Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels

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Studies in the literature have reported an increased incidence of hypotonia, intubation in the delivery room, a higher need for mechanical ventilation and patent ductus arteriosus, among other respiratory, haemodynamic,<a class="elsevierStyleCrossRef" href="#bib0165">11</a> neurologic and gastrointestinal<a class="elsevierStyleCrossRefs" href="#bib0145">7,12</a> adverse effects.On the other hand, there is currently no consensus regarding the dose, standard regimen, therapeutic window and safety of the use of MgSO4 for neuroprotection. The cumulative dose of magnesium received by the mother that is safe to the newborn is not known, as its association with the serum levels of magnesium in the newborn has not been sufficiently studied.<a class="elsevierStyleCrossRef" href="#bib0175">13</a> Thus, although there is a therapeutic window in which the neuroprotective effects of magnesium are observed, it is known that neonatal morbidity and mortality increase after serum magnesium exceeds certain levels in the newborn.<a class="elsevierStyleCrossRef" href="#bib0180">14</a>The main aim of our study was to assess the initial clinical outcomes of patients admitted to a tertiary level neonatal intensive care unit (NICU) that received prenatal MgSO4 for neuroprotection, to analyse the potential side effects of its administration, and last of all to determine the association between the dose of magnesium given to the mother and the serum levels of magnesium in the newborn.Materials and methodsWe conducted a prospective cohort study from December 2012 to July 2015. We included newborns delivered at less than 29 weeks’ gestation to mothers that were given MgSO4 for neuroprotection admitted to the NICU of the Complejo Hospitalario Universitario de Vigo. We compared these preterm newborns to a control group of the same gestational age born during the same period. We excluded newborns with other risk factors leading to immediately poor outcomes, which in our series included one patient with polymalformation syndrome and one that died a few hours after birth following placental abruption. We chose newborns of less than 29 weeks of gestational age because this group is more likely to require advanced resuscitation measures in the delivery room or respiratory support with invasive mechanical ventilation, and is at higher riskof neurologic sequelae.<a class="elsevierStyleCrossRefs" href="#bib0115">1,5</a>We collected data for the following perinatal variables: gestational age, weight, small for gestational age (defined as birth weight below the 10th percentile), sex, twin pregnancy, caesarean delivery, exposure to prenatal corticosteroids, chorioamnionitis (diagnosed by histological examination), preeclampsia, gestational diabetes and timing of rupture of membranes.We analysed the need in the first hour of life of advanced or intensive cardiopulmonary resuscitation (CPR) (defined as any of the following: intubation,chest compressions, administration of epinephrine), the Apgar score at 1 and 5min, and the umbilical artery pH.We studied a series of haemodynamic, respiratory, neurologic, gastrointestinal, ophthalmologic and infectious variables.The haemodynamic analysis included the sonographic assessment for patent ductus arteriosus, the need for volume expansion and the administration of inotropic agents for low blood pressure.To assess the impact of MgSO4 from a respiratory perspective, we took into account the need for invasive mechanical ventilation, surfactant administration, the total duration of oxygen therapy (in days), the presence of bronchopulmonary dysplasia (BPD) and its severity (based on the definition given by the Standards Committee of the Sociedad Española de Neonatología [Spanish Society of Neonatology], 2013)<a class="elsevierStyleCrossRef" href="#bib0185">15</a> and administration of intravenous corticosteroids for BPD.The study of gastrointestinal variables included the presence of necrotising enterocolitis (NEC),<a class="elsevierStyleCrossRef" href="#bib0190">16</a> the day since birth at which enteral feedings were initiated, and the day when exclusive enteral feeding without need for any type of parenteral supplementation was achieved.We also analysed neurologic outcomes (development of intraventricular haemorrhage [HIV] and periventricularleukomalacia), ophthalmologic outcomes (retinopathy of prematurity), infectious outcomes (nosocomial sepsis, defined as elevated acute phase reactants combined with clinical manifestations of sepsis) and mortality.In our hospital, the MgSO4 regimen used for neuroprotection is the same that has been used for the treatment of preeclampsia and/or prevention of eclampsia.<a class="elsevierStyleCrossRef" href="#bib0175">13</a> Treatment with MgSO4 is initiated with a loading dose of 4g delivered over half an hour and continues with infusion of 1g/hour until delivery. Administration of MgSO4 should be discontinued if delivery does not occur within 24h of initiating infusion. If the risk of imminent preterm birth recurs after discontinuation, treatment with MgSO4 should be resumed. If less than 6h have elapsed from discontinuation, treatment should resume with the maintenance dose, and otherwise should be reinitiated with a loading dose.To study the association between the cumulative dose of magnesium received by mothers and the levels of magnesium in the newborn, we measured these levels in the first 24h from birth in all preterm newborns whose mothers had received MgSO4 by adding this parameter to blood tests performed for other reasons.We analysed the data with SPSS version 21. We used the Kolmogorov–Smirnov test to analyse distribution of the variables, and based the analysis of quantitative variables on its results, using Student's t test and ANOVA for normally distributed variables and the Mann–Whitney U test for nonparametric variables. We analysed differences between nominal variables by means of the chi square test. We conducted linear regression analysis to determine the statistically significant correlations between qualitative variables. We considered differences to be statistically significant when the p-value obtained in any of the tests mentioned above was less than 0.05.ResultsThe total sample consisted of 42 newborns of less than 29 weeks of gestational age, of whom 28 were exposed to MgSO4 prenatally, and 14 were not.Both groups had similar perinatal characteristics, which allowed the comparison of the treatment and control groups. The percentage of caesarean deliveries (85.7%) and twin pregnancies (46.4%) was higher in the group treated with MgSO4 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>), and these differences were statistically significant.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>We did not find any differences in the outcomes of the two groups in terms of need for advanced CPR, Apgar score, umbilical artery pH, respiratory variables, neurologic variables, retinopathy (grade >2),and nosocomial sepsis (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). However, the mortality was greater in the group that was not treated with MgSO4 (21.4%), a difference that was statistically significant. Furthermore, while the incidence of BPD was similar in both groups, the subset of patients born before 29 weeks’ gestation and not treated with MgSO4 had a higher incidence of moderate-to-severe BPD (five cases of moderate-severe BPD compared to 2).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>All newborns and their mothers were included in the analysis of the association between maternal magnesium dose and neonatal magnesium levels. In the group treated with MgSO4, the prenatal exposure was of 4g in eight newborns, more than 8g in twelve newborns, and between 4 and 8g in the rest. The mean cumulative dose of MgSO4 given to mothers was 10.09g, with a median of 7.5g.<a class="elsevierStyleCrossRef" href="#bib0180">14</a> The mean serum levels of magnesium in exposed newborns was 2.68mg/dL (median, 2.65mg/dL), which differed significantly from magnesium levels measured the first day of life in newborns that were not treated with MgSO4 (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). We found a statistically significant linear correlation between the MgSO4 dose received by mothers and the magnesium serum levels measured in newborns in the first 24h of life (r2=0.436; p<0.001). In our series, the highest serum level of magnesium was 4.04mg/dL and corresponded to a newborn whose mother had received 20g of MgSO4.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>Using the cumulative dose of magnesium received by the mother and the serum levels of magnesium in the newborn (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>), we conducted an analysis to assess the correlation between birth weight and serum magnesium levels, but found no statistically significant differences.We also compared the levels of magnesium in preterm newborns whose mothers had only received the loading bolus with 4g of MgSO4 with the levels in newborns of mothers that were not treated with MgSO4. The group with mothers that received the loading dose of 4g of MgSO4 had a mean serum level of magnesium of 2.39mg/dL (median, 2.3mg/dL), while the group that was not exposed to magnesium had a mean serum level of magnesium of 1.89mg/dL (median, 1.86mg/dL), a difference that was statistically significant.DiscussionWhen it came to the initial outcomes in the delivery room, we found no significant differences in the need for advanced CPR, Apgar score or umbilical artery pH. These results were consistent with those of other cohort studies that already supported the safety of the use of MgSO4 under these circumstances.<a class="elsevierStyleCrossRef" href="#bib0195">17</a>From a respiratory perspective, there were no differences in the need for invasive mechanical ventilation, use of surfactant and total days of oxygen therapy, so we could not attribute any respiratory side effects to MgSO4, contrary to what has been assumed historically, as treatment with MgSO4 was associated with an increased incidence of respiratory depression.<a class="elsevierStyleCrossRef" href="#bib0200">18</a> Bronchopulmonary dysplasia was less severe in the treated group.From a haemodynamic perspective, the absence of adverse effects was also consistent with the finding of other studies, as we did not observe an increased prevalence of patent ductus arteriosus or increased use of inotropic agents.<a class="elsevierStyleCrossRef" href="#bib0205">19</a> We did not find differences in the remaining outcome variablesduring the stay in the NICU, and we observed that, at the neurologic level, the incidence of IVH and leukomalacia were similar in both groups. In this regard, it would be interesting to conduct a long-term followup of these patients to study their psychomotor development. We also found no differences at the gastrointestinal level in either the development of NEC, initiation of enteral nutrition or the number of days post birth at which full enteral nutrition was achieved. Furthermore, we observed similar outcomes in relation to the development of retinopathy of prematurity from an ophthalmologic perspective, and of nosocomial sepsis from an infectious perspective.We did find differences in mortality in the group treated with MgSO4. Once again, the small sample size requires that we interpret this result with caution and continue collecting data for future comparisons. We must keep in mind that the Cochrane systematic review of 2009<a class="elsevierStyleCrossRef" href="#bib0175">13</a> established that when MgSO4 was administered for the sole purpose of neuroprotection, there was a reduction in the composite outcome of death and cerebral palsy at age 2 years in exposed children.<a class="elsevierStyleCrossRefs" href="#bib0155">9,20</a>It would be worth exploring whether the association of MgSO4 exposure with a decrease in childhood mortality starts as early as the neonatal period. Other studies in the literature have also found a lower mortality in the group treated with MgSO4,<a class="elsevierStyleCrossRef" href="#bib0195">17</a> although its mechanism of action remains unclear. Studies conducted in recent years have found an association between antenatal MgSO4 and decreased oxygen consumption in the newborn brain, with a decreased cerebral fractional tissue oxygenation extraction (cFTOE).<a class="elsevierStyleCrossRef" href="#bib0215">21</a>When it came to the dose of MgSO4 administered to the mothers, we found a linear correlation between the cumulative dose and magnesium levels in newborns of less than 29 weeks of gestational age in the first 24h post birth. This finding allows the establishment of safe maternal doses to prevent the development of side effects in preterm newborns.The mean level of magnesium in the newborns was 2.68mg/dL, below the 4.5mg/dLthreshold potentially associated with the development of side effects and poor clinical outcomes in the neonatal period.<a class="elsevierStyleCrossRef" href="#bib0220">22</a> It is very likely that the absence of side effects from the use of MgSO4 in our series was due to the generally low doses administered to the mothers. In the group of exposed children in our study, the highest level of magnesium was 4.04mg/dL and corresponded to a boy whose mother had received 20g of MgSO4. Therefore, we could establish a safety threshold of 20g for the cumulative dose and 16h of continuous infusion, after which the dose would come dangerously close to levels associated with worse outcomes.In eight out of the twenty-eight newborns of mothers treated with MgSO4, the mother was only given the loading bolus with 4g due to the short time elapsed to delivery. Even these newborns had a statistically significant increase in magnesium levels compared to the newborns of mothers that had not received MgSO4. For this reason, we recommend that at least the loading dose of 4g be given to mothers at risk of giving birth at less than 29 weeks’ gestation, even if the birth is imminent.We also recommend the measurement of magnesium levels in all newborns of mothers treated with MgSO4 before birth. The reasons for this are, first, the increased mortality detected in association with serum levels of magnesium greater than 4.5mg/dL<a class="elsevierStyleCrossRef" href="#bib0220">22</a> and, second, the adjustments that need to be made in the composition of the parenteral feeds administered to these newborns in the first days of life until their magnesium levels normalise.In conclusion, our study found that MgSO4 was safe at the administered dose, with a linear correlation between serum levels of magnesium in the newborn in the first 24h of life and the cumulative dose of magnesium received by the mother.Long-term follow-up studies of the patients included in this study are requiredto assess the impact of MgSO4 therapy on future neurodevelopmental outcomes.Conflict of interestsThe authors have no conflict of interests to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:10 [ 0 => array:3 [ "identificador" => "xres805124" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec803280" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres805123" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec803281" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Materials and methods" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Results" ] 7 => array:2 [ "identificador" => "sec0020" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0025" "titulo" => "Conflict of interests" ] 9 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-02-16" "fechaAceptado" => "2016-04-25" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec803280" "palabras" => array:3 [ 0 => "Magnesium sulphate" 1 => "Neuroprotection" 2 => "Mortality" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec803281" "palabras" => array:3 [ 0 => "Sulfato de magnesio" 1 => "Neuroprotección" 2 => "Mortalidad" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "IntroductionAntenatal magnesium sulphate (MgSO4) administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years.The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO4, as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates. Material and methodsA prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit (NICU) of Hospital Universitario de Vigo from December 2012 to July 2015. Comparative analysis was performed on the perinatal outcomes, neonatal morbidity, mortality, and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group. ResultsA total of 42 neonates were included in the study. The mothers of 28 of them had received MgSO4 as a neuroprotective agent.Statistical significance was obtained in the mortality variable. There were no significant differences in the rest of studied variables. There was a significant correlation between the full dose of MgSO4 received by the mother and the levels of magnesium in the neonate in the first 24h of life (r2 0.436; P<0.001). ConclusionsA lower mortality was observed in the group that had been exposed to MgSO4. No significant side effects were found as a result of administering of MgSO4. The MgSO4 dose received by mother has a linear relationship with the magnesium levels obtained in neonates." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Material and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "IntroducciónLa administración prenatal de MgSO4 ha mostrado su eficacia en reducir la parálisis cerebral y la disfunción motora severa a los 2 años de edad.El objetivo de este trabajo es estudiar la evolución clínica inicial de los neonatos menores de 29 semanas, que han recibido prenatalmente MgSO4 con indicación neuroprotectora y dilucidar la asociación entre la dosis de magnesio administrada a la madre y las concentraciones de magnesio en suero neonatal. Material y métodosEstudio prospectivo de cohortes en el que se incluyó a los neonatos menores de 29 semanas ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Universitario de Vigo desde diciembre del 2012 hasta julio del 2015. Análisis comparativo de resultados perinatales, de morbimortalidad neonatal y magnesemia entre el grupo expuesto prenatalmente al sulfato de magnesio y un grupo control. ResultadosSe incluyó a un total de 42 recién nacidos, en 28 de los cuales sus madres habían recibido MgSO4.Se encontró significación estadística en la variable mortalidad. No hubo diferencias significativas en el resto de las variables estudiadas. Se obtuvo una correlación significativa entre la dosis total de MgSO4 recibida por la madre y los niveles de magnesio del recién nacido en las primeras 24 h de vida (r2 0,436; p<0,001). ConclusionesSe ha obtenido una menor mortalidad en el grupo expuesto a MgSO4. No se han encontrado efectos secundarios significativos derivados de la administración de MgSO4. La dosis de MgSO4 recibida por las madres tiene una relación lineal con los niveles de magnesio obtenidos en los recién nacidos." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Material y métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "Please cite this article as: García Alonso L, Pumarada Prieto M, González Colmenero E, Concheiro Guisán A, Suárez Albo M, Durán Fernández-Feijoo C, et al. Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal. An Pediatr (Barc). 2017;86:135–141." ] ] "multimedia" => array:3 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "HBP, high blood pressure; MgSO4, prenatal treatment with magnesium sulphate; No MgSO4, no prenatal treatment with magnesium sulphate; NS, not significant; SD, standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Frequency (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 (66.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (33.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight in g (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">869.68±207.19 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">951.43±244.07 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational age in weeks (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">27.26±1.18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">26.84±1.93 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (57.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Small for gestational age (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prenatal corticosteroids (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 (100) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (92.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chorioamnionitis (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (48.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (69.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preeclampsia (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (17.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBP (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Twin (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (46.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.016 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Caesarean (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">24 (85.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.022 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational diabetes (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (7.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1351136.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Perinatal variables." ] ] 1 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "BPD, bronchopulmonary dysplasia; CPR, cardiopulmonary resuscitation; IMV, invasive mechanical ventilation; IV, intravenous; IVH, intraventricular haemorrhage; MgSO4, prenatal treatment with magnesium sulphate; No MgSO4, no prenatal treatment with magnesium sulphate; NS, not significant; PDA, patent ductus arteriosus; PVL, periventricular leukomalacia; ROP>2, retinopathy of prematurity grade>2; SD, standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum magnesium (mg/dL) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.68±0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.89±0.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum calcium (mg/dL) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.87±0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.2±0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Advanced CPR (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">18 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (71.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Umbilical artery pH (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.27±0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.21±0.17 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apgar 1 (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.03±1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.36±1.15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apgar 5 (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.34±0.72 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.00±0.88 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IMV (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (82.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13 (92.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surfactant (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">23 (82.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (85.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total days of O2 (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">42.10±21.25 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">47.09±25.50 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BPD (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (75) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (72.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate-severe BPD (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (62.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.007 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IV corticosteroids (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (20.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inotropes (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">15 (53.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9 (64.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PDA (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 (42.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (50) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initiation enteral nutrition (days) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.41±0.98 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.38±1.80 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Full enteral nutrition (days) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">20.48±15.55 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">25.09±13.59 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Death (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (21.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.029 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVH (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7 (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (42.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVH grade III–IV (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (17.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NEC (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5 (17.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (30.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PVL (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 (14.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ROP>2 (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10 (35.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2 (18.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nosocomial sepsis (%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17 (60.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 (61.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">NS \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1351138.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Neonatal outcomes." ] ] 2 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:2 [ 0 => array:2 [ "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">P \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Newborns (N) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">28 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mg (mg/dL) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.68±0.10 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.89±0.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1351137.png" ] ] 1 => array:2 [ "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"><th class="td" title="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO4 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4≤4g \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4>4g and <8g \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO4≥8g \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Newborns (N) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Neonatal Mg (mg/dL) (mean±SD) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.89±0.66 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.39±0.13 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.40±0.11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.07±0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " colspan="2" align="center" valign="top">p=0.002</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1351139.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Mean levels of magnesium, and levels by cumulative maternal dose." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:22 [ 0 => array:3 [ "identificador" => "bib0115" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Cerebral palsy in preterm infants: a population-based case–control study of antenatal and intrapartal risk factors" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "B. 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"vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/23412879/0000008600000003/v1_201702231638/S2341287917300030/v1_201702231638/en/main.assets" "Apartado" => array:4 [ "identificador" => "26005" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/23412879/0000008600000003/v1_201702231638/S2341287917300030/v1_201702231638/en/main.pdf?idApp=UINPBA00005H&text.app=https://analesdepediatria.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917300030?idApp=UINPBA00005H"]

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Prenatal treatment with magnesium sulphate: Initial clinical outcomes in pre-term infants less than 29 weeks and correlation with neonatal magnesium levels

Terapia prenatal con sulfato de magnesio: evolución clínica de los recién nacidos pretérmino menores de 29 semanas y correlación con la magnesemia neonatal

Laura García Alonso

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laura14_01_88@hotmail.com

Corresponding author.

, Marcelino Pumarada Prieto, Eva González Colmenero, Ana Concheiro Guisán, María Suárez Albo, Cristina Durán Fernández-Feijoo, Luisa González Durán, José Ramón Fernández Lorenzo

Servicio de Pediatría, Hospital Universitario Álvaro Cunqueiro, Vigo, Pontevedra, Spain

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Although the survival rates of preterm newborns have increased significantly in the past 20 years&#44; the incidence of cerebral palsy &#40;CP&#41; in children has remained stable through time&#44; probably due to the increased survival of extremely preterm NBs and the associated morbidity and neurosensory impairment&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">The main risk factor for CP in children is preterm birth&#44; and 35&#37; of cases occur in children born at less than 34 weeks&#8217; gestation&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">3</span></a> Cerebral palsy is 70 times more frequent in children born at less than 28 weeks and 40 times more frequent in children born at 28&#8211;32 weeks compared to children born to term&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">4&#8211;7</span></a> The risk is inversely proportional to gestational age&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">A Cochrane systematic review<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">8</span></a> published in 2009 concluded that administration of magnesium sulphate &#40;MgSO<span class="elsevierStyleInf">4</span>&#41; to women at risk of preterm birth&#44; regardless of its purpose or route of administration&#44; significantly reduces the incidence of cerebral palsy and severe motor dysfunction at age 2 years in children born before 32 weeks&#8217; gestation&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">Two metaanalyses<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">9&#44;10</span></a> published in 2009 suggest that the number needed to treat to prevent one case of CP is 63 pregnant women&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">However&#44; few studies have assessed the initial outcomes of newborns exposed to MgSO<span class="elsevierStyleInf">4</span> before birth or described their clinical course during admission in the neonatal period&#46; Studies in the literature have reported an increased incidence of hypotonia&#44; intubation in the delivery room&#44; a higher need for mechanical ventilation and patent ductus arteriosus&#44; among other respiratory&#44; haemodynamic&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">11</span></a> neurologic and gastrointestinal<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">7&#44;12</span></a> adverse effects&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">On the other hand&#44; there is currently no consensus regarding the dose&#44; standard regimen&#44; therapeutic window and safety of the use of MgSO<span class="elsevierStyleInf">4</span> for neuroprotection&#46; The cumulative dose of magnesium received by the mother that is safe to the newborn is not known&#44; as its association with the serum levels of magnesium in the newborn has not been sufficiently studied&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> Thus&#44; although there is a therapeutic window in which the neuroprotective effects of magnesium are observed&#44; it is known that neonatal morbidity and mortality increase after serum magnesium exceeds certain levels in the newborn&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The main aim of our study was to assess the initial clinical outcomes of patients admitted to a tertiary level neonatal intensive care unit &#40;NICU&#41; that received prenatal MgSO<span class="elsevierStyleInf">4</span> for neuroprotection&#44; to analyse the potential side effects of its administration&#44; and last of all to determine the association between the dose of magnesium given to the mother and the serum levels of magnesium in the newborn&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Materials and methods</span><p id="par0040" class="elsevierStylePara elsevierViewall">We conducted a prospective cohort study from December 2012 to July 2015&#46; We included newborns delivered at less than 29 weeks&#8217; gestation to mothers that were given MgSO<span class="elsevierStyleInf">4</span> for neuroprotection admitted to the NICU of the Complejo Hospitalario Universitario de Vigo&#46; We compared these preterm newborns to a control group of the same gestational age born during the same period&#46; We excluded newborns with other risk factors leading to immediately poor outcomes&#44; which in our series included one patient with polymalformation syndrome and one that died a few hours after birth following placental abruption&#46; We chose newborns of less than 29 weeks of gestational age because this group is more likely to require advanced resuscitation measures in the delivery room or respiratory support with invasive mechanical ventilation&#44; and is at higher riskof neurologic sequelae&#46;<a class="elsevierStyleCrossRefs" href="#bib0115"><span class="elsevierStyleSup">1&#44;5</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">We collected data for the following perinatal variables&#58; gestational age&#44; weight&#44; small for gestational age &#40;defined as birth weight below the 10th percentile&#41;&#44; sex&#44; twin pregnancy&#44; caesarean delivery&#44; exposure to prenatal corticosteroids&#44; chorioamnionitis &#40;diagnosed by histological examination&#41;&#44; preeclampsia&#44; gestational diabetes and timing of rupture of membranes&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">We analysed the need in the first hour of life of advanced or intensive cardiopulmonary resuscitation &#40;CPR&#41; &#40;defined as any of the following&#58; intubation&#44;chest compressions&#44; administration of epinephrine&#41;&#44; the Apgar score at 1 and 5<span class="elsevierStyleHsp" style=""></span>min&#44; and the umbilical artery pH&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We studied a series of haemodynamic&#44; respiratory&#44; neurologic&#44; gastrointestinal&#44; ophthalmologic and infectious variables&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">The haemodynamic analysis included the sonographic assessment for patent ductus arteriosus&#44; the need for volume expansion and the administration of inotropic agents for low blood pressure&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">To assess the impact of MgSO<span class="elsevierStyleInf">4</span> from a respiratory perspective&#44; we took into account the need for invasive mechanical ventilation&#44; surfactant administration&#44; the total duration of oxygen therapy &#40;in days&#41;&#44; the presence of bronchopulmonary dysplasia &#40;BPD&#41; and its severity &#40;based on the definition given by the Standards Committee of the Sociedad Espa&#241;ola de Neonatolog&#237;a &#91;Spanish Society of Neonatology&#93;&#44; 2013&#41;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">15</span></a> and administration of intravenous corticosteroids for BPD&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The study of gastrointestinal variables included the presence of necrotising enterocolitis &#40;NEC&#41;&#44;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">16</span></a> the day since birth at which enteral feedings were initiated&#44; and the day when exclusive enteral feeding without need for any type of parenteral supplementation was achieved&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We also analysed neurologic outcomes &#40;development of intraventricular haemorrhage &#91;HIV&#93; and periventricularleukomalacia&#41;&#44; ophthalmologic outcomes &#40;retinopathy of prematurity&#41;&#44; infectious outcomes &#40;nosocomial sepsis&#44; defined as elevated acute phase reactants combined with clinical manifestations of sepsis&#41; and mortality&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">In our hospital&#44; the MgSO<span class="elsevierStyleInf">4</span> regimen used for neuroprotection is the same that has been used for the treatment of preeclampsia and&#47;or prevention of eclampsia&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> Treatment with MgSO<span class="elsevierStyleInf">4</span> is initiated with a loading dose of 4<span class="elsevierStyleHsp" style=""></span>g delivered over half an hour and continues with infusion of 1<span class="elsevierStyleHsp" style=""></span>g&#47;hour until delivery&#46; Administration of MgSO<span class="elsevierStyleInf">4</span> should be discontinued if delivery does not occur within 24<span class="elsevierStyleHsp" style=""></span>h of initiating infusion&#46; If the risk of imminent preterm birth recurs after discontinuation&#44; treatment with MgSO<span class="elsevierStyleInf">4</span> should be resumed&#46; If less than 6<span class="elsevierStyleHsp" style=""></span>h have elapsed from discontinuation&#44; treatment should resume with the maintenance dose&#44; and otherwise should be reinitiated with a loading dose&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">To study the association between the cumulative dose of magnesium received by mothers and the levels of magnesium in the newborn&#44; we measured these levels in the first 24<span class="elsevierStyleHsp" style=""></span>h from birth in all preterm newborns whose mothers had received MgSO<span class="elsevierStyleInf">4</span> by adding this parameter to blood tests performed for other reasons&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">We analysed the data with SPSS version 21&#46; We used the Kolmogorov&#8211;Smirnov test to analyse distribution of the variables&#44; and based the analysis of quantitative variables on its results&#44; using Student&#39;s <span class="elsevierStyleItalic">t</span> test and ANOVA for normally distributed variables and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test for nonparametric variables&#46; We analysed differences between nominal variables by means of the chi square test&#46; We conducted linear regression analysis to determine the statistically significant correlations between qualitative variables&#46; We considered differences to be statistically significant when the <span class="elsevierStyleItalic">p</span>-value obtained in any of the tests mentioned above was less than 0&#46;05&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><p id="par0095" class="elsevierStylePara elsevierViewall">The total sample consisted of 42 newborns of less than 29 weeks of gestational age&#44; of whom 28 were exposed to MgSO<span class="elsevierStyleInf">4</span> prenatally&#44; and 14 were not&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Both groups had similar perinatal characteristics&#44; which allowed the comparison of the treatment and control groups&#46; The percentage of caesarean deliveries &#40;85&#46;7&#37;&#41; and twin pregnancies &#40;46&#46;4&#37;&#41; was higher in the group treated with MgSO<span class="elsevierStyleInf">4</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; and these differences were statistically significant&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">We did not find any differences in the outcomes of the two groups in terms of need for advanced CPR&#44; Apgar score&#44; umbilical artery pH&#44; respiratory variables&#44; neurologic variables&#44; retinopathy &#40;grade &#62;2&#41;&#44;and nosocomial sepsis &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#46; However&#44; the mortality was greater in the group that was not treated with MgSO<span class="elsevierStyleInf">4</span> &#40;21&#46;4&#37;&#41;&#44; a difference that was statistically significant&#46; Furthermore&#44; while the incidence of BPD was similar in both groups&#44; the subset of patients born before 29 weeks&#8217; gestation and not treated with MgSO<span class="elsevierStyleInf">4</span> had a higher incidence of moderate-to-severe BPD &#40;five cases of moderate-severe BPD compared to 2&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0110" class="elsevierStylePara elsevierViewall">All newborns and their mothers were included in the analysis of the association between maternal magnesium dose and neonatal magnesium levels&#46; In the group treated with MgSO<span class="elsevierStyleInf">4</span>&#44; the prenatal exposure was of 4<span class="elsevierStyleHsp" style=""></span>g in eight newborns&#44; more than 8<span class="elsevierStyleHsp" style=""></span>g in twelve newborns&#44; and between 4 and 8<span class="elsevierStyleHsp" style=""></span>g in the rest&#46; The mean cumulative dose of MgSO<span class="elsevierStyleInf">4</span> given to mothers was 10&#46;09<span class="elsevierStyleHsp" style=""></span>g&#44; with a median of 7&#46;5<span class="elsevierStyleHsp" style=""></span>g&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">14</span></a> The mean serum levels of magnesium in exposed newborns was 2&#46;68<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;median&#44; 2&#46;65<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; which differed significantly from magnesium levels measured the first day of life in newborns that were not treated with MgSO<span class="elsevierStyleInf">4</span> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; We found a statistically significant linear correlation between the MgSO<span class="elsevierStyleInf">4</span> dose received by mothers and the magnesium serum levels measured in newborns in the first 24<span class="elsevierStyleHsp" style=""></span>h of life &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;436&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; In our series&#44; the highest serum level of magnesium was 4&#46;04<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and corresponded to a newborn whose mother had received 20<span class="elsevierStyleHsp" style=""></span>g of MgSO<span class="elsevierStyleInf">4</span>&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Using the cumulative dose of magnesium received by the mother and the serum levels of magnesium in the newborn &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; we conducted an analysis to assess the correlation between birth weight and serum magnesium levels&#44; but found no statistically significant differences&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">We also compared the levels of magnesium in preterm newborns whose mothers had only received the loading bolus with 4<span class="elsevierStyleHsp" style=""></span>g of MgSO<span class="elsevierStyleInf">4</span> with the levels in newborns of mothers that were not treated with MgSO<span class="elsevierStyleInf">4</span>&#46; The group with mothers that received the loading dose of 4<span class="elsevierStyleHsp" style=""></span>g of MgSO<span class="elsevierStyleInf">4</span> had a mean serum level of magnesium of 2&#46;39<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;median&#44; 2&#46;3<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; while the group that was not exposed to magnesium had a mean serum level of magnesium of 1&#46;89<span class="elsevierStyleHsp" style=""></span>mg&#47;dL &#40;median&#44; 1&#46;86<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#41;&#44; a difference that was statistically significant&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">When it came to the initial outcomes in the delivery room&#44; we found no significant differences in the need for advanced CPR&#44; Apgar score or umbilical artery pH&#46; These results were consistent with those of other cohort studies that already supported the safety of the use of MgSO<span class="elsevierStyleInf">4</span> under these circumstances&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">From a respiratory perspective&#44; there were no differences in the need for invasive mechanical ventilation&#44; use of surfactant and total days of oxygen therapy&#44; so we could not attribute any respiratory side effects to MgSO<span class="elsevierStyleInf">4</span>&#44; contrary to what has been assumed historically&#44; as treatment with MgSO<span class="elsevierStyleInf">4</span> was associated with an increased incidence of respiratory depression&#46;<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">18</span></a> Bronchopulmonary dysplasia was less severe in the treated group&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">From a haemodynamic perspective&#44; the absence of adverse effects was also consistent with the finding of other studies&#44; as we did not observe an increased prevalence of patent ductus arteriosus or increased use of inotropic agents&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">19</span></a> We did not find differences in the remaining outcome variablesduring the stay in the NICU&#44; and we observed that&#44; at the neurologic level&#44; the incidence of IVH and leukomalacia were similar in both groups&#46; In this regard&#44; it would be interesting to conduct a long-term followup of these patients to study their psychomotor development&#46; We also found no differences at the gastrointestinal level in either the development of NEC&#44; initiation of enteral nutrition or the number of days post birth at which full enteral nutrition was achieved&#46; Furthermore&#44; we observed similar outcomes in relation to the development of retinopathy of prematurity from an ophthalmologic perspective&#44; and of nosocomial sepsis from an infectious perspective&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We did find differences in mortality in the group treated with MgSO<span class="elsevierStyleInf">4</span>&#46; Once again&#44; the small sample size requires that we interpret this result with caution and continue collecting data for future comparisons&#46; We must keep in mind that the Cochrane systematic review of 2009<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">13</span></a> established that when MgSO<span class="elsevierStyleInf">4</span> was administered for the sole purpose of neuroprotection&#44; there was a reduction in the composite outcome of death and cerebral palsy at age 2 years in exposed children&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">9&#44;20</span></a></p><p id="par0145" class="elsevierStylePara elsevierViewall">It would be worth exploring whether the association of MgSO<span class="elsevierStyleInf">4</span> exposure with a decrease in childhood mortality starts as early as the neonatal period&#46; Other studies in the literature have also found a lower mortality in the group treated with MgSO<span class="elsevierStyleInf">4</span>&#44;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">17</span></a> although its mechanism of action remains unclear&#46; Studies conducted in recent years have found an association between antenatal MgSO<span class="elsevierStyleInf">4</span> and decreased oxygen consumption in the newborn brain&#44; with a decreased cerebral fractional tissue oxygenation extraction &#40;cFTOE&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">21</span></a></p><p id="par0150" class="elsevierStylePara elsevierViewall">When it came to the dose of MgSO<span class="elsevierStyleInf">4</span> administered to the mothers&#44; we found a linear correlation between the cumulative dose and magnesium levels in newborns of less than 29 weeks of gestational age in the first 24<span class="elsevierStyleHsp" style=""></span>h post birth&#46; This finding allows the establishment of safe maternal doses to prevent the development of side effects in preterm newborns&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">The mean level of magnesium in the newborns was 2&#46;68<span class="elsevierStyleHsp" style=""></span>mg&#47;dL&#44; below the 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dLthreshold potentially associated with the development of side effects and poor clinical outcomes in the neonatal period&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> It is very likely that the absence of side effects from the use of MgSO<span class="elsevierStyleInf">4</span> in our series was due to the generally low doses administered to the mothers&#46; In the group of exposed children in our study&#44; the highest level of magnesium was 4&#46;04<span class="elsevierStyleHsp" style=""></span>mg&#47;dL and corresponded to a boy whose mother had received 20<span class="elsevierStyleHsp" style=""></span>g of MgSO<span class="elsevierStyleInf">4</span>&#46; Therefore&#44; we could establish a safety threshold of 20<span class="elsevierStyleHsp" style=""></span>g for the cumulative dose and 16<span class="elsevierStyleHsp" style=""></span>h of continuous infusion&#44; after which the dose would come dangerously close to levels associated with worse outcomes&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">In eight out of the twenty-eight newborns of mothers treated with MgSO<span class="elsevierStyleInf">4</span>&#44; the mother was only given the loading bolus with 4<span class="elsevierStyleHsp" style=""></span>g due to the short time elapsed to delivery&#46; Even these newborns had a statistically significant increase in magnesium levels compared to the newborns of mothers that had not received MgSO<span class="elsevierStyleInf">4</span>&#46; For this reason&#44; we recommend that at least the loading dose of 4<span class="elsevierStyleHsp" style=""></span>g be given to mothers at risk of giving birth at less than 29 weeks&#8217; gestation&#44; even if the birth is imminent&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">We also recommend the measurement of magnesium levels in all newborns of mothers treated with MgSO<span class="elsevierStyleInf">4</span> before birth&#46; The reasons for this are&#44; first&#44; the increased mortality detected in association with serum levels of magnesium greater than 4&#46;5<span class="elsevierStyleHsp" style=""></span>mg&#47;dL<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">22</span></a> and&#44; second&#44; the adjustments that need to be made in the composition of the parenteral feeds administered to these newborns in the first days of life until their magnesium levels normalise&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">In conclusion&#44; our study found that MgSO<span class="elsevierStyleInf">4</span> was safe at the administered dose&#44; with a linear correlation between serum levels of magnesium in the newborn in the first 24<span class="elsevierStyleHsp" style=""></span>h of life and the cumulative dose of magnesium received by the mother&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">Long-term follow-up studies of the patients included in this study are requiredto assess the impact of MgSO<span class="elsevierStyleInf">4</span> therapy on future neurodevelopmental outcomes&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interests</span><p id="par0180" class="elsevierStylePara elsevierViewall">The authors have no conflict of interests to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2016-02-16"
    "fechaAceptado" => "2016-04-25"
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            1 => "Neuroprotection"
            2 => "Mortality"
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          "palabras" => array:3 [
            0 => "Sulfato de magnesio"
            1 => "Neuroprotecci&#243;n"
            2 => "Mortalidad"
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    "resumen" => array:2 [
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Antenatal magnesium sulphate &#40;MgSO<span class="elsevierStyleInf">4</span>&#41; administration has shown to be effective in minimising cerebral palsy and severe motor dysfunction at the age of 2 years&#46;</p><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The aim of this study is to analyse the initial clinical outcome of preterm neonates less than 29 weeks who have received prenatal MgSO<span class="elsevierStyleInf">4</span>&#44; as well as to determine the relationship between the magnesium dose delivered to the mother and the magnesium concentration in the neonates&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Material and methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A prospective cohort study was conducted on neonates of less than 29 weeks gestation admitted to the Neonatal Intensive Care Unit &#40;NICU&#41; of Hospital Universitario de Vigo from December 2012 to July 2015&#46; Comparative analysis was performed on the perinatal outcomes&#44; neonatal morbidity&#44; mortality&#44; and magnesium levels between the groups of neonates exposed to magnesium sulphate and the control group&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">A total of 42 neonates were included in the study&#46; The mothers of 28 of them had received MgSO<span class="elsevierStyleInf">4</span> as a neuroprotective agent&#46;</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Statistical significance was obtained in the mortality variable&#46; There were no significant differences in the rest of studied variables&#46; There was a significant correlation between the full dose of MgSO<span class="elsevierStyleInf">4</span> received by the mother and the levels of magnesium in the neonate in the first 24<span class="elsevierStyleHsp" style=""></span>h of life &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span> 0&#46;436&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">A lower mortality was observed in the group that had been exposed to MgSO<span class="elsevierStyleInf">4</span>&#46; No significant side effects were found as a result of administering of MgSO<span class="elsevierStyleInf">4</span>&#46; The MgSO<span class="elsevierStyleInf">4</span> dose received by mother has a linear relationship with the magnesium levels obtained in neonates&#46;</p></span>"
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          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Material and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
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        "titulo" => "Resumen"
        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducci&#243;n</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">La administraci&#243;n prenatal de MgSO<span class="elsevierStyleInf">4</span> ha mostrado su eficacia en reducir la par&#225;lisis cerebral y la disfunci&#243;n motora severa a los 2 a&#241;os de edad&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este trabajo es estudiar la evoluci&#243;n cl&#237;nica inicial de los neonatos menores de 29 semanas&#44; que han recibido prenatalmente MgSO<span class="elsevierStyleInf">4</span> con indicaci&#243;n neuroprotectora y dilucidar la asociaci&#243;n entre la dosis de magnesio administrada a la madre y las concentraciones de magnesio en suero neonatal&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Estudio prospectivo de cohortes en el que se incluy&#243; a los neonatos menores de 29 semanas ingresados en la Unidad de Cuidados Intensivos Neonatales del Hospital Universitario de Vigo desde diciembre del 2012 hasta julio del 2015&#46; An&#225;lisis comparativo de resultados perinatales&#44; de morbimortalidad neonatal y magnesemia entre el grupo expuesto prenatalmente al sulfato de magnesio y un grupo control&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Se incluy&#243; a un total de 42 reci&#233;n nacidos&#44; en 28 de los cuales sus madres hab&#237;an recibido MgSO<span class="elsevierStyleInf">4</span>&#46;</p><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Se encontr&#243; significaci&#243;n estad&#237;stica en la variable mortalidad&#46; No hubo diferencias significativas en el resto de las variables estudiadas&#46; Se obtuvo una correlaci&#243;n significativa entre la dosis total de MgSO<span class="elsevierStyleInf">4</span> recibida por la madre y los niveles de magnesio del reci&#233;n nacido en las primeras 24 h de vida &#40;<span class="elsevierStyleItalic">r</span><span class="elsevierStyleSup">2</span> 0&#44;436&#59; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#44;001&#41;&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se ha obtenido una menor mortalidad en el grupo expuesto a MgSO<span class="elsevierStyleInf">4</span>&#46; No se han encontrado efectos secundarios significativos derivados de la administraci&#243;n de MgSO<span class="elsevierStyleInf">4</span>&#46; La dosis de MgSO<span class="elsevierStyleInf">4</span> recibida por las madres tiene una relaci&#243;n lineal con los niveles de magnesio obtenidos en los reci&#233;n nacidos&#46;</p></span>"
        "secciones" => array:4 [
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            "titulo" => "Introducci&#243;n"
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            "identificador" => "abst0030"
            "titulo" => "Material y m&#233;todos"
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            "titulo" => "Resultados"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Garc&#237;a Alonso L&#44; Pumarada Prieto M&#44; Gonz&#225;lez Colmenero E&#44; Concheiro Guis&#225;n A&#44; Su&#225;rez Albo M&#44; Dur&#225;n Fern&#225;ndez-Feijoo C&#44; et al&#46; Terapia prenatal con sulfato de magnesio&#58; evoluci&#243;n cl&#237;nica de los reci&#233;n nacidos pret&#233;rmino menores de 29 semanas y correlaci&#243;n con la magnesemia neonatal&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;86&#58;135&#8211;141&#46;</p>"
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          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">HBP&#44; high blood pressure&#59; MgSO<span class="elsevierStyleInf">4</span>&#44; prenatal treatment with magnesium sulphate&#59; No MgSO<span class="elsevierStyleInf">4</span>&#44; no prenatal treatment with magnesium sulphate&#59; NS&#44; not significant&#59; SD&#44; standard deviation&#46;</p>"
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO<span class="elsevierStyleInf">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO<span class="elsevierStyleInf">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Frequency &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28 &#40;66&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;33&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Weight in g &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">869&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>207&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">951&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>244&#46;07&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational age in weeks &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">27&#46;26<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">26&#46;84<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;93&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Male sex &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;57&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Small for gestational age &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Prenatal corticosteroids &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">28 &#40;100&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;92&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chorioamnionitis &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;48&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;69&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Preeclampsia &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">HBP &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Twin &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;46&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;016&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Caesarean &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">24 &#40;85&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;022&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Gestational diabetes &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;7&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">BPD&#44; bronchopulmonary dysplasia&#59; CPR&#44; cardiopulmonary resuscitation&#59; IMV&#44; invasive mechanical ventilation&#59; IV&#44; intravenous&#59; IVH&#44; intraventricular haemorrhage&#59; MgSO<span class="elsevierStyleInf">4</span>&#44; prenatal treatment with magnesium sulphate&#59; No MgSO<span class="elsevierStyleInf">4</span>&#44; no prenatal treatment with magnesium sulphate&#59; NS&#44; not significant&#59; PDA&#44; patent ductus arteriosus&#59; PVL&#44; periventricular leukomalacia&#59; ROP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#44; retinopathy of prematurity grade<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2&#59; SD&#44; standard deviation&#46;</p>"
          "tablatextoimagen" => array:1 [
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                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">MgSO<span class="elsevierStyleInf">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No MgSO<span class="elsevierStyleInf">4</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum magnesium &#40;mg&#47;dL&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;68<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">1&#46;89<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;66&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Serum calcium &#40;mg&#47;dL&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4&#46;87<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Advanced CPR &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">18 &#40;64&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;71&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Umbilical artery pH &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;21<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apgar 1 &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7&#46;03<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6&#46;36<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Apgar 5 &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;34<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;72&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&#46;00<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;88&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IMV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;82&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">13 &#40;92&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Surfactant &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">23 &#40;82&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;85&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Total days of O<span class="elsevierStyleInf">2</span> &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">42&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>21&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">47&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>25&#46;50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">BPD &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">21 &#40;75&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;72&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moderate-severe BPD &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;62&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;007&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IV corticosteroids &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;20&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Inotropes &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">15 &#40;53&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">9 &#40;64&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PDA &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;50&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Initiation enteral nutrition &#40;days&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2&#46;41<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;98&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3&#46;38<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Full enteral nutrition &#40;days&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">20&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>15&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">25&#46;09<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Death &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">3 &#40;21&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&#46;029&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVH &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">7 &#40;25&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">6 &#40;42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">IVH grade III&#8211;IV &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;35&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">NEC &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">5 &#40;17&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;30&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">PVL &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">4 &#40;14&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">ROP<span class="elsevierStyleHsp" style=""></span>&#62;<span class="elsevierStyleHsp" style=""></span>2 &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">10 &#40;35&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">2 &#40;18&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Nosocomial sepsis &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">17 &#40;60&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8 &#40;61&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">NS&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Mg &#40;mg&#47;dL&#41; &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">14&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">12&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">Mean levels of magnesium&#44; and levels by cumulative maternal dose&#46;</p>"
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      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0005"
          "bibliografiaReferencia" => array:22 [
            0 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cerebral palsy in preterm infants&#58; a population-based case&#8211;control study of antenatal and intrapartal risk factors"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "B&#46; Jacobsson"
                            1 => "G&#46; Hagberg"
                            2 => "B&#46; Hagberg"
                            3 => "L&#46; Ladfors"
                            4 => "A&#46; Niklasson"
                            5 => "H&#46; Hagberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2002"
                        "volumen" => "91"
                        "paginaInicial" => "946"
                        "paginaFinal" => "951"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/12222720"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "2"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Antenatal antecedents and the impact of obstetric care in the etiology of cerebral palsy"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "S&#46;M&#46; Clark"
                            1 => "L&#46;M&#46; Ghulmiyyah"
                            2 => "G&#46;D&#46; Hankins"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/GRF.0b013e3181870994"
                      "Revista" => array:6 [
                        "tituloSerie" => "Clin Obstet Gynecol"
                        "fecha" => "2008"
                        "volumen" => "51"
                        "paginaInicial" => "775"
                        "paginaFinal" => "786"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18981802"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "3"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Economic costs associated with mental retardation&#44; cerebral palsy&#44; hearing loss&#44; and vision impairment-United States&#44; 2003"
                      "autores" => array:1 [
                        0 => array:2 [
                          "colaboracion" => "Centers for Disease Control and Prevention &#40;CDC&#41;"
                          "etal" => false
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:5 [
                        "tituloSerie" => "Morb Mortal Wkly Rep"
                        "fecha" => "2004"
                        "volumen" => "53"
                        "paginaInicial" => "57"
                        "paginaFinal" => "59"
                      ]
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                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "4"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The changing panorama of cerebral palsy in Sweden&#46; IX&#46; Prevalence and origin in the birth-year period 1995&#8211;1998"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "K&#46; Himmelmann"
                            1 => "G&#46; Hagberg"
                            2 => "E&#46; Beckung"
                            3 => "B&#46; Hagberg"
                            4 => "P&#46; Uvebrant"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:6 [
                        "tituloSerie" => "Acta Paediatr"
                        "fecha" => "2005"
                        "volumen" => "94"
                        "paginaInicial" => "287"
                        "paginaFinal" => "294"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/16028646"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "5"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Incidence and prediction of periventricular-intraventricular hemorrhage in very preterm infants"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "M&#46; Van de Bor"
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  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2341287917300030?idApp=UINPBA00005H"
]

Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2016.04.006

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Year/Month	Html	Pdf	Total

2024 November	13	12	25
2024 October	69	55	124
2024 September	61	40	101
2024 August	80	80	160
2024 July	91	38	129
2024 June	79	40	119
2024 May	82	37	119
2024 April	72	55	127
2024 March	55	37	92
2024 February	53	31	84
2024 January	76	23	99
2023 December	81	30	111
2023 November	50	30	80
2023 October	57	37	94
2023 September	54	20	74
2023 August	53	18	71
2023 July	57	28	85
2023 June	57	25	82
2023 May	45	27	72
2023 April	49	24	73
2023 March	56	24	80
2023 February	50	21	71
2023 January	41	26	67
2022 December	66	31	97
2022 November	67	32	99
2022 October	85	45	130
2022 September	71	41	112
2022 August	70	40	110
2022 July	33	38	71
2022 June	42	38	80
2022 May	60	32	92
2022 April	80	39	119
2022 March	105	48	153
2022 February	106	35	141
2022 January	81	32	113
2021 December	73	41	114
2021 November	76	48	124
2021 October	58	81	139
2021 September	29	32	61
2021 August	32	53	85
2021 July	49	47	96
2021 June	39	48	87
2021 May	36	48	84
2021 April	98	111	209
2021 March	66	40	106
2021 February	30	27	57
2021 January	39	56	95
2020 December	44	32	76
2020 November	32	24	56
2020 October	23	25	48
2020 September	32	22	54
2020 August	30	48	78
2020 July	41	46	87
2020 June	51	32	83
2020 May	29	18	47
2020 April	22	22	44
2020 March	38	24	62
2020 February	26	22	48
2020 January	25	22	47
2019 December	48	30	78
2019 November	21	22	43
2019 October	36	27	63
2019 September	20	21	41
2019 August	38	27	65
2019 July	34	32	66
2019 June	31	36	67
2019 May	79	28	107
2019 April	74	37	111
2019 March	23	16	39
2019 February	25	24	49
2019 January	30	21	51
2018 December	28	19	47
2018 November	62	27	89
2018 October	104	16	120
2018 September	39	13	52
2018 August	3	0	3
2018 July	1	0	1
2018 June	2	0	2
2018 May	5	0	5
2018 April	16	0	16
2018 March	19	0	19
2018 February	10	0	10
2018 January	6	0	6
2017 December	13	0	13
2017 November	15	0	15
2017 October	11	0	11
2017 September	19	0	19
2017 August	9	0	9
2017 July	18	1	19
2017 June	24	11	35
2017 May	31	13	44
2017 April	111	101	212
2017 March	40	31	71
2017 February	10	16	26
2017 January	0	3	3

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