Oxygen and oxidative stress in the perinatal period

Abstract

Fetal life evolves in a hypoxic environment. Changes in the oxygen content in utero caused by conditions such as pre-eclampsia or type I diabetes or by oxygen supplementation to the mother lead to increased free radical production and correlate with perinatal outcomes.In the fetal-to-neonatal transition asphyxia is characterized by intermittent periods of hypoxia ischemia that may evolve to hypoxic ischemic encephalopathy associated with neurocognitive, motor, and neurosensorial impairment. Free radicals generated upon reoxygenation may notably increase brain damage. Hence, clinical trials have shown that the use of 100% oxygen given with positive pressure in the airways of the newborn infant during resuscitation causes more oxidative stress than using air, and increases mortality.Preterm infants are endowed with an immature lung and antioxidant system. Clinical stabilization of preterm infants after birth frequently requires positive pressure ventilation with a gas admixture that contains oxygen to achieve a normal heart rate and arterial oxygen saturation. In randomized controlled trials the use high oxygen concentrations (90% to 100%) has caused more oxidative stress and clinical complications that the use of lower oxygen concentrations (30–60%). A correlation between the amount of oxygen received during resuscitation and the level of biomarkers of oxidative stress and clinical outcomes was established. Thus, based on clinical outcomes and analytical results of oxidative stress biomarkers relevant changes were introduced in the resuscitation policies. However, it should be underscored that analysis of oxidative stress biomarkers in biofluids has only been used in experimental and clinical research but not in clinical routine. The complexity of the technical procedures, lack of automation, and cost of these determinations have hindered the routine use of biomarkers in the clinical setting. Overcoming these technical and economical difficulties constitutes a challenge for the immediate future since accurate evaluation of oxidative stress would contribute to improve the quality of care of our neonatal patients.

Impact of the Neonatal Resuscitation Program–Recommended Low Oxygen Strategy on Outcomes of Infants Born Preterm

“…[38, 39] In animal models, even a brief exposure to 100% O 2 results in very high PaO2 levels in the brain and other tissues. [40, 41] Further, multiple animal and human studies have found adverse effects of hyperoxemia during resuscitation resulting in tissue injury and worse outcomes.…”

Particularities of Oxidative Stress in Newborns

“…In case of iron overloading or severe oxidative stress, the antioxidant defense capacity is exceeded, making nontransferrin bonds available, with the release of low molecular mass iron, followed by lipid peroxidation. This may occur even if transferrin is not completely iron saturated [42].…”

“…In the reoxygenation stage, hypoxanthine is converted to uric acid under the action of xanthine oxidase, and superoxide and peroxide are released through the mediation of xanthine oxidase by molecular oxygen binding. Hydroxyl radical generated through the Fenton reaction will also be released, due to the catalytic effect of metals such as iron [42]. Perinatal hypoxic stress is a frequent cause of morbidity, mortality, and neurological damage in survivors.…”

“…Thus, a vicious circle is created. ROS will be formed, followed by tissue lesions and the genesis of new free radicals [42,43].…”

Topiramate plus Cooling for Hypoxic-Ischemic Encephalopathy: A Randomized, Controlled, Multicenter, Double-Blinded Trial

“…Neuron viability is intimately reliant on a continuous blood-borne supply of both oxygen and glucose to avoid ATP exhaustion and subsequently cells swelling, apoptosis, and necrosis [2, 3]. …”