Hypoxic-Ischemic EncephalopathyCORDMILKNCT03657394
Comparative Outcomes Related to Delivery-room Cord Milking In Low-resourced Kountries
A study testing Umbilical cord milking in people with Hypoxic-Ischemic Encephalopathy and Birth Asphyxia, run by Nemours Children's Clinic at 9 sites in India.
Trial summary
The investigators will conduct a study on non-vigorous infants at birth to determine if umbilical cord milking (UCM) results in lower rate of moderate to severe hypoxic ischemic encephalopathy (HIE) or death than early clamping and for infants who are non-vigorous at birth and need immediate resuscitation. Read more about this study
- Who is it for?
- Ages 35 to 42 weeks
- Conditions the study is for
- Hypoxic-Ischemic Encephalopathy, Birth Asphyxia
- What is being tested?
- Umbilical cord milking
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 3,442 participants
- Where
- 9 sitesIndia
- Study dates
- 17 Oct 2022to 31 Oct 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 35 to 42 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Non-vigorous neonates born between 35-42 weeks
Who cannot join
- Congenital malformation of CNS.
- Chromosomal abnormalities.
- Major congenital malformations.
- Abruption/cutting through the placenta at delivery.
- Umbilical cord knots or inadequate cord length.
- Mono-chorionic twins or twins with no information on amnion/chorion.
- Multiple gestation >2 .
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
India9 sites
KLE Academy of Higher Education and Research (Deemed-to-be-University) Jawaharlal Nehru Medical College
Belagavi, Karnataka, 590010
Government Medical College
Chandrapur, MS, 442401
Sawai Man Singh (SMS) Medical College
Jaipur, Rajasthan, 302004
Indira Gandhi Government Medical College & Hospital
Nagpur, Maharashtra, 440018
Daga Memorial Woman and Children Hospital
Nagpur, MS, 440002
Government Medical College and Hospital
Nagpur, MS, 440009
All India Institute of Medical Science
Nagpur, MS, 441108
Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital
Pune, Maharashtra, 411018
Mahatma Gandhi Institute of Medical Sciences/ Kasturba Hospital
Wardha, MS, 442102
About this study
Official title: A Cluster Randomized Clinical Trial of Umbilical Cord Milking Versus Early Cord Clamping on Short and Long-term Outcomes in Neonates Who Are Non-Vigorous at Birth
The investigators will conduct a study on non-vigorous infants at birth to determine if umbilical cord milking (UCM) results in lower rate of moderate to severe hypoxic ischemic encephalopathy (HIE) or death than early clamping and for infants who are non-vigorous at birth and need immediate resuscitation.
Read the detailed description
Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by inadequate blood flow and oxygen delivery to the neonatal brain. Almost all infants with severe HIE and 30-50% infants with moderate HIE either die or develop significant developmental delay, cerebral palsy or other disabilities.The incidence of HIE is 1-3 per 1,000 term births in developed countries and 15-20 times higher in developing countries (Worldwide, 0.5 to 1 million infants develop HIE each year). Therapeutic hypothermia is the only proven therapy for infants with HIE. Even after receiving therapeutic hypothermia, one-half of all infants with moderate and severe HIE die or develop neurological and functional impairment. Therapeutic hypothermia is not widely available and ineffective in developing nations.There is an urgent need for a new therapy for neonates with HIE, which can complement hypothermia and be readily available in developing nations. Stem cell transplantation is a potential therapy for infants with HIE. Umbilical cord blood is a rich source of stem cells. Umbilical cord milking (UCM) may have similar effect as autologous umbilical cord blood cell transplantation.
Preliminary evidence suggests a placental transfusion in term infants may be a neuroprotective mechanism that can also facilitate cardiovascular transition for neonates depressed at birth and result in decreased mortality and improved neurodevelopmental outcomes. Infants with HIE, due to varied complications during the birth process, have poor perfusion due to fetal blood volume loss to the placenta. However, the most common method of providing placental blood, delayed cord clamping (DCC) cannot be performed since infants with HIE are non-vigorous and providers often need to perform resuscitation immediately after birth. The World Health Organization and the American College of Obstetrics and Gynecology (ACOG) also does not recommended DCC in neonates who are non-vigorous (limp, pale, and not breathing) at birth and require immediate resuscitation. Umbilical cord milking (UCM) or gently squeezing cord blood toward the baby, is an alternative to DCC, which can achieve significant placental transfusion without delaying resuscitation. Further, UCM can be completed as quickly as immediate cord clamping (ICC) and UCM requires minimal training and no additional staff.
The investigators hypothesized that UCM will reduce the number of infants developing moderate to severe HIE or death in neonates who are non-vigorous at birth compared to early cord clamping (ECC). This will be a cluster crossover randomized controlled trial. Each hospital will be randomly assigned to use either ECC or UCM for any infant who is non-vigorous at birth and needing resuscitation over a period of 6 months. Then the site will change to the other method for an additional 6 months.
- Conditions
- Hypoxic-Ischemic Encephalopathy, Birth Asphyxia
- Being tested
- Umbilical cord milking
- Keywords
- Placental transfusion
- Medical subject headings
- Hypoxia-Ischemia, Brain, Asphyxia Neonatorum, Fetofetal Transfusion
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Umbilical cord milkingOther
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 1--15 seconds.
| Study group | Role | What they receive |
|---|---|---|
| Umbilical Cord Milking | Active comparator | 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 20-30 centimeters length of the umbilical cord over two seconds, repeating three additional times as described previously. This time is not significantly different from the time for ECC. Receives: Other: Umbilical cord milking |
| Early Cord Clamping | No intervention | Umbilical cord will be clamped immediately after birth (within 60 seconds) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Moderate to severe HIE or death
Number of infants with moderate to severe HIE or death
Measured: From date of birth until the date of discharge from the hospital or date of death from any cause, whichever come first, asessed up to 10 weeks.
Secondary outcomes (1)
MRI of the brain
Number of infants with moderate to severe HIE who have abnormal brain MRI
Measured: 4 days to 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2018
- Study start17 Oct 2022
- Primary completion1 Sep 2025
- Study completion31 Oct 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypoxic-Ischemic EncephalopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Cluster Randomized Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 3,442 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Nemours Children's Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- Sharp HealthCare, Thomas Jefferson University, University of San Diego, St. Louis University, Jawaharlal Nehru Medical College, Daga Memorial Maternity and Children's Hospital, Nagpur, India, Mahatma Gandhi Institute of Medical Sciences, Karnataka Institue of Medical Sciences, Hubbali, India, Jawaharlal Institute of Postgraduate Medical Education & Research, All India Institute of Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Indira Gandhi Government Medical College & Hospital, Nagpur, India, Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital, Pune, India, Government Medical College, Nagpur
- Responsible party
- Principal investigator, Zubair Aghai, Nemours Children's Clinic
- Investigators
- Zubair H Aghai, MD, Principal investigator, Nemours Children's ClinicAnup Katheria, MD, Principal investigator, Sharp Mary Birch Hospital for Women & NewbornsSangappa Dhaded, MD, Principal investigator, KLE Academy of Higher Education and Research
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03657394
- Sponsor's protocol ID
- CORDMILK
- Other IDs
- R01HD102967
- Acronym
- CORDMILK
- Status last verified
- Aug 2026
- First submitted
- 30 Aug 2018
- Last updated
- 1 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Yogeshkumar S, Vernekar SS, Dhaded SM, Talekar K, Leiby BE, Hartman R, Vaucher Y, Chouthai N, Girish M, Jain M, Jain S, Parvekar S, Jain V, Patankar A, Suryawanshi M, Tiwari M, Waikar M, Nashine N, Ambike D, Asalkar M, Kulkarni R, Haribhaktha S, Narkhede H, Chaudhari S, Kamble M, Shrirame D, Falke B, Mehta S, Verma A, Gothwal S, Goudar SS, Derman R, Katheria A, Aghai ZH. CORDMILK: Umbilical Cord Milking versus Early Cord Clamping on short-and long-term outcomes in neonates who are non-vigorous at birth-study protocol of a multi-center, cluster-randomized, crossover-controlled trial. Trials. 2025 Nov 17;26(1):509. doi: 10.1186/s13063-025-09197-8.
PubMed 41250198
Study at a glance
From the registry record, last updated by the sponsor on 1 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Cluster Randomized Clinical Trial of Umbilical Cord Milking Versus Early Cord Clamping on Short and Long-term Outcomes in Neonates Who Are Non-Vigorous at Birth
- ClinicalTrials.gov ID
- NCT03657394
- Acronym / sponsor ID
- CORDMILK / CORDMILK
- Conditions
- Hypoxic-Ischemic Encephalopathy, Birth Asphyxia
- Keywords
- Placental transfusion
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 3,442 participants (estimated)
- Lead sponsor
- Nemours Children's ClinicUniversity, hospital or other
- Collaborators
- Sharp HealthCare, Thomas Jefferson University, University of San Diego, St. Louis University, Jawaharlal Nehru Medical College, Daga Memorial Maternity and Children's Hospital, Nagpur, India, Mahatma Gandhi Institute of Medical Sciences, Karnataka Institue of Medical Sciences, Hubbali, India, Jawaharlal Institute of Postgraduate Medical Education & Research, All India Institute of Medical Sciences, Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Indira Gandhi Government Medical College & Hospital, Nagpur, India, Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Yashwantrao Chavan Memorial Hospital, Pune, India, Government Medical College, Nagpur
- Study start
- 17 Oct 2022 (actual)
- Primary completion
- 1 Sep 2025 (actual)
- Study completion
- 31 Oct 2026 (estimated)
- First posted
- 5 Sep 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators will conduct a study on non-vigorous infants at birth to determine if umbilical cord milking (UCM) results in lower rate of moderate to severe hypoxic ischemic encephalopathy (HIE) or death than early clamping and for infants who are non-vigorous at birth and need immediate resuscitation.
Detailed description
Hypoxic-ischemic encephalopathy (HIE) is a brain injury caused by inadequate blood flow and oxygen delivery to the neonatal brain. Almost all infants with severe HIE and 30-50% infants with moderate HIE either die or develop significant developmental delay, cerebral palsy or other disabilities.The incidence of HIE is 1-3 per 1,000 term births in developed countries and 15-20 times higher in developing countries (Worldwide, 0.5 to 1 million infants develop HIE each year). Therapeutic hypothermia is the only proven therapy for infants with HIE. Even after receiving therapeutic hypothermia, one-half of all infants with moderate and severe HIE die or develop neurological and functional impairment. Therapeutic hypothermia is not widely available and ineffective in developing nations.There is an urgent need for a new therapy for neonates with HIE, which can complement hypothermia and be readily available in developing nations. Stem cell transplantation is a potential therapy for infants with HIE. Umbilical cord blood is a rich source of stem cells. Umbilical cord milking (UCM) may have similar effect as autologous umbilical cord blood cell transplantation.
Preliminary evidence suggests a placental transfusion in term infants may be a neuroprotective mechanism that can also facilitate cardiovascular transition for neonates depressed at birth and result in decreased mortality and improved neurodevelopmental outcomes. Infants with HIE, due to varied complications during the birth process, have poor perfusion due to fetal blood volume loss to the placenta. However, the most common method of providing placental blood, delayed cord clamping (DCC) cannot be performed since infants with HIE are non-vigorous and providers often need to perform resuscitation immediately after birth. The World Health Organization and the American College of Obstetrics and Gynecology (ACOG) also does not recommended DCC in neonates who are non-vigorous (limp, pale, and not breathing) at birth and require immediate resuscitation. Umbilical cord milking (UCM) or gently squeezing cord blood toward the baby, is an alternative to DCC, which can achieve significant placental transfusion without delaying resuscitation. Further, UCM can be completed as quickly as immediate cord clamping (ICC) and UCM requires minimal training and no additional staff.
The investigators hypothesized that UCM will reduce the number of infants developing moderate to severe HIE or death in neonates who are non-vigorous at birth compared to early cord clamping (ECC). This will be a cluster crossover randomized controlled trial. Each hospital will be randomly assigned to use either ECC or UCM for any infant who is non-vigorous at birth and needing resuscitation over a period of 6 months. Then the site will change to the other method for an additional 6 months.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- Cluster Randomized Crossover
| Arm | Type | Receives |
|---|---|---|
| Umbilical Cord Milking | Active comparator | Other: Umbilical cord milkingThe 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 20-30 centimeters length of the umbilical cord over two seconds, repeating three additional times as described previously. This time is not significantly different from the time for ECC. |
| Early Cord Clamping | No intervention | –Umbilical cord will be clamped immediately after birth (within 60 seconds) |
Who may qualify
- Ages
- 35 to 42 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Non-vigorous neonates born between 35-42 weeks
Key exclusion criteria (7 listed)
- Congenital malformation of CNS.
- Chromosomal abnormalities.
- Major congenital malformations.
- Abruption/cutting through the placenta at delivery.
- Umbilical cord knots or inadequate cord length.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Umbilical cord milkingAt 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 1--15 seconds. | Other | Umbilical Cord Milking |
Primary outcome
Moderate to severe HIE or death
Time frame: From date of birth until the date of discharge from the hospital or date of death from any cause, whichever come first, asessed up to 10 weeks.
Number of infants with moderate to severe HIE or death
1 secondary outcome
MRI of the brain
Time frame: 4 days to 2 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Sep 2026.
- Derived from this study: PubMed 41250198Yogeshkumar S, Vernekar SS, Dhaded SM, Talekar K, Leiby BE, Hartman R, Vaucher Y, Chouthai N, Girish M, Jain M, Jain S, Parvekar S, Jain V, Patankar A, Suryawanshi M, Tiwari M, Waikar M, Nashine N, Ambike D, Asalkar M, Kulkarni R, Haribhaktha S, Narkhede H, Chaudhari S, Kamble M, Shrirame D, Falke B, Mehta S, Verma A, Gothwal S, Goudar SS, Derman R, Katheria A, Aghai ZH. CORDMILK: Umbilical Cord Milking versus Early Cord Clamping on short-and long-term outcomes in neonates who are non-vigorous at birth-study protocol of a multi-center, cluster-randomized, crossover-controlled trial. Trials. 2025 Nov 17;26(1):509. doi: 10.1186/s13063-025-09197-8.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Zubair H Aghai, MD principal investigator
Nemours Children's Clinic
Anup Katheria, MD principal investigator
Sharp Mary Birch Hospital for Women & Newborns
Sangappa Dhaded, MD principal investigator
KLE Academy of Higher Education and Research
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Umbilical cord milking in people with Hypoxic-Ischemic Encephalopathy and Birth Asphyxia, run by Nemours Children's Clinic at 9 sites in India.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in India. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Moderate to severe HIE or death (time frame: From date of birth until the date of discharge from the hospital or date of death from any cause, whichever come first, asessed up to 10 weeks.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03657394, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Sep 2026.