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CLINICAL SCIENCE
Longitudinal study of Cystatin C in healthy term newborns
Ana Carolina de Albuquerque Cavalcanti Ferreira Novo, Lílian dos Santos Rodrigues Sadeck, Thelma Suely Okay, Cléa Rodrigues Leone
Corresponding author
clearleone@uol.com.br

Tel.: 55 11 3069-8500
Department of Pediatrics, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">NB blood pressure and post conceptual gestational age according to reference values of Zubrow<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="cesec10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle70">INTRODUCTION</span><p id="para10" class="elsevierStylePara elsevierViewall">Newborns have a peculiar renal function and their glomerular filtration rate may vary depending on the degree of renal development at birth&#46;<a class="elsevierStyleCrossRef" href="#bib1">1</a></p><p id="para20" class="elsevierStylePara elsevierViewall">In newborns at term&#44; the glomerular filtration rate reaches values below 10&#37; of the adult level&#44; even when considered in relation to body surface or weight&#46; However&#44; the glomerular filtration rate increases progressively to adult values only at 2 years of age&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a></p><p id="para30" class="elsevierStylePara elsevierViewall">In order to detect properly the presence of abnormal renal function&#44; it is crucial to understand the normal value of expected glomerular filtration rate for each gestational and postnatal age&#44; using reliable methods for evaluation&#46;</p><p id="para40" class="elsevierStylePara elsevierViewall">In general&#44; renal function has been evaluated by the creatinine clearance&#44; which allows the glomerular filtration rate estimation in regular conditions&#44; but can overestimate its value when glomerular filtration rate is less than 2 ml&#47;min&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a> In the neonatal period&#44; because of the technical difficulty in collecting urine for a few hours on a non invasive procedure&#44; serum creatinine has been used for the evaluation of renal function&#46;<a class="elsevierStyleCrossRef" href="#bib3">3</a> However&#44; creatinine depends not only on its renal excretion&#44; but also on its production and metabolism&#46; Moreover&#44; at birth&#44; it is a reflection of maternal creatinine and it&#39;s not known how long this effect will last&#46;<a class="elsevierStyleCrossRef" href="#bib4">4</a> In order to find a more precise endogenous marker of glomerular filtration rate&#44; serum cystatin C has been studied&#46;</p><p id="para50" class="elsevierStylePara elsevierViewall">Cystatin C is a low molecular weight protein&#44; freely filtered by the glomerulus&#44; and almost completely reabsorbed and metabolized in the proximal tubule&#46; It is produced on a constant rate by nucleated cells and its serum concentration depends fundamentally of the glomerular filtration rate&#46;<a class="elsevierStyleCrossRefs" href="#bib5">5&#44;6&#44;7</a> It does not suffer interference of sex&#44; race&#44; height or body composition&#44;<a class="elsevierStyleCrossRefs" href="#bib8">8&#44;9</a> but varies with the age of the individual&#44; being highest at birth&#44; reducing up progressively until 1 year of life&#44;<a class="elsevierStyleCrossRefs" href="#bib10">10-13</a> when reaches levels similar to those of adults&#46; Unlike creatinine&#44; serum cystatin C in the newborn is not influenced by the mother&#39;s renal function&#44; <a class="elsevierStyleCrossRef" href="#bib14">14</a> which encourages its use to assess the glomerular filtration rate soon after birth&#46;</p><p id="para60" class="elsevierStylePara elsevierViewall">However&#44; there are not yet standard values defined for this period&#46; This study aims at analyzing the evolution of serum levels of cystatin C in healthy term newborns&#44; during the first month of life&#46;</p></span><span id="cesec20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle80">MATERIALS AND METHODS</span><p id="para70" class="elsevierStylePara elsevierViewall">A cohort study was carried out in the Nursery Annex to the Maternity of Hospital das Cl&#237;nicas&#44; University of S&#227;o Paulo&#44; School of Medicine&#46; It was performed in the period from July 1<span class="elsevierStyleSup">st</span> 2005 to January 31<span class="elsevierStyleSup">th</span>&#44; 2006&#46; This research project was approved by the Ethics Committee for Review of Research Projects - CAPPesq of the hospital where it was held&#44; on March 24<span class="elsevierStyleSup">st</span>&#44; 2005&#46;</p><p id="para80" class="elsevierStylePara elsevierViewall">Newborns were included&#44; according to the following criteria&#58; gestational age between 37 and 41<span class="elsevierStyleSup">6</span>&#47;<span class="elsevierStyleInf">7</span> weeks &#40;full term newborns&#41;&#59;<a class="elsevierStyleCrossRefs" href="#bib15">15&#44;16</a> birth weight appropriate for gestational age&#59;<a class="elsevierStyleCrossRef" href="#bib17">17</a> first minute Apgar score equal to or higher than 7&#59; and whose mother had given consent after being adequately informed&#46;</p><p id="para90" class="elsevierStylePara elsevierViewall">Exclusion criteria were&#58; mothers with renal failure&#44; chronic or pregnancy-induced hypertension and use of drugs that could have interfered with the fetal renal function during pregnancy&#59;<a class="elsevierStyleCrossRef" href="#bib18">18</a> newborns with major or kidney malformations&#59; first diuresis after 12 hours of life or diuresis between 24 and 72 hours of life less than 1 ml&#47;kg&#47;h&#44; weight loss until the third day of life higher than 10&#37; of the birth weight&#59; hypertension&#59;<a class="elsevierStyleCrossRef" href="#bib19">19</a> heart or kidney failure&#59; hemolytic disease&#59; jaundice needing phototherapy&#59; infection&#59; need for intravenous hydration or diuretics&#44; vasoactive or any drug use that could interfere with renal function&#59; or inability to collect all the samples as planed&#46;</p><p id="para100" class="elsevierStylePara elsevierViewall">The newborns included received usual care according to the rules of the neonatal unit&#46; They were submitted in the first three days of life to systematized clinical evaluation&#44; daily&#44; always held by the same researcher which included control of weight&#44; length and blood pressure as described by Zubrow<a class="elsevierStyleCrossRef" href="#bib19">19</a> &#40;monitor blood pressure noninvasive&#44; oscilometric - the DINAMAP&#174;&#41; and determination of 24 hours diuresis&#46; All outpatients returned to control at 7 and 28 days&#44; and were evaluated clinically by the same person and submitted to the weight&#44; length and blood pressure control&#46;</p><p id="para110" class="elsevierStylePara elsevierViewall">Blood was obtained for the determination of the laboratory cystatin C and creatinine of the mother at the time of delivery&#44; and in the newborn at birth in the umbilical cord&#40;Day-0&#41;&#44; with 3&#40;Day-3&#41;&#44; 7 and 28&#40;Day-28&#41; days&#46;</p><p id="para120" class="elsevierStylePara elsevierViewall">The cystatin C was measured in samples by immunonephelometry&#44; using the Testkit N Latex Cystatin C&#44; code OQNM&#44; manufactured by DADE BEHRING&#174;&#46; The creatinine was determined by the method of Jaff&#233; without desproteinization&#46; All dosages were performed at the Laboratory of Medical Research in Pediatric Clinic of the Department of Pediatrics&#44; University of S&#227;o Paulo&#44; School of Medicine&#46;</p><p id="para130" class="elsevierStylePara elsevierViewall">An ultrasound scan of the kidney and urinary tract until the third day of life was done&#44; always by the same person&#46;</p><span id="cesec30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle90">Statistical analysis</span><p id="para140" class="elsevierStylePara elsevierViewall">The sample size was calculated based on the mean serum cystatin C &#40;1&#46;36 &#177; 0&#46;35 mg&#47;L&#41;<a class="elsevierStyleCrossRef" href="#bib20">20</a> and creatinine &#40;0&#46;50 &#177; 0&#46;30 mg&#47;dl&#41;<a class="elsevierStyleCrossRef" href="#bib3">3</a> values and the objective was to detect differences equal or greater than 0&#46;24 mg&#47;L &#40;18&#37;&#41; for the mean cystatin C concentrations and 0&#46;20 mg&#47;dl &#40;40&#37;&#41; for the creatinine values&#46;</p><p id="para150" class="elsevierStylePara elsevierViewall">For an &#945; of 5&#37; and a power test &#40;&#946;&#41; of 80&#37;&#44; the sample was calculated on 20 newborns&#46;</p><p id="para160" class="elsevierStylePara elsevierViewall">The comparisons between groups were made by the paired Student t test or tests of non parametric Wilcoxon Signed Rank Sum Friedman and 2-way ANOVA&#46; The Pearson&#39;s correlation coefficient was used for correlation analysis&#46; The significance was set under 5&#37; &#40;p &#60; 0&#46;05&#41;&#46;</p></span></span><span id="cesec40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle100">RESULTS</span><p id="para170" class="elsevierStylePara elsevierViewall">21 newborns were included in the study&#46;</p><p id="para180" class="elsevierStylePara elsevierViewall">The characterization of the study population can be seen in <a class="elsevierStyleCrossRef" href="#tbl1">Table 1</a>&#46; The evolution of weight in the 1<span class="elsevierStyleSup">st</span> month of life has been as expected &#40;<a class="elsevierStyleCrossRef" href="#tbl2">Table 2</a>&#41;&#46; Throughout the study period&#44; 13 newborns had jaundice&#44; without the need for phototherapy &#40;61&#46;90&#37;&#41;&#46; One newborn had an atrial septal defect and another one a ventricular septal defect&#44; both without repercussions and which were closed in the third month of life&#46; Blood pressure values were in accord with the reference<a class="elsevierStyleCrossRef" href="#bib19">19</a> &#40;<a class="elsevierStyleCrossRef" href="#fig1">Figura 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl1"></elsevierMultimedia><elsevierMultimedia ident="tbl2"></elsevierMultimedia><elsevierMultimedia ident="fig1"></elsevierMultimedia><p id="para190" class="elsevierStylePara elsevierViewall">As for the evaluation of diuresis&#44; the first urination occurred at 4&#46;90 &#177; 3&#46;90 hours of life&#44; and the mean diuresis in the Day-2 and Day-3 was of 2&#46;10&#177;0&#46;60 and 2&#46;40&#177; 0&#46;70 ml&#47;kg&#47;h&#44; respectively&#44; ranging from 1&#46;30 to 3&#46;70 ml&#47;kg&#47;h&#46; There were no differences between the diuresis in these two days &#40;p &#8200;&#61;&#8200; 0&#46;14&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl3">Table 3</a>&#41;&#46;</p><elsevierMultimedia ident="tbl3"></elsevierMultimedia><p id="para200" class="elsevierStylePara elsevierViewall">All the ultrasound scans of the newborn kidneys and urinary tracts were normal&#46;</p><p id="para210" class="elsevierStylePara elsevierViewall">The newborn&#39;s cystatin C values showed consistently higher values than mother&#39;s cystatin C&#46; The maximum value occurred on the Day- 0&#44; getting their values stable from Day-3 on&#46; In turn&#44; newborn creatinine did not differ from the mother creatinine in the Day-0&#44; and decreased progressively until the Day-28 &#40;<a class="elsevierStyleCrossRef" href="#tbl4">table 4</a>&#59; <a class="elsevierStyleCrossRef" href="#fig2">figure 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl4"></elsevierMultimedia><elsevierMultimedia ident="fig2"></elsevierMultimedia><p id="para220" class="elsevierStylePara elsevierViewall">The maternal cystatin C and creatinine concentrations showed a positive correlation &#40;r&#8200;&#61;&#8200;0&#46;537&#44;p&#8200;&#61;&#8200;0&#46;012&#41; as Day-3&#40;r&#8200;&#61;&#8200;0&#46;437&#59;p&#8200;&#61;&#8200;0&#46;047&#41; and Day-28&#40;r&#8200;&#61;&#8200;0&#46;498&#59;p&#8200;&#61;&#8200;0&#46;022&#41; cystatin C and creatinine values&#46;</p></span><span id="cesec50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle110">DISCUSSION</span><p id="para230" class="elsevierStylePara elsevierViewall">The cystatin C comes out as a reliable marker of renal function&#44; particularly in the first week of life&#46; However&#44; there was not yet in the literature determinations of serum levels of cystatin C in healthy newborns&#44; during the neonatal period&#46; In this study&#44; it was possible to verify that the newborn-term exhibit stable levels of cystatin C from the third day of life and that there was not placental passage of the cystatin C&#46; In view of the need for the selection of case series which were the closest possible to the normal&#44; we established a selection based on strict criteria for inclusion&#46; Furthermore&#44; some clinical data were analyzed&#44; such as&#58; weight&#44; urine output&#44; blood pressure and kidneys ultrasound&#44; so that there was greater safety in relation to the normal physiological development of renal function in these newborns&#46;</p><p id="para240" class="elsevierStylePara elsevierViewall">The included newborns had a weight loss that occurred within the limits of 5 to 10&#37;&#44; considered normal for healthy term newborns&#46;<a class="elsevierStyleCrossRef" href="#bib21">21</a> The first urination and urinary output have remained within the expected&#46;<a class="elsevierStyleCrossRef" href="#bib2">2</a> The systolic and diastolic blood pressure were always within the limits considered normal for corrected gestational age&#44; <a class="elsevierStyleCrossRef" href="#bib19">19</a> ultrasonography kidneys evaluation showed no morphological alterations and no disturb of thyroid function was detected&#46;</p><p id="para250" class="elsevierStylePara elsevierViewall">Thus&#44; it was possible to infer a diagnosis of normal renal function of these newborns&#44; which was corroborated by the analysis of creatinine&#46; On Day-0&#44; creatinine was equal to the mother&#44; decreasing gradually to the Day-28&#46; The levels of creatinine were in line with the values considered normal for healthy term newborns&#46;<a class="elsevierStyleCrossRefs" href="#bib3">3&#44;10</a></p><p id="para260" class="elsevierStylePara elsevierViewall">The mother creatinine was not different from that of the newborn at birth&#44; which was expected&#44; given the known placental passage of creatinine&#46; In turn&#44; the cystatin C of the mother was different from the newborn cystatin C at birth&#44; as has been described by Cataldi &#44; showing no placental passage of the cystatin C&#46;<a class="elsevierStyleCrossRef" href="#bib14">14</a> The levels of maternal cystatin C and creatinine were consistent with the values described by Cataldi<a class="elsevierStyleCrossRef" href="#bib14">14</a> and by Babay<a class="elsevierStyleCrossRef" href="#bib22">22</a> and showed a correlation between them&#44; as expected&#44; since a number of searches already demonstrated the accuracy of cystatin C to estimate the glomerular filtration rate and its correlation with creatinine&#46;<a class="elsevierStyleCrossRefs" href="#bib10">10&#8211;14&#44;20&#44;23-26</a></p><p id="para270" class="elsevierStylePara elsevierViewall">The cystatin C in the newborns were higher on the Day-0&#44; decreasing from birth to the third day and then the levels remained constant&#44; always higher than the maternal ones&#46; Some authors have sought to determine the normal values of cystatin C in term newborns in the neonatal period&#58; B&#246;kenkamp<a class="elsevierStyleCrossRef" href="#bib11">11</a> - 1&#46;64 to 2&#46;59 mg&#47;L from 0 to 3 days and 1&#46;52 to 2&#46;40 mg&#47;L from 3 to 30 days&#59; Finney<a class="elsevierStyleCrossRef" href="#bib10">10</a> - 0&#46;81 to 2&#46;32 mg&#47;L from 0 to 3 months&#59; Harmoinen<a class="elsevierStyleCrossRef" href="#bib13">13</a> - 1&#46;36 to 2&#46;23 mg&#47;L from 0 to 7 days&#59; Bahar<a class="elsevierStyleCrossRef" href="#bib20">20</a> - 0&#46;69 to 2&#46;43 mg&#47;L in the umbilical cord and 0&#46;78 to 2&#46;40 mg&#47;L to 3 days and Treiber<a class="elsevierStyleCrossRef" href="#bib25">25</a> - 1&#46;97 &#177; 0&#46;36 mg&#47;L &#40;1&#44; 38 to 3&#46;23&#41; in the umbilical cord and 1&#46;93 &#177; 0&#46;33 mg&#47;L &#40;1&#46;28 to 2&#46;66&#41; in the third day&#46; The results obtained here are contained in each of these bands of normal values&#44; which are very large&#44; since the age groups were not always so restricted and the inclusion criteria to ensure normal renal function were not as stringent as those used here&#46;</p><p id="para280" class="elsevierStylePara elsevierViewall">We observed a positive correlation between the maternal values of creatinine and cystatin C&#44; as expected&#46;<a class="elsevierStyleCrossRefs" href="#bib14">14&#44;22</a> Besides that other positive correlations were obtained on Day-3 and Day-28 between cystatin C and creatinine values&#46; The significance of these results has yet to be proved&#44; as the glomerular filtration rate could not be studied by us through clearances analysis as desirable because of methodological limitations in term newborns&#46;</p><p id="para290" class="elsevierStylePara elsevierViewall">It&#39;s possible that cystatin C could be a reliable indicator of renal function in newborns&#44; especially in the first week of life&#44; for not having placental passage and being stable from the third day of life&#46;</p><p id="para300" class="elsevierStylePara elsevierViewall">Nevertheless&#44; from the results obtained in this study&#44; we only can indicate these values of cystatin C as reference serum levels for healthy term newborns&#46; New studies are needed in order to evaluate the reliability of newborn cystatin C values as a marker of renal function in the neonatal period&#46;</p><p id="para310" class="elsevierStylePara elsevierViewall">This work was supported by a grant from FAPESP &#40;Foundation to Aid Research of the State of S&#227;o Paulo&#41;&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
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        0 => array:2 [
          "identificador" => "xpalclavsec1581454"
          "titulo" => "KEYWORDS"
        ]
        1 => array:2 [
          "identificador" => "cesec10"
          "titulo" => "INTRODUCTION"
        ]
        2 => array:3 [
          "identificador" => "cesec20"
          "titulo" => "MATERIALS AND METHODS"
          "secciones" => array:1 [
            0 => array:2 [
              "identificador" => "cesec30"
              "titulo" => "Statistical analysis"
            ]
          ]
        ]
        3 => array:2 [
          "identificador" => "cesec40"
          "titulo" => "RESULTS"
        ]
        4 => array:2 [
          "identificador" => "cesec50"
          "titulo" => "DISCUSSION"
        ]
        5 => array:1 [
          "titulo" => "REFERENCES"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2010-08-04"
    "fechaAceptado" => "2010-11-03"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "KEYWORDS"
          "identificador" => "xpalclavsec1581454"
          "palabras" => array:5 [
            0 => "Serum Cystatin C"
            1 => "Glomerular filtration rate"
            2 => "Serum creatinine"
            3 => "Reference values"
            4 => "Infant newborn"
          ]
        ]
      ]
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    "resumen" => array:1 [
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        "resumen" => "<span id="ceabs10" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle10">OBJECTIVE</span><p id="spara130" class="elsevierStyleSimplePara elsevierViewall">The purpose of this study was to determine the levels of Cystatin C in healthy term newborns in the first month of life&#46;</p></span> <span id="ceabs20" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle20">INTRODUCTION</span><p id="spara140" class="elsevierStyleSimplePara elsevierViewall">Cystatin C may be a suitable marker for determining the glomerular filtration rate because it is not affected by maternal renal function&#46;</p></span> <span id="ceabs30" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle30">METHODS</span><p id="spara150" class="elsevierStyleSimplePara elsevierViewall">Cohort study&#46; Inclusion&#58; term newborns with appropriate weight&#59; mother without renal failure or drugs that could affect fetal glomerular filtration rate&#46; Exclusion&#58; malformations&#59; hypertension or any condition that could affect glomerular filtration rate&#46; Cystatin C &#40;mg&#47;L&#41; and creatinine &#40;mg&#47;dl&#41; were determined in the mother &#40;Mo&#41; and in the newborn at birth &#40;Day-0&#41;&#44; 3<span class="elsevierStyleSup">rd</span> &#40;Day-3&#41;&#44; 7<span class="elsevierStyleSup">th</span>&#40;Day-7&#41; and 28<span class="elsevierStyleSup">th</span>&#40;Day-28&#41; days&#46; Statistics&#58; one way ANOVA and Pearson&#39;s correlation tests&#46; Sample size of 20 subjects for &#945; &#8200;&#61;&#8200; 5&#37; and a power test &#8200;&#61;&#8200; 80&#37; &#40;p&#60;0&#46;05&#41;&#46;</p></span> <span id="ceabs40" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle40">RESULTS</span><p id="spara160" class="elsevierStyleSimplePara elsevierViewall">Data from 21 newborns were obtained &#40;mean &#177; standard deviation&#41;&#58; MoCystatin C&#8200;&#61;&#8200;1&#46;00&#177;0&#46;20&#59; Day-0 Cystatin C 1&#46;70&#177;0&#46;26&#59; Day-3 Cystatin C&#8200;&#61;&#8200;1&#46;51&#177;0&#46;20&#59; Day-7 Cystatin C&#8200;&#61;&#8200;1&#46;54&#177;0&#46;10&#59; Day-28 Cystatin C&#8200;&#61;&#8200;1&#46;51&#177;0&#46;10&#46;</p><p id="spara170" class="elsevierStyleSimplePara elsevierViewall">MoCystatin C was smaller than Day-0 Cystatin C &#40;p&#60;0&#46;001&#41;&#44; while MoCreatinine was not different from Day-0 Creatinine&#46; Cystatin C only decreased from Day-0 to Day-3 &#40;p&#8200;&#61;&#8200;0&#46;004&#41; but newborns Creatinine decreased along the time&#46; Correlations were obtained between MoCystatin C and MoCreatinine &#40;p&#8200;&#61;&#8200;0&#46;012&#41;&#44; as well as Day-3 &#40;p&#8200;&#61;&#8200;0&#46;047&#41; and Day-28 &#40;p&#8200;&#61;&#8200;0&#46;022&#41; Cystatin C and Creatinine values&#46;</p></span> <span id="ceabs50" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cestitle50">CONCLUSION</span><p id="spara180" class="elsevierStyleSimplePara elsevierViewall">Neonatal Cystatin C values were not affected by MoCystatin C and became stable from the 3<span class="elsevierStyleSup">rd</span> day of life&#46;</p></span>"
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            "titulo" => "INTRODUCTION"
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          "en" => "<p id="spara10" class="elsevierStyleSimplePara elsevierViewall">NB blood pressure and post conceptual gestational age according to reference values of Zubrow<a class="elsevierStyleCrossRef" href="#bib20">20</a>&#46;</p>"
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          "en" => "<p id="spara20" class="elsevierStyleSimplePara elsevierViewall">Mean values of mother creatinine and cistatina C at birth and the newborn during the 1<span class="elsevierStyleSup">st</span> month of life&#46;</p>"
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mother characteristics&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Age in years &#40;mean &#177; standard deviation&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">29&#46;10 &#177; 8&#46;20&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>1<span class="elsevierStyleSup">st</span> pregnancy &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">28&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Prenatal care &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Cesarean section &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">52&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Newborn characteristics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">39&#46;40 &#177; 0&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Birth Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">3224&#46;30 &#177; 306&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Adequate for Gestational Age &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t"><span class="elsevierStyleHsp" style=""></span>Male &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t">57&#46;10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black"><span class="elsevierStyleHsp" style=""></span>Exclusive Breastfeeding &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">81&#46;00&nbsp;\t\t\t\t\t\t\n
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          "en" => "<p id="spara30" class="elsevierStyleSimplePara elsevierViewall">Characterization of the population &#40;n &#8200;&#61;&#8200; 21&#41;&#46;</p>"
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          "leyenda" => "<p id="spara60" class="elsevierStyleSimplePara elsevierViewall">Data presented as mean &#177; standard deviation or percent &#40;&#37;&#41;&#46;BW-Birth Weight</p>"
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                  <table border="0" frame="\n
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                  \t\t\t\t">Loss of BW &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7&#46;10 &#177; 1&#46;70&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Age at maximum weight loss &#40;days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">2&#46;40 &#177; 0&#46;60&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Weight at 28 days&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">4017&#46;60 &#177; 376&#46;30&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">First urination &#40;hours&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;90 &#177; 3&#46;90&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Diuresis on the 2<span class="elsevierStyleSup">nd</span> day of life &#40;ml&#47;kg&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&#46;10 &#177; 0&#46;60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">Diuresis on the 3<span class="elsevierStyleSup">rd</span> day of life &#40;ml&#47;kg&#47;h&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" style="border-bottom: 2px solid black">2&#46;40 &#177; 0&#46;70&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
            ]
          ]
        ]
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          "en" => "<p id="spara70" class="elsevierStyleSimplePara elsevierViewall">Evaluation of Diuresis&#46;</p>"
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      5 => array:7 [
        "identificador" => "tbl4"
        "etiqueta" => "Table 4"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "tabla" => array:2 [
          "leyenda" => "<p id="spara100" class="elsevierStyleSimplePara elsevierViewall">Data presented as mean &#177; standard deviation&#46;</p><p id="spara110" class="elsevierStyleSimplePara elsevierViewall">Creatinine&#58; mother X Day-0&#44; p &#8200;&#61;&#8200; 0&#46;545&#59; Day-0 X Day-3&#44; p &#8200;&#61;&#8200; 0&#46;007&#59; Day-3 X Day-7&#44; p &#8200;&#61;&#8200; 0&#46;002&#59; Day-7 X Day-28&#44; p &#60;0&#46;001&#46;</p><p id="spara120" class="elsevierStyleSimplePara elsevierViewall">Cistatina C&#58; mother X Day-0&#44; p &#60;0&#46;001&#59; Day-0 X Day-3&#44; p &#8200;&#61;&#8200; 0&#46;004&#59; Day-3 X Day-7&#44; p &#8200;&#61;&#8200; 0&#46;419&#59; Day-7 X Day-28&#44; p &#8200;&#61;&#8200; 0&#46;455&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
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                  \t\t\t\t  " align="center" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col">Cystatin C &#40;mg&#47;L&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="center" valign="\n
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                  \t\t\t\t" scope="col">Creatinine &#40;mg&#47;dl&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Mother&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;00 &#177; 0&#46;20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;63 &#177; 0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">NB&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Day-0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;70 &#177; 0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;63 &#177; 0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Day-3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;51 &#177; 0&#46;19&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;48 &#177; 0&#46;16&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">Day-7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">1&#46;54 &#177; 0&#46;15&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;37 &#177; 0&#46;10&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">Day-28&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">1&#46;51 &#177; 0&#46;15&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t" style="border-bottom: 2px solid black">0&#46;26 &#177; 0&#46;05&nbsp;\t\t\t\t\t\t\n
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                  """
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          "en" => "<p id="spara90" class="elsevierStyleSimplePara elsevierViewall">Levels of cystatin C and creatinine&#46;</p>"
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      "titulo" => "REFERENCES"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "cebibsec10"
          "bibliografiaReferencia" => array:26 [
            0 => array:3 [
              "identificador" => "bib1"
              "etiqueta" => "1"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Development of glomerular filtration and tubular sodium reabsorption in the human fetus and newborn"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              GM Haycock \n
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                              """
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1046/j.1464-410x.1998.0810s2008.x"
                      "Revista" => array:6 [
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                        "fecha" => "1998"
                        "volumen" => "81"
                        "paginaInicial" => "8"
                        "link" => array:1 [
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                            "web" => "Medline"
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                        "itemHostRev" => array:3 [
                          "pii" => "S0140673600041994"
                          "estado" => "S300"
                          "issn" => "01406736"
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                      "autores" => array:1 [
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                          "etal" => false
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                            0 => """
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                            2 => """
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                      "titulo" => "The use of plasma creatinine concentration for estimating glomerular filtration rate in infants&#44; children&#44; and adolescents"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => """
                              GJ Schwartz \n
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                              """
                            2 => """
                              A Spitzer \n
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                  ]
                  "host" => array:1 [
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            3 => array:3 [
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              "etiqueta" => "4"
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                    0 => array:2 [
                      "titulo" => "Renal aspects of the term and preterm infant&#58; a selective update"
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                        0 => array:2 [
                          "etal" => false
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                            0 => """
                              A Drukker \n
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                              """
                            1 => """
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                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1097&#47;00008480-200204000-00006"
                      ]
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            4 => array:3 [
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                      "autores" => array:1 [
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                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              LD Dworkin \n
                              \t\t\t\t\t\t\t\t
                              """
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                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:4 [
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                        "fecha" => "2001"
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                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1097&#47;00041552-200109000-00001"
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            5 => array:3 [
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              "etiqueta" => "6"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystatin C &#8211; properties and use as diagnostic marker"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => """
                              AO Grubb \n
                              \t\t\t\t\t\t\t\t
                              """
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                        ]
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                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Adv Clin Chem"
                        "fecha" => "2000"
                        "volumen" => "35"
                        "paginaInicial" => "99"
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                    ]
                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1016&#47;S0065-2423&#40;01&#41;35015-1"
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            ]
            6 => array:3 [
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              "etiqueta" => "7"
              "referencia" => array:1 [
                0 => array:2 [
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                    0 => array:2 [
                      "titulo" => "Biochemistry and clinical role of human cistatin C"
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                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => """
                              M Mussap \n
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                              """
                            1 => """
                              M Plebani \n
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                      ]
                    ]
                  ]
                  "host" => array:2 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Crit Rev Clin Lab Sci&#46;"
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                        "volumen" => "41"
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                    1 => array:1 [
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            7 => array:3 [
              "identificador" => "bib8"
              "etiqueta" => "8"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Cystatin C- a new marker of glomerular filtration rate in children independent of age and height"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => """
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                            1 => """
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                              G Schumann \n
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                            4 => """
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                            5 => """
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                  "host" => array:2 [
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                      "Revista" => array:4 [
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                        "fecha" => "1998"
                        "volumen" => "101"
                        "paginaInicial" => "81"
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                    1 => array:1 [
                      "WWW" => array:1 [
                        "link" => "https&#58;&#47;&#47;doi&#46;org&#47;10&#46;1542&#47;peds&#46;101&#46;5&#46;875"
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            8 => array:3 [
              "identificador" => "bib9"
              "etiqueta" => "9"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Serum cystatin C values in children by age and their fluctuation during dehydration"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => """
                              S Takuwa \n
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                              """
                            1 => """
                              Y Ito \n
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                              """
                            2 => """
                              K Ushijima \n
                              \t\t\t\t\t\t\t\t
                              """
                            3 => """
                              K Uchida \n
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Article information
ISSN: 18075932
Original language: English
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