The Timing of Cord Clamping and Oxidative Stress in Term Newborns

Javier Diaz-Castro, Jesus Florido, Naroa Kajarabille, Maria Garrido-Sanchez, Carmen

Padilla, Catalina de Paco, Luis Navarrete and Julio J. Ochoa
Pediatrics 2014;134;257; originally published online July 14, 2014;
DOI: 10.1542/peds.2013-3798

The online version of this article, along with updated information and services, is
located on the World Wide Web at:
http://pediatrics.aappublications.org/content/134/2/257.full.html

PEDIATRICS is the official journal of the American Academy of Pediatrics. A monthly

publication, it has been published continuously since 1948. PEDIATRICS is owned,
published, and trademarked by the American Academy of Pediatrics, 141 Northwest Point
Boulevard, Elk Grove Village, Illinois, 60007. Copyright 2014 by the American
Academy of Pediatrics. All rights reserved. Print ISSN: 0031-4005. Online ISSN: 10984275.

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ARTICLE

The Timing of Cord Clamping and Oxidative Stress in

Term Newborns
r

Clamping and cutting of the umbilical cord at

hypothermia, and a possible risk of
with oxygen, thereby producing superoxide
birth is by far the oldest and most prevalent
anions.15
intraventricular hemorrhage.11 On the other
Taking into account the oxidative stress and
operation in humans. Although the World
hand, several studies have reported that
inflammation induced during delivery, we
Health Organization stated that late cord
parturition features a strong oxidative stress
designed a study that, for the first time,
clamping or not clamping at all represents a
for both mother and neonate, implying an
correlates the influence of cord clamping'
more physiologic method of neonatal care, 1
increased production of free radicals that
AUTHORS:
Javier Daz-Castro, PhD,ab Jesus Florido, MD,c Naroa Kajarabille,
timing
with oxidative
stressofand
the optimal
timing
of
cord
clamping
has
been
must be controlled
by their ON
antioxidant
WHATS KNOWN
THIS SUBJECT:
Clamping
and cutting
the inflammation
BD,a,b Maria Garrido-Snchez, MD,c,d Carmen Padilla, MD,c,d Catalina de Paco,
1314
signaling.
Our
study
was
based on the
a controversial
issue for decades, and there
umbilicalconsumption
cord at birth increases
is the most prevalent of all operations;
systems. Oxygen
MD,c,d Luis Navarrete, MD,c and Julio J. Ochoa, PhDa,b
2
hypothesis
that
cord
clamping
timing may
is still
debate on the issue. The current
however, the optimal
of cord clamping is still a
during
pregnancy,
and timing
therefore
a
Department of Physiology and blnstitute of Nutrition and Food Technology
have offering
a significant
influence on placenta-tocontroversial
different timings
advantages
obstetric
approach
Western
medicine
is toSpain;mitochondrial
c
respiration issue,
also with
increases,
Jos Mataix
Verd",inUniversity
of Granada,
Granada,
Department of
infant
blood
transfer
(thereby modifying
and
disadvantages.
Obstetrics
and Gynaecology,
School
of Medicine,
Granada,
clamp
the cord
within the
first
10 to University
15 ofwhich
in turn causes an increase in the
d
3
Granada,
Spain;
and
Service
of
Obstetrics
and
Gynaecology,
University
oxygenation
of
both
maternal
and fetal
seconds after birth. However, there has
formation of reactiveWHAT
oxygen
THIS STUDY
speciesADDS: Our findings suggest a protective effect
Hospital San Cecilio, Granada, Spain
tissues),
oxygen
consumption,
and the
been no sound evidence in favor of this
of late
clamping,
(ROS).15 In addition, there
arecord
other
factors increasing the antioxidant capacity and
KEY WORDS
transfer
of
inflammatory
mediators
approach
in comparison
theneonate,
age- antioxidant
old
decreasing
inflammatory-mediated
effects induced during toward
cord clamping
timing (early or with
late), term
todefense,
consider, such as a rapid
changethe
from
the
delivery
term neonates.the placenta, parameters directly linked with
practice
of clamping
the cord between 1 and
oxidative
damage, inflammation
hypoxic intrauterine to
the ofextrauterine
4
postdelivery antioxidant status and
3 minutes
after birth. Earlier physiologic
ABBREVIATIONS
environment, where alveolar PO 2 is almost
inflammatory signaling in healthy neonates.
CATcatalase
IL-6interleukin
6
PGE
2prostaglandin E 2 ROSreactive
studies have shown that, of the total blood
5times
oxygen species SODsuperoxide dismutase sTNF-RIIsoluble
TNF-a higher, or the mediation of several
volume
in combined fetal-placental
receptor II TAStotal antioxidant status TNF-atumor necrosis
factor a
physiologic
processes involved in the
circulation
at
full gestation, ~25%to 60% (54Dr Daz-Castro drafted the initial manuscript and participated finalization
in the analysis; of gestation and delivery, thus
METHODS
160 mL)
is found
in placental
and and reviewed and
Drs Florido
and Kajarabille
carried circulation,
out the initial analyses
promoting the Fenton reaction and leading to
Study
Design
revisedas
the 60%
manuscript;
Drsfetal
Garridoas many
ofthe
redSnchez,
bloodPadilla,
cells de Paco, and Navarrete
Clamping
and
cutting
of and
the Subjects
umbilical cord is the most
13
the production
of BACKGROUND:
highly toxic free radicals.
designed the data56collection instruments, coordinated and supervised
data
are found
therein.
The
oxidative
status
and
inflammatory
prevalent
of
all
operations,
but
the
optimal
timing
of cord
clamping is
collection in the Obstetrics and Gynecology Department and Obstetrics
and
The neonate
is able to cope with this
signaling
of
64
pregnant
subjects
were
EarlyGynecology
cord clamping
at
birth
has
become
a
controversial,
with
different
timings
offering
advantages
and
disadServices, and critically reviewed the manuscript; Dr Ochoa
enormous aggression effectively through a
conceptualized
and designed
the study
and coordinated
measured
in
Obstetrics
and
Gynecology
routine
procedure;
however,
it means
that a and supervised data
vantages. This study, for the first time, compares the influence of
perfectly
collection at the Institute of Nutrition and Department of Physiology;
and alldeveloped antioxidant system and
Servicesin of correlation
the Clinico San
Hospital
early and late cord clamping
withCecilio
oxidative
stress
part authors
of theapproved
bloodthethat
would
naturally
be
final manuscript as submitted.
with the indispensable help of the mother's
February
to October
and inflammation signaling, (Granada,
Because Spain)
cord from
clamping
timing
may have
proportioned to the child remains in the
www.pediatrics.org/cgi/doi/10.1542/peds.2013-3798
defense system, which is of great
Subject inclusion
criteria
were the
a significant influence on 2011.
placenta-to-infant
blood
transfer,
thereby
placenta.7 This practice may deprive
doi:10.1542/peds.2013-3798
importance in the first minutes of life in case
following:
free, normal
course
modifying oxygenation of maternal
anddiseasefetal tissues,
and on
the oftransneonates of significant blood volume and
Accepted for publication May 21, 2014
the newborn's antioxidant system needs
pregnancy,
of 18 to 30 at the start of
fer of inflammatory mediators throughout
theBMI
placenta.
couldAddress
causecorrespondence
short- andto long-term
problems
Julio J. Ochoa, PhD, Institute of Nutrition
and Food
activating.
In this
sense,
the
oxidative
pregnancy,
weight
gain selected
of 8 to 12atkgthe
since
METHODS: Sixty -four pregnant subjects were
GynesuchTechnology
as respiratory
distress,
cerebralof Granada,
palsy, Biomedical Research
"Jos Mataix
Verd, University
1314
aggression
is
diminished
in
<3
hours.
68-10
pregnancy
onset, gestational
period San
of 37 Cecilio
to
Health Sciences
Technological Park,Benefits
Avenida del Conocimiento s/n,
cology and Obstetrics Services
Department
of the Clinico
and Centre,
mental
retardation.
Another importantHospital,
factor to Granada,
consider during
Armilla, 18071 Granada, Spain. E-mail: jjoh@ugr.es
42 weeks
delivery, singlewomen
fetus in who
cephalic
Spain, based
on at disease-free
experiassociated with delayed clamping include
birth, which
can contribute
to
the increase
in of presentation,
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online, 1098-4275).
Copyright
spontaneous
vaginal
delivery,
enced
a
normal
course
pregnancy
and
a
spontaneous,
vaginal,
sinimproved cardiopulmonary adaptation, a
ROS production, is
thedelivery.
evoked inflammation.
2014 by the American Academy of Pediatrics
newborn
of
appropriate
weight
for
gle
Half
of
the
subjects
had
deliveries
with
early-clamped
lower frequency of respiratory distress and
FINANCIAL DISCLOSURE: The authors have indicated theyParturition
have no financial
has been
identifiedinfants
as a source
gestational
age other
and withhalf
Apgar
$7 at
newborn
(at of
10 s),
and the
hadscore
late-clamped
anemia
in infancy, and a longer period of
relationships relevant to this article to disclose.
proinflammatory
mediators,
such
as
61011
first
and
fifth
minutes
of
life,
and
normal
deliveries (at 2 min).
earlyFUNDING:
breastfeeding.
One of the more
No external funding.
metabolites
of
arachi- Erythrocyte
donic acidcatalase
monitoring
None of thegreater
subjects
RESULTS:
activity results.
was significantly
in the
widely
accepted
ofthese
consequences
is have indicated
POTENTIAL
CONFLICT
OF INTEREST:
The authors
(prostaglandin
E
cytokines,
experienced
any
abnormalities
during
labor
2 [PGE2]) andgroup
late-clamped
than
in
the
early-clamped
group
(P
<
.01
for
the
they
have
no
potential
conflicts
of
interest
to
disclose.
the increase in placenta-to-infant blood
and
delivered
spontaneously.
Clinical
including
tumor
necrosis
factor
a
(TNF-a),
umbilical
vein
and
P
<
.001
for
the
artery).
The
values
for
superoxide
volume transfer, supplying an additional 30
parameters
weresoluble
monitored
throughout
the facand interleukin 6 (IL-6).
These total
mediators
are
dismutase,
antioxidant
status, and
tumor
necrosis
to 75 mg of iron at delivery.12 The concerns
delivery.
Variables
such
as
age,
parity,
potent stimulators
ROS production.
tor ofreceptor
II were all significantly higher in the late-clamped
about delayed cord clamping include the
gestational period,
Therefore,
a
rise
in
the
concentration
of early-clamped
group
compared
with the
group and
(P <clinical
.01, Ppregnancy
< .001, and
possibility of polycythemia, hyperviscosity,
outcome
were
obtained
from
the
mother's
P
<
.001,
respectively).
cytokines
and
PGE
could
be
responsible
for
2
hyperbilirubinemia, transient tachypnea of
medical
history.
Means
of
variables
were cord
CONCLUSIONS:
The results suggest a beneficial effect of late
increased oxidative
stress. Furthermore,
the newborn, delay in resuscitation,
compared
clamping,
TNF-a also increases
the produced
interactionbyof an increase in antioxidant capacity and modelectrons

258 DAZ-CASRTO
et al 134, Number 2, August 2014
PEDIATRICS Volume

eration of the inflammatory-mediated effects induced during delivery

of term neonates. Pediatrics 2014;134:257-264

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257

Age of mother, y

Early Cord Clamping (n = 33)

Late Cord Clamping (n = 31)

30.8 0.9

29.1 0.8

Parity, primiparous/multiparous
12/21
Gestational age, wk
38.9 0.4
20
Gender of newborn,
male/female
17/16 this
with
method
theofStudent's
Crapo et t al.test,
The
because
method
is
Wt of newborn, g
3341.4 85.8
approximation
could
be
applied
given
the
based
on
SOD
inhibition
of
cytochrome
c
Maternal-fetal ejection, min
46.2 4.8

sample
We assigned
70 fullterm
reduction,size.
measured
spectrophotometrically
pregnant
women
2 groups
upon
at 550 nm.
One tounit1 of SOD
activity
is
arrival
in ourneeded
hospital:
definedtoasthe
thedelivery
amount room
of enzyme
to
the
early-clamped
group,
which thec
produce
50% inhibition
of theincytochrome
umbilical
reduction cord
rate. was clamped within 10 s of
fetus
expulsion,
and the late-clamped
Plasma
hydroperoxide
content group,
was
in
which
the
umbilical
cord
was
at 20 cm
determined by using an left
Oxystat
kit
below
the vaginal
introitusVienna,
and then clamped
(Biomedica
Gruppe,
Austria).
at
2 min after
The selection
of athe
2Oxystat
is aexpulsion.
colorimetric
assay for
3
min
interval
was
based
on
current
literature
quantitative determination of peroxides in
and
the results
a preliminary
study where
plasma,
serum,ofand
other biological
fluids.
we
observed
that
numerous
umbilical
The peroxide concentration is determined
by
arteries
bledbiological
after thisperoxides
period. For
reaction had
of the
andthea
first
subject,color
the reaction
expectantusing
mother
was
subsequent
3,3',5,5'assigned
to
a
treatment
group
by
coin
toss,
tetramethylbenzidine as the substrate. The
and
plate for
wassubsequent
measured atcases,
450 nmthe
on subject's
a BioTek
order
of
arrival
at
the
delivery
room
microplate reader.
determined her group (assigned alternately
Erythrocyte
membrane
hydroperoxide
to each group). The sample size was
content was estimated according to the
determined the number of normal deliveries
method described previously by Ochoa et
at 13our hospital and laboratory availability. Of
al, which is based on the rapid peroxidethe 35 women assigned to2 the early-clamped
mediated oxidation of Fe + to Fe3+ in acidic
group, 2 were excluded from the study, 1 for
conditions. The latter, in the presence of
an Apgar score <7 and the second
for
xylenol orange, forms an Fe3+xylenol
inadequate birth weight; therefore, the final
orange complex that can be measured
early-clamped study group comprised 33
spectrophotometri- cally at 560 nm (Perkin
cases. Of the 35 women assigned to the
Elmer UV-VIS L-16, Norwalk, CT).
late-clamped group, 4 were excluded from
the study, 1 for an Apgar score <7, 2 for
Statistical Analyses
operative
delivery, and 1 because of
anomalies
observed analysis,
during we
monitoring;
Before any statistical
checked
therefore,
theforfinal
late-clamped
study group
all variables
normality
and homogeneous
comprised
31 cases.
Newborn Smirnov
infants in and
the
variance using
Kolmogorovlate-clamped
were heldCategorical
in their
Levene tests,group
respectively.
mothers'
while waiting
forData
the
variables arms
were compared
withsupine
x2 tests.
cord
to be clamped.
The maternal-fetal
were expressed
as the mean
SEM. A 2ejection
period lasted
45.2used
5.5to min
for all
tailed Student's
ttest was
determine
subjects.
consent
was Student's
obtained
significant Informed
differences.
Unpaired
from
the nature
and
ttests the
wereparents
used toafter
determine
differences
purpose
study(early
had versus
been fully
between of
the the
groups
late
explained
to
them
and
they
understood
it.
clamping), and a paired Student's ttest was
This
study was
approveddifferences
by the University
of
performed
to determine
between
Granada
ethical committee
blood samples
from veins(PI030780).
and arteries in
each group (vein versus artery). A level of P
< .05 was

PEDIATRICS Volume 134, Number 2, August 2014

ARTICLE

11/20
39.6 0.3
Blood
considered
Samplingto16/15 indicate
statistical
3325.8 79.0
significance.
SPSS
software
version
20.0
Blood samples 44.9
were
5.9 collected from the

were
complete,arteries
samplesthan
were
an
from umbilical
in read
those atfrom
appropriate
wavelength
(450-490
nm)group,
using
veins (P < .001
in the earlyclamped
(IBM SPSS
IBM immediately
Corporation) after
was
aP < BioTek
reader
.01 in themicroplate
late- clamped
group).(BioTek,
There
umbilical
veinStatistics,
and arteries
used clamping.
for dataBytreatment
and statistical
Winooski,
were alsoVT).lower levels of membrane
cord
taking a sample
of each
The
sTNF-RII
kit is a solid phase
analysis.
erythrocyte
hydroperoxides
of the sandwich
umbilical
blood
type, we could assess the substances
enzyme-linked
immunosorbent
assay.
artery
in
the
early-clamped
group
than
inThe
the
circulating in the maternal-fetal bidirectional
RESULTS
microtiter
plate
was
read
at
an
appropriate
other
group
(P
<
.01
for
the
umbilical
vein
in
transfer system during delivery. During the
wavelength
(450
nm)
with
a
BioTek
early cord clamping and P < .05 for the
examination,
the Spanish
size, shape,
consistency,
All parents were
Caucasians,
and
microplate
artery and reader.
vein in late cord clamping). TAS
and
completeness
of thewere
placenta
at delivery
no differences
found inwere
the
concentration
was greater in the lateobserved
and
the
absence
of
pathologic
age and parity of the mothers, the
clamped
group
(P < .001) than in the earlyfindings
recorded.
The total
gestational
age, gender,
andprocessing
weight oftime
the
Oxidative Stress Parameters
clamped group. With regard to inflammatory
was
<15 and
min. the
Blood
was immediately
newborns,
maternal-fetal
ejection
Plasma total antioxidant status (TAS) was
centrifuged
at 1750
g for followed a term
signaling, there was greater expression of
(Table 1); all
pregnancies
analyzed with a TAS Randox kit (Randox
10 min
4C in a presentation
Beckman GS-6R
IL-6 in the umbilical artery than in the vein in
gestation
withat cephalic
and
Laboratories Ltd, Crumlin, UK). Results were
refrigerated
both early and late cord clamping (P < .001)
normal delivery.
Bilirubincentrifuge
was also (Beckman
assessed,
expressed in millimoles per liter of Trolox
Instruments,
Inc,
Fullerton,
CA)
to
and the results for early clamping were
(Fig 1A). Moreover, TNF-a (Fig 1B) is lower
equivalents. The linearity of calibration
separate
and vein
red
31.55 2.55
mmol/Lthein plasma
the umbilical
in the umbilical vein of the early-clamped
extends to 2.5 mmol/L of Trolox. The
and 24.53blood
2.03 cell
mmol/Lpellets.
in artery.Plasma
In the
group than in the artery (P < .001), and also
reference range for human blood plasma is
samples
immediately
frozen
late-clamped
group were
the results
were 29.42

differences were found between both groups

given by the manufacturer as 1.30 to 1.77
and andstored
80C until
1.49 mmol/L
28.82 at 1.70mmol/L
for
in the umbilical artery, being lower in the
mmol/L. Duplicate measurements were used
analysis.
Erythrocyte
cytosolic
vein and artery,
respectively.
No differences
late-clamped group (P < .05). It is
to calculate intraassay variability. Glutathione
membrane
were foundand
between
groups;fractions
however, were
they
noteworthy that we observed a remarkable
peroxidase activity was measured according
prepared
by
differential
were observed
for vein versus
artery
in the
increase in sTNF-RII concentration (Fig 1C)
to the method of Floh and Gunzler,18 which
centrifugation
with hypotonic
early-clamped
group (P < .001).
in the late-clamped group compared with the
is based on the instantaneous formation of
hemolysis
andare summarized
successive
Oxidative stress
biomarkers
early one (P < .001). Finally, no differences
oxidized glutathione during the glutathione
differential
centrifugations
in Table 2.
In our study, erythrocyte
CAT
were observed in umbilical vein and artery
peroxidase catalyzed reaction. The resulting
according
to thehigher
method
of
activity was
significantly
in the
PGE2 concentrations, whether between or
16
oxidized glutathione is continually reduced
Hanahan
final
umbilical vein
than inand
theEkholm.
artery for The
the early
within either of the experimental groups
by an excess of glutathione reductase and
fractions
aliquoted,
cord clamping
groupwere
(P< .001),
and wesnapalso
(early-clamped, 871.6 50.79 pg/mL and
reduced nicotinamide adenine dinucleotide
liquid nitrogen,
and
observed frozen
greaterin activity
for the late878.8 37.94 pg/mL; late- clamped, 862.3
phosphate present in the cuvette. The
stored compared
at 80C with
until the
analysis.
clamped group
early40.71 pg/mL and 863.27 36.74 pg/mL,
subsequent
oxidation
of
reduced
Cytosolic
protein
clamped group
(P < .01
for the content
umbilical was
vein
both measured in the vein and artery,
17
nicotinamide
adenine
dinucleotide
measured
by
the
Lowry
method.
and P< .001 for the artery). SOD was
respectively).
phosphate
was
monitored
significantly higher in the late- clamped
Biochemical Parameters
spectrophotometrically
(Thermo Spectronic,
DISCUSSION
group than in the early- clamped group (P < .
Total
bilirubin
was
measured
in
umbilical
Rochester,
NY)
at
340 nm. Cumene
01).
This study was designed to simultaneously
arterial
and
venous
blood
using
Spinreact
hydroperoxide
was
used
as the substrate for
In addition, we observed lower levels of
assess the oxidative stress and
enzymatic
kits
(Spinreact
SA,
Girona,
the
reaction.
plasma hydroperoxides in samples
Spain), according to the manufacturer's
Catalase (CAT) activity was determined
instructions.
using a spectrophotometer operating at 240
nm to monitor the H2O2 decomposition that
Inflammatory Parameters
results from CAT ac- tivity. 19 Activity was
TNF-a, IL-6, and soluble TNF-a receptor
calculated from the first-order rate constant
11 (sTNF-RII) plasma levels were
K (per second).
TABLE 1 General Characteristics of Mothers and Their Neonates at Delivery
determined by using Biosource
Superoxide dismutase (SOD) activity was
kits (Biosource Europe, Nivelles,
determined according to the
Belgium), and PGE2 was
determined using an R&D kit
(R&D Systems Europe, Abingdon,
UK). The tests for TNF-a, IL-6,
and PGE2 are solid phase enzyme
amplified
sensitivity

Downloaded from pediatrics.aappublications.org at Linkopings Universitetsbibliotek on August 21, 2014

259

Early Cord Clamping

Umbilical
Vein

Late Cord Clamping

Umbilical
Artery

Umbilical
Vein

Umbilical
Artery

Plasma parameters

TABLE 2 Oxidative Stress Biomarkers in Umbilical Cord Veins and Arteries Taken From Both Groups
TAS, nmol/mL
0.903 6 0.03**
0.962 6 0.03**
1.038
0.03* 1.192 6 0.06
Plasma hydroperoxides,
8.021 6 0.30*
6.752 6 0.35
7.739
0.32* 6.641 6 0.44
nmol/mL
6

Erythrocyte parameters
Erythrocyte cytosol
CAT, K/sec-mg
Glutathione peroxidase, U/mg
SOD, U/mg
Membrane hydroperoxides,
nmol/mL

0.281
33.79
218.7
26.85

6
6

0.02*,**
1.78
8.79**
1.48*

0.233 6 0.01**
33.86 6 1.81
199.35 6 11.32**
21.776 1.38

0.329
31.96
250.1
24.91

0.01*
1.12
10.25
1.30

0.289 6 0.01
32.40 6 1.58
243.1 6 9.30
23.45 6 1.32

Values are means SEM. No significant differences were found between groups.

260 DAZ-CASRTO et al

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ARTICLE

Values are means SEM. *Mean values differ between vein and artery within the same group, P < .05. **Mean values differ between groups for either
veins or arteries, P < .05.

inflammatory signaling induced by different

another possible oxidative stress- inducing
timings of umbilical cord clamping (early
factor is the concentration offree Fe2+. One
versus late), because there is little
ofthe most universally accepted benefits of
information available about this issue in the
late cord clamping is the lower incidence of
scientific literature. Approximately half of the
anemia, caused by higher plasma Fe
subjects delivered early-clamped newborns
levels.610 In the perinatal period, especially in
(at 10 s) and the other half late- clamped
preterm babies, low levels of iron carriers
babies (at 2 min). Cord blood samples were
can increase plasma free iron, which is a
collected from the umbilical vein and artery,
prooxidant factor in both the fetus and
therefore allowing the maternal-fetal
newborn.2223 This element increases the
bidirectional transfer of substances to be
necessity to understand how late cord
assessed at the time of delivery. One of the
clamping can influence the newborn's
most controversial points regarding timing is
antioxidant system.
the concern that delayed clamping can
Cord clamping timing (early versus late)
increase the possibility of hyperbilirubinemia
involves diverse changes in antioxidant
and jaundice.21 This misgiving is not
status. In our study, erythrocyte CAT activity
supported by the current study because no
was greater inthe umbilical vein than in the
differences in bilirubin levels were observed
artery in the early- clamped group, and we
between early- and late- clamped groups.
also observed an increase in the lateclamped group compared with the earlyThe importance of oxidative stress
clamped group. SOD was significantly
duringchildbirth and pregnancy is well
higher in the late-clamped group than in the
known, and it originates from several
early-clamped group. Sugino et al 24 suggest
sources, including a higher production of
FIGURE radicals
1
that SOD is steroidally regulated and that
free
caused by increased
(A) IL-6, (B) TNF-a, and (C) sTNF-RII in umbilical cord veins and arteries. Values are means SEM.*Mean values differ
decreased
activity of this enzyme is
mitochondrial
activity,
thesame
change
a values
between vein and artery
within the
group, P from
< .05. **Mean
differ between groups for either veins or arteries, P < .
implicated in miscarriages, so we can
05.
hypoxic
to a hyperoxic environment, and
conclude that the higher level recorded in
diverse mediators in the childbirth
1315
the late-clamped group may have a positive
process.
These factors are featured in
particularly sensitive to oxidative damage
concentration
and heme
The aueffect on the neonate's
futureiron.
development,
both late and early cord clamping;
because of its high polyunsaturated fatty
toxidation
of hemoglobin,
generating
increasing
their
protection
against
the
nevertheless,1314
in late cord clamping
acid content ; therefore, it is an important
superoxide
anion
radicals,
is
the
main
oxidative stress induced by labor. TAS
system for evaluating the effect of oxidative
source of ROS in red blood cells.22 In this
stress. Erythrocytes are continuously
sense, the lower plasma and membrane
exposed to ROS injury because of their high
erythrocyte hydroperoxide concentrations in
cellular oxygen
umbilical arteries
262
DAZ-CASRTO
al Number 2, August 2014
PEDIATRICS
Volumeet134,

compared
was also higher
with the
in veins
the late-clamped
in both earlygroup,
and
late-clamped
suggesting a protective
groups indicate
effect of that
late cord
the
neonate
clamping;has
because
enoughan
antioxidant
imbalancecapacity
between
to
scavenge
oxidant and
for antioxidant
and neutralize
levelsfreehasradicals
been
produced
noted in preterm
during infants,
the delivery.
that places
We think
themthat
at
this
a greater
result can
risk be
of directly
diseases
correlated
associated
with with
the
levels
prematurity,
of CATwhereas
and SOD,term
which
infants
both reduce
appear
the
better
oxidative
adapteddamage
to withstand
causedoxidative
by ROSinjury
that
are
caused
capable
by maturation
of initiatingoflipid
theirperoxidation,
antioxidant
25
releasing
defense systems.
destructive
catalytic enzymes, and
damaging
There are cell
several
membranes.
causes Inofthe
addition,
oxidative
the
activity
stress induced
of theseduring
enzymes
birth. was
Potential
observed
sources
to
be
of ROS
greater
duringinparturition
the late-clamped
include the mother,
group,
providing
the placenta
a and
noteworthy
the fetus.advantage
If the fetusinwere
the
erythrocyte.
the main source of ROS, then the umbilical
Delivery
cord arterial
at all
ROS
gestational
levels would
agesbehas
expected
clear
biochemical
to be higherparallels
than umbilical
with anvenous
inflammatory
levels.
response,
However, typified
wedidobservea
by the increased
lowerlevel
output of
prostaglandins,
plasma hydroperoxidescytokines,
in umbilical arteries
and
proinflammatory
than in umbilicalmediators,
veins. This
which
finding
can incould
turn
increase
suggest that
the evoked
the fetus
oxidative
metabolizes,
stress.30rather
The
mechanisms
than produces,
underlying
these the
radicals.
onset of
Another
labor
remain
potentialunclear.
source Parturition
of free radicals
consists isofthe
5
separate
mother. Although
but integrated
several physiologic
studies haveevents:
found
membrane
elevated levels
rupture,of cervical
protein dilatation,
or lipid
myometrial
peroxidationcontractility,
productsplacental
in pregnancies
separation,
and
complicated
uterine involution.
by Evidence
hypertension
increasingly
or
supports
preeclampsia,
the 26roles
other ofstudies
prostaglandins
do not support
and
27
cytokines
these findings.
in each
Nevertheless,
of these events.
the The
effectrole
of
of
maternal
the proinflammatory
oxidative stress
cytokines
on the interleukin
fetus may
1b,
be IL-6,
minimal;
interleukin
previous
8, and TNF-a
studies
is evident
have
in
consistently
term and shown
preterma delivery.
low levelThe
of correlation
uterus is
activated
between maternal
by proinflammatory
and cord bloodcytokines
plasma
through
levels ofstimulation
lipid peroxidation
of the expression
products. The
and
production
remaining potential
of uterinesource
activation
of free
proteins.
radicals
One
is
of
the these
placenta.
actions Some
is the studies
stimulationhave
of
prostaglandin
demonstrated synthesis.
lipid peroxidation
Together inthese
the
feedforward
placenta inmechanisms
complicated
activate
pregnancies.
the uterus,28
trigger
However,
theWalsh
production
et al29ofhave
uterine
shown
contractile
that in
31-33
stimulants,
vitro secretion
andoflead
isoprostane
to labor and
by the
delivery.
placenta
Ais limitation
8 times greater
of this study
on theismaternal
that the number
side ofthe
of
patients
placenta was
than the
small,
fetalreflecting
side.
limitations in
the
Erythrocytes
number have
of normal
a key role
deliveries
in the evoked
at our
hospital,
oxidativelaboratory
stress availability,
of the neonate.
and budget.
The
erythrocyte membrane is

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21, 2014
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21, 2014

261

ARTICLE

18.
In

Flohcurrent
L, Gnzler
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21. American Academy of Pediatrics Subcommittee on
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Del Vecchio A,
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263

The Timing of Cord Clamping and Oxidative Stress in Term Newborns

Javier Diaz-Castro, Jesus Florido, Naroa Kajarabille, Maria Garrido-Sanchez, Carmen
Padilla, Catalina de Paco, Luis Navarrete and Julio J. Ochoa
Pediatrics 2014;134;257; originally published online July 14, 2014;
DOT- 10 1542/peds 2013-3798
Updated Information &
Services

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References

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