Beyond newborn survival: Paper 4
Intrapartum-related neonatal encephalopathy incidence and neurodevelopmental
impairment at a regional and global level for 2010 and trends from 1990
Supplementary information
Table of Contents
I) Definitions/Diagnostic Criteria for Neonatal Encephalopathy ................................................. 2
Web appendix 1: Different definitions/diagnostic criteria for grading of neonatal
encephalopathy .......................................................................................................................... 2
II) Searches and data selection process ........................................................................................ 3
Web appendix 2: Neonatal encephalopathy – searches and data selection process ............... 3
III) Neonatal encephalopathy incidence ....................................................................................... 4
Web appendix 3: Included studies of neonatal encephalopathy / hypoxic ischemic
encephalopathy incidence ......................................................................................................... 4
Web appendix 4: Historical Trends in NE Incidence reported in the literature ......................... 7
Webappendix 5: Distribution of Residuals from Linear Regression Model and Tests of
Normality..................................................................................................................................... 8
Web appendix 6a: Studies reporting sex ratio among incident NE cases .................................. 9
Web appendix 6b: Meta-analysis of proportion male NE (adjusted for sex ratio at birth),
including 10 studies .................................................................................................................. 10
IV) Neonatal encephalopathy case fatality ................................................................................ 11
Web appendix 7a: Included studies reporting neonatal encephalopathy case fatality ........... 11
Web appendix 7b: Meta-analysis of neonatal encephalopathy case fatality in NMR level 1
studies…………………………….………………....14
Web appendix 7c: Meta-analysis of neonatal encephalopathy case fatality in NMR level 2
studies……………………..............................15
Web appendix 7d: Meta-analysis of neonatal encephalopathy case fatality in NMR level 3
studies…………………….............................16
V) Neonatal encephalopathy impairment .................................................................................. 17
Web appendix 8a: Included studies of moderate-severe impairment among neonatal
encephalopathy cases .............................................................................................................. 17
Web appendix 8b: Included studies of mild impairment among NE cases ............................. 22
VI) References ................................................................................................................... …24
1
Web appendix 1: Different Definitions/Diagnostic Criteria for Grading of Neonatal Encephalopathy
Sarnat &
Sarnat(1)
2
Mental State
Lethargy/(obtunded)
Stupor/coma
Neuromuscular control
Hypotonia
Posture (hyperextension)
Spontaneous activity
Impaired swallowing
Impairment of reflexes
Primitive
Moro
Grasp
Suck
Brainstem
Gag/corneal
Autonomic Nervous system
Respirations
Occasional Apnea
Severe Apnea
Heart rate
Bradycardia
Variable
Pupils
Seizures
Occasional or not described
Repetitive/Prolongegd
Fontanelle (full/tense)
Timing of symptoms
Low(2)
3
*
Mod
Sev
*
*
*
Amiel Tilson(4)
Fenichel(5)
Ellis(6)
II
St 2
Mod
2
III
*
*
*
Levene(3)
*
*
*
*
*
St 3
*
*
**
*
**
*
*
**
*
**
*
**
*
**
*
**
*
**
*
**
*
*
*
*
*
Mod or Sev
b
*
*
NICHD(9)
Mod
*
*
**
Sev
*
*
b
*
*
*
*
**
*
**
*
*
*
*
**
*
**
*
*
*
b
*
**
**
*
b
b
*
*
Capetown
Scoring(8)
*
*
**
3
*
*
*
*
Sev
Badawi
(a or 2b’s)(7)
*
*
*
*
*
*
**
*
*
*
*
Continuum in
first 2 wk,
onset within
24hr
*
**
*
NS
*
*
Onset in first 48
hr
*
Onset in first 1
week of life
*
*
*
*
Onset first 24
hr
*
Onset within
first 24 hr
a
First 1 week of
life
*
*
First 1 week
of life
By 6 hours of
age
2
Web appendix 2:
Neonatal Encephalopathy – Searches and data selection process
DATABASES
Medline, Popline, LILACS, BioMed Central, African Index
Medicus, Cochrane, Web of science, and EMRO
SEARCH TERMS
‘Neonatal encephalopathy’
‘Hypoxic Ischemic encephalopathy’
Total search results (3701)
Unpublished data sets (2)
Studies remaining after
screening title or abstract (n=132)
80 Studies Included
NE
incidence
N= 40
Gender
Split
N=14
Neonatal
Case Fatality
N=33
Excluded studies
Duplicate studies of same cohort (n=27)
Did not specify or meet criteria for NE (n= 3)
Did not exclude preterms (n= 2)
Did not report outcome of interest (n=5)
High percentage excluded from enrollment (n=2)
Improper inclusion criteria (n=1)
No relevant data (n=2)
Extreme outlying for NE incidence modeling (n=2)
Before 1980 (n=3)
High losses to follow up (n=5)
Long Term
Impairment
N=45
3
Web appendix 3: Included 40 studies of neonatal encephalopathy/hypoxic ischemic encephalopathy incidence
Author
NMR Level 1
Adamson,
S(10)
Badawi, N(7)
Country
Australia
Australia
Median
study year
1992
Study Population
Case definition/classification of NE
Regional hospitals, Perth (2
referral, 3 peripheral)
At least one: seizures of any type/duration; absent
responsiveness to stimuli; abnormal tone for more
than 24 hours; poor suck (not due to mechanical
or peripheral causes) for more than 24 hours;
difficulty control of respiration, including cyanotic
attacks and recurrent apnea, Sarnat staging
1994
2 tertiary care hospitalsNICUs, Perth
Seizures alone OR any 2 of the following lasting
for more than 24 hours (abnormal consciousness,
abnormal respiration, difficulty feeding, abnormal
tone/reflexes)
seizures OR any 2 of the following: altered
consciousness, abnormal respiration, diff feeding,
abnormal tone/reflexes - NOT include mild, stage
1; grading Sarnat
Number of
term or near
term babies
with NE
Incidence of
NE per 1000
live births
3.75
moderatesevere
Evidence of “asphyxia / intrapartum
insult"
Case Exclusions
Not required
GA <37 wk or ≥2500 g if
unknown gestation
89
NOT required
GA <37 wk, (Down’s syndrome
and neural tube defects
164
Not required
GA <37 wk, chromosomal
abnormalities,open neural tube
defects,drug withdrawal
90
3.80
1.64
moderatesevere /term
live births
1.4/term live
births
3.01
moderatesevere
Pierrat, V(11)
France
2000
Regional surveillance of
deliveries In North Pasde
Calais France
Palsoditiir(12)
Iceland
1999
Landspitali university hospital
NS
NS
NS
NS
Impey, LW(13)
Ireland
1999
Referral/Tertiary Care Hospital
- Maternity hospital Dublin
Sarnat 2 or 3 within 7 days of life
Not required
GA <37wk, congenital
anomalies, breech, stillbirth
25
Sarnat criteria/staging
Not required
preterm, metabolic disorders,
malformations, chromosome
abnormalities, viral infections
27
Sarnat
ICD 10 coding: mild "neonatal cerebral irritability",
moderate "neonatal cerebral depression, severe
"neonatal coma"
Not required
GA <36 wk, mild cases
64
Not required
congenital abnormalities,
<2500g
841
GA <37 weeks, major congenital
malformations
116
3.10
0.77 in 2005
(term
livebirths)
Preterm
110
1.088
Locatelli,
A(14)
Italy
1998
tertiary care center NE of Milan
West, C(15)
New
Zealand
1998
Referral Hospital, National
Women's Hospital database
Moster, D(16)
Norway
2002
Birth registry, Norway
Becher,
JC(17)
Scottland /
UK
1999
Simpson Memorial Maternity
Pavillion/Perinatal Centre
Garcia-Alix,
A.(18)
Spain
2005
Hellstrom,
L(19)
Sweden
Thornberg,
E(20)
Sweden
0.88
1.30
moderatesevere
La Paz Hospital, Tertiary Care
Hospital
Encephalopathy in first 12 hours, Sarnat
Difficulty initiating or maintaining breathing,
abnormal tone or mental status with or without
convulsions
pH<7, 5 minute Apgar <5, or multiorgan
involvement
Non-reassuring FHT, sentinel event,
dystocia; 5min Apgar <5, pH<7, need
resuscitation
2001
All births Sweden; SMBR
ICD 10: P910 P909
1min Apgar <4,
GA <37 wk, multiple pregnancy,
IUGR, congenital malformations
64
0.68
1988
All births Goteborg, Sweden;
Swedish Medical Birth Register
Modified Fenichel
5min Apgar <7
GA <37 wk
75
1.80
4
Smith, J(21)
District Health Authority,
Central England
UK
1994
Author
Country
Median
study year
Study Population
Yates, H(22)
UK
2008
"The Neonatal Survey" hospital-based
2000
John Radcliffe Hospital
(Oxford), Horton Hospital
(North Oxfordshire)
Yeh, P(23)
UK
Blume, H(24)
USA
1997
Birth registry- Washington
state; Comprehensive Hospital
reporting system
Wu, Y(25)
USA
2001
all infants born in California at
gestation of >=36 wk
1980
University hospital, NICU Royal Alexandra Hospital
2007
Levene
Case definition/classification of NE
either acidosis in first hour of life, Apgar <5 at 10
min, or need for ongoing resuscitation at 10 min of
age AND either seizures or moderate/severe
encephalopathy
ICD 9/10 coding, encephalopathy with seizures
ICD 9 (severe asphyxia, asphyxia with neurologic
involvement, unspecified asphyxia in live born
infant, newborn convulsions, other and unspecified
irritability in the newborn, or cerebral depression,
coma
one of following - severe birth asphyxia, neonatal
seizure, mechanical ventilation associated with
diagnoses suggestive of NE, neonatal death
associated with aforementioned diagnoses
"infants with encephalopathy clearly
attributable to a cause other than
asphyxia were excluded"
GA <37 wk
Evidence of “asphyxia / intrapartum
insult"
Case Exclusions
349
Number of
term or near
term babies
with NE
1.90
acidosis or Apgar <5 at 10 min or need
for ongoing resuscitation at 10 min.
NS
46
1.26
GA <37 wks, congenital
abnormalities
222
1.80 (term live
births)
1060
1.81
2131
1.14
Incidence of
NE per 1000
live births
---
GA <37 wk, congenital
anomalies, drug withdrawal
Preterm, infants (<1500g,
>5500g) maternal ages (<12 or
>55) infants with missing data
regarding hour of birth
Sarnat
Intrapartum distress, neonatal distress,
5min Apgar <5, need for resuscitation,
ventilation
GA <37 wk, congenital
malformations, infection, CNS
malformations
95
3.32
8 regional hospitals, Sichuan
abnormal neurologic signs in first 24 hrs
(conscious, tone, suck, seizure, respiration) +
imaging
Some with CT or MRI findings with
hypoxia
---
2208
10.20
Amiel-Tison
GA <37 wk, congenital
anomalies
26
1.67
60
1.50
95
6.31
43
9.40
18
4.48
70
5.50 (term live
births)
---
NMR Level 2
Finer, N(26)
Wan, C(27)
Canada
China
Lam, B(28)
ChinaHong Kong
1986
Tertiary care/University
hospital, NICU Queen Mary
Hospital HK
McShane,
M(29)
Ireland
1983
Referral/ Tertiary Care Hospital
- Royal Maternity Hospital
Sarnat
1 min Apgar <3,
5min Apgar <5; fetal distress (meconium
or pH<7.2); intubation during
resuscitation
Garbutt, A(30)
Jamaica
2001
University of West Indies
hospital
Modified Sarnat
NS
Preterm, did not exclude
infections, hypoglycemia
Preterm,
chromosomal/congenital
anomalies
Al-alfy, A(31)
Kuwait
1989
Maternity Hospital, Kuwait
Fenichel
5min Apgar <5, late decerebration,
Brady, resuscitation, umbilical pH <7.1
GA <37 wk
Boo, NY(32)
Malaysia
1989
Sarnat
Fetal distress and 1min Apgar <8 or
require PPV
Itoo, B(33)
Saudi
Arabia
1996
Sarnat
---
Maternity hospital, Kuala
Lumpur
Referral Hospital - MaternalChild Hospital of Madina
Region
preterms not excluded, but only
7% were preterm
GA <37 wk, congenital
malformation; born out of
hospital
5
Hull, J(34)
UK
1986
Author
Country
Median
study year
Levene, M(3)
UK
1982
District healty authority, central
England
Levene
---
Study Population
Case definition/classification of NE
Evidence of “asphyxia / intrapartum
insult"
Referral/Tertiary Care HospitalLeicester Maternity
Levene
University Hospital of Kinshasa
Sarnat, Thompson
GA <37 wk, hypoglycemia
4.62
Case Exclusions
112
Number of
term or near
term babies
with NE
abnormalities on fetal monitoring, Apgar
GA <37 wk, hypoglycemia
126
6.01
Apgar <6 after 5min, resuscitation till 10
min after birth, pH<7 nd base excess
>16
<36, congenital malformations
44
43
Incidence of
NE per 1000
live births
NMR Level 3
Bisele, T(35)
Democratic
Republic of
Congo
2010
NPPD(36)
India
1995
NPPD Network - 16 tertiary
care centers
NPPD(37)
India
2002
NPPD Network - 18 tertiary
care centers
Nair, M(38)
Ellis, M(6)
Lee, AC(39)
India
Nepal
Nepal
NS
1995
Rural Community, Sarlahi
NICU admissions,
Teaching/referral tertiary care
hospital- Jos University
Nigeria
1988
Oswyn, G(41)
Papua New
Guinea
1997
Harrison,
V(42)
South
Africa
2001
South
Africa
Velaphi, S(44)
South
Africa
Maternity Hospital, Katmandu
2004
Airede, A(40)
Linley, L (43)
Referral/Medical College
2001
2001
Tertiary/Referral hospital, NICU
admissions
Midwife Obstetric Units
(community based clinics) and
2 referral hospitals
Peninsula Maternal and
Neonatal Service of University
of Capetown- referral hospital,
maternity hospital and MOU
PIPP: 142 hospitals, S.Africa
NS
NS
NS
513
13.83
NS
NS
NS
2075
14.25
clinical "birth asphyxia"
GA <37 wk, hypoglycemia,
meningitis, congenital,
hyperbilirubinemia
174
8.05
modified Fenichel, signs starting 6-24h
---
Preterm, congenital abnormality,
signs of infection, normal sugar
131
6.06
Badawi
not cry at birth, not breathing within 1
min, resuscitation
GA <37 wk, congenital
anomalies
279
13.40
history of evidence of IP asphyxia
GA <37 wk;
metabolic/hypoglycemia
166
26.51
prolonged resuscitation or 5min Apgar
<5
GA <34 wk, <2000g
129
5.50
---
Preterms not excluded, but 96%
of birth cohort term
22
10.70
100
3.64
---
1.87 HIE
deaths/1000
live births
Clinical encephalopathy in first week, >37 wk
Fenichel
Perinatal Asphyxia: 1) death 24hr not congenital
malformations OR 2) neurological abnormalities irritability, tone, consciousness, convulsions,
reflexes
altered tone/consciousness, bulging fontanelle,
poor suck, hematuria, U/S with cerebral edema;
classify by Fenichel
Thompson score
"hypoxic-ischemic encephalopathy"
NS
---
GA <37 wk (Ballard), brain
anomaly,
Metabolic/chromosomal
disorders, clinical hypoglycemia,
infections, multiple births
<37 wks, Structural brain
anomaly,
Metabolic/chromosomal
disorders, hypoglycaemia,
severe infection, multiple births.
6
Mwakyusa,
SD(45)
Robertson,
N(46)
Tanzania
2002
Uganda
2007
Referral/Tertiary Care Hospital,
Muhimbili National Hospital
Referral/Tertiary Care Hospital
- Mulago
Sarnat, HIE score
5min Apgar <7
Preterm, congenital
malformation
140
23.33
Sarnat
5 min Apgar <6 , require resuscitation
GA <37 wk
110
22.19
Web appendix 4. Historical Trends in NE Incidence reported in the literature
7
.4
.2
0
Density
.6
.8
Web appendix 5. Distribution of Residuals from Linear Regression Model and Tests of Normality
-1
-.5
0
Residuals
.5
1
8
Web appendix 6a. Included studies of sex ratio in NE birth cohorts
Author
Country
Median year
of data
collection
Bisele, T(35)
Democratic Republic of Congo
2010
25
25
50.0%
48.5%
Ancora, G.(47)
Italy
2004
24
8
75.0%
70.6%
Locatelli, A.(14)
Italy
1998
18
9
66.7%
62.7%
Pisani F.(48)
Italy
2001
41
16
71.9%
67.7%
Garbutt, A.(30)
Jamaica
2001
55
40
55.6%
52.9%
Lee, AC(39)
Nepal
2004
115
72
61.5%
58.6%
Airede, A.(40)
Nigeria
1988
91
75
54.8%
53.0%
Majeed, R(49)
Pakistan
2005
50
30
62.5%
59.5%
Seyal, T(50)
Pakistan
2007
88
41
68.2%
65.0%
Itoo, B(33)
Saudi Arabia
1996
45
25
64.3%
62.4%
Becher, J(17)
Scotland
1999
66
50
56.9%
54.1%
Pfenninger, J. (51)
Switzerland
1994
24
14
63.2%
60.0%
Hallioglu, O.(52)
Turkey
1995
31
16
66.0%
62.8%
Levene, M(3)
UK
1982
71
55
56.3%
53.6%
Number
NE Male
Number
NE female
Ratio Male:Female
Adjusted proportion
male*
9
Web appendix 6b. Meta-analysis of proportion male NE (adjusted for sex ratio at birth) including 14 studies
(698 NE cases)
Citations: Democratic Republic of Congo (2010)(35), Italy (1998)(14), Italy (2001)(48), Italy (2004)(47), Jamaica (2001)(30), Nepal (2004)(53), Nigeria (1988)(40),
Pakistan (2005)(49), Pakistan (2007)(50), Saudi Arabia (1996)(33), Scotland (1999)(17), Switzerland (1994)(51), Turkey (1995)(52), UK (1982)(3)
10
11
Web appendix 7a: Included studies reporting neonatal encephalopathy case fatality
Author
NMR LEVEL 1
Badawi, N(7)
Carli, G(54)
Pierrat, V.(11)
Ancora,
G(47)
Ferrari, F(55)
Locatelli,
A(14)
Country
Australia
Australia
France
Italy
Italy
Italy
Median year
of data
collection
Study Population
1994
2 tertiary care
hospitals- NICUs,
Perth
1996
Referral/Tertiary
Care Hospital, NICU;
Sydney, Australia
2000
Regional surveillance
of deliveries In North
Pasde Calais France
2004
University of Bologna
hospital, NICU
2005
University Hospital of
Modena
1998
tertiary care center,
northeast of Milan
Van Schie,
PE(56)
Netherlands
2001
West, C(15)
New Zealand
1998
Toh, V(57)
Singapore
1994
Thornberg,
E(20)
Sweden
1988
VU University
Medical Center
Referral Hospital,
National Women's
Hospital database
Referral tertiary care
hospital - Women's
Childrens Hospital
Singapore
All births Goteborg,
Sweden; Swedish
Birth Register
Case Exclusions
Number of term
or near term
babies with NE
Neonatal
Case Fatality
NOT required
GA <37 wk, congenital anomalies Downs/neural tube
164
9%
Sarnat
"likely asphyxial event", ACOG
GA <37 wk, hypoglycemic, opiate,
congenital malformations,
hemorrhage, metabolic, jaundice,
hypernatremia
42
32%
seizures OR any 2: alt consciousness, abnl
resp, diff feeding, abnormal tone/reflexes NOT include mild, stage 1; grading Sarnat
Late decels fetal monitoring,
delayed breathing, pH<7, 5min
Apgar <7, Multiple organ failure,
acute hypoxic event
<37wk, chromosomal abnormalities,
drug withdrawal
90
27%
Sarnat
Heart rate abnormalities and/or
meconium staining and/or need for
birth cardiopulmonary resuscitation,
Apgar score <=5 at 5 min and/or
umbilical artery pH<=7.1 with base
excess >=12mmol/L)
GA <37 wk, congenital malformations
and congenital
infections
32
3%
Apgar score <=5 at 1 minute and
<=7 at 5 minutes
GA <37 wk, congenital malformations
or major dysmorphic features,
congenital viral infections, and
defined metabolic syndromes
43
2%
preterm, metabolic disorders,
malformations, chromosome
abnormalities, viral infections
27
4%
preterm, dysmorphic syndromes,
malformations, evidence of
intrauterine or perinatal infections,
intracranial hemorrhage, requiring
surgical intervention in neonatal
period
42
24%
GA <36 wk, mild excluded
70
13%
Case definition / classification of NE
Evidence of "asphyxia /
intrapartum insult"
Either seizures alone OR any 2 for over
24hr (abnormal consciousness, abnormal
respiration, difficulty feeding, abnormal
tone/reflexes)
Sarnat
Sarnat
Sarnat- HIE ("defined as clinical status of
HIE that include: lethargy, hypotonia,
hyperreflexia, convulsions, and myoclonic
seizures")
1 of following (intrauterine asphyxia
such as late decerebrations or
meconium-stained amniotic fluid,
umbilical cord artery pH <7.10,
respiratory insufficiency at birth, in
need of mechanics ventilation, or
Apgar score <5 at 5 min)
Sarnat
Sarnat
5 min Apgar<6, require
resuscitation, intubation
GA <3 wk7, congenital malformation,
chromosomal abnormality
22
30%
Fenichel
5min Apgar <7
GA <37 wk
75
17%
12
Author
LippZwahlen,
AE(58)
Country
Median year
of data
collection
Switzerland
1981
Case Exclusions
Number of term
or near term
babies with NE
Neonatal
Case Fatality
1 min Apgar <5 or requiring
ventilation
GA <37 wk
23
12%
Sarnat
abnormal fetal tracing, meconium,
low Apgar or umbilical pH, or need
for CPR
GA <38 wk, sepsis, cardiac
malformations, chromosomal
abnormalities, metabolic d/o,
dysmorphic syndromes
38
37%
Sarnat
1 min Apgar <5
preterm, congenital malformations,
genetic, metabolic syndromes
80
22%
Encephalopathy score: based on Sarnat,
addition of feeding sign by Nelson
5min Apgar <5, umbilical pH<7.1, or
base def>10
GA <35 wk; congenital malformations;
metabolic do; congenital infections
68
7%
GA <37 wk, congenital malformations,
infection, CNS malformations
95
7%
Case definition / classification of NE
Evidence of "asphyxia /
intrapartum insult"
Mod Sarnat
Pfenninger,
J(51)
Switzerland
1994
Barnett,
AL(59)
UK
1997
Study Population
NICU admissions Lausanne
Switzerland
Referral/ Tertiary
Care Hospital, NICU
admissions Children's hospital
Bern
Referral/Tertiary
Care Hospital,
Hammersmith
Hospital London
1997
University Teaching
Hospital, UCSF NICU admissions
1980
University hospital,
NICU - Royal
Alexandra Hospital
Sarnat
Intrapartum distress, neonatal
distress, 5min Apgar <5, need for
resuscitation, ventilation
1980s
Referral/Tertiary
Care Hospital, NICU
Toronto Sick Kids
Sarnat
5min Apgar<7, scalp pH<7, late
decerebration or meconium
Preterm
36
22%
Fenichel
5min Apgar <5, late decerebration,
Brady, resuscitation, umbilical pH
<7.1
GA <37 wk
43
12%
Fetal distress and 1min Apgar <8 or
require PPV
Preterms not excluded, but only 7%
were preterm
18
33%
GA <37 wk, congenital malformation;
born out of hospital
70
17%
GA <37 wk, hypoglycemia
126
9%
Preterm, congenital abnormality,
signs of infection, normal sugar
131
33%
GA <37 wk, congenital anomalies
279
49%
Miller, S(60)
NMR Level 2
Finer, N(26)
Muttit, S(61)
US
Canada
Canada
Al-alfy, A(62)
Kuwait
1989
Maternity Hospital,
Kuwait
Boo, NY(32)
Malaysia
1989
Maternity hospital,
Kuala Lumpur
Sarnat
1996
Referral Hospital Maternal-Child
Hospital of Madina
Region
Sarnat
Levene
Itoo, B(33)
Saudi Arabia
Levene, M(3)
NMR Level 3
UK
1982
Referral/Tertiary
Care HospitalLeicester Maternity
Ellis, M(6)
Nepal
1995
Maternity Hospital,
Katmandu
mod Fenichel, sign starting 6-24h
Lee, AC(39)
Nepal
2004
Rural Community,
Sarlahi
Badawi
abnormalities on fetal monitoring,
depression of Apgar score
not cry at birth, not breathing within
1 min, resuscitation
13
Author
Airede, A(40)
Country
Nigeria
Median year
of data
collection
Study Population
Case definition / classification of NE
Evidence of "asphyxia /
intrapartum insult"
1988
NICU admissions,
Teaching/referral
tertiary care hospitalJos University
Fenichel
history of evidence of IP asphyxia
Sarnat
Case Exclusions
Number of term
or near term
babies with NE
Neonatal
Case Fatality
GA <37 wk; metabolic/hypoglycemia
166
19%
63
43%
22
16%
129
45%
Abbasey,
R(63)
Pakistan
1997
Tertiary carereferral/teaching
Children's Hospital;
Islamabad
Qureshi,
AM(64)
Pakistan
2008
Teaching hospital,
Abbottabad
Sarnat
Seyal, T(50)
Pakistan
2007
Fatima Jinah Medical
College
Sarnat
Apgar <7 at 5 min
preterm
<34 wk, <1500g, respiratory
depression due to intracranial
bleeding, neonates with major
congenital malformations, severe
hyperbilirubinemia, hypoglycemia or
meningitis as cause of
encephalopathy
Tertiary/Referral
hospital, NICU
admissions
Perinatal Asphyxia: 1) death 24hr not
congenital malformations OR 2)
neurological abnormalities - irritability, tone,
consciousness, convulsions, reflexes
prolonged resuscitation or 5min
Apgar <5
GA <34 wk, <2000g
129
31%
Thompson score
GA <37 wk (Ballard), Structural brain
anomaly, Metabolic/chromosomal
disorders, hypoglycemia, septicemia
meningitis, multiple births
100
10%
Sarnat
GA <37 wk
40
10%
Oswyn, G(41)
Papua New
Guinea
1997
Linley, L(43)
South Africa
2001
Thompson,
CM(8)
South Africa
1997
Mwakyusa,
SD(45)
Tanzania
2002
Hallioglu,
O(52)
Turkey
1995
PMNS- referral
hospital, maternity
hospital and MOU
Referral hospital,
NICU; Groote Schur
Hospital
Referral/Tertiary
Care Hospital,
Muhimbili National
Hospital
Referral hospital,
University; Dr Sami
Ulus Children's
Hospital, Ankara
Sarnat, HIE score
5min Apgar <7
preterm, congenital malformation
140
20%
Sarnat
5min Apgar<3, acidosis, delayed
respiration, mechanical ventilation
those who were not near-term or fullterm
57
28%
14
Web appendix 7b: Meta-analysis of NE case fatality in NMR level 1 (NMR <5/1000 live births) studies [14 studies, 995 NE
cases]
Citations: Australia (1994)(7), Australia (1996)(54), France (2000)(11), Italy (1998)(14), Italy (2004)(47), Italy (2005)(55), Netherlands (2001)(56), New Zealand (1998)(15),
Singapore (1994)(57), Sweden (1988)(20), Switzerland (1981)(58), Switzerland (1994)(51), United Kingdom (1997)(59), United States (1997)(60)
15
Web appendix 7c: Meta-analysis of NE case fatality in NMR level 2 studies (5-<15) [6 studies, 602 NE cases]
Citations: Canada (1980)(26), Canada (1980s)(61), Kuwait (1989)(62), Malaysia (1989)(32), Saudi Arabia (1996)(33), United Kingdom (1982)(3)
16
Web appendix 7d: Meta-analysis of NE case fatality in NMR level 3 studies (>15) [11 studies, 1256 NE cases]
Citations: Nepal (1995)(65), Nepal (2004)(53), Nigeria (1988)(40), Pakistan (1997)(63), Pakistan (2007)(50), Pakistan (2008)(64), Papua New Guinea (1997)(41), South Africa
(1997)(8), South Africa (2001)(43), Tanzania (2004)(45), Turkey (1995)(52)
17
Web appendix 8a. Included studies of moderate-severe impairment among NE cases
Author
Country
Median
study
year
1996
Study Population
% drop
out from
follow-up
Case definition / classification
of NE
Referral/Tertiary Care
Hospital, NICU;
Sydney, Australia
20%
Sarnat
Evidence of "asphyxia /
intrapartum insult"
Number of
term or near
term babies
with NE
N
survivors
assessed*
Case definition of
moderate-severe
impairment
Age of
impairment
assessment
(in years)
% of NE
survivors
with
moderatesevere
impairment
"likely asphyxial event", ACOG
42
40
CP or significant delay
(Griffin <2SD)
1.0
32.5
276
195
CP or Griffin <2SD below
population mean
1.5
27.2
26
19
1.0
52.6
375
89
CP or severe
developmental delay
Severe adverse outcome:
severe CP, severe
developmental delay,
sensorineural deafness or
cortical blindness
1.0
43.8
90
63
CP or severe MR
2.0
17.5
52
52
21/52 with abnormal
neurodevelopmental
outcome ( Griffith's quotient
<87, significant motor
disability), not broken down
2
40.4
NMR Level 1
Carli, G(54)
Dixon, G(66)
Gray, P(67)
Shah, P(68)
Pierrat,
V(11)
Nadeem,
M(69)
Australia
Australia
Australia
Canada
France
Ireland
1995
2 tertiary care hospitalsNICUs, Perth
19%
Seizures alone OR any 2 of the
following lasting for more than 24
hours (abnormal consciousness,
abnormal respiration, difficulty
feeding, abnormal tone/reflexes),
severity
1989
Referral/Tertiary Care
Hospital, Mater
Mothers' Brisbane
N/A
Fenichel: mod or severe
--at least 2: intrapartum distress,
5min Apgar <6 or cord pH<7.15,
need for resuscitation or
intubation
1993
Referral/ Tertiary Care
Hospital, NICU
admissions - Toronto
Sick Kids
19%
Sarnat
ACOG: 5min Apgar <5;
acidosis; delayed onset
respiration 5min; mechanical
ventilation;
N/A
seizures OR any 2: alt
consciousness, abnormal
respration, diff feeding, abnormal
tone/reflexes - NOT include mild,
stage 1; grading Sarnat
2000
2004
Regional surveillance of
deliveries In North
Pasde Calais France
Cork University
maternity hospital NICU
5%
Sarnat
Late decerebration, fetal
monitoring, delayed breathing,
pH<7, 5min Apgar <7, Multiple
organ failure, acute hypoxic
event
HIE if at least 2 fulfilled (initial
capillary or arterial pH <7.1,
Apgar score <5 at 5 min, initial
capillary or arterial lactate
>7mmol/L, abnormal
neurology/clinical seizures)
32
31
CP
2
9.7
43
34
CP, 4/34 with mild motor
impairment
2
47.1
Ancora,
G(47)
Italy
2004
University of Bologna
hospital, NICU
0%
Sarnat
heart rate abnormalities and/or
meconium staining and/or need
for birth cardiopulmonary
resuscitation, Apgar score <=5
at 5 min and/or umbilical artery
pH<=7.1 with base excess
>=12mmol/L
Ferrari, F(55)
Italy
2005
University Hospital of
Modena
19%
Sarnat
Apgar score <=5 at 1 minute
and <=7 at 5 minutes
18
Locatelli,
A(14)
Author
Pisani F(48)
Italy
1998
Country
Median
study
year
Gluckman,
P(70)
Italy
Multicountry
(Canada,
New
Zealand,
U.K.,
U.S.)
Jacobs,
S.(71)
Multicountry
(Australia,
New
Zealand,
Canada,
U.S.)
Simbruner,
G(72)
Multicountry
(Europe)
L'Abee,
C(73)
Netherlan
ds
Van Kooij,
B(74)
Netherlan
ds
Van Schie,
P(56)
Netherlan
ds
2001
2001
2004
tertiary care center,
northeast of Milan
0%
Study Population
% drop
out from
follow-up
Referral/NICU
25 perinatal centers
NICUs, "Infant cooling
evaluation
collaboration"
2004
neo.nEURO.network,
NICU
1998
Referral/Tertiary Care
Hospital - Children
Hospital, Utretch
Sarnat
27
25
CP (n=4) though no
qualification of severity/type
at least up to 3
years
Number of
term or near
term babies
with NE
N
survivors
assessed*
Case definition of
moderate-severe
impairment
Age of
impairment
assessment
(in years)
16.0
% of NE
survivors
with
moderatesevere
impairment
57
57
CP, dev delay, epilepsy,
blindness or deafness or
death
2.0
17.5
1.5
39.3
2
42.4
N/A
Sarnat & Amiel Tison
Evidence of "asphyxia /
intrapartum insult"
intrapartum distress,
bradycardia, decerebration,
meconium, Apgar, PPV O2 or
pH <7.1
8%
Mod Sarnat: mild, moderate,
severe encephalopathy
10min Apgar <5, need for
resuscitation/ventilation, pH<7,
base deficit >16
118
61
peripartum hypoxia-ischemia
diagnosed if 2 of the following
clinical characteristics met
(Apgar <5 at 10 min, continued
need for mechanical ventilation
at 10 min, metabolic acidosis)
109
59
GMF 3-5, Bayley MDI <70,
bilateral visual impairment
major sensorineural
disability, neuromotor delay,
CP, moderate or severe CP,
GMFCS disability level 2-5,
motor score on Bayley
scales <-2SD,
developmental score on
Bayley scales <-23 Ds, legal
blindness, deafness
requiring amplification
58
25
developmental quotients <2SD, disabling CP, cortical
blindness, severe hearing
loss requiring cochlear
implants
1.5-1.75
60.0
11
4
CP (spastic quadriplegia,
dyskinetic)
2.0
50.0
9-10
19.8
2
37.5
9%
11%
N/A
1995
University Medical
Center Utrecht, level 3
NICU
27%
2001
VU University Medical
Center
9%
Case definition / classification
of NE
---
Sarnat
birth asphyxia (Apgar score <5 at
10 min, continued need for
resuscitation at 10 min, umbilical
cord pH or any arterial pH of
<7.00 w/I 60 min. after birth,
base deficit of >16mmol/L w/I 60
min. after birth), and
encephalopathy with lethargy,
stupor, or coma and 1+ of
following (hypotonia, abnormal
reflexes, absent or weak suck,
clinical seizures) AND abnormal
standard EEG or aEEG findings
Sarnat
Sarnat
Sarnat- HIE ("defined as clinical
status of HIE that include:
lethargy, hypotonia,
Apgar score <5 at 10 min,
continued need for resuscitation
at 10 min, umbilical cord pH or
any arterial pH of <7.00 w/I 60
min. after birth, base deficit of
>16mmol/L w/I 60 min. after
birth
FHR abnormality or meconium;
delayed respiration; pH <7.1; 5
min Apgar <7; multiorgan failure
meet at least 3 of following
(signs of fetal distress - late
decerebrations on fetal
monitoring or meconium
staining), Apgar score <7 at 5
min, arterial umbilical pH <7.1,
delay in onset of spontaneous
respiration, multiorgan failure)
late decerebrations, meconiumstained fluid, umbilical cord
artery pH <7.10, mechanical
164
86
42
32
total impairment score (TIS)
<15%, IQ<=85 (below 1SD), CP, epilepsy, special
ed (from earlier follow-up 17/118 with CP)
poor motor outcome (BSIDII - <-2SD), poor mental
outcome (BDID-II - <-2SD),
19
hyperreflexia, convulsions, and
myoclonic seizures")
ventilation, or Apgar score <5 at
5 min)
CP
Evidence of "asphyxia /
intrapartum insult"
Number of
term or near
term babies
with NE
N
survivors
assessed*
Case definition of
moderate-severe
impairment
Age of
impairment
assessment
(in years)
% of NE
survivors
with
moderatesevere
impairment
Sarnat
5 min Apgar <7; pH<7.1
15
11
CP - severe spastic
quadriparesis, seizures
1.5
9.1
N/A
Sarnat
---
70
33
1.0
24.2
1.5
57.1
17.0
34.9
1.5
15.0
1.6
15.0
1.5
54.2
1.5
35.9
Author
Country
Median
study
year
% drop
out from
follow-up
Battin, M(75)
New
Zealand
1998
West, C(15)
New
Zealand
1998
Study Population
Referral/Tertiary Care
Hospital, National
Women's, New Zeal
Referral Hospital,
National Women's
Hospital database
Case definition / classification
of NE
15%
N/A
Sarnat
5 min Apgar<6, require
resuscitation, intubation
22
14
23%
Sarnat
5min Apgar <8
43
43
Severe neurologic
impairment
Major neurological disability
(CP, developmental
retardation, convulsive
disorder, deafness or
blindness)
Severe-mod (CP); mild
learning (ADHD, Autism
spec, DAMP, learning
problems- from B study)
Neuromotor disability
(spastic diplegia, dyskinetic
or hemiplegic CP)
Toh, V(57)
Singapor
e
1994
Referral tertiary care
hospital - Women's
Childrens Hospital
Singapore
Lindstrom,
K(76)
Sweden
1985
All births Sweden;
SMBR
Sweden
1988
All births Goteborg,
Sweden; Swedish
Medical Birth Register
1%
Fenichel
5min Apgar <7
75
75
Switzerla
nd
1981
NICU admissions Lausanne Switzerland
N/A
Mod Sarnat
1 min Apgar <5 or requiring
ventilation
23
22
1994
Referral/ Tertiary Care
Hospital, NICU
admissions - Children's
hospital Bern
Sarnat
abnormal fetal tracing,
meconium, low Apgar or umbil
pH, or need for CPR
38
24
2004
TOBY network (42
hosp- UK, Hung,
Sweden, Israel,
Finland)
N/A
Sarnat-mod-sev
Apgar <5 at 10 min, continued
need resuscitation, acidosis
9pH<7 base def >=16)
161
117
CP, mental retardation or
epilepsy
Glasgow Outcome Scale 24(persistent vegetative state
or severely disabled,
functionally dependent;
moderately disabled)
severe neuro dev disability:
MDI Bayley, score 3-5 on
Gross Motor Function
Classification,OR bilateral
cortical visual impairment,
no useful vision
1997
Referral/Tertiary Care
Hospital, Hammersmith
Hospital London
16%
Sarnat
80
53
CP
5.0
35.8
1994
District Health Authority,
Central England
95
severe motor disability with
definite signs of cerebral
palsy at 18 months
1.5
20.0
1
63.6
2.5
23.3
Thornberg,
E(20)
LippZwahlen,
AE(58)
Pfenninger,
J(51)
Azzopardi,
D(77)
Barnett,
AL(59)
Smith, J(21)
Eicher D(78)
Miller, S(60)
Switzerla
nd
UK
UK
UK
US
US
1999
1997
N/A
N/A
17%
University Teaching
Hospital, UCSF - NICU
admissions
N/A
Levene
Neuro findings of
hypoxia/ischemia: require 2:
posturing, seizure, autonomic
dysfunction, tone, reflexes or
state of consciousness
Encephalopathy score: based on
Sarnat, addition of feeding sign
by Nelson
1 min Apgar <5
"infants with encephalopathy
clearly attributable to a cause
other than asphyxia were
excluded"
pH<7, base def >=13, Apgar <5
at10 min, continuous
resuscitation, fetal Brady lasting
15 min, hypoxic event post natal
desat <70 for 20 min
5min Apgar <5, umbilical
pH<7.1, or base def>10
48
33
11
68
60
> 2 SD off Bayley MDI or
PDI, CAT/CLAMS or
Vineland at 12 months
MDI <70 (2SD), NMS >=3
(spastic hemipleg, tri or
quadriplegia)
20
Author
Shankaran,
S(79)
Country
US
Median
study
year
Study Population
2002
NICHD network
1986
Tertiary care/University
hospital, Maternity
hospital, Brisbane
% drop
out from
follow-up
Case definition / classification
of NE
12%
moderate or severe
encephalopathy, with severe
acidosis or resuscitation at birth
after an acute perinatal event
Evidence of "asphyxia /
intrapartum insult"
Number of
term or near
term babies
with NE
N
survivors
assessed*
severe acidosis or resuscitation
at birth after an acute perinatal
event
93
52
Case definition of
moderate-severe
impairment
severe disability (IQ <-3SD,
GMFCS level IV or V,
bilateral blindness),
moderate (IQ score -3 - 2SD, GMFCS level III,
bilateral deafness or
refractory epilepsy), mild (IQ
score -2 - -1SD, or GMFCS
I or II)
Age of
impairment
assessment
(in years)
% of NE
survivors
with
moderatesevere
impairment
6-7
36.5
varying
47.1
1.6
30.1
1.0
41.9
2.0
44.0
0.5
18.8
1.5
40.8
2.5
5.6
NMR Level 2
Yeo, CL(80)
Australia
Finer, N(26)
Canada
1980
Low, JA(2)
Canada
1985
University hospital,
NICU - Royal Alexandra
Hospital
University hospital,
NICU - Queen's
Kingston Health
Science
1980
Referral/Tertiary Care
Hospital, NICU Toronto
Sick Kids
Muttit, S(61)
Canada
Wang, Y(81)
China
2009
Zhu, C(82)
China
2005
First Yulin Hospital,
Xi'an
Referral/Tertiary Care
Hospital- Children's
Hospital
Lam, B(28)
ChinaHong
Kong
1986
Tertiary care/University
hospital, NICU Queen
Mary Hospital HK
Sarnat
intrapartum stillbirth; 1 min
Apgar 0
35
17
6%
Sarnat
Intrapartum distress, neonatal
distress, 5min Apgar <5, need
for resuscitation, ventilation
95
83
Mod-Severe (spastic
quadriplegia, epilepsy,
severe visual or hearing
handicap)
Moderate handicap:
epilepsy, hearing /visual
impairment, spastic
diplegia, hemiplegia; Severe
spastic quad, severe
psychomotor, neurosen
deafness or blindness
N/A
Low
---
42
86
Significant motor and
cognitive deficit
N/A
Sarnat
5min Apgar<7, scalp pH<7, late
decerebration or meconium
36
25
9%
clinical grading criteria for
neonatal HIE established by
Neonatal Group of Chinese
Pediatric Society
---
35
32
3%
Sarnat
5min Apgar <6; resuscitation
153
76
N/A
Amiel-Tison
1 min Apgar <3,
26
36
11%
spastic quadriparesis and
mental retardation
Child Development Center
of China physical and
mental tests, PDI<70, MDI
<70 (<70 abnormal, 70-90
doubtful >90 normal)
MDI<70 or CP
Mod-Severe handicapsevere behavioral disorder
or convulsive disorder with
mild moderate
neurosensory deafness,
spastic diple/hemiplegia or
visual impairment; spastic
quadriplegia, severe
psychomotor retardation,
severe neurosensory
deafness or blindness
21
Author
Country
Median
study
year
Study Population
McShane,
M(29)
Ireland
1983
Prechtl
HF(83)
Italy
1988
Referral/ Tertiary Care
Hospital - Royal
Maternity Hospital
Referral/Tertiary Care
Hospitals; Modena or
Pisa
1994
Referral/Tertiary Care
Hospital, NICU
Belgrade
Cerovac,
N(84)
NMR Level 3
Serbia
Zhou, W(85)
China
2004
George,
B(86)
India
After
1990
12 children's hospitals /
children's and women's
health care centers
Child development
Center, tertiary care
hospital
Ellis, M(6)
Nepal
1995
Maternity Hospital,
Katmandu
Thompson,
CM(8)
South
Africa
1997
Referral hospital, NICU;
Groote Schur Hospital
Referral/Tertiary Care
Mwakyusa,
Hospital, Muhimbili
SD(45)
Tanzania
2002
National Hospital
Referral hospital,
University; Dr Sami
Hallioglu,
Ulus Children's
O(52)
Turkey
1995
Hospital, Ankara
*excludes post-neonatal mortality for those that reported
**unadjusted for severity
Age of
impairment
assessment
(in years)
% of NE
survivors
with
moderatesevere
impairment
1.0
30.0
2.0
50.0
7.0
8.7
Case definition / classification
of NE
Evidence of "asphyxia /
intrapartum insult"
Number of
term or near
term babies
with NE
N/A
Sarnat
5min Apgar <5; fetal distress
(meconium or pH<7.2);
intubation during resuscitation
60
50
N/A
Levene
Fetal distress, pH <7.1, low
Apgar, need for resuscitation
26
26
N/A
Encephalopathy sign in first 48hr
- abnormal tone, suck, reflexes,
consciousness, seizure
1) low Apgar, acidosis; 2) fetal
distress
103
103
CP or mental retardation
severe cerebral palsy,
spastic diparesis, spastic
hemiparesis, dykinetic
cerebral palsy
19%
Sarnat
Apgar score <=3 at 1 minute
and <=5 at 5 min, cord blood
gas pH<7.0 or base deficit <=16
mmol/L, and need for
resuscitation or ventilation at 5
min of age
94
67
GMFCS level 3-5, DQ <70
1.5
28.4
N/A
"hypoxic ischemic
encephalopathy"
---
48
48
12
12.5
22%
Ellis: mod Fenichel, signs
starting 6-24h
---
131
57
1.0
31.6
11%
Sarnat
---
40
36
Mod-Severe (IQ<70)
Major: functional disability
or mental DI<55,
psychomotor DI<55 Bayley;
Minor: neurodev impairment
without functional disability
and MDI 55-83 or PDI 5583.
Development quotient < 70
or clinical evidence of
cerebral palsy
1.0
33.3
21%
Sarnat, HIE score
5min Apgar <7
140
82
Abnormal tone, convulsions,
developmental delay, CP
0.5
29.0
Sarnat
5min Apgar<3, acidosis,
delayed respiration, mechanical
ventilation
57
34
Major neurologic deficit (CP
or epilepsy)
0.5
20.6
% drop
out from
follow-up
18%
N
survivors
assessed*
Case definition of
moderate-severe
impairment
Adverse outcome: death,
CP, developmental delay,
seizures, visual or heading
loss
22
Web appendix 8b. Included studies of mild impairment among NE cases
Author
NMR Level 1
Ferrari, F(55)
Van Kooij,
B(74)
Country
Italy
Netherlands
Median year
of data
collection
Study Population
2005
University Hospital
of Modena
1995
Battin, M(75)
New Zealand
1998
Lindstrom,
K(76)
Sweden
1985
Azzopardi,
D(77)
UK
2004
Barnett, AL(59)
UK
1997
Eicher D(78)
Shankaran,
S(87)
US
US
1999
University Medical
Center Utrecht, level
3 NICU
Referral/Tertiary
Care Hospital,
National Women's,
New Zealand
All births Sweden;
SMBR
TOBY network (42
hosp- UK, Hung,
Sweden, Israel,
Finland)
Referral/Tertiary
Care Hospital,
Hammersmith
Hospital London
Not available
2002
NICHD network
1986
Tertiary
care/University
hospital, Maternity
hospital, Brisbane
% drop out
from followup
19%
27%
Case definition /
classification of NE
Sarnat
Sarnat
Evidence of "asphyxia /
intrapartum insult"
Apgar score <=5 at 1 minute
and <=7 at 5 minutes
meet at least 3 of following
(signs of fetal distress - late
decerebrations on fetal
monitoring or meconium
staining), Apgar score <7 at 5
min, arterial umbilical pH
<7.1, delay in onset of
spontaneous respiration,
multiorgan failure)
Number of
term or near
term babies
with NE
43
164
Case definition of
mild impairment
Age of
impairment
assessment
(in years)
% of NE
survivors
with mild
impairment
34
clumsiness and/or poor
balance but no
evidence of CP
2
12
86
IQ score between -1 to
-2 SD below norm; 21%
need for special
education
9-10
19
1.5
9
17.0
N
survivors
assessed*
15%
Sarnat
5 min Apgar <7; pH<7.1
15
11
23%
Sarnat
5min Apgar <8
43
43
Moderately impaired
mental development
score 71
learning disabilities,
problems with executive
functions, etc.
N/A
Sarnat-mod-sev
Apgar <5 at 10 min, continued
need resuscitation, acidosis
pH<7 base def >=16)
161
117
BSID-II (MDI, PMDI 7084)
1.5
47
11
(mental)/13
(psychomoto
r)
16%
Sarnat
Neuro findings of
hypoxia/ischemia:
require 2: posturing,
seizure, autonomic
dysfunction, tone,
reflexes or state of
consciousness
moderate or severe
encephalopathy, with
severe acidosis or
resuscitation at birth
after an acute
perinatal event
1 min Apgar <5
80
53
Touwen's neurological
score <33
5.0
17
pH<7, base def >=13, Apgar
<5 at10 min, continuous
resuscitation, fetal Brady
lasting 15 min, hypoxic event
post natal desat <70 for 20
min
33
11
1-2 SD abnormal
1
8
severe acidosis or
resuscitation at birth after an
acute perinatal event
93
52
MDI 70-84
6-7
20
17
Griffiths Scale 76-87,
mild cerebral palsy
(walking by 2 years of
age), or sensory
handicap
varying
6
17%
12%
NMR Level 2
Yeo, CL(80)
Australia
11%
Sarnat
intrapartum stillbirth; 1 min
Apgar 0
35
23
Author
Finer, N(26)
Country
Canada
Median year
of data
collection
Study Population
1980
University hospital,
NICU - Royal
Alexandra Hospital
Low, JA(2)
Canada
1985
Lam, B(28)
China-Hong
Kong
1986
University hospital,
NICU - Queen's
Kingston Health
Science
Tertiary
care/University
hospital, NICU
Queen Mary
Hospital HK
1994
Referral/Tertiary
Care Hospital, NICU
Belgrade
Cerovac, N(84)
Serbia
Case definition /
classification of NE
Evidence of "asphyxia /
intrapartum insult"
Number of
term or near
term babies
with NE
6%
Sarnat
Intrapartum distress, neonatal
distress, 5min Apgar <5, need
for resuscitation, ventilation
95
83
N/A
Low
---
42
86
Case definition of
mild impairment
variations from normal
on neurologic or
developmental
examination without a
specific diagnosis
Suspicious neurological
examination and/or
borderline physical
development index
(motor) or borderline
mental development
index and/or abnormal
Uzgiris and Hunt scale
(cognitive)
N/A
Amiel-Tison
Encephalopathy signs
in first 48hr abnormal tone, suck,
reflexes,
consciousness,
seizure
1 min Apgar <3,
26
36
Mild handicap
2.5
14
7.0
7
% drop out
from followup
N/A
N
survivors
assessed*
Age of
impairment
assessment
(in years)
% of NE
survivors
with mild
impairment
1.6
17
1.0
58
1) low Apgar, acidosis; 2) fetal
distress
103
103
Mild neurologic signs
(behavioral
disturbances,
clumsiness, hypotonia)
Apgar score <=3 at 1 minute
and <=5 at 5 min, cord blood
gas pH<7.0 or base deficit
<=16 mmol/L, and need for
resuscitation or ventilation at
5 min of age
94
67
DQ 70-84
1.5
27
48
48
IQ 70-89
Neurodevelopmental/se
nsory impairment(s) not
resulting in functional
disability and/or a
mental developmental
index 55-83 or a
psychomotor
developmental index
55-83 on Bayley testing
Hypotonic with motor
delay but functioning
normally in all other
areas
1
56
1.0
7
1.0
3
NMR Level 3
Zhou, W(85)
China
2004
George, B(86,
88)
India
After 1990
12 children's
hospitals / children's
and women's health
care centers
Child development
Center, tertiary care
hospital
Ellis, M(6)
Nepal
1995
Maternity Hospital,
Katmandu
Referral hospital,
Thompson,
NICU; Groote Schur
CM(8)
South Africa
1997
Hospital
*excludes post-neonatal mortality for those that reported
**unadjusted for severity
19%
Sarnat
N/A
"hypoxic ischemic
encephalopathy"
22%
Ellis: mod Fenichel,
signs starting 6-24h
---
131
57
11%
Sarnat
---
40
36
24
25
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