Dallas 2015

TFQO: Marya Strand, MD, MS; COI#222EVREV 1: Marya Strand, MD, MS; COI#222EVREV 1: Takahiro Sugiura, MD; COI#224Taskforce: NLS

Umbilical Cord Milking(NRP #849)

Dallas 2015COI Disclosure

Marya Strand, MD, MS COI#222Commercial/industry• None

Potential intellectual conflicts• None

Takahiro Sugiura, MD COI#224Commercial/industry• None

Potential intellectual conflicts• None

Dallas 20152010 Treatment Recommendation

Evidence from a single, small, randomized controlled trial (LOE 1, Hosono 2008, p.F14) suggest that, among premature newborns (24-28 weeks gestation), milking the umbilical cord immediately after birth may decrease the need for packed red blood cells transfusions during the initial hospital stay. This single study was not adequately powered to fully assess the safety or efficacy of this intervention.A secondary analysis of data from this small randomized trial (LOE 1, Hosono 2009, p.F328) suggests that, among premature newborns (24-28 weeks gestation), milking the umbilical cord immediately after birth may increase hemoglobin at birth, improve hemodynamic stability during the first 5 days of life, and decrease the incidence of chronic lung disease at 36 weeks postmenstrual age.

Dallas 2015C2015 PICO

Population: Very preterm infants (≤28 weeks’)Intervention: Umbilical cord milkingComparison: Immediate umbilical cord clamping

Outcomes: 9—Death8—Neurodevelopmental outcome at 2-3 years8—Cardiovascular stability

– Need for pressors, need for fluid bolus, initial mean blood pressure

6—ICH – Any grade, severe grade

6—Temperature on admission5—Hematologic indices

– Initial hemoglobin, need for transfusion3—Hyperbilirubinemia

– Need for phototherapy, need for exchange transfusion

Dallas 2015Inclusion/Exclusion& Articles Found

Inclusions/ExclusionsRandomized or observational studiesInfants born at ≤28 weeks’ gestation

Search terms initially identified 690 potential articles Number Included in Evidence Profile tables

RCTs: 4non-RCTs: 1

Dallas 20152015 Proposed Treatment Recommendations

When delayed cord clamping cannot be accomplished, we suggest that cord milking be performed at delivery for VLBW infants as opposed to immediate cord clamping. (Moderate recommendation, moderate level of evidence)

Dallas 2015

Risk of Bias in studies

Study Year DesignTotal

PatientsPopulation

IndustryFunding

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Alan 2014 RCT 48≤32 wks &

<1500gNo Unclear Low High Unclear High Low

Hosono 2007 RCT 40 24-28 wks No Unclear Low Unclear Low Low Low

Katheria 2014 RCT 60 23-32 wks No Low Low Low Low Low Low

March 2013 RCT 75 24-28 wks No Low Low High Unclear Low Low

<RCT>

<Non-RCT>

Study Year DesignTotal

PatientsPopulation

IndustryFunding

Elig

ibili

tyCr

iter

ia

Expo

sure

/O

utco

me

Conf

ound

ing

Follo

w u

p

Takami 2012nonRCT

50<29wks &

<1250gNo High Low High High

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<RCT>

<Non-RCT>

Outcome- Infant death

Dallas 2015Evidence profile table-Infant death

<RCT>

<Non-RCT>

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<Need for pressor: RCT>

Outcome- CV stability

<Need for volume expander: RCT>

<Mean initial blood pressure: RCT>

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<Need for pressor: non-RCT>

Outcome- CV stability

<Need for volume expander: non-RCT>

< Mean initial blood pressure : non-RCT>

Dallas 2015Evidence profile table-CV stability <RCT>

<Non-RCT>

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<Severe ICH-RCT>

Outcome- ICH

<Any ICH non-RCT>

<Any ICH-RCT>

Dallas 2015Evidence profile table-IVH <RCT>

<Non-RCT>

Dallas 2015Outcome- hematologic indices<Initial hemoglobin: RCT>

<Initial hemoglobin: non-RCT>

<Need for transfusion: RCT>

Dallas 2015Evidence profile table -hematologic indices

<RCT>

<Non-RCT>

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<RCT>

Outcome- temperature

Evidence profile table-temperature<RCT>

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Outcome- bilirubin indices<Need for phototherapy: RCT>

<Maximum bilirubin level : RCT>

Dallas 2015Evidence profile table-bilirubin

indices

Dallas 2015

Proposed Consensus on Science Statements

For the critical outcome of death we found moderate quality evidence from 3 RCTs that there is no difference in death (OR 0.76, 95% CI 0.25-2.29).We did not identify any evidence to address the critical outcome of “neurologic outcome at 2-3 years”.For the critical outcome of cardiovascular stability we found low quality evidence from 2 studies that the intervention group received fewer pressor (OR 0.44, 95% CI 0.19-0.98). We found moderate quality evidence that the initial mean blood pressure was 5.43 mm Hg higher (1.98-8.87 mm Hg) in the intervention group.

Dallas 2015Proposed Consensus on Science Statements

For the important outcome of IVH, we found moderate quality evidence from 2 studies of a reduction of any IVH (OR 0.37, 95% CI 0.18-0.77) but no difference (from 1 study) in severe IVH (OR 0.44, 95% CI 0.07-2.76).

For the important outcome of hematologic indices, we found moderate quality evidence from 2 studies that cord milking increased the initial hemoglobin measurement (2.27 g/dl, 95% CI 1.57-2.98 g/dl) and high quality evidence from 3 studies that cord milking decreased the need for transfusion (OR 0.2, 95% CI 0.09-0.44).

For the important outcome of temperature on admission, we found low quality evidence from 1 study that the milking group temperature was not different on admission.

Dallas 2015

Proposed Consensus on Science Statements

For the outcome of bilirubin indices we found moderate quality evidence that the maximum bilirubin measurement and need for phototherapy was not different between groups.

Cost: There is little or no cost associated with the intervention of umbilical cord milking.

Dallas 2015Draft Treatment Recommendations

When delayed cord clamping cannot be accomplished, we suggest that cord milking be performed at delivery for VLBW infants as opposed to immediate cord clamping. (Moderate recommendation, moderate level of evidence)All studies included in this evidence review milked 20 cm of umbilical cord toward the umbilicus 3 times while the infant was held at the level of the introitus or below the level of the placenta.

Dallas 2015

Values and Preferences Statement:

In making this recommendation we place a high value on the simplicity/economy of this intervention with no demonstrated negative outcome.

Dallas 2015Knowledge Gaps

Specific research requiredCord milking vs Delayed cord clamping• One RCT [Rabe 2011] demonstrated similar

hematologic indices between cord milking and delayed cord clamping.

There is no evidence regarding neurodevelopmental outcomes for cord milking compared to immediate cord clamping.