A related topic pertinent to high-risk deliveries i

n the developed world is the use of autologous

placental blood for transfusion of neonates. This
alternative was not reviewed in detail for the
current evidence evaluation.
Preliminary draft/outline/bullet points of Guidelin
es revision:
Include points you think are important for inclus
ion
by the person assigned to write this section. Use
extra pages if necessary.
Attachments:
Printed (paper) bibliography; and on diskette using
a reference manager. It is recommended that the
bibliography be printed in annotated format. This w
ill include the article abstract and any notes you
would
like to make providing specific comments on the qua
lity, methodology and/or conclusions of the study.
Key figures or tables from evidence-based analysis
Full hard copies of most critical cited papers
Citation List
Citation
Marker
Full Citation*
{Buckels, 1965}
{Colozzi, 1954 #1}
{Emmanouilides,
1971 #9}
{Geethanath, 1997
#3}
{Grajeda, 1997 #4}
{Gupta, 2002 #5}
{Ibrahim, 2000 #6}
{Kinmond, 1993
#7}
{Kliot, 1984 #14}
{Linderkamp, 1992
#15}
{McDonnell, 1997
#27}
{Mercer, 2003
#17}
{Nelle, 1993 #18}
{Nelle, 1995 #19}
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{Nelle, 1996 #21}
{Nelson, 1980
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{Oh, 1966 #22}
{Oh, 1967 #23}
{, 1991 #24}
{Rabe, 2000 #25}
{Usher, 1963 #26}
{Wilson, 1941}
{Wu, 1960 #62}
{Yao, 1968 #60}
{Duckman, 1953
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{Lind, 1968 #29}
{Philip, 1977 #30}
{Anderson, 1992
#64}
{, 1967 #31}
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{Arcilla, 1966
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{Arcilla, 1966
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{Perez Bousono,
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{Brown, 1975
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{Brune, 2002 #33}
{Burnard, 1963
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{Capasso, 2003
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{Chou, 1973 #34}
{Daniel, 1996 #71}
{DeMarsh, 1940}
{DeMarsh, 1941}
{DeMarsh, 1942}
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{Franklin, 1931}
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{Linderkamp, 1978
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{Linderkamp, 1978
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Buckels LJ, Usher R. Cardiopulmonary effects of pla
cental transfusion. The Journal of Pediatrics.
1965;67:239-247.
LOE 3
Observations were collected from 32 normal newborns
from 38 to 44 weeks (2470 to 4590 g) delivered
vaginally (22 spontaneous, 9 low forceps, 1 breech)
. All infants breathed within 1 min without
resuscitation. Early cord clamping was attempted w
ithin 5 sec and delayed cord clamping 5 min after b
irth.
Those with delayed cord clamping were held on the l
ap of the obstetrician 15cm below the introitus; th
ey
were warmed with towels, their mouths were suctione
d, and the umbilical cords were left free and not
handled or stripped.
Flush bood pressures were taken at 5-10 min interva
ls from cord clamping until 1 hour of age and again
at
4 hours. CXR was taken at 15 min., unwarmed heel b
lood pH and pCO2 at 30 min, ECG at 1 hr., and
capillary hct on heel blood at 4 hours, serum bilir
ubin at 72 hours.
Infants with early cord clamping had hct < 65% (1 e
xception) and those with delayed clamping had hct
>65%. Flush blood pressures were highly significan
tly different at 5-10 min., (early 43.7 v. late 68.
6
mmHg); there was a tendency toward acidosis (mixed)
in the early clamping group. Transverse diameter
of
the heart, ECG, and bilirubin were not significantl
y different.
Infants with delayed cord clamping had hematocrits
between 67 and 86%. They frequently had chest
retraction, decreased air entry, rales, accentuated
second heart sound, hepatomegaly, and cyanosis bet
ween
10-30 min of age; signs then resolved.
Comment: Hypotension was the most remarkable findin
g; however, it did not seem to adversely affect the
infants, who all compensated, with flush blood pres
sures > 45 mmHg by 4 hours. Even at 4 hours, there
was no overlap in BPs between the 2 groups.
Colozzi AE. Clamping of the umbilical cord: its eff
ect on the placental transfusion. New England Journ
al
of Medicine. 1954;250:629-632.LOE 3
Four groups of term infants (25 each) were compared
with respect to red cell number and hemoglobin at
24
and 72 hours after birth with 4 techniques of cord
clamping. Group 1 was placed on the mother's abdom
en
and the cord was clamped after the arteries stopped
pulsating and the vein no longer filled; group 2 h
ad
immediate cord clamping; group 3 was placed on a ta
ble below the level of the placenta and the cord wa
s
stripped until no longer distended with blood; grou
p 4 was placed on a table below the level of the pl
acenta
and the cord was clamped when all pulsations and di
stention ceased. Blood was obtained by heel punctu
re.
Comments: Cases were "consecutive" and "unselected"
but not strictly randomized. "No particular
differences in general well-being were noted."
Emmanouilides GC, Moss AJ. Respiratory distress in
the newborn: effect of cord clamping before and aft
er
onset of respiration. Biology of the Neonate. 1971;
18:363-368.
LOE 2 (alternate day randomization)
Preterm infants (N=147 with bw < 2500g and > 1000g
and ga < 38 wks) were randomized by delivery date
to early clamping (before the 2nd breath, generally
within 15 sec) and late clamping (after the 2nd br
eath,
average 46 sec). Infants were held at the level of
the placenta until cord clamping. 117 babies were
delivered vaginally and 30 by C/S. Early and late
groups were further subdivided into early-early, ea
rly-
late, late-late, and late-early when conditions did
not permit strict adherence to the protocol. (In t
he latter
group, maternal or fetal condition argued against l
ate clamping in 7 and in 8 others the cord was allo
wed to
pulsate for 1min or more, but onset of respirations
was delayed.)
There was a higher incidence of respiratory distres
s in early clamped infants (40%) as compared to lat
e
clamped (11%).
Comment: The definition of "early" and "late" in th
is study, relative to onset of respirations, may ha
ve
included a greater proportion of depressed infants
in the early group. This may have skewed the incid
ence
of respiratory distress. Respiratory distress was
less in subgroup 4 as compared to 1 (47 sec v. 7 se
c clamp
time) and less in subgroup 1 and 2 as compared to 3
and 4.
Geethanath RM, Ramji S, Thirupuram S, Rao YN. Effec
t of timing of cord clamping on the iron status of
infants at 3 months. Indian Pediatrics. 1997;34:103
-106.
LOE 2
This prospective randomized trial examined 107 infa
nts born to mothers with uncomplicated pregnancies
and Hgb>10g/dL to determine the effect of timing of
cord clamping on iron stores of term infants at 3
months. Maternal and cord ferritin and Hgb values
at birth were comparable, as were infant ferritin v
alues
at 3 months. Iron stores at 3 months in term infan
ts born to mothers with Hgb > 10g/dL did not reflec
t the
timing of cord clamping at birth.
Comment: Sufficient details are not provided about
the timing of cord clamping and the position of th
e
newly delivered infant relative to the introitus.
Grajeda R, Perez-Escamilla R, Dewey KG. Delayed cla
mping of the umbilical cord improves hematologic
status of Guatelmalan infants at 2 mo of age. Ameri
can Journal of Clinical Nutrition. 1997;65:425-431.
LOE 2
Sixty-nine Guatemalan infants were randomly assigne
d to one of 3 groups: immediate cord clamping
(within 20 sec), clamping when the cord stopped pul
sating with the infant held at the level of the pla
centa,
or clamping when the cord stopped pulsating, with t
he infant placed below the level of the placenta.
At
baseline, mothers and infants had similar hematocri
t status. At 2 months, infants in the 2 groups wit
h
delayed cord clamping had signficantly higher hct a
nd Hgb than did those in the early clamping group.
The
proportion with hct < 33% was significantly less in
the late-clamped than early-clamped groups. Two
infants in the late-clamping group with position be
low the placenta had hct 65% and 66% respectively,
but
were asymptomatic with respect to polycythemia. Th
e authors conclude that waiting until the cord stop
s
pulsating (approx. 1 min) is a feasible low-cost in
tervention that can reduce anemia in infants in dev
eloping
countries.
Comment: Multivariate regression analyses were perf
ormed to rule out effects of potentially confoundin
g
variable on infant hct and Hgb at 2 mo.
Gupta R, Ramji S. Effect of delayed cord clamping o
n iron stores in infants born to anemic mothers: a
randomized controlled trial. Indian Pediatrics. 200
2;39:130-135.
LOE 2
This randomized controlled trial examined 102 infan
ts born to mothers with Hb < 100g/L; infants were
randomized to immediate cord clamping or clamping d
elayed until descent of the placenta into the vagin
a.
The newborn was held below, but within 10 cm of the
introitus. The infant was dried and wrapped in wa
rm
linen. Mean infant ferritin and Hb at 3 mos were s
ignificantly higher in the delayed clamping group.
The
mean decrease in Hb at 3 mos, adjusted for covariat
es, was less in the delayed clamping group, and the
odds for anemia were 7.7 times higher in the early
group.
Comment: Randomization by computer-generated random
number sequences in opaque sealed envelopes.
Follow-up at 3 mos occurred in only 58 infants, 29
in each of the early and delayed clamping groups.
Mothers in the lost-to-followup group had fewer pre
natal visits and lower ferritin levels compared to
the
study group. No infants received iron supplementat
ion before 3 mos.
Ibrahim HM, Krouskop RW, Lewis DF, Dhanireddy R. Pl
acental transfusion: umbilical cord clamping and
preterm infants. Journal of Perinatology. 2000;20:3
51-354.
LOE 2
This randomized, controlled trial followed 32 prema
ture infants (bw 501-1250g and ga 24 <29 wks) with
respect to hct, Hgb, red cell counts, frequency of
transfusions, peak bilirubin, mean blood pressure,
oxygen
index, intraventricular hemorrhage, and significant
PDA. Cord clamping was immediate or delayed until
20 seconds after complete delivery of the infant, h
eld supine at the level of the introitus. MBP was
higher
at 4 hours and the initial hct Hgb and RBC counts w
ere higher in the delayed cord clamping group. Apga
r
score at 5 min was higher in the delayed clamping g
roup. Less volume expansion was necessary in the f
irst
24 hours and fewer transfusions during the first 4
weeks. There were no differences in OI, bilirubin,
IVH,
PDA, respiratory distress.
Comment: Randomization was adequate; the study was
inadequately powered to draw firm conclusions
about all secondary endpoints.
Kinmond S, Aitchison TC, Holland BM, Jones JG, Turn
er TL, Wardrop CAJ. Umbilical cord clamping and
preterm infants: a randomised trial. BMJ. 1993;306:
172-175.
LOE 2
This randomized, controlled trial examined 36 vagin
ally delivered preterm infants >27 and <36 weeks.
Infants in the "regulated" group were held 20 cm be
low the introitus and cord was clamped after 30s.
The
"random" group had a median interval to clamping of
10s, with all but one cord clamped within 20s (one
at
25 s); only one infant was held below the introitus
. In the "regulated" group, PCV and alveolar-arter
ial
oxygen tensions were higher, with fewer transfusion
s needed and shorter duration of supplemental oxyge
n.
Maximum serum bilirubin concentrations were compara
ble.
Comment: The physiologic outcomes measured resulte
d in economic and clinical benefit to the "regulate
d"
group.
Kliot D, Silverstein L. Changing maternal and newbo
rn care: a study of the Leboyer approach to childbi
rth
management. New York State Journal of Medicine. 198
4;84:169-174.
LOE 3
The study included three groups: 39 infants deliver
ed with Leboyer management and cord clamping within
60 sec, 40 infants with Leboyer management and cord
clamping delayed 10 minutes, and 12 control infant
s
with routine delivery room management. Leboyer man
agement involved placing the infant prone on the
mother's abdomen after birth for massage/drying. C
-section deliveries were not included; most deliver
ies
were spontaneous vaginal or forceps with local or n
o anesthesia.
There were no differences among the groups with r
espect to temperature, heart rate, hematocrit, bili
rubin,
blood pH in the first 24 hours, or Apgar scores. P
ost-hospital complications were no different, refle
cting
no readmissions for hyperbilirubinemia or sepsis.
Comment: Small sample size may not be adequate to d
etect differences among the groups (no sample size
calculation).
Linderkamp O, Nelle M, Kraus M, Zilow EP. The effec
t of early and late cord-clamping on blood viscosit
y
and other hemorheological parameters in full-term n
eonates. Acta Paediatrica. 1992;81:745-750.
LOE 3
30 healthy, term neonates were studied after clampi
ng of the umbilical cord within 10s of birth or aft
er 3
min level with the introitus. All infants were bre
ast fed. Postnatal alterations in blood viscosity,
hct,
plasma viscosity, and red cell aggregation and defo
rmability in the first 5 days were studied. Blood
volume
was 50% higher in the late-clamped infants. Hct de
creased from birth to 24 hours in the early-clamped
group. Hct rose in the late cord-clamping group an
d blood viscosity increased by 40% within the first
2 h.
Comment: non-randomized, prospective. No clinical
adverse effects were associated with the observed
differences in hemorheological properties.
McDonnell M, Henderson-Smart DJ. Delayed umbilical
cord clamping in preterm infants: a feasibility
study. Journal of Paediatric Child Health. 1997;33:
308-310.
LOE 2
Forty-six infants born at 26-33 wks were randomized
to cord clamping immediately or 30s after birth.
Infants were maintained at the level of the mother'
s legs (vaginal) or thighs (c-section). If an infa
nt
required resuscitation, the cord was clamped at onc
e. Syntocinon was administered after delivery. Ve
nous
hct at 1 and 4 hours tended to be higher in the del
ayed clamping group, but were not significant; tren
ds
were more marked in infants born by Caesarean secti
on and younger infants. Clinical outcome measure
(Apgar scores, cord pH, temp, ventilation and oxyge
n requirements, use of surfactant, peak bilirubin,
use of
inotropes, cranial ultrasound diagnoses, blood tran
sfusion, death) were no different in the 2 groups.
Comment: Randomization was adequate. Infants who
required resuscitation were excluded. A longer
delay (>30s) prior to cord clamping may be necessar
y if the infant is not held below the placenta in o
rder
to realize benefits of late clamping.
Mercer JS, McGrath MM, Hensman A, Silver H, Oh W. I
mmediate and delayed cord clamping in infants
born between 24 and 32 weeks: a pilot randomized co
ntrolled trial. Journal of Perinatology. 2003;23:46
6-
472.
LOE 2
This prospective randomized controlled trial examin
ed 32 deliveries allocated to either delayed (30-45
sec)
or immediate (5-10 sec) cord clamping. All pregnan
cies were between 24 and 316/7 weeks, singleton,
without placenta previa or abruption, bleeding, or
major fetal anomaly. In the delayed clamping group
, the
infant was held 10-15 inches below the introitus at
vaginal delivery or below the level of the incisio
n at
Cesarean section. No uterotonics were given before
cord clamping. 2 infants in the delayed group had
cord clamping at 3 sec; analysis was by intention-t
o-treat.
Groups were comparable with respect to birth weight
(approx. 1000g), ga, mode of deliv ery, Apgar scor
es
(6 at 1 min and 7 at 5 min). Groups differences we
re evident for initial mean blood pressure and init
ial
glucose. No significant differences were found in
temperature on admission, initial hct, mean blood
pressures over first 4 hours, use of volume expande
rs, or SNAPPE-II scores. Infants in the DCC group
had
fewer instances of suspected NEC or feeding intoler
ance; more infants in the ICC group were discharge
on
oxygen. There were no significant differences in m
ax bilirubin, days on ventilation, days on oxygen,
IVH,
transfusions, or days hospitalized.
Comments: No infants appeared so depressed that th
e obstetrician clamped the cord quickly for
resuscitation. The study was not masked to the del
ivery attendants, but delivery room personnel were
asked not to record the clamping interval in the in
fant chart.
Three issues related to harm were raise during prot
ocol development: 1) risk for hypothermia, 2) risk
for
increased hyperbilirubinemia, 3) effects of delayed
intubation. The protocol of Lindner (Pediatr
1999;103:961) also reported no increase in morbidit
y when selective intubation was carried out in VLBW
infants. All glucose levels < 40 mg/dL occurred in
ICC infants and were more likely to occur in those
> 28
weeks. The authors speculate that improved hepatic
perfusion supports earlier endogenous glucose
production. Less oxygen need at the time of discha
rge may result from placental transfusion serving a
sa
lung protective strategy. Jaykka (Acta Paediatr 19
58; 47:484) suggested that positive-pressure ventil
ation
prior to recruitment of the lung by pulmonary perfu
sion and capillary erection damages the alveoli and
causes irregular distension. No difference in hct
between the 2 groups may be the result of small sam
ple
size.
Nelle M, Zilow EP, Kraus M, Bastert G, Linderkanp O
. The effect of Leboyer delivery on blood viscosity
and other hemorheologic parameters in term neonates
. American Journal of Obstetrics and Gynecology.
1993;169:189-193.
LOE 3
Leboyer and conventional delivery methods were comp
ared in 30 births with respect to postnatal
alterations in blood viscosity, hematocrit value, p
lasma viscosity, red cell aggregation, and red cell
deformability in term neonates. Cords were clamped
within 10 seconds in the early group and at 3 min
in
the Leboyer deliveries. Residual placental blood v
olume was significantly less with the Leboyer metho
d.
Hct rose from 48% to 58% (birth to 2 hours) in the
Leboyer group and declined in the control group. B
lood
viscosity increased by 32% within the first 2 hours
, but did not change signficantly after that. Plas
ma
viscosity, red cell aggregation, and red cell defor
mability were not affected by the mode of cord clam
ping.
No infant had clinical manifestations of polycythem
ia; bilirubin exceeded 15 mg/dL in 4 of 15 infants
with
late cord clamping and none with early cord clampin
g.
Comment: No description of level relative to the p
lacenta. Discrepancies in postnatal rise in hct an
d
viscosity within results section.
Nelle M, Zilow EP, Bastert G, Linderkamp O. Effect
of Leboyer childbirth on cardiac output, cerebral a
nd
gastrointestinal blood flow velocities in full-term
neonates. American Journal of Perinatology.
1995;12:212-216.
LOE 3
Leboyer and control deliveries in 30 women were com
pared with respect to hct, blood viscosity, left an
d
right ventricular output, and cerebral blood flow v
elocities (internal carotid, anterior cerebral, tru
ncus
coeliacus). Cord clamping was performed at 10 s in
the control group and 3 min in the Leboyer deliver
ies.
After Leboyer birth, hct rose from 51% in cord bloo
d to 62% at 2-4 h age, increasing viscosity by 32%.
Stroke volume, heart rate, cardiac output, left-to-
right shunt across the ductus, and blood flow veloc
ity were
similar in both groups and did not change during th
e first 5 d. On day 1, red cell flow was 25% highe
r in
the Leboyer group compared with the controls. Vasc
ular hindrance (resistance to blood viscosity), an
indicator of vasoconstriction, was 25% lower in the
Leboyer group, suggesting marked vasodilation.
Comment: non-randomized, physiologic outcomes
Nelle M, Kraus M, Bastert G, Linderkamp O. Effects
of Leboyer childbirth on left-and right systolic ti
me
intervals in healthy term neonates. Journal of Peri
natal Medicine. 1996;24:513-520.
LOE 3
30 healthy infants born vaginally at 38-41 weeks we
re studied. In 15 infants, the cords were clamped
within 10 s of birth; 15 infants delivered accordin
g to the Leboyer method were placed on their mother
's
aabdomen and cords were clamped 3 minutes after bir
th. Cord values were similar; in the early clamping
group, hct did not change signficantly during the f
irst 5 days. In the late group, the hct rose from
51% to
61% at 2-4 hrs age. No infant developed clinical s
igns of polycythemia. There were no differences in
LVET and RVET between the 2 groups during the first
5 days. LPEP/LVET and RPEP/RVET were
significantly elevated in the late group on day 1 a
nd RTPV/RVET decreased, but PVR was normal on day
5.
Comment: The echocardiographic findings suggest a
transient increase in afterload on the LV and high
pulmonary vascular resistance, consistent with prol
onged pulmonary hypertension after birth.
Nelson NN, Enkin MW, Saigal S, Bennett KJ, Milner R
, Sackett DL. A randomized clinical trial of the
Leboyer approach to childbirth. New England Journal
of Medicine. 1980;302:655-660.
LOE 3
54 deliveries were divided between Leboyer and cont
rol delivery. Leboyer births took place in bed; th
e
baby was placed skin-to-skin on the mother's abdome
n and massaged by the mother; the cord was cut when
it stopped pulsating. Control deliveries took plac
e in a delivery room; the cord was cut within 60 s
of
delivery, and the baby was returned to the mother.
In the Leboyer group, time to cord clamping median
was 180 s and control group median 45 s. There was
a trend toward greater residual placental blood
volume in the Leboyer group. There were no statisti
cally significant differences in infant morbidity (
Apgar
< 5 at 1 min, median Hgb at 24 h, Hbg > 25 g/dL, ta
chypnea. Bilirubin > 12 mg/dL was more frequent in
the Leboyer group, but this was explained by more A
BO incompatibility.
Comment: In this series, both groups might qualify
for the definition of delayed cord clamping. In t
he
Leboyer group, the baby was held above the placenta
for a median time of 3 minutes.
Oh W, Lind J, Gessner IH. The circulatory and respi
ratory adaptation to early and late cord clamping i
n
newborn infants. Acta Paediatrica Scandinavica. 196
6;55:17-25.
LOE 3
The prospective, controlled study examined 32 term
infants whose umbilical cords were clamped early (a
s
soon as the buttocks were delivered) and 30 infants
with late clamping (after pulsations ceased - mean
nearly 4 min). All deliveries were vaginal with in
termittent nitrous oxide or no analgesia. Infants
were
held approx 10 cm below the introitus. Time to fir
st spontaneous breath was shorter in the early clam
ped
group (6.3+ 0.6 vs. 9.2+1.3 sec); 5 min Apgars and
time to first cry were not different. 22 infants i
n the
early clamped group initiated respiration after the
cord was clamped. Systolic blood pressure was
significantly higher in the late clamped group of i
nfants during the first 24 h. Venous hct was also
higher
during the first 4h. and correlated positively with
blood pressure. Repiratory rate in the early clam
ped
group was significantly slower during the 1st - 3rd
hours of life.
Comment: Non-randomized; only healthy infants. Th
e authors speculate on increased transudation of
pulmonary fluid as being responsible for the increa
sed respiratory rate (always < 60 bpm) during
transition.
Oh W, Lind J. Body temperature of the newborn infa
nt in relation to placental transfusion. Acta
Paediatrica Scandinavica. 1967;Supplement 172:137-1
45.
LOE 3
This study compared body and skin temperature in 30
term infants, 16 with cord clamping after pulsatio
n
stopped (mean 3m 48sec) and 14 with immediate cord
clamping (mean 9sec). All deliveries were vginal
and uncomplicated with no analgesia or intermittent
nitrous oxide. Infants were held 10 cm below the
introitus in the delayed clamping group. During th
e first 4h of life the early clamped infants had
significantly lower skin temperature in the heel an
d palm than the late-clamped infants. The authors
speculate that decreased skin blood flow, due to pe
ripheral vasoconstriction and smaller blood volume,
explain the observed differences.
Oxford Midwives Research Group. A study of the rela
tionship between the delivery to cord clamping
interval and the time of cord separation. Midwifery
. 1991;7:167-176.
LOE 2
This randomized, controlled trial of 554 women was
carried out to compare the effect of early and late
cord
clamping on time of cord separation from the infant
abdominal wall. Early clamping was defined as
immediately after birth and late clamping as taking
place after 3 min or when the cord stopped pulsati
ng.
Oxytocin was administered with delivery of the ante
rior shoulder, and the infant was placed on the mot
her's
abdomen after delivery. Only singleton pregnancies
at 37-42 weeks were included. Operative deliverie
s
and pregnancies with signs of fetal distress were e
xcluded. 256 early-clamped deliveries and 296 late
-
clamped deliveries were comparable except in the us
e of syntocinon for induction of augmentation of la
bor
(greater in late group). There were no differences
in maternal or neonatal outcomes except that more
of the
late clamped group continued predominant or exclusi
ve breatfeeding at home. There was a trend toward
more jaundice in the late-clamped group.
Comment: The sample size did not reach that calcul
ated to have an 80% chance of detecting a change
from 10% or the percentage of umbilical cords adher
ent on day 8 to 5% with 5% significance level. Acu
te
neonatal outcome assessment was limited. Of the 29
6 deliveries in the late-clamped group, 15 had earl
y
clamping because of cord around the neck and 7 beca
use of asphyxia and need for resuscitation. There
was no comment on Apgar scores or overall need for
resuscitation in either group.
Rabe H, Wacker A, Hulskamp G, Hornig-Franz I, Schul
ze-Everding A, Harms E, Cirkel U, Louwen F,
Witteler R, Schneider HPG. A randomised controlled
trial of delayed cord clamping in very low birth
weight preterm infants. European Journal of Pediatr
ics. 2000;159:775-777.
LOE 2
This randomized controlled trial examined the feasi
bility of late cord clamping (45s) in 40 preterm in
fants
(<33 wks) delivered mainly by c-section and the eff
ects on past-partum adaptation and anemia of
prematurity. Oxytocin was given after delivery of
the shoulder and the infant was held below the leve
l of
the placenta. Infants with Rh incompatibility, hyd
rops, congenital anomalies, Apgar < 3 at birth and
multiple gestation were excluded. Cord was clamped
after 20 or 45 s. The requirement for transfusion
by
d42 was significantly less in the late-clamped grou
p. Oral iron was begun at 2mg/kg after 4 weeks. T
here
were no significant differences in Apgar scores, te
mperature on admission, heart rate, blood pressure,
and
ventilatory requirements. Volume expansion need wa
s less in the late group, but not significantly dif
ferent;
no infant had signs of volume overload.
Comment: The distance below the placenta was not s
pecified for infant position before cord clamping.
Usher R, Shephard M, Lind J. The blood volume of th
e newborn infant and placental transfusion. Acta
Paediatrica. 1963;52:497-512.
LOE 3
The study investigated the blood volume of term inf
ants with cord clamping at various intervals after
birth.
27 infants at term, delivered by uncomplicated vagi
nal route were studied. 9 infants had immediate co
rd
clamping; 11 infants had the cord clamped after pul
sations ceased (approx 5 min); 7 infants had the co
rd
stripped firmly toward the infant once every 30 sec
for 5 min. Infants were held approx 10 cm below t
he
level of the introitus. Blood volumes were measure
at 30min, 4, 24, and 72 hours by I131 tagged album
in.
The blood volume of infants with delayed cord clamp
ing was 126 ml/kg at 5 min of age and equilibrated
to
93 ml/kg at 72 hours. Blood bolume of infants with
stripped cords was not significantly different fro
m
those with delayed clamping. Infants with immediat
e cord clamping had a blood volume of 78 ml/kg at
birth and 82 ml/kg at 72 hours. Venous hct rose in
delayed-clamping infants from 48% at birth to 60%
at
72 hours. Infants with immediate cord clamping had
estimated early values of 48% and 72-hours values
of
44%. The rate of placental transfusion is rapid du
ring the first seconds adn becomes progressively sl
ower,
with approximately 1/4 of total transfer in the fir
st 15 sec and 1/2 in the the first 60 sec. Paired
comparisons of 10 infants who did/did not establish
spontaneous respirations before cord clamping show
ed
no systematic differences in blood volume.
Comment: No details of clinical course are provide
d. The authors question whether a 61% expansion of
blood volume is good or bad.
Wilson EE, Windle WF, Alt HL. Deprivation of placen
tal blood as a cause of iron deficiency in infants.
American Journal of Diseases of Children 1941;63:32
0-327.
LOE 3
Follow-up was obtained on 28 term infants who had
participated in a trial of delayed cord clamping; 1
5
infants had immediate clamping of the cord after bi
rth and 13 had clamping delayed until the placenta
began to descend into the vagina. All infants were
of low socioeconomic status; no mother were anemic
at
the time of delivery; none had received iron therap
y during pregnancy. Total RBCs and %hbg were highe
r
in the delayed clamping group during the first week
of life (5.4M and 19.4 g/dl vs. 6.2M and 22.8g/dl)
. At
8-10 months of age the corresponding values were 5.
1M and 10.8g/dl for the immediate clamping group
and 4.4M and 11.9g/dl for the delayed clamping grou
p. MCH was signficantly higher in the delayed
clamping group (21.8 mcg vs. 27.0 mcg). An increase
d erythrocyte count accompanied by a decrease in
hgb content was interpreted as a sign of iron defic
iency.
Comment: Details of the original protocol are pres
ented in DeMarsh QB, Alt HL, Windle WF, Hillis DS.
The effect of depriving the infant of its placental
blood on the blood picture during the first week o
f life.
JAMA 1941; 116:2568. Laboratory methods used diffe
r from modern techniques. The diagnosis of iron
deficiency is somewhat presumptive according to mod
ern criteria. The follow-up study reported on only
a
Nyberg R, Westin B. On the influence of uterine con
tractions on the blood pressure in the umbilical ve
in at
birth. Acta Paediatrica. 1958;47:350-353.
Ogata, E. S., J. A. Kitterman, et al. (1977). "The
effect of time of cord clamping and maternal blood
pressure on placental transfusion with cesarean sec
tion." Am J Obstet Gynecol
128
(2): 197-200.
We measured the residual placental blood volume (RP
BV) of 20 infants delivered at term by cesarean
section of women not in labor. In all cases, the um
bilical cord was clamped within 40 seconds of birth
.
RPBV decreased significantly with increasing age at
cord clamping. In addition, RPBV for infants with
cords clamped within 20 seconds of birth correlated
inversely with maternal systolic blood pressure (m
ean
RPBV = 54.8 ml. per kilogram at 105 torr and 28.4 m
l. per kilogram at 148 torr). However, RPBV did not
correlate with maternal blood pressure for the whol
e group of 20 infants or for those with cords clamp
ed
later than 20 seconds after birth. These data indic
ated that in infants delivered by cesarean section
placental
transfusion is time related during the first 40 sec
onds of life and that maternal blood pressure also
influences the magnitude of placental transfusion d
uring the first 20 seconds after birth. Analysis of
data
from this study combined with data from a previous
study shows that after 40 seconds the net flow betw
een
placenta and infant reverses and that cord clamping
delayed beyond this point is accompanied by a rise
in
RPBV back to the level found when the cord was clam
ped before 20 seconds.
Oh W, Arcilla RA, Lind J, Gessner IH. Arterial bloo
d gas and acid base balance in the newborn infant:
effects of cord clamping at birth. Acta Paediatrica
Scandinavica 1966;55:593-599.
Oh W, Lind J. Venous and capillary hematocrit in ne
wborn infants and placental transfusion. Acta
Paediatrica Scandinavica 1966;55:38-40.
O, W., K. Omori, et al. (1975). "Placenta to lamb f
etus transfusion in utero during acute hypoxia." Am
J
Obstet Gynecol
122
(3): 316-22.
Maternal and fetal hemodynamics, placental blood fl
ow, fetal-placental blood volume, placental blood
volume, and fetal blood volumes were measured in si
x chronic sheep prepartions to evaluate their chang
es
during acute fetal hypoxia induced by maternal hypo
xia. During fetal hypoxia, the maternal and fetal
arterial blood pressure and heart rate were essenti
ally unchanged. The placental blood flow (control e
qual
to 325 ml.per kilogram per minute) was also unchang
ed during the hypoxia period. However, the placenta
l
blood volume decreased significantly from 65 to 60
and 51 ml. per kilogram at 15 and 30 minutes of
hypoxia period, respectively. The fetal blood volum
e increased reciprocally and significantly from 86
to
109 and 102 ml. per kilogram at the same periods of
hypoxia since the fetal-placental blood volumes we
re
unchanged. These blood volume changes persisted for
30 to 60 minutes following the stoppage of hypoxia
experiments. The placental vascular resistance meas
ured in six experiments showed a significant increm
ent
during hypoxia, suggesting placental vasoconstricti
on as the responsible mechanism for the reduction o
f
placental blood volume and reciprocal increase in f
etal blood volume. The data suggest that significan
t
placental transfusion to the lamb fetus may occur i
n utero during fetal hypoxia resulting in a higher
fetal
blood volume before birth.
Oh W, Wallgren G, Hanson JS, Lind J. The effects of
placental transfusion on respirato ry mechanics of
normal term newborn infants. Pediatrics 1967;40(1):
6-12.
Peltonen T. Placental transfusion - advantage and d
isadvantage. European Journal of Pediatrics.
1981;137:141-146.
Philip AGS, Yee AB, Rosy M, Surti N, Tsamtsouris A,
Ingall D. Placental transfusion as an intrauterine
phenomenon in deliveries complicated by foetal dist
ress. British Medical Journal 1969;2:11-13.
Philip AGS. Further observations on placental trans
fusion. Obstetrics and Gynecology. 1973;42:334-343.
Pietra GG, D'Amodio MD, Leventhal MM, Oh W, Braudo
JL. Electron microscopy of cutaneous capillaries
of newborn infants: effects of placental transfusio
n.678-683.
Electron microscopy of cutaneous capillaries showe
d distention and a larger number of fenestrated sma
ll
blood vessels in infants with late cord clamping as
compared to early-clamped group.
Pinter S, Kovacs L, Szollosi J, Sztano P, Boda D. A
cid-base homeostasis, prompt or delayed clamping of
the cord, and the effect of postnatal warming. Acta
Paediatrica Academiae Scientiarum Hungaricae
1971;12(1):59-67.
Piscane A. Neonatal prevention of iron deficiency.
BMJ 1996;312:136-137.
Redmond A, Isana S, Ingall D. Relation of onset of
respiration to placental transfusion. The Lancet
1965;1(7380):283-285.
Saigal S, O'Neill A, Surainder Y, Chua L, Usher R.
Placental transfusion and hyperbilirubinemia in the
premature. Pediatrics. 1972;49:406-419.
Bilirubin concentrations of 15mg/dl developed in 6%
of premature infants when cord clamping was
immediate, in 14% when cord clamping was delayed 1
min, and in 38% after a 5-min delay in cord
clamping.
Saigal S, Usher RH. Symptomatic neonatal plethora.
Biology of the Neonate. 1977;32:67-72.
LOE 5
Blood volume and clinical data are reported on 8 p
remature and 3 full-term infants who presented with
symptoms apparently due to polycythemia or hypervol
emia associated with delayed clamping of the
umbilical cord.
Saigal S, Wison R, Usher R. Radiological findings i
n symptomatic neonatal plethora resulting from
placental transfusion. Pediatric Radiology. 1977;12
5:185-188.
8 premature and 3 full-term infants presented with
cardiorespiratory and neurological symptoms referea
ble
to delayed cord clamping with confirmed polycythemi
a or hypervolemia. The radiological findings
included pulmonary vascular congestion, hyperaerati
on, pleural effusion, and mild cardiomegaly. Infan
ts
responded to conservative management or phlebotomy.
Sisson TRC. The placental transfusion. Clinical Ped
iatrics. 1972;11:251-252.
LOE 8
Commentary outlining the advantages, disadvantages,
and basic physiology of the placental transfusion.
Sosa MLC, Rubio GG, Karchmer K. S. Influencia de la
transfusion placentaria en el electrocardiograma d
el
recien nacido. Arch Inst Cardiol Mex. 1973;43:80-8
6.
Strauss RG, Mock DM, Johnson K, et al. Circulating
RBC volume, measured with biotinylated RBCs, is
superior to the Hct to document the hematologic eff
ects of delayed versus immediate umbilical cord
clamping in preterm neonates. Transfusion 2003;43:1
168-1172.
LOE 2 - small RCT
The data presented, part of a randomized clinical t
rial of delayed cord clamping, focus on the correla
tion of
circulating RBC volume (measured directly with biot
inylated RBCs) with indirect estimation by hematocr
it
or mathematical calculation. Significant expansion
of circulating RBC volume was demonstrated after
delayed cord clamping with vaginal delivery (60 sec
ond, 10-12 inches below the placenta), using the di
rect
measurement method; however, the indirect measureme
nts failed to detect a change. There was no increa
se
in circulating RBC volume after c-section delivery
(60 sec, neonate beside mother's thigh).
Tamayo JG. The use of residual placental blood for
transfusion. Journal of PMA. 1966;42:399-406.
Taylor PM, Bright NH, Birchard EL. The effect of im
mediate versus delayed clamping of the umbilical
cord on mortality and respiratory rates of the newb
orn infant. American Journal of Diseases of Childre
n
1959;98:649-650.
Tiisala R, Tahti E, Lind J. Heart volume variations
during first 24 hours of life of infants with earl
y and late
clamped umbilical cord. Annales Paediatriae Fenniae
. 1966;12:151-153.
In 30 term newborn infants, a comparison was made
between 15 with immediate cord clamping and 15
with cord clamping at 3 min. Heart volume determin
ations by x-ray showed a smaller average heart
volume in the early-clamped infants.
Usher RH, Saigal S, O'Neill A, Surainder Y, Chua L.
Estimation of red blood cell volume in premature
infants with and without respiratory distress syndr
ome. Biology of the Neonate. 1975;26:241-248.
LOE 5 (subgroup LOE 2)
262 consecutively delivered preterm infants (26-36
wks, 850-3550g, 257 vaginal and 5C/S, no oxytocics
before delivery of placenta) had blood volume deter
minations with radioactive iodine labeled albumin.
139
subjects had their umiblical cords ligated accordin
g to a randomized protocol at 1) < 5 sec, 2) 1 min
or 3)
at 5 min. For the remaining 132, delivery was unex
pected and the umbilical cord was clamped at the
discretion of the obstetrician.
Red cell volume was largest in infants who did not
develop RDS, lower in those who were affected and
survived, and lowest in fatal cases; this associati
on was not a function of g.a. When divided into 3
groups
according to red cell volume, those with smallest R
CV (immediate cord clamping) had a fatality rate of
10.3%; the intermediate group (3-45 sec delay) had
a 5.7% rate, and those with the largest RCV (5 min)
had a 2.3% rate.
Comment: a delay of 1-1.5min in clamping is recomme
nded to provide RCV > 42 ml/kg and minimize heat
loss and difficulty in resuscitation.
Walsh SZ. Early clamping versus stripping of cord:
comparative study of electrocardiogram in neonatal
period. British Heart Journal 1969;31:122-126.
Walsh SZ, Gyulai F. The effect of cry on heart rate
and the Q-A2 interval in early and late clamped in
fants.
Biology of the Neonate. 1973;23:193-204.
Wardrop, C. A. and B. M. Holland (1995). "The roles
and vital importance of placental blood to the
newborn infant." J Perinat Med
23
(1-2): 139-43.
At 30 weeks' gestation, half of the approximately 1
10 ml/kg total blood volume (BV) of the feto-placen
tal
circulation is in the fetus, rising, by term, to ab
out 90 ml/kg. In preterm infants at birth, subnorma
l blood
volume is the rule, because of immediate cord clamp
ing. Blood volume, typically 50-60 ml/kg during
critical care, limits systemic oxygen (O2) transpor
t and, because of shunting, causes hepato-splanchni
c
ischaemia and impaired lung function. Haemoconcentr
ation results from plasma extravasation because of
vascular endothelial damage. This elevates the haem
atocrit, masking the red cell lack. By allowing
placental transfusion at birth, delaying cord clamp
ing by 30-60 seconds, initial oligovolaemia is obvi
ated,
and post-natal lung adaptation greatly facilitated.
The complications and costs of care can thereby be
much
reduced. Losses of haemopoietic stem cells are redu
ced, vital for haematologic and immunologic
constitution and for response to haemopoietic growt
h factors. Further work is urgently needed to deter
mine
how to optimize this vital opportunity in preventiv
e medicine in perinatology, with the objective of
preventing complications, and reducing costs of all
kinds, in management of the infant born preterm.
Whipple GA, Sisson TRC, Lund CJ. Delayed ligation o
f the umbilical cord - its influence on the blood
volume of the newborn. Obstetrics and Gynecology 19
57;10(6):603-610.
Yao AC, Hirvensalo M, Lind J. Placental transfusion
-rate and uterine contraction. The Lancet.
1968;1(7539):380-383.
Yao AC, Lind J. Effect of gravity on placental tran
sfusion. The Lancet 1969;2(7619):505-508.
Yao AC, Lind J. Blood volume in the asphyxiated ter
m neonate. Biology of the Neonate 1972;21:199-209.
Yao AC, Lind J. Blood flow in the umbilical vessels
during the third stage of labor. Biol Neonate
1974;25:186-193.
Yao AC, Lind J. Placental transfusion. American Jou
rnal of Diseases of Children 1974;127:128-141.
Yao, A. C. and J. Lind (1977). "Effect of early and
late cord clamping on the systolic time intervals
of the
newborn infant." Acta Paediatr Scand
66
(4): 489-93.
The effect of early and late cord clamping on the l
eft ventricular performance of the newborn infant w
as
assessed by measuring the systolic time intervals f
rom the indirect carotid pulse tracings and simulta
neous
phonocardiogram and electrocardiogram. The study wa
s performed in 13 normal, full-term infants
sequentially at 20-105 min, 6-6 1/2 hrs, and 24-27
hrs of age. The umbilical cords were clamped early
in 7
(E.C.) and clamped late in 6 infants (L.C.). The ra
tio of the pre-ejection period (PEP) to the left ve
ntricular
ejection time (LVET) was found to be significantly
higher in the L.C. infants (mean +/- S.E., 0.400 +/
-
0.18, 0.433 +/- 0.018, 0.410 +/- 0.021) compared wi
th those of the E.C. (0.334 +/- 0.010, 0.347 +/- 0.
009,
0.361 +/- 0.007) with p values of less than 0.01, l
ess than 0.005 and less than 0.05, respectively in
the three
examination periods. The higher PEP/LVET ratios in
the L.C. infants were mainly attributable to a
prolongation of the PEP. It is suggested that late
cord clamping, by allowing a sizable placental tran
sfusion,
appeared to affect adversely the left ventricular p
erformance of the neonate. Furthermore, it is sugge
sted
that in evaluating systolic time intervals of the n
eonate during the first days of life, the volumic s
tate or
status of placental transfusion should be taken int
o consideration as a determinant.
Yao AC, Moinian M, Lind J. Distribution of blood be
tween infant and placenta after birth. The Lancet
1969;2(7626):871-873.