Oxidative Stress In Preterm Infants Research Articles

TO THE ISSUE OF THE DEVELOPMENT AN ALGORITHM FOR A DIFFERENTIATED APPROACH TO THE MANAGEMENT OF PERSISTENT PULMONARY HYPERTENSION IN PREMATURE INFANTS

The management of premature infants with persistent pulmonary hypertension (PPH) remains a major problem in modernneonatology. In recent years, scientifi c studies have identifi ed the role of oxidative stress (OS) in the development and course of PPH. The reserve for reducing mortality and optimizing the management of premature infants with respiratory distress syndrome (RDS) and asphyxia is the development of an algorithm for a diff erentiated approach to the management of PPH in premature infants, taking into account the severity and dynamics of OS, and its implementation into clinical practice.
 Aim of the study. To increase the eff ectiveness of management of premature infants with persistent pulmonary hypertension with asphyxia and respiratory distress syndrome based on the development of an algorithm for a diff erentiated approach to the management of pulmonary hypertension taking into account the levels of oxidative stress as determined by urinary 8-hydroxy-2-deoxyguanosine (8-OHdG).Material and methods. 100 premature infants between 26/1-34/6 weeks of gestation were included in the study: groupI consisted of 50 infants with RDS, group II – 50 newborns with RDS associated with perinatal asphyxia. The presence and severity of PPH was determined in all infants on the fi rst and third to fi fth day of life by echocardiography (EchoCG), and quantitative determination of 8-OHdG level (ng/ml) – in 44 infants on the fi rst day, and in dynamics – on the third to fi fth day of life by enzyme- linked immunosorbent assay (ELISA). For radiographic evaluation of PPH, all infants underwent chest radiography with determination of Moore’s, Schwedel’s and cardiothoracic index (CTI). The research was conducted in compliance with bioethical requirements as part of the planned scientifi c work of the Department (state registration number 0122U000025).Results. It was found that the characteristics of pulmonary hypertension in premature infants with RDS were signifi cantly lower levels of mean pressure in the pulmonary artery (mPAP) on the fi rst and 3-5 days of life than in children with perinatal asphyxia. It was noted that the factors with high diagnostic signifi cance determining the occurrence of persistent pulmonary hypertension are: birth weight <1500 g; presence of perinatal asphyxia; low Apgar score on the 1st (1-3 points) and on the 5th minute of life (<7 points); gestational age <30 weeks; non-appropriateness for gestational age; male sex. Furthermore, it was found that urinary 8-OHdG levels as a biomarker of OS in preterm infants with RDS and perinatal asphyxia correlated with mPAP on the fi rst and third to fi fth days of life, and that urinary 8-OHdG levels had a high diagnostic value for determining the risk of developing severe PPH on the third to fi fth days of life. The diagnostic signifi cance of the data of the comprehensive radiological assessment of PPH – the radiological indices of Moore, Schwedel, CTI for the development of severe PPH was analyzed and the correlations between the indices and mPAP and between the indices and the level of 8-OHdG were established. The Schwedel index showed the highest reliability in all cases.Conclusion. On the basis of scientifi cally established relationships between clinical, laboratory, radiological and genderaspects of premature infants with perinatal pathology and the identifi ed diagnostic and prognostic values of urinary 8-OHdG, an algorithm for a diff erentiated approach to the management of PPH was developed. Determination of the degree of OS and mPAP in premature infants allows us to adjust and individualize the tactics of respiratory support in the management of premature infants, thus improving the quality of medical care of premature infants with RDS and perinatal asphyxia. In prematurely born children in perinatal centers, additional determination of the severity of RDS based on the level of 8-OHdG in urine allows to predict the adverse course of PPH and the development of complications: bronchopulmonary dysplasia, intraventricular hemorrhage III-IV grade, retinopathy II-III grade, hearing impairment, hypoxic- ischemic lesions of the central nervous system II-III grade in prematurely born children.

Hypoxemia events in preterm neonates are associated with urine oxidative biomarkers.

Intermittent hypoxemia (IH) events are common in preterm neonates and are associated with adverse outcomes. Animal IH models can induce oxidative stress. We hypothesized that an association exists between IH and elevated peroxidation products in preterm neonates. Time in hypoxemia, frequency of IH, and duration of IH events were assessed from a prospective cohort of 170 neonates (<31 weeks gestation). Urine was collected at 1 week and 1 month. Samples were analyzed for lipid, protein, and DNA oxidation biomarkers. At 1 week, adjusted multiple quantile regression showed positive associations between several hypoxemia parameters with various individual quantiles of isofurans, neurofurans, dihomo-isoprostanes, dihomo-isofurans, and ortho-tyrosine and a negative correlation with dihomo-isoprostanes and meta-tyrosine. At 1 month, positive associations were found between several hypoxemia parameters with quantiles of isoprostanes, dihomo-isoprostanes and dihomo-isofurans and a negative correlation with isoprostanes, isofurans, neuroprostanes, and meta-tyrosine. Preterm neonates experience oxidative damage to lipids, proteins, and DNA that can be analyzed from urine samples. Our single-center data suggest that specific markers of oxidative stress may be related to IH exposure. Future studies are needed to better understand mechanisms and relationships to morbidities of prematurity. Hypoxemia events are frequent in preterm infants and are associated with poor outcomes. The mechanisms by which hypoxemia events result in adverse neural and respiratory outcomes may include oxidative stress to lipids, proteins, and DNA. This study begins to explore associations between hypoxemia parameters and products of oxidative stress in preterm infants. Oxidative stress biomarkers may assist in identifying high-risk neonates.

Clinical significance of correlation between persistent pulmonary hypertension and 8-hydroxy-2-desoxyguanosine level in premature newborns.

Persistent pulmonary hypertension is a problem that leads to high morbidity and mortality in preterm infants. In clinical studies, oxidative stress (OS) contributes to the development of pulmonary hypertension (PH). The most specific biomarker of OS in preterm infants is urinary 8-hydroxy-2-deoxyguanosine (8-OHdG).The aim of the study was to determine the clinical correlation between the value of 8-OHdG and the level of a mean pressure in the pulmonary artery (mPAP) in premature infants with respiratory distress syndrome (RDS) and asphyxia in the early neonatal period. Determination of the urinary 8-OHdG value and PH in 96 premature infants born at gestational age of 26-32 weeks on the 1st and the 3rd-5th days of life in two groups: group I -52 children with respiratory distress syndrome; II -44 children with RDS associated with perinatal asphyxia. The 2nd group of children had higher average mPAP level, mmHg, both in the 1st and in the 3rd-5th day of life compared with the 1st group. The value of the urinary 8-OHdG correlated with the manifestation of PH that required prolonged respiratory support in group II. Perinatal asphyxia in preterm infants with RDS on the 1st day of life complicates the course of PH, as indicated by a higher level of the urinary 8-OHdG and correlated to mPAP. Gender characteristics of the dynamics of 8-OHdG levels in children with perinatal pathology reveal reduced adaptability and reactivity of boys to OS at birth.

Antenatal and Postnatal Sequelae of Oxidative Stress in Preterm Infants: A Narrative Review Targeting Pathophysiological Mechanisms.

The detrimental effects of oxidative stress (OS) can start as early as after conception. A growing body of evidence has shown the pivotal role of OS in the development of several pathological conditions during the neonatal period, which have been therefore defined as OS-related neonatal diseases. Due to the physiological immaturity of their antioxidant defenses and to the enhanced antenatal and postnatal exposure to free radicals, preterm infants are particularly susceptible to oxidative damage, and several pathophysiological cascades involved in the development of prematurity-related complications are tightly related to OS. This narrative review aims to provide a detailed overview of the OS-related pathophysiological mechanisms that contribute to the main OS-related diseases during pregnancy and in the early postnatal period in the preterm population. Particularly, focus has been placed on pregnancy disorders typically associated with iatrogenic or spontaneous preterm birth, such as intrauterine growth restriction, pre-eclampsia, gestational diabetes, chorioamnionitis, and on specific postnatal complications for which the role of OS has been largely ascertained (e.g., respiratory distress, bronchopulmonary dysplasia, retinopathy of prematurity, periventricular leukomalacia, necrotizing enterocolitis, neonatal sepsis). Knowledge of the underlying pathophysiological mechanisms may increase awareness on potential strategies aimed at preventing the development of these conditions or at reducing the ensuing clinical burden.

DIAGNOSTIC ASPECTS OF PERSISTENT PULMONARY HYPERTENSION IN PREMATURE INFANTS WITH OXIDATIVE STRESS

Introduction. Persistent pulmonary hypertension is a problem that leads to high morbidity and mortality in preterminfants. In clinical studies, oxidative stress (OS) contributes to the development of pulmonary hypertension (PH). Themost specific biomarker of OS in preterm infants is urinary 8-hydroxy-2-deoxyguanosine (8-OHdG).The aim of the study. To determine the clinical and diagnostic relationship between the value of 8-hydroxy-2-deoxyguanosine and the level of mean trunk pulmonary artery pressure in premature infants with respiratory distresssyndrome and asphyxia in the early neonatal period.Material and methods. Determination of 8-OHdG (ng/ml) by enzyme-linked immunosorbent assay (ELISA) andPH by echocardiography (EchoCG) in 60 premature infants at 26-32 weeks of gestation at 1 and 3-5 days of life in2 groups: I - 32 children with respiratory distress syndrome (RDS); II - 28 children with RDS in combination withperinatal asphyxia.Results. The average value of pulmonary artery pressure (mmHg) in the group II of children in comparison withgroup I was higher both in 1 and 3-5 days of life. The level and dynamics of 8-OHdG correlated with the severity of PH,which required longer respiratory support in group II. Sexual dimorphism of 8-OHdG levels and dynamics was noted.Conclusions. Perinatal asphyxia in preterm infants with RDS on the 1st day of life complicates the course of PH, asindicated by a higher level of the urinary 8-OHdG and correlated to mPAP. Gender characteristics of the dynamics of8-OHdG levels in children with perinatal pathology reveal reduced adaptability and reactivity of boys to OS at birth.Dynamics in the form of a decrease in the level of 8-OHdG in the urine is a favorable prognostic sign of pulmonaryhypertension. Gender characteristics of the dynamics of 8-OHdG levels in children with perinatal pathology revealreduced adaptability and reactivity of boys to OS at birth.

Patent ductus arteriosus and oxidative stress in preterm infants: a narrative review.

The role of oxygen, reactive oxygen species (ROS), and isoprostanes (IsoPs) in regulating patency and closure of patent ductus arteriosus (PDA) have been studied in preterm infants. Also the possible correlation between a hemodynamically significant PDA and its pharmacological treatment with oxidative stress has been investigated. The National Library of Medicine (MEDLINE) database was searched without time limits. Available data demonstrate that free radicals are not always harmful and that ROS and IsoPs play a relevant role in DA closure. On the other hand, a hemodynamically significant PDA can cause oxidative stress and this can partially explain its association with other complications of prematurity related to oxidative stress, such as bronchopulmonary dysplasia (BPD), intraventricular haemorrhage (IVH), and necrotizing enterocolitis (NEC). Some drugs used for pharmacological closure, such as ibuprofen, also have antioxidant effects, and the closure of PDA can restore a proper tissue oxygenation and the balance between pro-oxidant and antioxidant factors. These data support the importance of the relationship between PDA and oxidative stress whose understanding increase our awareness when we approach this prematurity complication in the clinical practice. Further studies might assess the reliability of ROS as possible biomarkers of the risk of developing a hsPDA.

Predictors of adverse outcomes in preterm infants in the early neonatal period

Introduction. Extremely and very preterm infants are a special cohort of newborns with inherent functional immaturity and specific pathological conditions which are accompanied by hypoxia, reoxygenation, tissue hypoperfusion, increased risk of oxidative stress. Premature infants are prone to oxidative deterioration which plays a key role in the pathogenesis of severe diseases such as respiratory distress syndrome, necrotizing enterocolitis, periventricular leukomalacia, patent ductus arteriosus, bronchopulmonary dysplasia, and retinopathy of prematurity.Objective. The aim of the research was to estimate the predictors of adverse outcomes in preterm infants with gestational age less than 32 weeks in the early neonatal period by assessment of oxidative stress markers.Material and methods. A total amount of 46 preterm infants with gestational age less than 32 weeks in the early neonatal period were included in the research. According to the results of early outcomes newborns were divided into two groups: I group – 12 infants with adverse outcomes and II group - 34 preterm infants with favorable outcomes. Twenty healthy newborns were included in the control group (III group). Clinical examination of infants and laboratory determination of oxidative stress markers were done for all participants.Results. Asphyxia, early onset sepsis, intraventricular hemorrhage in preterm infants less than 32 weeks of gestation had increased the risk of mortality in the early neonatal period. The level of 8-isoprostane, ROS, TBP, LHP was significantly higher in neonates with adverse outcomes (group I). It was found that the level of 8-isoprostane more than 595.4 mg/ml, ROS level above 0.483 IU, TBP higher than 5.14 μmol/l and LHP levels above 5.91 U/m were associated with unfavorable outcomes in the early neonatal period. Decreased activity of the antioxidant system (catalase, SOD) increases the risk of early neonatal mortality.Conclusions. The activation of oxidative stress in preterm infants may be a predictor of adverse outcomes in the early neonatal period.

Oxidative Stress in Preterm Infants: Overview of Current Evidence and Future Prospects.

Preterm birth (PTB), defined as parturition prior to 37 weeks of gestation, is the leading cause of morbidity and mortality in the neonatal population. The incidence and severity of complications of prematurity increase with decreasing gestational age and birthweight. The aim of this review study is to select the most current evidence on the role of oxidative stress in the onset of preterm complication prevention strategies and treatment options with pre-clinical and clinical trials. We also provide a literature review of primary and secondary studies on the role of oxidative stress in preterm infants and its eventual treatment in prematurity diseases. We conducted a systematic literature search of the Medline (Pubmed), Scholar, and ClinicalTrials.gov databases, retroactively, over a 7-year period. From an initial 777 articles identified, 25 articles were identified that met the inclusion and exclusion criteria. Of these, there were 11 literature reviews: one prospective cohort study, one experimental study, three case-control studies, three pre-clinical trials, and six clinical trials. Several biomarkers were identified as particularly promising, such as the products of the peroxidation of polyunsaturated fatty acids, those of the oxidation of phenylalanine, and the hydroxyl radicals that can attack the DNA chain. Among the most promising drugs, there are those for the prevention of neurological damage, such as melatonin, retinoid lactoferrin, and vitamin E. The microbiome also has an important role in oxidative stress. In conclusion, the most recent studies show that a strong relationship between oxidative stress and prematurity exists and that, unfortunately, there is still little therapeutic evidence reported in the literature.

Feeding practice influences gut microbiome composition in very low birth weight preterm infants and the association with oxidative stress: A prospective cohort study

Knowledge about the development of the preterm infant gut microbiota is emerging and is critical to their health. Very-low-birth-weight (VLBW; birth weight, <1500 g) infants usually have special dietary needs while showing increased oxidative stress related to intensive care. This prospective cohort study assessed the effect of feeding practice on gut microbiome development and oxidative stress in preterm infants.Fecal samples were collected from each infant in the early (1–2 weeks of enteral feeding) and late (2–4 weeks of enteral feeding) feeding stages. We performed high-throughput sequencing of V3–V4 regions of the 16S rRNA gene to analyze the fecal microbiome composition of 20 VLBW preterm infants and to determine the association of gut bacterial composition with feeding practice using an oxidative stress marker (urinary F2-isoprostane). Our results showed that feeding practices in the late stage significantly influenced the gut microbiome composition and oxidative stress in preterm infants. Preterm infants fed human milk + human milk fortifier and only formula diets showed a significant increase in F2-isoprostane levels (P < 0.05) compared with those fed human milk + formula diet. The gut microbiome of the infants fed the human milk + Human milk fortifier diet showed the lower relative abundance of Veillonella (P < 0.05) compared with that of the infants fed the human milk + formula diet. The gut microbiome of the infants fed the only formula diet showed the lowest microbial diversity and the highest relative abundance of Terrisporobacter (P < 0.05) compared with the gut microbiome of the infants fed the other diets. Correlation network analysis showed that urinary F2-isoprostane level was positively correlated with Terrisporobacter and Enterobacteriaceae abundance (P < 0.05) in the preterm infants.In conclusion, these data suggest that feeding practice affects the bacterial diversity and composition in the gut microbiome and is associated with oxidative stress in VLBW preterm infants.

Source and Quality of Enteral Nutrition Influences Oxidative Stress in Preterm Infants: A Prospective Cohort Study.

Preterm infants are at risk of oxidative stress from neonatal intensive care interventions. 8-Oxo-2'-deoxyguanosine (8-oxodG), generated by oxygen radical attack on DNA, is a potential marker of oxidative stress. The aim of the present study was to investigate the impact of quality and source of enteral nutrition (EN) on renal excretion of 8-oxodG in preterm infants. Spontaneous urine samples were collected on postnatal days 26-31 in 33 preterm infants. Infants were fed either breast milk (BM), formula (FM), or BM/FM mixtures. Daily iron (Fe) supplementation was started day 28 ± 1 postnatally. 8-oxodG was determined by highperformance liquid chromatography-electrochemical detection (HPLC-EC). The 8-oxodG/creatinine ratio was significantly higher in infants fed FM vs FM/BM (38.7 ± 28.7 vs 16.7 ± 12.2 nmol 8-oxodG/mmol creatinine, P < 0.0001) or BM (11.6 ± 10.4 nmol 8-oxodG/mmol creatinine, P < 0.0001). There was no significant effect of Fe supplementation (P = 0.547). 8-OxodG excretion showed significant interindividual variation but was similar within pairs of twins. Quality and source of EN seem to influence oxidative stress in preterm infants. The underlying pathophysiological mechanism is unclear and needs further investigation. It may be speculated that other mechanisms than Fe supplementation contribute to oxidative stress, such as cow's milk protein-mediated up-regulation of the intestinal inflammatory cascade.

Oxidative Stress and Necrotizing Enterocolitis: Pathogenetic Mechanisms, Opportunities for Intervention, and Role of Human Milk.

This review will examine the role of oxidative stress (OS) in the pathogenesis of necrotizing enterocolitis (NEC) and explore potential preventive and therapeutic antioxidant strategies. Preterm infants are particularly exposed to OS as a result of several perinatal stimuli and constitutive defective antioxidant defenses. For this reason, OS damage represents a contributing factor to several complications of prematurity, including necrotizing enterocolitis (NEC). Being NEC a multifactorial disease, OS may act as downstream component of the pathogenetic cascade. To counteract OS in preterm infants with NEC, several antioxidant strategies have been proposed and different antioxidant compounds have been experimented. It is well known that human milk (HM) is an important source of antioxidants. At the same time, the role of an exclusive HM diet is well recognized in the prevention of NEC. However, donor HM (DHM) processing may impair antioxidant properties. As DHM is becoming a common nutritional intervention for high risk PI, the antioxidant status of preterm and DHM and potential ways to preserve its antioxidant capacity may merit further investigation.

Ventilator-induced lung injury, proinflammatory cytokines, and oxidative stress in preterm infants with respiratory distress syndrome

Ventilator-induced lung injury, proinflammatory cytokines, and oxidative stress in preterm infants with respiratory distress syndrome

Placental histological examination and the relationship with oxidative stress in preterm infants

BackgroundPrenatal conditions of enhanced oxidative stress (OS) linked to inflammation or hypoxia have been associated with impaired fetal growth and preterm delivery. Little is known regarding biomarkers of OS in the cord blood of preterm infants and placental histological patterns. ObjectivesTo test the hypothesis that placental lesions indicating chorioamnionitis (CA) or vascular underperfusion (VU) are associated with increased OS in the offspring. Methods120 neonates born below 29+6 weeks of gestational age (GA) were enrolled. Histological characteristics of placentas from their mothers were classified as normal (CTRL group), histological CA (HCA) and vascular underperfusion (VU). Serum concentrations of isoprostanes (IsoPs), non-protein bound iron (NPBI) and advanced oxidative protein products (AOPP), were determined in cord blood. ResultsIsoPs, NPBI and AOPP were significantly increased in HCA group compared to CTRL group. The multivariable regression model, adjusted for GA, maternal age, parity, maternal diabetes, maternal obesity and presence/absence of fetal growth restriction (FGR), showed a significant association between the presence of HCA and increased OS biomarkers levels in cord blood (IsoPs: p = 0.006; NPBI: p = 0.014; AOPP: p = 0.007). Placental VU lesions were significantly associated with higher umbilical IsoPs, NPBI and AOPP levels (IsoPs: p = 0.008; NPBI: p = 0.002; AOPP: p = 0.040). In the cases of placental VU lesions associations were also found between high AOPP levels and low GA (p = 0.002) and the presence of fetal growth restriction (p = 0.014). ConclusionsPlacental lesions indicating inflammation or impaired perfusion are associated with higher cord blood levels of OS biomarkers explaining the fetal susceptibility to oxidative injury and the need of antioxidant protection.

Role of oxidative stress in preterm infants with bronchopulmonary dysplasia after exposure to chorioamnionitis

Inflammation is one of the main causes of preterm birth, frequently associated to intrauterine infection or chorioamnionitis. Oxidative stress is involved in preterm birth. On the one hand, reactive oxygen species are released by inflammatory cells against infection; on the other hand it is responsible of placental tissue damage after chorioamnionitis. Because of improvement in obstetric and perinatal care, survival rate in preterm births has increased, leading to changes in pathology of several processes, such as bronchopulmonary dysplasia. Bronchopulmonary dysplasia is a multifactorial entity which is consequence of multiple mechanisms, including perinatal inflammation and oxygen free radicals. Preterm newborn is very susceptible to chronic lung damage because of both, low antioxidant capacity, and exposure to high oxygen fractions during postnatal life. Modest lung oxidative stress damage after exposure to fetal endotoxin in premature newborns has been shown. Postnatal injury is needed to amplify the intrauterine inflammatory damage. Cell death induction by reactive oxygen species has been suggested as mechanism of lung damage. Several antioxidant therapies have been used in experimental studies in order to reduce or prevent bronchopulmonary dysplasia. So far, care is needed to standardize its use, because of its undesirable effects on inflammatory defense and development.

Role of oxidative stress in preterm infants with bronchopulmonary dysplasia after exposure to chorioamnionitis

Role of oxidative stress in preterm infants with bronchopulmonary dysplasia after exposure to chorioamnionitis

Resuscitating preterm infants with 100% oxygen is associated with higher oxidative stress than room air.

The starting fraction of inspired oxygen for preterm resuscitation is a matter of debate, and the use of room air in full-term asphyxiated infants reduces oxidative stress. This study compared oxidative stress in preterm infants randomised for resuscitation with either 100% oxygen or room air titrated to internationally recommended levels of preductal oxygen saturations. Blood was collected at birth, two and 12 hours of age from 119 infants <32 weeks of gestation randomised to resuscitation with either 100% oxygen (n = 60) or room air (n = 59). Oxidative stress markers, including advanced oxidative protein products (AOPP) and isoprostanes (IsoP), were measured with high-performance liquid chromatography and mass spectrometry. Significantly higher levels of AOPP were found at 12 hours in the 100% oxygen group (p < 0.05). Increases between two- and 12-hour AOPP (p = 0.004) and IsoP (p = 0.032) concentrations were significantly higher in the 100% oxygen group. Initial resuscitation with room air versus 100% oxygen was associated with lower protein oxidation at 12 hour and a lower magnitude of increase in AOPP and IsoP levels between two and 12 hours of life. Correlations with clinical outcomes will be vital to optimise the use of oxygen in preterm resuscitation.

Antioxidants and Biomarkers of Oxidative Stress in Preterm Infants with Symptomatic Patent Ductus Arteriosus.

Immature antioxidant and oxygen-sensing mechanisms are involved in the pathogenesis of the patent ductus arteriosus (PDA). We conducted a prospective, observational, pilot study to test the hypothesis that antioxidant activity is low at birth in preterm infants at risk for symptomatic PDA. Blood and urine samples were collected within 24 to 48 hours of life in 53 preterm infants (≤32 weeks' gestation) who developed early PDA symptoms and in 30 term (≥37 weeks' gestation) control infants. Thirty preterm infants developed hemodynamically significant PDA (hsPDA) and required pharmacologic treatment and/or PDA ligation. For these infants, blood and urine samples were also collected at 24 hours posttreatment. Samples were analyzed for biomarkers of antioxidant activity, oxidative stress, and lipid peroxidation. At 24 to 48 hours after birth, plasma superoxide dismutase (SOD), urinary catalase, and plasma and urinary 8-isoPGF2α were significantly lower in preterm infants who developed hsPDA. Plasma 8-isoPGF2α levels rebounded post-PDA treatment, while urinary prostaglandin E2, plasma and urinary thromboxane B2, and plasma SOD declined. The antioxidant status is low in preterm infants at risk for developing hsPDA. SOD may be a key antioxidant regulating functional ductus arteriosus closure. Therefore, low levels may result in persistence of a hsPDA.

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Adduct of Malondialdehyde to Hemoglobin: A New Marker of Oxidative Stress That Is Associated with Significant Morbidity in Preterm Infants

Preterm infants (PT) are particularly exposed to oxidative stress (OS), and a blood-sparing marker, the malondialdehyde adduct to hemoglobin (MDA-Hb), may be useful to accurately assess OS-related neonatal morbidity. In a prospective study, MDA-Hb concentrations were assessed in two groups of PT, one with and one without severe neonatal morbidity as estimated by a composite index of severe morbidity (ISM). All PT born in a single tertiary care NICU (<32 weeks and birth weight <1500 g) were consecutively included. MDA-Hb and blood glutathione (GSH) concentrations were measured by liquid chromatography-mass spectrometry during the first 6 weeks of life. Linear regressions and a multilevel model were fitted to study the relationship between MDA-Hb or GSH and ISM. Of the 83 PT (mean ± SD: 28.3 ± 2 weeks, 1089 ± 288 g), 21% presented severe neonatal morbidity. In the multivariate model, MDA-Hb concentrations were significantly higher in the ISM+ group than in the ISM– group during the first 6 weeks of life (P = 0.009). No significant difference in GSH concentrations was observed between groups (P = 0.180). MDA-Hb is a marker of interest for estimating oxidative stress in PT and could be useful to evaluate the impact of strategies to improve perinatal outcomes.

610 Total Parenteral Nutrition as a Source of Oxidant Load Leading to Bronchopulmoanry Dyplasia

BackgroundImmaturity of antioxidant defense coupled with oxidant load is suspected to induce the development of bronchopulmonary dyplasia (BPD) in premature infants. Peroxide load from total parenteral nutrition (TPN) is associated...