9/30/2015

Delayed Cord Clamping:

Transferring Evidence into
Practice

Ryan M. McAdams MD

Disclosure
Neither I nor any member of my immediate
family has a financial relationship or interest
with any proprietary entity producing health
care goods or services related to the content
of this CME activity.
My content will not include discussion/
reference of any commercial products or
services.
I do not intend to discuss an unapproved/
investigative use of commercial
products/devices.

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Objectives
Participants will learn the latest evidence
concerning the recommendations on
optimizing placental transfusion after birth,
including the physiological rationale for the
practice
Understand steps to consider regarding
implementation of delayed cord clamping in a
hospital settings
Identify communication strategies to help
ensure effective teamwork and patient safety

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Recommended practice guidelines for delayed cord clamping

WHO
ACOG
AAP
SOGC

RCOG

ILCOR

Extremely Preterm

Preterm

Term

<28 WGA

2837 WGA

>37 WGA

Delay of umbilical cord clamping for 1 - 3 minutes after birth is recommended for all births with
simultaneous essential newborn care.
Evidence supports delayed umbilical cord
clamping in preterm infants.

Insufficient evidence exists to support or refute

the benefits of delayed umbilical cord clamping
for term infants born in resource-rich settings.

Endorsed recommendations of ACOG (above)

Delayed cord clamping by at least 60
seconds is recommended

The risk of jaundice is weighed against the

physiological benefits of delayed cord clamping.

Do not clamp umbilical cord earlier than necessary unless exigent circumstances such as heavy
maternal blood loss or the need for immediate neonatal resuscitation take priority.
Delay umbilical cord clamping for at least 1 min for newborn infants not requiring resuscitation.
Evidence does not support or refute delayed cord clamping when resuscitation is needed.

Abbreviations: WHO, World Health Organization; ACOG, American College of Obstetricians and
Gynecologists; AAP, American Academy of Pediatrics; SOGC, Society of Obstetricians and
Gynaecologists of Canada; RCOG, Royal College of Obstetricians and Gynaecologists; ILCOR,
International Liaison Committee on Resuscitation; WGA, weeks gestational age.

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Assumption of Evidence

Immediate cord clamping (ICC) practiced on

hundreds of millions of babies
NoLive
evidence
to support
this19202012
practice
births and fertility
rates: United States,

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Etiology of ICC?
Not totally clear
Early 1900s, pregnant mothers routinely
given general anesthesia before delivery
Newborns had severe respiratory
depression
Doctors quickly clamped and cut the
umbilical cord to prevent babies from
receiving further chloroform or ether

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Postpartum Hemorrhage (PPH)

Active Management to Reduce PPH
1. Prophylactic uterotonic drug
2. Immediate umbilical CC
3. Controlled cord traction
Delayed CC (DCC) does not risk of hemorrhage
Cochrane review: 15 trials, 3911 women/infant pairs
No significant difference in PPH rates when ICC and
DCC compared (RR 1.04, 95% CI 0.65 to 1.65)
McDonald SJ, Middleton P. Effect of timing of umbilical cord clamping of term
infants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013.

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UC Length: 50-60 cm
UC Blood Flow: ~110-125 mL/min/kg

3 mm

2 cm

6 mm

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Immediate Cord Clamping

Systemic peripheral resistance
increases

Venous return
decreases
by 3050%

Arterial pressure increase

Cardiac afterload increases

Cardiac preload decreases

Increased potential for impaired cardiac output

Vali et al. Maternal Health, Neonatology, and Perinatology (2015) 1:4

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Natural Umbilical Vessel Closure

After Birth
Umbilical artery closure begins after 15 sec
Functional closure by 45 sec

Umbilical vein closure begins shortly after

Diameter decreases significantly by 1-2 min

Placenta Blood Volumes

Term fetus blood
volume is ~70 ml/kg
Total fetoplacental
volume 115 ml/kg

Preterm fetus blood

volume is ~90 ml/kg
Fetoplacental volume:
150 ml at 26 wks
gestation
Up to 2/3 of the
preterm infants blood
amount can be
distributed in the
placenta at the time of
delivery

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Placental Transfusion After Birth

(40 ml) enters term infant within 15 sec
(80 ml) within 60 sec
Within hours, additional plasma lost to the
circulation, leaving a high red cell mass
RBCs broken down in 1st two months of
age and iron is re-used or stored

DCC
Allows extra transfer of fetal blood from
the placenta to the infant
Results in ~10 -15 ml/kg of additional
whole cord blood for a VLBW infant
8% - 24% increase in blood volume with
DCC of 30 - 45 sec in preterm infants
Aladangady N, et al. Infants blood volume in a controlled trial of placental transfusion at preterm delivery.
Pediatrics 2006; 117(1): 9398.
Aladangady N, et al. Is it possible to promote placental transfusion at preterm delivery? Pediatr Res.
1998;44:454.

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Whats the big deal?

Most Preterm Births Occur

in Africa and Asia
0.5 million preterm births

10.9 million preterm births

(2005)
Beck, et al. The worldwide incidence of preterm birth: a systematic review of maternal
mortality and morbidity. Bulletin of the World Health Organization. Vol 88 (1), Jan 2010, 3138.

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Preterm births in the US

Affects 11.73% of pregnancies (2011 data)

~10,000 infants born prematurely per wk
600 (6%) of these are ELBW
~90% of ELBW neonates will receive at
least one RBC transfusion

Martin JA, et al. Births: final data for 2008 national Vital Statistics Reports. Centers Disease
Control Prevent 2009;57:7.
Maier RJ, et al. Changing practices of red blood cell transfusions in infants with birth weights less
than 1000 g. J Pediatr 2000;136: 2204.
Sacher RA, et al. Blood component therapy during the neonatal period: a national survey of red cell
transfusion practices, 1985. Transfusion 1990;30:2716.

Premature infants at risk for:

Respiratory problems
Blood pressure instability
Anemia of prematurity (AOP)
Hyperbilirubinemia
Necrotizing Enterocolitis
Intraventricular hemorrhage (IVH)
Neurodevelopmental delays
Cerebral palsy
Prevalence rates vary from 19 to 152 per 1,000 live
births for very premature and VLBW infants

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Cerebral
Palsy
10%
Normal

3,952,841 Live Births

Preterm
Term
3,496,288

Deficits*

VLBW

456,553

*Deficits: cogni ve, behavior,

a en on, or socializa on
56,130

2012 data: CDC Na onal Vital Sta s cs System

Anemia of prematurity (AOP)

Typically occurs at 4 to 6 weeks after birth in
infants < 32 weeks gestation
Causes:
Reduced RBC life span
60 to 80 days: Term infants
45 to 50 days: Extremely low birth weight infants

Blood loss from phlebotomy

2 to 4 ml/kg per week

Iron depletion
May impair recovery from AOP
Lin, JC et al. Phlebotomy overdraw in the neonatal intensive care nursery.
Pediatrics. 2000;106(2):E19.

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Pregnant women

Worldwide prevalence of anaemia 1993-2005, WHO Global Database on Anaemia

Preschool-age
children

Worldwide prevalence of anaemia 1993-2005, WHO Global Database on Anaemia

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The Anemia Argument

Blood is a scarce and costly resource
Risk of multiple donor exposures
Iron stores at birth show large individual
variations, but correlate with later iron
status in infancy
Iron deficiency & anemia in infancy may
be associated with later cognitive deficits
Michaelsen KJ, et al. A longitudinal study of iron status in healthy Danish infants: effects of early iron status, growth velocity and dietary factors.
Acta Paediatr 1995;84:103544.
Grantham-Mcgregor S, et al. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:64966S.
Lozoff B, et al. Iron deficiency and iron therapy effects on infant developmental test performance. Paediatrics 1987;79:98195.
Algarn C, et al. Iron-deficiency anemia in infancy and poorer cognitive inhibitory control at age 10 years. Dev Med Child Neurol. 2013

Maternal & Infant Anemia by Race/Ethnicity

in Federally Funded Programs for Women &
Infants in the US

1.6 million infants

Dalenius, K. et al. (2012). Pregnancy nutrition surveillance 2010 report.

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The brain changes while the baby is in the NICU

Infants, born at 23 - 30 wks
gestation, measured from
birth to 48 weeks PMA.
N=113
Kapellou et al. 2006 PLoS Med

DCC:
What does the literature say?

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DCC vs ICC in preterm infants: Major benefits based on RCTs

DCC

Raju TN. Timing of umbilical cord clamping after birth for optimizing placental transfusion. Curr Opin Pediatr. 2013.

DCC: Benefits in Preterm Infants

Increased
Hct during early
neonatal period
Systemic BP
4 & 24 h of age

Blood volume
Urine output (1st 48 h)
Cerebral oxygenation
Transfer of stem cells
Myocardial function

Decreased
Need for inotropic
medications
Need for blood
transfusions for anemia
IVH incidence (all
grades)
Necrotizing enterocolitis
Death in neonates <32
weeks gestation

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Decreased Mortality with DCC

Backes et al. Placental Transfusion Strategies in Very Preterm Neonates. Obstet Gynecol 2014.

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DCC: Benefits in Term Infants

Increased
Hgb and Hct in early neonatal period
Total body iron stores, 24 mo of age
Circulating ferritin level, 24 mo of age

Decreased
Incidence of iron-deficiency anemia (4 mo of age)

No published RCT in 33 years has shown a link

between DCC and hyperbilirubinemia or
symptomatic polycythemia

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Implementing DCC

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Not All or None

Likely situations where ICC is indicated
Ruptured vasa previa results in fetal blood loss &
need for urgent delivery
Baby likely hypovolemic
Waiting for a placental transfusion may be fruitless due
to continued loss of blood from the cord vein
May create a placental transfusion by cord milking and
lowering the baby below the placenta

RCTs unlikely to study these situations

Assuming that ICC will always be the best
management is not evidence based

Unresolved issues
What is the optimal time to CC for high-risk
infants?
Multiple gestations
At risk fetal polycythemia
IUGR, LGA, IDM

Should NRP be started before CC?

Should newborns be ventilated before CC?
Effects on long-term outcomes?

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Whats the optimal position to hold

the baby for DCC?
Vain et al. (2014) compared infants
weights as an indirect measure of blood
volume
Weight checked at birth and 2 min after
cutting the cord
2 positions: level of perineum & on maternal
abdomen

No statistical difference in weight change

Vain, N. E. et al. Lancet, 2014: 384(9939), 235240.

Delay is preferable to error.

Thomas Jefferson

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Conclusions
The focus at birth should be on optimizing the
babies blood supply
ICC has no physiological rationale and may
cause harm
Doubled risk of anemia at 3-6 months in term
infants

Placental transfusion should benefit

newborns compromised at birth
More studies looking at resuscitation with an
intact cord are needed
McDonald, S. J. et al (2013). Cochrane Database of Systematic Reviews, 7, CD004074.

Conclusions
Implementation of DCC requires:
An assessment of organizational readiness to adopt a
DCC protocol
Methods to measure and encourage staff compliance
Ways to track outcome data of infants who underwent
DCC

Strategies to improve DCC implementation

effectiveness are recommended since compliance
may decrease over time.
More research on long-term neurodevelopmental
outcomes is needed

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References

McDonald SJ, Middleton P, Dowswell T, Morris PS. Effect of timing of umbilical cord clamping of term
infants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013 Jul 11;7:CD004074.
Mercer JS et al. Delayed cord clamping in very preterm infants reduces the incidence of intraventricular
hemorrhage and late-onset sepsis: a randomized, controlled trial. Pediatrics 2006; 117(4): 12351242.
Mercer JS, et al. Seven-month developmental outcomes of very low birth weight infants enrolled in a
randomized controlled trial of delayed versus immediate cord clamping. Journal of Perinatology
2010;30(1):116.
Philip AGS, Teng SS. Role of respiration in effecting transfusion at cesarean section. Biol Neonate
1977;31:21944.
Philip AGS, Saigal S. When should we clamp the umbilical cord? NeoReviews
2004;5:e14253.
Rabe H, Wacker A, Hulskamp G, et al. A randomized controlled trial of delayed cord clamping in very low
birth weight preterm infants. Eur J Pediatr 2000;159: 7757.
Rabe H. Effect of timing of umbilical cord clamping and other strategies to influence placental transfusion
at preterm birth on maternal and infant outcomes. Cochrane Database Syst Rev. 2012
Sisson TRC, Knutson S, Kendall N. The blood volume of infants: IV. Infants born by cesarean section.
Am J Obstet Gyenecol. 1973;117:351357
Sommers R, et al. Hemodynamic effects of delayed cord clamping in premature infants. Pediatrics.
2012;129(3):e667-72
Yao AC, Lind J. Effect of gravity on placental transfusion. Lancet. 1969;2:505508
Yao AC, Moinian M, Lind J. Distribution of blood between the infant and the placenta after birth. Lancet
1969;7626(2):8713.
Yao AC, Hirvensalo M, Lind J. Placental transfusion rate and uterine contraction. Lancet 1968;1:3803.
Yao AC, Lind J. Blood volume in the asphyxiated term neonate. Biol Neonate 1972;21:199209.
Yao AC, Wist A, Lind T. The blood volume of the newborn infant delivered by caesarean section. Acta
Paediatr Scand 1967;56:58592.

Thank-you

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