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.

Keywords: Biomarkers; High-risk pregnancy; Ischemia-reperfusion; Newborn; Oxidative stress; Oxygen.

Graphical abstract

Fig. 1

Partial pressure of oxygen achieved by the embryo is strictly related to the oxygen content of inspired air, alveolar oxygen content, partial pressure of oxygen in the mother and placental fetal gas exchange. Changes at any of these stages will inevitably affect embryo/fetal/newborn oxygenation.

Fig. 2

Maturation of the antioxidant defense system occurs late in gestation in fetal lung coupled to lung surfactant adapting the respiratory and antioxidant system to face postnatal afflux of oxygen to tissue. The graph represents changes experimented by the antioxidant enzyme activity in fetal rabbits at the end of gestation. Modified from Frank et al. .

Fig. 3

Certain clinical conditions in utero cause hypoxia or hyperoxia in the fetus or during fetal to neonatal transition. Recovery of normality through resuscitation/reperfusion is going to generate a burst of oxygen free radicals by activation of oxidases, NO synthase and OXPHOS. Oxidative stress will induce pro-apoptotic and pro-inflammatory cascades thus contributing to the amplification of the initial damage. Abbreviations: XD=xanthine dehydrogenase; XO=xanthine oxidase; NOX=NADPH oxidases; NOS=nitric oxide synthase.

Fig. 4

Isofurans urinary levels are represented in the Y-axis and days after birth in the X-axis. The graph depicts mean (darker line) and standard deviations of the mean (dotted lines) for urinary isofurans (IsoFs) in healthy preterm infants <32 weeks’ gestation without oxidative stress-associated conditions (Refs. [75], [76]). Preterm infants who developed bronchopulmonary dysplasia (red squares) exhibited significantly higher values for urinary IsoFs in the first 4 days after birth. Expressed in Intensity of Signal Arbitrary Units. Modified from Kuligowski et al. .