Delayed Cord Clamping - University of Utah...Delayed cord clamping (DCC) − Cord milking (MUC) −...

Delayed Cord Clamping

T. Flint Porter, MD, MPH

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

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

Potential Drawbacks• Delayed resuscitation

• Increase risk of neonatal hypothermia, polycythemia, hyperbilirubinemia

• Increase risk for maternal hemorrhage

• Interfere with cord blood collection

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

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

UCBF After DeliveryVenous Flow

• Flow stopped during deep breathsBreathing

• Flow stopped• Flow reversed flow

with “hard” cryingCrying

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%)

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)

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

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


• Severe PPH or mortality• Maternal blood loss • Apgar scores • NICU admission• RDS• Polycythemia


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


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.”

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)


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


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

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)


Primary Outcome• Full scale IQ scores: No difference

• Low IQ (<85): No difference

• No difference in verbal, performance, processing speed, or general language


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


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


Gender Differences


• 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.

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.”

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?

Preterm Infants

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


• Neonatal death• Severe IVH• PVL• Neurodevelopmental

outcome


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)


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

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


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


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


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

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

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

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

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


0%

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100%

PRBC Dopamine NEC Severe IVH Death Composite

Control (160)MUC (158)


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5

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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

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

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

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

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.

© 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

• “…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.”

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

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.

What do I think?

“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

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