Effect of Intact Umbilical Cord Milking on Neonatal and First Year Neurodevelopmental Outcomes in Very Preterm Infants.

Study Overview
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Brief Summary
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The investigators hypothesise that intact umbilical cord milking (I-UCM) will reduce neonatal morbidity and improve long term neurodevelopmental outcome in very preterm infants. All babies born less than 32 weeks gestation, meeting the inclusion criteria will be randomly assigned to either I-UCM or immediate cord clamping (ICC) and their short and long term outcome measures analyzed.

Detailed Description
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Optimizing placental transfusion at birth promotes a more physiologic transition from intrauterine to extrauterine life. There is increasing evidence about the benefits of enhanced placental transfusion in improving neonatal outcomes, such as higher hemoglobin concentration, improved hemodynamic stability, reduced incidence of intraventricular hemorrhage, less need for blood transfusions and better neurodevelopmental outcome in preterm infants. The investigators propose to evaluate the the safety and effectiveness of I-UCM versus ICC in mothers undergoing preterm delivery before 32 weeks, by randomly assigning them to one of two groups - study and control. The study group will undergo I-UCM during delivery and the control group will have ICC, which is the current standard of care. Both groups will subsequently receive routine care for mother and infant. In the study group the infants will be placed at or ∼20 cm below the level of the placenta and about 20 cm of the intact umbilical cord will be milked towards the umbilicus three times. The technique consists of pinching the cord close to the placenta and milking about 20 cm segment of the cord proximal to the umbilicus, towards the infant over a 2-second duration. The cord will then be released and allowed to refill with blood for a brief 2-second pause between each milking motion. After completion of milking three times, the cord will be clamped close to the umbilicus and the neonate handed over to the neonatal team. The procedure of cord milking will be completed within 20 seconds. Prenatal and delivery data will be collected from the mother's charts. Infant data will be collected from hospital admission records and from follow up for a period up to 12 months of corrected age. The infant data collected will include hemoglobin levels at birth, incidence and severity of intraventricular hemorrhage in the first week of life and neonatal morbidity (resuscitation measures, peak bilirubin, need for phototherapy and blood transfusion, sepsis, necrotizing enterocolitis, retinopathy of prematurity and chronic lung disease) and mortality. The neurodevelopmental status of both the study and control group of infants will be assessed at 6 months and one year of corrected age. The investigators hypothesize that I-UCM provides a greater placental transfusion and better neonatal outcomes when compared to ICC. It is a simple procedure which can be practiced universally and of great relevance to both developed and developing countries.

Official Title
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Effect of Intact Umbilical Cord Milking Versus Immediate Cord Clamping on Neonatal Outcomes and First Year Neurodevelopmental Outcomes in Very Preterm Infants - A Randomised Controlled Trial

Conditions
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Preterm Infant, Umbilical Cord Milking

Intervention / Treatment
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* Procedure: Intact Umbilical Cord Milking


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All the preterm infants of less than 32 weeks of gestation born of consenting parents in the hospital Exclusion Criteria: Neonates depressed at birth, MCMA, MCDA Twin pregnancy (DCDA twins are included), Severe IUGR in antenatal scans (< 10th Centile), Known case of Hydrops fetalis, Known major congenital anomaly, Placenta previa and abruptions, bleeding, accreta, nuchal cord, anhydramnios, PROM > 2 weeks before 24 weeks and Refusal to Consent by the Parents

Ages Eligible for Study
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Minimum Age: 1 Minute
Maximum Age: 5 Minutes

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intact Umbilical Cord Milking<br>Umbilical Cord Milking involves pinching of the cord close to the placenta and milking about 20 cm segment of the cord proximal to the umbilicus, towards the infant over a 2-second duration. The cord will be then released, allowing for a brief 2-second pause between each milking motion. This will be repeated for a total of 3 times over a duration less than 20 seconds. | Procedure: Intact Umbilical Cord Milking<br>* Immediately after delivery, the infant will be placed at or ∼20 cm below the level of the placenta and about 20 cm of the intact umbilical cord will be milked towards the umbilicus three times. The technique consists of pinching the cord close to the placenta and milking about 20 cm segment of the cord proximal to the umbilicus, towards the infant over a 2-second duration. The cord will then be released and allowed to refill with blood for a brief 2-second pause between each milking motion. After completion of milking three times, the cord will be clamped close to the umbilicus and the neonate handed over to the neonatal team. The procedure of cord milking will be completed within 20 seconds.<br>* Other names: Milking of the Umbilical Cord;|
| No Intervention: Early Cord Clamping<br>Umbilical cord will be clamped immediately after delivery and baby will be handed over to the neonatal team. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Haemoglobin levels at birth | Haemoglobin levels at birth | 1 hour | 
| Intraventricular Haemorrhage | Incidence and severity of Intraventricular Haemorrhage in the first week of life - Cranial Ultrasound done on day 7 | 7 days of life | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The resuscitation interventions required with and without umbilical cord milking. | The resuscitation interventions required that will be assessed are requirement of Continuous Positive Airway Pressure (CPAP), oxygen, mask and bag ventilation, endotracheal intubation and ventilation, chest compressions, drugs, and fluid boluses | 20 minutes after delivery | 
| Resuscitation outcomes with and without umbilical cord milking. | 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. 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 | 
| Incidence of hypotension | Incidence of hypotension | 24 hours of life | 
| Requirement of inotropic support | Number of inotropes required for support | 24 hours of life | 
| symptomatic polycythemia | The number of neonates with symptomatic polycythemia (defined as lethargy, plethora, jitteriness, tachycardia, tachypnea and with venous hematocrit > 65%). | 48 hours of life | 
| Sepsis (culture positive) | Incidence of Sepsis (culture positive) | 72 hours of life | 
| Peak bilirubin levels | Serum peak bilirubin levels | 72 hours of life | 
| Requirement of phototherapy or exchange transfusion | Neonates requiring phototherapy or exchange transfusion will be evaluated according to the NICE 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. | 72 hours of life | 
| Incidence of Necrotising Enterocolitis (NEC) | Incidence of Necrotising Enterocolitis as defined by modified Bell's Criteria | 14 days of life | 
| Requirement of Oxygen | Requirement of Oxygen at 28 days of life and at 36 weeks gestation | 36 weeks of gestational age | 
| Requirement of red blood cell transfusions | Requirement of red blood cell transfusions before discharge | 4 weeks of life | 
| Number of days of Hospital Stay after Birth | Number of days of Hospital Stay after Birth | 4 weeks of life | 
| Death prior to discharge | Death prior to discharge | 4 weeks of life | 
| Serum iron stores | Serum iron stores (ferritin levels) at 6 weeks and 6 months of age | 6 months of age | 
| Developmental Assessment Scales for Indian Infants (DASII) | Developmental Assessment Scales for Indian Infants (DASII) tests carried out at 6 months and 1 year of corrected age. The DASII scale is divided into motor scale and mental scale. The motor scale consists of 67 items and mental scale consists of 163 items. (P Phatak, et al, 1996) | 1 year of corrected age |