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 hyp othermia (TH ) impr oves the
sur
vival
and neu
rodevelopmental
outc
ome
of
inf
ants
wit
h
mod
erate
to sev
ere
hypo
xic
ischae
mic
enc
ephalopathy
(HI
E)
1–3 ) and has
be com
e
sta
ndard
car
e
in the dev
eloped
worl
d.
In
Swi
tzerland\b
TH has bee
n
off
ered
sin
ce
200
5
acc
ording
to a TH pro
tocol
4). A retros-
pe
ctive
ana
lysis
of all coo
led
inf
ants
sho
wed
tha
t
pas
sive
coo
ling
is the mos
t
com
mon
coo
ling
met
hod
in Swi
tzerland
and tha
t
neu
–
romonitoring
with cer
ebral
MRI and amp
litude
EEG dur
ing
coo
ling
and the
reafter
is not ap-
p
lied
un
ifor mly
an
d
th
us
co
uld
be im
proved
4).
Fur
thermore\b
pas
sive
coo
ling
sho
wed
the
hig
hest
varia
bility
in tem
perature
com
pared
to act
ive
coo
ling.
So far
\b
no pro
spective
sys
–
tematic
data rec
ording
or foll
ow-up
ass
ess –
ment
has been under
taken
for coo
led
infa
nts
bor
n
in Swi
tzerland.
The
refore\b
to imp
rove
clin
ical
mana
gement
and pro
vide
sta
ndar –
dized
long-
term
fol
low-up
ass
essments
of
chi
ldren
wit
h
HIE
\b
a Nat
ional
Asp
hyxia
and
Coo
ling
reg
ister
was estab
lished
in 201
1.
This
reg
ister
enab
les
the eva
luation
of the effi
cacy
of TH in Swi
tzerland\b
ens
ures
a saf
ety
con
trol
of ap
plie d
co
oling
me
tho ds \b
al
lows
co
mpar ing
neu
rodevelopmental
outc
ome
depen
ding
on
dif
ferent
coo
ling
met
hods
and in compar
ison
wit
h
pu
blished
ou
tcome
da
ta.
TH is off
ered
in nin
e
neo
natal
int
ensive
car
e
uni
ts
and in two pae
diatric
int
ensive
car
e
uni
ts
in Swi
tzerland
( F i
g .1) .
The aim of the
reg
ister
is to sys
tematically
rec
ord
per
inatal
data
\b
de
tails
on re
suscitation\b
on co
oling
cri –
t
eria\b
tempe
rature
man
agement
and neu
ro –
monitoring
in orde
r
to impr
ove
clin
ical
man
a –
gement
of th
ese
in
fants.
En
try
cr
iteria
fo
r
TH
wer
e
set acc
ording
to the ran
domized
tri
al
( Tab
l e 1)
1). A TH protocol on man agement of
inf
ants
und
er
TH has bee
n
agr
eed
on by all
participating cent ers. Ele ctronic cas e rep ort
for
ms
(eC
RF)
are fill
ed
in for eac
h
inf
ant
who
und
erwent
coo
ling
and thi
s
dat
a
is ent
ered
into the reg
ister
dat
abase
by a clin
ic
repr
esen-
tative.
Sin
ce
201
4\b
a min
imal
eCR
F
for all
inf
ants
wit
h
HIE who wer
e
not coo
led
is
als
o
rec
orded.
The eCR
F
is ava
ilable
onl
ine
( www
.neonet.unibe.ch/php/manuel.php ) .
The dat
abase
is man
aged
by a dat
a
man
ager.
In addi
tion\b
a reg
ister
coo
rdinator/nurse
con
ducts
reg
ular
dat
a
mon
itoring
vis
its
in
eac
h
cen
ter
to ens
ure
cor
rect
dat
a
rec
ording.
The reg
ister
is sup
ervised
by two neo
natal
con
sultants\b
reg
ular
reg
ister
mee
tings
are
hel
d
with the clin
ic
repr
esentatives
and new
s-
let ter s
ar
e
p o
sted
fo
ur
ti
mes
a ye
ar.
Fo
llow – up
is per
formed
at the Neo
natal
Fol
low-up
cen
–
ters
wit
hin
the Neo
natal
Net
work
(se
e
art
icle
in this editio
n).
Since
the int
roduction
of the reg
ister\b
257
inf
ants
hav
e
bee
n
reg
istered
of who
m
193
wer
e
coo
led
and 64 not
.
Fro
m
201
5
onw
ards\b
inf
ants
who are bor
n
wit
h
a mil
d
enc
ephalo
–
pathy
at a sec
ondary
neo
natal
car
e
uni
t
not
off
ering
TH (e.
g.
Sion
\b
Biel
\b
Münst
erlingen\b
Bad
en\b
Zur
ich
(Zo
llikerberg\b
Trie
mli)
and
Sch
affhausen)
wi
ll
al
so
be re
gistered.
Ano
ther
imp
ortant
aim of the reg
ister
is to
org
anize and ensu re shor t-and long- term fol
–
l ow-up
ass
essments.
Con
sistent
dat
a
are
lac
king
wit
h
res
pect
to sch
ool
out
comes
in
coole
d
chi
ldren:
the Cool
Cap
stud
y
eva
luated
the ef
ficacy
of se
lective
hea
d
co
oling
of 46 %
of the chi
ldren
at 7 to 8 yea
rs
on the bas
is
of
par
ental
ques
tionnaires
and dem
onstrated
a
mod
erate
cor
relation
wit
h
the 18 mon
th
as-
s
essments\b
alt
hough
the stu
dy
was under-
p
owered
to exam
ine
the eff
ect
on TH on co –
g
nitive
fun
ction
at an old
er
age 5). In the
NIC
HD
stu
dy\b
the
re
was a hig
h
fol
low-up
rat
e
amo
ng
ch
ildr en
at ag
e
6 to 7 ye
ar s \b
w i
th
ch
ild-
ren
in the TH gro
up
hav
ing
low
er
dea
th
rat
e
tha
n
tho
se
in the con
trol
gro
up\b
how
ever\b
no
sig
nificant
dif
ferences
in the rat
es
of cog
ni-
tive
outc
omes
wer
e
dete
cted
6). Long-term
ass
essments
of the chi
ldren
who par
ticipated
in th
e
TO
BY
tr
ial
1) showed that ch ildren in th e
hyp
othermia
group
\b
as compar
ed
wit
h
those
in th
e
co
ntrol
g r
oup
ha
d
si
g ni ficant
r e
ductions
in the ris
k
of cer
ebral
pal
sy
and the ris
k
of
National Asphyxia and Cooling Register
in Switzerland
Barbara Brotschi 1)\b Bea Latal 2)\b Verena Rathke 1)\b Cornelia Hagmann 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 centers (bl ue cir cles): NIC Us in Gen eva\b Lau sanne\b Bas el\b Luc erne\b Zur ich\b Chu r\b
St. Ga
llen\b
Wi
nterthur\b
Aa
rau;
PI
CUs
at Ch
ildren’s
Un
iversity
Ho
spital
in Be
rn
an
d
Zu
rich.
1· Intennr·Inenntviw
1· Inte·rvi·rterwa
12
moderate to sev ere dis ability; and the y
sho
wed
be
tter
mo
tor
fu
nction 7).
These
inf
ants
wer
e
all par
t
of ran
domized
con
trolled
stu
dies
in which str
ict
ent
ry
cri
teria
for TH wer
e
set and the inf
ants
wer
e
tre
ated
acc
ording
to a defi
ned
pro
tocol.
How
ever\b
sin
ce
TH ha
s
b e
come
st
andar d
of ca
r e\b
it is to
the cli
nician’s
discr
etion
which inf
ants
sho
uld
be tre
ated
wi
th
TH an
d
ho
w
th
is
tre
atment
is
app
lied
in rea
lity.
In ord
er
to kno
w
how coo
led
inf
ants
in Swi
tzerland
dev
elop
at old
er
age a
sys
tematic
and uni
form
fol
low-up
has to tak
e
pla
ce.
All coo
led
chi
ldren
aft
er
HIE (re
gardless
of HIE sev
erity)
and tho
se
wit
h
a Sar
nat
II or
III or a T h
omson
sc
or e
of 7 or hi
gher
w h
o
we
r e
not co
ole d
ar
e
b e
ing
fo
llowe d
w i
thin
th
e
Sw
is s
Neon
atal
Fol
low-up
Net
work.
The fol
low-up
pro
tocol
is th
e
sa
me
as fo
r
ch
ildren
bo
rn
be-
l
ow
32 we
eks
of ge
s t ation
an
d
is pr
esente d
in
tab
le 2 .
A reg
ister
is esse
ntial
as modi
fying
the trea
t-
ment
pro
tocol
for TH is bei
ng
inv
estigated
both within and out
side
a form
al
ran
domised
tri
al
desi
gn\b
which incl
udes
chan
ges
in deg
ree
and dur
ation
of TH (Op
timizing
Coo
ling
for
neo
natal
HIE stu
dy\b
Clin
ical
Tri
als
Ide
ntifier
NCT
01192776)\b
tim
e
win
dow
>6 h aft
er
bir
th
Ide
ntifier
NCT
00614744)
and coo
ling
inf
ants
< 36 wee
ks
ges
tational
age (GA
)
(Cl
inical
Tri
als
Ide
ntifier
NCT
01793
129
).
A rec
ent
stu
dy
ha
s
sh
ow n
th
at
in
fant s
w h
o
do no
t
f u
l fill
sta
ndard
TH ent
ry
cri
teria
may ben
efit
fro
m
TH. Thi
s
stu
dy
sho
wed
tha
t
sho
rt-
and lon
g-
ter m
ou
tcome
in co
ole d
in
f ant s
w i
th
ne
onat al
enc
ephalopathy
foll
owing
pos
tnatal
col
lapse\b
pre
term
bir
th
or wit
h
an und
erlying
sur
gical
or car
diac
con
dition
and infa
nts
sta
rting
coo-
l
ing
> 6 pos
tnatal
hou
rs
wer
e
sim
ilar
to tho
se
in coo
led
inf
ants
ful
filling
the ent
ry
cri
teria
(Sm
it\b
Liu et al. 201
4).
A reg
ister
wil
l
pro
vide
us wit
h
det
ailed
inf
ormation
on how Swi
ss
cli
nicians
ad
apt
to su
ch
ch
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 for hypothermia when resuscitation is completed and infant is stable
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 assessment of all registered children
1· Intennr·Inenntviw
1· Inte·rvi·rterwa
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