Role of Umbilical Cord Milking in the Management of Hypoxic-ischemic Encephalopathy in Neonates

February 27, 2021 updated by: Dr. Manoj Varanattu, Jubilee Mission Medical College and Research Institute

Role of Umbilical Cord Milking in the Management of Hypoxic-ischemic Encephalopathy in Neonates: a Randomized Controlled Trial

The purpose of this study is to investigate the efficacy and safety of umbilical cord milking in depressed neonates at birth for prevention of hypoxic ischemic encephalopathy.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by inadequate supply of oxygen and blood to the brain of a newborn baby. Therapeutic hypothermia is the only proven therapy for these infants. Even after receiving therapeutic hypothermia, 50% of all infants with moderate and severe HIE die or develop neurological and functional impairment. There is a need for a new intervention for neonatal HIE, which is readily available in developing countries and can complement hypothermia.

The American College of Obstetricians and Gynecologists and American Academy of Pediatrics recommend a delay in umbilical cord clamping in vigorous term and preterm infants for at least 30-60 seconds after birth. Immediate umbilical cord clamping is contraindicated in maternal hemodynamic instability, need for immediate resuscitation of the newborn and in conditions where placental circulation is not intact. Umbilical cord milking (UCM) is a simple method of delivering volume and possibly stem cells to those neonates, where resuscitation cannot be postponed for obtaining the benefits of delayed cord clamping.

We hypothesize that depressed neonates who receive umbilical cord milking will have lower incidence and severity of hypoxic ischemic encephalopathy compared to depressed neonates who receive immediate cord clamping.We propose to investigate the safety and effectiveness of UCM in term and late preterm (≥35 week's gestation) infants who are depressed at birth, in preventing the development and/or progression of hypoxic ischemic encephalopathy. The need for immediate resuscitation measures, abnormal parameters (clinical, hematological and biochemical) and neuroimaging will be compared in depressed neonates with and without UCM. If UCM is found to be safe and beneficial, it can be a useful substitute for delayed cord clamping in depressed neonates worldwide.

Conditions: Depressed neonate, Hypoxic-ischemic encephalopathy Intervention: Umbilical cord milking

Study Design Study Type: Interventional Study Design: Allocation: Randomized Endpoint Classification: Efficacy/Safety Study Intervention Model: Parallel Assignment Number of Arms: 2 Masking: Single Blind (Subject) Primary Purpose: Prevention Enrollment: 400 [Anticipated]

Arms and Interventions:

Arms:2, Assigned Interventions: 1. Experimental: Umbilical Cord Milking and 2. No Intervention: Immediate Umbilical Cord Clamping

  1. Experimental: Umbilical Cord Milking,Other Name: Umbilical cord stripping Umbilical Cord Milking involves milking a 30 cm long segment of umbilical cord at birth, after initiation of ventilation Procedure: Umbilical Cord Milking (UCM) At birth the umbilical cord of a depressed newborn is clamped immediately and cut 30 cm from the umbilicus and the neonate placed on the resuscitation table. After completion of initial steps, if the baby does not have adequate spontaneous respirations and a heart rate of 100 bpm or higher, positive pressure ventilation (PPV) is given for 30 seconds, along with UCM. The cord is untwisted and held in a vertical position. It is milked 3 times towards the baby at a speed of 10 cm/s and then clamped 3 cm from the umbilicus. The time of cord clamping will be recorded using a timer. After completion of PPV along with UCM, if the baby requires further resuscitation, the NRP 2015 guidelines will be followed. Depressed newborns who respond to initial steps of resuscitation with normal breathing and heart rate of 100 bpm or higher, will receive UCM after this.
  2. No Intervention: Immediate Umbilical Cord Clamping, Other Name: routine clamping of the umbilical cord Procedure: Immediate Cord Clamping, At birth the umbilical cord of a depressed newborn is clamped immediately (current recommendation) and cut 3 cm from the umbilicus and the neonate placed on the resuscitation table. The time of cord clamping will be recorded using a timer. After completion of initial steps, if the baby requires further resuscitation, the NRP 2015 guidelines will be followed.

Study Type

Interventional

Enrollment (Anticipated)

400

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • India
    • Kerala
      • Thrissur, Kerala, India, 680006

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 minute to 5 months (CHILD)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

• Neonates of ≥35 week's gestation and born depressed (defined by NRP 2015 criteria: as those neonates who doesn't cry or breathe at birth and whose tone is poor) in the hospital

Exclusion Criteria:

  • MCDA Twin pregnancy (DCDA twins are included)
  • Triplet or quadruplet pregnancy
  • Presence of IUGR in antenatal scans (< 10th Centile)
  • Short umbilical cord length (<30 cm)
  • Rh-negative or retrovirus positive mothers
  • Major chromosomal or congenital anomalies
  • Hydrops fetalis
  • Severe placental abruption
  • Cord prolapse and cord abnormalities such as true knots
  • Culture positive early onset neonatal sepsis

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: PREVENTION
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: SINGLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Umbilical Cord Milking
Umbilical Cord Milking involves milking 30 cm length of cord at birth, after initiation of ventilation.
Procedure: Umbilical Cord Milking
At birth the cord of a depressed newborn is clamped immediately and cut 30 cm from the umbilicus. After completion of initial steps, if required, positive pressure ventilation (PPV) is given for 30 seconds, along with UCM. The cord is untwisted and held in a vertical position. It is milked 3 times towards the baby at a speed of 10 cm/s and then clamped 3 cm from the umbilicus. After completion of PPV along with UCM, if the baby requires further resuscitation, the NRP 2015 guidelines will be followed. Depressed newborns who respond to initial steps of resuscitation with normal breathing and heart rate of 100 bpm or higher, will receive UCM after this.
Other Names:
  • Umbilical cord stripping
  • UCM
NO_INTERVENTION: Immediate Umbilical Cord Clamping
Procedure: No Intervention: Immediate Umbilical Cord Clamping or Immediate Cord Clamping.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence and severity of HIE in depressed neonates with and without umbilical cord milking
Time Frame: 72 hours

The severity of HIE if any will be assessed by modified Sarnat staging which is based on level of consciousness, spontaneous activity, neuromuscular control, primitive reflexes, autonomic function and seizures.

[Designated as safety issue: No];

Ref:Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976; 33:696-705. PMID: 987769
72 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The resuscitation interventions required and the short term outcomes for depressed newborns with and without umbilical cord milking.
Time Frame: 20 minutes after delivery

The resuscitation interventions required (use of CPAP, oxygen, mask and bag ventilation, endotracheal intubation and ventilation, chest compressions, drugs, and fluid boluses) and the short term outcomes of resuscitation will be assessed using the validated Combined Apgar score (consisting of the Expanded and Specified Apgar scoring systems) introduced by Rudiger et al, in depressed neonates with and without UCM.

[Designated as safety issue: No];

Ref:Dalili H, Nili F, Sheikh M, Hardani AK, Shariat M, Nayeri F (2015) Comparison of the Four Proposed Apgar Scoring Systems in the Assessment of Birth Asphyxia and Adverse Early Neurologic Outcomes. PLoS ONE 10(3): e0122116
20 minutes after delivery
Requirement of Neonatal Intensive Care Unit (NICU) admission
Time Frame: 1st 24 hours after delivery
Requirement of Neonatal Intensive Care Unit (NICU) admission [Designated as safety issue: No]
1st 24 hours after delivery
Blood lactate at 24 hours
Time Frame: 1st 24 hours after delivery

Lactate in the peripheral blood at 24 hours after birth in neonates with any grade of HIE.

[Designated as safety issue: No]
1st 24 hours after delivery
CD34+ stem cell count at 24 hours
Time Frame: 24 hours after birth

CD34+ stem cell count in the peripheral blood at 24 hours after birth in neonates with any grade of HIE.

[Designated as safety issue: No]
24 hours after birth
The number of neonates with symptomatic polycythemia
Time Frame: 48 hours after birth

The number of neonates with symptomatic polycythemia defined as lethargy, plethora, jitteriness, tachycardia, tachypnea and with venous hematocrit > 65%.

[Designated as safety issue: No];
48 hours after birth
The number of neonates with hyperbilirubinemia requiring phototherapy or exchange transfusion.
Time Frame: 72 hours after birth

Neonates requiring phototherapy or exchange transfusion will be evaluated according to the NICE/AAP guidelines and serum bilirubin levels will be interpreted according to the baby's age in hours. Physicians who assess the neonate and advice phototherapy or exchange transfusion will be blinded to the intervention.

[Designated as safety issue: No]
72 hours after birth
The number of neonates with anemia
Time Frame: 2 hours after birth
The number of neonates with anemia defined as venous hemoglobin < 12.5 g/dL [Designated as safety issue: No];
2 hours after birth
MRI changes in the brain of neonates with moderate and severe degrees of HIE who underwent whole body hypothermia.
Time Frame: 14 days after birth

MRI examination will be performed in neonates who underwent whole body hypothermia 7-14 days after birth and the changes in brain scored as per a validated MR scoring system (Barkovich et al, Am J Neuroradiol 1998;19:143-9) by a neuroradiologist blinded to the intervention.

[Designated as safety issue: No];

Ref:Barkovich AJ, Hajnal BL, Vigneron D, Sola A, Partridge JC, Allen F, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. Am J Neuroradiol 1998;19:143-9. [PubMed: 9432172]
14 days after birth
Duration of hospital stay in neonates with any grade of HIE.
Time Frame: Duration of hospital stay, an expected average of 7-14 days
Duration of hospital stay in neonates with any grade of HIE. [Designated as safety issue: No]
Duration of hospital stay, an expected average of 7-14 days
Survival at 6 weeks of age
Time Frame: 6 weeks after birth
Survival at 6 weeks of age [Designated as safety issue: No]
6 weeks after birth
Haemoglobin levels at 6 weeks of age
Time Frame: 6 weeks after birth
Haemoglobin levels at 6 weeks of age [Designated as safety issue: No]
6 weeks after birth
Serum ferritin levels at 6 weeks of age
Time Frame: 6 weeks after birth
Serum ferritin levels at 6 weeks of age [Designated as safety issue: No]
6 weeks after birth

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Jubilee Mission Medical College and Research Institute

Investigators

  • Principal Investigator: Manoj Varanattu, MD, Jubilee Mission Medical College and Research Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 1, 2018

Primary Completion (ANTICIPATED)

December 31, 2021

Study Completion (ANTICIPATED)

July 1, 2022

Study Registration Dates

First Submitted

March 1, 2017

First Submitted That Met QC Criteria

April 19, 2017

First Posted (ACTUAL)

April 21, 2017

Study Record Updates

Last Update Posted (ACTUAL)

March 2, 2021

Last Update Submitted That Met QC Criteria

February 27, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • JubileeMMCRI

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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