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.

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.