Background-Blood transfusion has been recognised as a risk factor for the development of retinopathy of prematurity (ROP) or chronic lung disease (CLD) in preterm infants, but the precise mechanism involved is not understood. Aim-To investigate the level of nontransferrin bound "free" iron, which has the potential to promote the generation of reactive oxygen species, and its redox status in the plasma of preterm infants immediately before and after blood transfusion. Methods-Twenty one preterm infants with a median gestational age and birth weight of 27 weeks and 1021 g respectively were prospectively enrolled in the study. Sixteen of the 21 infants developed ROP and/or CLD. The infants were transfused with concentrated red blood cells at a median age of 32 days. The plasma concentration of total bleomycin detectable iron (BDI) was measured and also the ferrous iron (Fe 2+ ) activity by bleomyciniron complex dependent degradation of DNA. Results-Even before blood transfusion, BDI was detectable in one third of the blood samples, and all but one sample had ferrous iron activity. After transfusion, both BDI and ferrous iron activity were significantly increased, in contrast with the situation in full term infants. Plasma ascorbic acid (AA) concentration was significantly decreased after blood transfusion, whereas the level of its oxidation product, dehydroascorbic acid (DHAA), and the DHAA/AA ratio were significantly increased compared with before the transfusion. The activity of plasma ferroxidase, which converts iron from the ferrous to the ferric state, was appreciably decreased in preterm infants, as expected from their very low plasma caeruloplasmin concentration. Conclusions-Plasmanon-transferrin bound iron was significantly increased in preterm infants after blood transfusion and existed partly in the ferrous form, because of the low ferroxidase activity and the reduction of ferric iron (Fe 3+ ) by ascorbic acid. This finding was specific to preterm infants and was not observed in full term infants after blood transfusion. Non-transferrin bound "free" iron may catalyse the generation of reactive oxygen species, which may be responsible for the clinical association of blood transfusion with ROP and CLD. (Arch Dis Child Fetal Neonatal Ed 2001;84:F188-F193)

Circulating KL-6 is a specific indicator of pulmonary injury affecting the alveolar epithelium and interstitium. Our preliminary study suggested the usefulness of plasma KL-6 as a marker of bronchopulmonary dysplasia (BPD). To confirm the diagnostic value of KL-6 for BPD as well as to determine the reference range, we conducted a larger prospective study in 135 preterm infants Ͻ32 wk GA. Among the infants without oxygen dependence at a postconceptional age of 36 wk, the plasma KL-6 level showed no significant association with GA at any time. Among 42 infants Ͻ28 wk GA, plasma KL-6 levels were significantly higher in those with moderate/ severe BPD compared with those with no/mild BPD. A plasma level of 199 U/mL at 1 wk or 232 U/mL at 2 wk was an excellent predictor of moderate/severe BPD Ͻ28 wk GA (positive predictive value of 83% and 80%, respectively). Unlike nonspecific markers of inflammation or fibrosis, KL-6 objectively reflects the severity of pulmonary injury irrespective of the treatment or the radiographic changes. Therefore, not only as a good marker, measurement of KL-6 may also help to provide new insights into the pathogenesis of BPD.

Among various hypothetical mechanisms for the in vivo production of reactive oxygen species, transition metalcatalyzed 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 M, p ϭ 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 ϭ 0.018 for ortho-tyrosine/phenylalanine; 104.6 versus 67.7 (nM/M ϫ 10 2 ), p ϭ 0.048 for meta-tyrosine/phenylalanine]. Both ratios were significantly correlated with non-proteinbound 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. Abbreviations ROS, reactive oxygen species HIE, hypoxic ischemic encephalopathy CSF, cerebrospinal fluid NPBI, non-protein-bound iron NPBC, non-protein-bound copper o-Tyr, ortho-tyrosine m-Tyr, meta-tyrosine Phe, phenylalanine AA, ascorbic acid DHAA, dehydroascorbic acid UA, uric acid GC/MS, gas chromatography-mass spectrometry Advanced perinatal and obstetric management cannot yet prevent brain damage in newborn infants after perinatal asphyxia. Current therapeutic strategies for HIE occurring after perinatal asphyxia are not specific and are only supportive. Numerous studies have suggested that free radicals could have a key role in causing hypoxic ischemic damage to the brain, especially during the reoxygenation/reperfusion phase (1, 2).Among various hypothetical mechanisms for the production of ROS in living organisms, transition metal-catalyzed reactions may be some of the most important (3). When transition metals like iron or copper exist in their non-protein-bound "free" form in vivo, these metals can convert less reactive radicals to more reactive species. Thus, the human body is normally very careful to sequestrate these metal ions to be incorporated into specific me...

No abstract

No abstract