Umbilical Cord Milking in Non-Vigorous Infants (MINVI)

The investigators will conduct a study of non-vigorous term infants to determine if umbilical cord milking (UCM) results in a lower rate of NICU admissions than early clamping and cutting of the umbilical cord at birth for infants who need resuscitation.

Study Overview

• Status: Completed
• Conditions: Birth Asphyxia
• Intervention / Treatment: Procedure: Umbilical Cord Milking; Procedure: Early Cord Clamping

Detailed Description

At birth, it is critical that an infant begins breathing quickly. The infant has to switch from relying on the placenta for oxygen to using its lungs for the first time. The currently recommended practice for infants who need resuscitation is to immediately clamp the umbilical cord. Animal studies show that clamping the cord before the baby breathes can cause the heart beat to slow and can decrease the amount of blood being pumped out of the heart each minute. This study will test whether infants will benefit from UCM. The cord will be quickly milked four times before cutting and will not delay the resuscitation procedures. This study is important because when there is need for resuscitation, neither UCM or delayed cord clamping, are recommended by national and international organizations due to lack of evidence. Yet, several large studies from around the world have identified that infants needing resuscitation are more likely to develop conditions such as cerebral palsy, autism and other developmental problems.

The trial is a cluster crossover design in which each hospital will be randomly assigned to use either early cord clamping or UCM for any infant needing resuscitation over a period of 12 months. Then sites will change to the other method for an additional 12 months.

• Study Type: Interventional
• Enrollment (Actual): 1730
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2R3
      • University of Alberta
  • New Brunswick
    • Dalhousie, New Brunswick, Canada, E8C 2R6
      • Dalhousie University
• Poland
  • Poznań, Poland
    • Poznan University of Medical Science
• United States
  • California
    • Davis, California, United States, 95616
      • University of California, Davis
    • Loma Linda, California, United States, 92350
      • Loma Linda Medical Center
    • San Diego, California, United States, 92123
      • Sharp Mary Birch Hospital for Women and Newborns
    • San Diego, California, United States, 91942
      • Sharp Grossmont Hospital
  • District of Columbia
    • Washington, District of Columbia, United States, 20052
      • George Washington University
  • Oregon
    • Portland, Oregon, United States, 97225-6603
      • Providence St. Vincent Medical Center
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah/IMH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 8 months to 9 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Non-vigorous newborns born between 35-42 weeks gestation

Exclusion Criteria:

• Known major congenital or chromosomal anomalies of newborn
• Known cardiac defects other than small ASD, VSD and PDA
• Complete placental abruption/cutting through the placenta at time of delivery
• Monochorionic multiples
• Cord anomaly (i.e. cord avulsion, true knot)
• Presence of non-reducible nuchal cord
• Perinatal providers unaware of the protocol
• Incomplete delivery data
• Infants born in extremis, for whom additional treatment will not be offered

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Umbilical Cord Milking; The delivering practitioner will place the newborn below the level of the incision (at the edge of the table) at C/S and a second team member will milk the cord four times. For vaginal delivery, the delivering obstetrician, midwife or perinatal provider will hold the infant against their body or place the infant on the mother's abdomen and the cord will be milked either four times by the obstetrical provider or by a second team member. For the cord milking procedure, the obstetrical provider will milk the entire length of umbilical cord over two seconds, repeating three additional times as described previously. This time is not significantly different from the time for ECC as we have demonstrated in our previous trials.	Procedure: Umbilical Cord Milking; At delivery, the umbilical cord is grasped, and blood is pushed toward the infant 4 times before the cord is clamped. This procedure infuses a placental transfusion of blood into the infant and can be done in 15-20 seconds.
Active Comparator: Early Cord Clamping; This will occur by clamping the umbilical cord as soon as possible. Since both ECC and UCM will occur after a brief assessment, it is important to note that the cord clamping time will be longer than in previously conducted preterm trials (average 20 seconds) which performed the intervention on all subjects regardless of whether or not they were vigorous. In all cases, the cord clamping time will be documented to ensure consistency.	Procedure: Early Cord Clamping; The umbilical cord is clamped within 30 seconds of delivery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NICU Admission	Admission to the Neonatal Intensive Care Unit for Study-specific criteria	Delivery room death or Admission to the NICU in the first 48 hours of life

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Placental Transfusion	Estimated by single hemoglobin measurement	12-48 hours of life
Therapeutic Hypothermia ("Cooling")	Cooling to 33.5 degrees C for 72 hours within the first 6 hours of life	72 hours of life
Use of volume expander	Treated with blood products or normal saline bolus to support blood pressure	Through hospital stay, up to 120 days
Hyperbilirubinemia	Total bilirubin per Bhutani nomogram	First week of life
Death	Death prior to discharge	From birth to date of death or discharge, whichever occurs first, assessed up to 180 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory-Level of Hypoxic Ischemic Encephalopathy	Mild, moderate or severe	Through hospital stay, up to 120 days
Exploratory-Length of Stay	Number of days from birth to discharge home	Through hospital stay, up to 120 days
Exploratory-Blood Pressure	Blood Pressure on Admission to NICU	First 48 hours of life
Exploratory-Resuscitation interventions	Level of resuscitation interventions at delivery	First hour of life

Collaborators and Investigators

• Sponsor: Sharp HealthCare
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Alberta; University of California, Davis; George Washington University; University of Utah; Loma Linda University; Poznan University of Medical Sciences; IWK Health Centre; Providence Hospital; Sharp Mary Birch Hospital for Women & Newborns; Sharp Grossmont Hospital
• Investigators: Principal Investigator: Anup Katheria, MD, Sharp HealthCare

Publications and helpful links

Helpful Links

• MINVI NIRS Substudy
• MINVI Follow-up study
• MINVI Echocardiogram Substudy

Study record dates

Study Major Dates

• Study Start (Actual): January 5, 2019
• Primary Completion (Actual): June 1, 2021
• Study Completion (Actual): September 26, 2023

Study Registration Dates

• First Submitted: August 6, 2018
• First Submitted That Met QC Criteria: August 13, 2018
• First Posted (Actual): August 15, 2018

Study Record Updates

• Last Update Posted (Actual): January 3, 2024
• Last Update Submitted That Met QC Criteria: January 2, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Resuscitation; Umbilical Cord Milking; Immediate Cord Clamping
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Infant, Newborn, Diseases; Death; Asphyxia; Asphyxia Neonatorum
• Other Study ID Numbers: MINVI; 5R01HD096023-02 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No