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Preterm infants are not small term infants: Should the resuscitation of a <26-week preterm infant be initiated with 100% oxygen?

Journal of Perinatology (2024)Cite this article

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Current neonatal resuscitation program (NRP) guidelines recommend that the initial use of 21% oxygen in term and late preterm newborns (≥ 35 weeks gestation) requiring respiratory support at birth is reasonable [1]. These recommendations are based on systematic reviews and meta-analyses demonstrating higher mortality in term hypoxic infants resuscitated with 100% oxygen [2]. In preterm newborns (<35 weeks gestation), NRP suggests that it may be reasonable to begin resuscitation with 21% to 30% oxygen which is then titrated based on pulse oximetry [3]. However, there are emerging concerns with these recommendations. For example, in a retrospective analysis, the Canadian Neonatal Network reported higher rates of mortality and neurologic injury among preterm infants ≤27 weeks gestation after low-oxygen recommendations were implemented [4]. In randomized controlled trials (RCT) comparing low, intermediate, and high concentrations of initial oxygen for preterm infant resuscitation, there are concerns that mortality may be lower if resuscitation is initiated with 100% oxygen [5]. A non-prespecified subgroup analysis of a trial comparing 21% to 100% oxygen showed lower hospital mortality in infants <29 weeks gestation when resuscitation was initiated with 100% oxygen [6]. Oei et al. showed that infants <32 weeks gestation that did not achieve SpO2 ≥ 80% by 5 minutes after birth had increased risk of major intraventricular hemorrhage (IVH) and death [7].

From a physiological perspective, it is intriguing as to why high concentration (90–100%) but not an intermediate concentration of oxygen (50–65%) is not associated with a lower mortality compared to low (21-30%) oxygen in preterm infants. In studies evaluating preterm infants < 32 weeks gestation, a high proportion of deaths are accounted by <26 weeks gestation infants, who are in the canalicular state of lung development with a wide airspace-capillary interface (Fig. 1B). Pulmonary vasculature in preterm infants is less sensitive to oxygen compared to term infants and the decrease in pulmonary vascular resistance (PVR) with 21-65% oxygen ventilation may be inadequate to reverse ductal shunting to increase postnatal pulmonary blood flow [9]. Hypoxia from inadequate gas exchange may then potentially contribute to respiratory depression and lower ventilation. Indeed, higher tidal volumes in preterm infants following resuscitation initiated with 100% oxygen compared to 21% oxygen supports the role of hypoxia in contributing to respiratory depression [10].

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Fig. 1: NETMOTION and the newborn cardiorespiratory system.

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Authors and Affiliations

  1. Department of Pediatrics, UC Davis Children’s Hospital, Sacramento, CA, USA

    Sylvia P. Bowditch & Satyan Lakshminrusimha

  2. Department of Newborn Care, The Royal Hospital for Women, Randwick, NSW, Australia

    Ju Lee Oei

  3. School of Paediatrics and Child Health, University of New South Wales, Randwick, NSW, Australia

    Ju Lee Oei

  4. NHMRC Clinical Trial Centre, Faculty of Medicine and Health, University of Sydney, Camperdown, NSW, Australia

    Ju Lee Oei

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All three authors contributed to the writing and editing of the manuscript.

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Correspondence to Sylvia P. Bowditch.

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Competing interests

Dr. Lakshminrusimha is a former member of the AAP Neonatal Resuscitation Program (NRP) Committee and a co-investigator on the DOXIE trial. Dr. Oei has received support from Mallinckrodt Inc and is the principal investigator of the TORPIDO trial. The remaining authors have no relevant conflicts of interest pertaining to this article. Opinions expressed in this article are the author’s own and do not reflect official position of the ILCOR or NRP.

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Bowditch, S.P., Oei, J.L. & Lakshminrusimha, S. Preterm infants are not small term infants: Should the resuscitation of a <26-week preterm infant be initiated with 100% oxygen?. J Perinatol (2024). https://doi.org/10.1038/s41372-024-02073-4

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