The Effect of Cord Milking on Hemodynamic Status of Preterm Infants

• ClinicalTrials.gov Identifier: NCT01487187
• Recruitment Status: Unknown
• First Posted: December 7, 2011
• Last Update Posted: March 9, 2017
• Sponsor: Walid El-Naggar
• Information provided by (Responsible Party): Walid El-Naggar, IWK Health Centre

Tracking Information

• First Submitted Date: November 22, 2011
• First Posted Date: December 7, 2011
• Last Update Posted Date: March 9, 2017
• Study Start Date: November 2011
• Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: December 5, 2011): Systemic blood flow as reflected by mean SVC flow measured by echocardiographic study at 4-6 hours after birth. [ Time Frame: at 4-6 hours of age ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: December 5, 2011)

• low SVC flow (< 40 ml/kg/min), as assessed by echocardiography [ Time Frame: at 4-6 and 10-12 hours of age ]
• Hypotension [ Time Frame: during the first 48 hours of life ]
  Hypotension is defiined as mean blood pressure < corresponding gestational age number for > 30 minutes
• Hyperbilirubinemia and peak bilirubin level recording [ Time Frame: during first 2 weeks of age ]
  Hyperbilirubinemia requiring phototherapy (as per routine unit practice)
• Systemic blood flow as reflected by mean SVC flow measured by echocardiographic study at 10-12 hours after birth. [ Time Frame: at 10-12 hours of age ]
• Number of blood transfusions during hospital stay [ Time Frame: at 40 weeks of corrected gestational age ]
• Intraventricular hemorrhage (IVH) [ Time Frame: during first 2 weeks of life ]
  Intraventricular hemorrhage (IVH) as diagnosed by standard-practice cranial ultrasounds
• Neurodevelopmental outcome [ Time Frame: At 36 months of age ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: The Effect of Cord Milking on Hemodynamic Status of Preterm Infants
• Official Title: The Effect of Umbilical Cord Milking on Hemodynamic Status of Preterm Infants: a Randomized Controlled Trial

Brief Summary

Very preterm babies frequently develop problems with their blood circulation during the first few days after birth. These circulation problems could affect the oxygen and blood flow to their brain and lead to effects such as bleeding in the head or delayed developmental milestones later in life. Currently the care for such problems may include transfusion of intravenous fluids or blood to the baby and/or giving the baby medications that can help circulation.

The current practice at the delivery of these babies is to immediately clamp their umbilical cords after birth. Recent research studies have shown that giving more of the baby's own blood to them at birth by delayed cord clamping (waiting for clamping the cord for about 30-90 seconds) or by milking the cord, may reduce the number of blood transfusions that these babies may need later on. It may also improve their initial blood pressure and reduce the chances of bleeding in their heads.

More research is needed to prove if either delayed cord clamping or milking the cord at birth will be better in terms of improving these babies' health.

The aim of this study is to find out if adding some blood to these babies' circulation, through milking the cord at birth, could prevent or reduce the possible problems with blood circulation and the reduced blood flow to the brain that some of these babies may have after birth.

The investigators will also investigate if milking the cord at birth could improve their long-term developmental outcome.

Hypothesis: In preterm infants less than 31 weeks' gestation, milking the umbilical cord 3 times prior to clamping, compared to immediate clamping after birth will improve systemic blood flow (as assessed by improving superior vena cava flow measured by heart ultrasound in the first 24 hours after birth)

• Detailed Description: Eligible mothers will be randomized prior to delivery once preterm labour is established (cervical dilatation > 4cm and preterm birth is considered inevitable or delivery is indicated for maternal or fetal indications) to either milking of the umbilical cord of their infants (intervention group) or to clamp the cord as per standard practice (currently it is the immediate cord clamping) after birth (control group). Randomization will be done in variable block sizes and will be concealed by using opaque envelopes prepared ahead of time from a randomization table. Envelopes will be opened before the time of delivery.
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Prevention
• Condition: Preterm Infants

Intervention

• Procedure: Milking the umbilical cord at birth
  Infants in the cord-milked group will be placed at or below the level of the placenta, and about 20 cm of the umbilical cord (or the length of cord that is accessible if less than 20 cm) will be vigorously milked towards the umbilicus three times before clamping the cord
  Other Name: Transfusion of blood from umbilical cord to the baby
• Procedure: immediate umbilical cord clamping
  immediate cord clamping without milking as per standard practice
  Other Name: standard practice-cord clamping

Study Arms

• Active Comparator: immediate umbilical cord clamping
  The control group will receive immediate cord clamping at birth which is the standard of care in our institution
  Intervention: Procedure: immediate umbilical cord clamping
• Experimental: Milking the umbilical cord at birth
  Infants in the cord-milked group will be placed at or below the level of the placenta, and about 20 cm of the umbilical cord (or the length of cord that is accessible if less than 20 cm) will be vigorously milked towards the umbilicus three times before clamping the cord.
  Intervention: Procedure: Milking the umbilical cord at birth

Publications *

• El-Naggar W, McMillan D, Hussain A, Armson A, Dodds L, Warren A, Whyte R, Vincer M, Simpson CD. Neurodevelopmental outcomes of very preterm infants who received cord milking at birth: a randomized controlled trial. Eur J Pediatr. 2022 Dec;181(12):4215-4220. doi: 10.1007/s00431-022-04638-x. Epub 2022 Oct 4.
• El-Naggar W, McMillan D, Hussain A, Armson A, Warren A, Whyte R, Simpson D. The effect of umbilical cord milking on cerebral blood flow in very preterm infants: a randomized controlled study. J Perinatol. 2021 Feb;41(2):263-268. doi: 10.1038/s41372-020-00780-2. Epub 2020 Aug 11.
• El-Naggar W, Simpson D, Hussain A, Armson A, Dodds L, Warren A, Whyte R, McMillan D. Cord milking versus immediate clamping in preterm infants: a randomised controlled trial. Arch Dis Child Fetal Neonatal Ed. 2019 Mar;104(2):F145-F150. doi: 10.1136/archdischild-2018-314757. Epub 2018 Jun 14.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: August 31, 2015): 73
• Original Estimated Enrollment (submitted: December 5, 2011): 70
• Estimated Study Completion Date: January 2018
• Estimated Primary Completion Date: January 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:Preterm infants < 31 weeks' gestation if their mothers fulfill the following inclusion criteria:

1. admitted to the hospital for at least 2 hours before delivery in preterm labor (cervical dilatation >2 cm or having premature rupture of membranes) or if a decision to induce labour has been made by treating physician for a maternal or fetal indications).
2. at 24+0 weeks - 30+6/7 weeks gestation (by best estimate based on date of last menstrual period or early ultrasound)

Exclusion Criteria:

1. monochorionic twin or any higher order multiple pregnancy
2. major fetal congenital or chromosomal anomalies
3. significant placental abruption
4. fetal anemia/transfusion
5. Rh isoimmunization
6. intent to withhold or withdraw treatment of the infant

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 24 Weeks to 31 Weeks (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01487187
• Other Study ID Numbers: 1002554
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: Yes

• Current Responsible Party: Walid El-Naggar, IWK Health Centre
• Original Responsible Party: Same as current
• Current Study Sponsor: Walid El-Naggar
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Walid I El-Naggar, MD; IWK Health Centre- Dalhousie University

• PRS Account: IWK Health Centre
• Verification Date: March 2017