Neonatal diseases and oxidative stress in premature infants: an integrative review

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UAW, Upper airways; ROS, Reactive oxygen species." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Cláudio D'Elia, David Gozal, Oliviero Bruni, Ekaterini Goudouris, Miguel Meira e Cruz" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Cláudio" "apellidos" => "D'Elia" ] 1 => array:2 [ "nombre" => "David" "apellidos" => "Gozal" ] 2 => array:2 [ "nombre" => "Oliviero" "apellidos" => "Bruni" ] 3 => array:2 [ "nombre" => "Ekaterini" "apellidos" => "Goudouris" ] 4 => array:2 [ "nombre" => "Miguel" "apellidos" => "Meira e Cruz" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0021755721001765?idApp=UINPBA000049" "url" => "/00217557/0000009800000005/v1_202209230625/S0021755721001765/v1_202209230625/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Review article" "titulo" => "Neonatal diseases and oxidative stress in premature infants: an integrative review" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "455" "paginaFinal" => "462" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Versiéri Oliveira de Almeida, Renan Augusto Pereira, Sérgio Luís Amantéa, Cláudia Ramos Rhoden, Maurício Obal Colvero" "autores" => array:5 [ 0 => array:4 [ "nombre" => "Versiéri Oliveira" "apellidos" => "de Almeida" "email" => array:1 [ 0 => "versieri.almeida@iffarrroupilha.edu.br" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0001" ] ] ] 1 => array:3 [ "nombre" => "Renan Augusto" "apellidos" => "Pereira" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 2 => array:3 [ "nombre" => "Sérgio Luís" "apellidos" => "Amantéa" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] 3 => array:3 [ "nombre" => "Cláudia Ramos" "apellidos" => "Rhoden" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0002" ] ] ] 4 => array:3 [ "nombre" => "Maurício Obal" "apellidos" => "Colvero" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0001" ] ] ] ] "afiliaciones" => array:2 [ 0 => array:3 [ "entidad" => "Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-graduação em Pediatria: Atenção à Saúde da Criança e ao Adolescente, Porto Alegre, RS, Brazil" "etiqueta" => "a" "identificador" => "aff0001" ] 1 => array:3 [ "entidad" => "Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-graduação em Ciências da Saúde, Laboratório de Poluição Atmosférica, Porto Alegre, RS, Brazil" "etiqueta" => "b" "identificador" => "aff0002" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0001" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1958 "Ancho" => 2730 "Tamanyo" => 280652 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flowchart of the study selection process for the integrative review on oxidative stress in premature newborns." ] ] ] "textoCompleto" => "IntroductionPrematurity is a major public health problem. Complications from premature birth are the leading cause of death in children under five years of age.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> In 2017, of the 2.5 million newborns who died from preventable causes, nearly two-thirds were premature.<a class="elsevierStyleCrossRef" href="#bib0002">2</a>Oxidative stress has been implicated as a possible pathophysiological condition to contribute to this unfavorable situation. Premature neonates lack well-developed antioxidant and immune defense mechanisms, making them more susceptible to oxidative stress injury.<a class="elsevierStyleCrossRefs" href="#bib0003">3-5</a> The main reasons for this susceptibility are a hypoxic-hyperoxic challenge, presence of infections, deficiency in antioxidant defense, and high levels of free iron.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>,<a class="elsevierStyleCrossRef" href="#bib0007">7</a>The transition from intrauterine to the extrauterine environment greatly increases free radical production, which is normally downregulated by the antioxidant defense system.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> Oxidative stress is caused by excessive reactive oxygen species (ROS), which are generated when there is an imbalance in this regulation. In oxidative stress, there is an inability of the antioxidant defense system to repair the ROS damage<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0009">9</a> due to either an excessive formation or impaired inactivation of ROS, or a combination of both.<a class="elsevierStyleCrossRef" href="#bib0009">9</a>ROS include free radicals and oxygenated molecules of non-free radicals. Both of them can generate oxidative stress and redox reaction imbalance.<a class="elsevierStyleCrossRef" href="#bib0006">6</a> Oxygen-free radicals are extremely reactive chemical species; they react with various cellular molecules – such as phospholipids, amino acids, and nucleic acids – and lead to lipid peroxidation, DNA strand breaks, and other damaging processes which culminate in cellular injury.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>,<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRefs" href="#bib0010">10-12</a>Oxidative stress-induced damage has an important role in several pathological pathways involved in neonatal diseases.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>,<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRef" href="#bib0014">14</a> For example, some studies point out that most complications of prematurity, such as bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC), intraventricular hemorrhage (IVH), periventricular leukomalacia (PVL), and white matter lesions seem to be related to oxidative injury.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>,<a class="elsevierStyleCrossRef" href="#bib0015">15</a>According to Ozsurekci et al.,<a class="elsevierStyleCrossRef" href="#bib0006">6</a> there are still gaps in knowledge about the potential role of oxidative injury in the pathogenesis of neonatal diseases. New studies should be conducted to investigate more extensively diagnostic and prognostic values of various oxidative stress and antioxidant biomarkers in order to reduce oxidative tissue injury in neonates.Cord blood has been the most widely used matrix when evaluating mechanisms related to prematurity<a class="elsevierStyleCrossRef" href="#bib0016">16</a> as are allows monitoring of biomarkers without causing any distress to the babies and providing relevant information.<a class="elsevierStyleCrossRef" href="#bib0017">17</a>From this perspective, the objective of this study is to describe the relationship between oxidative stress and antioxidant biomarkers in cord blood of premature newborns and the development of diseases in the neonatal period of preterm newborns.MethodThis study consists of an integrative literature review, which is a method that enables the analysis and synthesis of results in a systematized manner, providing support for decision making and improvement of clinical practice. The preparation of this review respected all the pre-established phases for its realization, covering the following steps: formulation of guiding questions; selection and retrieval of articles according to inclusion and exclusion criteria; data collection; evaluation of selected studies; discussion and interpretation of results, and presentation of the review.<a class="elsevierStyleCrossRef" href="#bib0018">18</a>Studies that evaluated biomarkers of oxidative stress and/or antioxidant levels in cord blood of preterm newborns and evaluated clinical outcomes were included. Searches were conducted from January to March 2021, and studies published between 2016 and 2021 in Portuguese, English, or Spanish were included. Original peer-reviewed articles and indexed in the electronic databases Scopus (Elsevier), PubMed (via National Library of Medicine), Web of Science (main collection), and Medline/Lilacs through the Virtual Health Library were chosen. Specific descriptors and their synonyms were used, according to the Medical Subject Headings (MeSH) terms and their equivalents in Portuguese, established by the Health Sciences Descriptors (DeCS). The terms were combined using the Boolean operators “AND” and “OR” to compose the search strategy. The following terms were used in searches: “premature infants” OR “preterm infants” OR “preterm birth” OR “preterm” AND “oxidative stress” OR “antioxidants” AND “infant, premature, diseases.” The search equation used was: (“premature infants” OR “preterm infants” OR “preterm birth” OR preterm) AND (“oxidative stress” OR antioxidants) AND diseases.To be included in this review, studies should evaluate oxidative stress and/or antioxidant biomarkers in cord blood of preterm infants (i.e. born before 37 weeks of gestational age (GA)) and associate them with a clinical outcome (a clinical condition, disease or epidemiological indicators, such as morbidity or mortality). Quantitative or qualitative data were extracted from included articles. Studies were excluded if they were duplicate publications; review studies; if they evaluated oxidative stress and/or antioxidants in premature newborns but did not associate it with a clinical outcome; studies that did not evaluate oxidative stress and/or antioxidants using cord blood; experimental studies with animals; or studies with objectives out of the scope of this review.Two authors independently screened the titles and identified by the searches, and those which met the eligibility criteria were selected for the full-text review. The selected full-text articles were further evaluated by two independent authors, and the studies were definitively included in the review when they met all the inclusion criteria. Any differences between the two reviewers were resolved through a third independent author. The analysis of the studies was conducted in a systematized way, using a structured instrument containing the following information: title of the article; journal; database; Qualis evaluation; authors; country; language; year; objectives; sample characteristics; analyzed variables; data analysis; results; and conclusions. The studies were critically analyzed regarding their authenticity, methodological quality, the relevance of the information, and representations to ensure the scientific integrity of the review.ResultsOne thousand and three articles were identified by the search strategy. Were excluded 968 articles after title/abstract analysis and after excluding duplicates, so 35 articles were fully assessed for eligibility. Two additional studies were included by assessing article references. After full-text analysis, 19 articles were excluded because they did not meet the inclusion criteria. Thus, a total of 18 studies were included in the review. <a class="elsevierStyleCrossRef" href="#fig0001">Figure 1</a> shows the flowchart of the article selection process. Included studies were presented as follows concerning the year of publication: 5 in 2016, 3 in 2017, 2 in 2018, 3 in 2019, 3 in 2020, and 2 publications in 2021. Synthesis of the articles, year of publication, type of study, sample, source of specimen, biomarkers, diseases evaluated, and the main outcomes are described in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>.<a class="elsevierStyleCrossRefs" href="#bib0003">3-5</a>,<a class="elsevierStyleCrossRefs" href="#bib0008">8-10</a>,<a class="elsevierStyleCrossRef" href="#bib0012">12</a>,<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRefs" href="#bib0019">19-28</a><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia>Most of the studies were published in the English language (94.4%, n = 17), and one was in Portuguese. Regarding study methodology, six articles were case-control studies, five were prospective studies, three were cross-sectional studies, two were cohort studies, one was a clinical trial, and one was an observational analytic study.Most studies had their sample composed only of premature newborns (61.1%, n = 11). In the remaining (38.8%, n = 7), term newborns were also included. Sample specimens differed in some articles. 50% (n = 9) evaluated only cord blood, 16.6% (n = 3) analyzed cord blood and venous blood a few hours after birth, and 33.3% (n = 6) evaluated cord blood together with urine, saliva, maternal blood, and venous blood.The following biomarkers of oxidative stress were assessed in the studies: 8-hydroxydeoxyguanosine (8-OHdG) (n = 3); malondialdehyde (MDA) (n = 10), isoprostanes (n = 2) and 8-iso-prostaglandin (n = 1); advanced oxidative protein products (AOPP) / carbonyls protein (n = 3); total antioxidant capacity (TAC) (n = 6); total oxidant status (TOS) and oxidative stress index (OSI) (n = 1); cortisol (n = 1); non-protein bound iron (NPBI) (n = 1). ROS and nitrate markers were also analyzed (n = 1). Antioxidants evaluated in the studies were superoxide dismutase (SOD), catalase, vitamin E (n = 3); copper, zinc, vitamin A (n = 2); glutathione, paraoxonase-1 (PON-1), glutathione peroxidase (GPx) and vitamin C (n = 1).Evaluated pathologies included: HIV (5 articles); IUGR, BPD, ROP (4 articles); sepsis (3 articles); NEC, RDS and morbidity/mortality (2 articles); and chronic lung disease (CLD), white matter injury, DNA damage, neurological disease, fetal inflammatory response syndrome (FIRS), cardiac functions and endothelial dysfunction (one article).The studies that reported a positive association between oxidative stress and/or development of diseases related to prematurity were 72.2% (n = 13); 27.7% (n = 5) showed no significant association. Positive correlations were found in IUGR;<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRef" href="#bib0025">25</a> NEC;<a class="elsevierStyleCrossRef" href="#bib0010">10</a>,<a class="elsevierStyleCrossRef" href="#bib0020">20</a> morbidity and mortality;<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0026">26</a> BPD, IVH;<a class="elsevierStyleCrossRef" href="#bib0010">10</a> FIRS;<a class="elsevierStyleCrossRef" href="#bib0021">21</a> early-onset neonatal sepsis;<a class="elsevierStyleCrossRef" href="#bib0022">22</a> RDS<a class="elsevierStyleCrossRef" href="#bib0012">12</a> and ROP.<a class="elsevierStyleCrossRef" href="#bib0027">27</a> CLD,<a class="elsevierStyleCrossRef" href="#bib0019">19</a> DNA damage,<a class="elsevierStyleCrossRef" href="#bib0004">4</a> IVH,<a class="elsevierStyleCrossRef" href="#bib0024">24</a> cardiac functions,<a class="elsevierStyleCrossRef" href="#bib0023">23</a> and endothelial dysfunction<a class="elsevierStyleCrossRef" href="#bib0009">9</a> were not associated with oxidative stress levels in included studies.<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a><a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0010">10</a>,<a class="elsevierStyleCrossRef" href="#bib0012">12</a>,<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRefs" href="#bib0020">20-22</a>,<a class="elsevierStyleCrossRefs" href="#bib0025">25-27</a> shows levels of oxidative stress and/or antioxidants correlated with clinical outcomes. It was observed the following associations: 1) MDA and vitamin A were associated with ROP;<a class="elsevierStyleCrossRef" href="#bib0027">27</a> 2) AOPP,<a class="elsevierStyleCrossRef" href="#bib0013">13</a> MDA, 8-OHdG<a class="elsevierStyleCrossRef" href="#bib0008">8</a> and vitamin E<a class="elsevierStyleCrossRef" href="#bib0025">25</a> were associated with intrauterine growth restriction; 3) Cortisol,<a class="elsevierStyleCrossRef" href="#bib0020">20</a> vitamin A and vitamin E<a class="elsevierStyleCrossRef" href="#bib0010">10</a> were associated with NEC; 4) Vitamins A and E were associated with BPD and IVH;<a class="elsevierStyleCrossRef" href="#bib0010">10</a> 5) PON-1 was associated with FIRS;<a class="elsevierStyleCrossRef" href="#bib0021">21</a> 6) GPx was associated with sepsis;<a class="elsevierStyleCrossRef" href="#bib0022">22</a> 7) AOPP and 8-OHdG were associated with RDS<a class="elsevierStyleCrossRef" href="#bib0012">12</a> and 8) MDA;<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0026">26</a> and ROSs,<a class="elsevierStyleCrossRef" href="#bib0026">26</a> nitrates, vitamin C, and vitamin E<a class="elsevierStyleCrossRef" href="#bib0005">5</a> were associated with morbidity and mortality.<elsevierMultimedia ident="tbl0002"></elsevierMultimedia>Three of the 13 studies which found an association between oxidative biomarkers and disease development used different samples to analyze data: venous blood drawn a few hours after birth,<a class="elsevierStyleCrossRef" href="#bib0028">28</a> maternal blood,<a class="elsevierStyleCrossRef" href="#bib0003">3</a> and salivary cortisol.<a class="elsevierStyleCrossRef" href="#bib0020">20</a>In general, studies have shown that premature newborns have a higher level of oxidative stress biomarkers compared to term newborns due to several factors. Moreover, worse prognosis (low Apgar score, admission to the neonatal intensive care unit, assisted ventilation and hospital stay time) and increased morbidity and mortality have been related to higher levels of oxidative stress and lower levels of antioxidants with the development of some pathologies.DiscussionIn premature newborns, oxidative stress is a physiological event during the normal transition from the intrauterine to the extrauterine environment. Outside the uterus, free radical production increases significantly and must be counterbalanced by the antioxidant defense system. Healthy full-term newborns can tolerate these drastic changes; however, when intrauterine development is incomplete or abnormal, this tolerance might be affected.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> The identification of reliable biomarkers to analyze the oxidant-antioxidant system dysregulation is essential to improve neonatal care. Furthermore, evaluation of oxidative stress through cord blood may be useful in determining the prognosis of some pathologies.<a class="elsevierStyleCrossRef" href="#bib0029">29</a>Most of the studies included in this review showed a relationship between increased levels of oxidative stress biomarkers and/or decreased levels of antioxidants in cord blood and higher risk of clinical outcomes, such as neonatal diseases and morbimortality. Among the conditions that showed a greater association with increased oxidative stress and/or reduced antioxidant levels were ROP,<a class="elsevierStyleCrossRef" href="#bib0027">27</a> IUGR,<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0013">13</a>,<a class="elsevierStyleCrossRef" href="#bib0025">25</a> RDS,<a class="elsevierStyleCrossRef" href="#bib0012">12</a> sepsis<a class="elsevierStyleCrossRef" href="#bib0022">22</a> and morbidity and mortality.<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0026">26</a> Falsaperla et al.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> also observed that the imbalance between the newborn's oxidant and antioxidant factors seems to play an important role in the onset of the main pathologies of the preterm infant, such as BPD, ROP, NEC, IVH, periventricular leukomalacia, and white matter lesions.One of the selected studies evaluated 189 premature newborns (38 with ROP and 151 without ROP) in a case-control study and showed that MDA and vitamin A concentration in cord blood are independent predictor variables of ROP.<a class="elsevierStyleCrossRef" href="#bib0027">27</a> ROP is an eye disease that affects 7 to 15% of premature infants and is caused by abnormal vascular growth in the retina and may cause significant visual impairment or even blindness.<a class="elsevierStyleCrossRef" href="#bib0020">20</a>To monitor ROP progression among neonates, AOPPs and 8-OHdG might be relevant biomarkers of oxidative stress. In a study conducted by Elkabany et al.,<a class="elsevierStyleCrossRef" href="#bib0012">12</a> these markers were measured in the cord blood of 80 premature newborns at <34 weeks GA (40 newborns with RDS and 40 newborns without RDS), with a positive association. Another marker that might be considered as a diagnostic tool is GPx. One study evaluated 21 preterm infants (30 and 36 weeks) and showed that early-onset neonatal sepsis had a significant correlation with GPx levels in preterm infants from mothers with risk factors for this disease.<a class="elsevierStyleCrossRef" href="#bib0022">22</a>A review by Casavant et al.<a class="elsevierStyleCrossRef" href="#bib0030">30</a> showed that, compared to term infants, premature newborns had lower levels of antioxidants, vitamin A, vitamin E and catalase (an enzyme that neutralizes ROS and is linked to increased rates of NEC and BPD). In a case-control study conducted by Ghany et al.<a class="elsevierStyleCrossRef" href="#bib0010">10</a> with 100 preterm and 100 full-term newborns, levels of vitamin A, vitamin E, catalase, TAC, and MDA were analyzed. The study described a significant relationship between decreased antioxidant levels at birth and the risk of neonatal morbidities, including BPD, NEC, and IVH. In addition, cortisol was another marker that showed a significant association with NEC. NEC is the main cause of morbidity and mortality in premature babies, with a mortality rate of up to 30% and an increased risk of delayed neurological development, especially in pregnancies with inadequate prenatal care.<a class="elsevierStyleCrossRef" href="#bib0020">20</a>Among the reports which evaluated IUGR, Silva et al.<a class="elsevierStyleCrossRef" href="#bib0025">25</a> analyzed the concentration of vitamin E in umbilical cord serum in 140 newborns (64 premature and 76 terms) to test a correlation between the biomarker and intrauterine growth. Results showed that IUGR was more frequent in premature newborns, and most of them had low vitamin E levels. IUGR is a complication of pregnancy, often described when the fetus is estimated to be small for the GA and has an incidence ranging between 3 and 7% of births. In the study by Perrone et al.<a class="elsevierStyleCrossRef" href="#bib0013">13</a> with 129 premature newborns, it was observed that newborns with vascular perfusion lesions had higher levels of AOPP, low GA, and IUGR. Bandyopadhyay et al.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> evaluated 109 newborns (27 premature and 82 term ones) and related IUGR to higher levels of AOPP, MDA and 8-OHdG.The study by Pajai and Bezalar<a class="elsevierStyleCrossRef" href="#bib0005">5</a> associated higher morbidity and mortality rates with increased levels of MDA and nitrates and decreased levels of vitamins C and E, especially in premature male newborns. Liu et al.<a class="elsevierStyleCrossRef" href="#bib0026">26</a> stated an association between MDA and ROS levels and a higher risk of a low Apgar score, NICU admission and mechanical ventilation. Ozalkaya et al.<a class="elsevierStyleCrossRef" href="#bib0021">21</a> determined TAC, PON-1, TOS, and OSI levels in 51 preterm infants (<34 weeks). They showed a significant association between PON-1 levels and PPROM and FIRS, alongside a higher incidence of RDS and higher mortality of infants with FIRS.Alternative markers used in the studies are the antioxidant activity levels. Antioxidant activity measurement may be generally more useful than oxidative stress levels because the results allow a greater understanding of potential mechanisms and therapeutic interventions.<a class="elsevierStyleCrossRef" href="#bib0014">14</a> In this review, antioxidants that showed a significant association between their levels and the development of morbidities were PON-1,<a class="elsevierStyleCrossRef" href="#bib0021">21</a> GPx,<a class="elsevierStyleCrossRef" href="#bib0022">22</a> and vitamins A, C, and E.<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0010">10</a> It is essential to measure multiple antioxidants and include measures that identify specific ROS or RNS that may be associated with imbalanced antioxidant levels or activity. The inclusion of these additional measures provides a more comprehensive comprehension of the biological processes involving antioxidants.<a class="elsevierStyleCrossRef" href="#bib0014">14</a>Also, data obtained from some studies reveal a positive association between oxidative stress and neurological diseases. However, these analyses were not obtained from cord blood. One of them stated that analysis of plasma IsoPs (24 and 48 h after birth) might represent an early biomarker to identify the risk of brain damage in premature patients.<a class="elsevierStyleCrossRef" href="#bib0028">28</a> Bharadwaj et al.<a class="elsevierStyleCrossRef" href="#bib0003">3</a> evaluated the neurodevelopment of 71 children and measured oxidative/antioxidant stress levels. They concluded that maternal TAC in PE is useful for predicting impaired motor development at one year of corrected age. Dietze et al.<a class="elsevierStyleCrossRef" href="#bib0020">20</a> observed through salivary cortisol analysis that newborns whose mothers smoked more than ten cigarettes per day were at higher risk for IVH. IVH affects 30 to 60% of preterm infants and is characterized as white matter lesion due to microvascular events that occur in the germ matrix, putting the infant at increased risk for neurodevelopmental delays and additional brain damage.<a class="elsevierStyleCrossRef" href="#bib0020">20</a>On the other hand, several studies did not confirm the association between oxidative stress biomarkers and the development of pathologies, morbimortality or prognosis. Moore et al.<a class="elsevierStyleCrossRef" href="#bib0019">19</a> examined 31 premature newborns to evaluate the association between CLD and 8-OHdG levels. They observed that CLD was associated with lower levels of oxidative stress, which contradicts previous studies. Authors justify these conflicting results by different methodologies used in sample collection and analysis, alongside other additional factors that might have affected 8-OHdG levels. Dekker et al.<a class="elsevierStyleCrossRef" href="#bib0024">24</a> evaluated 52 preterm infants for 8iPGF2α levels in order to find a higher risk of developing IVH, but no significant association was found. Norishadkam et al.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> compared 25 premature and 25 term newborns to verify the relationship between oxidative stress and DNA damage and also found no significant association. Stefanov et al.<a class="elsevierStyleCrossRef" href="#bib0009">9</a> evaluated the relationship between glutathione, MDA, and endothelin-1 levels to analyze endothelial dysfunction in 63 infants born between 24 to 42 weeks. Still, there was no significant relationship between the two factors analyzed. Finally, Arman et al.<a class="elsevierStyleCrossRef" href="#bib0023">23</a> evaluated the global oxidant and antioxidant status in newborns of mothers with and without PE; there was no statistical difference between groups. The absence of significant associations in these studies may be justified by clinical factors affecting biomarkers levels, the small sample size in most studies, and the complexity of the neonatal transition period, in which a not fully comprehended mixed-redox state might occur.<a class="elsevierStyleCrossRef" href="#bib0009">9</a>The present study has some limitations. Although the utility of cord blood samples for the assessment of oxidative stress biomarkers and their possible clinical implications is evident, they cannot be used in follow-up analysis after birth. Alternative non-invasive monitoring options that have shown some positive results are newborn saliva and urine samples, which may be used for longitudinal follow-ups.<a class="elsevierStyleCrossRef" href="#bib0029">29</a> Also, different methodologies, biomarkers, and the limited number of participants in each study make results unreliable when extrapolating to the general population of preterm babies.An accurate assessment of oxidative damage and the possibility of targeted treatments might improve neonatal care.<a class="elsevierStyleCrossRef" href="#bib0031">31</a> Currently, none of these biomarkers are used in clinical practice. However, further researches on the field might help to overcome the technical and economic barriers and enable their routine use. As a future perspective, in the next few years, diagnostic strategies directed to the identification of the risk of oxidative stress-related pathologies might be developed, and guidelines for their prevention and treatment might be updated, reducing the morbidity and mortality of premature newborns.The authors of the present study conclude that the analysis of oxidative stress and antioxidant levels in cord blood of premature newborns might be useful in assessing the diagnosis and prognosis of some clinically relevant pathologies. Oxidative stress and antioxidant activity are involved in the pathophysiology of the development of several neonatal diseases, and their consequences are associated with increased short- and long-term morbidity, impaired neurodevelopment, and increased mortality. More information and research in the area are needed to impact these clinical outcomes." "textoCompletoSecciones" => array:1 [ "secciones" => array:7 [ 0 => array:3 [ "identificador" => "xres1773434" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1557774" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 3 => array:2 [ "identificador" => "sec0002" "titulo" => "Method" ] 4 => array:2 [ "identificador" => "sec0003" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0004" "titulo" => "Discussion" ] 6 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-07-23" "fechaAceptado" => "2021-11-16" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1557774" "palabras" => array:5 [ 0 => "Infant, premature" 1 => "Oxidative stress" 2 => "Antioxidants" 3 => "Diseases" 4 => "Cord blood" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo describe the relationship of oxidative stress and antioxidant biomarkers in cord blood of premature newborns and the prognosis of diseases in the neonatal period. SourcesThis study consists of an integrative review. Searches were conducted in electronic databases Scopus, PubMed, Web of Science, and Medline/Lilacs through the Virtual Library on Health Issues, using the descriptors: “premature infants”, “preterm infants”, “preterm birth”, “preterm”, “oxidative stress”, “antioxidants”, “infant, premature, diseases” and “cord blood”. Original articles published between 2016 and 2021 in Portuguese, English, or Spanish, which analyzed oxidative stress and/or antioxidant levels through cord blood of premature newborns and evaluated clinical outcomes, were included. Summary of the findingsOf the 1,003 studies reviewed, after exclusion of duplicate articles, analysis of titles, abstracts, and full texts, 18 articles were included. 72.2% (n = 13) of analyzed studies reported a positive association between oxidative stress and the development of prematurity-related diseases; 27.7% (n = 5) showed no significant relation. Outcomes that showed a positive association were: intrauterine growth restriction, necrotizing enterocolitis, bronchopulmonary dysplasia, intraventricular hemorrhage, fetal inflammatory response syndrome, early-onset neonatal sepsis, retinopathy of prematurity, morbidity, and mortality. ConclusionThe analysis of oxidative stress and antioxidants in cord blood of premature newborns may be useful in the prognosis of some pathologies. The consequences of oxidative damage are known to be associated with increased morbidity in the short and long term. Further investigation is needed in this population in order to define normality parameters of biomarkers, clinical manifestations, diagnosis and treatment of these conditions." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Sources" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Summary of the findings" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] ] "NotaPie" => array:1 [ 0 => array:1 [ "nota" => "Study conducted at the Universidade Federal de Ciências da Saúde de Porto Alegre, Porto Alegre, RS, Brazil." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1958 "Ancho" => 2730 "Tamanyo" => 280652 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Fig " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flowchart of the study selection process for the integrative review on oxidative stress in premature newborns." ] ] 1 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AOPP, advanced oxidative protein products; BPD, bronchopulmonary dysplasia; CLD, chronic lung disease; DNA, deoxyribonucleic acid; ET-1, endothelin-1; FIRS, fetal inflammatory response syndrome; FT, full-term; GA, gestational age; GPx, glutathione peroxidase; IVH, intraventricular hemorrhage; IsoPs, isoprostanes; IUGR, intrauterine growth restriction; MDA, malondialdehyde; NB, newborns; NEC, necrotizing enterocolitis; NICU, neonatal intensive care unit; NPBI, non-protein bound iron; OS, oxidative stress; OSI, oxidative stress index; PE= preeclampsia; PON-1, paraoxonase-1; PPROM, preterm premature rupture of membrane; PTN, preterm newborn; RDS, respiratory distress syndrome; ROP, retinopathy of prematurity; ROS, reactive oxygen species; SOD= superoxide dismutase; TAC, total antioxidant capacity; TOS, total oxidant status; WMI, white matter injury; 8-OHdG, 8- hydroxydeoxyguanosine; 8iPGF2α, 8-iso-prostaglandin F2." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Article / Country \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Type of study \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Sample \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Source of specimen \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Oxidative stress and antioxidants biomarkers \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Diseases evaluated \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Main outcomes \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Moore et al., 2016<a class="elsevierStyleCrossRef" href="#bib0019">19</a>United States \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">31 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and urine \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8-OHdG \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">CLDIVHBPDROP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">CLD was associated with lower levels of 8-OHdG. There were no significant differences regarding IVH, BPD, and ROP incidences. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Perrone et al., 2016<a class="elsevierStyleCrossRef" href="#bib0013">13</a> Italy \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cohort \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">120 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IsoPsNPBIAOPP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IUGR \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Placental injuries (inflammation or impaired perfusion) were associated with elevated OS levels. PTN with vascular perfusion lesions had higher levels of AOPP, low GA, and the IUGR. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dietze et al., 2016<a class="elsevierStyleCrossRef" href="#bib0020">20</a> United States \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">31 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and saliva \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cortisol \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">NECIVHBPDROP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">The higher the GA at the beginning of prenatal care, the lower cord blood cortisol and tended to have a higher risk of NEC. In salivary cortisol, NB whose mothers smoked had a higher risk of IVH. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ghany et al., 2016<a class="elsevierStyleCrossRef" href="#bib0010">10</a> Egypt \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Case-control study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">200 NB100 PTN100 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and venous blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDA; TACCatalaseVitamin AVitamin E \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">NECBPDIVH \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Positive relationship between reduced antioxidant levels at birth and the risk of neonatal morbidities, including BPD, IVH, NEC. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Bandyopadhyay et al., 2017<a class="elsevierStyleCrossRef" href="#bib0008">8</a> India \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Transversal \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">109 NB27 PTN82 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDA8-OHdG \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IUGR \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Term NB and late PTN with IUGR had higher levels of MDA and 8-OHdG compared to infants suitable for GA through meconium-stained amniotic fluid. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Norishadkam et al., 2017<a class="elsevierStyleCrossRef" href="#bib0004">4</a> Iran \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Case-control study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">50 NB25 PTN25 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDACatalaseSODTAC \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">DNA damage \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">There was no significant association between MDA, SOD, TAC, catalase, and early DNA damage in cord blood plasma for PTN. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Ozalkaya et al., 2017<a class="elsevierStyleCrossRef" href="#bib0021">21</a> Turkey \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Prospective \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">51 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">TACPON-1TOSOSI \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">FIRSRDSIVHBPDROPSepsis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Higher levels of TOS were associated with NB with PPROM; Higher PON-1 was associated with higher risk of PPROM, FIRS or both. NB with PPROM and FIRS had higher incidence of RDS. NB with FIRS had higher mortality. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Bharadwaj et al., 2017<a class="elsevierStyleCrossRef" href="#bib0003">3</a> India \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cohort \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">143 NB71 w/ GA >35 e 72 w/ GA >39 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Maternal blood and cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Protein carbonylsMDATAC \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Neurologic deseasesIUGRSepsis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">OS increases in NB and mothers with PE. Decreased maternal TAC is associated with negative neuromotor results. Maternal TAC during PE is useful to predict poor motor development at the corrected age of one year. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Coutinho et al., 2018<a class="elsevierStyleCrossRef" href="#bib0022">22</a> Brazil \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Transversal \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood, saliva, and urine \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDASODGPxCatalase \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Sepsis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">GPx in cord blood can be a diagnostic tool for suspicion of early-onset neonatal sepsis in PTNs of mothers with risk factors for sepsis. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Armann et al., 2018<a class="elsevierStyleCrossRef" href="#bib0023">23</a> Turkey \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Case-control study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">80 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">TACTOSOSI \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cardiac functions \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">TAC, TOS, and OSI were significantly higher for NB of mothers with PE. Echocardiographic parameters are not affected by the oxidant state. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0078"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Elkabany et al., 2019<a class="elsevierStyleCrossRef" href="#bib0012">12</a> Egypt \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ProspectiveCase-control study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDA; AOPP8-OHdGTACCopper; Zinc \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">RDS \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">AOPPs and 8-OHdG can be used as serum biomarkers for OS among NBs with RDS to monitor disease progression. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0085"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Dekker et al., 2019 Netherlands<a class="elsevierStyleCrossRef" href="#bib0024">24</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Clinical trial \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">52 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and venous blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8iPGF2α \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Grade III IVH \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">8iPGF2α did not differ among groups. There were also no differences regarding intubation, the incidence of grade III IVH, or death before hospital discharge. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Silva et al., 2019Brazil<a class="elsevierStyleCrossRef" href="#bib0025">25</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Transversal \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">140 NB54 PTN and 76 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Vitamin E \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IUGR \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IUGR was more frequent in PTB; most of the infants had low vitamin E levels. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Stefanov et al., 2020<a class="elsevierStyleCrossRef" href="#bib0009">9</a> United States \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ProspectivePilot study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">63 NB50 PTN and 13 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and venous blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDAGlutathione \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Endothelial dysfunction \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDA was higher in cord blood than at 24 hours of life, regardless of GA. PTN had higher ET-1 levels in cord blood than 24 hours of life, but overall, ET-1 had no significant association with OS. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0106"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Liu et al., 2020China<a class="elsevierStyleCrossRef" href="#bib0026">26</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Case-control study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">816 NB182 PTN634 FT NB \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDASODROSs \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Morbidity and mortality \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Higher levels of MDA and ROSs are associated with lower Apgar scores; NICU admission and ventilation, i.e., are significantly associated with higher morbidity and mortality. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0113"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Pajai e Bezalwar 2020<a class="elsevierStyleCrossRef" href="#bib0005">5</a> India \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Observational Analytic \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">45 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDANitratesVitamin CVitamin E \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Morbidity and mortality \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">PTN shows higher MDA and nitrates levels and reduced levels of vitamins C and E, especially in males, indicating increased morbidity and mortality. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0120"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Agrawal et al., 2021Índia<a class="elsevierStyleCrossRef" href="#bib0027">27</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Nested case-control \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">189 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and venous blood (both from NB and mother) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDACopperZincVitamin A \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ROP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">MDA and vitamin A in umbilical cord plasma were independent predictive variables of ROP. \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0127"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Coviello et al., 2021Netherlands<a class="elsevierStyleCrossRef" href="#bib0028">28</a> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Prospective observational study \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">44 PTN \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Cord blood and plasma \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">F2-isoprostanes \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">White matter injury \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Early verification of plasma IsoPs can help discriminate abnormal WMI scores at term-equivalent age; and represents an early biomarker for identifying PTN at risk of brain injury. \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Studies reviewed by oxidative stress biomarker category." ] ] 2 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "AOPP, advanced oxidative protein products; BPD, bronchopulmonary dysplasia; FIRS, fetal inflammatory response syndrome; GPx, glutathione peroxidase; IVH, intraventricular hemorrhage; IUGR, intrauterine growth restriction; MDA, malondialdehyde; NEC, necrotizing enterocolitis; PON-1, paraoxonase-1; RDS, respiratory distress syndrome; ROP, retinopathy of prematurity; ROS, reactive oxygen species; 8-OHdG, 8- hydroxydeoxyguanosine." "tablatextoimagen" => array:1 [ 0 => array:1 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0134"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Condition \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0135"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarker \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0136"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">ROP \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↑ MDA27↓ Vitamin A27 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IUGR \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↑ AOPP13↑ MDA8↑ 8-OHdG8↓ Vitamin E25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0140"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">NEC \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↑ Cortisol20↓ Vitamin A10↓ Vitamin E10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0142"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">BPD \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↓ Vitamin A10↓ Vitamin E10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0144"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">IVH \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↓ Vitamin A10↓ Vitamin E10 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">FIRS \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↓ PON-121 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0148"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Sepsis \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↓ GPx22 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0150"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">RDS \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↑ AOPP12↑ 8-OHdG12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0152"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Morbidity and mortality \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">↑ MDA5,26↑ ROS26↑ Nitrates5↓ Vitamin C5↓ Vitamin E5 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] ] ] ] "descripcion" => array:1 [ "en" => "Oxidative stress biomarkers and antioxidants correlated with evaluated conditions." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "cebibsec1" "bibliografiaReferencia" => array:31 [ 0 => array:3 [ "identificador" => "bib0001" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "World Health Organization. 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Versiéri Oliveira de Almeidaa,

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versieri.almeida@iffarrroupilha.edu.br

Corresponding author.

, Renan Augusto Pereiraa, Sérgio Luís Amantéaa, Cláudia Ramos Rhodenb, Maurício Obal Colveroa

a Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-graduação em Pediatria: Atenção à Saúde da Criança e ao Adolescente, Porto Alegre, RS, Brazil

b Universidade Federal de Ciências da Saúde de Porto Alegre, Programa de Pós-graduação em Ciências da Saúde, Laboratório de Poluição Atmosférica, Porto Alegre, RS, Brazil

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          "en" => "<p id="spara001" class="elsevierStyleSimplePara elsevierViewall">Flowchart of the study selection process for the integrative review on oxidative stress in premature newborns&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0006" class="elsevierStylePara elsevierViewall">Prematurity is a major public health problem&#46; Complications from premature birth are the leading cause of death in children under five years of age&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> In 2017&#44; of the 2&#46;5 million newborns who died from preventable causes&#44; nearly two-thirds were premature&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">Oxidative stress has been implicated as a possible pathophysiological condition to contribute to this unfavorable situation&#46; Premature neonates lack well-developed antioxidant and immune defense mechanisms&#44; making them more susceptible to oxidative stress injury&#46;<a class="elsevierStyleCrossRefs" href="#bib0003"><span class="elsevierStyleSup">3-5</span></a> The main reasons for this susceptibility are a hypoxic-hyperoxic challenge&#44; presence of infections&#44; deficiency in antioxidant defense&#44; and high levels of free iron&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a></p><p id="para0008" class="elsevierStylePara elsevierViewall">The transition from intrauterine to the extrauterine environment greatly increases free radical production&#44; which is normally downregulated by the antioxidant defense system&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> Oxidative stress is caused by excessive reactive oxygen species &#40;ROS&#41;&#44; which are generated when there is an imbalance in this regulation&#46; In oxidative stress&#44; there is an inability of the antioxidant defense system to repair the ROS damage<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> due to either an excessive formation or impaired inactivation of ROS&#44; or a combination of both&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a></p><p id="para0009" class="elsevierStylePara elsevierViewall">ROS include free radicals and oxygenated molecules of non-free radicals&#46; Both of them can generate oxidative stress and redox reaction imbalance&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> Oxygen-free radicals are extremely reactive chemical species&#59; they react with various cellular molecules &#8211; such as phospholipids&#44; amino acids&#44; and nucleic acids &#8211; and lead to lipid peroxidation&#44; DNA strand breaks&#44; and other damaging processes which culminate in cellular injury&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">10-12</span></a></p><p id="para0010" class="elsevierStylePara elsevierViewall">Oxidative stress-induced damage has an important role in several pathological pathways involved in neonatal diseases&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> For example&#44; some studies point out that most complications of prematurity&#44; such as bronchopulmonary dysplasia &#40;BPD&#41;&#44; retinopathy of prematurity &#40;ROP&#41;&#44; necrotizing enterocolitis &#40;NEC&#41;&#44; intraventricular hemorrhage &#40;IVH&#41;&#44; periventricular leukomalacia &#40;PVL&#41;&#44; and white matter lesions seem to be related to oxidative injury&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a></p><p id="para0011" class="elsevierStylePara elsevierViewall">According to Ozsurekci et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> there are still gaps in knowledge about the potential role of oxidative injury in the pathogenesis of neonatal diseases&#46; New studies should be conducted to investigate more extensively diagnostic and prognostic values of various oxidative stress and antioxidant biomarkers in order to reduce oxidative tissue injury in neonates&#46;</p><p id="para0012" class="elsevierStylePara elsevierViewall">Cord blood has been the most widely used matrix when evaluating mechanisms related to prematurity<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> as are allows monitoring of biomarkers without causing any distress to the babies and providing relevant information&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a></p><p id="para0013" class="elsevierStylePara elsevierViewall">From this perspective&#44; the objective of this study is to describe the relationship between oxidative stress and antioxidant biomarkers in cord blood of premature newborns and the development of diseases in the neonatal period of preterm newborns&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Method</span><p id="para0014" class="elsevierStylePara elsevierViewall">This study consists of an integrative literature review&#44; which is a method that enables the analysis and synthesis of results in a systematized manner&#44; providing support for decision making and improvement of clinical practice&#46; The preparation of this review respected all the pre-established phases for its realization&#44; covering the following steps&#58; formulation of guiding questions&#59; selection and retrieval of articles according to inclusion and exclusion criteria&#59; data collection&#59; evaluation of selected studies&#59; discussion and interpretation of results&#44; and presentation of the review&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a></p><p id="para0015" class="elsevierStylePara elsevierViewall">Studies that evaluated biomarkers of oxidative stress and&#47;or antioxidant levels in cord blood of preterm newborns and evaluated clinical outcomes were included&#46; Searches were conducted from January to March 2021&#44; and studies published between 2016 and 2021 in Portuguese&#44; English&#44; or Spanish were included&#46; Original peer-reviewed articles and indexed in the electronic databases Scopus &#40;Elsevier&#41;&#44; PubMed &#40;via National Library of Medicine&#41;&#44; Web of Science &#40;main collection&#41;&#44; and Medline&#47;Lilacs through the Virtual Health Library were chosen&#46; Specific descriptors and their synonyms were used&#44; according to the Medical Subject Headings &#40;MeSH&#41; terms and their equivalents in Portuguese&#44; established by the Health Sciences Descriptors &#40;DeCS&#41;&#46; The terms were combined using the Boolean operators &#8220;AND&#8221; and &#8220;OR&#8221; to compose the search strategy&#46; The following terms were used in searches&#58; <span class="elsevierStyleItalic">&#8220;premature infants&#8221; OR &#8220;preterm infants&#8221; OR &#8220;preterm birth&#8221; OR &#8220;preterm&#8221; AND &#8220;oxidative stress&#8221; OR &#8220;antioxidants&#8221; AND &#8220;infant&#44; premature&#44; diseases&#46;&#8221;</span> The search equation used was&#58; <span class="elsevierStyleItalic">&#40;&#8220;premature infants&#8221; OR &#8220;preterm infants&#8221; OR &#8220;preterm birth&#8221; OR preterm&#41; AND &#40;&#8220;oxidative stress&#8221; OR antioxidants&#41; AND diseases&#46;</span></p><p id="para0016" class="elsevierStylePara elsevierViewall">To be included in this review&#44; studies should evaluate oxidative stress and&#47;or antioxidant biomarkers in cord blood of preterm infants &#40;i&#46;e&#46; born before 37 weeks of gestational age &#40;GA&#41;&#41; and associate them with a clinical outcome &#40;a clinical condition&#44; disease or epidemiological indicators&#44; such as morbidity or mortality&#41;&#46; Quantitative or qualitative data were extracted from included articles&#46; Studies were excluded if they were duplicate publications&#59; review studies&#59; if they evaluated oxidative stress and&#47;or antioxidants in premature newborns but did not associate it with a clinical outcome&#59; studies that did not evaluate oxidative stress and&#47;or antioxidants using cord blood&#59; experimental studies with animals&#59; or studies with objectives out of the scope of this review&#46;</p><p id="para0017" class="elsevierStylePara elsevierViewall">Two authors independently screened the titles and identified by the searches&#44; and those which met the eligibility criteria were selected for the full-text review&#46; The selected full-text articles were further evaluated by two independent authors&#44; and the studies were definitively included in the review when they met all the inclusion criteria&#46; Any differences between the two reviewers were resolved through a third independent author&#46; The analysis of the studies was conducted in a systematized way&#44; using a structured instrument containing the following information&#58; title of the article&#59; journal&#59; database&#59; Qualis evaluation&#59; authors&#59; country&#59; language&#59; year&#59; objectives&#59; sample characteristics&#59; analyzed variables&#59; data analysis&#59; results&#59; and conclusions&#46; The studies were critically analyzed regarding their authenticity&#44; methodological quality&#44; the relevance of the information&#44; and representations to ensure the scientific integrity of the review&#46;</p></span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Results</span><p id="para0018" class="elsevierStylePara elsevierViewall">One thousand and three articles were identified by the search strategy&#46; Were excluded 968 articles after title&#47;abstract analysis and after excluding duplicates&#44; so 35 articles were fully assessed for eligibility&#46; Two additional studies were included by assessing article references&#46; After full-text analysis&#44; 19 articles were excluded because they did not meet the inclusion criteria&#46; Thus&#44; a total of 18 studies were included in the review&#46; <a class="elsevierStyleCrossRef" href="#fig0001">Figure 1</a> shows the flowchart of the article selection process&#46; Included studies were presented as follows concerning the year of publication&#58; 5 in 2016&#44; 3 in 2017&#44; 2 in 2018&#44; 3 in 2019&#44; 3 in 2020&#44; and 2 publications in 2021&#46; Synthesis of the articles&#44; year of publication&#44; type of study&#44; sample&#44; source of specimen&#44; biomarkers&#44; diseases evaluated&#44; and the main outcomes are described in <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a>&#46;<a class="elsevierStyleCrossRefs" href="#bib0003"><span class="elsevierStyleSup">3-5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0008"><span class="elsevierStyleSup">8-10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0019"><span class="elsevierStyleSup">19-28</span></a></p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0019" class="elsevierStylePara elsevierViewall">Most of the studies were published in the English language &#40;94&#46;4&#37;&#44; n&#160;&#61;&#160;17&#41;&#44; and one was in Portuguese&#46; Regarding study methodology&#44; six articles were case-control studies&#44; five were prospective studies&#44; three were cross-sectional studies&#44; two were cohort studies&#44; one was a clinical trial&#44; and one was an observational analytic study&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">Most studies had their sample composed only of premature newborns &#40;61&#46;1&#37;&#44; n&#160;&#61;&#160;11&#41;&#46; In the remaining &#40;38&#46;8&#37;&#44; n&#160;&#61;&#160;7&#41;&#44; term newborns were also included&#46; Sample specimens differed in some articles&#46; 50&#37; &#40;n&#160;&#61;&#160;9&#41; evaluated only cord blood&#44; 16&#46;6&#37; &#40;n&#160;&#61;&#160;3&#41; analyzed cord blood and venous blood a few hours after birth&#44; and 33&#46;3&#37; &#40;n&#160;&#61;&#160;6&#41; evaluated cord blood together with urine&#44; saliva&#44; maternal blood&#44; and venous blood&#46;</p><p id="para0021" class="elsevierStylePara elsevierViewall">The following biomarkers of oxidative stress were assessed in the studies&#58; 8-hydroxydeoxyguanosine &#40;8-OHdG&#41; &#40;n&#160;&#61;&#160;3&#41;&#59; malondialdehyde &#40;MDA&#41; &#40;n&#160;&#61;&#160;10&#41;&#44; isoprostanes &#40;n&#160;&#61;&#160;2&#41; and 8-iso-prostaglandin &#40;n&#160;&#61;&#160;1&#41;&#59; advanced oxidative protein products &#40;AOPP&#41; &#47; carbonyls protein &#40;n&#160;&#61;&#160;3&#41;&#59; total antioxidant capacity &#40;TAC&#41; &#40;n&#160;&#61;&#160;6&#41;&#59; total oxidant status &#40;TOS&#41; and oxidative stress index &#40;OSI&#41; &#40;n&#160;&#61;&#160;1&#41;&#59; cortisol &#40;n&#160;&#61;&#160;1&#41;&#59; non-protein bound iron &#40;NPBI&#41; &#40;n&#160;&#61;&#160;1&#41;&#46; ROS and nitrate markers were also analyzed &#40;n&#160;&#61;&#160;1&#41;&#46; Antioxidants evaluated in the studies were superoxide dismutase &#40;SOD&#41;&#44; catalase&#44; vitamin E &#40;n&#160;&#61;&#160;3&#41;&#59; copper&#44; zinc&#44; vitamin A &#40;n&#160;&#61;&#160;2&#41;&#59; glutathione&#44; paraoxonase-1 &#40;PON-1&#41;&#44; glutathione peroxidase &#40;GPx&#41; and vitamin C &#40;n&#160;&#61;&#160;1&#41;&#46;</p><p id="para0022" class="elsevierStylePara elsevierViewall">Evaluated pathologies included&#58; HIV &#40;5 articles&#41;&#59; IUGR&#44; BPD&#44; ROP &#40;4 articles&#41;&#59; sepsis &#40;3 articles&#41;&#59; NEC&#44; RDS and morbidity&#47;mortality &#40;2 articles&#41;&#59; and chronic lung disease &#40;CLD&#41;&#44; white matter injury&#44; DNA damage&#44; neurological disease&#44; fetal inflammatory response syndrome &#40;FIRS&#41;&#44; cardiac functions and endothelial dysfunction &#40;one article&#41;&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall">The studies that reported a positive association between oxidative stress and&#47;or development of diseases related to prematurity were 72&#46;2&#37; &#40;n&#160;&#61;&#160;13&#41;&#59; 27&#46;7&#37; &#40;n&#160;&#61;&#160;5&#41; showed no significant association&#46; Positive correlations were found in IUGR&#59;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> NEC&#59;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> morbidity and mortality&#59;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> BPD&#44; IVH&#59;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> FIRS&#59;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> early-onset neonatal sepsis&#59;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> RDS<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> and ROP&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> CLD&#44;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> DNA damage&#44;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> IVH&#44;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> cardiac functions&#44;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> and endothelial dysfunction<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> were not associated with oxidative stress levels in included studies&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a><a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">20-22</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">25-27</span></a> shows levels of oxidative stress and&#47;or antioxidants correlated with clinical outcomes&#46; It was observed the following associations&#58; 1&#41; MDA and vitamin A were associated with ROP&#59;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> 2&#41; AOPP&#44;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> MDA&#44; 8-OHdG<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> and vitamin E<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> were associated with intrauterine growth restriction&#59; 3&#41; Cortisol&#44;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> vitamin A and vitamin E<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> were associated with NEC&#59; 4&#41; Vitamins A and E were associated with BPD and IVH&#59;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> 5&#41; PON-1 was associated with FIRS&#59;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> 6&#41; GPx was associated with sepsis&#59;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> 7&#41; AOPP and 8-OHdG were associated with RDS<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> and 8&#41; MDA&#59;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> and ROSs&#44;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> nitrates&#44; vitamin C&#44; and vitamin E<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> were associated with morbidity and mortality&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><p id="para0025" class="elsevierStylePara elsevierViewall">Three of the 13 studies which found an association between oxidative biomarkers and disease development used different samples to analyze data&#58; venous blood drawn a few hours after birth&#44;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a> maternal blood&#44;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> and salivary cortisol&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a></p><p id="para0026" class="elsevierStylePara elsevierViewall">In general&#44; studies have shown that premature newborns have a higher level of oxidative stress biomarkers compared to term newborns due to several factors&#46; Moreover&#44; worse prognosis &#40;low Apgar score&#44; admission to the neonatal intensive care unit&#44; assisted ventilation and hospital stay time&#41; and increased morbidity and mortality have been related to higher levels of oxidative stress and lower levels of antioxidants with the development of some pathologies&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Discussion</span><p id="para0027" class="elsevierStylePara elsevierViewall">In premature newborns&#44; oxidative stress is a physiological event during the normal transition from the intrauterine to the extrauterine environment&#46; Outside the uterus&#44; free radical production increases significantly and must be counterbalanced by the antioxidant defense system&#46; Healthy full-term newborns can tolerate these drastic changes&#59; however&#44; when intrauterine development is incomplete or abnormal&#44; this tolerance might be affected&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> The identification of reliable biomarkers to analyze the oxidant-antioxidant system dysregulation is essential to improve neonatal care&#46; Furthermore&#44; evaluation of oxidative stress through cord blood may be useful in determining the prognosis of some pathologies&#46;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a></p><p id="para0028" class="elsevierStylePara elsevierViewall">Most of the studies included in this review showed a relationship between increased levels of oxidative stress biomarkers and&#47;or decreased levels of antioxidants in cord blood and higher risk of clinical outcomes&#44; such as neonatal diseases and morbimortality&#46; Among the conditions that showed a greater association with increased oxidative stress and&#47;or reduced antioxidant levels were ROP&#44;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> IUGR&#44;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> RDS&#44;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> sepsis<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> and morbidity and mortality&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> Falsaperla et al&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> also observed that the imbalance between the newborn&#39;s oxidant and antioxidant factors seems to play an important role in the onset of the main pathologies of the preterm infant&#44; such as BPD&#44; ROP&#44; NEC&#44; IVH&#44; periventricular leukomalacia&#44; and white matter lesions&#46;</p><p id="para0029" class="elsevierStylePara elsevierViewall">One of the selected studies evaluated 189 premature newborns &#40;38 with ROP and 151 without ROP&#41; in a case-control study and showed that MDA and vitamin A concentration in cord blood are independent predictor variables of ROP&#46;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> ROP is an eye disease that affects 7 to 15&#37; of premature infants and is caused by abnormal vascular growth in the retina and may cause significant visual impairment or even blindness&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a></p><p id="para0030" class="elsevierStylePara elsevierViewall">To monitor ROP progression among neonates&#44; AOPPs and 8-OHdG might be relevant biomarkers of oxidative stress&#46; In a study conducted by Elkabany et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> these markers were measured in the cord blood of 80 premature newborns at &#60;34 weeks GA &#40;40 newborns with RDS and 40 newborns without RDS&#41;&#44; with a positive association&#46; Another marker that might be considered as a diagnostic tool is GPx&#46; One study evaluated 21 preterm infants &#40;30 and 36 weeks&#41; and showed that early-onset neonatal sepsis had a significant correlation with GPx levels in preterm infants from mothers with risk factors for this disease&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a></p><p id="para0031" class="elsevierStylePara elsevierViewall">A review by Casavant et al&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">30</span></a> showed that&#44; compared to term infants&#44; premature newborns had lower levels of antioxidants&#44; vitamin A&#44; vitamin E and catalase &#40;an enzyme that neutralizes ROS and is linked to increased rates of NEC and BPD&#41;&#46; In a case-control study conducted by Ghany et al&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> with 100 preterm and 100 full-term newborns&#44; levels of vitamin A&#44; vitamin E&#44; catalase&#44; TAC&#44; and MDA were analyzed&#46; The study described a significant relationship between decreased antioxidant levels at birth and the risk of neonatal morbidities&#44; including BPD&#44; NEC&#44; and IVH&#46; In addition&#44; cortisol was another marker that showed a significant association with NEC&#46; NEC is the main cause of morbidity and mortality in premature babies&#44; with a mortality rate of up to 30&#37; and an increased risk of delayed neurological development&#44; especially in pregnancies with inadequate prenatal care&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a></p><p id="para0032" class="elsevierStylePara elsevierViewall">Among the reports which evaluated IUGR&#44; Silva et al&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a> analyzed the concentration of vitamin E in umbilical cord serum in 140 newborns &#40;64 premature and 76 terms&#41; to test a correlation between the biomarker and intrauterine growth&#46; Results showed that IUGR was more frequent in premature newborns&#44; and most of them had low vitamin E levels&#46; IUGR is a complication of pregnancy&#44; often described when the fetus is estimated to be small for the GA and has an incidence ranging between 3 and 7&#37; of births&#46; In the study by Perrone et al&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> with 129 premature newborns&#44; it was observed that newborns with vascular perfusion lesions had higher levels of AOPP&#44; low GA&#44; and IUGR&#46; Bandyopadhyay et al&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> evaluated 109 newborns &#40;27 premature and 82 term ones&#41; and related IUGR to higher levels of AOPP&#44; MDA and 8-OHdG&#46;</p><p id="para0033" class="elsevierStylePara elsevierViewall">The study by Pajai and Bezalar<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> associated higher morbidity and mortality rates with increased levels of MDA and nitrates and decreased levels of vitamins C and E&#44; especially in premature male newborns&#46; Liu et al&#46;<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> stated an association between MDA and ROS levels and a higher risk of a low Apgar score&#44; NICU admission and mechanical ventilation&#46; Ozalkaya et al&#46;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> determined TAC&#44; PON-1&#44; TOS&#44; and OSI levels in 51 preterm infants &#40;&#60;34 weeks&#41;&#46; They showed a significant association between PON-1 levels and PPROM and FIRS&#44; alongside a higher incidence of RDS and higher mortality of infants with FIRS&#46;</p><p id="para0034" class="elsevierStylePara elsevierViewall">Alternative markers used in the studies are the antioxidant activity levels&#46; Antioxidant activity measurement may be generally more useful than oxidative stress levels because the results allow a greater understanding of potential mechanisms and therapeutic interventions&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> In this review&#44; antioxidants that showed a significant association between their levels and the development of morbidities were PON-1&#44;<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> GPx&#44;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> and vitamins A&#44; C&#44; and E&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> It is essential to measure multiple antioxidants and include measures that identify specific ROS or RNS that may be associated with imbalanced antioxidant levels or activity&#46; The inclusion of these additional measures provides a more comprehensive comprehension of the biological processes involving antioxidants&#46;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a></p><p id="para0035" class="elsevierStylePara elsevierViewall">Also&#44; data obtained from some studies reveal a positive association between oxidative stress and neurological diseases&#46; However&#44; these analyses were not obtained from cord blood&#46; One of them stated that analysis of plasma IsoPs &#40;24 and 48 h after birth&#41; might represent an early biomarker to identify the risk of brain damage in premature patients&#46;<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a> Bharadwaj et al&#46;<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> evaluated the neurodevelopment of 71 children and measured oxidative&#47;antioxidant stress levels&#46; They concluded that maternal TAC in PE is useful for predicting impaired motor development at one year of corrected age&#46; Dietze et al&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> observed through salivary cortisol analysis that newborns whose mothers smoked more than ten cigarettes per day were at higher risk for IVH&#46; IVH affects 30 to 60&#37; of preterm infants and is characterized as white matter lesion due to microvascular events that occur in the germ matrix&#44; putting the infant at increased risk for neurodevelopmental delays and additional brain damage&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a></p><p id="para0036" class="elsevierStylePara elsevierViewall">On the other hand&#44; several studies did not confirm the association between oxidative stress biomarkers and the development of pathologies&#44; morbimortality or prognosis&#46; Moore et al&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> examined 31 premature newborns to evaluate the association between CLD and 8-OHdG levels&#46; They observed that CLD was associated with lower levels of oxidative stress&#44; which contradicts previous studies&#46; Authors justify these conflicting results by different methodologies used in sample collection and analysis&#44; alongside other additional factors that might have affected 8-OHdG levels&#46; Dekker et al&#46;<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> evaluated 52 preterm infants for 8iPGF2&#945; levels in order to find a higher risk of developing IVH&#44; but no significant association was found&#46; Norishadkam et al&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> compared 25 premature and 25 term newborns to verify the relationship between oxidative stress and DNA damage and also found no significant association&#46; Stefanov et al&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> evaluated the relationship between glutathione&#44; MDA&#44; and endothelin-1 levels to analyze endothelial dysfunction in 63 infants born between 24 to 42 weeks&#46; Still&#44; there was no significant relationship between the two factors analyzed&#46; Finally&#44; Arman et al&#46;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> evaluated the global oxidant and antioxidant status in newborns of mothers with and without PE&#59; there was no statistical difference between groups&#46; The absence of significant associations in these studies may be justified by clinical factors affecting biomarkers levels&#44; the small sample size in most studies&#44; and the complexity of the neonatal transition period&#44; in which a not fully comprehended mixed-redox state might occur&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a></p><p id="para0037" class="elsevierStylePara elsevierViewall">The present study has some limitations&#46; Although the utility of cord blood samples for the assessment of oxidative stress biomarkers and their possible clinical implications is evident&#44; they cannot be used in follow-up analysis after birth&#46; Alternative non-invasive monitoring options that have shown some positive results are newborn saliva and urine samples&#44; which may be used for longitudinal follow-ups&#46;<a class="elsevierStyleCrossRef" href="#bib0029"><span class="elsevierStyleSup">29</span></a> Also&#44; different methodologies&#44; biomarkers&#44; and the limited number of participants in each study make results unreliable when extrapolating to the general population of preterm babies&#46;</p><p id="para0038" class="elsevierStylePara elsevierViewall">An accurate assessment of oxidative damage and the possibility of targeted treatments might improve neonatal care&#46;<a class="elsevierStyleCrossRef" href="#bib0031"><span class="elsevierStyleSup">31</span></a> Currently&#44; none of these biomarkers are used in clinical practice&#46; However&#44; further researches on the field might help to overcome the technical and economic barriers and enable their routine use&#46; As a future perspective&#44; in the next few years&#44; diagnostic strategies directed to the identification of the risk of oxidative stress-related pathologies might be developed&#44; and guidelines for their prevention and treatment might be updated&#44; reducing the morbidity and mortality of premature newborns&#46;</p><p id="para0039" class="elsevierStylePara elsevierViewall">The authors of the present study conclude that the analysis of oxidative stress and antioxidant levels in cord blood of premature newborns might be useful in assessing the diagnosis and prognosis of some clinically relevant pathologies&#46; Oxidative stress and antioxidant activity are involved in the pathophysiology of the development of several neonatal diseases&#44; and their consequences are associated with increased short- and long-term morbidity&#44; impaired neurodevelopment&#44; and increased mortality&#46; More information and research in the area are needed to impact these clinical outcomes&#46;</p></span></span>"
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    "fechaRecibido" => "2021-07-23"
    "fechaAceptado" => "2021-11-16"
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            0 => "Infant&#44; premature"
            1 => "Oxidative stress"
            2 => "Antioxidants"
            3 => "Diseases"
            4 => "Cord blood"
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    "resumen" => array:1 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara006" class="elsevierStyleSimplePara elsevierViewall">To describe the relationship of oxidative stress and antioxidant biomarkers in cord blood of premature newborns and the prognosis of diseases in the neonatal period&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Sources</span><p id="spara007" class="elsevierStyleSimplePara elsevierViewall">This study consists of an integrative review&#46; Searches were conducted in electronic databases Scopus&#44; PubMed&#44; Web of Science&#44; and Medline&#47;Lilacs through the Virtual Library on Health Issues&#44; using the descriptors&#58; &#8220;premature infants&#8221;&#44; &#8220;preterm infants&#8221;&#44; &#8220;preterm birth&#8221;&#44; &#8220;preterm&#8221;&#44; &#8220;oxidative stress&#8221;&#44; &#8220;antioxidants&#8221;&#44; &#8220;infant&#44; premature&#44; diseases&#8221; and &#8220;cord blood&#8221;&#46; Original articles published between 2016 and 2021 in Portuguese&#44; English&#44; or Spanish&#44; which analyzed oxidative stress and&#47;or antioxidant levels through cord blood of premature newborns and evaluated clinical outcomes&#44; were included&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Summary of the findings</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">Of the 1&#44;003 studies reviewed&#44; after exclusion of duplicate articles&#44; analysis of titles&#44; abstracts&#44; and full texts&#44; 18 articles were included&#46; 72&#46;2&#37; &#40;n&#160;&#61;&#160;13&#41; of analyzed studies reported a positive association between oxidative stress and the development of prematurity-related diseases&#59; 27&#46;7&#37; &#40;n&#160;&#61;&#160;5&#41; showed no significant relation&#46; Outcomes that showed a positive association were&#58; intrauterine growth restriction&#44; necrotizing enterocolitis&#44; bronchopulmonary dysplasia&#44; intraventricular hemorrhage&#44; fetal inflammatory response syndrome&#44; early-onset neonatal sepsis&#44; retinopathy of prematurity&#44; morbidity&#44; and mortality&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusion</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">The analysis of oxidative stress and antioxidants in cord blood of premature newborns may be useful in the prognosis of some pathologies&#46; The consequences of oxidative damage are known to be associated with increased morbidity in the short and long term&#46; Further investigation is needed in this population in order to define normality parameters of biomarkers&#44; clinical manifestations&#44; diagnosis and treatment of these conditions&#46;</p></span>"
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          "leyenda" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">AOPP&#44; advanced oxidative protein products&#59; BPD&#44; bronchopulmonary dysplasia&#59; CLD&#44; chronic lung disease&#59; DNA&#44; deoxyribonucleic acid&#59; ET-1&#44; endothelin-1&#59; FIRS&#44; fetal inflammatory response syndrome&#59; FT&#44; full-term&#59; GA&#44; gestational age&#59; GPx&#44; glutathione peroxidase&#59; IVH&#44; intraventricular hemorrhage&#59; IsoPs&#44; isoprostanes&#59; IUGR&#44; intrauterine growth restriction&#59; MDA&#44; malondialdehyde&#59; NB&#44; newborns&#59; NEC&#44; necrotizing enterocolitis&#59; NICU&#44; neonatal intensive care unit&#59; NPBI&#44; non-protein bound iron&#59; OS&#44; oxidative stress&#59; OSI&#44; oxidative stress index&#59; PE&#61; preeclampsia&#59; PON-1&#44; paraoxonase-1&#59; PPROM&#44; preterm premature rupture of membrane&#59; PTN&#44; preterm newborn&#59; RDS&#44; respiratory distress syndrome&#59; ROP&#44; retinopathy of prematurity&#59; ROS&#44; reactive oxygen species&#59; SOD&#61; superoxide dismutase&#59; TAC&#44; total antioxidant capacity&#59; TOS&#44; total oxidant status&#59; WMI&#44; white matter injury&#59; 8-OHdG&#44; 8- hydroxydeoxyguanosine&#59; 8iPGF2&#945;&#44; 8-iso-prostaglandin F2&#46;</p>"
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                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Article &#47; Country&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Type of study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Sample&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Source of specimen&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0005"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Oxidative stress and antioxidants biomarkers&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0006"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Diseases evaluated&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0007"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Main outcomes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0008"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Moore et al&#46;&#44; 2016<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a>United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">31 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and urine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8-OHdG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CLDIVHBPDROP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">CLD was associated with lower levels of 8-OHdG&#46; There were no significant differences regarding IVH&#44; BPD&#44; and ROP incidences&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Perrone et al&#46;&#44; 2016<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> Italy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">120 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IsoPsNPBIAOPP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IUGR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Placental injuries &#40;inflammation or impaired perfusion&#41; were associated with elevated OS levels&#46; PTN with vascular perfusion lesions had higher levels of AOPP&#44; low GA&#44; and the IUGR&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Dietze et al&#46;&#44; 2016<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">31 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and saliva&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cortisol&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NECIVHBPDROP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">The higher the GA at the beginning of prenatal care&#44; the lower cord blood cortisol and tended to have a higher risk of NEC&#46; In salivary cortisol&#44; NB whose mothers smoked had a higher risk of IVH&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Ghany et al&#46;&#44; 2016<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> Egypt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Case-control study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">200 NB100 PTN100 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and venous blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDA&#59; TACCatalaseVitamin AVitamin E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NECBPDIVH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Positive relationship between reduced antioxidant levels at birth and the risk of neonatal morbidities&#44; including BPD&#44; IVH&#44; NEC&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Bandyopadhyay et al&#46;&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Transversal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">109 NB27 PTN82 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDA8-OHdG&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IUGR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Term NB and late PTN with IUGR had higher levels of MDA and 8-OHdG compared to infants suitable for GA through meconium-stained amniotic fluid&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Norishadkam et al&#46;&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> Iran&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Case-control study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">50 NB25 PTN25 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDACatalaseSODTAC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">DNA damage&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">There was no significant association between MDA&#44; SOD&#44; TAC&#44; catalase&#44; and early DNA damage in cord blood plasma for PTN&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Ozalkaya et al&#46;&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Prospective&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">51 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TACPON-1TOSOSI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">FIRSRDSIVHBPDROPSepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Higher levels of TOS were associated with NB with PPROM&#59; Higher PON-1 was associated with higher risk of PPROM&#44; FIRS or both&#46; NB with PPROM and FIRS had higher incidence of RDS&#46; NB with FIRS had higher mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Bharadwaj et al&#46;&#44; 2017<a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a> India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cohort&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">143 NB71 w&#47; GA &#62;35 e 72 w&#47; GA &#62;39&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Maternal blood and cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Protein carbonylsMDATAC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Neurologic deseasesIUGRSepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">OS increases in NB and mothers with PE&#46; Decreased maternal TAC is associated with negative neuromotor results&#46; Maternal TAC during PE is useful to predict poor motor development at the corrected age of one year&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Coutinho et al&#46;&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> Brazil&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Transversal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&#44; saliva&#44; and urine&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDASODGPxCatalase&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">GPx in cord blood can be a diagnostic tool for suspicion of early-onset neonatal sepsis in PTNs of mothers with risk factors for sepsis&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Armann et al&#46;&#44; 2018<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> Turkey&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Case-control study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">80 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TACTOSOSI&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cardiac functions&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0077"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">TAC&#44; TOS&#44; and OSI were significantly higher for NB of mothers with PE&#46; Echocardiographic parameters are not affected by the oxidant state&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0078"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Elkabany et al&#46;&#44; 2019<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> Egypt&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0079"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ProspectiveCase-control study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0080"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">40 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0081"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0082"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDA&#59; AOPP8-OHdGTACCopper&#59; Zinc&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0083"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">RDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0084"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">AOPPs and 8-OHdG can be used as serum biomarkers for OS among NBs with RDS to monitor disease progression&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0085"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Dekker et al&#46;&#44; 2019 Netherlands<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Clinical trial&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0087"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">52 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0088"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and venous blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8iPGF2&#945;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Grade III IVH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">8iPGF2&#945; did not differ among groups&#46; There were also no differences regarding intubation&#44; the incidence of grade III IVH&#44; or death before hospital discharge&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0092"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Silva et al&#46;&#44; 2019Brazil<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0093"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Transversal&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">140 NB54 PTN and 76 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0095"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Vitamin E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IUGR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IUGR was more frequent in PTB&#59; most of the infants had low vitamin E levels&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0099"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Stefanov et al&#46;&#44; 2020<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> United States&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ProspectivePilot study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0101"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">63 NB50 PTN and 13 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0102"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and venous blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0103"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDAGlutathione&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0104"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Endothelial dysfunction&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0105"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDA was higher in cord blood than at 24 hours of life&#44; regardless of GA&#46; PTN had higher ET-1 levels in cord blood than 24 hours of life&#44; but overall&#44; ET-1 had no significant association with OS&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0106"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Liu et al&#46;&#44; 2020China<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0107"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Case-control study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0108"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">816 NB182 PTN634 FT NB&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0109"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0110"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDASODROSs&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0111"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Morbidity and mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0112"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Higher levels of MDA and ROSs are associated with lower Apgar scores&#59; NICU admission and ventilation&#44; i&#46;e&#46;&#44; are significantly associated with higher morbidity and mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0113"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Pajai e Bezalwar 2020<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> India&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0114"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Observational Analytic&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0115"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">45 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0116"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0117"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDANitratesVitamin CVitamin E&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0118"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Morbidity and mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0119"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">PTN shows higher MDA and nitrates levels and reduced levels of vitamins C and E&#44; especially in males&#44; indicating increased morbidity and mortality&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0120"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Agrawal et al&#46;&#44; 2021&#205;ndia<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0121"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Nested case-control&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0122"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">189 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0123"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and venous blood &#40;both from NB and mother&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0124"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDACopperZincVitamin A&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0125"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ROP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0126"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">MDA and vitamin A in umbilical cord plasma were independent predictive variables of ROP&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0127"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Coviello et al&#46;&#44; 2021Netherlands<a class="elsevierStyleCrossRef" href="#bib0028"><span class="elsevierStyleSup">28</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0128"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Prospective observational study&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0129"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">44 PTN&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0130"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Cord blood and plasma&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0131"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">F2-isoprostanes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0132"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">White matter injury&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0133"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Early verification of plasma IsoPs can help discriminate abnormal WMI scores at term-equivalent age&#59; and represents an early biomarker for identifying PTN at risk of brain injury&#46;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Studies reviewed by oxidative stress biomarker category&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0002"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "alt0003"
            "detalle" => "Table "
            "rol" => "short"
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        "tabla" => array:2 [
          "leyenda" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">AOPP&#44; advanced oxidative protein products&#59; BPD&#44; bronchopulmonary dysplasia&#59; FIRS&#44; fetal inflammatory response syndrome&#59; GPx&#44; glutathione peroxidase&#59; IVH&#44; intraventricular hemorrhage&#59; IUGR&#44; intrauterine growth restriction&#59; MDA&#44; malondialdehyde&#59; NEC&#44; necrotizing enterocolitis&#59; PON-1&#44; paraoxonase-1&#59; RDS&#44; respiratory distress syndrome&#59; ROP&#44; retinopathy of prematurity&#59; ROS&#44; reactive oxygen species&#59; 8-OHdG&#44; 8- hydroxydeoxyguanosine&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0134"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Condition&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><a name="en0135"></a><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Biomarker&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0136"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">ROP&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0137"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8593; MDA<span class="elsevierStyleSup">27</span>&#8595; Vitamin A<span class="elsevierStyleSup">27</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0138"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IUGR&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0139"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8593; AOPP<span class="elsevierStyleSup">13</span>&#8593; MDA<span class="elsevierStyleSup">8</span>&#8593; 8-OHdG<span class="elsevierStyleSup">8</span>&#8595; Vitamin E<span class="elsevierStyleSup">25</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0140"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">NEC&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0141"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8593; Cortisol<span class="elsevierStyleSup">20</span>&#8595; Vitamin A<span class="elsevierStyleSup">10</span>&#8595; Vitamin E<span class="elsevierStyleSup">10</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0142"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">BPD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0143"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8595; Vitamin A<span class="elsevierStyleSup">10</span>&#8595; Vitamin E<span class="elsevierStyleSup">10</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0144"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">IVH&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0145"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8595; Vitamin A<span class="elsevierStyleSup">10</span>&#8595; Vitamin E<span class="elsevierStyleSup">10</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0146"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">FIRS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0147"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8595; PON-1<span class="elsevierStyleSup">21</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0148"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Sepsis&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0149"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8595; GPx<span class="elsevierStyleSup">22</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0150"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">RDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0151"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8593; AOPP<span class="elsevierStyleSup">12</span>&#8593; 8-OHdG<span class="elsevierStyleSup">12</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0152"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Morbidity and mortality&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0153"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8593; MDA<span class="elsevierStyleSup">5&#44;26</span>&#8593; ROS<span class="elsevierStyleSup">26</span>&#8593; Nitrates<span class="elsevierStyleSup">5</span>&#8595; Vitamin C<span class="elsevierStyleSup">5</span>&#8595; Vitamin E<span class="elsevierStyleSup">5</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Oxidative stress biomarkers and antioxidants correlated with evaluated conditions&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec1"
          "bibliografiaReferencia" => array:31 [
            0 => array:3 [
              "identificador" => "bib0001"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "World Health Organization&#46; Preterm birth &#8211;19 February 2018&#46; &#91;Internet&#93;&#46; World Health Organization&#59; c2018 &#91;Cited 2021 Mar 5&#93;&#46; Available from&#58; <a target="_blank" href="http://www.who.int/mediacentre/factsheets/fs363/en/">http&#58;&#47;&#47;www&#46;who&#46;int&#47;mediacentre&#47;factsheets&#47;fs363&#47;en&#47;</a>"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0002"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Organiza&#231;&#227;o Pan-Americana da Sa&#250;de&#46; Organiza&#231;&#227;o Mundial da Sa&#250;de&#46; OPAS Brasil Quase 30 Milh&#245;es de Rec&#233;m-Nascidos Prematuros e Doentes Necessitam de Tratamento Para Sobreviver Todos os anos&#46; &#91;Internet&#93;&#46; Organiza&#231;&#227;o Pan-Americana da Sa&#250;de&#59; c2018 &#91;Cited 2021 Mar 5&#93;&#46; Available from&#58; https&#58;&#47;&#47;www&#46;paho&#46;org&#47;bra&#47;index&#46;php&#63;option&#61;com&#95;content&#38;view&#61;article&#38;id&#61;5821&#58;quase-30-milhoes-de-recem-nascidos-prematuros-e-doentes-necessitam-de-tratamento-para-sobreviver-todos-os-anos&#38;Itemid&#61;820&#35;&#58;&#8764;&#58;text&#61;De&#37;20acordo&#37;20com&#37;20o&#37;20relat&#37;C3&#37;B3rio&#44;beb&#37;C3&#37;AAs&#37;20que&#37;20morrem&#37;20nasceram&#37;20prematuros"
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0003"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress&#44; antioxidant status and neurodevelopmental outcome in neonates born to pre-eclamptic mothers"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "SK Bharadwaj"
                            1 => "BV Bhat"
                            2 => "V Vickneswaran"
                            3 => "B Adhisivam"
                            4 => "Z Bobby"
                            5 => "S Habeebullah"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s12098-017-2560-5"
                      "Revista" => array:6 [
                        "tituloSerie" => "Indian J Pediatr"
                        "fecha" => "2018"
                        "volumen" => "85"
                        "paginaInicial" => "351"
                        "paginaFinal" => "357"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/29264827"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0004"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Oxidative stress and dna damage in the cord blood of preterm infants"
                      "autores" => array:1 [
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Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2021.11.008

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Year/Month	Html	Pdf	Total

2024 November	6	4	10
2024 October	37	25	62
2024 September	19	27	46
2024 August	53	35	88
2024 July	41	37	78
2024 June	24	18	42
2024 May	25	20	45
2024 April	31	28	59
2024 March	22	17	39
2024 February	37	20	57
2024 January	37	23	60
2023 December	22	29	51
2023 November	36	36	72
2023 October	29	37	66
2023 September	51	39	90
2023 August	41	16	57
2023 July	29	16	45
2023 June	34	15	49
2023 May	50	18	68
2023 April	32	21	53
2023 March	93	17	110
2023 February	61	19	80
2023 January	51	43	94
2022 December	115	53	168
2022 November	80	41	121
2022 October	154	83	237
2022 September	64	58	122
2022 August	47	47	94
2022 July	56	47	103
2022 June	47	41	88
2022 May	37	26	63
2022 April	54	36	90
2022 March	60	43	103
2022 February	32	26	58
2022 January	25	21	46

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