delayed cord clamping - university of utah...delayed cord clamping (dcc) − cord milking (muc) −...
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Delayed Cord Clamping
T. Flint Porter, MD, MPH
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Background• Placental transfusion: blood volume
transfused to baby after delivery• Umbilical Cord Blood Flow (UCBF)• Factors that influence transfusion
− Delayed cord clamping (DCC)− Cord milking (MUC)− Gravity− Uterotonics
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Mechanisms of DCC and Improved Outcome
• Increased neonatal blood volume− Improved perfusion− Reduction in organ injury
• Allow spontaneous breathing to begin− Smoother transition of cardiopulmonary
and cerebral circulation− Reduce need for resuscitation
• Increase iron stores, reduce anemia• Transfusion of blood enriched with
stem cells and immunoglobulin
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Potential Drawbacks• Delayed resuscitation
• Increase risk of neonatal hypothermia, polycythemia, hyperbilirubinemia
• Increase risk for maternal hemorrhage
• Interfere with cord blood collection
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How long does umbilical cord blood flow continue?
• Prospective observational trial of UCBF after delivery in 30 term infants
• Protocol− Placed skin-to-skin by CNM− Doppler of straight portion until clamping− Cord clamped at CNM discretion (pulsation)− Pulse cessation determined by researcher− Measurements after 1st breath (30/30) and
oxytocin (28/30)Boere et al, Arch Dis Child Fet Neo Ed, 2014
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UCBF After DeliveryVenous Flow
• No venous flow at initial exam3/30 (10%)
• Flow stopped 04:36 (03:03–08:22)• Cord clamped 06:02 (04:47–09:35)17/30 (57%)
• Flow still present when cord clamped 05:13 (02:56–09:15)10/30 (33%)
Boere et al, Arch Dis Child Fet Neo Ed, 2014
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UCBF After DeliveryVenous Flow
• Flow stopped during deep breathsBreathing
• Flow stopped• Flow reversed flow
with “hard” cryingCrying
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UCBF After DeliveryArterial Flow
• No flow at initial exam5/30 (17%)
• Flow stopped 04:22 (02:29–07:17)• Cord clamped 06:15 (05:02–09:30)12/30 (40%)
• Flow still present when cord clamped 05:16 (03:32–10:10)13/30 (43%)
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UCBF After DeliveryTime Differences
In 15 infants arterial and venous flow stopped simultaneously
• Flow to baby7 infants
Arterial stopped first01:08 (00:51–03:03)
• Net flow from baby!
8 infantsVenous stopped first01:43 (00:51–02:45)
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UCBF After DeliveryConclusions
• UCBF longer than previously described• Complex process affected by
− Breathing and crying− Differing arteriovenous flow cessation− Arterial flow toward the placenta
• UCBF unrelated to pulsations… reconsider as a time point for cord clamping
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Term InfantsCochrane 2013
• 15 RCTs of 3911 women > 37 weeks• Clamping Groups
1. < 60 seconds after delivery2. > 60 seconds after delivery or pulse cessation
• Primary outcomes− PP hemorrhage− maternal and neonatal mortality
• Secondary outcomes− Maternal blood loss and related morbidity− Neonatal morbidity
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Term InfantsCochrane 2013
• Severe PPH or mortality• Maternal blood loss • Apgar scores • NICU admission• RDS• Polycythemia
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Term InfantsCochrane 2013
Hemoglobin (g/dL)Newborn -2.17 g/dL (-4.06 to -0.28)24 – 48 hours -1.49 g/dL (-1.78 to -1.21)
3 – 6 months No difference
Iron Deficiency (3-6 months) 2.7 (1.04 to 6.7)
JaundicePhototherapy 0.62 (0.41 to 0.96)
Clinical jaundice 0.84 (0.66 to 1.07) ND
Hemoglobin (g/dL)Newborn -2.17 g/dL (-4.06 to -0.28)24 – 48 hours -1.49 g/dL (-1.78 to -1.21)
3 – 6 months No difference
Iron Deficiency (3-6 months) 2.7 (1.04 to 6.7)
JaundicePhototherapy 0.62 (0.41 to 0.96)
Clinical jaundice 0.84 (0.66 to 1.07) ND
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Term InfantsCochrane 2013
Authors’ Conclusion• “DCC in healthy term infants appears to
be warranted… growing evidence that DCC increases early hemoglobin concentrations and iron stores...
• … as long as access to treatment for jaundice requiring phototherapy is available.”
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Iron and Neuro. Status at 1 YearAndersson, JAMA Ped 2014
• Randomized controlled trial of DCC in full term infants
• Groups− Delayed: >180 secs after delivery− Early: < 10 secs after delivery
• Outcomes− Ferritin levels at 12 months− Neurodevelopment at 12 months assessed
by ASQ (Ages and Stages Questionnaire)
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Iron and Neuro. Status at 1 YearAndersson, JAMA Ped 2014
Cord ClampingMeasure DCC (174) ECC (163) P
Hb 11.8 12.0 NS
Hematocrit 35 35 NS
Ferritin 35.4 33.6 NS
Proportion with Iron Status Outside Norm (%)
Anemia 16.1 11.6 NS
Iron deficiency 3.4 5.4 NS
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Iron and Neuro. Status at 1 YearAndersson, JAMA Ped 2014
Proportion of infants with low ASQ Scores (%)Cord Clamping
ASQ Measure DCC (174) ECC (163) PCommunication 3.5 3.6 NS
Gross Motor 5.9 4.8 NS
Fine Motor 6.5 4.2 NS
Problem Solving 4.1 2.4 NS
Personal-Social 5.9 4.2 NS
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
• Iron deficiency associated with poor neurodevelopmental outcome
• Follow up study at 4 years• Outcomes
− “Full scale” IQ (Primary Outcome)− Fine motor testing (Movement ABC)− Ages and Development (ASQ) − Behavior (SDQ)
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
Primary Outcome• Full scale IQ scores: No difference
• Low IQ (<85): No difference
• No difference in verbal, performance, processing speed, or general language
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
Movement ABC – Proportion with low test scoresDelayed (%) Early (%) P Value
Manual dexterity 18 26 NS
Coins in box 30 35 NS
Bead threading 16 20 NS
Drawing bike trail 4 13 0.02
Secondary Outcomes
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
ASQ – Proportion with low test scoresDelayed (%) Early (%) P Value
Communication 8.3 4.3 NSGross Motor 5.2 6.7 NSFine motor 3.7 11.0 0.03Problem solving 5.2 8.5 NSPersonal/Social 3.0 8.4 0.006Pencil Grip 13.2 25.6 0.01
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
Gender Differences
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DCC in Term Infants, F/U at Age 4Anderson et al, JAMA Ped 2015
• Reduction in children with low scores in fine motor and social domains
• Boys have the most improved results− Fine motor skills
• Optimizing the time to cord clamping may effect neurodevelopment in a low risk population of children born in high income countries.
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Editorial CommentJAMA Ped 2015
“The potential benefit of improving maternal and neonatal care by a simple no-cost intervention of delayed CC should be championed by the international community beginning now and leading into the next decade.”
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DCC in Term InfantsConclusions
• Iron deficiency• Long term effects, possible• Doesn’t matter if you keep the baby
below the placenta…• How long to wait? For the cord to
stop pulsating?
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Preterm Infants
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Preterm InfantsCochrane 2012
• 15 studies, 738 infants, < 37 weeks• Study Groups
− Immediate− Placental transfusion strategies:
Delayed (≥ 30 - 120 seconds)Cord milking
• Outcomes− Death, severe IVH, PVL, neurodevelopment
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Preterm InfantsCochrane 2012
• Neonatal death• Severe IVH• PVL• Neurodevelopmental
outcome
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Preterm InfantsCochrane 2012
Secondary Outcomes RR (95% CI)
Inotropic support 0.42, (0.23 to 0.77)
NEC 0.62, (0.43 to 0.90)
Transfusion 0.61 (0.46 to 0.81)
Phototherapy 1.21 (0.94 to 1.55)
Secondary Outcomes RR (95% CI)
Inotropic support 0.42, (0.23 to 0.77)
NEC 0.62, (0.43 to 0.90)
Transfusion 0.61 (0.46 to 0.81)
Phototherapy 1.21 (0.94 to 1.55)
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Preterm InfantsCochrane 2012
Authors’ Conclusion• Less need for transfusion• Better circulatory stability• Less IVH (all grades)• Lower NEC • Insufficient data for reliable
conclusions about any of the primary outcomes
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Placental Transfusion in VPNBackes et al, OG 2014
• Systematic review and meta-analysis of DCC and MUC < 32 week neonates (28 wks)
• RCTs with the following interventions− Early clamping: < 15 seconds− DCC: at least 20 seconds− MUC: milking at least 3 times
• Outcomes− Maternal and obstetric− Safety− Hematological status− Neonatal Outcomes
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Placental Transfusion in VPNBackes et al, OG 2014
Safety Variables RCT # MD (95% CI) P
BP (4 hours) 4 3.24 (1.76, 4.72) <.01
Apgar5 4 -0.07 (-.48, 0.33) NS
Temp 3 0.02 (-.18, 0.22) NS
Safety Variables RCT # MD (95% CI) P
BP (4 hours) 4 3.24 (1.76, 4.72) <.01
Apgar5 4 -0.07 (-.48, 0.33) NS
Temp 3 0.02 (-.18, 0.22) NS
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Placental Transfusion in VPNBackes et al, OG 2014
Hematologic Outcomes
RCT # RR (95% CI) P
Transfusion 6 0.75 (0.63, 0.90) <.01
MD (95% CI)Transfusion (#) 6 -1.14 (-2.01, 0.27) <.01
Hematocrit (1st) 10 4.49 (2.48, 6.5) <.01
Bilirubin 8 0.53 (-0.01, 1.07) 0.05
Hematologic Outcomes
RCT # RR (95% CI) P
Transfusion 6 0.75 (0.63, 0.90) <.01
MD (95% CI)Transfusion (#) 6 -1.14 (-2.01, 0.27) <.01
Hematocrit (1st) 10 4.49 (2.48, 6.5) <.01
Bilirubin 8 0.53 (-0.01, 1.07) 0.05
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Placental Transfusion in VPNBackes et al, OG 2014
Neonatal Outcomes RCT # Risk Ratio (95% CI) PTotal IVH 9 0.62 (0.43,0.91) <.01
Severe IVH 6 0.64 (0.34, 1.21) NS
NEC 4 0.55 (0.23, 1.31) NS
Sepsis 5 0.73 (0.44, 1.20) NS
Mortality 8 0.42 (0.19, 0.95) .04
Neonatal Outcomes RCT # Risk Ratio (95% CI) PTotal IVH 9 0.62 (0.43,0.91) <.01
Severe IVH 6 0.64 (0.34, 1.21) NS
NEC 4 0.55 (0.23, 1.31) NS
Sepsis 5 0.73 (0.44, 1.20) NS
Mortality 8 0.42 (0.19, 0.95) .04
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DCC in Preterm NeonateElimian et al, OG 2014
• RCT of DCC for neonates 24-34 weeks • Groups
− < 5 seconds− > 30 seconds (3-4 passes of milking allowed)
• Intention to treat• Primary outcome
− Need for transfusion (hb < 10 or symptomatic)• Secondary outcomes
− Hematocrit and IVH
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DCC in Preterm NeonateElimian et al, OG 2014
Clamping
Outcome Delayed (99) Immediate (101) P
Transfusion 25 (25.3) 24 (23.7) .80
Anemia 36 (36.4) 48 (47.5) .11
Phototherapy 55 (55.6) 55 (54.5) .89
IVH (grade III) 3 (3.0) 3 (3.0) 1.0
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Cord Milking in ELGANsPatel et al, AJOG 2014
• MUC provides benefits of placental transfusion but avoids delay in resuscitation
• Cohort study of outcomes < 30 weeks− MUC from 9/2011 – 8/2013− Historical EGLANs from 1/2010-8/2011
• Composite outcome− IVH, NEC, death before discharge
• Improvement in markers of hemodynamic stability
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MUC in ELGANsPatel et al, AJOG 2014
MUC Procedure• Neonate held 10 cm below placenta• Twisting and nuchal cords released• Milking technique
− Pinched close to the placenta− Milked over 2-3 seconds X 3− Pause for 2-3 seconds between milking− Total procedure < 30 seconds
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MUC in ELGANsPatel et al, AJOG 2014
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
PRBC Dopamine NEC Severe IVH Death Composite
Control (160)MUC (158)
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MUC in ELGANsPatel et al, AJOG 2014
0
5
10
15
20
25
30
35
40
45
0-6 hours 6-12 hours 12-24 hours
ControlMUC
Effect of MUC on Mean BP First Day of Life
P < 0.01 P < 0.01P < 0.01
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DCC with and without MUCKrueger, AJOG 2015
• RCT − DCC: 30 second delay in cord clamping− DCC + MUC (4 times, 4-5 sec. between)
• 24 – 31 6/7 weeks− Stratified results by gestational age
• Primary outcome: hematocrit• Secondary outcomes
− Mortality, days on ventilator, LOS, peak bilirubin, days of phototherapy, “neonatal complications
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DCC with and without MUCKrueger, AJOG 2015
• No difference in primary outcome − Hematocrit
• No difference in secondary outcomes− Bilirubin− Phototherapy− Days on ventilator− Length of stay− Other neonatal morbidities
• MUC added nothing to DCC
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Placental Transfusion StrategiesConclusions for Preterm Babies
• Seems to improve short term outcomes− Longer term?
• Better for < 30 weeks• Inconsistent findings among latest
round of trials− Different protocols
• MUC as good as DCC?− May be easier in high risk settings
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Summary from AAP/AHANeonatal Resuscitation Program (NRP®)
• Current evidence suggests that cord clamping should be delayed for at least 30-60 seconds for most vigorous term and preterm newborns.
• There is insufficient evidence to recommend an approach to cord clamping for newborns who require resuscitation at birth.
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© World Health OrganizationDelayed umbilical cord clamping for improved
maternal and infant health and nutrition outcomes(2014)
• “The cord should not be clamped earlier than 1 min after birth.”
• Regardless of route of delivery• Regardless of gestational age• Stimulation before cord clamping
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• “…the cord is not clamped in the first 60 seconds…
• The cord should be clamped before 5 minutes, although women should be supported if they wish this to be delayed further.”
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ACOG 2017• In term infants, delayed umbilical cord
clamping increases hemoglobin levels at birth and improves iron stores in the first several months of life, which may have a favorable effect on developmental outcome
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ACOG 2017• Given the benefits to most newborns and
concordant with other professional organizations, the American College of Obstetricians and Gynecologists now recommends a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30–60 seconds after birth.
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What do I think?
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“Perinatal medicine is replete with examples of promising interventions the short-term benefits of which did not translate into long-term benefits, including some that caused harm.”
Tarnow-Mordi et al, AJOG 2014