Inflammation of the umbilical cord in cases of foetal asphyxia of unknown clinical etiology


Widholm, O.; Meyer, B.; Numers, C.

Gynaecologia 15(5): 386-399

1963


Umbilical cord biopsies were examined from 35 patients with fetal asphyxia of clinically undetectable etiology, and from 24 control cases. The histological examination was particularly concerned with inflammatory changes in the umbilical cord. The control series comprised 9 cases of complicated pregnancy and 15 normal pregnancies without signs of asphyxia. Inflammatory changes occurred in 14 of the 35 cases of the asphyxia material (40%). Only 1 patient of the control series showed cord changes; the same patient also had toxemia. Attempts to explain the high incidence of inflammatory cord changes in the asphyxia series have taken into account the patients' age, parity, pregnancy complications, possible post-maturity, duration of delivery, the lapse of time from the discharge of amniotic fluid, fetal weight, umbilical cord length, and placental weight. No direct correlation could be found with any of these factors, except that most of the asphyxia patients with umbilical cord changes were delivered after calculated term. The explanation of the umbilical cord changes in the material examined is obviously to be sought in the plentiful admixture of meconium to the amniotic fluid, despite the fact that appreciable meconium resorption in the umbilical cord could only be demonstrated in 1 case.

Gynaceologia
155:
385-399
(1%3)
Front
the
Second
Department
of
Obstetrics
and
Gynecology,
Helsinki
I
niversity
Central
Hospital
(Chief:
Prof.
P.
Vara)
Inflammation
of
the
Umbilical
Cord
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
13.
O.
IDH01,11*,
B.
MEYER
and
C.
v.
\
'BIERS
In
1869,
Hintze,'
described
inflammatory
changes
in
the
umbilical
cords
of
two
syphilitic
foetuses.
For
the
next
40
years,
these
changes
were
considered
more
or
less
characteristic
of
syphilis
(Bondi
1903,
Wohn
1907),
but
extensive
studies
early
in
the
20th
century,
by
Simmonds
(1912)
and
others,
revealed
that
inflammatory
changes
of
the
cord
without
syphilis
were
not
so
uncommon
as
had
been
believed.
The
incidence
of
inflammatory
changes
in
the
umbilical
cord
has
in
later
studies
ranged
from
10
to
30
O/
(Kobak
1930,
Beckmann
and
Zimmer
1931,
Kllckens
1938,
Nielsen
1950,
Mance
1959,
Benirschke
and
Clifford
1959,
Bourne
1962).
The
etiology
of
inflammatory
cord
changes
cannot
vet
be
consider-
ed
fully
clarified,
and
opinions
on
the
subject
differ,
though
they
generally
agree
that
such
changes
are
a
component
in
the
"amniotic
infection
syndrome"
described
by
Mance
(1959).
The
majority
of
writers
believe
that
this
syndrome
develops
from
bacterial
infection,
and
is
in
most
eases
attributable
to
an
ascending
infection
during
delivery
(Siddal
1927,
Ktickens
1938,
Sorbs
1948,
Morison
1952,
Midler
195(i,
Blanee
1959,
Flarnm
1959,
and
others;
for
the
mecha-
nism
and
the
routes
of
infection,
reference
is
made
to
Bourne,
1962).
It
has
been
possible
to
produce
inflammatory
changes
experimentally
by
lowering
the
pH
of
the
amniotic
fluid
(Ikeda
1927).
In
human
beings,
inflammatory
cord
changes
have
been
observed
after
injec-
tion
of
hypertonic
saline
solution
into
the
amniotic
fluid
to
induce
therapeutic
abortion
(Mance
1959).
Beckmann
and
Zimmer
(1931)
and
Morison
(1952)
believe
that
inflammation
is
provoked
by
irrita-
This
investigation
was
supported
by
a
grant
froin
the
"Sigrid
Juselius
Stiftelse",
Helsinki.
,
i!-a.•
386
II
idlitdrit.
llrvrr.
r.
\
uniers.
Inflammation
of
the
Cnibilical
Cord
4
2*.,,
,
,..,
...
,
-
.
4;,.
.$-fq,j44
,
;;
;
;p,w.f.v
,
k
:
i.:
,..
t.
,t,
-,.
;
1
-
,e's
-
.
ovidiV
,
1.
1
•674
4
!
1
;i:
'
•,:
,
•.
1
.404
'
-
i.."
?,..,,'•:'
,
,•••!.-!.:cv
.
6:
i'..,/,r•
'.
,
.•!..
.,,..!
,
,•!•
v
.
:;;:
..
:
,,,
.'4'
''
..
1:1
..
.
:::::k1;..
:
00
,.
.
7
4.1g
2
'S
e
t,
'"4.7
.
;74''/9
ii‘
_:
4 ;
1
-:.
I'
t
:
X.).14..P
-•::•1'.!..:,
-
',f
.
r
‘.
q!
A
%.,
...X
••
t
rdi
,
.
;
t
‘..•."
r
"r•
0
1
1P
r
'
r,
r
,
...
;
-
f..
y
.
'..
:`..
.-:•‘
,,..
4
1-.
.
..
4
,0
.
:
,....;
e
-
,;:,'.
-
-
•••
"
.,
.
.
.
e
-
.
,
-
•'•-
4
-
-,
.•
7:94-
.,
-•
...,
,..:,-
z
..,.
;
,
..::-
.
.
7
let
t,
*
.
-
-
.44;.
*
::„..,..
-
.&•:-
-
;:::-
,
4....4.
4,
-.,
4
?
:
••4
.
1-
..
::-.---r-r-s.....
'
'
.
4
••Q`i.
.
"_.
l
ir
.
.:i
..
....
...
'i
.'
C
e
r
"
‘••••••
„a..•
,
-
•••
.....t
.....
i
n•
of';'1
••••.:
I-
...-
Z
Aft-,
i;•.....f:,±1.-:.4t...*Wyllo're
-;•
-
3
,,,
.
::;;',•:‹:.:
y.
-,:.
,••
_
....,..
:t
„,.
-
.::,•,../,
••-"...
‘...••••=fz"it
.-
71
-
4_
i
,„,
-si,-.1.
....,..,••
-
,„
..
-
.....
-••
..
.
--
,
seP
''.?'
.);•rsv
...
;
4
,
4
,,
:t
.
•?;.:-?-ts.,:11,sfai.,,
-
c.
,._,,..
,
-
.?.."'s•--
7
6
r
7
,
,`•
-
-
'
;
4:
,
-
"
---
;.,
-
4
,
-*
-
-:.,...-b•ws:
....:.
,
i.
:•-••,--.
w
-
"'e-
i
i,.4!'
..
,_,
;•
,..g_t_.....
.......
i
r
.
..
1
.
:*
:, ..
-.-.
•-•-.-.,...4-,,
::
'
,
4
*
-
t
-
-...
::-4...
-
t-7
-
'
"
:
4
"
1
44"
''''•
-""-
414
-
.:.
f':"
.
-;:-.--;•.-:.
'
••'•-•=.
'
--''"
.
-
4
---
.
--
.1
$
:
..-
r
,i.1...j'..1-1.
..
.'
.0
.
1
.
4
::::
,•%
,..e
t.
..i:
,
,ltailit
..
..cp.,
"
....;
o
'
t
).
-'';:
-'
tt"--,:f.
,
#,o•-,.'
.
•.
-
..C.u..4.
='...,,:
1
!=4
;tr
'
'
1.4k
...
...
.
Fi
r
.
I.
Endothelial
proliferation
and
profuse
gri
loeyte
infiltration
of
the
interior
intinial
layer.
The
other
layers
of
the
vascular
all
show
few
granulocyte•:.
Wharton's
jelly
is
intact.
van
Giseon
staining.
Alain.
ISO
X.
Fig.
2.
Profuse.
diffuse
granulocyte
infiltration
of
all
layers
of
the
vascular
wall
and
of
Wharton.'
jelly.
Vali
CIM/11
staining.
Map.
1511
Y.
tion
from
various
substances,
and
Morison
assumes
that
meconium
might
be
one
of
those.
Inflammatory
cord
changes
are
characterized
by
leucocyte
infil-
tration,
and
the
diagnosis
is
based
on
the
presence
of
polymorpho-
nuclear
leucocytes
(Bourne
1962).
The
histological
changes
seen
in
umbilical
cords
have
been
thouroughly
described
by
Nielsen
(1950).
Inflammatory
changes
vary
considerably,
and
every
degree
of
in-
flammation
from
simple
margination
in
the
lumen
of
the
vein
to
acute
phlebitis
or
arteritis
can
be
found. Inflammatory
changes
may
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
387
also
occur
along
the
whole
length
of
the
umbilical
cord
or
they
maN
be
restricted
to
certain
parts
of
it.
Inflammatory
changes
start
in
the
lumen
of
the
umbilical
vein
with
a
migration
of
polymorphonuclear
lencocytes,
visible
in
that
part
of
the
infirm'
next
to
the
umbilical
cord
surface.
From
here
the
leucocytes
migrate
to
the
wall
of
the
vein,
and
a
gathering
becomes
visible,
first
in
the
intima
and
next
in
the
muscular
layer.
From
the
wall
of
the
vein
the
hbucocytes
continue
to
the
stroina
of
the
umbilical
cord
(Wharion's
jelly)
but
even
in
the
most
severe
inflammations
they
seldom
reach
the
epithelium
of
the
cord.
The
process
is
through-
out
one
of
radical
centrifugal
distribution,
and
the
area
of
penetration
is
always
clearly
demarcated.
The
extent
of
penetration
is
considered
to
depend
on
the
duration
and
intensity
of
response.
Similar
changes
can
often
be
shown
in
arteries.
The
object
of
the
present
study
was
to
examine
the
incidence
and
etiology
of
inflammatory
changes
in
the
umbilical
cord
in
cases
of
asphyxia
where
the
cause
of
asphyxia
could
not
be
clinically
traced.
Material.
The
material
comprised
umbilical
cord
biopsies
from
59
parturients
treated
in
the
Second
Women's
Clinic
at
Helsinki
Uni-
versity
Central
Hospital
during
1959-1961.
Of
these
59
patients,
35
were
cases
of
foetal
asphyxia
the
development
of
which
could
not
be
clinically
explained
either
before
or
after
delivery.
The
remaining
24
cases
constitute
the
control
material,
mostly
normal
parturients,
and
individual
pathological
cases,
mostly
toxaemias.
Diagnosis
of
asphyxia
was
based
on
the
following
symptoms:
irregularity
or
fre-
quency-changes
in
heart
sounds,
and
perceptible
discolouration
of
amniotic
fluid.
In
examining
the
series
of
patients,
all
available
in-
formation
and
observations
on
the
course
of
the
delivery
have
been
taken
into
account,
and
essential
data
on
the
series
are
collated
in
Table
I.
The
material
has
been
divided
into
3
groups:
A
=
asphyxia
with
cord
changes,
B
=
asphyxia
without
cord
changes,
C
=
control
material.
Methods.
Immediately
after
the
expulsion
of
the
placenta
the
whole
umbilical
cord
was
placed
in
10
0
/
formalin
solution.
Samples
were
taken
from
three
sections
of
the
cord
for
histological
study:
from
the
part
closest
to
the
foetus
(section
1),
from
the
middle
of
the
cord
(section
2),
and
from
the
part
closest
to
the
placenta
(section
3).
Several
samples
were
taken
from
each
section
and
they
were
stained
by
the
v.
Gipson
method.
Positive
results
were
divided
into
three
388
g
idhoint,
11eyer.
v.
,\timers.
Inflammation
of
the
Umbilical
Cord
A131.,F.
I
Case
Parity
Age
Diagnosis
Days
Days
Duration
Foetal
No.
before
after
of
delivery
heart
eaten-
eaten-
(hours)
rate
hated
kited
per
term
term
_____
____
_
Group
A
I
I
23
Oedema.
Hypertensio
gray.
16
23
h
130
2
I
26
Anaemia
gray.
12
18
h
3
min
11.0
3
I
28
8
II
b
25
'
110
4
II
27
14
IS
h
15
min
1301
150
5
IN'
27
I
9
It
50
min
125
160
6
II
32
5
10
It
15
'
120
7
I
26
10
13
h
5
'
120
8
I
29
Oedema
gray.
II
5
h
25
min
160
9
III
29
Nephropathia
gran•.
2
3
h
45
.
120
I))
III
35
I
6
h
50
min
161)
11
I
35
14
3
h
35
min
140
12
IV
41
3
9
b
15
110-130
13
II
32
2
15
h
120-140
14
I
37
Eelampsis
,
gray.
6
9
h
10
min
1311
150
Pyelitis
gray.
Average
31
2
12
11
h
Group
B
15
I
25
Nephropathia
gray.
18
14
h
35
min
100
140
16
I
22
11
10
h
50
'
1•1.0
160
17
I
.).)
Pvelitis
gray.
3
17
h
10
min
120
18
I
23
16
21
h
10
min
131)
19
1
41
Oedema
gray.
2
13
h
20
min
140
20
I
20
6
31
h
20
min
70
130
21
I
21
Oedema
gran.
I
20
b
25
min
150
22
I
20
I
11
h
15
min
140
23
I
27
3
10
h
45
min
11)0
140
21
I
19
Anaemia
gray.
15
h
40
min
130-150
25
1
I
31
18
8
h
30
min
150
26
II
21
13
2h
5
'
160
27
III
36
Ordrina
gray.
III
2
h
45
min
110
Anaemia
gray.
28
III
33
16
8
11
10
min
II))
29
III
23
9
13
h
30
Mill
120
30
11
26
Nophropathia
gray.
4
IS
h
IS
'
120
31
III
23
14
15
h
15
min
121)
1111
32
II
40
Pyelitis
gray.
20
8
h
30
min
130
33
IV
40
11
9
h
20
min
1211
34
III
40
Oedema
gray.
10
17
h
25
min
130
150
35
II
21
6
7
11
15
'
120
160
Average
't
7
12
136
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
389
Degree
of
dis-
Duration
of
labour
after
Pitmen-
eolouration
of
rupture
of
membranes
tar
amniotic
fluid
(hours)
weight
+ +
+
1-
+
+
0-3
3-6
6-12
>12
grams
Length
of
tun-
bilicul
cord
cm
Foetid
birth
weight
grainy
Degree
of
in-
Ilam-
!nation
Section
of
umbilical
cord
1
2
3
+
+
+
19.08
650
50
3.900
III
X
X
X
+
+
x
480
38
3.100
III
X
X X
+
H
+
x
580
40
4.400
111
X
X
X
-i•
-
x
480
58
3.540
1 1
I
X
X
X
+
4+
x
850
60
4.100
III
X
X X
+
x
550
56
3.550
III
X
++
x
560
47
4.040
1
X
X
X
1-
++
x
550
80
3.200
I
X
X
X
+
++
x
660
80
3.550
1
X
X X
+
++
x
670
50
4.310
1
X
X
X
1-
+
560
86
3.600
1
X
X
X
+
++
x
430
53
2.500
I
X
X
X
1-
+
x
480
44
3.100
1
X
X
+
+
375
57
2.000
I
X
3
562
57
+
+
+
x
540
59
3.320
+
+
x
980
87
4.700
-i-
x
500
48
2.860
+
25.10
600
65
3.550
-F
+
x
620
45
3.240
+
+
x
520
62
3.720
+
+
x
550
82
3.150
+
+
x
590
76
3.330
i-++
x
570
50
3.380
++
x
610
72
3.300
+
-I-
x
550
52
3.440
+ +
+
x
850
64
4.390
+ +
+
x
670
52
3.250
+
+
+
x
580
48
2.890
-1-
x
480
53
2.720
+
+
x
750
50
3.830
+++
40,05
860
66
1.070
++
16,20
650
60
3.570
++
27,20
850
65
4.450
+ +
x
650
65
3.290
+
+
x
420
50
2.660
...___
637
60
10
390
IT
idholm.
Weyer.
r.
l'urners.
Infl
ation
of
the
Umbilical
Cord
Case
Parity
Age
Diagnosis
No.
Days
Days
Duration
Foetal
before
after
of
delivery
heart
calm-
caleu-
(hours)
rate
lated
dated
per
min
term
term
Group
C
2
It
5min-31
1
20
min
36
IV
32
Nephropathia
gray.
6
4
h
50
min
130
37
1
22
Eciampsis
s
gray.
2
5
h
45
125
38
I
22
Nephropathia
gray.
3
21
h
20
min
130
39
I
24
Diabetes
mellitus
27
11
120
10
I
211
Oedema
gray.
15
23
h
45
min
120
41
1
23
Oedema
gray.
term
17
It
5
140
42
II
35
Nephropathia
gray.
13
14
h
45
min
120
43
II
33
Placenta
praevia
48
margin:Ills
21
h
15
min
140
44
I
24
Praesentattio
clunium
54
6
h
45
min
130
45
I
211
I
9
Ii
50
.
120
46
I
18
12
11
h
35
min
120
.1.7
1
21
58
2
It
IS
.
120
48
I
20
7
13
h
50
min
140
19
III
24
14
18
h
IS
min
130
50
II
30
7
16
h
30
min
120
51
IV'
29
29
12
h
40
140
52
II
34
4
10
h
120
53
II
21
18
2
h
55
min
120
54
II
27
3
26
It
40
min
120
55
II
21
17
14
It
25
min
140
56
II
27
6
16
It
5
min
120
57
I I
33
2
15
It
30
mita
140
58
V
26
1
I
11
It
211
130
59
VII
31
It
5
h
40
120
Average
26
10
I3
13
Ik
groups,
according
to
the
sections
of
the
cord
in
which
inflammatory
changes
were
seen:
Group
I
Umbilical
cords
with
inflammatory
changes
in
the
vessels
alone
(the
vein
and
or
one
or
both
arteries).
Group
11
Umbilical
cords
with
changes
in
Wharton's
jelly
only.
Group
III
Umbilical
cords
with
changes
both
in
Wharton's
jelly
and
the
vessels.
(Coin
in
ini
t
io
ii)
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
391
Degree
of
di,-
Duration
of
labour
after
Platen-
Length
Foetal
Degree
Section
of
(-admiration
of
rupture
of
membranes
tar
of
11111-
birth
weight
of
in-
umbilical
amniotic
fluid
(hours)
weight
bilical
cord
Clam-
matiou
cord
.
-1
0-3
3-6
6-12
'7
,
12
grains
cm
grams
I
2
3
x
6011
60
3.970
1
X
X X
14.50
850
1011
1.140
x
480
10
3.930
600
50
3.750
x
550
32
4.680
x
600
60
3.650
x
700
50
1.240
360
50
2.260
x
4.90
35
1.610
x
570
60
3..410
x
570
47
4.060
x
360
16
1.820
x
500
5.4
3.450
x
680
54
3.720
x
550
61
3.950
x
530
60
3.210
x
600
60
3.740
x
520
12
3.500
x
500
52
3.720
x
520
45
3.240
N
450
62
3.270
x
530
45
2.800
x
550
56
4.180
x
570
64
4.0411
550
53
Results.
Table
I
shows
that
cord
changes
were
detected
in
14
cases
of
the
asphyxia
group,
while
the
control
material
only
displayed
less
pronounced
changes
in
one
case
with
nephropathy.
Of
the
umbilical
cord
infiltrates,
6
belonged
to
Group
III
and
8
to
Group
I.
In
Group
III
these
changes
occurred
in
all
sections,
1,
2
and
3.
in
5
cases,
and
in
Section
I
in
one
case.
In
Group
1
changes
were
seen
in
Sections
1,
2
and
3
in
6
cases,
in
Sections
I
and
2
in
one
ease,
and
in
Section
3
in
392
IT
idhohn,
Weyer.
r.
Numers,
Inflammation
of
the
l
mbilieal
Cord
one
case.
The
cord
preparations
were
also
studied
for
the
occurrence
of
meconiurn
resorption,
but
only
a
relatively
slight
resorption
was
visible
in
one
case.
There
was
an
even
distribution
of
parity
within
the
groups.
The
mean
age
in
the
asphyxia
group
with
demonstrable
cord
changes
was
31
years,
in
that
of
the
other
asphyxias
27
years,
and
in
the
control
series
26
years.
No
correlation
could
be
shown
between
umbilical
cord
changes
and
complicated
pregnancies.
It
is
noticeable
that
for
12
of
the
14
demonstrated
cord
changes
there
was
more
or
less
pro-
nounced
postmaturity,
calculated
on
the
basis
of
the
time
indicated
by
the
menstruation
cycle.
Postmaturity
ranged
from
I
to
14
days.
In
the
remainder
of
the
asphyxia
cases
and
in
the
control
cases
no
such
correlation
could
be
shown.
Nor
was
any
correlation
evident
between
duration
of
delivery,
method
of
delivery
or
degree
of
asphyxia
on
the
one
hand
and
umbilical
cord
changes
on
the
other.
For
the
development
of
cord
infiltrations,
great
etiological
significance
has
been
attributed
in
literature
to
an
extended
interval
between
the
discharge
of
the
amniotic
fluid
and
the
time
of
delivery.
In
the
present
material,
the
laps
of
time
from
the
rupture
of
membranes
to
delivery
was
extremely
short
(11
hours)
in
the
asphyxia
group
with
umbilical
cord
changes,
while
the
dispersion
of
time
intervals
is
greater
in
the
group
of
the
other
asphyxias
(13
hours)
and
particularly
in
the
control
group
(13
hours).
No
correlation,
therefore,
was
found
in
this
series
between
the
time
of
discharge
of
the
amniotic
fluid
and
parturition,
and
the
umbilical
cord
changes.
Nor
was
there
any
correlation
to
be
found
between
cord
changes,
placental
weights
and
the
length
of
the
umbilical
cord.
In
the
group
of
asphvxias
with
cord
infiltration,
one
delivery
was
premature,
while
the
control
group
had
3
premature
deliveries.
The
rest
of
the
children
in
the
material
were
mature,
and
the
dispersion
of
their
weight
groups
was
fairly
even.
The
occurrence
of
maternal
infections
before
and
after
part
us
has
also
been
studied,
but
it
did
not
correlate
to
cord
changes.
In
8
out
of
the
14
cases
in
the
asphyxia
group
with
cord
changes
a
vaginal
examination
was
performed.
In
the
total
series,
there
were
29
vaginal
examinations
among
59
patients.
Neither
vaginal
examination
nor
the
rupture
of
membranes
could
be
shown
to
have
affected
umbilical
cord
infiltrations.
Delirery
mechanism.
All
except
one
control
case
were
parietal
pre-
sentations.
In
the
asphyxia
group,
there
were
two
ceasarean
sections
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
393
and
3
suction
cup
extractions
according
to
MalmstrOm;
in
the
control
group,
there
occurred
one
section,
one
suction
cup
and
one
extraction
of
a
breech
presentation.
The
remaining
deliveries
took
a
normal,
uncomplicated
course.
Children's
prognosis.
Two
babies
of
the
present
series
died
on
deliv-
ery.
One
of
them
(Case
27)
was
a
boy,
weight
3.250
g;
the
child
belonged
to
the
asphyxia
group
without
umbilical
cord
changes,
was
heavily
asphyxiated
and
could
not
be
revived.
The
other
child
(Case
12)
was
a
premature
girl,
weight
1.820
g,
who
was
horn
after
a
rapid
delivery
(2
hours
45
minutes)
and
died
of
intraventricular
cerebral
hemorrhage
within
24
hours
in
the
Children's
Clinic.
The
remaining
children
were
all
well
after
partus
and
while
in
the
hospital
they
showed
no
signs
of
inflammatory
or
other
pathological
conditions,
despite
the
fact
that
a
number
of
them
had
more
or
less
pronounced
changes
in
the
umbilical
cord.
Discussion
A
study
of
the
results
of
the
present
investigation
must
be
based
on
the
fact
that
asphyxia
is
a
relative
concept
and
that
no
definite
clinical
symptoms
or
tests
arc
available
to
show
beyond
dispute
whether
or
not
asphyxia
has
occurred.
The
series
was
selected
accord-
ing
to
current
criteria
for
the
diagnosis
of
asphyxia
prior
to
parturi-
tion,
i.e.
auscultation
of
foetal
heart
sounds
and
observation
of
the
colour
of
amniotic
fluid.
Ten
of
the
35
asphyxia
cases
examined
reveal-
ed
normal
frequency
of
foetal
sounds,
13
had
greatly
varying
foetal
sounds,
and
12
a
heart-sound
frequency
steadily
exceeding
140
per
minute.
No
distinct
difference
could
be
noted
in
heart-sound
fre-
quencies
between
asphyxia
with
and
without
umbilical
cord
changes.
Discolouration
of
amniotic
fluid
was
moderate
in
4
cases,
pronounced
in
18
and
exceedingly
pronounced
in
13
cases.
Assessment
of
the
discolouration
of
amniotic
fluid
is
an
extremely
subjective
matter,
and
it
is
impossible
to
say
with
certainity
if
this
change
was
more
conspicuous
in
cases
with
umbilical
cord
changes.
In
literature
the
incidence
of
inflammatory
changes
in
the
umbilical
cord
varies
between
10
and
30
%.
Siddal
(1927)
detected
umbilical
cord
changes
in
6
%
of
1000
infants,
in
25
%
of
36
premature
births
and
in
18.5
%
of
stillborn
children.
Beckmann
and
Zimmer
(1931)
recorded
such
changes
in
71
(18.3
%)
of
420
parturitions;
16
of
these
were
connected
with
syphilis.
Kiickens
(1938)
reports
an
incidence
of
31
Gyouecolugle,
Vol.
153.
Nu.
6
(1963)
394
Widho1m,
Meyer,
v.
Numers,
Inflammation
of
the
Umbilical
Cord
10
%
in
600
cases
examined.
Nielsen
(1950)
found,
in
a
series
of
390
cases,
that
cord
changes
were
present
in
25
%
(slight
in
20
and
pro-
nounced
in
5
%)
of
children
with
hirthweights
exceeding
2.500
g
and
in
27
%
(slight
in
11
and
pronounced
in
16
%)
of
children
with
a
birthweight
under
2.500
g.
In
his
series
of
syphilitic
cases
the
figures
were
four
times
higher
for
children
weighing
under
2.500
g
and
about
twice
as
high
for
children
weighing
over
2.500
g
at
birth
than
for
those
of
the
same
weight
among
the
non-syphilitics.
Benirschke
and
Clifford (1959)
report
an
incidence
of
10
%
among
1300
consecutive
deliveries,
and
Blance
(1959)
a
similar
incidence
(23
cases
out
of
200).
The
incidence
of
cord
changes
in
the
present
series
has
been
higher
by
far
than
the
previously
quoted
40
%
(14
of
35
asphyxia
cases
examined).
The
parallel
control
study
of
24
cases
revealed
a
cord
change
in
only
one
(some
4
%)
although
pathological
pregnancies
were
included
in
the
series
(see
table).
This
series
is,
however,
too
small
to
permit
any
general
conclusions
on
the
overall
incidence
of
umbilical
cord
changes.
According
to
Bourne
(1962),
inflammatory
changes
begin
in
the
lumen
of
blood
vessels
and
spread
centrifugally
to
the
vascular
walls
and
into
the
stroma
of
the
cord
(Wharton's
jelly).
They
usually
begin
in
the
wall
of
the
vein,
and
the
extent
of
leucocyte
penetration
is
a
standard
by
which
to
measure
the
intensity
and
duration
of
the
in-
flammation.
The
present
series
included
pronounced
changes,
that
is
to
say,
a
penetration
into
the
stroma,
in
all
three
sections
of
the
cord
in
5
cases
of
asphyxia
and
in
one
more
case
in
section
1
only.
Changes
in
the
vessels
only
were
noted
in
6
cases
in
all
3
sections,
in
one
case
in
sections
1
and
2,
and
in
one
case
in
section
3.
In
the
present
series,
the
incidence
of
pronounced
changes
is
far
higher
than
that
reported
by
Nielsen
(1950)
for
babies
with
a
birthweight
exceeding
2.500
g.
Bourne
(1962)
found
that
the
venous
wall
was
more
affected
than
the
arterial
wall
in
89
%
of
a
series
of
300
umbilical
cords
examined.
In
the
14
positive
cases
of
the
present
material,
the
vascular
inflammatory
changes
occurred
in
the
venous
wall
only
for
11,
in
the
arterial
wall
only
for
1,
while
2
cases showed
changes
both
in
the
vein
and
in
the
arteries.
The
only
positive
case
in
the
control
group
showed
slight
inflammatory
changes
in
the
venous
wall,
and
it
should
be
added
that
this
mother
suffered
from
toxaemia
of
pregnancy.
How
can
the
high
incidence
of
cord
changes
in
the
present
material
be
explained
?
A
detailed
study
of
the
series
reveals
that
the
mean
age
in
Group
A
was
somewhat
higher
than
in
Groups
B
and
C.
'No
parti-
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
395
cular
significance
can,
however,
be
attributed
to
this.
Nor
does
the
parity
distribution
between
the
groups
show
any
marked
differences.
The
examined
series
showed
no
signs
of
other
infections,
except
for
a
few
individual
cases
of
pyelitis.
This,
however,
was
more
frequent
in
the
cases
without
cord
changes
and
showed
no
correlation
to
leuco-
cyte
infiltration.
WaR
was
taken
of
all
patients
and
was
unfailingly
negative.
An
intrauterine
infection
is
usually
attributed
to
an
ascending
infection
or
discharge
of
amniotic
fluid
(Sle
nons
1915,
Ikeda
1927,
Kobak
1930,
Kiickens
1938,
Sorba
1948,
Benirschke
and
Clifford
1959,
Blance
1959,
and
others).
Siddal
(1928),
Nielsen
(1950),
Mcllwaine
(1952)
and
Blance
(1959)
believe
that
there
is
a
direct
correlation
between
the
incidence
of
inflammatory
changes
and
the
time
interval
between
the
rupture
of
membranes
and
delivery.
An
increased
risk
of
infection
is
also
present
with
an
extended
duration
of
delivery
and
intrauterine
manipulations,
as
has
been
shown
by
Langley
and
Smith
(1959)
in
uterine
inertia
and
forceps
deliveries.
Nielsen
(1950)
points
out
that
inflammations
are
often
found
if
delivery
has
lasted
2-3
days,
and
almost
always
if
the
delivery
has
lasted
over
3
days.
Sorba
(1948)
assumes
that
the
uterus,
by
contractions
after
the
rupture
of
membranes,
absorbs
infected
matter
from
the
vagina.
For
the
present
series,
the
mean
duration
of
delivery
in
cases
with
umbilical
cord
changes
was
about
11
hours,
which
is
much
less
than
the
mean
duration
of
deliveries
in
the
other
two
groups.
The
interval
between
the
rupture
of
membranes
and
partus
in
Group
A
was
about
3
hours,
much
shorter
than
that
in
Group
B
(10
hours)
and
in
Group
C
(4
hours).
Only
in
1
case
out
of
14
was
the
interval
over
6
hours,
and
in
1
case
over
12
hours.
The
total
of
vaginal
examinations
performed
was
as
high
in
the
asphyxia
group
with
cord
changes
as
in
the
other
two
groups.
The
inflammatory
changes,
therefore,
cannot
be
explained
on
the
basis
of
these
facts,
nor
do
the
placental
weight
and
the
length
of
the
cord
provide
explanatory
distinct
differences.
By
virtue
of
the
above
facts
no
conclusive
proof
has
been
found
of
the
cause
of
intrauterine
infection.
Bacterial
cultures
of
amniotic
fluid
were
not
made,
because
once
the
fluid
is
discharged
their
value
is
disputable
since
sampling
is
done
vaginally.
According
to
Bourne
(1962),
there
is
a
growing
body
of
opinion
supporting
the
theory
that
intrauterine
inflammatory
changes
arise
from
irritation
of
a
toxic
sub-
stance,
and
if
a
bacterial
infection
supervenes
it
must
be
considered
a
secondary
phenomenon.
Benirschke
and
Raphael
(1958)
assume
that
396
Widholm.
Meyer,
v.
Numers,
Inflammation
of
the
Umbilical
Cord
infection
is
the
primary
cause
in
extremely
rare
cases.
The
possibility
of
irritation
by
a
toxic
substance
has
been
much
discussed
and
the
conclusion
reached
is
that
the
amniotic
fluid,
saline,
vernix,
epithelial
cells
and
meconium
could
provoke
these
changes
(Grhff
1922,
Ikeda
1927,
Morison
1952,
Benirschke
and
Clifford
1959,
Blance
1959).
Morison
(1952),
in
particular,
has
advanced
the
hypothesis
that
meco-
nium
might
act
as
a
toxically
irritating
substance.
This
would
be
a
very
noteworthy
factor
for
the
present
series
in
which
all
cases
of
asphyxia
showed
a
marked
admixture
of
meconium
in
the
amniotic
fluid.
Resorption
of
meconium
into
the
umbilical
cord
biopsies
could
only
be
demonstrated
in
one
case.
It
may
be,
however,
that
this
resorption
into
the
foetus
is
perhaps
somewhat
greater
in
the
present
material
because
it
is
believed
to
occur
for
the
most
part
through
the
placental
part
of
the
amnion
and
the
site
of
insertion
of
the
cord.
No
biopsies
were
taken
from
the
amnion
in
the
present
study.
The
question
remains
as
to
whether
the
inflammatory
changes
in
this
material
arc
the
causative
factor
of
intrauterine
asphyxia
or
vice
versa.
It
is
a
known
fact
that
even
grave
intrauterine
infections
need
not
affect
the
foetus
at
all.
This
was
in
fact
true
for
the
present
series:
only
1
of
the
14
children
of
Group
A
was
transferred
to
the
Children's
Clinic
for
observation,
and
this
due
to
prematurity.
All
the
others
were
vigorous
immediately
on
delivery.
An
interesting
observation
made
in
this
study
was
that
delivery
in
most
Group
A
cases
occurred
past
term.
A
postmature
delivery
is
known
to
be
much
more
danger-
ous
for
the
foetus
and
may
readily
lead
to
intrauterine
asphyxia.
One
gains
the
impression
that
this
might
be
a
cause
of
asphyxia
and
it
also
provokes
the
discharge
of
great
quantities
of
meconium
which
is
normally
not
discharged
until
after
partus.
There
is
therefore
an
inclination
to
consider
the
inflammatory
cord
changes
as
secondary
to
asphyxia
and
possibly
provoked
by
the
abundant
meconium
ad-
mixture
in
amniotic
fluid,
as
has
been
previously
assumed
e.g.
by
Morison
(1952).
This
would
also
account
for
the
high
incidence
of
umbilical
cord
infiltrations
in
the
present
series
of
patients.
Summary
Umbilical
cord
biopsies
were
examined
from
35
patients
with
foetal
asphyxia
of
clinically
unelectable
etiology,
and
from
24
control
cases.
The
examinations
were
carried
out
at
the
Second
Women's
Clinic
of
Helsinki
University
Central
Hospital
during
the
period
1959-61.
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
397
The
histological
examination
was
particularly
concerned
with
in-
flammatory
changes
in
the
umbilical
cord.
The
control
series
com-
prised
9
cases
of
complicated
pregnancy
and
15
normal
pregnancies
without
signs
of
asphyxia.
Inflammatory
changes
occurred
in
14
of
the
35
cases
of
the
asphyxia
material
(40
%).
Only
one
patient
of
the
control
series
showed
cord
changes;
the
same
patient
also
had
toxae-
mia.
Attempts
to
explain
the
high
incidence
of
inflammatory
cord
changes
in
the
asphyxia
series
have
taken
into
account
the
patients'
age,
parity,
pregnancy
complications,
possible
post-maturity,
dura-
tion
of
delivery,
the
lapse
of
time
from
the
discharge
of
amniotic
fluid,
foetal
weight,
umbilical
cord
length,
and
placental
weight.
No
direct
correlation
could
be
found
with
any
of
these
factors,
except
that
most
of
the
asphyxia
patients
with
umbilical
cord
changes
were
delivered
after
calculated
term.
The
explanation
of
the
umbilical
cord
changes
in
the
material
examined
is
obviously
to
be
sought
in
the
plentiful
admixture
of
meconium
to
the
amniotic
fluid,
despite
the
fact
that
appreciable
meconium
resorption
in
the
umbilical
cord
could
only
be
demonstrated
in
one
case.
Zusammenfassung
Von
35
Patientinnen
mit
fetaler
Asphyxie
klinisch
nicht
auffind-
barer
Atiologie
und
von
24
Kontrollfallen
wurden
Biopsien
der
Nabel-
schnur
untersucht.
Die
Untersuchungen
wurden
1959-61
an
der
II.
Univcrsitatsfrauenklinik
ausgefiihrt.
Die
histologische
Untersuchung
richtete
sich
vor
allem
auf
ent-
ziindliche
Veranderungen
der
Nahelschnur.
Entziindliche
Zeichen
kamen
in
14
von
35
Asphyxiefallen
vor
(40
%).
Die
Kontrollserie
umfaf3te
9
Falle
von
komplizierter
Schwangerschaft
und
15
normale
Schwangerschaften
ohne
Zeichen
von
Asphyxie.
Nur
1
Patientin
der
Kontrollen
zeigte
Nabelschnurveranderungen;
diese
Patientin
hatte
eine
Toxikose.
Versuche,
das
gehaufte
Vorkommen
von
entziindlichen
Nabel-
schnurveranderungen
bei
Asphyxiefallen
zu
erklaren,
haben
das
Alter
der
Patientinnen,
die
Paritat,
Schwangerschaftskomplikati-
onen,
Ubertragung,
Geburtsdauer,
das
Zeitintervall
vom
Blasen-
sprung
bis
zur
Geburt,
das
Gewicht
des
Kindes,
die
Nabelschnur-
lange
und
das
Gewicht
der
Placenta
beriicksichtigt.
Zu
keinem
dieser
Fak
toren
konnte
eine
direkte
Beziehung
gefunden
werden,
aufler
dafl
398
Widholm.
Meyer,
v.
Numers,
Inflammation
of
the
Umbilical
Cord
(he
meisten
Asphyxiefalle
mit
Nabelschnurveranderungen
nach
dem
berechneten
Termin
cntbunden
wurden.
Die
Erklarung
der
Nabelschnurveranderungen
im
untersuchten
Material
ist
offensichtlich
in
der
reichlichen
Mekoniumbeimischung
zum
Fruchtwasser
zu
suchen,
obwohl
eine
wesentliche
Mekonium-
resorption
in
der
Nabelschnur
nur
in
einem
Fall
nachgewiesen
werden
konnte.
Resumé
Les
auteurs
examinent
des
biopsies
du
cordon
ombilical
dans
35
cas
d'asphyxie
ftetale
cliniquement
inexpliquee,
ainsi
que
dans
24
cas
servant
de
contrOle.
Les
travaux
sont
effectues
a
la
Clinique
Gyneco-
logique
de
l'HOpital
Central
Universitaire
de
Helsinki
de
1959
a
1961.
Une
importance
primordiale
est
attribuee
aux
lesions
inflammatoires
du
cordon
ombilical.
Les
series
de
contrOle
comprennent
9
grossesses
compliquees
et
15
grossesses
normales
sans
signes
d'asphyxie
fcetale.
Les
auteurs
ont
releve
des
lesions
inflammatoires
dans
14
cas
d'as-
phyxie
sur
35
(40
%).
Un
patient
seulement
de
la
serie
de
contrOle
presenta
ces
lesions;
it
s'agissait
d'une
toxemic
gravidique.
Pour
essayer
de
trouver
unc
explication
a
la
frequence
des
lesions
inflammatoires
du
cordon
dans
les
asphyxies
fcetales,
les
auteurs
ont
pris
en
consideration
rage
des
patients,
la
parite,
les
complications
de
la
grossesse,
la
postmaturite,
la
duree
du
travail,
le
temps
ecoule
entre
la
rupture
des
membranes
amniotiques
et
la
delivrance,
le
poids
fcetal,
la
longueur
du
cordon,
le
poids
du
placenta.
Aucune
correlation
directe
ne
put
etre
observee
entre
ces
differents
facteurs,
si
ce
n'est
pie
la
plupart
des
asphyxies
fcetales
avec
lesions
inflammatoires
du
cordon
concommittente
furent
retrouvees
lors
des
accouchements
survenus
apres
le
terme
theorique.
La
presence,
en
quantites
impor-
tantes,
de
meconium
dans
le
liquide
amniotique
pourrait
expliquer,
d'apres
les
auteurs,
les
lesions
funiculaires,
bien
qu'une
resorption
appreciable
de
meconium
par
le
cordon
ombilical
ne
put
etre
demon-
tree
que
dans
un
seul
cas.
References
1.
Beckmann,
S.
and
Zimmer,
E.:
fiber
die
Bedeutung
der
«Nabelschnurentziin-
dung».
Arch.
Gynalc.
145:
194-218
(1931).
2.
Benirschke,
K.
and
Clifford,
S.
H.:
Intrauterine
bacterial
infection
of
the
new-
born
infant.
Frozen
sections
of
the
cord
as
an
aid
to
early
detection.
J.
Pediat.
54:
11
18
(1959).
in
Cases
of
Foetal
Asphyxia
of
Unknown
Clinical
Etiology
399
3.
Benirschke,
K.
and
Raphael,
S.
I.:
Candida
albicans
infection
of
the
amniotic
sac.
Amer.
J.
Obstet.
Gynec.
75:
200-202
(1958).
4.
Blance,
W.
A.:
Amniotic
infection
syndrome.
Clin.
Obstet.
Gynec.
2:
705-734
(1959).
5.
Bondi,
J.:
Die
syphilitisehen
Veranderungen
der
Nabelschnur.
Arch
Gynak.
69:
223-248
(1903).
6.
Bourne,
G.
L.:
The
human
amnion
and
chorion.
(Lloyd-Luke,
London
1962).
7.
Flamm,
H.:
Die
pranatalen
Infektionen
des
Menschen.
(Thieme,
Stuttgart
1959.)
8.
Graff,
S.:
Die
Abhangigkeit
der
Leukocytenbewegung
von
der
H-Ionenkonzen-
tration.
Munch.
med.
Wschr.
69:
1721-1726
(1922).
9.
Hintzen,
L.:
Beitrage
zur
Anatomie
und
Histologic
der
congenitalen
Syphilis.
Inaug.
Diss.
(Tubingen,
Fues
1869).
10.
Ikeda,
K.:
rber
Atiologie
und
Pathogenese
der
Leucocyteninfiltration
in
der
menschlichen
Placenta.
Beitr.
path.
Anat.
78:
16-43
(1927).
11.
Kobak,
A.
J.:
Foetal
bacteriemia:
a
contribution
to
the
mechanism
of
intra-
uterine
infection
and
to
the
pathogenesis
of
placentitis.
Amer.
J.
Obstet.
Gynec.
19:
299-316
(1930).
12.
Kiickens,
H.:
rber
Rundzelleninfiltrate
in
reifer
Placenta
mit
Anhangen,
sowie
ihre
Beziehung
zum
Geburts-
und
Wochenbettsverlauf.
Arch.
Gynak.
167:
564-621
(1938).
13.
Langley,
F.
A.
and
Smith,
J.
A.
McC.:
Perinatal
pneumonia:
a
retrospective
study.
J.
Obstet.
Gynaec.
Brit.
Emp.
66:
12-25
(1959).
14.
Mcllwaine,
H.:
(1952).
Quoted
by
Morison.
15.
Mohn,
F.:
Die
Veranderungen
an
Placenta,
Nabelschnur
und
Eihiiuten
bei
Syphilis.
Z.
Geburtsh.
Gyniik.
59:
263-312
(1907).
16.
Morison,
J.
E.:
Foetal
and
neonatal
pathology.
(Butterworth,
London
1952).
17.
Muller,
G.:
Die
primare
Fruchtwasserinfektion
und
die
Moglichkeiten
ihrer
Enstehung.
Arch.
Path.
Anat.
328:
68-97
(1956).
18.
Nielsen,
N.
B.:
Track
of
efterbyrdens
pathologi.
)led
saerligt
Henblik
paa
som
syfilitiske
beskrevne
Betaendelseforandringar
i
Navlesnor,
Hinder
og
Placenta.
Dissertation
1949.
(Ejnar
Munksgaard,
Copenhagen
1950).
19.
Siddal,
R.
S.:
Significance
of
inflammation
of
the
umbilical
cord.
Amer.
J.
Obstet.
Gynec.
14:
192-196
(1927).
20.
Simmonds,
M.:
Nabelschnurentziindung
und
Syphilis.
Arch.
path.
Anat.
209:
146-156
(1912).
21.
Slemons,
J.
M.:
Placental
bacteriemia.
J.
amer.
med.
Ass.45:
1665-1668
(1915).
22.
Sorba,
M.:
Etudes
de
Pathologic
foetale
et
Neonatale
(Rouge,
Lausanne
1948).
Authors'
address:
Dr.
0.
Widholm;
Dr.
B.
Meyer
and
Dr.
C.
v.
Numers,
Second
Department
of
Obstetrics
and
Gynecology,
Helsinki
University
Central
Hospital,
Helsinki
(Finnland)