Newborn infants are susceptible to a range of problems attributed to excessive production of free radicals. Because of a higher content of antioxidants, above all bilirubin, and a lower content of oxidizable lipids, newborn plasma should be better protected against oxidation than adult plasma. To test this hypothesis, we measured the susceptibility of plasma to in vitro oxidation in microsamples (7 L) from 57 healthy newborns and 18 adults. Heparin plasma was diluted 150-fold and oxidized by 50 M Cu 2ϩ . Oxidation was monitored as an increase in sample absorbance at 234 nm. Plasma oxidizability was found to be significantly lower in newborns than in adults. Accordingly, the level of bilirubin, an important antioxidant, was significantly higher, and the level of polyunsaturated fatty acids, a major substrate of lipid peroxidation, was significantly lower in newborn plasma. In addition, plasma oxidizability correlated positively with the level of polyunsaturated fatty acids and negatively with that of bilirubin. These data indicate that plasma is better protected against oxidative stress in newborns than in adults, owing to its higher content of antioxidants like bilirubin and its lower content of oxidizable lipids. Abbreviations MUFA, monounsaturated fatty acid PUFA, polyunsaturated fatty acid SFA, saturated fatty acid TRAP, total radical-trapping ability of plasma Newborn infants, especially premature ones, are susceptible to a wide range of problems related to an excessive production of free radicals (1, 2). In utero, fetal organs are exposed to relatively hypoxic tensions, which increase abruptly after birth (3). This transition may cause oxidative injury.In healthy humans, a balance exists between oxygen-derived free radical production and their removal by antioxidants (4). In preterm infants, inadequate antioxidant defenses may contribute to the pathogenesis of some complications of prematurity. Oxygen radical injury may be a common pathogenic mechanism in several neonatal diseases. For this reason, the term "oxygen radical disease of prematurity" was proposed for intracerebral hemorrhage, bronchopulmonary dysplasia, and retinopathy in premature neonates (1).Antioxidants are therefore of critical importance in protecting newborns against oxygen toxicity. Low plasma antioxidant activity at birth has been reported to be an independent risk factor for mortality in preterm babies (5). The measured and calculated TRAP was higher in newborns than in adults (6) and declined postnatally with increasing age (7). Accordingly, the susceptibility of cord plasma to in vitro oxidation by Cu 2ϩ was significantly lower in comparison with maternal plasma (8).Increased TRAP in newborns and the decreased susceptibility of neonatal plasma to oxidation are likely related to its higher content of two potent antioxidants, namely urate and, more importantly, bilirubin, which is highly increased in newborn plasma (7, 9 -11). Similarly, higher levels of selenium and other important antioxidants such as sulfhydryl groups have also bee...