Can Delayed Cord Clamping Protect the Preterm Lung from Oxygen Damage?

Preterm birth remains one of the leading causes of newborn illness and death worldwide. Because preterm infants are often born with immature lungs, many require help to breathe immediately after birth. Oxygen is a lifesaving therapy in this setting, but too much oxygen can damage fragile lung tissue, leading to long-term problems such as bronchopulmonary dysplasia. Finding the right balance between providing enough oxygen to support life while avoiding injury remains one of the great challenges in neonatal care.

One strategy under investigation is physiological-based cord clamping (PBCC). Instead of clamping the umbilical cord immediately after birth, PBCC allows resuscitation to begin while the infant is still connected to the placenta. This may help stabilize the transition to life outside the womb by maintaining blood flow and oxygen delivery from the placenta. But does this strategy also protect the lungs from oxygen-related injury?

The Study

To answer this question, researchers studied preterm lambs, which provide a well-established model for understanding the physiology of preterm infants. The lambs, delivered at 125 days of gestation (comparable to very preterm human infants), were given 100% oxygen for 10 minutes after birth. They were randomly assigned to one of two groups:

• PBCC group: Resuscitation with the cord intact before clamping

• Immediate cord clamping (ICC) group: Cord clamped within 30 seconds, followed by resuscitation

After resuscitation, oxygen was gradually reduced to maintain target oxygen saturation levels. Lung tissue was collected one hour later for detailed analysis, including RNA sequencing to study inflammation pathways.

Key Findings

• PBCC helped stabilize oxygenation: Lambs in the PBCC group avoided the initial dip in oxygen levels seen in the ICC group and also avoided excessive oxygen levels during resuscitation.

• No reduction in lung injury: Despite these benefits, PBCC did not reduce markers of oxidative stress or inflammation compared to ICC. In fact, PBCC lambs showed higher expression of inflammatory genes such as IL1β and IL6.

• New insights from transcriptome analysis: Advanced gene expression studies revealed activation of novel pathways related to inflammation, immune response, and cytokine signaling.

The Bottom Line

Physiological-based cord clamping helps preterm infants transition more smoothly at birth by preventing both early hypoxia (too little oxygen) and subsequent hyperoxia (too much oxygen). However, when high concentrations of oxygen are used for resuscitation, PBCC does not protect the lungs from oxidative stress or inflammation.

The findings highlight a crucial message: the oxygen level used during resuscitation matters just as much as the cord clamping strategy. Prolonged use of 100% oxygen should be avoided in the delivery room, no matter when the cord is clamped.

here is the link to the paper: https://www.nature.com/articles/s41390-025-04285-6