In the realm of neonatal care, the timing of umbilical cord clamping has long been a topic of pivotal importance. Traditionally, immediate clamping was the norm, yet recent evidence has shifted clinical practice toward deferred cord clamping (DCC), a technique that allows continued placental blood flow to the newborn after birth. This practice has demonstrated numerous benefits, particularly in enhancing neonatal iron stores and stabilizing hemodynamics. However, the nuanced interplay between oxygen administration and deferred cord clamping presents a complex physiological puzzle, one that researchers Katheria and Lakshminrusimha tackle head-on in their latest study published in Pediatric Research in 2025.
Oxygen, a molecule fundamental to metabolism and life, paradoxically has the potential to inflict harm when administered excessively to neonates, especially during the vulnerable transition from fetal to neonatal life. The study delves into whether supplemental oxygen given to newborns during the period of deferred cord clamping might actually lead to deleterious effects, challenging previously held assumptions about its unmitigated benefits. The authors call into question whether the well-intentioned provision of supplementary oxygen, widely accepted in neonatal resuscitation protocols, could inadvertently contribute to oxidative stress and impair the very outcomes DCC seeks to improve.
From a physiological perspective, the transition at birth involves a rapid shift in oxygenation status. In utero, the fetus exists in a relatively hypoxic state, relying on maternal oxygen supply via the placenta. The sudden exposure to ambient air stimulates pulmonary vasodilation and increased oxygen saturation. DCC allows the newborn’s lungs to begin this oxygenation process while still receiving placental blood flow, facilitating a smoother cardiovascular and respiratory adaptation. However, when supplemental oxygen is introduced during this delicate window, it may disturb the oxidative balance, potentially exacerbating free radical generation and cellular injury.
Katheria and Lakshminrusimha’s research synthesizes emerging data that highlight the potential risks of hyperoxia in the immediate neonatal period. Excessive oxygen exposure during DCC may increase the production of reactive oxygen species (ROS), molecules known to damage lipids, proteins, and DNA. These oxidative injuries are particularly concerning in premature infants, whose antioxidant defenses are underdeveloped. The authors hypothesize that controlled, judicious oxygen supplementation—or even room air breathing without supplemental oxygen—may be more beneficial during deferred cord clamping to avoid the harmful sequelae of oxidative stress.
Their work critically examines the balance between ensuring adequate oxygen delivery and avoiding oxidative damage, underscoring the need for precision in neonatal oxygen management. The paper advocates for revising current neonatal resuscitation guidelines to reflect the risks associated with indiscriminate oxygen use during DCC. It also calls for improved monitoring techniques that can dynamically assess oxygen saturation and oxidative biomarkers in real time, enabling clinicians to tailor oxygen delivery with unprecedented accuracy.
This intriguing study also anchors its hypothesis in the molecular mechanisms of oxygen toxicity. The newborn’s exposure to high oxygen concentrations can overwhelm endogenous antioxidant systems such as superoxide dismutase, catalase, and glutathione peroxidase. The excessive ROS generated may precipitate cellular apoptosis or necrosis, influencing long-term outcomes such as bronchopulmonary dysplasia and retinopathy of prematurity, diseases historically linked to oxygen toxicity. The authors point out the necessity of integrating these molecular insights into clinical practice to optimize neonatal outcomes.
Moreover, the research highlights the heterogeneity among neonates, emphasizing that oxygen needs may vary significantly according to gestational age, birth weight, and intrauterine conditions. Hence, a universal oxygen supplementation strategy during DCC might not be appropriate. Individualized care, informed by continuous monitoring and assessment, could represent the future standard of care. This precision medicine approach could reconcile the dual imperatives of avoiding hypoxia-induced injury while preventing oxygen-driven oxidative stress.
Katheria and Lakshminrusimha also provide a critical review of current clinical trials exploring oxygen supplementation during deferred cord clamping. Highlighting limitations such as small sample sizes and inconsistent protocols, they champion the execution of large-scale, randomized controlled trials with standardized oxygen titration parameters. Their call to action aims to shape evidence-based guidelines that can be confidently implemented worldwide, enhancing neonatal survival and development.
Importantly, the study reminds us that oxygen therapy, despite its ubiquity and lifesaving potential, remains a double-edged sword. The notion that ‘more oxygen is better’ is increasingly being replaced by an appreciation for moderation and timing. This paradigm shift is especially relevant in delivery room practices where decisions have immediate and lifelong consequences for newborns.
The ethical considerations of modifying oxygen protocols during one of the most critical periods of human development receive due attention in the authors’ discourse. Informed consent, parental counseling, and transparent communication about the rationale behind oxygen management strategies are vital for fostering trust and adherence to new clinical practices emerging from this research.
Looking forward, the integration of advanced biomedical technology such as noninvasive oxygen sensors, oxidative stress markers, and imaging modalities may revolutionize how clinicians approach oxygen management during deferred cord clamping. These innovations could provide a comprehensive, real-time physiological snapshot, guiding therapeutic decisions down to the molecular level.
In conclusion, this seminal work by Katheria and Lakshminrusimha opens a critical dialogue on the intertwined relationship between oxygen administration and deferred cord clamping. It challenges entrenched clinical dogma and highlights the delicate biochemical balancing act underlying neonatal transition. Their insights may ultimately catalyze a global reevaluation of neonatal resuscitation practices, promising better outcomes through smarter oxygen use—acknowledging that in neonatal care, as in so many realms, sometimes less is indeed more.
With ongoing research and clinical innovation, the goal of optimizing both the timing of the umbilical cord clamping and the precise oxygen environment promises to elevate neonatal care to unprecedented heights. Neonatologists, obstetricians, and researchers alike will watch closely as this evolving landscape unfolds, poised to embrace more nuanced, evidence-driven strategies that honor the intricacies of human physiology at birth.
As the neonatal community continues to weigh the benefits and risks of oxygen supplementation during deferred cord clamping, this study serves as a watershed moment. It compels us to rethink neonatal oxygen management and to refine our protocols to safeguard the fragile beginnings of life. In this balancing act of oxygen’s promise and peril, the pursuit of knowledge is not only scientific but profoundly humanitarian.
Subject of Research: Oxygen administration during deferred cord clamping and its impact on neonatal outcomes.
Article Title: Oxygen during deferred cord clamping: too much of a good thing?
Article References:
Katheria, A.C., Lakshminrusimha, S. Oxygen during deferred cord clamping: too much of a good thing?. Pediatr Res (2025). https://doi.org/10.1038/s41390-025-04711-9
Image Credits: AI Generated
DOI: https://doi.org/10.1038/s41390-025-04711-9
Tags: deferred cord clamping benefitshemodynamics in newbornsiron stores in neonatesKatheria and Lakshminrusimha studyneonatal care practicesneonatal resuscitation protocolsoxidative stress in neonatesoxygen risks in newbornsphysiological transition at birthplacental blood flow advantagessupplemental oxygen effects on infantsumbilical cord clamping timing
