Oxygen Toxicity at Birth: the Pieces Are Put Together

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Oxygen Toxicity at Birth: The Pieces Are Put Together

A review of: Naumburg E, Bellocco R, Cnattingius S, et al. 2002 Supplementary oxygen and risk of childhood lymphatic leukaemia. Acta Paediatr 91:1328–1333; and Vento M, Asensi M, Sastre J, et al. 2003 Oxidative stress in asphyxiated term infants resuscitated with 100% oxygen. J Pediatr 142:240–246

ECENTLY NAUMBURG ET al. (1) pre- development, as well as cell death, both OLA DIDRIK SAUGSTAD R sented data indicating there is an apoptosis and necrosis. Since a brief oxy- association between a brief exposure of neonatal research (3–5). Toxicity may be gen exposure at birth seems to induce rel- pure oxygen at birth and childhood lym- the end result because our patients are so atively long lasting oxidative stress, the phatic leukemia. In a population based often exposed to augmented oxidative results from Vento et al. therefore might case-control study, the authors searched stress either caused by oxygen, inflamma- give us a key to understand the results of for predisposing factors exerting their tion/infections, or low oxidative defense. the Swedish study. Although the toxic na- influence early in life. Five hundred sev- In this context, another study is of par- ture of high oxygen concentrations has enty-eight children with lymphatic leu- ticular interest. Vento et al previously have been known for more than two centuries, kemia were identified through the Swed- demonstrated that resuscitation at birth only recently an understanding is emerging ish Cancer Register and each matched with 100% oxygen by contrast to resusci- that oxygen might be more toxic than be- with one control randomly selected from tation with room air, triggers an increased lieved up to now (8). Therefore any possi- the Swedish Birth Register. oxidative stress at least four weeks postna- ble mutagenic, carcinogenic or other long- Fortunately, no association was found tally (6). In a recent study, this same group term detrimental effects of oxygen between childhood lymphatic leukemia of investigators analyzed these aspects in exposure immediately after birth urgently and birth related factors such as mode of more detail, from birth until 10 min after need to be investigated. delivery, birth weight, gestational age, clinical stabilization in 51 asphyxiated small or large for gestational age, pulmo- newborn infants resuscitated with room air REFERENCES nary disorders, or congenital malforma- and 55 with 100% oxygen (7). Pure oxy- tions. Low Apgar scores (1 min Ͻ 4, or gen delays the first cry and breath, this was 1. Naumburg E, Bellocco R, Cnattingius S, Jonzon A, Ekbom A 2002 Supplementary oxygen and risk of 5minϽ 6) did not give significant in- once more confirmed and should by now childhood lymphatic leukaemia. Acta Paediatr creased risk for developing leukemia. By be considered an established fact. Hence, 91:1328–1333 2. Saugstad OD, Ramji S, Vento M 2003 Neonatal mor- contrast, oxygen given by mask resulted duration of supportive efforts such as oxy- tality is lower in depressed newborn infants if resusci- in an odds ratio (OR) of 2.87 (95% CI ϭ gen supplementation is prolonged in in- tation is performed with ambient air instead of pure oxygen. A meta-analysis. Pediatr Res 53:376A 1.21–6.82). When these data were split fants given pure oxygen. Needless to say, 3. Saugstad OD 1988 Hypoxanthine as an indicator of up into 0–2 min and 3–10 min oxygen the babies resuscitated with pure oxygen hypoxia: its role in health and disease through free Ϯ radical production. Pediatr Res 23:143–150 exposure an OR for the latter group of were hyperoxemic with a paO2 of 126 4. Fellman V, Raivio KO 1997 Reperfusion injury as the 3.54 (95% CI ϭ 1.16–10.80) was found. 22 mm Hg versus the normal level of 72 Ϯ mechanism of brain damage after perinatal asphyxia. Pediatr Res 41:599–606 Oxygen exposure later in the neonatal 7 mm Hg in the room air group at 5-6 min 5. Jankov RP, Negus A, Tanswell AK 2001 Antioxidants period did not reveal an increased risk of age and still 10 min after stabilization a as therapy in the newborn: some words of caution. Pediatr Res 50:681–687 for childhood lymphatic leukemia. higher paO2 was detected in the former 6. Vento M, Asensi M, Sastre J, García-Sala F, Pallardó Although these findings must be con- group. On this basis, the authors calculated FV, Viña J 2001 Resuscitation with room air instead of 100% oxygen prevents oxidative stress in moderately trolled preferably by larger, prospective that on average infants resuscitated with asphyxiated term neonates. Pediatrics 107:642–647 studies, they still are alarming. Espe- 100% oxygen received 350 mL more ox- 7. Vento M, Asensi M, Sastre J, Lloret A, García-Sala F, Pallardó FV, Viña J 2003 Oxidative stress in asphyx- cially on the basis that it now becomes ygen than those given room air. Oxidized iated term infants resuscitated with 100% oxygen. J Pe- more and more clear that oxygen admin- glutathione was higher and reduced gluta- diatr 142:240–246 8. Saugstad OD 2001 Is oxygen more toxic than currently istration is not needed routinely for new- thione lower in the oxygen than in the believed? Pediatrics 108:1203–1205 born resuscitation and might even in- room air group demonstrating higher oxi- crease neonatal mortality (2). dative stress in the former group. Department of Pediatric Research How can such a brief exposure to oxy- Elevated oxidative stress can alter signal University of Oslo gen be toxic? Previous review articles in transduction, DNA and RNA synthesis, Rikshospitalet, 0027 Oslo, Norway Pediatric Research have described the crit- protein synthesis, enzyme activation, and e-mail: [email protected] ical aspects of oxidative stress and impor- directly influence the cell cycle. Oxidative DOI: 10.1203/01.PDR.0000103390.01854.0E tant clues might be found in perinatal/ stress might influence both cell growth and

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