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 hypothermia (TH) improves the
survival and neurodevelopmental outcome
of infants with moderate to severe hypoxic
ischaemic encephalopathy (HIE)
1–3 ) and has
be
come
standard care in the developed wor –
ld.
In Switzerland, TH has been offered since
2005 according to a TH protocol
4). A retros-
pective analysis of all cooled infants showed
that passive cooling is the most common
cooling method in Switzerland and that neu-
romonitoring with cerebral MRI and amplitude
EEG during cooling and thereafter is not ap –
plied unifor mly and thus could be improved
4).
Furthermore, passive cooling showed the hi –
ghest variability in temperature compared to
active cooling. So far, no prospective syste-
matic dat a r e cor ding or follow – up as ses sment
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 ef ficacy of TH in Sw it zer –
land, ensures a safety control of applied
cooling methods, allows comparing neurode –
velopmental outcome depending on different
cooling methods and in comparison with pu-
blished outcome data.
TH is offered in nine neonatal intensive care
units and in two paediatric intensive care
units in Switzerland ( F i g .1). The aim of the
register is to systematically record perinatal
data, details on resuscitation, on cooling
criteria, temperature management and neu –
romonitoring in order to improve clinical
management of these infants. Entry criteria
for TH were set according to the randomized
trial ( Tab l e 1)
1). A TH pr oto col on management
of inf ant s under TH has b e en ag r e e d on by all
participating centers. Electronic case report
for ms ( eCRF ) are filled in for each infant who
underwent cooling and this data is entered
into the register database by a clinic repre –
sentative. Since 2014, a minimal eCRF for all
infants with HIE who were not cooled is
also recorded. The eCRF is available online
( www.neonet.unibe.ch/php/manuel.php ) .
The database is managed by a data manager.
In addition, a register coordinator/nurse
conducts regular data monitoring visits in
each center to ensure correct data recording.
The register is supervised by two neonatal
consultants, regular register meetings are
held with the clinic representatives and news –
letters are posted four times a year. Fol –
low-up is performed at the Neonatal Fol –
low-up centers within the Neonatal Network
(see article in this edition).
Since the introduction of the register, 257
infants have been registered of whom 193 were cooled and 64 not. From 2015 onwards,
infants who are born with a mild encephalo
–
pathy at a secondary neonatal care unit not
offering TH (e.g. Sion, Biel, Münsterlingen,
Baden, Zurich (Zollikerberg, Triemli) and
Schaffhausen) will also be registered.
Another important aim of the register is to
organize and ensure short-and long-term fol –
low-up assessments. Consistent data are
lacking with respect to school outcomes in
cooled children: the CoolCap study evaluated
the efficacy of selective head cooling of 46
%
of
the children at 7 to 8 years on the basis of
parental questionnaires and demonstrated a
moderate correlation with the 18 month as-
sessments, although the study was underpo –
wered to examine the effect on TH on cogni-
tive function at an older age
5). In the NICHD
study, there was a high follow-up rate among
children at age 6 to 7 years, with children in
the TH group having lower death rate than
those in the control group, however, no signi –
ficant differences in the rates of cognitive
outcomes were detected
6). Long – ter m as ses s –
ments of the children who participated in the
TOBY trial
1) showed that children in the hypo –
ther mia g roup, as compar e d w ith those in the
control g roup had sig ni ficant r e ductions in the
r isk of cer ebr al palsy and the r isk of mo der ate
National Asphyxia and Cooling Register
in Switzerland
Barbara Brotschi 1), Bea Latal 2), Verena Rathke 1), 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 (blue circles): NICUs in Geneva, Lausanne, Basel, Lucerne, Zurich, Chur,
St. Gallen, Winterthur, Aarau; PICUs at Children’s University Hospital in Bern and Zurich.
1Prof. ffRTof ff.abi
1Prof. RTab
12
to severe disability; and they showed better
motor function 7).
These infants were all part of randomized
controlled studies in which strict entry criteria
for TH were set and the infants were treated
according to a defined protocol. However,
since TH has b ecome st andar d of car e, it is to
the clinician’s discretion which infants should
be treated with TH and how this treatment is
applied in reality. In order to know how cooled
infants in Switzerland develop at older age a
systematic and uniform follow-up has to take
place. All cooled children after HIE (re –
gardless of HIE severity) and those with a
Sarnat II or III or a Thomson score of 7 or hi-
gher who were not cooled are being followed
within the Swiss Neonatal Follow-up Network.
The follow-up protocol is the same as for
children born below 32 weeks of gestation
and is presented in table 2 .
A register is essential as modifying the treat –
ment protocol for TH is being investigated
both within and outside a formal randomised
trial design, which includes changes in degree
and duration of TH (Optimizing Cooling for
neonatal HIE study, Clinical Trials Identifier
NCT01192776), time window >6 h after birth
Identifier NCT00614744) and cooling infants
< 36 weeks gestational age (GA) (Clinical
Trials Identifier NCT01793 129). A recent
study has show n that infant s w ho do not f ul fill
standard TH entry criteria may benefit from
TH. This study showed that short- and long-
ter m outcome in coole d inf ant s w ith neonat al
encephalopathy following postnatal collapse,
preterm birth or with an underlying surgical
or cardiac condition and infants starting coo -
ling > 6 postnatal hours were similar to those
in cooled infants fulfilling the entry criteria
(Smit, Liu et al. 2014). A register will provide
us with detailed information on how Swiss
clinicians adapt to such changes.
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 en –
cephalopathy. 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
1Prof. ffRTof ff.abi
1Prof. RTafT
Weitere Informationen
Autoren/Autorinnen
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
