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

Status

Indicates the current recruitment status or the expanded access status.
Unknown

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Anticipated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
400

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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 Contact

Study Contact

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Study Contact Backup

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Jubilee Mission Medical College and Research Institute

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Manoj Varanattu, MD, Jubilee Mission Medical College and Research Institute

Publications and helpful links

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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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
January 1, 2018

Primary Completion (ANTICIPATED)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2021

Study Completion (ANTICIPATED)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 1, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
March 1, 2017

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 19, 2017

First Posted (ACTUAL)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 21, 2017

Study Record Updates

Last Update Posted (ACTUAL)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 2, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 27, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2021

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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