Arch Dis Child 2012;97(Suppl 2):A1–A539 A85
Background and Aims Hypoxic Ischemic Encephalopathy (HIE)
following perinatal asphyxia in term neonates is associated with
long term neurological sequelae or demise. The aim of this system-
atic review was to investigate the prognostic value of currently used
clinical tests in neonatal patients with HIE.
Methods MEDLINE, EMBASE, Central and CINAHL were
searched until November 2011. Studies were included if they: (1)
concerned infants with a gestational age ≥ 36 weeks suffering peri-
natal asphyxia and HIE; (2) evaluated prognostic tests in either
cooled or non-cooled patients; (3) reported on neurodevelopmental
outcome results at a follow up age ≥ 18 months. Study selection,
assessment of methodological quality, and data extraction was per-
formed by three independent reviewers. Pooled sensitivities and
specificities of investigated tests were calculated when possible.
Results Included in the analysis were 29 studies describing 13 dif-
ferent prognostic tests conducted 1631 times in 1306 term neo-
nates. Investigated tests comprised a range of imaging modalities,
neurophysiological tests and clinical neurological exams. Most
promising neurophysiology tests (first week of life) were: aEEG
(sens. 0.93, [95%CI 0.78–0.98]; spec. 0.90 [0.60–0.98]); EEG (sens.
0.92 [0.66–0.99]; spec. 0.83 [0.64–0.93]) and VEP (sens. 0.90
[0.74–0.97]; spec. 0.92 [0.68–0.98]).
Conclusions The available evidence suggests an important role for
aEEG, EEG, and VEP. Given the heterogeneity of the tests’ perfor-
mance and outcomes studied, accurate predictions of long term out-
comes in these critically ill neonates await the results of well
designed large prospective studies that evaluate the best possible
combination and timing of diagnostic tests.
THE IMPACT OF HYPOTHERMIA ON POST-NATAL BLOOD
BIOMARKERS OF NEONATAL HYPOXIC ISCHAEMIC
BH Walsh, GB Boylan, EM Dempsey, DM Murray. Neonatal Brain Research Group,
Department of Paediatrics and Child Health, University College Cork, Cork, Ireland
Numerous post-natal biomarkers of hypoxic ischaemic encephalop-
athy (HIE) severity have been proposed before the era of hypother-
mia. It is unclear if hypothermia impacts upon these potential
biomarkers, and therefore whether previous findings are now valid.
The aim of this study was to determine if hypothermia alters the
discriminative ability of post-natal nucleated red blood cells
(NRBCs) to distinguish between mild and moderate/severely
Methods A prospective cohort study recruited term infants with
HIE. The grade of HIE was categorised using Sarnat score, and
multi-channel EEG. The recruitment period (2003–2012), spanned
the introduction of hypothermia. Therefore the discriminative abil-
ity of the NRBC count for grade of encephalopathy could be com-
pared in moderate/severely encephalopathic infants who did and
did not receive hypothermia.
Results 86 infants with HIE were included in the study, 40 were
mild, 26 moderate (14 normothermic, 12 hypothermic), and 18
severe (10 normothermic, 8 hypothermic). In the normothermic
group, the NRBC count discriminated between mild and moderate/
severe Sarnat scores (p=0.016), but not in the hypothermic group
(p=0.297). This change was due to a decrease in NRBCs among
infants with a moderate Sarnat score receiving hypothermia, This
occurred despite these infants having a significantly worse 5 minute
Apgar score (p<0.001) and background EEG at 6 hours (p=0.032)
than their normothermic counterparts.
Conclusion This study has demonstrated that hypothermia can
impact upon early post-natal blood biomarkers of HIE. We therefore
advise caution in the use of these samples when studying novel
diagnostic biomarkers for HIE in the hypothermic era.
subjects (neuromotor score, NMS >2, or Bayley Scales of Infant
Development II or III MDI < 70 or cognitive score < 85).
Chorioamnionitis (42 subjects) was associated with a lower risk
of moderate-severe brain injury (OR 0.3; 95%CI 0.1–0.7; p=0.003),
and trended toward lower risk of adverse neurodevelopment. Infant
infection (32 subjects) trended toward association with moderate-
severe injury (OR 1.6; 95%CI 0.8–3.5; p=0.2), and was significantly
associated with an abnormal NMS (OR 3.4; 95%CI 1.2–10.2;
p=0.03) but not cognitive outcome. After adjusting for hypothermia
and severity of encephalopathy, maternal infection remained associ-
ated with a lower risk of brain injury, whereas the association
between infant infection and NMS was no longer significant.
These preliminary results are in keeping with animal studies that
suggest that the timing of an inflammatory signal may determine
whether infection is injurious or protective.
Acknowledgements NIH UL1 RR024131&P50NS035902.
GENES IMPORTANT IN INFLAMMATION, APOPTOSIS,
TRANSCRIPTION REGULATION AND ANGIOGENESIS
ARE INDUCED IN THE NEWBORN MOUSE BRAIN AFTER
1,2AGW Rognlien, 1,2EJ Wollen, 2,3M Atneosen-Åsegg, 4M Bjørås, 1,2OD Saugstad.
1Department of Pediatric Research, Oslo University Hospital HF; 2Women and
Children’s Division, University of Oslo, Oslo; 3Department of Clinical Molecular Biology
and Laboratory Sciences, Akershus University Hospital, Lørenskog; 4Department of
Microbiology, Oslo University Hospital HF, Oslo, Norway
Background and Aims Pathogenesis of birth asphyxia has yet to
be fully elucidated. To explore the mechanism of HR injury we fol-
lowed the temporal profile of a priori selected genes in the newborn
Methods 84 C57BL/6 mice (postnatal day 7) were randomized to
120 minutes of hypoxia (FiO2 0.08, n=64) or 180 minutes in air (con-
trols (C21), n=20). The hypoxia group was randomized to 30 min
reoxygenation with FiO2 0.60 (H60) or air (H21). After observation
in air for 0, 150, 300 minutes or 3 days, organs were harvested.
Homogenate of hippocampus and striatum was analyzed for mRNA
expression of 44 genes by real-time PCR.
Results Lcn2, Mt1, Hmox1 and Vegfa were significantly up-regulated
(p<0.05) after 0–300 min observation when comparing H21vsC21
and H60vsC21. Ccl2, Ccl12 and Tnf were up-regulated from 0–150
min, Stat3 from 150–300 min, while Ccnd1 was down-regulated at
0 min in both comparisons. In the H21vsC21 comparison at 0 min,
Neil3 and Apaf1 were down-regulated. When comparing H60vsH21,
Cxcl10 (0 min) and Hmox1 (300 min) were up-regulated while Neil3
(0 min) was down-regulated. There were no significant gene expres-
sion changes after 3 days.
Conclusions Genes important in inflammation (Lcn2, Mt1, Ccl2,
Ccl12, Cxcl10, Tnf, Hmox1), apoptosis (Lcn2, Mt1, Tnf, Hmox1, Vegfa),
angiogenesis (Vegfa), and transcription regulation (Stat3) were
induced up to 300 minutes after hypoxia-reoxygenation while the
DNA-glycosylase Neil3 was suppressed. The up-regulation of the
pro-inflammatory cytokine Cxcl10 after hyperoxic compared to nor-
moxic reoxygenation, confirms that hyperoxia induces additional
PROGNOSTIC TESTS IN TERM NEONATES WITH HYPOXIC
ISCHEMIC ENCEPHALOPATHY: A SYSTEMATIC REVIEW
1H van Laerhoven, 2TR de Haan, 3M Offringa, 4B Post, 5JH van der Lee. 1Academic
Medical Center - Emma Children’s Hospital; 2Neonatology, Academic Medical Center -
Emma Children’s Hospital, Amsterdam, Netherlands Antilles; 3Hospital for Sick Children
Research Institute, Toronto, ON, Canada; 4UMCN St Radboud, Nijmegen; 5Woman and
Child Centre, Academic Medical Centre, Amsterdam, Netherlands Antilles
group.bmj.com on September 21, 2015 - Published by http://adc.bmj.com/Downloaded from
H van Laerhoven, TR de Haan, M Offringa, B Post and JH van der Lee
Hypoxic Ischemic Encephalopathy: A
291 Prognostic Tests in Term Neonates with
2012 97: A85 Arch Dis Child
Updated information and services can be found at:
box at the top right corner of the online article.
Receive free email alerts when new articles cite this article. Sign up in the
To request permissions go to:
To order reprints go to:
To subscribe to BMJ go to:
group.bmj.com on September 21, 2015 - Published by http://adc.bmj.com/ Downloaded from