation
awit
h
athe a18amon
th
aas-
s
essments,
aalt
hough
athe astu
dy
awas aunder-
p
owered
atoaexam
ine
athe aeff
ect
aonaTHaonaco –
g
nitive
afun
ction
aataanaold
er
aage 5).aInathe a
NIC
HD
astu
dy,
athe
re
awas aaahig
h
afol
low-up
arat
e
a
amo
ng
ach
ildr en
aataag
e
a6atoa7aye
ar s ,
aw i
th
ach
ild-
ren
ainathe aTHagro
up
ahav
ing
alow
er
adea
th
arat
e
a
tha
n
atho
se
ainathe acon
trol
agro
up,
ahow
ever,
anoa
sig
nificant
adif
ferences
ainathe arat
es
aofacog
ni-
tive
aoutc
omes
awer
e
adete
cted
6).aLong-term a
ass
essments
aofathe achi
ldren
awho apar
ticipated
a
inath
e
aTO
BY
atr
ial
1)ashowed athat ach ildren ainath e a
hyp
othermia
agroup
,
aasacompar
ed
awit
h
athose a
inath
e
aco
ntrol
ag r
oup
aha
d
asi
g ni ficant
ar e
ductions
a
inathe aris
k
aofacer
ebral
apal
sy
aand athe aris
k
aofa
National Asphyxia and Cooling Register
in Switzerland
Barbara aBrotschi 1),aBea aLatal 2),aVerena aRathke 1),aCornelia aHagmann 3)
1) Department of Paediatric and Neonatal Intensive
Car e, University Children`s Hospital Zurich, Zurich,
Switzerland.
2)
Chi
ld Development Center, University Children’s
Hospital, Zurich, Switzerland.
3)
Cli
nic of Neonatology, University Hospital Zurich,
Zurich, Switzerland.
Fig. 1: Cooling acenters a(bl ue acir cles): aNIC Us ainaGen eva, aLau sanne, aBas el, aLuc erne, aZur ich, aChu r, a
St. aGa
llen,
aWi
nterthur,
aAa
rau;
aPI
CUs
aataCh
ildren’s
aUn
iversity
aHo
spital
ainaBe
rn
aan
d
aZu
rich.
aa
(Table ll1Tbl lle)Fi
(Table T1)FT1e 1ig
12
moderate atoasev ere adis ability; aand athe y a
sho
wed
abe
tter
amo
tor
afu
nction 7).
These
ainf
ants
awer
e
aallapar
t
aofaran
domized
a
con
trolled
astu
dies
ainawhich astr
ict
aent
ry
acri
teria
a
for aTHawer
e
aset aand athe ainf
ants
awer
e
atre
ated
a
acc
ording
atoaaadefi
ned
apro
tocol.
aHow
ever,
a
sin
ce
aTHaha
s
ab e
come
ast
andar d
aofaca
r e,
aitaisatoa
the acli
nician’s
adiscr
etion
awhich ainf
ants
asho
uld
a
beatre
ated
awi
th
aTHaan
d
aho
w
ath
is
atre
atment
aisa
app
lied
ainarea
lity.
aInaord
er
atoakno
w
ahow acoo
led
a
inf
ants
ainaSwi
tzerland
adev
elop
aataold
er
aage aaa
sys
tematic
aand auni
form
afol
low-up
ahas atoatak
e
a
pla
ce.
aAllacoo
led
achi
ldren
aaft
er
aHIE a(re
gardless
a
ofaHIE asev
erity)
aand atho
se
awit
h
aaaSar
nat
aIIaora
IIIaoraaaT h
omson
asc
or e
aofa7aorahi
gher
aw h
o
awe
r e
a
not aco
ole d
aar
e
ab e
ing
afo
llowe d
aw i
thin
ath
e
aSw
is s
a
Neon
atal
aFol
low-up
aNet
work.
aThe afol
low-up
a
pro
tocol
aisath
e
asa
me
aasafo
r
ach
ildren
abo
rn
abe-
l
ow
a32awe
eks
aofage
s t ation
aan
d
aisapr
esente d
aina
tab
le 2 .
a
Aareg
ister
aisaesse
ntial
aasamodi
fying
athe atrea
t-
ment
apro
tocol
afor aTHaisabei
ng
ainv
estigated
a
both awithin aand aout
side
aaaform
al
aran
domised
a
tri
al
adesi
gn,
awhich aincl
udes
achan
ges
ainadeg
ree
a
and adur
ation
aofaTHa(Op
timizing
aCoo
ling
afor a
neo
natal
aHIE astu
dy,
aClin
ical
aTri
als
aIde
ntifier
a
NCT
01192776),
atim
e
awin
dow
a>6ahaaft
er
abir
th
a
Ide
ntifier
aNCT
00614744)
aand acoo
ling
ainf
ants
a
< 36 awee
ks
ages
tational
aage a(GA
)
a(Cl
inical
a
Tri
als
aIde
ntifier
aNCT
01793
a129
).
aAarec
ent
a
stu
dy
aha
s
ash
ow n
ath
at
ain
fant s
aw h
o
adoano
t
af u
l fill
a
sta
ndard
aTHaent
ry
acri
teria
amay aben
efit
afro
m
a
TH. aThi
s
astu
dy
asho
wed
atha
t
asho
rt-
aand alon
g-
ter m
aou
tcome
ainaco
ole d
ain
f ant s
aw i
th
ane
onat al
a
enc
ephalopathy
afoll
owing
apos
tnatal
acol
lapse,
a
pre
term
abir
th
aorawit
h
aanaund
erlying
asur
gical
a
oracar
diac
acon
dition
aand ainfa
nts
asta
rting
acoo-
l
ing
a>a6apos
tnatal
ahou
rs
awer
e
asim
ilar
atoatho
se
a
inacoo
led
ainf
ants
aful
filling
athe aent
ry
acri
teria
a
(Sm
it,
aLiu aetaal.a201
4).
aAareg
ister
awil
l
apro
vide
a
usawit
h
adet
ailed
ainf
ormation
aonahow aSwi
ss
a
cli
nicians
aad
apt
atoasu
ch
ach
anges.
Die Autoren haben keine finanzielle Unter –
stützung und keine anderen Interessenkon –
flikte im Zusammenhang mit diesem Beitrag. Referenzen 1) Azzopardi, D.V., et al., Moderate hypothermia to
tr
eat perinatal asphyxial encephalopathy. N Engl J
Med, 2009. 361 (14): p. 1349–58.
2)
Sha
nkaran, S., et al., Whole -body hypothermia for
neonates with hypoxic-ischemic encephalopathy.
N Engl J Med, 2005. 353 (15): p. 1574–84.
3)
Sim
bruner, G., et al., Systemic hypothermia after
neonatal encephalopathy: outcomes of neo.nEURO.
network RCT. Pediatrics, 2010. 126 (4): p. e771–8.
4)
Ram
os, G., et al., Therapeutic hypothermia in term
infants after perinatal encephalopathy: the last 5
years in Switzerland. Early Hum Dev, 2013. 89 (3):
p. 159– 64.
5)
Gui
llet, R., et al., Seven – to eight-year follow- up of
the CoolCap trial of head cooling for neonatal ence –
phalopathy. Pediatr Res. 71 (2): p. 205–9.
6)
Sha
nkaran, S., et al., Childhood outcomes after
hypothermia for neonatal encephalopathy. N Engl
J Med, 2012. 366 (22): p. 2085–92.
7)
Azz
opardi, D., et al., Ef fects of hypothermia for
perinatal asphyxia on childhood outcomes. N Engl
J Med, 2014. 371 (2): p. 140–9.
Term and near term infants less than six hours old who meet the following treat-
ment criteria (A and B) may be considered for treatment with hypothermia:
A. Infants ≥ 36 we eks gestation admitted to the neonatal unit, with at least two of the
fo llowing:
a. Apg
ar score of ≤
5 at (5
)10 minutes after birth
b. Con
tinued need for resuscitation, including endotracheal or mask ventilation,
at 10 m
inutes after birth
c. Aci
dosis within 60 minutes of birth defined as any occurrence of umbilical cord,
art
erial or capillar y pH ≤
7. 0
0
d. Bas
e Deficit ≥
16 mm
ol/L in umbilical cord or any blood sample
(ar
terial, venous or capillar y) within 60 minutes of birth
e. La
ctate ≥
12m
mol/l in umbilical cord or any blood sample
(ar
terial, venous or capillar y) within 60 minutes of birth
B.
Sei
zures or moderate to severe encephalopathy defined by Sarnat (Stage II or III)
or Th
ompson Score ≥
7
Table 1: Eligibility afor ahypothermia awhen aresuscitation aisacompleted aand ainfant aisastable
Minimal follow-up protocol
A) At 2 years of age Bayley III (cognition, language and motor composite scores) a) Neuro logical examination: Cerebral palsy classification according to Surveillance
of C
erebral Palsy in Europe (SCPE) and gross motor function classification system
b) Vis
ual examination
c) Heari
ng examination
B)
At 5 ye
ars of age
a) Inte
llectual examination: Kaufmann Assessment Battery for Children (K-ABC)
b) Neuro
logical examination: Cerebral palsy classification according to SCPE and
gros
s motor function classification system
c) Mot
or examination: Zürcher Neuromotor Assessment
d) Beha
vior Strength and Difficulties Questionnaire (SDQ)
e) Vis
ual examination
Table 2: Follow-up aassessment aofaallaregistered achildren
(Table ll1Tbl lle)Fi
(Table T1)FT1e 1ig
Informations complémentaires
Auteurs
Dr. med. Barbara Brotschi , Universitätskinderspital Zürich Prof. Dr. med. Bea Latal , Abteilung Entwicklungspädiatrie, Universitäts-Kinderspital Zürich, Steinwiesstrasse 75, 8032 Zürich Verena Rathke C. Hagmann Andreas Nydegger