Neonatology pp 439-456 | Cite as

Oxygen Toxicity in Newborns

  • Rodolfo BracciEmail author
  • Serafina Perrone
  • Maximo Vento
  • Giuseppe Buonocore
Reference work entry


The first evidence of a relationship between oxygen toxicity and neonatal diseases emerged in the early 1950s, when retinopathy was observed in premature infants breathing high concentrations of oxygen. Oxygen toxicity is due to the development of reactive oxygen species (ROS), such as the superoxide anion (O2), hydrogen peroxide (H202), lipid peroxide (LOOH), peroxyl radicals RO, electron delocalized phenoxyl radical (C6H50), nitric oxide (NO), and the hydroxyl radical (OH). OH is one of the strongest oxidants in nature and may damage tissues. There is no specific scavenger for this radical, and once released, OH reacts with lipoproteins, cell membranes, lipids, proteins, DNA, amino acids, and other molecules causing structural and functional damage to these structures. The main sources of ROS are NADPH oxidase reactions (principally in phagocytes after activation upon exposure to microbes, microbial products, or inflammatory mediators), mitochondrial metabolism, hypoxia-reoxygenation (hypoxanthine-xanthine oxidase reaction), hyperoxia, and paradoxically hypoxia. Abnormal percentage of ROS generation can have pathological consequences if they are lower as well as they are higher than normal. An excess of ROS, in relation to detoxification capacity, is called oxidative stress, a term which expresses the imbalance between oxidants and antioxidants that is a potential cause of damage. If oxidative stress is mild, cell defenses may increase by a mechanism which generally involves enhanced gene expression of ROS scavenging activities. Severe oxidative stress is generally followed by cell injury and plays a role in many kinds of cell death, i.e., apoptosis, necrosis, autophagy, and mitophagy. Oxidative stress has been suggested as a causative agent in pregnancy-related disorders such as recurrent pregnancy loss, preeclampsia, preterm premature rupture of membranes, intrauterine growth restriction, and fetal death. In the fetal-to-neonatal transition, both blood oxygen content and oxygen availability abruptly increase in the first few minutes after birth, eliciting the generation of a burst of ROS. Oxidative stress following hyperoxia has been recognized to be responsible for lung, retina, and red blood cell injury and possibly generalized tissue damage.

Several methods have been proposed in the attempt to detect the presence and the severity of the oxidative stress. Measurements of protein, lipid, and DNA bases oxidation and intracellular redox status are accurate methods. Prevention of ROS tissue damage involves the avoidance of conditions such as infections, asphyxia, hyperoxia, and retinal light exposure, under which excessive ROS occurs. When supplemental oxygen is needed for care, the most prudent approach would be not to tolerate possible hypoxia and not to accept SpO2 values associated with potential hyperoxia, setting the low alarm never <85% and the high alarm never more than 95%. It is imperative to avoid a flip-flop phenomenon that leads to acute and significant changes and fluctuations in SpO2. Preterm infants should be fed early with human expressed milk, which offers an additional protection against free radicals. Although the usefulness of antioxidant protection during pregnancy and in the neonatal period is still under investigation, the risk of tissue damage due to oxidative stress in perinatal period should not be underestimated.


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© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  • Rodolfo Bracci
    • 1
    Email author
  • Serafina Perrone
    • 2
  • Maximo Vento
    • 3
  • Giuseppe Buonocore
    • 1
  1. 1.University of SienaSienaItaly
  2. 2.Department of Molecular and Developmental MedicineUniversity Hospital of SienaSienaItaly
  3. 3.Neonatal Research Unit, Health Research Institute Hospital La FeUniversity and Polytechnic Hospital La FeValenciaSpain

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