Study on growth hormone treatment in small for gestational age children

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Sánchez Zahonero, María José López García" "autores" => array:2 [ 0 => array:4 [ "nombre" => "Julia" "apellidos" => "Sánchez Zahonero" "email" => array:1 [ 0 => "ju-san-za@hotmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "María José" "apellidos" => "López García" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Hospital Clínico Universitario de Valencia, Valencia, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Estudio valenciano sobre tratamiento con hormona de crecimiento en pequeños para la edad gestacional" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => 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The numbers in parentheses correspond to the mean chronological age in each phase of treatment. Initial sample (115 patients), first year (115 patients), second year (115 patients), last year (96 patients)." ] ] ] "textoCompleto" => "IntroductionSmall for gestational age (SGA) refers to newborns whose birth weight or length are 2 or more standard deviations (SDs) below the mean for their sex and gestational age in the reference population.<a class="elsevierStyleCrossRef" href="#bib0145">1</a> This results from abnormalities in intrauterine growth, whose cause is unknown in 40% of cases.<a class="elsevierStyleCrossRef" href="#bib0150">2</a>Approximately 90% of these children exhibit spontaneous catch-up growth in the first two years of life, although this may be delayed until age 3–4 years in children born preterm.<a class="elsevierStyleCrossRef" href="#bib0145">1</a> This catch-up growth does not occur in the remaining 10%, in most cases for unknown reasons.<a class="elsevierStyleCrossRefs" href="#bib0155">3,4</a> Some of the possible causes that have been proposed include a decreased cell mass at the time of birth and alterations of endocrine-metabolic pathways involved in postnatal growth, especially in the GH-IGF-1 axis. However, growth hormone stimulation tests show normal or even elevated levels of growth hormone (GH) in most SGA children,<a class="elsevierStyleCrossRef" href="#bib0165">5</a> which suggests some degree of peripheral resistance to GH activity or a reduced biological activity of GH.Job and colleagues were the first to use recombinant human growth hormone (rhGH) for the treatment of delayed postnatal growth seen in some children born SGA,<a class="elsevierStyleCrossRefs" href="#bib0170">6,7</a> and set the foundations for subsequent research, the results of which suggests that rhGH is a safe and effective treatment to partially reduce stature deficits in the adult height of individuals born SGA. However, the response to treatment varies widely between studies, which may be related to the diverse aetiology of SGA.<a class="elsevierStyleCrossRefs" href="#bib0180">8–11</a>The use of this hormone for the treatment of short children born SGA was authorised by the Food and Drug Administration (FDA) in July 2001 and by the European Agency for the Evaluation of Medicinal Products (EMA) in June 2003.<a class="elsevierStyleCrossRef" href="#bib0145">1</a> The Spanish Agency of Medicines and Health Care Products (Agencia Española del Medicamento y Productos Sanitarios [AEMPS]) follows the criteria set by the EMA.The dosage of rhGH recommended for children born SGA is higher than the one in children with GH deficiency, and ranges between 0.035 and 0.067mg/kg/day.<a class="elsevierStyleCrossRef" href="#bib0145">1</a> The reason for this is that, as noted above, SGA patients exhibit a degree of peripheral resistance to GH activity rather than decreased GH release.No studies have been conducted on the effectiveness of treatment in individuals born SGA in the Autonomous Community of Valencia since this indication for rhGH was approved. In this article, we present the growth outcomes in a sample of children treated over a 10-year period.Objectives<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005">(a)To assess the effectiveness of growth hormone in children born SGA in our area, between January 01, 2003 and December 31, 2013, based on the proportion of these patients that reached their target height by the end of treatment, or the corresponding growth trajectory if treatment was not completed.</li><li class="elsevierStyleListItem" id="lsti0010">(b)To compare the obtained results with those published by other research groups in Spain and abroad.</li></ul>PatientsWe used the information gathered in the request forms for initiation, renewal and completion of rhGH therapy submitted to the Growth Hormone Assessment Committee of the Autonomous Community of Valencia by every paediatric endocrinology unit in the hospitals of the three provinces between January 1, 2003 and December 31, 2013.We obtained permission to access these data from the Clinical Research Ethics Committee of the Fundación de Investigación of the Hospital Clínico Universitario de Valencia. The study was classified as an observational post-authorisation study—other designs (OPA-OD) based on the directives of Order SAS/3470/2009, of December 16 of the Ministry of Health. These are retrospective studies in which due to the size of the sample or the long time elapsed since data collection, the informed consent of included individuals is not required, as long as their anonymity is safeguarded. Furthermore, the study was approved by the Department of Health of the Autonomous Community of Valencia, as these documents are stored for safekeeping in its facilities, where we carried out data collection.We obtained the study sample applying the following criteria:<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015">(a)Inclusion: we only included children born SGA that strictly fulfilled all the following prerequisites:<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020">-Birth weight or length of less than −2 SDS.</li><li class="elsevierStyleListItem" id="lsti0025">-Height from birth consistently below −2.5 SDS.</li><li class="elsevierStyleListItem" id="lsti0030">-Had not reached puberty.</li><li class="elsevierStyleListItem" id="lsti0035">-Had received treatment with growth hormone for a minimum of two years.</li></ul></li><li class="elsevierStyleListItem" id="lsti0040">(b)Exclusion: of all children that met the inclusion criteria, we excluded those whose target height was unknown and those in whom treatment was discontinued prematurely due to the development of adverse reactions or poor adherence.</li></ul>We studied the following variables retrospectively:<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0045">1.Prescribed dosage of GH (mg/kg/day).</li><li class="elsevierStyleListItem" id="lsti0050">2.Family anthropometric data: target height (TH) SDS and height SDS of the shortest parent.</li><li class="elsevierStyleListItem" id="lsti0055">3.Patient anthropometric data: decimal age in years, SDS for height and growth velocity (GV). Specifically, these data were collected at five phases: 1st, prior to starting treatment; 2nd, after one year of treatment; 3rd, after two years of treatment; 4th, the last year they received treatment; and 5th, adult height.</li></ul>MethodsAnthropometric methodsWe found the SDS of the aforementioned anthropometric measures by applying the tables of the 2010 Spanish Cross-sectional Growth Study<a class="elsevierStyleCrossRefs" href="#bib0200">12,13</a> (TH, height of the shortest parent and patient heights in the five phases of the study) and of the 1978–2000 Spanish LongitudinalStudy<a class="elsevierStyleCrossRef" href="#bib0210">14</a> (for GV, keeping into account the maturation stage of the patient).We considered that patients had reached their adult height when their grow rate became less than 2cm per year or their growth plates had closed.Statistical methodsWe have described the baseline characteristics of our sample using the mean and standard deviation. To assess the effectiveness of treatment, we compared the mean height achieved in each phase of the study with the height of the phase immediately preceding it using Student's t test for paired samples with the Bonferroni correction. We used Student's t test for independent samples to compare the mean adult height with the TH (both variables followed a normal distribution) and the Mann–Whitney U test to compare the mean adult height with the height of the shortest parent (in this case, we used a nonparametric test because the distribution of the standard deviation scores [SDS] for the height of the shortest parent was not normal).We considered the results statistically significant when the p-value was less than .05. We performed the statistical calculations with SPSS version 20®.ResultsA total of 1361 requests for GH treatment were submitted to the Assessment Committee of the Autonomous Community of Valencia during the period under study, but only 134 met the inclusion criteria. The remaining 1216 corresponded to requests that were denied because they did not meet the established criteria for SGA or to requests for adult or paediatric patients with indications different than the one under study (GH deficiency, Turner syndrome, Prader-Willi syndrome, renal failure, SHOX mutations).Exclusion criteria applied to 19 of the 134 cases. In 14 out of the 19, there was no record of the mean parental height. In two, there was clear documentation of non-adherence by the family: the prescribing physician personally informed the Committee of the discontinuation of the treatment. In three, treatment was discontinued due to adverse events that were attributed to GH treatment: one patient with left-side slipped capital femoral epiphysiolysis that required surgery, one patient with Perthes disease, and one patient with hyperglycaemia of several months’ duration. Therefore, the final sample consisted of 115, 60 male and 55 female, all of them Caucasian.The mean administered dose of GH was 0.035±0.004mg/kg/day. The 115 patients received treatment for a minimum of two years (as was required for inclusion in the study), and only 96 of the 115 reached the fourth phase (three or more years of treatment). Information on the adult height was only available for 35 of the 115 patients.<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a> show the evolution of height and GV in the patients that did not reach their final height. <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> show the evolution of the 35 children that reached their final height during the period under study.<elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia>We found a statistically significant increase in height from treatment initiation to the fourth phase of the study (P<.0001). As seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>, the mean height of the shortest parent was reached and even surpassed, and there seems to be a trend towards approximating the TH. When we did a separate analysis of the 35 patients that reached their adult height, we found that their evolution in the first four phases was the same as the evolution in the rest of the sample, that is, they had a statistically significant increase in height (P<.0001), but starting in the fourth phase there was a marked decrease in growth and the adult height that was ultimately achieved was short (SDS, −2.22±0.86). When we compared their adult height with their TH (SDS, −1.72±0.75), the difference was statistically significant (Student's t, −2.545; P=.013), but when we compared the adult height achieved with the height of the shortest parent (SDS, −1.95±1.28) the difference was not statistically significant (Mann–Whitney U test z score, −0.582; P=.561).Of the 35 patients that reached their adult height, 42.9% experienced an increase of more than one SDS in height with GH treatment.DiscussionThis is the first study that presents growth outcomes in Valencian children born SGA treated with GH.Although the protocol of our autonomous community does not allow GH treatment in individuals with certain syndromes (Silver Russell, Noonan, Down), our sample was still not homogeneous, as treatment protocols do not guarantee the exclusion of children with syndromes or with certain bone dysplasias (especially those that are not clinically significant in the first years of life). However, the aim of this study was to assess the overall response to GH treatment of patients classified as SGA. It is important to note that we studied the data of treatment request documents as opposed to actual patients. Therefore, we were only aware of patients having abnormal phenotypes if the physician that put in the request for GH treatment documented it (these cases were excluded from the study). The heterogeneity of the sample may have influenced the results. In future prospective studies on this subject, it may be useful to document the presence of syndromic features as well as the measurements of body segments in children born SGA prior to treatment initiation, as opposed to height alone.It would be fair to say that the children in our sample achieved a statistically significant increase in their height SDS in the first four phases of the study (P<.0001). However, we found a substantial deceleration of starting in the fourth phase in the subset of 35 patients that reached their adult height, which was short (SDS, −2.22±0.86). Therefore, contrary to the outcomes reported in other series,<a class="elsevierStyleCrossRefs" href="#bib0215">15–17</a> the patients born SGA in our sample that reached their adult height did not reach normal heights nor approximate their TH. Nevertheless, they succeeded in approximating the height SDS of the shortest parent. None of the studies that we reviewed had considered the assessment of adult height in relation to the height of the shortest parent. We believed that such a comparison would be of interest in our study, considering the suboptimal adult height outcomes that we found.We analysed the factors that may have influenced the poor growth outcomes achieved in Valencian children born SGA. According to the models for the prediction of the response to rhGH in children born SGA published by Ranke et al.,<a class="elsevierStyleCrossRefs" href="#bib0230">18,19</a> the factors that correlate most strongly with growth during the first year of treatment are the age of initiation and the GH dose, while in the second year, the most relevant factor was the GV achieved during the first year. All of these factors were unfavourable in our sample.In our case series, children started treatment at an older age than children in other studies that had better outcomes<a class="elsevierStyleCrossRefs" href="#bib0215">15–17,20</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). The age at the start of treatment was particularly high in the 35 patients that reached their final heights (10.22±1.87 years). The literature emphasises the importance of initiating treatment as early as possible to achieve good outcomes<a class="elsevierStyleCrossRefs" href="#bib0220">16,21,22</a>; in fact, it seems that this is one of the most relevant factors.<a class="elsevierStyleCrossRefs" href="#bib0185">9,17,19,23</a>One possible reason for the delayed initiation in our study is that the sample includes patients that were already older when the indication for treatment was approved in Spain in 2003. Another possible reason, which may have had a greater weight, is the delayed referral of children from primary care to endocrinology clinic.<elsevierMultimedia ident="tbl0015"></elsevierMultimedia>The mean dose of rhGH administered to the patients in our study (0.035±0.004mg/kg/day) was similar to the dose given in other samples<a class="elsevierStyleCrossRefs" href="#bib0215">15–17,20</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>), at the lower end of the recommended range for individuals born SGA.<a class="elsevierStyleCrossRefs" href="#bib0145">1,24</a> There is evidence that the higher the dose used—within the therapeutic ranges—the better the outcomes achieved.<a class="elsevierStyleCrossRefs" href="#bib0145">1,25,26</a> Still, if treatment is initiated at 4–6 years of age with 0.033mg/kg/day, the response is very good. However, prepubertal children with extremely short stature (below −3 SDS)and children that start treatment when they are approaching puberty may require higher doses of 0.055mg/kg/day or more.<a class="elsevierStyleCrossRefs" href="#bib0275">27,28</a> Children in either of these two categories were included in the subset of 35 cases that reached their final height, as treatment in this subset started at a mean age of 10.22 years with a mean height SDS of −3.06. The height outcomes in this group may have been better if they had been treated with doses in the upper recommended range.The growth velocity SDS achieved by the children born SGA in our sample in the first twelve months of treatment was clearly inferior to the one achieved by other groups<a class="elsevierStyleCrossRefs" href="#bib0215">15–17,20</a> (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). It is fair to assume that this outcome was influenced by the factors previously discussed (late age at initiation of treatment and suboptimal rhGH dosage).The truly relevant data in our study corresponds to the subset of 35 patients that reached their adult height. Nevertheless, we present the evolution of the stature of the rest of the patients to underscore that it was very similar to that of those 35 subjects up to the fourth phase. In other words, the charts in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs. 1 and 2</a> are practically superimposable. We believe that this is worth highlighting, as the mean age of the patients in the fourth stage (12.65 years) probably coincides with the timing of the growth spurt, and therefore, the improvement in the height SDS seen in this phase (SDS, −1.76±0.75) may be due to this event rather than to treatment. This may account for the decrease in the height SDS of the 35 patients that reached their final height relative to the previous phase, with an abrupt halt in growth following the pubertal growth spurt. We expect that the final adult height of the patients that have yet to reach it will be similar to that of the patients that already have. However, we cannot be certain until the final adult height data is available for the 115 cases.ConclusionsThe growth outcomes of the studied sample of Valencian children born SGA treated with rhGH for short stature were not as satisfactory as those reported for other published case series. Although their height SDS did improve, they failed to approach their TH and remained with a SDS similar to that of their shortest parent. We believe that these suboptimal results were due to the advanced age at which these children started treatment, and to not having increased the dosage of rhGH taking into account the considerably delayed start, as is recommended in the literature. In order to improve these outcomes, we think it is essential that primary care paediatricians refer children born SGA that have a height SDS of less than −2.5 at around 4 years of age for prompt initiation of treatment, and that the dosage be customised based on the characteristics of the patients.Conflict of interestThe authors have no conflict of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:13 [ 0 => array:3 [ "identificador" => "xres794536" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec792860" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres794537" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 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" => "xpalclavsec792861" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Objectives" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Patients" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "Methods" "secciones" => array:2 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Anthropometric methods" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical methods" ] ] ] 8 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 9 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 10 => array:2 [ "identificador" => "sec0045" "titulo" => "Conclusions" ] 11 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflict of interest" ] 12 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2015-09-21" "fechaAceptado" => "2016-02-23" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec792860" "palabras" => array:3 [ 0 => "Small for gestational age" 1 => "Human growth hormone" 2 => "Short stature" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec792861" "palabras" => array:3 [ 0 => "Pequeño para la edad gestacional" 1 => "Hormona de crecimiento humana" 2 => "Talla baja" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo analyse the effectiveness of growth hormone (GH) therapy in short-stature children born small for gestational age (SGA) without catch-up growth (height at the beginning of treatment<−2.5 SDS), in Valencia (Spain), between 01/01/2003 and 12/31/2013; and to compare our findings with previously published data. Materials and methodsAnthropometric data from the SGA children were obtained from the database of the “Ministry of Health of Valencia”. These data were retrospectively reviewed. ResultsA total of 115 SGA children, with a mean age of 8.10±2.75 years and height of −3.14±0.59 SDS started treatment (dose: 0.035±0.004mg/kg/day) between January 1st, 2003 and March 31st, 2013. After 2 years of therapy (n=115, age: 10.50±2.72 years) the height SDS was −2.11±0.66; and after 4 years (n=96, age: 12.65±2.46 years) of −1.76±0.75 SDS. This latest improvement in stature matches ages at which the growth spurt usually occurs. Only 35 out of 115 children reached adult height, although impaired (−2.22±0.86 SDS), and failed to achieve their target height (−1.72±0.75 SDS). However, this sub-group grew to near the height of the shorter parent (−1.95±1.28 SDS), and 42.9% of these 35 cases increased their stature by more than 1 SDS. ConclusionsThe studied sample did not achieve satisfactory growth results, as in other published series. Our findings might be improved by starting treatment earlier, and with doses individualised according to patient characteristics." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "ObjetivoValorar la efectividad del tratamiento con hormona de crecimiento (GH) en niños pequeños para la edad gestacional (PEG) sin crecimiento recuperador (talla al iniciar la terapia<−2,5 DE), en la Comunidad Valenciana, entre el 01/01/2003 y el 31/12/2013, y comparar los resultados con los ya publicados. Material y métodosLos datos antropométricos de los PEG que constituyeron la muestra de estudio se recogieron retrospectivamente de los documentos de solicitud de tratamiento existentes en la Consejería de Sanidad de Valencia. ResultadosUn total de 115 sujetos comenzaron a tratarse entre el 01/01/2003 y el 31/12/2013, con dosis de GH de 0,035±0,004mg/kg/día, a una edad de 8,10±2,75 años y con una talla de −3,14±0,59 DE. Talla alcanzada tras 2 años de terapia (n=115, edad: 10,50±2,72 años): −2,11±0,66 DE; y tras 4 años (n=96, edad: 12,65±2,46 años): −1,76±0,75 DE. Esta última mejoría de talla coincide con edades a las que suele producirse el estirón puberal. Solo 35 de los 115 niños finalizaron el crecimiento, en el periodo de estudio, a una edad de 16,22±1,19 años. Este subgrupo no consiguió normalizar la talla adulta (−2,22±0,86 DE), ni alcanzar su talla diana (−1,72±0,75 DE); no obstante, hubo una buena aproximación a la talla del progenitor más bajo (−1,95±1,28 DE). El 42,9% de estos 35 casos experimentaron un incremento de estatura superior a 1 DE. ConclusionesLa muestra estudiada no obtiene una respuesta de crecimiento tan satisfactoria como las de otras series publicadas. Probablemente, estos resultados mejorarían iniciando el tratamiento más precozmente, e individualizando las dosis según las características del paciente." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivo" ] 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: Sánchez Zahonero J, López García MJ. Estudio valenciano sobre tratamiento con hormona de crecimiento en pequeños para la edad gestacional. An Pediatr (Barc). 2017;86:87–93." ] ] "multimedia" => array:5 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1191 "Ancho" => 1416 "Tamanyo" => 77281 ] ] "descripcion" => array:1 [ "en" => "Graphic representation of the evolution of the mean height standard deviation scores in the first four phases of the study. The numbers in parentheses correspond to the mean chronological age in each phase of treatment. Initial sample (115 patients), first year (115 patients), second year (115 patients), last year (96 patients)." ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1295 "Ancho" => 1501 "Tamanyo" => 87971 ] ] "descripcion" => array:1 [ "en" => "Evolution of the height of the 35 patients that reached their adult height during the study." ] ] 2 => 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:1 [ "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=""><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Family anthropometric data \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=115 \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">Target height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.35±0.80 \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">Height SDS of the shortest parent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.83±0.83 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Before treatment initiation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=115 \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.10±2.75 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.14±0.59 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After one year of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=115 \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.27±2.73 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−2.50±0.63 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.12±2.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">After two years of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=115 \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.50±2.72 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−2.11±0.66 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.25±1.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Last year of treatment \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">N=96 \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">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.65±2.46 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.76±0.75 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.48±1.35 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328995.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Anthropometric data of the sample throughout the study (mean±standard deviation)." ] ] 3 => 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:1 [ "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=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Family anthropometric data</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Target height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.72±0.75 \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">Height SDS of the shortest parent \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.95±1.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Before treatment initiation</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">10.22±1.87 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−3.06±0.62 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">After one year of treatment</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">11.43±1.87 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.55±0.69 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">1.48±1.63 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">After two years of treatment</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">12.66±1.92 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.18±0.74 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.85±0.99 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Last year of treatment</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">14.71±1.41 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−1.90±0.80 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.43±1.34 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top"></td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">Data on final height</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Chronological age at which adult height was reached (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.22±1.19 \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">Adult height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.22±0.86 \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">Δ (adult height SDS−initial height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.85±0.67 \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">Δ (adult height SDS−target height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.49±0.71 \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">Δ (adult height SDS−shortest parent height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.27±1.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328991.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Anthropometric data of the 35 patients that reached the target height (mean±standard deviation)." ] ] 4 => 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:2 [ "leyenda" => "SD, standard deviation; SDS, standard deviation score; X, mean." "tablatextoimagen" => array:4 [ 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Data prior to initiation of treatment with rhGH \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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240">20</a> (n=65) Median (P10/P90) \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">Van Pareren et al.<a class="elsevierStyleCrossRef" href="#bib0225">17</a> (n=28) \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">Carrascosa et al.<a class="elsevierStyleCrossRef" href="#bib0215">15</a> (n=49) \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">Güemes-Hidalgo et al.<a class="elsevierStyleCrossRef" href="#bib0220">16</a> (n=52) \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">Our sample (n=115) \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">Chronological age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.9 (3.6/11.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD 7.9±1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD H: 7.8±1.8 M: 6.5±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD 5.90±2.29 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD 8.10±2.75 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) −3.6 (−5.0/−2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) −2.9±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.3±0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.12±0.62 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−3.14±0.59 \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">Prescribed rhGH dosage (mg/kg/day) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.035 (0.022/0.061) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: 0.033 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.0319±0.0035 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Range: 0.033–0.045 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.035±0.004 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328993.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="left" valign="top" scope="col" style="border-bottom: 2px solid black">After 1 year of treatment \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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240">20</a> (n=65) Median (P10/P90) \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">Van Pareren et al.<a class="elsevierStyleCrossRef" href="#bib0225">17</a> (n=28) \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">Carrascosa et al.<a class="elsevierStyleCrossRef" href="#bib0215">15</a> (n=49) \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">Güemes-Hidalgo et al.<a class="elsevierStyleCrossRef" href="#bib0220">16</a> (n=45) \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">Our sample (n=115) \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) −3.0 (4.6/−2.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Δheight SDS in 1 year: 0.8±0.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: −2.2 P5: −2.4 P95: −1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: −2.50±0.63 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(cm/year) 7.5 (5.6/10.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD 4.5±1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: 3.22 P5: 2.59 P95: 3.85 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: 2.12±2.01 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328994.png" ] ] 2 => 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">After two years of treatment \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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240">20</a> (n=65) Median (P10/P90) \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">Van Pareren et al.<a class="elsevierStyleCrossRef" href="#bib0225">17</a> (n=28) \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">Carrascosa et al.<a class="elsevierStyleCrossRef" href="#bib0215">15</a> (n=49) \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">Güemes-Hidalgo et al.<a class="elsevierStyleCrossRef" href="#bib0220">16</a> (n=36) \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">Our sample (n=115) \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: −1.5±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Δheight SDS in 2 years: 1.2±0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: −1.8 P5: −2.0 P95: −1.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: −2.11±0.66 \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">Growth velocity SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: 2.0±1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: 2.28 P5: 1.7 P95: 2.87 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: 1.25±0.66 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328990.png" ] ] 3 => 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adult height \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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240">20</a> (n=65) Median (P10/P90) \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">Van Pareren et al.<a class="elsevierStyleCrossRef" href="#bib0225">17</a> (n=28) \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">Carrascosa et al.<a class="elsevierStyleCrossRef" href="#bib0215">15</a> (n=49) X±SD \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">Güemes-Hidalgo et al.<a class="elsevierStyleCrossRef" href="#bib0220">16</a> \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">Our sample (n=35) X±SD \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">Chronological age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">16.8 (14.7/18.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: 15.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Male: 17.4±0.8 Female: 15.4±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.22±1.19 \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">Height SDS \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) −2.1 (−3.5/−1.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X±SD: −1.1±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−1.7±0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−2.22±0.86 \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">Δ (adult height SDS−initial height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) 1.3 (0.2/2.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">X: 1.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.6±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">0.85±0.67 \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">Δ (adult height SDS−parental height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Prader) −1.0 (2.4/0.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">−0.4±0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.49±0.71 \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">Δ (adult height SDS−shortest parent height SDS) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Not documented \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">– \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">−0.27±1.55 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1328992.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Comparison of results obtained in our sample of SGA children with those of other studies." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:28 [ 0 => array:3 [ "identificador" => "bib0145" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Management of the child born small for gestational age through to adulthood: a consensus statement of the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "P.E. 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Dunger" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1210/jcem.87.1.8293" "Revista" => array:6 [ "tituloSerie" => "J Clin Endocrinol Metab" "fecha" => "2002" "volumen" => "87" "paginaInicial" => "148" "paginaFinal" => "151" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11788639" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:3 [ "titulo" => "Acknowledgments" "texto" => "We want to thank the entire staff of the Conselleria de Sanitat, and especially Carmen Albeldaand María Antonia Grau. We also want to thank the physicians in all the hospitals of the Autonomous Community of Valencia that submitted the request forms for treatment with growth hormone to the Conselleria de Sanitat, as these were the source of the data for this study." 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Study on growth hormone treatment in small for gestational age children

Estudio valenciano sobre tratamiento con hormona de crecimiento en pequeños para la edad gestacional

Julia Sánchez Zahonero

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ju-san-za@hotmail.com

Corresponding author.

, María José López García

Hospital Clínico Universitario de Valencia, Valencia, Spain

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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of the evolution of the mean height standard deviation scores in the first four phases of the study&#46; The numbers in parentheses correspond to the mean chronological age in each phase of treatment&#46; Initial sample &#40;115 patients&#41;&#44; first year &#40;115 patients&#41;&#44; second year &#40;115 patients&#41;&#44; last year &#40;96 patients&#41;&#46;</p>"
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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">Small for gestational age &#40;SGA&#41; refers to newborns whose birth weight or length are 2 or more standard deviations &#40;SDs&#41; below the mean for their sex and gestational age in the reference population&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> This results from abnormalities in intrauterine growth&#44; whose cause is unknown in 40&#37; of cases&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Approximately 90&#37; of these children exhibit spontaneous catch-up growth in the first two years of life&#44; although this may be delayed until age 3&#8211;4 years in children born preterm&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> This catch-up growth does not occur in the remaining 10&#37;&#44; in most cases for unknown reasons&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#44;4</span></a> Some of the possible causes that have been proposed include a decreased cell mass at the time of birth and alterations of endocrine-metabolic pathways involved in postnatal growth&#44; especially in the GH-IGF-1 axis&#46; However&#44; growth hormone stimulation tests show normal or even elevated levels of growth hormone &#40;GH&#41; in most SGA children&#44;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">5</span></a> which suggests some degree of peripheral resistance to GH activity or a reduced biological activity of GH&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Job and colleagues were the first to use recombinant human growth hormone &#40;rhGH&#41; for the treatment of delayed postnatal growth seen in some children born SGA&#44;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">6&#44;7</span></a> and set the foundations for subsequent research&#44; the results of which suggests that rhGH is a safe and effective treatment to partially reduce stature deficits in the adult height of individuals born SGA&#46; However&#44; the response to treatment varies widely between studies&#44; which may be related to the diverse aetiology of SGA&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#8211;11</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The use of this hormone for the treatment of short children born SGA was authorised by the Food and Drug Administration &#40;FDA&#41; in July 2001 and by the European Agency for the Evaluation of Medicinal Products &#40;EMA&#41; in June 2003&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> The Spanish Agency of Medicines and Health Care Products &#40;Agencia Espa&#241;ola del Medicamento y Productos Sanitarios &#91;AEMPS&#93;&#41; follows the criteria set by the EMA&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The dosage of rhGH recommended for children born SGA is higher than the one in children with GH deficiency&#44; and ranges between 0&#46;035 and 0&#46;067<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> The reason for this is that&#44; as noted above&#44; SGA patients exhibit a degree of peripheral resistance to GH activity rather than decreased GH release&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">No studies have been conducted on the effectiveness of treatment in individuals born SGA in the Autonomous Community of Valencia since this indication for rhGH was approved&#46; In this article&#44; we present the growth outcomes in a sample of children treated over a 10-year period&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Objectives</span><p id="par0035" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">&#40;a&#41;</span><p id="par0040" class="elsevierStylePara elsevierViewall">To assess the effectiveness of growth hormone in children born SGA in our area&#44; between January 01&#44; 2003 and December 31&#44; 2013&#44; based on the proportion of these patients that reached their target height by the end of treatment&#44; or the corresponding growth trajectory if treatment was not completed&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">&#40;b&#41;</span><p id="par0045" class="elsevierStylePara elsevierViewall">To compare the obtained results with those published by other research groups in Spain and abroad&#46;</p></li></ul></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patients</span><p id="par0050" class="elsevierStylePara elsevierViewall">We used the information gathered in the request forms for initiation&#44; renewal and completion of rhGH therapy submitted to the Growth Hormone Assessment Committee of the Autonomous Community of Valencia by every paediatric endocrinology unit in the hospitals of the three provinces between January 1&#44; 2003 and December 31&#44; 2013&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">We obtained permission to access these data from the Clinical Research Ethics Committee of the Fundaci&#243;n de Investigaci&#243;n of the Hospital Cl&#237;nico Universitario de Valencia&#46; The study was classified as an observational post-authorisation study&#8212;other designs &#40;<span class="elsevierStyleItalic">OPA-OD</span>&#41; based on the directives of Order SAS&#47;3470&#47;2009&#44; of December 16 of the Ministry of Health&#46; These are retrospective studies in which due to the size of the sample or the long time elapsed since data collection&#44; the informed consent of included individuals is not required&#44; as long as their anonymity is safeguarded&#46; Furthermore&#44; the study was approved by the Department of Health of the Autonomous Community of Valencia&#44; as these documents are stored for safekeeping in its facilities&#44; where we carried out data collection&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">We obtained the study sample applying the following criteria&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">&#40;a&#41;</span><p id="par0065" class="elsevierStylePara elsevierViewall">Inclusion&#58; we only included children born SGA that strictly fulfilled all the following prerequisites&#58;<ul class="elsevierStyleList" id="lis0015"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0070" class="elsevierStylePara elsevierViewall">Birth weight or length of less than &#8722;2 SDS&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0075" class="elsevierStylePara elsevierViewall">Height from birth consistently below &#8722;2&#46;5 SDS&#46;</p></li><li class="elsevierStyleListItem" id="lsti0030"><span class="elsevierStyleLabel">-</span><p id="par0080" class="elsevierStylePara elsevierViewall">Had not reached puberty&#46;</p></li><li class="elsevierStyleListItem" id="lsti0035"><span class="elsevierStyleLabel">-</span><p id="par0085" class="elsevierStylePara elsevierViewall">Had received treatment with growth hormone for a minimum of two years&#46;</p></li></ul></p></li><li class="elsevierStyleListItem" id="lsti0040"><span class="elsevierStyleLabel">&#40;b&#41;</span><p id="par0090" class="elsevierStylePara elsevierViewall">Exclusion&#58; of all children that met the inclusion criteria&#44; we excluded those whose target height was unknown and those in whom treatment was discontinued prematurely due to the development of adverse reactions or poor adherence&#46;</p></li></ul></p><p id="par0095" class="elsevierStylePara elsevierViewall">We studied the following variables retrospectively&#58;<ul class="elsevierStyleList" id="lis0020"><li class="elsevierStyleListItem" id="lsti0045"><span class="elsevierStyleLabel">1&#46;</span><p id="par0100" class="elsevierStylePara elsevierViewall">Prescribed dosage of GH &#40;mg&#47;kg&#47;day&#41;&#46;</p></li><li class="elsevierStyleListItem" id="lsti0050"><span class="elsevierStyleLabel">2&#46;</span><p id="par0105" class="elsevierStylePara elsevierViewall">Family anthropometric data&#58; target height &#40;TH&#41; SDS and height SDS of the shortest parent&#46;</p></li><li class="elsevierStyleListItem" id="lsti0055"><span class="elsevierStyleLabel">3&#46;</span><p id="par0110" class="elsevierStylePara elsevierViewall">Patient anthropometric data&#58; decimal age in years&#44; SDS for height and growth velocity &#40;GV&#41;&#46; Specifically&#44; these data were collected at five phases&#58; 1st&#44; prior to starting treatment&#59; 2nd&#44; after one year of treatment&#59; 3rd&#44; after two years of treatment&#59; 4th&#44; the last year they received treatment&#59; and 5th&#44; adult height&#46;</p></li></ul></p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Methods</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Anthropometric methods</span><p id="par0115" class="elsevierStylePara elsevierViewall">We found the SDS of the aforementioned anthropometric measures by applying the tables of the 2010 Spanish Cross-sectional Growth Study<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;13</span></a> &#40;TH&#44; height of the shortest parent and patient heights in the five phases of the study&#41; and of the 1978&#8211;2000 Spanish LongitudinalStudy<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">14</span></a> &#40;for GV&#44; keeping into account the maturation stage of the patient&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">We considered that patients had reached their adult height when their grow rate became less than 2<span class="elsevierStyleHsp" style=""></span>cm per year or their growth plates had closed&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Statistical methods</span><p id="par0125" class="elsevierStylePara elsevierViewall">We have described the baseline characteristics of our sample using the mean and standard deviation&#46; To assess the effectiveness of treatment&#44; we compared the mean height achieved in each phase of the study with the height of the phase immediately preceding it using Student&#39;s <span class="elsevierStyleItalic">t</span> test for paired samples with the Bonferroni correction&#46; We used Student&#39;s <span class="elsevierStyleItalic">t</span> test for independent samples to compare the mean adult height with the TH &#40;both variables followed a normal distribution&#41; and the Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test to compare the mean adult height with the height of the shortest parent &#40;in this case&#44; we used a nonparametric test because the distribution of the standard deviation scores &#91;SDS&#93; for the height of the shortest parent was not normal&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We considered the results statistically significant when the <span class="elsevierStyleItalic">p</span>-value was less than &#46;05&#46; We performed the statistical calculations with SPSS version 20<span class="elsevierStyleSup">&#174;</span>&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results</span><p id="par0135" class="elsevierStylePara elsevierViewall">A total of 1361 requests for GH treatment were submitted to the Assessment Committee of the Autonomous Community of Valencia during the period under study&#44; but only 134 met the inclusion criteria&#46; The remaining 1216 corresponded to requests that were denied because they did not meet the established criteria for SGA or to requests for adult or paediatric patients with indications different than the one under study &#40;GH deficiency&#44; Turner syndrome&#44; Prader-Willi syndrome&#44; renal failure&#44; <span class="elsevierStyleItalic">SHOX</span> mutations&#41;&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Exclusion criteria applied to 19 of the 134 cases&#46; In 14 out of the 19&#44; there was no record of the mean parental height&#46; In two&#44; there was clear documentation of non-adherence by the family&#58; the prescribing physician personally informed the Committee of the discontinuation of the treatment&#46; In three&#44; treatment was discontinued due to adverse events that were attributed to GH treatment&#58; one patient with left-side slipped capital femoral epiphysiolysis that required surgery&#44; one patient with Perthes disease&#44; and one patient with hyperglycaemia of several months&#8217; duration&#46; Therefore&#44; the final sample consisted of 115&#44; 60 male and 55 female&#44; all of them Caucasian&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">The mean administered dose of GH was 0&#46;035<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;004<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#46; The 115 patients received treatment for a minimum of two years &#40;as was required for inclusion in the study&#41;&#44; and only 96 of the 115 reached the fourth phase &#40;three or more years of treatment&#41;&#46; Information on the adult height was only available for 35 of the 115 patients&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> and <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> show the evolution of height and GV in the patients that did not reach their final height&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0010">Fig&#46; 2</a> show the evolution of the 35 children that reached their final height during the period under study&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="fig0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0155" class="elsevierStylePara elsevierViewall">We found a statistically significant increase in height from treatment initiation to the fourth phase of the study &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; As seen in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#44; the mean height of the shortest parent was reached and even surpassed&#44; and there seems to be a trend towards approximating the TH&#46; When we did a separate analysis of the 35 patients that reached their adult height&#44; we found that their evolution in the first four phases was the same as the evolution in the rest of the sample&#44; that is&#44; they had a statistically significant increase in height &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#44; but starting in the fourth phase there was a marked decrease in growth and the adult height that was ultimately achieved was short &#40;SDS&#44; &#8722;2&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;86&#41;&#46; When we compared their adult height with their TH &#40;SDS&#44; &#8722;1&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#41;&#44; the difference was statistically significant &#40;Student&#39;s <span class="elsevierStyleItalic">t</span>&#44; &#8722;2&#46;545&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;013&#41;&#44; but when we compared the adult height achieved with the height of the shortest parent &#40;SDS&#44; &#8722;1&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;28&#41; the difference was not statistically significant &#40;Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> test <span class="elsevierStyleItalic">z</span> score&#44; &#8722;0&#46;582&#59; <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>&#46;561&#41;&#46;</p><p id="par0160" class="elsevierStylePara elsevierViewall">Of the 35 patients that reached their adult height&#44; 42&#46;9&#37; experienced an increase of more than one SDS in height with GH treatment&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0165" class="elsevierStylePara elsevierViewall">This is the first study that presents growth outcomes in Valencian children born SGA treated with GH&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">Although the protocol of our autonomous community does not allow GH treatment in individuals with certain syndromes &#40;Silver Russell&#44; Noonan&#44; Down&#41;&#44; our sample was still not homogeneous&#44; as treatment protocols do not guarantee the exclusion of children with syndromes or with certain bone dysplasias &#40;especially those that are not clinically significant in the first years of life&#41;&#46; However&#44; the aim of this study was to assess the overall response to GH treatment of patients classified as SGA&#46; It is important to note that we studied the data of treatment request documents as opposed to actual patients&#46; Therefore&#44; we were only aware of patients having abnormal phenotypes if the physician that put in the request for GH treatment documented it &#40;these cases were excluded from the study&#41;&#46; The heterogeneity of the sample may have influenced the results&#46; In future prospective studies on this subject&#44; it may be useful to document the presence of syndromic features as well as the measurements of body segments in children born SGA prior to treatment initiation&#44; as opposed to height alone&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">It would be fair to say that the children in our sample achieved a statistically significant increase in their height SDS in the first four phases of the study &#40;<span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#46;0001&#41;&#46; However&#44; we found a substantial deceleration of starting in the fourth phase in the subset of 35 patients that reached their adult height&#44; which was short &#40;SDS&#44; &#8722;2&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;86&#41;&#46; Therefore&#44; contrary to the outcomes reported in other series&#44;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#8211;17</span></a> the patients born SGA in our sample that reached their adult height did not reach normal heights nor approximate their TH&#46; Nevertheless&#44; they succeeded in approximating the height SDS of the shortest parent&#46; None of the studies that we reviewed had considered the assessment of adult height in relation to the height of the shortest parent&#46; We believed that such a comparison would be of interest in our study&#44; considering the suboptimal adult height outcomes that we found&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">We analysed the factors that may have influenced the poor growth outcomes achieved in Valencian children born SGA&#46; According to the models for the prediction of the response to rhGH in children born SGA published by Ranke et al&#46;&#44;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">18&#44;19</span></a> the factors that correlate most strongly with growth during the first year of treatment are the age of initiation and the GH dose&#44; while in the second year&#44; the most relevant factor was the GV achieved during the first year&#46; All of these factors were unfavourable in our sample&#46;</p><p id="par0185" class="elsevierStylePara elsevierViewall">In our case series&#44; children started treatment at an older age than children in other studies that had better outcomes<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#8211;17&#44;20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; The age at the start of treatment was particularly high in the 35 patients that reached their final heights &#40;10&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;87 years&#41;&#46; The literature emphasises the importance of initiating treatment as early as possible to achieve good outcomes<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">16&#44;21&#44;22</span></a>&#59; in fact&#44; it seems that this is one of the most relevant factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0185"><span class="elsevierStyleSup">9&#44;17&#44;19&#44;23</span></a>One possible reason for the delayed initiation in our study is that the sample includes patients that were already older when the indication for treatment was approved in Spain in 2003&#46; Another possible reason&#44; which may have had a greater weight&#44; is the delayed referral of children from primary care to endocrinology clinic&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">The mean dose of rhGH administered to the patients in our study &#40;0&#46;035<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;004<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41; was similar to the dose given in other samples<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#8211;17&#44;20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#44; at the lower end of the recommended range for individuals born SGA&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;24</span></a> There is evidence that the higher the dose used&#8212;within the therapeutic ranges&#8212;the better the outcomes achieved&#46;<a class="elsevierStyleCrossRefs" href="#bib0145"><span class="elsevierStyleSup">1&#44;25&#44;26</span></a> Still&#44; if treatment is initiated at 4&#8211;6 years of age with 0&#46;033<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#44; the response is very good&#46; However&#44; prepubertal children with extremely short stature &#40;below &#8722;3 SDS&#41;and children that start treatment when they are approaching puberty may require higher doses of 0&#46;055<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day or more&#46;<a class="elsevierStyleCrossRefs" href="#bib0275"><span class="elsevierStyleSup">27&#44;28</span></a> Children in either of these two categories were included in the subset of 35 cases that reached their final height&#44; as treatment in this subset started at a mean age of 10&#46;22 years with a mean height SDS of &#8722;3&#46;06&#46; The height outcomes in this group may have been better if they had been treated with doses in the upper recommended range&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">The growth velocity SDS achieved by the children born SGA in our sample in the first twelve months of treatment was clearly inferior to the one achieved by other groups<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#8211;17&#44;20</span></a> &#40;<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#41;&#46; It is fair to assume that this outcome was influenced by the factors previously discussed &#40;late age at initiation of treatment and suboptimal rhGH dosage&#41;&#46;</p><p id="par0200" class="elsevierStylePara elsevierViewall">The truly relevant data in our study corresponds to the subset of 35 patients that reached their adult height&#46; Nevertheless&#44; we present the evolution of the stature of the rest of the patients to underscore that it was very similar to that of those 35 subjects up to the fourth phase&#46; In other words&#44; the charts in <a class="elsevierStyleCrossRefs" href="#fig0005">Figs&#46; 1 and 2</a> are practically superimposable&#46; We believe that this is worth highlighting&#44; as the mean age of the patients in the fourth stage &#40;12&#46;65 years&#41; probably coincides with the timing of the growth spurt&#44; and therefore&#44; the improvement in the height SDS seen in this phase &#40;SDS&#44; &#8722;1&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75&#41; may be due to this event rather than to treatment&#46; This may account for the decrease in the height SDS of the 35 patients that reached their final height relative to the previous phase&#44; with an abrupt halt in growth following the pubertal growth spurt&#46; We expect that the final adult height of the patients that have yet to reach it will be similar to that of the patients that already have&#46; However&#44; we cannot be certain until the final adult height data is available for the 115 cases&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Conclusions</span><p id="par0205" class="elsevierStylePara elsevierViewall">The growth outcomes of the studied sample of Valencian children born SGA treated with rhGH for short stature were not as satisfactory as those reported for other published case series&#46; Although their height SDS did improve&#44; they failed to approach their TH and remained with a SDS similar to that of their shortest parent&#46; We believe that these suboptimal results were due to the advanced age at which these children started treatment&#44; and to not having increased the dosage of rhGH taking into account the considerably delayed start&#44; as is recommended in the literature&#46; In order to improve these outcomes&#44; we think it is essential that primary care paediatricians refer children born SGA that have a height SDS of less than &#8722;2&#46;5 at around 4 years of age for prompt initiation of treatment&#44; and that the dosage be customised based on the characteristics of the patients&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interest</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare&#46;</p></span></span>"
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    "fechaRecibido" => "2015-09-21"
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            0 => "Small for gestational age"
            1 => "Human growth hormone"
            2 => "Short stature"
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          "palabras" => array:3 [
            0 => "Peque&#241;o para la edad gestacional"
            1 => "Hormona de crecimiento humana"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To analyse the effectiveness of growth hormone &#40;GH&#41; therapy in short-stature children born small for gestational age &#40;SGA&#41; without catch-up growth &#40;height at the beginning of treatment<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;2&#46;5 SDS&#41;&#44; in Valencia &#40;Spain&#41;&#44; between 01&#47;01&#47;2003 and 12&#47;31&#47;2013&#59; and to compare our findings with previously published data&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Anthropometric data from the SGA children were obtained from the database of the &#8220;Ministry of Health of Valencia&#8221;&#46; These data were retrospectively reviewed&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A total of 115 SGA children&#44; with a mean age of 8&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;75 years and height of &#8722;3&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;59 SDS started treatment &#40;dose&#58; 0&#46;035<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;004<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;day&#41; between January 1st&#44; 2003 and March 31st&#44; 2013&#46; After 2 years of therapy &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#44; age&#58; 10&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;72 years&#41; the height SDS was &#8722;2&#46;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;66&#59; and after 4 years &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>96&#44; age&#58; 12&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;46 years&#41; of &#8722;1&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75 SDS&#46; This latest improvement in stature matches ages at which the growth spurt usually occurs&#46; Only 35 out of 115 children reached adult height&#44; although impaired &#40;&#8722;2&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;86 SDS&#41;&#44; and failed to achieve their target height &#40;&#8722;1&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75 SDS&#41;&#46; However&#44; this sub-group grew to near the height of the shorter parent &#40;&#8722;1&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;28 SDS&#41;&#44; and 42&#46;9&#37; of these 35 cases increased their stature by more than 1 SDS&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The studied sample did not achieve satisfactory growth results&#44; as in other published series&#46; Our findings might be improved by starting treatment earlier&#44; and with doses individualised according to patient characteristics&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Valorar la efectividad del tratamiento con hormona de crecimiento &#40;GH&#41; en ni&#241;os peque&#241;os para la edad gestacional &#40;PEG&#41; sin crecimiento recuperador &#40;talla al iniciar la terapia<span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>&#8722;2&#44;5 DE&#41;&#44; en la Comunidad Valenciana&#44; entre el 01&#47;01&#47;2003 y el 31&#47;12&#47;2013&#44; y comparar los resultados con los ya publicados&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Material y m&#233;todos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Los datos antropom&#233;tricos de los PEG que constituyeron la muestra de estudio se recogieron retrospectivamente de los documentos de solicitud de tratamiento existentes en la Consejer&#237;a de Sanidad de Valencia&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Un total de 115 sujetos comenzaron a tratarse entre el 01&#47;01&#47;2003 y el 31&#47;12&#47;2013&#44; con dosis de GH de 0&#44;035<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;004<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;d&#237;a&#44; a una edad de 8&#44;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;75 a&#241;os y con una talla de &#8722;3&#44;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;59 DE&#46; Talla alcanzada tras 2 a&#241;os de terapia &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#44; edad&#58; 10&#44;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;72 a&#241;os&#41;&#58; &#8722;2&#44;11<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;66 DE&#59; y tras 4 a&#241;os &#40;n<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>96&#44; edad&#58; 12&#44;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#44;46 a&#241;os&#41;&#58; &#8722;1&#44;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;75 DE&#46; Esta &#250;ltima mejor&#237;a de talla coincide con edades a las que suele producirse el estir&#243;n puberal&#46; Solo 35 de los 115 ni&#241;os finalizaron el crecimiento&#44; en el periodo de estudio&#44; a una edad de 16&#44;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;19 a&#241;os&#46; Este subgrupo no consigui&#243; normalizar la talla adulta &#40;&#8722;2&#44;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;86 DE&#41;&#44; ni alcanzar su talla diana &#40;&#8722;1&#44;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#44;75 DE&#41;&#59; no obstante&#44; hubo una buena aproximaci&#243;n a la talla del progenitor m&#225;s bajo &#40;&#8722;1&#44;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#44;28 DE&#41;&#46; El 42&#44;9&#37; de estos 35 casos experimentaron un incremento de estatura superior a 1 DE&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">La muestra estudiada no obtiene una respuesta de crecimiento tan satisfactoria como las de otras series publicadas&#46; Probablemente&#44; estos resultados mejorar&#237;an iniciando el tratamiento m&#225;s precozmente&#44; e individualizando las dosis seg&#250;n las caracter&#237;sticas del paciente&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; S&#225;nchez Zahonero J&#44; L&#243;pez Garc&#237;a MJ&#46; Estudio valenciano sobre tratamiento con hormona de crecimiento en peque&#241;os para la edad gestacional&#46; An Pediatr &#40;Barc&#41;&#46; 2017&#59;86&#58;87&#8211;93&#46;</p>"
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          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Graphic representation of the evolution of the mean height standard deviation scores in the first four phases of the study&#46; The numbers in parentheses correspond to the mean chronological age in each phase of treatment&#46; Initial sample &#40;115 patients&#41;&#44; first year &#40;115 patients&#41;&#44; second year &#40;115 patients&#41;&#44; last year &#40;96 patients&#41;&#46;</p>"
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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-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Family anthropometric data</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&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"><span class="elsevierStyleHsp" style=""></span>Target height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;35<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;80&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"><span class="elsevierStyleHsp" style=""></span>Height SDS of the shortest parent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;83<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;83&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Before treatment initiation</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&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"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#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;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;75&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">After one year of treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&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"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#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&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;73&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;2&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;63&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"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&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;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">After two years of treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&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"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#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&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;72&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;2&#46;11<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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&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;25<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Last year of treatment</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">N</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>96&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"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#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&#46;65<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;46&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;1&#46;76<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75&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"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&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;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;35&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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                0 => "xTab1328995.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Anthropometric data of the sample throughout the study &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#41;&#46;</p>"
        ]
      ]
      3 => 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:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Family anthropometric data</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Target height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;72<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;75&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"><span class="elsevierStyleHsp" style=""></span>Height SDS of the shortest parent&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;95<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Before treatment initiation</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;87&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;3&#46;06<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">After one year of treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;87&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;55<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;69&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"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&#46;48<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;63&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">After two years of treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&#46;66<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;92&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;18<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;74&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"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;99&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Last year of treatment</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">14&#46;71<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;41&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"><span class="elsevierStyleHsp" style=""></span>Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;1&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;80&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"><span class="elsevierStyleHsp" style=""></span>Growth velocity SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;43<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;34&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="2" align="left" valign="top"><span class="elsevierStyleItalic">Data on final height</span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Chronological age at which adult height was reached &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;19&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"><span class="elsevierStyleHsp" style=""></span>Adult height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;86&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"><span class="elsevierStyleHsp" style=""></span>&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>initial height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;67&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"><span class="elsevierStyleHsp" style=""></span>&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>target height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;71&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"><span class="elsevierStyleHsp" style=""></span>&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>shortest parent height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1328991.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Anthropometric data of the 35 patients that reached the target height &#40;mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation&#41;&#46;</p>"
        ]
      ]
      4 => 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:2 [
          "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">SD&#44; standard deviation&#59; SDS&#44; standard deviation score&#59; <span class="elsevierStyleItalic">X</span>&#44; mean&#46;</p>"
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            0 => array:2 [
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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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Data prior to initiation of treatment with rhGH&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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#41;<br>Median &#40;P10&#47;P90&#41;&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">Van Pareren et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;&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">Carrascosa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>49&#41;&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">G&#252;emes-Hidalgo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>52&#41;&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">Our sample<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#41;&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">Chronological age &#40;years&#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;9 &#40;3&#46;6&#47;11&#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"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD<br>7&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD<br><span class="elsevierStyleItalic">H</span>&#58; 7&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8<br><span class="elsevierStyleItalic">M</span>&#58; 6&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD<br>5&#46;90<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD<br>8&#46;10<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;75&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">Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Prader&#41;<br>&#8722;3&#46;6 &#40;&#8722;5&#46;0&#47;&#8722;2&#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">&#40;Prader&#41;<br>&#8722;2&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;3<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;62&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;3&#46;14<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;59&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">Prescribed rhGH dosage &#40;mg&#47;kg&#47;day&#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;035 &#40;0&#46;022&#47;0&#46;061&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span>&#58; 0&#46;033&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;0319<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;0035&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Range&#58; 0&#46;033&#8211;0&#46;045&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;035<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;004&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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                0 => "xTab1328993.png"
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            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="left" valign="top" scope="col" style="border-bottom: 2px solid black">After 1 year of treatment&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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#41;<br>Median &#40;P10&#47;P90&#41;&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">Van Pareren et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;&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">Carrascosa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>49&#41;&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">G&#252;emes-Hidalgo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>45&#41;&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">Our sample<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#41;&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">Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Prader&#41;<br>&#8722;3&#46;0 &#40;4&#46;6&#47;&#8722;2&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#916;height SDS in 1 year&#58;<br>0&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span>&#58; &#8722;2&#46;2<br>P5&#58; &#8722;2&#46;4<br>P95&#58; &#8722;1&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>&#8722;2&#46;50<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;63&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">Growth velocity SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;cm&#47;year&#41;<br>7&#46;5 &#40;5&#46;6&#47;10&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD<br>4&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span>&#58; 3&#46;22<br>P5&#58; 2&#46;59<br>P95&#58; 3&#46;85&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>2&#46;12<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
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            2 => array:2 [
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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="left" valign="top" scope="col" style="border-bottom: 2px solid black">After two years of treatment&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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#41;<br>Median &#40;P10&#47;P90&#41;&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">Van Pareren et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;&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">Carrascosa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>49&#41;&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">G&#252;emes-Hidalgo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>36&#41;&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">Our sample<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>115&#41;&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">Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>&#8722;1&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#916;height SDS in 2 years&#58;<br>1&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span>&#58; &#8722;1&#46;8<br>P5&#58; &#8722;2&#46;0<br>P95&#58; &#8722;1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>&#8722;2&#46;11<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></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Growth velocity SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>2&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span>&#58; 2&#46;28<br>P5&#58; 1&#46;7<br>P95&#58; 2&#46;87&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top"><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&#58;<br>1&#46;25<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></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1328990.png"
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            3 => 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="left" valign="top" scope="col" style="border-bottom: 2px solid black">Adult height&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">KIGS<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">20</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>65&#41;<br>Median &#40;P10&#47;P90&#41;&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">Van Pareren et al&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">17</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>28&#41;&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">Carrascosa et al&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a><br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>49&#41;<br><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&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">G&#252;emes-Hidalgo et al&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">16</span></a>&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">Our sample<br>&#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>35&#41;<br><span class="elsevierStyleItalic">X</span><span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&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">Chronological age &#40;years&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">16&#46;8 &#40;14&#46;7&#47;18&#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"><span class="elsevierStyleItalic">X</span>&#58; 15&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Male&#58; 17&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8<br>Female&#58; 15&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">16&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;19&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">Height SDS&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Prader&#41;<br>&#8722;2&#46;1 &#40;&#8722;3&#46;5&#47;&#8722;1&#46;3&#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">&#8722;1&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;2&#46;22<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;86&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">&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>initial height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Prader&#41;<br>1&#46;3 &#40;0&#46;2&#47;2&#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"><span class="elsevierStyleItalic">X</span>&#58; 1&#46;8&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;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;85<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;67&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">&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>parental height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#40;Prader&#41;<br>&#8722;1&#46;0 &#40;2&#46;4&#47;0&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8722;0&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;49<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>0&#46;71&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">&#916; &#40;adult height SDS<span class="elsevierStyleHsp" style=""></span>&#8722;<span class="elsevierStyleHsp" style=""></span>shortest parent height SDS&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">Not documented&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="left" valign="top">&#8211;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#8722;0&#46;27<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;55&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Comparison of results obtained in our sample of SGA children with those of other studies&#46;</p>"
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Article information

ISSN: 23412879
Original language: English

DOI:10.1016/j.anpede.2016.02.003

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	7	18	25
2024 October	57	46	103
2024 September	77	30	107
2024 August	79	64	143
2024 July	93	24	117
2024 June	62	17	79
2024 May	70	26	96
2024 April	84	32	116
2024 March	55	32	87
2024 February	40	31	71
2024 January	26	23	49
2023 December	18	19	37
2023 November	44	25	69
2023 October	29	27	56
2023 September	17	24	41
2023 August	39	10	49
2023 July	35	28	63
2023 June	36	27	63
2023 May	43	21	64
2023 April	29	16	45
2023 March	44	25	69
2023 February	42	14	56
2023 January	21	24	45
2022 December	51	33	84
2022 November	43	44	87
2022 October	51	34	85
2022 September	44	40	84
2022 August	42	56	98
2022 July	27	34	61
2022 June	44	39	83
2022 May	67	44	111
2022 April	39	35	74
2022 March	39	44	83
2022 February	31	34	65
2022 January	63	58	121
2021 December	36	64	100
2021 November	58	44	102
2021 October	95	86	181
2021 September	48	35	83
2021 August	43	44	87
2021 July	45	35	80
2021 June	43	49	92
2021 May	98	54	152
2021 April	250	69	319
2021 March	76	33	109
2021 February	59	23	82
2021 January	77	25	102
2020 December	58	32	90
2020 November	47	20	67
2020 October	78	20	98
2020 September	51	38	89
2020 August	40	25	65
2020 July	73	25	98
2020 June	51	17	68
2020 May	49	21	70
2020 April	41	19	60
2020 March	37	15	52
2020 February	48	19	67
2020 January	36	19	55
2019 December	66	21	87
2019 November	46	20	66
2019 October	67	18	85
2019 September	51	13	64
2019 August	36	24	60
2019 July	45	24	69
2019 June	59	40	99
2019 May	83	14	97
2019 April	102	31	133
2019 March	36	11	47
2019 February	38	12	50
2019 January	49	17	66
2018 December	55	38	93
2018 November	62	18	80
2018 October	60	16	76
2018 September	31	9	40
2018 August	3	0	3
2018 July	9	0	9
2018 June	3	0	3
2018 May	6	0	6
2018 April	23	0	23
2018 March	17	0	17
2018 February	16	0	16
2018 January	27	0	27
2017 December	25	0	25
2017 November	16	0	16
2017 October	15	0	15
2017 September	26	0	26
2017 August	28	0	28
2017 July	26	2	28
2017 June	33	14	47
2017 May	41	12	53
2017 April	95	101	196
2017 March	15	7	22
2017 February	31	31	62
2017 January	5	20	25

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