Effect of immediate cord clamping, intact cord milking, and cut cord milking on hemodynamics in non-vigorous preterm neonates born at 28+0 to 33+6 Weeks’ Gestation: A Randomized Controlled Trial (CORDIAL)

This randomized controlled trial is being conducted at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, to compare the efficacy of three umbilical cord management techniques in non-vigorous preterm neonates born between 28+0 and 33+6 weeks gestation. The aim is to determine which method best improves early cardiovascular stability, particularly when delayed cord clamping is not feasible due to the need for immediate neonatal resuscitation.

Current neonatal resuscitation guidelines recommend delayed cord clamping in vigorous preterm infants; however, evidence is lacking for non-vigorous preterms who require urgent intervention. Cord milking—both intact and cut—has emerged as a potential alternative, offering rapid placental transfusion without delaying resuscitation. This study evaluates Intact Umbilical Cord Milking (I-UCM) and Cut Umbilical Cord Milking (C-UCM) against Immediate Cord Clamping (ICC).

A total of 141 preterm neonates who meet the inclusion criteria (non-vigorous, 28–33+6 weeks GA, not requiring major resuscitation) will be randomized in a 1:1:1 ratio using block randomization into one of the three intervention arms. I-UCM involves milking the intact umbilical cord three times before clamping, C-UCM involves cutting and then milking the cord, and ICC refers to immediate clamping within 30 seconds after birth.

The primary outcome is Superior Vena Cava (SVC) flow at 12 ± 2 hours of life, measured by functional echocardiography. SVC flow is a validated surrogate marker for systemic perfusion in preterm infants and provides insight into cardiovascular transition. The study uses standard echocardiographic protocols and is conducted by personnel trained in neonatal functional echocardiography.

Secondary outcomes include:

• Hematological indices: hematocrit and serum ferritin levels at 12 hours
• Heart rate and blood pressure trends in the first 12 hours
• Incidence of intraventricular hemorrhage (IVH) on cranial ultrasound at 72 hours
• Need for respiratory or inotropic support
• Early neonatal mortality

Additional data on cord blood gases, APGAR scores, and NICU course (e.g., ventilation needs, oxygen days) will also be collected.

Ethical approval has been obtained from the JIPMER Institute Ethics Committee. Written informed consent will be obtained from parents prior to delivery.

This study addresses an important clinical challenge—optimizing cord management in non-vigorous preterm infants. By directly comparing I-UCM, C-UCM, and ICC, the findings may influence resuscitation practices, especially in resource-limited settings where delayed cord clamping with intact cord ventilation is not feasible. Positive results favoring cord milking could lead to broader adoption of these techniques and potentially improve early systemic perfusion and neonatal outcomes in vulnerable preterm populations.