Oxidative stress at childbirth

Childbirth is an oxidative challenge for newborns. The transition from fetal to neonatal life at birth implies acute and complex physiologic changes. The fetus transfers from an intrauterine hypoxic environment with a pO2 of 20 to 25 mm Hg to an extrauterine normoxic environment with a pO2 of 100 mm Hg.61 This four- to five-fold increase is believed to induce increased production of ROS.

Neonatal plasma has relatively poor antioxidative defenses.62 At birth, neonatal plasma concentrations of vitamins A, E and p-carotene were significantly lower than maternal plasma levels, while neonatal levels of vitamin C were significantly higher.63 Uric acid and vitamin C constitute most of the extracellular antioxidant capacity, totaling 75%. At 2 weeks of age, these two components represent only 35% of the extracellular capacity. This change is caused by the rapid decline of vitamin C levels during the first few days of life and the increasing concentration of bilirubin which acts as an antioxidant in the first 1 to 2 weeks post-partum.64

Term labor is associated with oxidative stress for the neonate. Reported MDA levels were higher for term infants born by cesarean section than for those born by spontaneous vaginal delivery.65 66 In a case controlled study, the serum levels of lipid peroxidation products were significantly higher (110%) in 20 women during labor compared to the 20 controls (pregnant women not in labor and matched for maternal gestational age).67 On the other hand, women during term labor showed up-regulations of red blood cell GSH in cord blood. Fetal (difference in GSH concentration in umbilical vein and artery) and maternal (pre- and post-delivery) GSH concentrations were significantly lower during labor at term than in elective cesarean section.68

Perinatal Asphyxia

Perinatal asphyxia is characterized by transient hypoxia during the ischemic phase followed by reperfusion. One definition of birth asphyxia is based on the finding of three of the following four criteria: (1) pH of umbilical arterial cord blood <7.00, (2) Apgar score <4 for more than 5 min, (3) multiple organ damage, and (4) hypoxic ischemic encephalopathy (HIE).69 HIE in newborns remains a major cause of both mortality and long-term morbidity and leaves significant handicaps in 100% of survivors of severe HIE and 20% of survivors of moderate HIE.70

Hypoxia and ischemia during perinatal asphyxia give rise to an inadequate substrate supply to brain tissue, resulting in damage of neuronal cells. During tissue ischemia, an intracellular accumulation of a large amount of hypoxanthine and conversion of xanthine dehydrogenase to xanthine oxidase occur.71 Upon reperfusion, xanthine oxidase promotes formation of large quantities of O2- and H2O2, and hypoxanthine is reconverted to xanthine (Figure 5.3). The amount of ROS produced is directly dependent on oxygen as well as on hypoxanthine and other purine concentrations in tissues. Production of ROS in the early reperfusion phase plays a substantial role in the resulting brain cell damage.35

The brain of a term fetus is at higher risk of oxidative stress than the brain of a preterm fetus. This appears to result from the term brain's higher concentration of PUFAs and the greater maturity of the N-methyl-D-aspartate receptor system — a system of heterotetrameric amino acid receptors that functions as a membrane calcium channel.72 Mishra et al. demonstrated in animal studies that term brains showed higher levels of lipid peroxidation than preterm brains73 and increased activation of NMDA receptors during brain development as gestation


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