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Delayed Cord Clamping:Transferring Evidence intoPractice
Ryan M. McAdams MD
Disclosure• Neither I nor any member of my immediate
family has a financial relationship or interestwith any proprietary entity producing healthcare goods or services related to the contentof this CME activity.
• My content will not include discussion/reference of any commercial products orservices.
• I do not intend to discuss an unapproved/investigative use of commercialproducts/devices.
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Objectives
• Participants will learn the latest evidenceconcerning the recommendations onoptimizing placental transfusion after birth,including the physiological rationale for thepractice
• Understand steps to consider regardingimplementation of delayed cord clamping in ahospital settings
• Identify communication strategies to helpensure effective teamwork and patient safety
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Recommended practice guidelines for delayed cord clamping
Extremely Preterm
37 WGA
WHO Delay of umbilical cord clamping for 1 - 3 minutes after birth is recommended for all births with
simultaneous essential newborn care.
ACOG Evidence supports delayed umbilical cord
clamping in preterm infants.
Insufficient evidence exists to support or refutethe benefits of delayed umbilical cord clampingfor term infants born in resource-rich settings.
AAP Endorsed recommendations of ACOG (above)
SOGC Delayed cord clamping by at least 60seconds is recommended
The risk of jaundice is weighed against thephysiological benefits of delayed cord clamping.
RCOG 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.
ILCOR 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 andGynecologists; AAP, American Academy of Pediatrics; SOGC, Society of Obstetricians andGynaecologists of Canada; RCOG, Royal College of Obstetricians and Gynaecologists; ILCOR,International Liaison Committee on Resuscitation; WGA, weeks gestational age.
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Live births and fertility rates: United States, 1920–2012
Assumption of Evidence
Immediate cord clamping (ICC) practiced onhundreds of millions of babies
No evidence to support this practice
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Etiology of ICC?
• Not totally clear • Early 1900’s, pregnant mothers routinely
given general anesthesia before delivery• Newborns had severe respiratory
depression• Doctors quickly clamped and cut the
umbilical cord to prevent babies fromreceiving further chloroform or ether
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Postpartum Hemorrhage (PPH)• Active Management to Reduce PPH
1. Prophylactic uterotonic drug2. Immediate umbilical CC3. 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 terminfants on maternal and neonatal outcomes. Cochrane Database Syst Rev. 2013.
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3 mm
6 mm
2 cm
UC Length: 50-60 cm
UC Blood Flow: ~110-125 mL/min/kg
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Immediate Cord Clamping
Systemic peripheral resistance Venous returnincreases decreases
by 30–50%
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 bloodvolume is ~90 ml/kg
• Fetoplacental volume:150 ml at 26 wks’gestation
• Up to 2/3 of thepreterm infant’s blood
amount can bedistributed in theplacenta at the time ofdelivery
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Placental Transfusion After Birth
• ¼ (40 ml) enters term infant within 15 sec• ½ (80 ml) within 60 sec• Within hours, additional plasma lost to the
circulation, leaving a high red cell mass• RBCs broken down in 1 st 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): 93–98.Aladangady N , et al. Is it possible to promote placental transfusion at preterm delivery? Pediatr Res.1998;44:454.
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What’s the big deal?
Most Preterm Births Occurin Africa and Asia
10.9 million preterm births(2005)
0.5 million preterm births
Beck , et al. The worldwide incidence of preterm birth: a systematic review of maternalmortality and morbidity. Bulletin of the World Health Organization. Vol 88 (1), Jan 2010, 31-
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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 DiseaseControl Prevent 2009;57:7.Maier RJ , et al. Changing practices of red blood cell transfusions in infants with birth weights lessthan 1000 g. J Pediatr 2000;136: 220–4.Sacher RA , et al. Blood component therapy during the neonatal period: a national survey of red celltransfusion practices, 1985. Transfusion 1990;30:271–6.
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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Normal
Deficits*
56,130
3,952,841 Live Births
456,5533,496,288
10%
CerebralPalsy
*Deficits: cogni ve, behavior,
a en on, or socializa on
2012 data: CDC Na onal Vital Sta s cs System
Term
Preterm VLBW
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-agechildren
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 ironstatus in infancy
• Iron deficiency & anemia in infancy maybe 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;84:1035–44.Grantham-Mcgregor S, et al. A review of studies on the effect of iron deficiency on cognitive development in children. J Nutr 2001;131:649–66S.Lozoff B , et al. Iron deficiency and iron therapy effects on infant developmental test performance. Paediatrics1987;79:981–95.Algarín 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/Ethnicityin Federally Funded Programs for Women &
Infants in the US
Dalenius, K. et al. (2012). Pregnancy nutrition surveillance 2010 report.
1.6 million infants
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The brain changes while the baby is in the NICU
Infants, born at 23 - 30 wksgestation, 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
Raju TN . Timing of umbilical cord clamping after birth for optimizing placental transfusion. Curr Opin Pediatr. 2013 .
DCC
DCC: Benefits in Preterm Infants
• Increased – Hct during early
neonatal period – Systemic BP
• 4 & 24 h of age
– Blood volume – Urine output (1 st 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
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Backes et al. Placental Transfusion Strategies in Very Preterm Neonates. Obstet Gynecol 2014.
Decreased Mortality with DCC
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DCC: Benefits in Term Infants
• Increased – Hgb and Hct in early neonatal period – Total body iron stores, 2–4 mo of age – Circulating ferritin level, 2–4 mo of age
• Decreased – Incidence of iron-deficiency anemia (4 mo of age)
• No published RCT in 33 years has shown a linkbetween DCC and hyperbilirubinemia orsymptomatic 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 bestmanagement 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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What’s the optimal position to hold
the baby for DCC?• Vain et al. (2014) compared infantsweights as an indirect measure of bloodvolume – 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), 235–240.
Delay is preferable to error.
Thomas Jefferson
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Conclusions
• The focus at birth should be on optimizing thebabies blood supply
• ICC has no physiological rationale and maycause harm – Doubled risk of anemia at 3-6 months in term
infants
• Placental transfusion should benefitnewborns compromised at birth – More studies looking at resuscitation with an
intact cord are neededMcDonald, S. J. et al (2013). Cochrane Database of Systematic Reviews, 7 , CD004074.
Conclusions• Implementation of DCC requires:
– An assessment of organizational readiness to adopt aDCC 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 compliancemay decrease over time.
• More research on long-term neurodevelopmentaloutcomes 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): 1235–1242.• 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 Perinatology2010; 30 (1):11–6.
• Philip AGS, Teng SS. Role of respiration in effecting transfusion at cesarean section. Biol Neonate1977;31:219–44.
• Philip AGS, Saigal S. When should we clamp the umbilical cord? NeoReviews• 2004;5:e142–53.• Rabe H, Wacker A, Hü lskamp G, et al. A randomized controlled trial of delayed cord clamping in very low
birth weight preterm infants. Eur J Pediatr 2000;159: 775–7.• 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;117:351–357• 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;2:505–508
• Yao AC, Moinian M, Lind J. Distribution of blood between the infant and the placenta after birth. Lancet1969;7626(2):871–3.
• Yao AC, Hirvensalo M, Lind J. Placental transfusion rate and uterine contraction. Lancet 1968;1:380–3.• Yao AC, Lind J. Blood volume in the asphyxiated term neonate. Biol Neonate 1972;21:199–209.• Yao AC, WistA, Lind T. The blood volume of the newborn infant delivered by caesarean section. Acta
Paediatr Scand 1967;56:585–92 .
Thank-you
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