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CTRI Number  CTRI/2025/01/079614 [Registered on: 28/01/2025] Trial Registered Prospectively
Last Modified On: 31/12/2024
Post Graduate Thesis  Yes 
Type of Trial  Interventional 
Type of Study   Other (Specify) [Comparing intact cord milking with cut cord milking among neonates requiring resuscitation at birth]  
Study Design  Randomized, Parallel Group Trial 
Public Title of Study   Comparison of cord milking techniques among neonates who require resuscitation at birth 
Scientific Title of Study   Comparison of intact cord milking and cut cord milking among neonates requiring resuscitation at birth a randomized controlled trial 
Trial Acronym  NIL 
Secondary IDs if Any  
Secondary ID  Identifier 
NIL  NIL 
 
Details of Principal Investigator or overall Trial Coordinator (multi-center study)  
Name  Niteesh R N 
Designation  DM resident 
Affiliation  St Johns medical college and hospital 
Address  Department of neonatology St johns medical college

Bangalore
KARNATAKA
560034
India 
Phone  9900094050  
Fax    
Email  rnniteesh8@gmail.com  
 
Details of Contact Person
Scientific Query
 
Name  Suman Rao P N 
Designation  Professor and Head of the department 
Affiliation  St Johns medical college and hospital 
Address  Department of neonatology St Johns Medical College

Bangalore
KARNATAKA
560034
India 
Phone  9900094050  
Fax    
Email  raosumanv@gmail.com  
 
Details of Contact Person
Public Query
 
Name  Niteesh R N 
Designation  DM resident 
Affiliation  St Johns medical college and hospital 
Address  Department of neonatology St Johns Medical College

Bangalore
KARNATAKA
560034
India 
Phone  9900094050  
Fax    
Email  rnniteesh8@gmail.com  
 
Source of Monetary or Material Support  
St johns medical college and hospital, Bengaluru, Karnataka, India, Pin code: 560034 
 
Primary Sponsor  
Name  Niteesh R N 
Address  Department of neonatology St johns medical college, Bengaluru, Karnataka, 560034 
Type of Sponsor  Other [Self] 
 
Details of Secondary Sponsor  
Name  Address 
NIL  NIL 
 
Countries of Recruitment     India  
Sites of Study  
No of Sites = 1  
Name of Principal Investigator  Name of Site  Site Address  Phone/Fax/Email 
DrNiteesh R N  St johns medical college hospital  Department of neonatology St johns medical college, Koramangala, Bengaluru, Karnataka 560034
Davanagere
KARNATAKA 
9900094050

rnniteesh8@gmail.com 
 
Details of Ethics Committee  
No of Ethics Committees= 1  
Name of Committee  Approval Status 
Institutional ethics committee, St johns medical college sarjapur road, city Bengaluru district Bengaluru Urban Karnataka 560034  Approved 
 
Regulatory Clearance Status from DCGI  
Status 
Not Applicable 
 
Health Condition / Problems Studied  
Health Type  Condition 
Healthy Human Volunteers  Neonates requiring resuscitation at birth  
 
Intervention / Comparator Agent  
Type  Name  Details 
Comparator Agent  Cut umbilical cord milking  Babies in comparator arm who require resuscitation at birth will receive cut cord milking. Over a period of 2 years, 120 babies will be recruited  
Intervention  Intact umbilical cord milking  Babies in intervention group are the ones who require resuscitation at birth. They will receive intact cord milking. Total of 120 babies will be recruited over a period of 2 years 
 
Inclusion Criteria  
Age From  0.00 Day(s)
Age To  28.00 Day(s)
Gender  Both 
Details  Babies born more than or equal to 28 weeks of gestation requiring resuscitation at birth 
 
ExclusionCriteria 
Details  1. Neonates less than 28 weeks of gestation
2. Multiple births
3. Antenatally detected major congenital anomalies
4. Umbilical cord abnormalities such as true knot
5. Hydrops
 
 
Method of Generating Random Sequence   Other 
Method of Concealment   Not Applicable 
Blinding/Masking   Open Label 
Primary Outcome  
Outcome  TimePoints 
Hemoglobin levels at 6 hours of life  Hemoglobin levels at 6 hours of life 
 
Secondary Outcome  
Outcome  TimePoints 
Vitals and cerebral oxygenation via NIRS  at birth, 1st hour and 6 hours of life 
 
Target Sample Size   Total Sample Size="240"
Sample Size from India="240" 
Final Enrollment numbers achieved (Total)= "Applicable only for Completed/Terminated trials"
Final Enrollment numbers achieved (India)="Applicable only for Completed/Terminated trials" 
Phase of Trial   N/A 
Date of First Enrollment (India)   15/02/2025 
Date of Study Completion (India) Applicable only for Completed/Terminated trials 
Date of First Enrollment (Global)  Date Missing 
Date of Study Completion (Global) Applicable only for Completed/Terminated trials 
Estimated Duration of Trial   Years="2"
Months="0"
Days="0" 
Recruitment Status of Trial (Global)   Not Applicable 
Recruitment Status of Trial (India)  Not Yet Recruiting 
Publication Details   N/A 
Individual Participant Data (IPD) Sharing Statement

Will individual participant data (IPD) be shared publicly (including data dictionaries)?  

Response - NO
Brief Summary  

·           Introduction

 

Placental transfusion is the additional volume of blood transferred to the baby during birth. This may be carried out by delayed cord clamping or cord milking. World Health Organization (WHO) recommends delaying cord clamping (60-180 seconds) as the standard of care in the delivery room for newborns not needing resuscitation.[1] 

In term neonates, delayed cord clamping (DCC) results in improvement in hemoglobin at 24-48 hours of life and iron stores at 3-6months of life.[2] For preterm neonates delaying cord clamping improves survival and is associated with fewer infants requiring transfusions for anemia, less intraventricular haemorrhage and lower risk for necrotising enterocolitis, compared with immediate clamping.[3] There is a considerable body of evidence to support the practice of providing additional blood volume to term and preterm neonates not needing resuscitation at birth by delaying cord clamping. Clamping the umbilical cord at least 60 s after birth reduced the risk of death or major disability at 2 years by 17%. [4]

Delayed cord clamping is the standard of care and is recommended for all neonates who cry at birth, not requiring resuscitation. However for babies who require resuscitation at birth, resuscitation takes priority over delayed cord clamping. In such cases, intact cord resuscitation where baby is resuscitated on a special trolley named “BASICS trolley” with continued intra partum transfusion has been studied but the trolley is not routinely available. [5]

Umbilical cord milking (UCM) also provides the extra placental transfusion mimicking delayed cord clamping. There are two types of cord milking cut cord milking and intact cord milking. A systematic review of umbilical cord milking in preterm neonates (<33 weeks) reported significantly higher hematocrit, and reduced risk of oxygen need at 36 weeks and intra ventricular hemorrhage. [6] Provision of additional placental blood at birth in preterm neonates is associated with higher bilirubin levels, but may not be a matter of concern as it does not translate to increased interventions for hyper bilirubinemia. [3] Patel et al  demonstrated that in neonates <30 weeks delivered by cesarean section, cord milking resulted in better systemic blood flow than those with delayed cord clamping.[7] 

In cut cord milking, umbilical cord in clamped at 25-30 cm distance from the neonatal end for those babies requiring resuscitation at birth. Immediately newborn is transferred to newborn corner when resuscitation is initiated. Simultaneously another person milks the umbilical cord for 2-4 times from clamped end to the baby’s end within 15 seconds after birth. A randomized control trial done at St John’s Medical College and Hospital by Ram Mohan et al showed that in preterm neonates requiring resuscitation, umbilical cord milking results in higher hemoglobin and ferritin at 6 weeks of life. It can be a used as a placental transfusion strategy in preterm neonates requiring resuscitation with no significant adverse effects. [8] The 2023 ILCOR recommendations suggests that for infants born > 28weeks’ gestational age who need resuscitation at birth and who do not receive delayed cord clamping, intact cord milking as a reasonable alternative to immediate cord clamping to improve infant hematologic outcomes. [9] During third stage of labour, placental blood is transferred at a greater pace by contracting uterus hence; blood gets refilled after each milking from the placental end to the neonate. Therefore intact cord milking may offer greater advantage over cut cord milking as higher colume of blood is transferred. Extreme preterms have been excluded in view of increased risk of intraventricular hemorrhage noted in this group.

In our unit we routinely follow cut cord milking for neonates who are more than or equal to 28 weeks of gestation, requiring resuscitation at birth.

While there is evidence to show that two methods of UCM are better than early cord clamping (ECC), there are no studies comparing the two methods of umbilical cord milking among neonates requiring resuscitation at birth. There is a need to compare the effect of intact umbilical cord milking (I-UCM) and cut umbilical cord milking (C-UCM) on neonatal outcomes.

 

·           Review of literature:

 

The transition period from fetal to postnatal life is characterized by major physiological changes in the cardiopulmonary functions. Therefore, International Resuscitation Guidelines recommended routine delayed cord clamping (DCC) for 30 to 60 seconds after birth in infants not requiring resuscitation, permitting passive transfer of placental blood to the newborn [10–12]. Besides blood volume and iron support, placental transfusion promotes transfer of immunoglobulins and multipotent stem cells, which are essential for tissue and organ repair [12, 13].

Although DCC provides greater blood pressure and cerebral oxygenation in term infants at risk for resuscitation [14], it results in an inadequate transfusion in depressed newborns not breathing during the delay [15]. Therefore, UCM, allowing placental transfusion in seconds, may be a reasonable alternative to ECC and DCC in infants requiring immediate resuscitation [16–18].

In fact, a previous study, comparing intact UCM (I-UCM) with ECC in near-term and term infants with abnormal cord blood gases (pH≤7.1, base deficit >-12), showed that fewer infants receiving I-UCM needed immediate resuscitation and respiratory support at NICU admission [19]. In addition, a study, comparing I-UCM with DCC, demonstrated that I-UCM provided hemodynamic improvement in preterm infants delivered by C/S [17].

Although a few studies demonstrated that C-UCM is much more effective than ECC, and has as comparable effects as DCC in term and near-term infants, there was no study comparing the two milking methods regarding cerebral oxygenation, hemodynamic and hematological adaptation during immediate transition period (ITP) [20–22].

Study done by McAdams et al showed that I-UCM provides a greater blood volume than C-UCM. [23]

Jain S N et al proved that application of milking of the umbilical cord can be seen to improve the health of hypoxic neonates, weight parameters, blood volume, hematocrit, hemoglobin, iron levels in the blood, red blood cell count, blood pressure, right ventricular output, left ventricular functions, cerebral oxygenation, urine output regulation, cognitive abilities, antioxidant levels, better outcomes in the resuscitation of infant and above all helps in lowering infant mortality rates. [24]

A RCT done by Katheria et al demonstrated higher systemic blood flow with UCM in preterm neonates compared with DCC. UCM may be a more efficient technique to improve blood volume in premature infants delivered by caesarean delivery. [25]

Another important aspect that is long term consequences with respect to neurodevelopmental outcomes was studied by Naggar et al. They concluded saying that there were no significant differences in the median cognitive, motor or language scores or in the rates of cerebral palsy, developmental impairment, deafness, or blindness between study groups. [26]

There are two small studies comparing I-UCM and C-UCM. The study by McAdams et al only mentioned the volume of blood that was collected in a cup by the two methods of milking. I-UCM provides a greater blood volume than C-UCM. [21] This study did not compare infant outcomes. The second study by Orpak et al compared the effects of I-UCM and C-UCM on cerebral oxygenation, hemodynamic and hematological adaptation of term infants. [27] However this study was done on healthy term neonates and those requiring resuscitation were excluded from the analysis.

There are no studies comparing the two methods of milking in newborns requiring resuscitation.

 

·           Justification / need for the study

 

Delayed cord clamping has been a gold standard norm for babies who cry immediately at birth. However for babies who require resuscitation at birth, DCC is not a feasible option as golden minute of resuscitation takes priority. There are studies which compare the superiority of cord milking over early cord clamping but none comparing intact versus cut cord milking among those who require resuscitation at birth. Hence our study will aid in enhancing the intra partum transfusion that helps term and preterm babies requiring resuscitation to achieve better hemoglobin levels and hemodynamic stability.

We hypothesize that intact umbilical cord milking, allowing both rapid placental transfusion and resuscitation simultaneously without time loss, heat loss and without disrupting the aseptic field in newborns can provide superior cerebral oxygenation, hemodynamic and hematological effects than cut cord milking in infants requiring resuscitation. As there are no studies comparing the two methods of UCM, there is a need to study the I-UCM and C-UCM to determine the best placental strategy for newborns who need resuscitation at birth.

 
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