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Intrapartum fetal asphyxia: A preliminary report in regard to long-term morbidity
Intrapartum fetal asphyxia: A preliminary report in regard to long-term morbidity J.
A.
LOW
R.
S. GALBRAITH
D.
MUIR
H.
KILLEN
J.
KARCHMAR
D.
CAMPBELL
Kingston, Ontario,
Canada
This is a preliminary report of a prospectii follow-up study of 42 infants who had @odes of intrapartum fatal asphyxia at delivery idantfffed by an a&-baaa BsLIBL)8ment and a control group of 69 babiis who had no evidence of intrapartum fetal a@!yxfa. The newborn infants wera mature at delii. There wera no major neuro@& diaabf gfuup.Thapatternofphysicalgrowthaitqfthamentafandf3hyaW thebabiesof~asphyriag~weresknUarto~oft)reconffdgrsupbaMesat12 months of age. Resufts have not as yet indica&d that the mature fetus with at least a terminal episode of asphyxia will exhii evidance of handicap due to central nervous system injury. (AM. J. OESTET. GYNECOL. 130: 525, 1978.)
. REVIEWS OF PERINATAL DEATHS with postmortem examinations have established the relationship between fetal asphyxia and perinatal death.‘, 2 Since the description by Clifford,3 many neuropathologists have identified the significance of perinatal asphyxia to central nervous system (CNS) injury in children who survive the perinatal period.*-‘* The pathogenesis of this CNS injury by fetal asphyxia has been demonstrated experimentally in animal studies, particularly in the fetal monkey.*2-‘” It has been difficult to establish the incidence of cerebral edema and injury in relation to fetal asphyxia in the surviving newborn infant. Studies of neonates witl. clinical evidence of severe perinatal asphyxial insults have shown the majority to have neonatal symptoms with residual disability that is due in some cases to injurv to the CNS.“-19 In the collaborative studies some
From the Departments of Obstetrics and Gynaecology Psychology, Queen’s University at Kingston.
and
Supported b research grants from the Ontario Mental Health Foundation and the Ontario Sociely for Crippled Children. Presented at tk Thirpthird Annual Meeting of the Society of Obstetricial?s and Gynaecologiits of Canada, Montreal, Quebec, Canada, June 14-18, 1977. Reprint requesti: Dr. J. A. Low, Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7. 000%9378/78/05130-0525$00.90/O
0
1978
The C. V. Mosby
Co.
newborn infants with clinical fetal distress and low five-minute Apgar scores had neurologic deficits at 1 year of age, but in subsequent follow-up at 4 years of age did not demonstrate major neurologic or mental impairment.20-21 There have been several problems in clinical followup studies. The diagnosis of fetal asphyxia has been retrospective based on clinical evidence of perinatal depression and subsequent neonatal compiicauons. The diagnosis of cerebral injury is difficult to establish due to the nonspecific reaction of the newborn infant to illness, and there are examples of sudden death in neonates with no cerebral symptoms but with evidence of unexpected cerebral injury on postmortem exztmination.” Major neurologic sequelae are easily identified. However, the more precise measure of mental retardation, disorders of abstract reasoning and behavior, and of visual and auditory impairment that may have resulted from perinatal asphyxial injury to the CNS remains a difficult problem. The present study has endeavored to recognize the problem of diagnosis of fetal asphyxia and is a prospective follow-up study of 111 newborn infants in whom the occurrence or absence of an episode of intrapartum fetal asphyxia was established by an acidbase assessment at delivery. This preliminary report includes the characteristics of the obstetric patients, 525
526
Low
et al.
March 1, 1978 Am. J. Obstet. Gynecol.
U.A.B.6
3
34
, 35
, 36
, 31
, 36
, 36
GESTATIONAL
, 40 AGE
,
(
,
,
41
42
43
44
IN WEEKS
Fig. 1. The present
study includes 69 newborn control infants in whom the umbilical artery buffer base at delivery was greater than 36.1 mEq. per liter and 42 newborn infants in whom the umbilical artery buffer base at delivery was less than 34.0 mEq. per liter representing the asphyxia group.
their pregnancies, and the newborn infants and the subsequent assessment in the babies of physical growth, neurologic characteristics, and mental and physical development at 3, 6, and- 12 months of age’.
The newborn infants in the present study were born of obstetric patients admitted to and managed in the perinatal intensive care unit of the Queen’s and Kingston health science complex. With two exceptions the newborn infants were mature at delivery-that is, 2 37 weeks of gestationai age. Acid-base assessments at delivery included fetal umbilical vein and artery blood acid-base, lactate, and pyrudate characteristics. Definition of the control and asphyxia groups was based upon a study previously reported from this unit in which the mean umbilical artery buffer base in the mature fetus of a normal obstetric patient was 41.2 k.2.5 mEq. per liter.23 The control group included 69 newborn infants, above the 25th percentile by weight for gestational age, in whom the’umbilical artery buffer base at delivery was greater than two standard deviations below the normal mean, i.e., >36.i‘ mEq. per liter. The asphyxia group included 42 newborn mfants, above the 10th percentile by’weight for gestational age, in whom the umbilical
artery buffer base at delivery was less than the range in the normal study, i.e., ~34.0 mEq. per liter (Fig. 1). Data in respect to the obstetric patients, their pregnancies, and the newborn infants were obtained from the medical records and, where necessary, by personal interview while the patient was hospitalized. The maternal characteristics included in this report are age at delivery, height, prepregnancy weight and weight gain during pregnancy, and smoking habits. Maternal medical complications associated with the current pregnancy included hypertension, chronic renal disease, cardiac disease, anemia, diabetes, and endocrine disorders. Socioeconomic indices recorded include the number of years of education, Canadian or non-Canadian nationality, and race of each parent. The Blishen score was derived from the father’s occupation and socioeconomic status.24 The family characteristics included annual income and the numbers of bedrooms and residents in the home. The features of the maternal obstetric history include maternal parity, the number of previous perinatal
deaths,
retarded anomalies. pregnancy
IUGR infants, and previous congenital Obstetric complications of the present include antepartum hemorrhage in the first
previous
intrauterine
growth-
Volume Number
lntrapartum fetal asphyxia
130 5
Table I. The maternal characteristics of the control and asphyxia groups
and socioeconomic
indices
of the parents -
Control group Total no. of observations Maternal Age
Mean
S.D.
26.5 163.1 61.6 12.2
5.8 6.0 14.3 6.1
13.1
2.9
AsPhe srmP No.
%
Total no. of observations
Mean
S.D.
25.7 160.9 61.3 Il.5
5.3 6.7 14.0 4.9
12.1
3.0
No.
%
P value.5
charactnistics:
69
Height Weight Weight gain Smoking Education Canadian Caucasian
Maternal
527
mdical
64 66 68 58 6% 69 69
66 64
96 93
42 40 40 37 23 42 40 40
13
19
39
17
29
x
35
40 37
100 92
4
10
comjkzticmr:
Hypertension-r&al disease Diabetes-endocrinoDa,athies Anemia Socioeconomic indices: Blishen score Family income Home-residents Home-bedrooms
69
63 33 50 48
46 15.2 3.5 2.7
17 7 0.9 0.9
and second halves of pregnancy, the latter including abnormal bleeding due to placenta previa, premature placental separation, or an unknown cause. Toxemia was defined as a systolic blood pressure of greater than 140 mm. Hg or a rise of 30 mm. Hg and a diastolic pressure of greater than 90 mm. Hg or a rise of 20 mm. Hg, with or without significant proteinurea. Multiple pregnancies were recorded. The labor and delivery characteristics include (1) the duration of labor defined as the time in hours from the onset of continuous contractions to delivery and (2) the method of delivery. The fetal characteristics established at delivery include maturity and sex. The gestational age was derived from the first day of the last menstrual period. The maternal urinary estrogen index was calculated from three or more 24 hour urinary estrogen estimations, the last determined within two weeks of delivery. A percentage was calculated for each estimation in relation to the normal mean for the appropriate week of gestational age; the “estrogen index” is the averaged percentages. An acid-base assessment was carried out on the blood of the umbilical vein and artery at delivery. The umbilical artery buffer base provided a measure of the .presence or absence of a metabolic acidosis due to an episode of intrapartum fetal asphyxia.25 The newborn characteristics include the following physical measures: birth weight and weight percentile according to the weight/gestational age scale of Gruenwaid,26 crown-heel length at birth, head and chest circumference, and the corresponding per-
35 20 30 30
42 10.8 4.1 2.8
16 4 1.7 0.7
centiles according to Lubchenko and colleagues.27 A weight-length ratio was calculated and the maximum per cent of weight loss was derived from the lowest weight during the subsequent nursery course. Measures of neonatal morbidity include Apgar scores at one and five minutes, hypothermia defined as a body temperature of less than 36” C., hypoglycemia defined as a blood sugar level of less than 30 mg. per 100 ml., and hyperbilirubinemia defined as requiring phototherapy or an exchange transfusion. Respiratory complications include any significant indrawing, grunt, retraction, or tachypnea requiring increased surveillance or oxygen therapy. CNS complications include any symptoms such as seizure or abnormalities of tone, consciousness, activity, or reflexes. Behavioral studies in the neonatal period include measures of activity, visual fixation and pursuit, and sleep patterns. General motor activity was measured with a modified self-winding calendar watch, an actometer.2* Activity is expressed in arbitrary units per hour. Visual activity was recorded by a trained observer. Visual fixation in response to pattern stimuli was scored on a four-point scale and visual pursuit to the same stimuli was scored on a three-point scale. The sleep pattern was similarly recorded by a trained observer and the sleep states that were described included active or rapid eye movement (REM) sleep, transitional sleep, and quiet sleep. Follow-up observations were recorded at 3,6, and 12 months of age. The numbers of observations at 3 and 6 months of age were less than the number at 12 months
Low et al.
528
March 1, 1978 Am. J. Obstet. Gynecol.
Table II. The characteristics fetal characteristics
of previous pregnancies and the obstetric complications of the present pregnancy in the control and asphyxia group Control Total no. observ&‘ons
Parit
ri
grmLp
AsPhrxdagrv@
of Mean
and labor and
S.D.
No.
%
43 26
62 38
6 3 1
23 11 4
11
Total no. obseruatim
of Mean
S.D.
NO.
%
28 14
67 33
2 4 1
14 29 7
16 9
4
10
2: 2
29 3
; 2
1; 5
37 32
54 46
25 17
60 40
P values
: ii
69
Past obstetric complic&‘m:
26
14
Perinatal death IUGR* fetus Congenital anomaly Obstetric
complications:
Antepartum hemorrhage Antepartum hemorrhage Toxemia Multiple pregnancy
42
69
42
<20 weeks >20 weeks
Fetal characteristics:
Gestational age at delivery
69
40.4
1.5
Male Female
Estrogen index Umbilical artery buffer base L&r
and delivery
93
69
39.9
30 2.0
60
11.4
8.2
40.4
2.2
9 42
91 31.1
34 3.0
29 42
9.9
7.3
characteristics:
Duration of labor Abdominal delivery-mid forceps Abdominal delivery-breech Abdominal delivery-cesarean section *Intrauterine
47
42
69
19
27
3
4
16 6
38 14
13
19
14
33
growth retarded.
because this part of the protocol was added when the study had been in progress for one year. The measures of physical growth, including weight, height, and head and chest circumference, were obtained at each visit with a detailed physical examination at 3 and 12 months of age. The Drillien test of tone was carried out at 3 months of age with a detailed neurologic examination at 12 months. Tone was assessed by passive movement of the limbs. Active movement was assessed by the symmetry and amount of movement, complex movement by the precision with which small objects were manipulated, and involuntary movement by the presence of tremors of choreiform movements. The deep tendon reflexes and superficial abdominal reflexes were tested. The cranial nerves tested were the second by vision; third, fourth, and sixth by eye movements; seventh by facial symmetry and movement; eighth by hearing; and ninth and tenth by the gag reflex. The Bayley test of mental and physical development and behavioral characteristics2g *vas carried out in the home at 6 months of age and in the clinic at 12 months. Results The maternal characteristics and socioeconomic indices of the parents of the control and asphyxia groups are outlined in Table I. The maternal characteristics of
the patients in the asphyxia group were similar to those of patients in the control group. There was no difference in the frequency of major medical complications in patients of the two groups. The socioeconomic indices were similar in the two groups with the exception of a lower family income in the asphyxia group. The characteristics of previous pregnancies and the obstetric complications and labor and fetal characteristics of the present pregnancy of the control and asphyxia groups are outlined in Table II. The parameters of parity and of incidence of complications in the past obstetric history and the present pregnancy were similar in the asphyxia and control groups. The fetal sex and gestational age at delivery were the same in the two groups. The low umbilical artery buffer base in the asphyxia group reflects the metabolic acidosis due to the fetal asphyxia. The increased frequency of abnormal delivery in both groups reilects the selection of patients admitted to and managed in the perinatal intensive care unit, with a greater incidence in the asphyxia group because of intervention due to the diagnosis of intrapartum fetal asphyxia. The characteristics of the newborn infants and the subsequent neonatal complications in the control and asphyxia groups are outlined in Table III. The physical measures in the newborn infants of the asphyxia and control groups are similar for weight, height, and head
Volume Number
lntrapartum fetal asphyxia
130 5
529
Table III. The characteristicsof the newborn infants and the subsequentneonatal complications in the control and asphyxia groups Control Total no. of observations Newborn characteristics: Weight: Height: Head
69
Gm. % cm. % cm.
circumference:
69 69
% Chest circumference (cm.) Weight-length ratio < 10 Neon& comp~catim: Apgar score 1 min. Apgar score 5 min. Resuscitation-IPPV * Hypothermia Hypoglycemia Hyperbilirubinemia Respiratory complications CNS complications *Intermittent
positive
68
AsphyJdagrmP
gnmp
Mean
S.D.
3,496 63 52.8 81 35.2 73 33.8
460 22 2.8 18 1.2 24
No.
42 42 42
1.8
69
15
69
7.8
25 63 67
9.2
41 40
22
1.9
Mean
S.D.
3,424 61 51.6 82 35.1 71 33.4
535 28 5.1
0.7
4 3 1 1 2 I
8
6 5 12 2 3 1
No.
5.5 8.1
P value
%
18 1.6 24 2.1
19
42
67 67 68
pressure
Total no. of obsewatiuns
%
37
2.8 1.8
co.01
92; 42 24 42 42 42
12
5 5 1 5 4
31 12 21
co.01
3 12
9
ventilation.
Table IV. The assessment of neonatal behavior of the newborn infants of the control and asphyxia groups* Control Total no. of obsenmtions Activity score Visual fixation Visual pursuit sleep: Rapid eye movements Quiet Transitional *There
were
group
Mean
37 37 31 37
0.71 4.81 8.32 27.2 13.4 17.7
no significant
Bayley
scores in
in
Table
S.D. 0.37 1.9 3.7 9.6 6.4 6.3
Totnl no. of observations 20 21 19 23
grag MeaTI
S.D.
0.64 4.76 8.05
0.23 1.7 3.5
26.2 12.6 19.3
8.6 5.9 4.9
p values.
and chest circumference. As compared to the control group the newborn infants of the asphyxia group had lower Apgar scoresat one and five minutes with an increased requirement for resuscitation with intermittent positive pressure ventilation. The incidence of subsequent neonatal complications in the asphyxia group was similar to that in the control group. The assessment of behavior of the newborn infants of the control and asphyxia groups is summarized in Table IV. The newborn infants of the asphyxia and control groups exhibited no differences in activity scores,visual fixation and pursuit scores,or sleep patterns. The follow-up observationsin the babiesof the control and asphyxia groups at 3, 6, and 12 months of age are outlined in respect to measuresof physical growth in Table V, neurologic examination in Table VI, and served
AsPIspdo
VII.
No
differences
were
ob-
the babies of the asphyxia and control
groups. The measuresof physical growth at 3, 6, and 12 months of age, the neurologic findings at 12 months, and the Bayley scoresat 6 and 12 months are similar in the two groups.
Comments In both groups the mothers and their pregnancies are comparable in respect to maternal characteristics, past obstetric history, and obstetric, labor, and delivery complications in the present pregnancy. The only difference in respect to the socioeconomicindices was a lower income in the asphyxia group. In the two groups the fetuses at delivery were of similar gestational age, 40 weeks,and were comparablein respect to the physical measuresof weight, height, and head and chest circumference. The newborn infants were, with two exceptions, mature and did not have intrauterine growth retardation or major congenital anomalies.
530
Low et al.
March 1, 1978 Am. J. Obstet. Gynecol.
Table V. The measures of physical at 3, 6, and 12 months of age
growth
3 Total no. of obseruations Weight
mo.
and asphyxia
groups
6 mo.
Mean
S.D.
36 27
6.3 6.2
0.7
36 28
61.8 61.3
2.9
41.3
1.1
41.3 41.8 41.1
Total no. of obseruations
Mean
12 Total no. of observations
S.D.
mo. Mean
S.D.
9.9 9.7
0.9 1.0
(Cm.):
Control Asphyxia Height
35 24
8.1
0.9
8.2
0.9
50 30
38 23
66.3
66.1
2.5 2.3
50 30
1.3
38 24
43.6 44.0
1.3 1.4
2.0 1.9
38 24
44.3 45.0
2.2
0.9
(cm.)
Control Asphyxia Head
in the babies of the control
circumference
(cm.):
Control Asphyxia Chest circumference
3.0
(cm.):
Control Asphyxia
36 26
Table VI. The results of neurologic
examination and asphyxia groups
of the of the babies control at 12 months of age
1.9
75.9
2.4
75.5
2.9
zx
46.4 46.3
1.5
49 30
47.9 47.6
2.0 2.3
Table VII. The Bayley scores in the infants the control and asphyxia groups at 6 and 12 months of age* Control
group
1.3
of
Asphyxia
grmq
No.
Mean
S.D.
No.
Mean
S.D.
39
114.8
19.3
24
111.6
14.3
38
109.2
19.1
23
111.3
17.1
49
108.9
16.0
31
108.1
13.5
49
100.8
19.0
1 6 ma:
Tone Movement:
48 49
30 30
0
Active Complex Involuntary
5
46 40 47
1
12 mix: 3
0
0 0 3
0 0
10
0
Rejlexes:
Deep Superficial Cranial nerves
0
Mental development index Physicaldevelopment index
28 6
z:,
0 0 0
The significant variable in the babies of the asphyxia group was an episode of intrapartum fetal asphyxia demonstrated by the presence of a metabolic acidosis at delivery. The severity of the asphyxia and the metabolic acidosis at delivery approached the critical levels observed in animal studies. However, information is incomplete in regard to the duration and pattern of development of the asphyxial episode. The importance of the duration of the asphyxia leading to the CNS injury in relation to survival has been emphasized in the fetal monkey studies in which severe asphyxia lasting 30 minutes to several hours was required to produce a critical level of brain damage.13* I59 I6 The newborn infants of the asphyxia group exhibited the characteristic low Apgar scores at one and five minutes with the increased requirement for resuscitation with intermittent positive pressure ventilation. Subsequently, during the neonatal period, these infants did not exhibit the neurologic signs of abnor-
Mental development index Physicaldevelopment index *There
98.2
13.5
were no significant p values.
mahties of tone, consciousness, or respiration or the seizures that are presently recognized as indicators of perinatal asphyxial encephalopathy.m-33 During the first year of life the babies of the asphyxia group demonstrate a pattern of physical growth as measured by weight, height, and head and chest circumference that is identical to that of babies of the control group (Fig. 2). There was no evidence of major neurologic disability in the babies of the asphyxia group at 1 year of age. It is recognized that in the older child further assessment is necessary to permit more discriminating neurologic examination and to identify impairments of vision and hearing and disorders of abstract reasoning. Finally, the mental and physical development indices of the Bayley score at 6 and 12 months of age in the babies of the asphyxia group were identical to those for the babies of the control group (Fig. 3). The cycle of events in response to fetal partial as-
Volume
130
Number
5
lntrapartum
fetal
9S?6-
Kgm
543-
HEIGHT
WEIGHT I DEUV.
401 3MON.
12 MON.
6MoH
D2UV
3MCW
6MON.
I2 MIN
Cm 40-
35-
HEAD CIRCUMFERENCE
CIRCUMFERENCE
30-
30I I DELIV. 311011 311011 WON. WON. DELIV. control
Group
-
Aaphyrio
1 12 uo1. Group ----
DELIV
SMON
I 6MON.
1 12 MON MON.
Fig. 4. The patterns of physical growth as measured by weight, height, and head ference in the babies of the control and asphyxia groups at 3, 6, and 12, months
SIX
MENTAL Control
MONTttS
TWELVE
uorms
DEVELOPMENT Group 0
Fig. 3. The mental and physical at 6 and 12 months of age.
91x
INDEX
MoNTltS
PHYSICAL
TWELVE
DEVELOPMENT
and chest of age.
circum-
MONTH6
INDEX
Asphyxia Group m development
indices
in the babies of the control
and asphyxia
groups
asphyxia
531
March 1, 1978 Am. J. Obstet. Gynecol.
this
stress
phyxial
is schematically episodes
while
at the
which
of
resolution
sidual
episode The
of intrapartum growth
phyxia of
is a vicious
blood
related
flow
and
upon
of
of brain
finally
to the duration
characteristics effects
one
the
the fetus
swelling
to cerebral and
severity
stressed and
fetus.
newborn
leading necrosis.
of asphyxia The infant
to stasis
fetal during
pattern
and
with
ability
asphyxia
in the group.
tinued
until
the similar
no evidence of
these
the
school
into
recognized
handicap.
establish
mental
the However,
suggest
that
the
asphyxia
experienced
fetuses
was
not
as severe
as the
of to
ing
REFERENCES 1. Butler, N. R., and Bonham, D. G.: The First Report of the British Perinatal Mortality Survey, Edinburg, 1963, E. & S. Livingstone, Ltd. 2. Low, J. A., Boston, R. W., and Crussi, F. G.: Classification of perinatal mortality, Can. Med. Assoc. J. 105: 1044, 1971. 3. Clifford, S. H.: The effects of asphyxia in the newborn infant, J. Pediatr. 18: 567, 1941. 4. Malamud, N.: Pattern of C.N.S. vulnerability in neonatal hypoxemia, in Schade, J. P., and McMenemey, W. H., editors: Selective Vulnerability of the Brain in Hypoxemia, Philadelphia, 1963, F. A. Davis Company, p. 211. 5. Freytagh, E., and Lindenberg, R.: Neuropathological findings in patients of a hospital for the mentally deficient: A study of 359 cases, Johns Hopkins Med. J. 121: 379, 1967. 6. Banker, B. Q.: The neuropathological effects of anoxia and hypoglycemia in the newborn, Dev. Med. Child Neurol. 9: 544, 1967. 7. Terplan, K. L.: Histopathologic brain changes in 1152 cases of the perinatal and early infancy , period, Biol. _ Neonate 11: g48, 1967. 8. Norman. R. M.: Late neuropathological sequelae of brain injury, in Greenfield’s NeuropatbGlogy, London, 1969, Edward Arnold (Publishers) Ltd., p. 304. 9. Towbin, A.: Central nervous system damage in the human fetus and newborn infant: Mechanical and hypoxic injury incurred in the fetal-neonatal period, Am. J. Dis. Child. 119: 259, 1970. 10. Griffiths, A. D., and Lawrence, K. M.: The effect of hypoxia and hypoglycemia on the brain of the newborn infant, Dev. Med. Child Neurol. 16: 308, 1974. 11. Urich, H.: Malformations of the nervous system,
12.
13.
14.
15.
16.
17.
18. 19. 20.
21.
system
injury
and
residual
critical disability
dis-
to the will
con-
be conthis
initial
of an as yet
the results
at this
by these level
a
physical
neurologic
to confirm
presence
suggest
and
children
is
sequence
re-
to delivery.
year
as compared
Follow-up or
in relation
with
of the asa terminal
prior
of major
group
entry
impression
CNS
edema
injury
first
and the
This
precise asphyxia,
in cerebral and
asphyxia
results
development trol of
perinatal
of
the mature newborn infants had experienced at least
follow-up
normal
asphyxia
result
edema
and
disability.
In this study phyxia group
of fetal
in
to a more
duration
will
cerebral
as-
injury,
severe
result
and
fetus
or
or
spectrum
relates
degree
4. Mild
edema
asphyxia
search
the
in Fig.
cerebral of the
of
present
in a particular
with
Fig. 4. The clinical CNS consequences increasing severity and duration.
end
episodes The
definition
no
opposite
prolonged death.
presented
cause
unstage
mature
leading
in the
to
surviv-
children.
perinatal damage, and related conditions in early life, in Greenfield’s Neuropathology, London, 1976, Edward Arnold (Publishers) Ltd., p. 422. Ranck, J. B., and Windle, W. F.: Brain damage in the monkey Macaca mu&a by asphyxia neonatorum, Exp. Neuroi. 1: 130, 1959. Windle. W. F.: Brain damage at birth. Functional and structural modifications wi& time, J. A. M. A. 206, 1967, 1968. Brown, A. W., and Brierley, J. B.: The nature and timecourse of anoxic-ischemic cell change in the rat brain. An optical electron microscopic study, in Brierley, J. B., and Meldrum, B. S., editors: Brain Hypoxia Clinics in Developmental Medicine No. 39-40, London, 1971, Spastics International Medical Publications, Heinemann Publishing Company, p. 49. Myers, R. W.: Two patterns of perinatal brain damage and their conditions of occurrence, AM. J. OBSTET. GYNECOL. 112: 246, 1972. Brann, A. W., Myers, R. E.: Central nervous system findings in the newborn monkey following severe in utero partiaiasphyxia, Neurology 2% 327, 1975. Brown. 1. K.. Purvis. R. 1.. Forfar. 1. 0.. and Cockbum, F.: Neu;olog& aspects Gf perinat’z asphyxia, Dev. Med. Child Neural. 16: 567, 1974. Steiner, H., and Neligan, G.: Perinatal cardiac arrest, quality of the survivors, Arch. Dis. Child. 50: 696, 1975. Scott, H.: Outcome of very severe birth asphyxia, Arch. Dis. Child. 51: 712, 1976. Drage, 1. S., Berendes, H. W., and Fischer, P. D.: The Ap& scores and four year psychological examination performance, in Perinatal Factors Affecting Human Development, Scientific Publication No. 185, Washington, D. C.. , 1969. Pan American Health Orwnization, p. 222. Berendes, H. W.: Fetal distress: Its si&ficance in neuro-
Volume Number
22.
23.
24.
25.
26.
lntrapartum fetal asphyxia
130
533
5
logical and mental impairment of childhood, in Perinatal Factors Affecting Human Development, Scientific Publication No. 185, Washington, D. C., 1969, Pan American Health Organization, p. 228. Thorn, I.: Cerebral symptoms in the newborn. Diagnostic and prognostic significance of symptoms of presumed cerebral origin, Acta Paediatr. Stand. (Suppl.) 195: 11, 1969. Low, J. A.. Pancham, S. R., Worthington, D., and Boston, R. W.: Acid-base, lactate and pyruvate of the normal obstetric patient and fetus during the intrapartum period, AM. J. OBSTET. GYNECOL. 120: 862, 1974. Blishen, B. R., and McRoberts, H. A.: A revised socioeconomic index for occupations in Canada, Can. Rev, Social. Anthropol. 13: 71, 1976. Low, J. A., Pancham, S. R., Worthington, D., and Boston, R. W.: The acid-base and biochemical characteristics of intrapartum fetal asphyxia, AM. J, OBSTET. GYNECOL. 121: 446, 1975. Gruenwald. P.: Growth of the human fetus. I. Normal growth and its variation, AM. J. OBSTET. GYNECOL. 94: 1112. 1966.
27.
28.
29. 30. 31.
32.
33.
Lubchenko. L. O., Hansman. C., and lkessler. M.: lntrauterine growth as estimated from livca born birth weight data at 24 to 42 weeks of gesration. Pediatrics 32: 793, 1963. Campbell, D., Kuyek, J., Lang, E.. and Partington, M. W.: Motor activity in early life. II. Daily motor activity output in the neonatal period, Bioi. Neonate 18: 108, 1971. Bayley. N.: Bayley Scales of Infant Development, Neu York, 1969, Psychological Corp. Brown, J. K.: Convulsions in the neonatal period, Dev. Med. Child Neural. 15: 823, 1973. Volpe, J. J.: Neurologic disorders. tn Aver?. G. B., editor: Neonatology. Philadelphia. 1975. J. R. l,ippincott Company, p. 729 Sarnat. H. S., and Sarnat. M. S.: Neonatal encephalopathology following fetal distress, Arch. Neural. 33: 696. 1976. Brann, ‘4. M’., and Dykes, F. D.: The cfferts of intrauterine asphyxia on the full term neonate, Clin. Perinatol. 4: 149, 1977.
A.
LOW
R.
S. GALBRAITH
D.
MUIR
H.
KILLEN
J.
KARCHMAR
D.
CAMPBELL
Kingston, Ontario,
Canada
This is a preliminary report of a prospectii follow-up study of 42 infants who had @odes of intrapartum fatal asphyxia at delivery idantfffed by an a&-baaa BsLIBL)8ment and a control group of 69 babiis who had no evidence of intrapartum fetal a@!yxfa. The newborn infants wera mature at delii. There wera no major neuro@& diaabf gfuup.Thapatternofphysicalgrowthaitqfthamentafandf3hyaW thebabiesof~asphyriag~weresknUarto~oft)reconffdgrsupbaMesat12 months of age. Resufts have not as yet indica&d that the mature fetus with at least a terminal episode of asphyxia will exhii evidance of handicap due to central nervous system injury. (AM. J. OESTET. GYNECOL. 130: 525, 1978.)
. REVIEWS OF PERINATAL DEATHS with postmortem examinations have established the relationship between fetal asphyxia and perinatal death.‘, 2 Since the description by Clifford,3 many neuropathologists have identified the significance of perinatal asphyxia to central nervous system (CNS) injury in children who survive the perinatal period.*-‘* The pathogenesis of this CNS injury by fetal asphyxia has been demonstrated experimentally in animal studies, particularly in the fetal monkey.*2-‘” It has been difficult to establish the incidence of cerebral edema and injury in relation to fetal asphyxia in the surviving newborn infant. Studies of neonates witl. clinical evidence of severe perinatal asphyxial insults have shown the majority to have neonatal symptoms with residual disability that is due in some cases to injurv to the CNS.“-19 In the collaborative studies some
From the Departments of Obstetrics and Gynaecology Psychology, Queen’s University at Kingston.
and
Supported b research grants from the Ontario Mental Health Foundation and the Ontario Sociely for Crippled Children. Presented at tk Thirpthird Annual Meeting of the Society of Obstetricial?s and Gynaecologiits of Canada, Montreal, Quebec, Canada, June 14-18, 1977. Reprint requesti: Dr. J. A. Low, Kingston General Hospital, Kingston, Ontario, Canada K7L 2V7. 000%9378/78/05130-0525$00.90/O
0
1978
The C. V. Mosby
Co.
newborn infants with clinical fetal distress and low five-minute Apgar scores had neurologic deficits at 1 year of age, but in subsequent follow-up at 4 years of age did not demonstrate major neurologic or mental impairment.20-21 There have been several problems in clinical followup studies. The diagnosis of fetal asphyxia has been retrospective based on clinical evidence of perinatal depression and subsequent neonatal compiicauons. The diagnosis of cerebral injury is difficult to establish due to the nonspecific reaction of the newborn infant to illness, and there are examples of sudden death in neonates with no cerebral symptoms but with evidence of unexpected cerebral injury on postmortem exztmination.” Major neurologic sequelae are easily identified. However, the more precise measure of mental retardation, disorders of abstract reasoning and behavior, and of visual and auditory impairment that may have resulted from perinatal asphyxial injury to the CNS remains a difficult problem. The present study has endeavored to recognize the problem of diagnosis of fetal asphyxia and is a prospective follow-up study of 111 newborn infants in whom the occurrence or absence of an episode of intrapartum fetal asphyxia was established by an acidbase assessment at delivery. This preliminary report includes the characteristics of the obstetric patients, 525
526
Low
et al.
March 1, 1978 Am. J. Obstet. Gynecol.
U.A.B.6
3
34
, 35
, 36
, 31
, 36
, 36
GESTATIONAL
, 40 AGE
,
(
,
,
41
42
43
44
IN WEEKS
Fig. 1. The present
study includes 69 newborn control infants in whom the umbilical artery buffer base at delivery was greater than 36.1 mEq. per liter and 42 newborn infants in whom the umbilical artery buffer base at delivery was less than 34.0 mEq. per liter representing the asphyxia group.
their pregnancies, and the newborn infants and the subsequent assessment in the babies of physical growth, neurologic characteristics, and mental and physical development at 3, 6, and- 12 months of age’.
The newborn infants in the present study were born of obstetric patients admitted to and managed in the perinatal intensive care unit of the Queen’s and Kingston health science complex. With two exceptions the newborn infants were mature at delivery-that is, 2 37 weeks of gestationai age. Acid-base assessments at delivery included fetal umbilical vein and artery blood acid-base, lactate, and pyrudate characteristics. Definition of the control and asphyxia groups was based upon a study previously reported from this unit in which the mean umbilical artery buffer base in the mature fetus of a normal obstetric patient was 41.2 k.2.5 mEq. per liter.23 The control group included 69 newborn infants, above the 25th percentile by weight for gestational age, in whom the’umbilical artery buffer base at delivery was greater than two standard deviations below the normal mean, i.e., >36.i‘ mEq. per liter. The asphyxia group included 42 newborn mfants, above the 10th percentile by’weight for gestational age, in whom the umbilical
artery buffer base at delivery was less than the range in the normal study, i.e., ~34.0 mEq. per liter (Fig. 1). Data in respect to the obstetric patients, their pregnancies, and the newborn infants were obtained from the medical records and, where necessary, by personal interview while the patient was hospitalized. The maternal characteristics included in this report are age at delivery, height, prepregnancy weight and weight gain during pregnancy, and smoking habits. Maternal medical complications associated with the current pregnancy included hypertension, chronic renal disease, cardiac disease, anemia, diabetes, and endocrine disorders. Socioeconomic indices recorded include the number of years of education, Canadian or non-Canadian nationality, and race of each parent. The Blishen score was derived from the father’s occupation and socioeconomic status.24 The family characteristics included annual income and the numbers of bedrooms and residents in the home. The features of the maternal obstetric history include maternal parity, the number of previous perinatal
deaths,
retarded anomalies. pregnancy
IUGR infants, and previous congenital Obstetric complications of the present include antepartum hemorrhage in the first
previous
intrauterine
growth-
Volume Number
lntrapartum fetal asphyxia
130 5
Table I. The maternal characteristics of the control and asphyxia groups
and socioeconomic
indices
of the parents -
Control group Total no. of observations Maternal Age
Mean
S.D.
26.5 163.1 61.6 12.2
5.8 6.0 14.3 6.1
13.1
2.9
AsPhe srmP No.
%
Total no. of observations
Mean
S.D.
25.7 160.9 61.3 Il.5
5.3 6.7 14.0 4.9
12.1
3.0
No.
%
P value.5
charactnistics:
69
Height Weight Weight gain Smoking Education Canadian Caucasian
Maternal
527
mdical
64 66 68 58 6% 69 69
66 64
96 93
42 40 40 37 23 42 40 40
13
19
39
17
29
x
35
40 37
100 92
4
10
comjkzticmr:
Hypertension-r&al disease Diabetes-endocrinoDa,athies Anemia Socioeconomic indices: Blishen score Family income Home-residents Home-bedrooms
69
63 33 50 48
46 15.2 3.5 2.7
17 7 0.9 0.9
and second halves of pregnancy, the latter including abnormal bleeding due to placenta previa, premature placental separation, or an unknown cause. Toxemia was defined as a systolic blood pressure of greater than 140 mm. Hg or a rise of 30 mm. Hg and a diastolic pressure of greater than 90 mm. Hg or a rise of 20 mm. Hg, with or without significant proteinurea. Multiple pregnancies were recorded. The labor and delivery characteristics include (1) the duration of labor defined as the time in hours from the onset of continuous contractions to delivery and (2) the method of delivery. The fetal characteristics established at delivery include maturity and sex. The gestational age was derived from the first day of the last menstrual period. The maternal urinary estrogen index was calculated from three or more 24 hour urinary estrogen estimations, the last determined within two weeks of delivery. A percentage was calculated for each estimation in relation to the normal mean for the appropriate week of gestational age; the “estrogen index” is the averaged percentages. An acid-base assessment was carried out on the blood of the umbilical vein and artery at delivery. The umbilical artery buffer base provided a measure of the .presence or absence of a metabolic acidosis due to an episode of intrapartum fetal asphyxia.25 The newborn characteristics include the following physical measures: birth weight and weight percentile according to the weight/gestational age scale of Gruenwaid,26 crown-heel length at birth, head and chest circumference, and the corresponding per-
35 20 30 30
42 10.8 4.1 2.8
16 4 1.7 0.7
centiles according to Lubchenko and colleagues.27 A weight-length ratio was calculated and the maximum per cent of weight loss was derived from the lowest weight during the subsequent nursery course. Measures of neonatal morbidity include Apgar scores at one and five minutes, hypothermia defined as a body temperature of less than 36” C., hypoglycemia defined as a blood sugar level of less than 30 mg. per 100 ml., and hyperbilirubinemia defined as requiring phototherapy or an exchange transfusion. Respiratory complications include any significant indrawing, grunt, retraction, or tachypnea requiring increased surveillance or oxygen therapy. CNS complications include any symptoms such as seizure or abnormalities of tone, consciousness, activity, or reflexes. Behavioral studies in the neonatal period include measures of activity, visual fixation and pursuit, and sleep patterns. General motor activity was measured with a modified self-winding calendar watch, an actometer.2* Activity is expressed in arbitrary units per hour. Visual activity was recorded by a trained observer. Visual fixation in response to pattern stimuli was scored on a four-point scale and visual pursuit to the same stimuli was scored on a three-point scale. The sleep pattern was similarly recorded by a trained observer and the sleep states that were described included active or rapid eye movement (REM) sleep, transitional sleep, and quiet sleep. Follow-up observations were recorded at 3,6, and 12 months of age. The numbers of observations at 3 and 6 months of age were less than the number at 12 months
Low et al.
528
March 1, 1978 Am. J. Obstet. Gynecol.
Table II. The characteristics fetal characteristics
of previous pregnancies and the obstetric complications of the present pregnancy in the control and asphyxia group Control Total no. observ&‘ons
Parit
ri
grmLp
AsPhrxdagrv@
of Mean
and labor and
S.D.
No.
%
43 26
62 38
6 3 1
23 11 4
11
Total no. obseruatim
of Mean
S.D.
NO.
%
28 14
67 33
2 4 1
14 29 7
16 9
4
10
2: 2
29 3
; 2
1; 5
37 32
54 46
25 17
60 40
P values
: ii
69
Past obstetric complic&‘m:
26
14
Perinatal death IUGR* fetus Congenital anomaly Obstetric
complications:
Antepartum hemorrhage Antepartum hemorrhage Toxemia Multiple pregnancy
42
69
42
<20 weeks >20 weeks
Fetal characteristics:
Gestational age at delivery
69
40.4
1.5
Male Female
Estrogen index Umbilical artery buffer base L&r
and delivery
93
69
39.9
30 2.0
60
11.4
8.2
40.4
2.2
9 42
91 31.1
34 3.0
29 42
9.9
7.3
characteristics:
Duration of labor Abdominal delivery-mid forceps Abdominal delivery-breech Abdominal delivery-cesarean section *Intrauterine
47
42
69
19
27
3
4
16 6
38 14
13
19
14
33
growth retarded.
because this part of the protocol was added when the study had been in progress for one year. The measures of physical growth, including weight, height, and head and chest circumference, were obtained at each visit with a detailed physical examination at 3 and 12 months of age. The Drillien test of tone was carried out at 3 months of age with a detailed neurologic examination at 12 months. Tone was assessed by passive movement of the limbs. Active movement was assessed by the symmetry and amount of movement, complex movement by the precision with which small objects were manipulated, and involuntary movement by the presence of tremors of choreiform movements. The deep tendon reflexes and superficial abdominal reflexes were tested. The cranial nerves tested were the second by vision; third, fourth, and sixth by eye movements; seventh by facial symmetry and movement; eighth by hearing; and ninth and tenth by the gag reflex. The Bayley test of mental and physical development and behavioral characteristics2g *vas carried out in the home at 6 months of age and in the clinic at 12 months. Results The maternal characteristics and socioeconomic indices of the parents of the control and asphyxia groups are outlined in Table I. The maternal characteristics of
the patients in the asphyxia group were similar to those of patients in the control group. There was no difference in the frequency of major medical complications in patients of the two groups. The socioeconomic indices were similar in the two groups with the exception of a lower family income in the asphyxia group. The characteristics of previous pregnancies and the obstetric complications and labor and fetal characteristics of the present pregnancy of the control and asphyxia groups are outlined in Table II. The parameters of parity and of incidence of complications in the past obstetric history and the present pregnancy were similar in the asphyxia and control groups. The fetal sex and gestational age at delivery were the same in the two groups. The low umbilical artery buffer base in the asphyxia group reflects the metabolic acidosis due to the fetal asphyxia. The increased frequency of abnormal delivery in both groups reilects the selection of patients admitted to and managed in the perinatal intensive care unit, with a greater incidence in the asphyxia group because of intervention due to the diagnosis of intrapartum fetal asphyxia. The characteristics of the newborn infants and the subsequent neonatal complications in the control and asphyxia groups are outlined in Table III. The physical measures in the newborn infants of the asphyxia and control groups are similar for weight, height, and head
Volume Number
lntrapartum fetal asphyxia
130 5
529
Table III. The characteristicsof the newborn infants and the subsequentneonatal complications in the control and asphyxia groups Control Total no. of observations Newborn characteristics: Weight: Height: Head
69
Gm. % cm. % cm.
circumference:
69 69
% Chest circumference (cm.) Weight-length ratio < 10 Neon& comp~catim: Apgar score 1 min. Apgar score 5 min. Resuscitation-IPPV * Hypothermia Hypoglycemia Hyperbilirubinemia Respiratory complications CNS complications *Intermittent
positive
68
AsphyJdagrmP
gnmp
Mean
S.D.
3,496 63 52.8 81 35.2 73 33.8
460 22 2.8 18 1.2 24
No.
42 42 42
1.8
69
15
69
7.8
25 63 67
9.2
41 40
22
1.9
Mean
S.D.
3,424 61 51.6 82 35.1 71 33.4
535 28 5.1
0.7
4 3 1 1 2 I
8
6 5 12 2 3 1
No.
5.5 8.1
P value
%
18 1.6 24 2.1
19
42
67 67 68
pressure
Total no. of obsewatiuns
%
37
2.8 1.8
co.01
92; 42 24 42 42 42
12
5 5 1 5 4
31 12 21
co.01
3 12
9
ventilation.
Table IV. The assessment of neonatal behavior of the newborn infants of the control and asphyxia groups* Control Total no. of obsenmtions Activity score Visual fixation Visual pursuit sleep: Rapid eye movements Quiet Transitional *There
were
group
Mean
37 37 31 37
0.71 4.81 8.32 27.2 13.4 17.7
no significant
Bayley
scores in
in
Table
S.D. 0.37 1.9 3.7 9.6 6.4 6.3
Totnl no. of observations 20 21 19 23
grag MeaTI
S.D.
0.64 4.76 8.05
0.23 1.7 3.5
26.2 12.6 19.3
8.6 5.9 4.9
p values.
and chest circumference. As compared to the control group the newborn infants of the asphyxia group had lower Apgar scoresat one and five minutes with an increased requirement for resuscitation with intermittent positive pressure ventilation. The incidence of subsequent neonatal complications in the asphyxia group was similar to that in the control group. The assessment of behavior of the newborn infants of the control and asphyxia groups is summarized in Table IV. The newborn infants of the asphyxia and control groups exhibited no differences in activity scores,visual fixation and pursuit scores,or sleep patterns. The follow-up observationsin the babiesof the control and asphyxia groups at 3, 6, and 12 months of age are outlined in respect to measuresof physical growth in Table V, neurologic examination in Table VI, and served
AsPIspdo
VII.
No
differences
were
ob-
the babies of the asphyxia and control
groups. The measuresof physical growth at 3, 6, and 12 months of age, the neurologic findings at 12 months, and the Bayley scoresat 6 and 12 months are similar in the two groups.
Comments In both groups the mothers and their pregnancies are comparable in respect to maternal characteristics, past obstetric history, and obstetric, labor, and delivery complications in the present pregnancy. The only difference in respect to the socioeconomicindices was a lower income in the asphyxia group. In the two groups the fetuses at delivery were of similar gestational age, 40 weeks,and were comparablein respect to the physical measuresof weight, height, and head and chest circumference. The newborn infants were, with two exceptions, mature and did not have intrauterine growth retardation or major congenital anomalies.
530
Low et al.
March 1, 1978 Am. J. Obstet. Gynecol.
Table V. The measures of physical at 3, 6, and 12 months of age
growth
3 Total no. of obseruations Weight
mo.
and asphyxia
groups
6 mo.
Mean
S.D.
36 27
6.3 6.2
0.7
36 28
61.8 61.3
2.9
41.3
1.1
41.3 41.8 41.1
Total no. of obseruations
Mean
12 Total no. of observations
S.D.
mo. Mean
S.D.
9.9 9.7
0.9 1.0
(Cm.):
Control Asphyxia Height
35 24
8.1
0.9
8.2
0.9
50 30
38 23
66.3
66.1
2.5 2.3
50 30
1.3
38 24
43.6 44.0
1.3 1.4
2.0 1.9
38 24
44.3 45.0
2.2
0.9
(cm.)
Control Asphyxia Head
in the babies of the control
circumference
(cm.):
Control Asphyxia Chest circumference
3.0
(cm.):
Control Asphyxia
36 26
Table VI. The results of neurologic
examination and asphyxia groups
of the of the babies control at 12 months of age
1.9
75.9
2.4
75.5
2.9
zx
46.4 46.3
1.5
49 30
47.9 47.6
2.0 2.3
Table VII. The Bayley scores in the infants the control and asphyxia groups at 6 and 12 months of age* Control
group
1.3
of
Asphyxia
grmq
No.
Mean
S.D.
No.
Mean
S.D.
39
114.8
19.3
24
111.6
14.3
38
109.2
19.1
23
111.3
17.1
49
108.9
16.0
31
108.1
13.5
49
100.8
19.0
1 6 ma:
Tone Movement:
48 49
30 30
0
Active Complex Involuntary
5
46 40 47
1
12 mix: 3
0
0 0 3
0 0
10
0
Rejlexes:
Deep Superficial Cranial nerves
0
Mental development index Physicaldevelopment index
28 6
z:,
0 0 0
The significant variable in the babies of the asphyxia group was an episode of intrapartum fetal asphyxia demonstrated by the presence of a metabolic acidosis at delivery. The severity of the asphyxia and the metabolic acidosis at delivery approached the critical levels observed in animal studies. However, information is incomplete in regard to the duration and pattern of development of the asphyxial episode. The importance of the duration of the asphyxia leading to the CNS injury in relation to survival has been emphasized in the fetal monkey studies in which severe asphyxia lasting 30 minutes to several hours was required to produce a critical level of brain damage.13* I59 I6 The newborn infants of the asphyxia group exhibited the characteristic low Apgar scores at one and five minutes with the increased requirement for resuscitation with intermittent positive pressure ventilation. Subsequently, during the neonatal period, these infants did not exhibit the neurologic signs of abnor-
Mental development index Physicaldevelopment index *There
98.2
13.5
were no significant p values.
mahties of tone, consciousness, or respiration or the seizures that are presently recognized as indicators of perinatal asphyxial encephalopathy.m-33 During the first year of life the babies of the asphyxia group demonstrate a pattern of physical growth as measured by weight, height, and head and chest circumference that is identical to that of babies of the control group (Fig. 2). There was no evidence of major neurologic disability in the babies of the asphyxia group at 1 year of age. It is recognized that in the older child further assessment is necessary to permit more discriminating neurologic examination and to identify impairments of vision and hearing and disorders of abstract reasoning. Finally, the mental and physical development indices of the Bayley score at 6 and 12 months of age in the babies of the asphyxia group were identical to those for the babies of the control group (Fig. 3). The cycle of events in response to fetal partial as-
Volume
130
Number
5
lntrapartum
fetal
9S?6-
Kgm
543-
HEIGHT
WEIGHT I DEUV.
401 3MON.
12 MON.
6MoH
D2UV
3MCW
6MON.
I2 MIN
Cm 40-
35-
HEAD CIRCUMFERENCE
CIRCUMFERENCE
30-
30I I DELIV. 311011 311011 WON. WON. DELIV. control
Group
-
Aaphyrio
1 12 uo1. Group ----
DELIV
SMON
I 6MON.
1 12 MON MON.
Fig. 4. The patterns of physical growth as measured by weight, height, and head ference in the babies of the control and asphyxia groups at 3, 6, and 12, months
SIX
MENTAL Control
MONTttS
TWELVE
uorms
DEVELOPMENT Group 0
Fig. 3. The mental and physical at 6 and 12 months of age.
91x
INDEX
MoNTltS
PHYSICAL
TWELVE
DEVELOPMENT
and chest of age.
circum-
MONTH6
INDEX
Asphyxia Group m development
indices
in the babies of the control
and asphyxia
groups
asphyxia
531
March 1, 1978 Am. J. Obstet. Gynecol.
this
stress
phyxial
is schematically episodes
while
at the
which
of
resolution
sidual
episode The
of intrapartum growth
phyxia of
is a vicious
blood
related
flow
and
upon
of
of brain
finally
to the duration
characteristics effects
one
the
the fetus
swelling
to cerebral and
severity
stressed and
fetus.
newborn
leading necrosis.
of asphyxia The infant
to stasis
fetal during
pattern
and
with
ability
asphyxia
in the group.
tinued
until
the similar
no evidence of
these
the
school
into
recognized
handicap.
establish
mental
the However,
suggest
that
the
asphyxia
experienced
fetuses
was
not
as severe
as the
of to
ing
REFERENCES 1. Butler, N. R., and Bonham, D. G.: The First Report of the British Perinatal Mortality Survey, Edinburg, 1963, E. & S. Livingstone, Ltd. 2. Low, J. A., Boston, R. W., and Crussi, F. G.: Classification of perinatal mortality, Can. Med. Assoc. J. 105: 1044, 1971. 3. Clifford, S. H.: The effects of asphyxia in the newborn infant, J. Pediatr. 18: 567, 1941. 4. Malamud, N.: Pattern of C.N.S. vulnerability in neonatal hypoxemia, in Schade, J. P., and McMenemey, W. H., editors: Selective Vulnerability of the Brain in Hypoxemia, Philadelphia, 1963, F. A. Davis Company, p. 211. 5. Freytagh, E., and Lindenberg, R.: Neuropathological findings in patients of a hospital for the mentally deficient: A study of 359 cases, Johns Hopkins Med. J. 121: 379, 1967. 6. Banker, B. Q.: The neuropathological effects of anoxia and hypoglycemia in the newborn, Dev. Med. Child Neurol. 9: 544, 1967. 7. Terplan, K. L.: Histopathologic brain changes in 1152 cases of the perinatal and early infancy , period, Biol. _ Neonate 11: g48, 1967. 8. Norman. R. M.: Late neuropathological sequelae of brain injury, in Greenfield’s NeuropatbGlogy, London, 1969, Edward Arnold (Publishers) Ltd., p. 304. 9. Towbin, A.: Central nervous system damage in the human fetus and newborn infant: Mechanical and hypoxic injury incurred in the fetal-neonatal period, Am. J. Dis. Child. 119: 259, 1970. 10. Griffiths, A. D., and Lawrence, K. M.: The effect of hypoxia and hypoglycemia on the brain of the newborn infant, Dev. Med. Child Neurol. 16: 308, 1974. 11. Urich, H.: Malformations of the nervous system,
12.
13.
14.
15.
16.
17.
18. 19. 20.
21.
system
injury
and
residual
critical disability
dis-
to the will
con-
be conthis
initial
of an as yet
the results
at this
by these level
a
physical
neurologic
to confirm
presence
suggest
and
children
is
sequence
re-
to delivery.
year
as compared
Follow-up or
in relation
with
of the asa terminal
prior
of major
group
entry
impression
CNS
edema
injury
first
and the
This
precise asphyxia,
in cerebral and
asphyxia
results
development trol of
perinatal
of
the mature newborn infants had experienced at least
follow-up
normal
asphyxia
result
edema
and
disability.
In this study phyxia group
of fetal
in
to a more
duration
will
cerebral
as-
injury,
severe
result
and
fetus
or
or
spectrum
relates
degree
4. Mild
edema
asphyxia
search
the
in Fig.
cerebral of the
of
present
in a particular
with
Fig. 4. The clinical CNS consequences increasing severity and duration.
end
episodes The
definition
no
opposite
prolonged death.
presented
cause
unstage
mature
leading
in the
to
surviv-
children.
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