Optimal Timing for Clamping of the
Umbilical Cord after Birth
American Academy of Pediatrics
2013 Annual Conference and Exhibition
Orlando, FL
Tonse N. K. Raju, MD, DCH
Chief, Pregnancy and Perinatology Branch
Eunice Kennedy Shriver National Institute of Child Health & Human Development
National Institutes of Health Bethesda, MD
Greetings from the NIH
National Library of Medicine Home of the PubMed
NIH-Building 1 Director’s Office
Eunice Kennedy Shriver National Institute of Child Health and Human
An Icelandic Mare
Giving Birth
Alexander, J. BMJ, Volume 306, 6th
February, 1993
79 seconds after birth 72 seconds after birth http://www.youtube.com/watch?v=b_2OY7IJ_hc
Umbilical cord clamping in
horses
“In equine practice, it is mandatory. . . to wait until the umbilical cord has
stopped pulsating before clamping it; this takes 30-60 seconds. . .”
Erasmus Darwin
(1731-1802)
l “Another thing very injurious to the child,
is the tying and cutting of the navel string too soon; which should always be left till the child has not only repeatedly breathed but till all pulsation in the cord ceases. As otherwise the child is much weaker than it ought to be, a portion of the blood being left in the placenta, which ought to have been in the child.. .
Zoonomia: Or the Laws of Organic Life
How Many Papers on Cord Clamping?
•
Since 2000: 291 publications
–Clinical trials (59)
–Physiological studies
–Cochrane & other systematic reviews (28)
–Editorials/opinions
–National and international professional
group recommendations & guidelines
•
All these bodies
recommend delay in
cord clamping for at
least 30 seconds (and
up to 2 minutes) in:
– WHO: All births – SOGC and ECG:
Preterm
– ILCOR and ACOG: Preterm when possible
European Consensus
Guidelines
Yao AC, Hirvensalo M, Lind J. Placental transfusion-rate and uterine contraction. Lancet. 1968 Feb 24;1(7539):380-3.
~25 ml/kg ~10 ml/kg
Weigh the baby with cord intact…
Blood Volume and Iron
•
1 minute delay ~70-80 mL extra blood
•
3 minute delay to ~ 100 mL extra blood.
•
Added with plasma leads to ~ 40–50 mg/kg of
body weight of extra iron.
•
Additional iron from may help prevent iron
deficiency during the first year of life
Iron Deficiency Anemia
•
~ 3.6 billion are iron deficient, and ~ 2 billion are
overtly iron deficiency anemic.
•
In low and middle income countries, iron
deficiency anemia is highly prevalent in women
and in children <5 years( ~30%)
•
Adequate iron is crucial for cognitive development
•
In industrialized nations, iron supplements have
reduced the prevalence of iron deficiency anemia
Meta Analysis: Term Infants
15 trials, 3011 women The Cochrane Library, Issue 7, 2013
Cochrane Systematic Review
Term Infants: Conclusions
• Delaying clamping of the cord for at least 2-3 minutes .
– Higher mean birth weight, ~100 grams (95% CI: 45—145 g) – Higher hemoglobin (~2 g/DL CI: 0.28—4.06) at birth
– Lower frequency of anemia 2-4 months – Higher ferritin levels up to 4 months
• Fewer in early clamping required phototherapy
– RR 0.62 (CI: 041, 0.96)
– Indications for phototherapy varied; mean peak bilirubin values were similar
• No difference in postpartum hemorrhage in any of the five trials which measured this outcome
• No clinical polycythemia McDonald SJ and Middleton P Cochrane Library, Issue 7, 2013
Rabe H, et al. Cochrane Database of Systematic
Reviews, 2012
2012 Cochrane Systematic Review
Preterm Infants
•
15 trials, 738 infants
•
24--36 weeks’ gestation
•
Maximum delay: 180 seconds
2012 Cochrane Systematic Review
Preterm Infants
•
Main Results:
– Higher BP at 1 and 4 hours
– Transfusions for anemia:
• 7 trials, 392 infants, RR: 0.61 (95% CI 0.46 to 0.81)
– All grades of IVH
• 10 trials, 539 infants, RR 0.59 (95% CI, 0.41 to 0.85)
– NEC
• 5 trials, 241 infants, RR 0.62, (95% CI, 0.43 to 0.90)
2012 Cochrane Systematic Review
Preterm Infants
•
Higher peak bilirubin concentrations
– 7 trials, 320 infants, mean difference 15.01 mmol/L (95% CI, 5.62 to 24.4)
•
Polycythemia: no difference
•
No clear difference in other outcomes
– Infant death
– Severe, grade 3 or 4 IVH – PVL, RDS etc.
Other
Physiological
Studies
in Preterm
Infants
SVC-Normal and Low Flow
Kluckow, M. Early Human Development, 2005, 81, 429
Stable preterm infant:
SVC flow 90 ml/kg/min; SVC velocity: 0.53 meters/s
Preterm infant with low SVC flow, 20 ml/kg/min; SVC velocity: 0.2 meters/s
Regional Cerebral Blood Flow
•
39 infants, 24 to 32 weeks
– 24 cord clamped within 20 seconds – 15 cord clamped 60-90 seconds
•
Cerebral oxygenation measured at 4, 24, 72
hours, and at 32 weeks of PMA (NIRS)
•
In the experimental group--
– 5%--6% higher hematocrit up to 72 hours
– Higher mean cerebral tissue oxygenation at 4 hours 69.9% versus 65.5%; @ hours: 71.3% versus 68.1%
Probability of NOT needing a transfusion
Milking Versus Immediate Cord Clamping
BP and Urine Output
Hosono S, et al Arch Dis Fetal , 2006
If delayed cord clamping is so
good, why are we not doing it!!
Why are we Worried about Delaying
Cord Clamping?
•
Delay in initiation of resuscitation of asphyxia
(term: nuchal cord—variable deceleration) and
respiratory support
•
Problem in collecting cord blood for banking
•
Hypothermia (especially in preterm infants)
Counterpoints?
• It is precisely those that require resuscitation may
benefit from delayed cord clamping
• The baby may be out, but the placenta keeps working
• Intrauterine asphyxia (nuchal cord) occludes umbilical
vein, but fetal heart keeps pumping blood through umbilical arteries
• Asphyxiated fetuses are hypovolemic & anemic.
• “Placental transfusion after birth is the first step of
resuscitation” (Huchon, DJR; BMJ, 2006)
• Warm blood from the placenta keeps the baby warmer
What Dr. George Gregory
might say. . .
Special Features of Fetal Circulation
Placenta is the fetal “lungs”
Umbilical vein carries oxygenated
blood from the placenta
Descending aorta (via umbilical
arteries perfuses the low resistance
placenta
Brain gets the most oxygenated
Fetal
Circulation
The oxygenated blood flows
in from the placenta
Enters the RA through ductus
venosus
Passes via the foramen ovale
to LA and LV.
LV output-->oxygenated
blood to the brain
Venous return to right flows
via PA, and bypasses via PDA to the descending aorta
Very little blood goes to and
At Birth
When all goes well…
Infant cries on obstetrician’s
hands
Someone shouts “time of birth,
please. . . .”
Cord tied and the baby handed
to the pediatric team
Basic resuscitation done under the warmer, Apgar scores given
Nurse shows off the baby Dad takes pictures
1
Meanwhile, behind the scene…
Physiological changes
Infant cries FRC PVR
RV output to the lungs
Oxygenated blood returns to
the LA, LA pressure, foramen ovale closes
Increasing LV filling increases
LV output
Lung perfusion continues to
increase & the PDA closes
Cord is tied
Everything looks nice and quiet
from the outside
1
When an infant does not cry
and the cord is clamped
Infant is handed to the resuscitation
team; NRP steps started
Bag and mask ventilation not effective:
infant blue
Intubated: stomach distends Infant is pale and gray
ET in the stomach
Senior takes over, re-inserts ETT Pulse <50; infant pale/gray/blue
Meanwhile, behind scene…
Immediate cord clamping
→
simultaneous decrease in preload and increase in afterload• Right ventricle (RV) filling volume drops due to the cessation of umbilical venous blood flow (of relatively oxygenated
blood) from the placenta
• 40%-50% drop in RV output to LA
• No lung expansion---no pulmonary
perfusion ---and no pulmonary venous return to the left atrium, and to LV.
• Increase in LV after-load (clamped UA)
• All these are risk factors for a drop in LV output
Results: Clamp 1st group Cardiovascular changes
Heart rate and RVO drop soon after cord clamping and recover
slowly after vent onset
Heart rate
RV Output
Bhatt et al. J Physiol 2013; 591:2113-26 Figure courtesy: Dr. Stuart Hooper
Cord clamped
Vent began
• In the Vent 1st group, HR and
RVO remain stable throughout
• HR and RVO drop precipitously soon after cord
clamping
• They rebound only after ventilation is started in the
Clamp 1st group
Both Groups: HR &
RVO Gr 2 Vent began
Gr 2 Cord clamped
Gr 1: Cord
clamped Gr 1: Vent began
Bhatt et al. J Physiol 2013; 591:2113-26; Figure courtesy: Dr. Stuart Hooper
Gr 1: Cord
clamped Gr 1: Vent began
Gr 2 Vent
began Gr 2 Cord clamped Gr 2 Vent
Results: Clamp-1st group
Carotid artery flow & pressure
There is a transient
increase in CA pressure and flow soon after cord clamping
But, by 1 minute both CA pressure and flow begin to drop profoundly to <50% baseline
They recover slowly after ventilation onset
Carotid artery pressure
Carotid artery flow
Bhatt et al. J Physiol 2013; 591:2113-26 Figure courtesy: Dr. Stuart Hooper
Cord clamped
Vent began
• Median heart rate among infants NOT requiring resuscitation was below 100 at 1 minute of age in both term and preterm
Arch Dis Child Fetal Neonatal Ed 2010;95:F177–F181. doi:10.1136/adc.2009.169102
Umbilical Cord Milking
Four RCTs have been published (n=75 milking & 87 comparison groups)
1. Two Japanese trials in preterm: milking versus immediate clamping (Hosono, 2008; and Takami 2012)
2. One UK study in preterm, milking compared to delayed clamping by obstetricians (Rabe 2011)
3. One US study in term, C-Section births, milking compared to immediate clamping (Erickson-Owens, 2012)
•
Compared to immediate clamping:
– Higher hematocrit, and higher blood volume
– Improved SVC flow, LV end-diastolic volume, and LV output
– Improved combined ventricular function index
– Improved cerebral blood flow, and higher cerebral-fraction of O2 extraction
– Stabilizes CBS swings
Takami et al, J Pediatr 2012
Summary of
•
Compared to delayed cord clamping
– Similar effects on hematocrit, blood pressure, cardiac and cerebral functions.
•
Can be carried out in term infants after elective
c/sections
•
No differences in any maternal complications
Takami et al, J Pediatr 2012
Why not resuscitate
with the cord
connected to the
placenta?
Cheetah chasing a baby gazelle Massi Mara, Kenya
BASICS Resuscitation Trolley
Take Home Points
• Clinical data and physiological
rationale are compelling:
• Cord clamping at least after 30s is
beneficial in all births
• Milking appears to be equally
beneficial
• Although many issues remain to be
solved, several organizations and societies are recommending it
• It is likely to become the standard
of care in the US, too.
White Rhinoceros, Botswana EMBO Cover, 16 November, 2006
Worst Scenario
• The infant does NOT breathe immediately after birth and the umbilical cord is occluded soon after birth
• 50% drop in RV output, and flow through foramen ovale.
• Assisted ventilation is not well established & pulmonary vascular resistance remains high, preventing the normal increase of
pulmonary blood flow and return of the oxygenated blood via the pulmonary veins into the left atrium.
• Plus, an increased afterload - drop in LV output
• If we give fluid boluses in rapid sequence, a stage is set to for IVH, especially in very preterm infants, with an already
maximally vasodilated cerebral vascular bed, superimposed upon an immature cerebral autoregulatory systems.
Unresolved Issues
Clamping versus Milking
•
What is the length and speed of the cord to
be “milked”?
•
Who should do the “milking”—OB? Peds?
•
Direct placental transfusion is pulsatile—
does it matter that milking may not be
exactly “physiological?”
Unresolved Issues
•
The best time: 30 seconds? 60 seconds?
•
In cases of maternal hemorrhage?
•
Should the cord-clamping time be different in
women positive for HIV?
•
IUGR, LGA, Infants born at high altitudes
•
Infant’s position in relation to placenta in
cesarean deliveries?
•
Recording the Apgar scores and resuscitation?
•
Effect of clamping time on cord blood gases?
•
“ Cord clamping is an intervention . . . no
evidence that “amputation of the functioning
placenta” soon after birth is beneficial either to
the baby or to the mother . . .Don’t rush to
clamp the cord”
Long Umbilical Cords in Primates
Homosepians
newborns have the longest Cords
•
“Long cords help the mother to pick
up her newborn. . .carry it away from
danger, without exerting traction on
the placenta, and put the infant to the
breast… This facilitates placental
delivery. . .”