Deferred Cord Clamping With High Oxygen in Extremely Preterm Infants: A Randomized Clinical Trial.

Importance: Deferred cord clamping (DCC) with high oxygen may reduce early hypoxia in preterm newborns. However, the safety and efficacy of this procedure has never been studied.

Objective: To determine whether providing 100% oxygen by face mask during the window of DCC in preterm infants reduces hypoxemia compared with 30% oxygen without hyperoxemia due to the continued mixing with umbilical venous blood.

Design, Setting, And Participants: This double-blinded randomized clinical trial took place from November 2021 to October 2024 at 2 universities and 1 private medical center in California. Participants included 140 preterm infants (born at 22 to 28 weeks' gestation). These data were analyzed from November 2024 to May 2025.

Interventions: During DCC, infants received continuous positive airway pressure or positive pressure ventilation via face mask and were randomized to either 30% (low oxygen group) or 100% (high oxygen group) using a concealed blender. After the umbilical cord was clamped and cut, each infant was resuscitated per contemporary guidelines (30% oxygen and titration based on saturation of peripheral oxygen).

Main Outcome: The primary outcome was the number of infants who achieve peripheral oxygen saturations of 80% by 5 minutes of life.

Results: There were 140 infants randomized (mean gestational age, 26 weeks; 69 female [49%] and 71 male [51%]). In the low oxygen group, 28 of 72 infants (39%) achieved a peripheral oxygen saturation of 80% by 5 minutes compared with 47 of 68 infants (69%) in the high oxygen group (adjusted odds ratio, 3.74; 95% CI, 1.80-7.79; P < .001). The absolute risk difference between the 2 groups was 0.3 (95% CI, 0.26-0.35), indicating that the high oxygen group had a 30% lower risk of experiencing hypoxemia 5 minutes after birth. Maximum median fraction of inspired oxygen during resuscitation after DCC, umbilical arterial partial pressure of oxygen in arterial blood, severe intraventricular hemorrhage, and death before 40 weeks' postmenstrual age were not different between groups.

Conclusion And Relevance: In this study, 100% oxygen during DCC reduced early hypoxemia without increased morbidity. A large randomized clinical trial is needed to determine if 100% oxygen during DCC improves survival and reduces longer-term morbidities in extremely preterm infants.

Trial Registration: ClinicalTrials.gov Identifier: NCT04413097.