Clinical trial NCT03123081: Role of Umbilical Cord Milking in the Management of Hypoxic-ischemic Encephalopathy in Neonates
Official title: Role of Umbilical Cord Milking in the Management of Hypoxic-ischemic Encephalopathy in Neonates: a Randomized Controlled Trial
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Hypoxic-Ischemic Encephalopathy
Lead sponsor: Jubilee Mission Medical College and Research Institute
Sponsor class: OTHER
First posted: 2017-04-21
Enrollment: 400
Sex: ALL
Minimum age (years): 1
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence and severity of HIE in depressed neonates with and without umbilical cord milking
timeFrame: 72 hours
Secondary outcomes:
measure: The resuscitation interventions required and the short term outcomes for depressed newborns with and without umbilical cord milking.
timeFrame: 20 minutes after delivery
measure: Requirement of Neonatal Intensive Care Unit (NICU) admission
timeFrame: 1st 24 hours after delivery
measure: Blood lactate at 24 hours
timeFrame: 1st 24 hours after delivery
measure: CD34+ stem cell count at 24 hours
timeFrame: 24 hours after birth
measure: The number of neonates with symptomatic polycythemia
timeFrame: 48 hours after birth
measure: The number of neonates with hyperbilirubinemia requiring phototherapy or exchange transfusion.
timeFrame: 72 hours after birth
measure: The number of neonates with anemia
timeFrame: 2 hours after birth
measure: MRI changes in the brain of neonates with moderate and severe degrees of HIE who underwent whole body hypothermia.
timeFrame: 14 days after birth
measure: Duration of hospital stay in neonates with any grade of HIE.
timeFrame: Duration of hospital stay, an expected average of 7-14 days
measure: Survival at 6 weeks of age
timeFrame: 6 weeks after birth
measure: Haemoglobin levels at 6 weeks of age
timeFrame: 6 weeks after birth
measure: Serum ferritin levels at 6 weeks of age
timeFrame: 6 weeks after birth
Other outcomes:
Locations:
city: Thrissur
country: India
facility: Jubilee Mission Medical College & Research Institute
state: Kerala
Study officials:
affiliation: Jubilee Mission Medical College and Research Institute
name: Manoj Varanattu, MD
role: PRINCIPAL_INVESTIGATOR
References:
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