Vitamin E and preterm infants.

In evaluating vitamin E (VE) nutritional status of preterm infants, it is essential that any data should be compared with those of healthy term infants, and never with those of adults. Moreover, it should be evaluated in terms of gestational age (GA), not birth weight (BW), because placental transfer of most nutrients from mother to fetus is dependent on GA, not BW. Judging from the limited data during the last 75 years, there was no significant correlation between GA and VE concentrations in circulation or in the red blood cells (RBCs), leukocytes, and buccal mucosal cells. In addition, the oxidizability of polyunsaturated fatty acids (PUFAs) in plasma or RBCs, as targets for protection by VE chain-breaking ability, was lower in preterm infants. However, because of the minimal information available about hepatic VE levels, which is considered a key determinant of whole body VE status, the decision on whether VE status of preterm infants is comparable with that of term infants should be postponed. Clinical trials of VE supplementation in preterm infants were repeatedly undertaken to investigate whether VE reduces severity or inhibits development of several diseases specific to preterm infants, namely retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and germinal matrix hemorrhage - intraventricular hemorrhage (GMH-IVH). Most of these trials resulted in a misfire, with a few exceptions for IVH prevention. However, almost all these studies were performed from 1980s to early 1990s, in the pre-surfactant era, and the study populations were composed of mid-preterm infants with GAs of approximately 30 weeks (wks). There is considerable difference in 'preterm infants' between the pre- and post-surfactant eras; modern neonatal medicine mainly treats preterm infants of 28 wks GA or less. Therefore, these results are difficult to apply in modern neonatal care. Before considering new trials of VE supplementation, we should fully understand modern neonatal medicine, especially the recent method of oxygen supplementation. Additionally, a deeper understanding of recent progress in pathophysiology and therapies for possible target diseases is necessary to decide whether VE administration is still worth re-challenging in modern neonatal intensive care units (NICUs). In this review, we present recent concepts and therapeutic trends in ROP, BPD, and GMH-IVH for those unfamiliar with neonatal medicine. Numerous studies have reported the possible involvement of reactive oxygen species (ROS)-induced damage in relation to supplemental oxygen use, inflammation, and immature antioxidant defense in the development of both BPD and ROP. Various antioxidants effectively prevented the exacerbation of BPD and ROP in animal models. In the future, VE should be re-attempted as a complementary factor in combination with various therapies for BPD, ROP, and GMH-IVH. Because VE is a natural and safe supplement, we are certain that it will attract attention again in preterm medicine.

Long-term alpha-tocopherol supplements may improve mental development in extremely low birthweight infants.

AIM: Methods to improve the mental development of extremely low birthweight (ELBW) children are currently lacking. We assessed the effects of long-term supplementation of alpha-tocopherol on the neurological development of 259 school-aged ELBW children. METHODS: Extremely low birthweight participants were divided into three groups: group A with no alpha-tocopherol supplementation (n = 121); group B with the supplementation for <6 months (n = 104) and group C with the supplementation for more than 6 months (n = 34). We analysed the participants' data at birth and between the ages of one-and-a-half to 8 years and evaluated potential factors associated with intellectual disabilities. RESULTS: Children from group C had the best outcome. The groups' mean gestational weeks and mean ventilator days were as follows: 27.5 weeks, 16.1 days (group A); 25.7 weeks, 41.7 days (group B); and 25.1 weeks, 75.5 days (group C). Multivariate regression analysis revealed that the odds ratios for impaired mental development at 8 years were 1.5 in group B and 0.19 (p = 0.017) in group C, compared with 1.0 in group A. The association between the duration of alpha-tocopherol administration and performance intelligence quotient (IQ) was dose dependent (p = 0.03). CONCLUSION: Long-term supplementation of alpha-tocopherol appeared to improve mental development, in particular, performance IQ, in school-aged ELBW children.

Non-protein-bound transition metals and hydroxyl radical generation in cerebrospinal fluid of newborn infants with hypoxic ischemic encephalopathy.

Among various hypothetical mechanisms for the in vivo production of reactive oxygen species, transition metal-catalyzed reactions in cooperation with a biologic reducing agent like ascorbic acid or superoxide may be some of the most important. In the present study, we retrospectively examined the existence of non-protein-bound metal ions, an essentially hazardous pro-oxidant form of various transition metals, and the occurrence of metal-catalyzed reactive oxygen species production in cerebrospinal fluid (CSF) of 10 infants with hypoxic ischemic encephalopathy (HIE) subsequent to perinatal asphyxia and 12 control infants within 72 h of birth. Non-protein-bound iron was detected in eight out of 10 CSF samples from the HIE infants and its level was significantly correlated with Sarnat's clinical stage, whereas none of the control infants had detectable non-protein-bound iron levels. Non-protein-bound copper was below the detection limit in all CSF samples from both groups. Ascorbic acid was significantly increased in the CSF of HIE infants when compared with that of controls (means, 664.9 versus 449.4 microM, p = 0.008). ortho-Tyrosine and meta-tyrosine, which are highly specific and sensitive markers of protein oxidation induced by hydroxyl radicals, were significantly higher in HIE infants than in controls when evaluated by the ratio relative to their source amino acid, phenylalanine [means, 110.5 versus 75.4, p = 0.018 for ortho-tyrosine/phenylalanine; 104.6 versus 67.7 (nM/microM x 10(2)), p = 0.048 for meta-tyrosine/phenylalanine]. Both ratios were significantly correlated with non-protein-bound iron, but not with ascorbic acid. Our preliminary observations provide direct evidence that hydroxyl radicals are generated in the CNS during asphyxiation. Iron chelation therapy could be worth developing as a neuroprotective strategy for perinatal asphyxia.