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.

S Yogeshkumar, Sunil S Vernekar, Sangappa M Dhaded, Kiran Talekar, Benjamin E Leiby, Rebecca Hartman, Yvonne Vaucher, Nitin Chouthai, Meenakshi Girish, Manish Jain, Shuchi Jain, Seema Parvekar, Vinita Jain, Alka Patankar, Milind Suryawanshi, Manish Tiwari, Manjushri Waikar, Nidhi Nashine, Deepali Ambike, Mahesh Asalkar, Rajesh Kulkarni, Sandhya Haribhaktha, Hemraj Narkhede, Sudha Chaudhari, Milind Kamble, Deepti Shrirame, Balchandra Falke, Seema Mehta, Asha Verma, Sunil Gothwal, Shivaprasad S Goudar, Richard Derman, Anup Katheria, Zubair H Aghai

Journal: Trials 2025;26(1):509

PMID: 41250198

View on PubMed

Abstract

BACKGROUND

Facilitating placental transfusion-the transfer of blood from the placenta to the newborn-via delayed cord clamping (DCC) or umbilical cord milking (UCM) at birth has been shown to improve iron stores in healthy term infants and may positively impact long-term neurodevelopmental outcomes. Infants who are non-vigorous at birth and at risk of developing hypoxic-ischemic encephalopathy (HIE) are particularly likely to benefit from placental transfusion. This process may offer neuroprotection by enhancing cardiopulmonary transition, supporting cardiac preload, improving systemic and cerebral perfusion, delivering stem cells and neurotrophic factors, and preventing iron deficiency. While DCC is not currently recommended for non-vigorous term infants requiring immediate resuscitation, UCM offers a viable alternative, as it can be performed quickly.

METHODS

This study is a multicenter, cluster-randomized, crossover-controlled trial comparing UCM with early cord clamping (ECC) in term and late preterm infants who are non-vigorous at birth. The trial will be conducted across seven centers in India. Before the trial begins, each site will be assigned to an initial study arm using a computer-generated randomization scheme. Once 50% of the enrollment is complete, sites will switch to the alternate study arm after a 2-month washout period. The study is designed with sufficient power to assess the composite outcome of death or moderate-to-severe HIE during birth hospitalization and survival without moderate-to-severe neurodevelopmental impairment at 2 years of age. Secondary outcomes include survival without moderate-to-severe neurodevelopmental impairment at 1 year of age and survival without evidence of brain injury on MRI during the birth hospitalization.

DISCUSSION

The CORDMILK trial aims to generate critical evidence on whether UCM can improve survival without moderate-to-severe HIE during birth hospitalization and survival without significant neurodevelopmental impairment at 2 years of age in late preterm and term neonates who are non-vigorous at birth.

TRIAL REGISTRATION

Clinical Trial Registry-India CTRI/2021/09/036759. Registered on 22/09/2021.

CLINICALTRIALS

Gov number NCT03657394 and NCT03682042.

Address: Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India.; Jawaharlal Nehru Medical College, KLE Academy of Higher Education and Research, Belagavi, Karnataka, India. [email protected].; Thomas Jefferson University, Philadelphia, PA, USA.; University of California, San Diego, CA, USA.; Children's Hospital of MI, Wayne State University, Detroit, MI, USA.; All India Institute of Medical Sciences, Nagpur, Maharashtra, India.; Mahatma Gandhi Institute of Medical Sciences/Kasturba Hospital, Sevagram, Wardha, Maharashtra, India.; Daga Memorial Maternity and Children's Hospital, Nagpur, Maharashtra, India.; Indira Gandhi Government Medical College & Hospital, Nagpur, Maharashtra, India.; Government Medical College, Nagpur, Maharashtra, India.; Yashwantrao Chavan Memorial Hospital, Pimpri Chinchwad Municipal Corporation's Post-Graduate Institute, Pune, Maharashtra, India.; KEM Hospital, Pune, Maharashtra, India.; Karmaveer Ma.Sa. Kannamwar Government Medical College, Chandrapur, Maharashtra, India.; Sawai Man Singh Medical College, Jaipur, Rajasthan, India.; Sharp Mary Birch Hospital for Women & Newborns, San Diego, CA, USA.; Thomas Jefferson University, Philadelphia, PA, USA.; Nemours Children's Health, Wilmington, DE, USA.

DOI: 10.1186/s13063-025-09197-8

MeSH Terms: Humans, Infant, Newborn, Multicenter Studies as Topic, Umbilical Cord Clamping, Female, Cross-Over Studies, Pregnancy, Randomized Controlled Trials as Topic, Umbilical Cord, Time Factors, India, Infant, Premature, Hypoxia-Ischemia, Brain, Treatment Outcome, Male, Term Birth, Constriction, Child Development