LATE VS

EARLY CLAMPING OF THE UMBILICAL

LATE VS
CORD
EARLY
IN FULL-TERM
CLAMPING OF
NEONATES
THE UMBILICAL CORD
IN FULL-TERM NEONATES
CLINICIAN'S
CORNER
REVIEW
cal cord.the
during
Of these,
first 68 randomized
months of
14,18
life.
(T
ABLE
Others
1)32,37-43
believe and
that the
7
increase in blood (Tvolume
nonrandomized
ABLE
2)
to19,44-49
the
neonatal circulation
controlled
trials were
resulting
included
from
in
delays
the
review.
in clamping
Three of
may
the
beincluded
harmful
and could
trials
wereresult
conducted
in overloading
by the same
the
neonatal group,
research
blood but
volume,
it was clear
thus
increasing
from
the descriptions
the
likelihood
that they
of
respiratory
were
based
distress,
on19,20 different
neonatal
21
jaundice,44,47,48
samples.
andThe
polycythemia.
remaining 22,23
22
In addition,
studies
were
early
excluded
clampingbecause
is part
of active
they
included
management
exclusively
of the
preterm
third
stage of
infants
(12 labor
trials)50-61
to or
assist
low-birthwith
delivery of the placenta, and this
management has been shown in a
Cochrane review to significantly
decrease
maternal
Eileen K. Hutton,
PhD blood
Eman S.loss
following birth.24
Hassan,
MBBCh
Several reviews have studied
the potential benefits and risks of
LAMPING AND CUTTING OF
late vs early clamping of the
THE
umbilical
cord.
In
a
recent
umbilical cord at birth is
Cochrane review of cord clamping
by
in the preterm population, late
far the oldest and most
clamping showed some potential
prevabenefit in terms of decreased need
lent intervention in hufor blood transfusion and lower
mans. In spite of that, the optimal
risk
of
intraventricular
timhemorrhage.25 Reviews to date of
ing of cord clamping has been a
studies in term infants provided
controversial issue for decades.1-4
no
strong
evidence
for
the
There
superiority of either clamping
are no formal
practice guidelines,
strategy.3,26,27
However,
these
but
reviews were based on studies
most practitioners in western
with small numbers of enrolled
couninfants and did not include 2 large,
tries clamp and cut the cord
well-designed trials published in
immedi2006.
One
additional
review
ately
after
birth,
while
the
combined studies of preterm and
practice
term infants in a meta-analysis
worldwide is variable.5,6
and focused the discussion on
Earlier
physiological
studies
practice in developing countries.28
have shown that, of the total
Thus, we believed that an updated
blood volume in the combined
rigorous review and metaanalysis
fetal-placental circulation at full
of the timing of cord clamping in
gestation, approximately 25% to
term infants was needed.
60% (54-160 mL) is found in the
placental circulation and that as
METHODS
many as
60% of thethe
fetal red
blood
We
compared
potential
7-10
cells
areand
found
This
benefits
harmstherein.
of late vs early
blood
is
also
known
to
be
rich
clamping of the umbilical cord in
in
9,11
hematopoietic
stem cells.
term infants. Outcomes
of interest

31
include
concentration
a
control
<10 pg/L).
group
We
(2
766
were
studies),
also
included
interested data
in
determining
previously
published
the short(1 trial),
and 67
longdid
term report
not
effects of
gestational
the timing age
of cord
(2
68,69
clamping
trials),
oron
did not
a include
number
any of
70
physiological
the
outcomes of interest
parameters
(1 trial).in
infants,
No
studies
including
including the
only cesarean
absolute
values ofwere
births
hemoglobin,
found, hematocrit,
and
no
blood volume
additional
data
andwere
viscosity,
obtained
and
bilirubin,
from
contacts
as well
with authors.
as iron status
measured by levels of ferritin and
Description of32Included Trials
stored iron.
Eight trials were conducted in

2
(<10
sets of
performs
1000
were
total
resolved
births),
by
rereviewing
including
Canada,
the
corresponding
Germany,
articles,
United Kingdom,
and theSweden,
final set
and was
the
agreed
United States;
on by2 in
consensus.
countries with
The
methodological
moderate perinatal
quality
mortality
of rates
each
trial
(10-20),
was
including
also Argentina
independently
and
assessed
Libya; and
using
5 a
in modified
countries
version
with
of
higher
the Jadad
perinatal
scale.33
mortality
Trials rated
rates
10
or
(>20),
more are
including
considered Egypt,
high
quality.
Guatemala,
No disagreements
India, and Mexico.
existed
Six
between
of the 15
reviewers
trials were
that impacted
of high
categorization
quality (Tables of
1 and
trials
2).as
There
being
was
of
low
no quality
clear evidence
vs high quality.
of substantial

Late vs Early Clamping of the

Umbilical
Cord
in
Full-term
Neonates

Inclusion and Exclusion Criteria

The review included controlled Analysis

trials
(both
randomized
and For the meta-analysis we used
34
nonrandom- ized) comparing late Revman version 4.2. Double entry
of
the
data
into
Revman
was
Context
vs earlyWith
cord
few exceptions,
clamping the
following
umbilical cord of every newborn is clamped
and cut
at
carried
out
by
the
2
reviewers.
For
birth,
yet
the
optimal
timing
for
this
intervention
remains
controversial.
birth in infants born vaginally or
Objective
To compare
the potential
benefits and
harms of late
vs early cord
in
continuous
variables,
we clamping
used the
by cesarean
delivery
at37ormore
term
infants.gestation. We included mean
and standard deviation
weeks
Data
Sources Search of 6 electronic databases (on November 15, 2006, starting from the
only those studies that reported reported in the original trials to
beginning of each): the Cochrane Pregnancy
and Childbirth
trials register,
the
theGroup
weighted
mean
original data on at least 1 of our calculate
Cochrane Neonatal Group trials register, the Cochrane library, MEDLINE, EMBASE, and
difference
(WMD).
We
expressed
outcomes
of interest.
excluded
CINHAL;
hand
search of We
secondary
references in relevant studies; and contact of
the
harmful
effects
of
each
studies that
involved
investigators
aboutexclusively
relevant published
research.
clamping
practice
as
the
relative
preterm
infants
or
low-birthStudy Selection Controlled trials comparing late vs early cord clamping following birth in
infants
weight
born at
infants,
37 or more because
weeks' gestation.
the risk (RR) of adverse events.
of pooled
outcomes
Data
Extraction
Two of
reviewers
assessed eligibility
and quality
of trialswith
and
potential
effects
earlyindependently
vs late Estimates
extracted
dataare
for outcomes
of interest:
hematologic
status; ironintervals
status; and risk
of
confidence
(CIs)
clamping
expected
to infant
be 95%
adverse
events
such
as
jaundice,
polycythemia,
and
respiratory
distress.
were
calculated
by
means
of
fixeddifferent in these 2 groups.
Data Synthesis The meta-analysis includedeffects
15 controlled
trials We
(1912
newborns).
Late
models.
also
performed
cord
clamping
was delayed for at least 2 minutes (n = 1001 newborns), while early clamping
Search
Strategy
tests of heterogeneity between
in
trials (n=911
newborns)
was performed
immediately after birth. Benefits
over ages 2
Tomost
identify
all relevant
studies,
we trials
using the y2 test for
to 6 months associated with late cord clamping include improved hematologic status
performed a literature search on significance. When heterogeneity
measured as hematocrit (weighted mean difference
[WMD], 3.70%; 95% confidence interval
November
15, 2006,
in 6 as
electronic
studies (WMD,
was found
to be
[CI],
2.00%-5.40%);
iron status
measured bybetween
ferritin concentration
17.89; 95%
CI,
databases and(starting
from 19.90;
the95%
significant
as and
indicated
by I2
16.58-19.21)
stored iron (WMD,
CI, 7.67-32.13);
a clinically important
beginning
ofrisk
each):
the (relative
Cochrane
reduction
in the
of anemia
risk (RR),
0.53; 95%
CI, 0.40-0.70).
Neonates
with
values
greater
than 50%,
pooled
Pregnancy
andat Childbirth
late
clamping were
increased risk Group
of experiencing
asymptomatic
(7 studies
estimates
basedpolycythemia
on randomeffects
35 infants]: RR,
[403
neonates]:
RR, 3.82;the
95% CI,
1.11-13.21; models
2 high- quality
studies
only [281
trials
register,
Cochrane
were
reported.
For those
3.91;
95% CI,Group
1.00-15.36).
Neonatal
trials register, the outcomes with adequate data, we
Conclusions
clampingMEDLINE,
of the umbilical cord in full-term neonates fora minimum of
Cochrane Delaying
library,
performed a sensitivity analysis by
2 minutes following birth is beneficial to the newborn, extending into infancy. Although there
EMBASE, and CINHAL. The search comparing the findings of the
was an increase in polycythemia among infants in whom cord clamping was delayed, this
was not restricted by language. metaanalysis of high- and lowcondition appeared to be benign.
We used
both the Medical Subject quality studies togetherwww.jama.com
JAMA.
2007;297:1241-1252
with only
Heading terms and text word those studies that had been
search for late, early, umbilical ranked as high quality.
cord
clamping,
placental
Subgroup
analyses
were
transfusion, and term infants: planned for possible confounding
(early
immediate
or birth-related practices that had
and ironorloss,
as well asor
of late
several
Author Affiliations: Department of Obstetrics and
delay*)
and
(umbilical-cord
and
Gynecology,
McMastertoUniversity,
Ontario
potential
alter Hamilton,
the rate
of
blood
disorders
and
type 2 the
(Dr Hutton); and The Child and Family Research
clamp*
or
placentaltransfusion, including
diabetes, as a consequence
of loss placental
Institute (Dr Hutton), Western Regional Training Centre
3,16,17
transfusion)
and stem
(termcells.
or fullmode
delivery
vs
for Health of
Services
Research (vaginal
(Dr Hassan), and
of hematopoietic
Department of Health
Care
and
Epidemiology
(Dr
term
or
infant).
We
also
cesarean),
height
of
infant
relative
Early cord clamping has been Hassan), University of British Columbia, Vancouver.
performed
a ahand
of to
that of the
maternal
or
postulated as
majorsearch
cause of
Corresponding
Author:
Eileen K.introitus
Hutton, PhD,
McMaster University,
1200
Maincord
St W, clamping
MDCL- 3101,
secondary
references
in relevant
during
the
anemia in infancy,
and this
has led placenta
Hamilton, Ontario, Canada L8N 3Z5 (huttone
studies.
Investigators
working in interval,
use of oxytocic drugs, and
some investigators
to recommend
@mcmaster.ca).
this
were contacted
about milking of the cord toward the
late area
clamping
as a low-cost

were decided a priori and included

For editorial comment see p 1257.
reported or clinically determined
CME available online at www.jama.com
jaundice,
use
ofphototherapy,
polycythemia
(defined
as
29
hematocrit
increased
to
>
65%),
Table 1. Included Randomized Controlled Trials (N = 8) Comparing Early vs Late Cord Clamping in Term Infants, Listed According to Study Quality Score
2007
American
Medical
Association.
rights reserved.
1242
JAMA,
March 21,
2007Vol
297, No. 11All
(Reprinted)

Source
Ceriani

Location
Argentina

Quality
Score/
Comments*

Randomization
Multicenter

12

Participants
276 Full-term infants born vaginally or by

2007
(Reprinted)
American
JAMA, Medical
March 21,Association.
2007Vol 297,All
No.rights
11 1241
reserved.

Intervention
ECC (n = 93) within

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

Outcomes
Primary: venous

Cernadas
et al,37
2006

Chaparro et
al,32 2006

(computer-

Outcome

Mexico City, Computer12

Mexico
generated random
numbers in sealed
opaque envelopes

Emhamed et
al,38 2004

Gupta and India

Ramji,39
2002

cesarean delivery

generated
assessors
Inclusion criteria: uneventful singleton
random numbers
blinded
pregnancy at term Fetal exclusion criteria:
in sealed opaque Compliance with
congenital
envelopes),
allocated
malformations or intrauterine growth
stratified by
intervention:
restriction (estimated fetal weight <10th
hospital and mode
ECC, 94.6%;
percentile)
of delivery using
LCC 1, 91.2%; Maternal exclusion criteria: diabetes,
variable block
LCC 2, 90.2%
(pre)eclampsia, hypertension, or any other
sizes
complications

Tripoli, Libya Randomized sealed

opaque
envelopes

Computer
generated
random-number
sequences in
sealed opaque
envelopes

hematocrit value

(mean, 12.7 s)
LCC 1 (n = 91; excluded) at 1
min after birth (mean,
59.8 s)
LCC 2 (n = 92) at 3 min after
birth (mean, 169.5 s);
newborns placed on
mothers abdomen or
lap

6 h after birth
Secondary: hematocrit,
bilirubin, early
morbidity and
mortality at age 24
to 48 h; any
neonatal disease
occurring within
the first month of
life

476 Mother-infant pairs

ECC (n = 239) 10 s after
Primary: infant
Inclusion criteria: women not in advanced labor
delivery
of
the
infants hematologic and iron
when admitted
shoulders (mean,
status at age 6 mo
Exclusion criteria: planned cesarean delivery;
16.5 [SD, 6.4] s)
Secondary: estimated
pregnancy of <36 or >42 weeks; multiple gestation; LCC (n = 237) at 2 min after
maternal blood
(pre)eclampsia; diabetes; hypertension;
delivery of the infants
loss at delivery,
cardiopathies, chronic renal disease; hemorrhage;
shoulders (mean, 99.3
newborn
placental abnormalities; newborns with low birth
[SD, 44.2] s), with
hematocrit, and
weight; or fetal anomalies Women excluded if not newborns placed at level of
reported clinical
planning to
jaundice between
uterus
breastfeed for at least 6 mo, smoked at all during
birth and age 14 d
pregnancy, unwilling to return for follow-up visits
at the same hospital, or were participating in
another research study at the hospital

10
104 Singleton term infants (37-42 wk) born
1 Lost to
vaginally
follow-up in
Fetal exclusion criteria: birth weight <2500 g or
each group
gestational age <37 wk
Significantly higher Maternal exclusion criteria: gestational diabetes or
proportion of
pre(eclampsia), instrument delivery, serious
anemic
hemorrhage during pregnancy or delivery,
mothers in the
major congenital abnormalities, and need for
LCC group
early cord clamping or resuscitation

10
44 Infants lost to

the first 10 s

102 Singleton term infants born vaginally to

anemic mothers (hemoglobin <10 g/dL)

follow-up at age 3 Fetal exclusion criteria: major congenital

mo
anomalies, needed resuscitation at birth Maternal
exclusion criteria: eclampsia, severe heart failure,
severe antepartum hemorrhage, Rh
isoimmunization

ECC (n = 46) within 10 s

Primary: hematologic
after birth (mean, 12.8 [SD, status 24 h after birth
5.5] s)
Secondary: possible
LCC (n = 58) after cessation of
adverse effects
cord pulsations (mean, 214.6
[SD, 50.6] s); newborns placed
on mothers abdomen In both
groups, intramuscular
oxytocin given after cord
clamping

ECC (n = 53) immediately Primary: levels of

after birth (mean time
serum ferritin and
unknown)
hemoglobin at age
LCC (n = 49) after
3 mo Secondary: full
descent of placenta in the breast feeding, adverse
vagina (mean time unknown) events
Newborns held within 10 cm
below the introitus

LATE VS EARLY CLAMPING OF THE UMBILICAL CORD IN FULL-TERM NEONATES

Table 1. Included Randomized Controlled Trials (N : 8) Comparing Early vs Late Cord Clamping in Term Infants, Listed According to Study
Quality Score (cont)

Source

Location

Nelson et al,40 Canada 1980

United

Oxford

Randomization

Quality
Score/
Comments*

Simple
random-number
tables in sealed
opaque envelopes 10
Outcomes assessors
were blinded
Oxytocic drugs for
third-stage
management
comparable
between groups
2 Women lost to
follow-up
8
Geethanath et New Delhi, India No description of
42
al, 1997
randomization
method,
withdrawals, or
dropouts
Midwives
Research
Group,41
1991

Saigal et al,43
1972

Kingdom

Montreal,
Quebec

Participants

Intervention

Randomization occurred 10
55 Singleton term infants born vaginally
ECC (n = 26) within the first 60
at 36th gestational 1 Dropped out
Maternal inclusion criteria: low obstetrical
s of delivery (median, 45
week, stratified by
risk (score <3), interested in
[range, 2-80] s)
after
parity and social
Leboyer approach to birth, intended LCC (n = 28) as part of Leboyer
randomization
class before
to attend prenatal classes
method after stopping of
randomization
Maternal exclusion criteria: expected
cord pulsation (median,
delivery before 36 wk of gestation or
180 [range, 30-375] s);
would not be available for the follownewborns placed on
up assessment period
mothers abdomen

Outcomes
Maternal primary
morbidity: postpartum
hemorrhage, extension of
episiotomy, infected
episiotomy, endometritis,
and urinary infections
Fetal primary morbidity:
asphyxia, hypothermia,
tachypnea, polycythemia,
hyperbilirubinemia
Secondary: maternal
perception of birth, infant
behavior

ECC (n = 256) as soon as

Primary: duration of cord
possible after delivery (mean
adherence Secondary:
time unknown) LCC (n = 296)
birth weight, feeding, fetal
after stopping of cord pulsation jaundice, postpartum
554 Singletonterm infants, of37-42 weeks or 3 min after delivery,
hemorrhage, manual
gestation, with an expected
whichever is sooner (mean time removal of placenta
spontaneous vertex delivery
unknown)
Fetal exclusion criteria: fetal distress,
Newborns placed at/above
resuscitation during labor, evidence of
placenta at 30 s
hypoxia Maternal exclusion criteria:
receiving medications other than iron and
vitamins, baby to be adopted, specific
preference for ECC or LCC
107 Singleton term infants, born vaginally
ECC (n = 48) immediately after birth Primary: serum ferritin
of nonanemic mothers (maternal
(mean time unknown)
level
hemoglobin >10g/dL) Fetal exclusion LCC (n = 59) after descent of placenta Secondary:
criteria: birth asphyxia, major congenital in vagina (mean time unknown);
hemoglobin level
anomalies
newborns held within 10 cm
Maternal exclusion criteria:
below introitus
eclampsia, heart failure, severe
antepartum hemorrhage, Rh
isoimmunization

5
ECC (n = 15) immediately after
45 Term infants (38-42 gestational wk) born birth (within 5 s; mean time
vaginally; epidural anesthesia was unknown) LCC 1 (n = 15;
used in all mothers
excluded) at 1 min after birth;
Fetal exclusion criteria: malformed infants newborns held 30 cm below
who developed systemic infections,
level of introitus LCC 2 (n =
erythroblastotic infants, small for dates
15)at 5 min after birth (mean
Maternal exclusion criteria: diabetes
time

Primary: volume of
placental transfusion
Secondary: bilirubin levels

(continued)

2007 American Medical Association. All rights reserved.

(Reprinted) JAMA, March 21, 2007Vol 297, No. 11

1243

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

Table 2.

Included Nonrandomized Controlled Trials (N = 7) Comparing Early vs Late Cord Clamping in Term Infants, Listed According to Study Quality Score

Source

Location
Germany

Nelle et al,44
1996

Quality
Score*
8

Participants LATE

Intervention
Outcomes
VS EARLY CLAMPING OF
THE UMBILICAL CORD IN FULL-TERM
NEONATES

30 Singleton term infants born vaginally at 39-40 wk

ECC (n = 15) within first 10 s of delivery (mean time Primary: postnatal changes in left and

Inclusion
3743criteria: uneventful full-term pregnancy Fetal
unknown)
right systolic time intervals Secondary:
time at 1 minute.
To minimize level at which
the newborn was cluding
delivery
of
the
exclusion criteria: malformations, high risk of
LCC (n = 15) as part of Leboyer method at 3 min (mean adverse events
41,43
the
chance infections,
of intrauterine
overlapping
kept
in
relation
to
the
level
of
placenta.
Milking
of
the
asphyxia Maternal exclusion
time unknown); newborns placed on mothers
criteria: high-risk
abdomen
between the timing
definitions of placenta or
introitus during the umbilical cord was not tested in
pregnancies, diabetes, twin pregnancies
late and early clamping in this clamping interval. In 2 trials, any of the trials. The majority of
data7 for30infants
included
in at compared
conventional
did
not adequately
Cairo,
Abdel Aziz et al, review,
Full-term infants
born vaginally
39-40 wk
ECC (n = 15)with
within the first
10 s of delivery (mean trials
time Primary:
determinants
of blood viscosity address
Egypt
1999
Inclusion criteria:
singleton
healthy full-term
jaundice, polycythemia
these 2 intermediary
groups
were
delivery unknown)
including
early
cord theSecondary:
hematologic
status of the
pregnancy
LCC (n = 15) at 3 min (mean time unknown);
excluded from Exclusion
the meta-analysis.
clamping,
late
clamping
was recruited mothers as a potential
criteria: unspecified
newborns kept at level of introitus
As
a result,7 the
earliest time at performed as part of an evaluation con- founder
in the relationship
Guatemala
89 Singleton term infants (37 wk or older), birth weight ECC (n = 29) immediately after birth (mean, 18 [SD, Primary:
Grajeda et
fetal
hematologic
status
more than 2000
g, born
vaginally Fetalof
exclusion
18] s) method of labor,
al,
Secondary: adverse
health effects
which cord clamping
was
defined
the Leboyer
between
clamping
interval and
criteria: major congenital abnormalities and need for LCC 1 (n = 30) after stopping of cord pulsation
1997
as late in this
review was 2 which
required
putting
the risk of anemia during infancy.
early cord clamping or resuscitation Maternal
(mean, 84 [SD, 48] s)
exclusion criteria:
gestational
diabetes
or
LCC
2 (n =mothers
30) after stopping
of cord pulsation
minutes. The majority
of trials
did
neonate
on
the
abdomen
Meta-analysis Findings
pre(eclampsia), previous cesarean delivery, serious
(mean, 84 [SD, 48] s); newborns placed below
not provide any
data about the after birth while
waiting for the
hemorrhage during pregnancy or delivery,
level of placenta
Among the 15 studies, a total of
mean clamping
timedisproportion
for the
cord to stop pulsating before
cephalopelvic
during delivery
1912 newborns underwent a trial
19 39 41-45 47 48
44,48
compared groups. , ,
, ,
clamping it.
Two of the 4 trials
of late (n = 1001) or early (n =
Our outcomes of interest were that
provided
information
Germany
7
Linderkamp
30 Singleton term infants born vaginally at 39-40 wk
ECC (n = 15) within the first 10 s of delivery (mean 911)
time Primary:
determinants ofof
bloodthe
viscosity
clamping
umbilical
reported
by allfull-term
regarding
the use of oxytocic
et al, not consistently
Inclusion
criteria: uneventful
pregnancy unknown)
(hematocrit, plasma viscosity, RBC
cord. Tests
ofand
heterogeneity
were
1992
Exclusion
criteria:
unspecified
LCC
(n
=
15)
at
3
min
(mean
time
unknown);
aggregation,
RBC
deformity)
trials,
resulting
in
several drugs limited administration to
newborns held at level of introitus
Secondary: bilirubin
measurements in
in 4 of the
statistically
significant
outcomes being reported in only 1 the period after the cord was
jaundiced infants
45

46

47

Nelle et al,48
1993

Yao et al,19
1971

Germany

New York
State

Oh and Lind,49 Sweden

1967

30 Singleton term infants born vaginally at 39-40 wk

Primary: postnatal changes in blood
ECC (n = 15) within first 10 s of delivery (mean time
Inclusion criteria: uneventful full-term pregnancy
viscosity and its determinants
unknown)
Exclusion criteria: unspecified
Secondary: adverse events
LCC (n = 15) as part of Leboyer method at 3 min (mean
time unknown); newborns placed on mothers
abdomen
57 Normal full-term infants born vaginally without any
ECC (n = 24) within the first 10 s of delivery (mean time Primary: respiratory frequency, pattern,
perinatal complications
unknown)
and occurrence of expiratory
LCC (n = 33) after 3-5 min after birth (mean time
grunting from birth through the
unknown)
first hours of life
36 Singleton term infants born vaginally at 38-42 wk
ECC (n = 22) immediately after birth (mean, 9
Primary: infant body temperature from 5
Inclusion criteria: uncomplicated full-term pregnancy
[range, 2-20] s)
min to 5 d of life Secondary: hematocrit
Exclusion criteria: unspecified
LCC (n = 14) after stopping of cord pulsation
at 0.5 h after birth
(mean, 3 min 48 s [range, 2.5-5 min);
newborns placed 10 cm below level of
introitus

unknown); newborns held

30 cm below level of
introitus
In both groups, oxytocic drugs
given after cord clamping
Abbreviations: ECC, early cord clamping; LCC, late cord clamping.
*Quality score determined using the Jadad scale.

between the late- and earlyclamping groups. Small yet similar

percentages (approximately 2.7%)
of infants in the late- and earlyclamping groups were delivered
by cesarean. Outcome data for
infants delivered by cesarean
were not reported separately from

ered vaginally.31 The majority of

trials (n = 8) defined early cord
clamping as clamping within the
first 10 seconds.19,32,37,38,44,45,47,48 Six
trials described early clamping as
immediate clamp- ing.39,4143,46,49 The
trial by Nelson et al40 was the only
trial that extended the early

1244 JAMA, March 21, 2007Vol 297, No. 11 (Reprinted)

cord clamping definition to be as

long as 60 seconds.
Most of the trials defined late
cord clamping as clamping either
after cessation of cord pulsation
or at 3 minutes. Two studies
included
an
additional
study
group,
with
an
intermediary

2007 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

LCC

ECC

Weighted Mean
Difference (95% CI)

Mean (SD)
Source

Mean (SD)

Random-Effects

LATE VS EARLY CLAMPING OF THE

IN FULL-TERM
NEONATES
No UMBILICAL
Hematocrit, % CORD
No.
Hematocrit,
%
Model

Ceriani Cernadas et al,37 2006

Neonatal Hematocrit at 6 Hours

92

59.40 (6.10)

90

53.50 (7.00)

32

Chaparro et al, 2006

5.90 (3.99 to 7.81)

166
62.00 (7.50) 155
(7.20)
(0.89 to 4.11)
meta-analysis (hematocrit
at 2410.01%; 59.50
95%
CI, 2.504.10%
to
Overall
258
245
4.16 (0.83 to 7.49)
48
hours
and
at
5
days,
bilirubin
15.92%).
This
significant
effect
Test for Heterogeneity: X = 7.13 (P = .008), / = 86.0%
at 24
was further demonstrated at age 5
Test for Overall
Effect:hours,
z = 2.45 (P =and
.01) risk of grunting
Neonatal Hematocrit at 24-48 Hours
or tachypnea). However, power
to days (4 trials, 120 infants)44454748
Nelle et al, 1 993
15
59.00 (5.00) 15
43.00 (6.00)
16.00 (12.05 to 19.95)
was
low
(WMD,
CI,(12.05
8.50%
Abdel Azizdetect
et al, 1999 heterogeneity
15
59.00 (5.00)
15 11.97%;
43.00 (6.00) 95%16.00
to 19.95)to
Emhamed because
et al, 2004
52.90 (6.30)
45
49.30 (5.70)
to 5.93) (1
of the relatively57 small
15.45%)
and
at age 3.60
2 (1.27
months
Ceriani Cernadas et al, 2006
90
56.40 (7.40) 89
51.10 (6.90)
5.30 (3.20 to 7.40)
number of available trials.
trial, 47 infants)46 (WMD, 3.70%;
Overall
177
164
10.01 (4.10 to 15.92)
95% CI, 2.00% to 5.40%). However,
Test for Heterogeneity: = 50.37 (P<.001), / = 94.0%
Physiological Parameters
Test for Overall Effect: z = 3.32 (P<.001)
no significant differences were
Neonatal Hematocrit at 5 Days
Mean
Hematocrit.
Mean
found in hematocrit at age 6
Linderkamp et al, 1992
15
59.00 (6.00) 15
44.00 (5.00)
15.00 (11.05 to 18.95)
neonatal hematocrit measured
in
32
months
(1
trial, 305
infants)
Nelle et al, 1 993
15
59.00 (5.00)
15
44.00 (5.00)
10.00 (6.42
to 13.58)
or venous blood samples
Nelle et al,capillary
1 996
15
57.00 (2.00)
15
49.00
(7.00)
8.00
(4.32
to
11.68)
(WMD, 0.10%; 95% CI, -0.62% to
Abdel Azizcollected
et al, 1999
15
59.00 (5.00) 15
44.00 (5.00)
15.00 (11.42 to 18.58)
from the newborns
at
0.82%).
A sensitivity11.97
analysis
for
Overall
60
60
(8.50 to 15.45)
around 6 hours after birth was hematocrit at 24 to 48 hours after
Test for Heterogeneity: %| = 10.63 (P = .001), / = 71.8%
i-------1------1------1-----higher for those allocated to late delivery comparing high-quality
Test for Overall Effect: z = 6.75 (P<.001)
vs early cord clamping (2 trials, studies with all studies showed no
494 infants)3237 (WMD, 4.16%; 95% substantial
changes
in
the
CI, 0.83% to 7.49%) ( FIGURE 1). observed differences (2 trials, 279
Similarly, 4 trials
infants)37,38 (WMD, 4.54%; 95% CI,
evaluating
341
infants37,38,45,48 2.98% to 6.10%).
found significantly higher levels of
Mean
Hemoglobin Level. At
No.
No.
Mean (SD)
Mean (SD)
2

48

45

38

37

47

48
44

45

Figure 1. Mean Hematocrit and

Geethanath et al,42 1997
Grajeda et al,46 1997
Gupta and Ramji,39 2002

Hemoglobin,
Hemoglobin
g/dLLevels
59
25
29

113

8.30 (2.10)
10.80 (1.10)
9.90 (0.90)

Hemoglobin,
Among Infants
g/dL
With

48
19
29

blood was higher

in newborns with
m
late cord clamping
(1 trial, 354
infants)32 (WMD, 0.60 g/dL; 95% CI,
0.11 to 1.09). No significant

differences in mean levels

were

found at ages 2 to 3 months (3

trials, 209 infants)39,42,46 (WMD,

0.47 g/dL; 95% CI, -0.48 to 1.42)
(Figure 1) or 6 months (1 trial, 356
infants)32 (WMD, 0.00 g/dL; 95%

CI, -0.21 to 0.21).

Of the 3 trials

assessing hemoglobin
levels at 2

to 3 months, only 1 was of high

m trial of 58
quality.39 In this small
iiii
-20 -15 -10were
-5 0 5 10 15higher
20
infants, levels
in
newborns who had late clamping
(WMD, 1.10 g/dL; 95% CI, 0.66 to
1.54).

Blood Volume and Plasma

and Blood Viscosity. Blood
volume during the first 2 to 4

Late Cord Clamping (LCC) Relative to Early Cord Clamping (ECC)

8.90 (1.60)
9.99 (0.93)
Hematocrit
Levels
8.80 (0.80)

96

Overall
Test for Heterogeneity: %2 = 16.50 (P<.001), /2 = 87.9%

Weighted Mean Difference (95% CI)

Hemoglobin at 2-3 Months

Abbreviations: ECC, early cord clamping; LCC, late cord clamping; RBC, red blood cell.
*Quality score determined using the Jadad scale.

2007 American Medical Association. All rights reserved.

(Reprinted) JAMA, March 21, 2007Vol 297, No. 11 1245

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

LCC

ECC

Weighted Mean
Difference (95% CI)

Mean (SD)
Mean (SD)
Blood Viscosity,
Blood Viscosity,
LATE
VS
EARLY
CLAMPING
No.
mPa.s
No.
mPa.s

Source
Linderkamp et al,47 1992

15
4348

Nelle et al,44 1 trials,

996
Abdel Aziz et al,45 1999

15
(WMD,
15

Mean Blood Viscosity at

4.20 (0.40)
15
5.40 (1.00)
9.07
4.20 (0.40)

2-4 Hours
2.80 (0.50)

Fixed-Effects

OF THE
ModelUMBILICAL CORD IN FULL-TERM NEONATES
1.40 (1.08-1.72)

15
4.10 (0.80)
Bilirubin
Level.
15
2.80 (0.40)

1.30 (0.65-1.95)
60 infants)
As
shown in
1.40 (1.11-1.69)
mL/kg;
95%
CI,
5.81
to
12.32).
F
IGURE 3, there was no significant
Overall
45
45
1.39 (1.19-1.59)
Three trials (90 neonates)45,47,48 difference in mean serum bilirubin
Test for Heterogeneity: = 0.08 (P = .96), / = 0% Test for
Overall Effect:found
z = 13.38 (P<.001)
no significant differences levels within the first 24 hours of
Mean Blood Viscosity at 5 Days
with respect to values of plasma
life (2 trials, 163 infants) 38,41
Linderkamp et al, 1992
15
4.00 (0.50)
15
3.10 (0.40)
0.90 (0.58-1.22)
viscosity at 24 hours after birth (WMD,
3.81
mmol/L;
95% CI,
Nelle et al, 1 996
15
5.00 (1.30)
15
3.70 (0.50)
1.30 (0.60-2.00)
(WMD,
0.01 mPa.s; 95% CI,15 -0.03
-17.55
to3.1025.18).
Similarly,
no
Abdel Aziz et al,
1999
4.00 (0.50)
15
(0.40)
0.90 (0.58-1.22)
Overall
45
0.94 (0.72-1.16)
to 0.05) and at age 5 days 45in the significant
differences
in levels
same population (WMD, -0.02 were noted between late and early
mPa.s; 95% CI, -0.07 to 0.02). cord clamping at or after 72 hours
Three
trials
(90
infants) 44,45,47 following
birth
(2
trials,
91
reported that values of blood infants)41,43 (WMD, 18.27 mmol/L;
viscosity during the first 2 to 4 95% CI, -2.47 to 39.00).
hours of life and again at age 5
Iron Status. Iron status was
days were significantly higher in assessed in terms of mean ferritin
neonates
allocated
to
late level and stored iron level. Ferritin
clamping (2-4 hours: WMD, 1.39 levels at ages 2 to 3 months were
2

47

44

45

to late vs early
cord clamping (2
------------
trials, 144 infants)4246 (WMD, 17.89
pg/L; 95% CI, 16.58 to 19.21)
(FIGURE 4). Two trials that included
a total of 165 infants 39,42 compared
the effects
of late vs early
-----------------clamping on
having ferritin levels
less than 50 pg/L at age 3 months
as an indicator for deficient iron
stores. Fewer infants allocated to
late clamping had ferritin levels
less than 50 pg/L (RR, 0.67; 95%
CI, 0.47 to 0.96). At age 6 months,
ferritin levels were also higher
with late clamping (1 trial, 315
infants)32 (WMD, 11.80 pg/L; 95%
CI, 4.07 to 19.53).

Figure 2. Mean Blood Viscosity Among Infants With Late Cord Clamping (LCC) Relative to Early Cord Clamping (ECC)
LCC

Mean (SD)
No. Bilirubin, mmol/L No.

Source

40
57

Oxford Midwives,41 1991 Emhamed et al,38 2004

ECC

Mean (SD)
Bilirubin, mmol/L

Bilirubin Level Within 24 Hours

192.80 (52.40)
175.70 (44.70)
21
99.18 (22.23) 45
104.31 (51.30)

Weighted Mean

Difference (95% CI)

Random-Effects Model

17.10 (-7.98 to 42.18) -5.13

(-21.19 to 10.93)

Overall
Test for Heterogeneity: X = 2.14 (P = .14), /2 = 53.3%
Test for Overall Effect: z = 0.35 (P = .73)
Fixed-Effects Model (95%
CI)
Bilirubin Level at or After 72 Hours
94.05 (73.53) 15
54.70 (54.70)
40
187.60 (36.00) 21
174.60 (47.50)
55
36
15

Saigal et al,43 1 9 72 Oxford Midwives,41 1991 Overall

Test for Heterogeneity: X = 0.99 (P = .32), /2 = 0% Test
for Overall Effect: z = 1.73 (P = .08)

39.35 (-7.03 to 85.73) 13.00

(-10.18 to 36.18) 18.27 (-2.47
to 39.00)
-50 -40 -30 -20 -10 0 10 20 30 40 50

Test for Heterogeneity: % = 1.12 (P = .57), / = 0%

Test for Overall Effect: z = 8.44 (P<.001)
2

,----------------,---------------j---------------,---------------,
2
1
0
1
2
Weighted Mean Difference (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval.

Figure 3. Mean Bilirubin Levels Among Infants With Late Cord Clamping (LCC) Relative to Early Cord Clamping (ECC)

-0.60 (-1.30 to 0.10)

0.81 (0.21 to 1.41) 1.10
(0.66 to 1.54) 0.47 (0.48 to 1.42)
-

Test for Overall Effect: z = 0.96 (P = .34)

12

Weighted Mean Difference (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval.
1246 JAMA, March 21, 2007Vol 297, No. 11 (Reprinted)

2007 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

Source

LCC

ECC

Mean (SD)

Mean (SD)

Fixed-Effects

No.
Ferritin, pg/L No.
pg/L
Model
LATE VS EARLY CLAMPING OF THE
UMBILICAL
CORD Ferritin,
IN FULL-TERM
NEONATES
42

Geethanath et al, 1997

59

Grajeda et al,46 1997

21 130.90 (54.00)
80

Overall

Weighted Mean
Difference (95% CI)

73.60 (3.10)

that
infants
with
late
cord
clamping at birth had higher levels
of stored iron vs those with early
clamping (WMD, 19.90 mg; 95%
CI, 7.67 to 32.13).

Clinical Outcomes

Risk of Anemia. Compared with

early cord clamping, the risk of
anemia was decreased with late
clamping at 24 to 48 hours after
birth (1 study, 179 infants)37 (RR,
0.20; 95% CI, 0.06 to 0.66) and at
ages 2 to 3 months (2 trials, 119
infants)3946 (RR, 0.53; 95% CI, 0.40
to 0.70) (FIGURE 5). At 6 months,
similar proportions of infants in
the
lateand
early-clamping
groups were anemic (1 trial, 356
infants)32 (RR, 0.85; 95% CI, 0.51
to 1.43). However, in the same
trial, 315 infants were evaluated
for risk of iron deficiency anemia
at age 6 months by considering
their levels of ferritin as well.
None in the late- clamping group
(n = 161) vs 6 in the earlyclamping group (n = 154) were
diagnosed with the deficiency (RR,
0.07; 95% CI, 0.00 to 1.30).

Risk of Clinical Jaundice and

Use of Phototherapy. A pooled

48
16
64

55.70 (3.70)

119.70 (83.20)

17.90 (16.59 to 19.21)

11.20 (-35.65 to 58.05)

17.89 (16.58 to 19.21)

24 to 48 hours oflife associated

with late cord clamping (RR, 1.35;
95% CI, 1.00 to 1.81) ( FIGURE 6).
When
low-quality
trials
were
excluded, findings still showed no
significant
difference
between
groups in the risk of jaundice (4
trials, 889 infants)37384041 (RR 1.16;
95% CI, 0.85 to 1.58). Similarly, no
significant differences were noted
between late and early clamping
in risk of jaundice at 3 to 14 days
after birth (1 trial, 332 infants)32
(RR, 1.27; 95% CI, 0.76 to 2.10). In
addition, no significant differences
were found between groups in the
proportions of infants who had
elevated bilirubin levels (>256.5
mmo/L
[15
g/dL])
thatnecessitated use of phototherapy (3
trials,
699
infants)384041
(RR,1.78;95%CI,0.71
to
4.46)
(Figure 6).
Risk of Polycythemia. Risk of
polycythemia after birth was more
common in neonates allocated to
late
rather
than
early
cord
clamping at 7 hours (2 trials, 236
neonates)3237 (RR, 3.44; 95% CI,
1.25 to 9.52) and at 24 to 48 hours
(7 trials, 403 neonates)3738424446-48
(RR,
3.82; 95% CI, Relative
1.11 Risk
to 13.21)
Anemia

LCC

ECC

(95% CI)

(RR, 3.91; 95% CI, 1.00 to 15.36),

although statistical significance
was lost (Figure 7).

Risk
of
Respiratory

Tachypnea
Grunting.

or

No
significant
difference
was
observed between late and early
cord clamping in terms of the risk
of developing either tachypnea or
respiratory grunting (3 trials, 296
infants)19,37,40 (RR, 2.48; 95% CI,
0.34 to 17.89) (FIGURE 8). The
estimate
for
risk
remained
nonsignificant when the single
low-quality trial was removed
from the analysis (2 trials, 239
infants)3740 (RR, 1.24; 95 CI, 0.49
to 1.37).

Risk of Admission to the

NICU. Only 1 trial (185 infants)37
reported on admission to the
NICU, and this study observed no
significant differences between
late and early cord clamping (RR,
2.02; 95% CI, 0.63 to 6.48).

Sensitivity and Subgroup Analyses

To determine whether the extreme
definition of early (up to 1 minute)
cord clamping used by Nelson et
al40 had an impact on the overall
findings, a sensitivity analysis was
undertaken. The results of the

Figure 4. Mean Ferritin Concentrations at Ages 2 to 3 Months Among Infants With Late Cord Clamping (LCC) Relative to Early Cord
Source

No./Total

No./Total

Fixed-Effects Model

Grajeda et al,46 1997

21/44

15/17

0.54 (0.38-0.77)

Gupta and Ramji,39 2002

13/29

25/29

0.52 (0.34-0.80)

----------- j

46

0.53 (0.40-0.70)

Clamping (ECC)

73
Overall
Test for Heterogeneity: = 0.02 (P = .89), /2 = 0%
Test for Overall Effect: z = 4.41 (P<.001)

0.2

....................i

11

1.0

Relative Risk (95% CI)

Test for Heterogeneity: % = 0.08 (P = .78), /2 = 0%

Test for Overall Effect: z = 26.74 (P<.001)

,------,-----,-----,-----,-----j------,-----,-----,-----,-----,
-50 -40 -30 -20 -10 0 10 20 30 40 50
Weighted Mean Difference (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval. To convert values to pmol/L, multiply by 2.247.

Figure 5. Anemia at Ages 2 to 3 Months Among Infants With Late Cord Clamping (LCC) Relative to Early Cord Clamping (ECC)

Weighted Mean Difference (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval. To convert bilirubin values to mg/dL, divide by 17.1.

2007 American Medical Association. All rights reserved.

1247

(Reprinted) JAMA, March 21, 2007Vol 297, No. 11

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

Clinical Jaundice
LCC
No./Total
LATE
12/28 VS

Source

Relative Risk

(95% CI)
ECC
No./Total
Fixed-Effects Model
EARLY
THE UMBILICAL
5/26 CLAMPING
2.23OF
(0.91-5.46)

Nelson et al,40 1980

Oxford Midwives,41 1991
49/296
35/256
1.21 (0.81-1.81)
Linderkamp et al,47 1992
3/15
0/15
7.00 (0.39-124.83)
48
Nelle et al, 1 993
0/15
9.00 (0.53-153.79)
4448
Due to lack of data in the trials 4/15
[2 trials,
60 infants]
: WMD,
44
Nelle et al, 1 996
2/15
0/15
5.00 (0.26-96.13)
45
on
potential
confounders,
9.03%;
95%
CI,
6.46%
to 11.60%;
Abdel Aziz et al, 1999
3/15
0/15
7.00 (0.39-124.83)
Emhamed et al,38 2004
14/45
0.85 (0.46-1.56)
subgroup analysis was possible 15/57
in infants
kept at level
of placenta
Ceriani Cernadas et al,37 2006
0/90
2/91
0.20 (0.01-4.15)
Overall

only
for
the
variable
that
represents height of the newborn
after birth in relation to the level
of introitus or placenta for a
limited number of the outcomes.
Our subgroup analyses are limited
to comparing composite data from
studies in which the newborns
level is known, rather than being
able
to
compare
data
for
individual infants. The favorable
effect of late clamping on neonatal
hematocrit
at
age
6
hours
remained
significant
whether
newborns were kept at the level of
the placenta31 or placed on the
mothers
abdomen.37
The
subgroup
analyses
for
data
collected for hematocrit at 24 to
48 hours and at age 5 days
showed significant differences in
favor of late clamping, irrespective
of the level of the infant during
the delayed time (hematocrit at
24-48 hours in infants kept above
level of placenta [3 trials, 311
infants]37,38,48: WMD, 6.08%; 95%
CI, 4.63% to 7.54%; in infants kept

Phototherapy
ECC
LCC
No./Total
2/28
11/292
0/57
377

Figure
No./Total
1/26

Relative Risk
(95% CI)

4547
[2
trials,478 60 infants]
: WMD,
531
1.35 (1.00-1.81)
15.00%;
95%
CI,
12.35%
to
17.65%).
The reducing effect of late
clamping on risk of anemia at
different points within the first 6
months of life appeared to be
sustained irrespective of the level
of the newborn after delivery. This
was
demonstrated
by
the
comparable results of the trial by
Ceriani Cernadas et al,37 in which
newborns were placed on the
mothers abdomen, and the trials
by Gupta and Ramji39 and Grajeda
et al,46 in which newborns were
kept at levels lower than that of
the introitus. Lower rates of iron
deficiency anemia at age 6 months
were also reported among infants
held at the level of the introitus in
the study by Chaparro et al.32
Values of ferritin during the first
6 months of life were higher in
infants allocated to late cord
clamping and kept either at the
level of the placenta (1 trial, 315
infants)32 (WMD, 11.80 pg/L; 95%

CORD IN FULL-TERM NEONATES

mia during the first 48 hours of

life were higher when clamping
was delayed, whether infants were
held at the level of the introitus 32
or below46 or placed on the
mothers abdomen.37,38
Although it was not possible to
control for the potential modifying
effect of breast feeding or ironfortified formula on iron stores
and risk of anemia, Chaparro et
al32 reported that late clamping
increased body iron stores more in
infants who still breastfed at 6
months than in those no longer
breastfed. These authors also
reported that late clamping had
greater effects with respect to
stored iron in infants not receiving
any iron-fortified formula or milk
at 6 months than in those
receiving such products (early vs
delayed clamping among those
receiving formula or milk: WMD,
-16.9 mg; 95% CI, -38.60 to 4.90;
among those receiving no formula
or milk: WMD, -46.80 mg; 95% CI,
-77.30 to -16.30).
In 1 large randomized trial, late
clamping was found to have a
greater effect in reducing the

6. Fixed-Effects
Clinical Jaundice
Model and Need for Phototherapy Among Infants With Late Cord Clamping (LCC) Relative to Early Cord Clamping (ECC)
1.86 (0.18-19.29)

3/251
2/45

Infants With Clinical Jaundice at 24-48 Hours

3.15 (0.89-11.17)
0.16 (0.01-3.22)

322

1.78 (0.71-4.46)

Test for Heterogeneity: X7 = 10.19 (P = .18), I 2 = 31.3%

Test for Overall Effect: z = 1.97 (P = .05)
Infants Receiving Phototherapy for Jaundice

Source
Nelson
Oxford
Emhamed

al,40

et

Midwives,41
et

1980
1991

al,38

2004

Overall
Test for Heterogeneity:
= 3.26 (P = .20), I2 = 38.7%
Test for Overall Effect: z = 1.23 (P = .22)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval.

1248 JAMA, March 21, 2007Vol 297, No. 11 (Reprinted)

reserved.

2007 American Medical Association. All rights

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

Source
LATE etVS
Ceriani Cernadas
al,37EARLY
2006

CLAMPING OF THE

Polycythemia
Relative Risk
(95% CI)
LCC
ECC
No./Total
No./Total
Fixed-Effects Model
UMBILICAL
IN FULL-TERM
NEONATES
13/90 CORD4/90
3.25 (1.10-9.59)

32

Chaparro et al, 2006

Overall

2/28
118

COMMENT
Our results showed that delaying
clamping of the umbilical cord for
at least 2 minutes after birth
consistently improved both the
short- and long-term hematologic
and iron status of full-term
infants.
Placental
transfusion
associated with late compared
with early cord clamping resulted
in consistently higher hematocrit
levels within normal physiologic
ranges and in improved markers of
iron status over the first months
of life without having a significant
impact on the absolute values of

!---------------------------------t----------------
-------------
\

5.00 (0.25-99.67)
3.44 (1.25-9.52)

of life. Although late clamping was

associated
with
a
moderate
increase in blood viscosity and
increased rates of polycythemia,
there was no evidence of any
significant harm as measured by
the need for phototherapy to treat
jaundice or by admission to the
NICU. The risk of polycythemia
was not significant when only
high-quality
studies
were
considered. In addition, none of
the
polycythemic
infants
evaluated in this review were
symptomatic (ie, had symptoms of
central
nervous
system,
Polycythemia
Relative Risk
LCC

Source

0/28
118

The presence of polycythemia in

both the late- and the earlyclamping groups suggests that
mild neonatal hyperviscosity with
subsequent
uncomplicated
polycythemia can occur in some
normal
healthy
neonates,
regardless of the time at which
the cord is clamped. This is the
consequence of a rapid change in
hematocrit that normally occurs
during the first 24 hours of life.72
The RRs of some other potential
adverse outcomes of late cord
clamping (tachypnea or grunting,
admission to the NICU) were

(95% CI)

ECC

Figure 7. Polycythemia Among Infants With Late

Cord Clamping
RelativeModel
to Early Cord Clamping (ECC)
No./Total
No./Total(LCC)
Fixed-Effects

Linderkamp et al,47 1992

Nelle et al,48 1 993
Nelle et al,44 1 996
Geethanath et al,42 1997
Grajeda et al,46 1997

0/15
0/15
Not Estimable
0/15Infants With 0/15
NotHematocrit
Estimable>65%) at 7 Hours
Polycythemia (Venous
0/15
0/1
2/18

0/15
0/1
0/12

Not Estimable
Not Estimable
3.42 (0.18-65.58) -----------------------------------------------------

-----------------

Emhamed et al,38 2004

Ceriani Cernadas et al,37 2006

3/57
7/90

0/45
2/89

5.55 (0.29-104.79) --------------------------------------------------3.46 (0.74-16.21)

----------------

Overall

211

192

3.82 (1.11-13.21)

Test for Heterogeneity: % = 0.07 (P = .79), / = 0%

Test for Overall Effect: z =2.38 (P = .02)
2

Source
Yao et al,19 1971
Nelson et al,40 1980
Ceriani Cernadas et al,37 2006
Overall

I---------1- - -1i.......... ...........1---1i...........

0.1
1.0
10
Relative Risk (95% CI)

Infants With Polycythemia (Venous Hematocrit >65%) at 24-48 Hours

Tachypnea or Grunting
Relative Risk
(95% CI)
LCC
ECC
No./Total
No./Total
Random-Effects
Model
13/33
0/24
19.85 (1.24-318.43)
3/28
5/26
0.56 (0.15-2.10)
6/92
2/93
3.03 (0.63-14.64)
153

143

2.48 (0.34-17.89)

Test for Heterogeneity: %2 = 0.08 (P = .96), /2 = 0%

Test for Overall Effect: z =2.12 (P = .03)

I............... ..............|................ ...............

0.01
0.1
1.0
10
100
Relative Risk (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval.

0.1
0.2
Figure 8. Tachypnea or Grunting Among Infants With Late Cord Clamping (LCC) Relative to Early Cord Clamping
(ECC)0.5

0.1

10

10

Relative Risk (95% CI)

0.1

0.2

0.5

0.1

Relative Risk (95% CI)

Sizes of data markers indicate the weight of each study in the analysis. CI indicates confidence interval.

2007 American Medical Association. All rights reserved.

(Reprinted) JAMA, March 21, 2007Vol 297, No. 11 1249

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

LATE VS EARLY CLAMPING OF THE UMBILICAL CORD IN FULL-TERM NEONATES

fants with tachypnea or grunting tency of findings across trials, we
after
late
clamping
needed believe our findings are reliable.
supplementary oxygen beyond 24
Few of the studies we reviewed
hours of life. This suggests that reported on maternal outcomes,
these respiratory signs are not including early postpartum blood
clinically significant but are part of loss. This is particularly significant
a
physiologic
compensatory because active management of the
mechanism. However, since these third stage of labor includes
outcomes were based on a small administration of a utero- tonic
number of trials and infants, agent before delivery of the
further study is warranted.
placenta, and early cord clamping
Perhaps the most important and cutting is recognized as a
finding was that the beneficial means of minimizing blood loss for
effects of late cord clamping women in the early postpartum
appear to extend beyond the early period.
Although
conclusions
neonatal
period.
Our
meta- about maternal outcomes cannot
analysis estimated a significant be drawn from our research, it is
47% reduction in risk of anemia likely that delayed clamping is
and 33% reduction in risk of compatible
with
active
having deficient iron stores at management of the third stage of
ages 2 to 3 months with late labor.
Uterotonic
agents
clamping.
Although
the
risk administered following birth and
estimate of anemia at ages 2 to 3 prior to cord clamping have been
months was pooled from 2 small shown to increase the rate of
studies39,46 and the loss to follow- placental transfusion and are thus
up in 1 of these was 40%, 39 this likely to enhance the effect of
finding agrees with the results of a delayed clamping.36 Although this
large, well-designed and well- approach has not been studied, a
executed randomized trial with joint
statement
from
the
respect to the sustained effect of International
Federation
of
late clamping on other indicators Gynaecology and Obstetrics and
of infant hematologic status at the International Confederation of
age 6 months: iron stores and Midwives on active management
ferritin concentrations.32
of the third stage of labor already
Because of the relatively small recommends
that
delayed
number of studies that reported clamping be incorporated as part
on any single outcome, use of a of
the
active
management
funnel
plot
to
explore
the approach to placental delivery.73 In
possibility of publication bias was a recent literature review, similar
not possible. We were reassured practice
recommendations
that not all studies had positive pertaining
to
third-stage
outcomes for all results and that management
were
made
for
we were unable to find any providing care in resource-poor
unpublished
results
through settings.28
contacting key researchers.
Late clamping of the umbilical
The strength of evidence may cord
is
a
physiological
and
be limited, since notall included inexpensive means of enhancing
trials were randomized. However, hematologic status, preventing
we attempted to control for this anemia over the first 3 months of
by stratifying our results by life and enriching iron stores and
quality of design, and our results ferritin levels for as long as 6
did not vary substantially. Not all months. Although this is of
Test for Heterogeneity: % = 7.31 (P = .03), / = 72.6%
studies
measured
the
same particular
importance
for
Test for Overall Effect: z = 0.90 (P = .37)
outcomes at the same points, and, developing countries in which
as a result, several outcomes that anemia
during
infancy
and
Sizesstudied
of data markers
the weight
studychildhood
in the analysis.
indicates prevalent,
confidence interval.
we
are indicate
reported
by of
1 each
or a
isCIhighly
it is
small number of studies. In likely to have an important impact
2

optimal time for clamping is

affected by the use of oxytocic
drugs before the delivery of the
placenta or by milking of the
umbilical cord. We believe that
this
meta-analysis
supports
incorporating into clinical practice
a minimum delay of 2 minutes
before clamping the umbilical cord
following birth for all full-term
newborns.
Author Contributions: Dr Hutton had full access to all of
the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data
analysis.
Study concept and design: Hutton.
Acquisition of data: Hutton, Hassan.
Analysis and interpretation of data: Hutton,
Hassan. Drafting of the manuscript: Hutton,
Hassan.

Critical revision of the manuscript for

important intellectual content: Hutton, Hassan.
Statistical analysis: Hutton, Hassan.
Obtained funding: Hutton.
Administrative,
technical,
or
material
support: Hutton, Hassan.
Study supervision: Hutton.
Financial
Disclosures:
None
reported.
Funding/Support: Dr Hutton is a Canadian Institutes of
Health Research New Investigator and a Research
Scholar with the Michael Smith Foundation for Health
Research at The Child and Family Research Institute,
University of British Columbia. Dr Hassan, who is
currently a PhD candidate in the Department of Health
Care and Epidemiology, University of British Columbia,
was funded for this project through a doctoral
studentship made possible with funds from the Michael
Smith Foundation for Health Research and from The
Child and Family Research Institute at the University of
British Columbia. She also holds a doctoral studentship
award from the Western Regional Training Centre for
Health Services Research. The award is jointly funded
by the Canadian Health Services Research
Foundation, Alberta Heritage Foundation for Medical
Research, and the Canadian Institutes of Health
Research.
Role of the Sponsors: No funding agency or sponsor
played any role in the design and conduct of the study;
the
collection,
management,
analysis,
and
REFERENCES
1.

2.
3.

4.

2007JAMA,
American
Association.
All rights
reserved.
1250
MarchMedical
21, 2007Vol
297, No.
11 (Reprinted)
reserved.

5.

Moss AJ, Monset-Couchard M. Placental

transfusion: early versus late clamping of
the
umbilical
cord.
Pediatrics.
1967;40:109-126.
Peltonen
T.
Placental
transfusion:
advantage and disadvantage. EurJ
Pediatr. 1981;137:141-146.
Mercer JS. Current best evidence: a
review of the literature on umbilical cord
clamping. J Midwifery Womens
Health. 2001;46:402-414.
World Health Organization. Maternal

and
Newborn
Health/Safe
Motherhood, Care of the Umbilical
Cord: A Review of the Evidence .
Geneva, Switzerland: Department of
Reproductive Health and Research, World
Health Organization; 1998. Document
WHO/RHT/MSM/98.4.
MorleyG. Cord
closure:
can hasty
0.1 1.0 10
100
clamping injure the newborn? OBG
Relative Risk (95% CI)
Manage.
July
1998:29-36.
http:
/
/www.gentlebirth.org/archives/hastyclampi
ng .html. Accessibility verified February

(Reprinted)
JAMA, March
21, 2007Vol
297, All
No. 11
1251
2007
American
Medical
Association.
rights

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015

LATE VS EARLY CLAMPING OF THE UMBILICAL CORD IN FULL-TERM NEONATES

between infant and placenta after birth. Lancet. 1969;
2:871-873.
8.
Dixon LR. The complete blood count:
physiologic basis and clinical usage.
JPerinatNeonatalNurs. 1997; 11:1-18.
9.
Wardrop CA, Holland BM. The roles and
vital importance of placental blood to the
newborn
infant.
J
PerinatMed.
1995;23:139-143.
10. Yao AC, Lind J. Effect of gravity on
placental
transfusion.
Lancet.
1969;2:505-508.
11. Ende N, Reddi A. Administration of human
umbilical cord blood to low birth weight
infants may prevent the subsequent
development of type 2 diabetes. Med
Hypotheses. 2006;66:1157-1160.
12. Linderkamp O. Placental transfusion:
determinants
and
effects.
Clin
Perinatol. 1982;9:559-592.
13. Usher R, Shephard M, Lind J. Blood
volume in the newborn infant and
placental transfusion. Acta Paediatr.
1963;52:497-512.
14. Pisacane A. Neonatal prevention of iron
deficiency: placental transfusion is a
cheap and physiological solution. BMJ.
1996;312:136-137.
15. Zlotkin S. Strategies for the prevention of
iron deficiency anemia in infants and
children.
2003.
http:
/
/www.hini.org/HINI/pdfs/InTouchVol20_1.p
df. Accessibility verified January 19, 2007.
16. Mercer JS, Skovgaard RL. Neonatal
transitional
physiology.
JPerinatNeonatalNurs. 2002;15:56-75.
17. Buckels L, Usher R. Cardiopulmonary
effects of placental transfusion. J Pediatr.
1965;67:239-246.
18. Wharton BA. Iron deficiency in children.
Br J Haematol. 1999;106:270-280.
19. Yao AC, Lind J, Vuorenkoski V. Expiratory
grunting in the late clamped normal
neonate. Pediatrics. 1971;48:865-870.
20. Oh W, Wallgren G, Hanson J, Lind J. The
effects of placental transfusion on
respiratory mechanics of normal term
newborn infants. Pediatrics. 1967;40:612.
21. Blackburn S. Hyperbilirubinemia and
neonatal jaundice. Neonatal Netw.
1995;14:15-25.
22. Oh W. Neonatal polycythemia and
hyperviscosity. Pediatr Clin North Am.
1986;33:523-532.
23. Austin T, Bridges N, Markiewicz M,
Abraham- son E, Abrahamson E. Severe
neonatal polycythae- mia after third stage
of
labour
underwater.
Lancet.
1997;350:1445.
24. Prendiville WJ, Elbourne D, McDonald S.
Active versus expectant management in
the third stage of labour [update].
Cochrane Database Syst Rev. 2000;
(3):CD000007.
25. Rabe H, Reynolds G, Diaz-Rossello J.
Early versus delayed umbilical cord
clamping in preterm infants. Cochrane
Database
Syst
Rev.
2004;
(4):CD003248.
26. Lainez Villabona B, Berger Alloyn E,
Cafferta Thompson ML, Belizan Chiesa
JM. Early or late umbilical cord clamping?
a systematic review of the literature [in
Spanish].
An
Pediatr
(Barc).
2005;63:14-21.
27. van Rheenen P, Brabin BJ. Late umbilical
cordclamping as an intervention for

Liz Cedillo R, Dewey KG. Effect of timing of umbilical

cord clamping on iron status in Mexican infants.
Lancet. 2006;367:1997-2004.
33. Jadad AR, Moore RA, Carroll D, etal.
Assessing the quality of reports of
randomized clinical trials: is blinding
necessary?
Control Clin Trials.
1996;17:1-12.
34. RevMan [computer program]. Version 4.2.
Copenhagen, Denmark: The Nordic
Cochrane
Centre,
The
Cochrane
Collaboration; 2003.
35. DeeksJJ, Higgins JPT, Altman DG.
Analysing and presenting results. In:
Higgins JPT, Green S, eds. Cochrane

Handbook for Systematic Reviews

of Interven- tions4.2.5 [updated May

36.
37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

48.

1252 JAMA, March 21, 2007Vol 297, No. 11 (Reprinted)

2005]. Section 8. Chichester, England:

John Wiley & Sons, Ltd; 2005.
Yao AC, Lind J. Blood flow in the umbilical
vessels during the third stage of labour.
Biol Neonate. 1974;25:186-193.
Ceriani CernadasJM, Carroli G, Pellegrini
L, etal. The effect of timing of cord
clamping on neonatal venous hematocrit
values and clinical outcome at term: a
randomized, controlled trial. Pediatrics.
2006; 117:e779-e786.
Emhamed MO, Van Rheenen P, Brabin
BJ. The early effects of delayed cord
clamping in term infants born to Libyan
mothers. Trop Doct. 2004;34:218-222.
Gupta R, Ramji S. Effect of delayed cord
clamping on iron stores in infants born to
anemic mothers. Indian
Pediatr.
2002;39:130-135.
Nelson NM, Enkin MW, Saigal S, Bennett
KJ, Milner R, Sackett DL. A randomized
clinical trial of the Leboyer approach to
childbirth. N Engl J Med. 1980; 302:655660.
Oxford Midwives Research Group. A study
of the relationship between the delivery to
cord clamping interval and the time of cord
separation. Midwifery. 1991;7:167-176.
Geethanath RM, Ramji S, Thirupuram S,
Rao YN. Effect of timing of cord clamping
on the iron status of infants at3 months.
Indian Pediatr. 1997;34:103- 106.
Saigal S, O'Neill A, Surainder Y, Chua L,
Usher R. Placental transfusion and
hyperbilirubinemia in the premature.
Pediatrics. 1972;49:406-419.
Nelle M, Kraus M, Basret G, Linderkamp
O. Effects of Leboyer childbirth on leftand right systolic time intervals in healthy
term
neonates.
JPerinatMed.
1996;24:513-520.
Abdel Aziz SF, Shaheen MY, Hussein S,
Suliman MS. Early cord clamping and its
effect
on
some
hematological
determinants of blood viscosity in
neonates.
1999.
http://www.obgyn.net/pb/articles
/cordclamping_aziz_0699.htm.
Accessibility verified January 19, 2007.
Grajeda R, Perez-Escamilla R, Dewey K.
Delayed clamping of the umbilical cord
improves
hematologic
status
of
Guatemalan infants at 2 months of age.
Am J Clin Nutr. 1997;65:425-431.
Linderkamp O, Nelle M, Kraus M, Zilow E.
The effects of early and late cord clamping
on
blood
viscosity
and
other
haemorheological parameters in full- term
neonates. Acta Paediatr. 1992;81:745750.
NelleM, Zilow E, Kraus M, BastertG,
Linderkamp O. The effect of Leboyer

52.

53.

54.
55.

56.

57.

58.

59.

60.

61.

62.

63.

64.

65.

66.
67.

68.

69.

Strauss RG, Mock MM, Johnson K, et al.

Circulating RBC volume, measured with
biotinylated RBCs, is superior to the Hct to
document the hematologic effects of
delayed versus immediate umbilical cord
clamping
in
preterm
neonates.
Transfusion. 2003;43: 1168-1172.
Oh W, Carlo WA, Fanaroff AA, et al.
Delayed cord clamping in extremely low
birth weight infants. Pediatr Res.
2002;51(suppl):365-366.
Emmanouilides GC, Moss AJ. Respiratory
distress in the newborn. BiolNeonate.
1971;18:363-368.
Ibrahim HM, Krouskop RW, Lewis DF,
Dhanireddy R. Placental transfusion:
umbilical cord clamping and preterm
infants. J Perinatol. 2000;20:351-354.
Rabe H, Wacker A, Hulskamp G, et al. A
randomised controlled trial of delayed cord
clamping in very low birth weight preterm
infants. Eur J Pediatr. 2000;159:775777.
Rabe H, WackerA, Hulskamp G, HomigFranz I, Jorch G. Late cord clamping
benefits extrauterine adaptation [abstract].
Pediatr Res. 1998;44:454.
NarendaA, BeckettC, Aitchison T, etal. Is it
possible to promote placental transfusion
at preterm delivery [abstract]? Pediatr
Res. 1998;44:454.
McDonnell M, Henderson-Smart DJ.
Delayed umbilical cord clamping in
preterm infants: a feasibility study. J
Paediatr Child Health. 1997;33:308310.
HofmeyrGJ, Bolton KD, Bowen DC, Govan
JJ.
Periventricular/intraventricular
haemorrhage and umbilical cord clamping.
S Afr Med J. 1988;73:104-106.
Kinmond S, Aitchison TC, Holland BM,
Jones JG, Turner TL, Wardrop CA.
Umbilical cord clamping and preterm
infants. BMJ. 1993;306:172-175.
Frank DJ, Gabriel M. Timing of cord
ligation and newborn respiratory distress.
Am J Obstet Gynecol. 1967;97:11421144.
Yao AC, Lind J, TiisalaR, Michelsson K.
Placental transfusion in the premature
infant with observation on clinical course
and outcome. Acta Paediatr Scand.
1969;58:561-566.
NelleM, FischerS, ConzeS, Beedgen B,
Brischke EM, Linderkamp O. Effects of
later cord clamping on circulation in
prematures (VLBWI) [abstract]. Pediatr
Res. 1998;44:454.
Hofmeyr GJ, Gobetz L, Bex PJM, et al.
Periventricular/intraventricular
hemorrhage following early and delayed
umbilical cord clamping [Doc No. 100].
Online J Curr Clin Trials. December
29, 1993.
Papagno L. Umbilical cord clamping.

Acta Physiol Pharmacol

Latinoam. 1998;48:224-227.

Ther

Nelle M, Zilow E, Bastert G, Linderkamp

O. Effect of Leboyerchildbirth on cardiac
output, cerebral and gastrointestinal blood
flow velocities in full-term neonates. Am J
Perinatol. 1995;12:212-216.
DeMarsh QB, Windle WF, Alt HL. Blood
volume of newborn infants in relation to
early and late clamping of umbilical cord.
AJDC. 1942;63:1123-1129.
Wilson EE, Windle WF, Alt HL. Deprivation
of placental blood as a cause of iron
deficiency in infants. AJDC. 1941;62:320-

2007 American Medical Association. All rights reserved.

Downloaded From: http://jama.jamanetwork.com/ by a University of North Dakota User on 05/16/2015