American Academy of Pediatrics 2013 Annual Conference and Exhibition Orlando, FL

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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

(2)

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

(3)

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. . .”

(4)

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

(5)

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

(6)

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

(7)

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

(8)

Weigh the baby with cord intact…

(9)

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

(10)

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

(11)

Meta Analysis: Term Infants

15 trials, 3011 women The Cochrane Library, Issue 7, 2013

(12)

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

(13)

Rabe H, et al. Cochrane Database of Systematic

Reviews, 2012

(14)

2012 Cochrane Systematic Review

Preterm Infants

15 trials, 738 infants

24--36 weeks’ gestation

Maximum delay: 180 seconds

(15)

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)

(16)

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.

(17)

Other

Physiological

Studies

in Preterm

Infants

(18)

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

(19)

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%

(20)

Probability of NOT needing a transfusion

Milking Versus Immediate Cord Clamping

(21)

BP and Urine Output

Hosono S, et al Arch Dis Fetal , 2006

(22)

If delayed cord clamping is so

good, why are we not doing it!!

(23)

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)

(24)

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

(25)

What Dr. George Gregory

might say. . .

(26)

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

(27)

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

(28)

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

(29)

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

(30)

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

(31)

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

(32)
(33)

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

(34)

• 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

(35)

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

(36)

• 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

(37)
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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)

(39)

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

(40)

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

(41)

Why not resuscitate

with the cord

connected to the

placenta?

Cheetah chasing a baby gazelle Massi Mara, Kenya

(42)

BASICS Resuscitation Trolley

(43)

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

(44)

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.

(45)

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?”

(46)

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?

(47)

“ 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”

(48)

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. . .”

Walker CW, Pye BG. The length of the human umbilical cord BMJ, Feb 20, 1960, 546-81

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