Vitamin A deficiency and association between serum retinol and IGF-1 concentrations in Brazilian children with Down syndrome

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Ribeirão Preto 2009-2011. Brazil. VAD, vitamin A deficiency." ] ] ] "textoCompleto" => "IntroductionVitamin A deficiency (VAD) represents a global public health problem, affecting 190 million preschoolers each year in the world, and 4.4 million children have a diagnosis of xerophthalmia, mainly in developing countries.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> Subclinical VAD starts before the onset of ocular clinical signs and leads to a reduction of immune response and cell differentiation and multiplication. Thus, VAD has negative effects on the immunological response and is associated with greater morbidity-mortality due to infections, in addition to interfering with the processes of child growth and development.<a class="elsevierStyleCrossRef" href="#bib0002">2</a>,<a class="elsevierStyleCrossRef" href="#bib0003">3</a>Retinoic acid can stimulate the secretion of growth hormone (GH) in vitro in rat pituitary cells.<a class="elsevierStyleCrossRef" href="#bib0004">4</a> In humans, serum retinol concentrations are positively correlated with nocturnal GH secretion. In addition, some studies have observed a positive correlation between the serum concentrations of retinol and insulin-like growth factor 1 (IGF-1), including in newborns and infants,<a class="elsevierStyleCrossRef" href="#bib0005">5</a>,<a class="elsevierStyleCrossRef" href="#bib0006">6</a> whose production is influenced by GH and by nutritional status. These components of the GH-IGF system axis, together with genetic inheritance, directly determine growth and development.<a class="elsevierStyleCrossRef" href="#bib0006">6</a>The nutritional status related to vitamin A needs to be screened and monitored, especially in populations at higher risk of VAD, such as preschoolers and pregnant and nursing women, because of the greater nutrient demand,<a class="elsevierStyleCrossRef" href="#bib0007">7</a> so that preventive and early diagnosis strategies may be effective. Children with Down Syndrome (DS) are also at a higher risk to develop VAD. In a Venezuelan study, Chávez et al.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> observed an 18.4% prevalence of VAD in preschoolers with DS aged 2 to 6 years, as opposed to a prevalence of 4% among children without the syndrome. Several hypotheses have been raised regarding VAD in children with DS. The increased gene expression of the enzyme superoxide dismutase (SOD) due to the third chromosome 21 increases the production of oxygen free radicals, which represents a risk factor for the reduction of serum retinol concentrations.<a class="elsevierStyleCrossRef" href="#bib0009">9</a> Children with DS have orofacial muscle hypotonia and oral motor dysfunction which impairs the mandibular movements. In addition, a narrow palate and tongue protrusion also cause suction, chew and swallowing difficulties, possibly contributing to a low intake of micronutrients, among them vitamin A.<a class="elsevierStyleCrossRef" href="#bib0010">10</a> In parallel, children with DS have more infectious episodes than persons without the trisomy.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> VAD may increase the severity of the infection, which in turn may reduce the intake and accelerate the body losses of vitamin A.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> Also, an increase in acute phase proteins, a phenomenon commonly occurring during infectious episodes, reduces the serum concentrations of retinol.<a class="elsevierStyleCrossRef" href="#bib0011">11</a>Short stature and delayed growth are some of the main characteristics of persons with DS and it seems to be associated with disorders of GH secretion and IGF-1.<a class="elsevierStyleCrossRef" href="#bib0012">12</a> There are scarce literature reports about the prevalence of this nutritional deficiency among children with DS and its relationship with IGF-1. The objectives of the present study were 1) to determine the prevalence of VAD and serum concentrations of retinol and IGF-1 among preschoolers with DS, and 2) to verify the correlation between serum concentrations of retinol and IGF-1 and to compare the mean serum concentrations of IGF-1 between the groups with and without VAD.Subjects and methodsStudy design and populationThis was a cross-sectional, observational, and analytical study of prevalence. All preschool children with DS aged 24 to 72 months, living in the city of Ribeirão Preto (São Paulo, Brazil) during the period from November 2009 to December 2011 were eligible for the study. To estimate the study population, the number of live-born infants registered in Ribeirão Preto in the year 2009, a total of 10.744, was obtained. Based on the proportion of one baby born with the trisomy per 700 live births and considering the babies born in the city but no longer living in it, as well as babies that might have died due to comorbidities linked to the trisomy, the authors estimated a population of approximately 60 children with DS aged two to six years during the study period. An active search was conducted in genetics and cardiology outpatient clinics and in institutions dedicated to the care of children with developmental delay in the city. This process permitted us to locate 55 subjects eligible for the study. On this basis, the authors estimate that they could have possibly contemplated the entire population of children with DS aged two to six years living in the city of Ribeirão Preto during the period from November 2009 to December 2011. The parents or guardians of six children did not permit their inclusion in the study. Two children did not participate in the blood collection to complete the relative dose-response (RDR) test and were excluded from the study. Thus, 47 children participated in the present investigation. The flow diagram of subject inclusion in the study is presented in <a class="elsevierStyleCrossRef" href="#fig0001">Fig. 1</a>.<elsevierMultimedia ident="fig0001"></elsevierMultimedia>The research protocol followed the Declaration of Helsinki and was approved by the Research Ethics Committee of Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo (HCRP n°. 9573/2009) and persons responsible for the participants gave written informed consent to participate in the study.Data collection and analysisData were collected at an academic primary health care center (“Vila Lobato” Community Social Medical Center – Ribeirão Preto, SP, Brazil). Vitamin A was determined using the relative dose-response (RDR) test. For the test, a venous blood sample was obtained from each child after a six-hour fast (A0). Children with fever and/or diarrhea at the time of collection were sent home and invited to return two weeks after the end of the episode to start participating in the study. Immediately after blood collection (A0) the child received an oral solution containing 600 μg retinyl palmitate and a new blood sample was obtained five hours after this intervention (A5). At each collection (A0 and A5), the tubes for the determination of serum retinol concentration were protected from light with aluminum foil to minimize vitamin A photodegradation. The samples were then taken to the laboratory, where they were centrifuged at 2500 rpm for 15 minutes. Serum was stored at -70°C in Eppendorf® tubes also protected from light until the time for analysis in the Nutrition and Metabolism Laboratory, Department of Internal Medicine (Ribeirão Preto Medical School, University of São Paulo). Serum retinol concentration was determined by high-performance liquid chromatography (HPLC) before (A0) and after (A5) supplementation according to a standard technique of the laboratory itself based on the method of Arnaud et al..<a class="elsevierStyleCrossRef" href="#bib0013">13</a> The detection limits of the method are 0.016 and 13.7 µmol/l. RDR was calculated by the formula (A5-A0/A5) x 100. Individual results of 20% or more are indicative of low hepatic reserves of vitamin A,<a class="elsevierStyleCrossRef" href="#bib0014">14</a> i.e., VAD. The adoption of a serum retinol concentration of 1.05 µmol/l as the cut-off value to consider a child as having VAD would result in a high proportion of deficiency even in a population of well-nourished preschoolers;<a class="elsevierStyleCrossRef" href="#bib0014">14</a> therefore, in the present study, the authors used the cutoff point recommended by the WHO as indicative of VAD, that is, ≤ 0.70 µmol/L.<a class="elsevierStyleCrossRef" href="#bib0015">15</a>Serum IGF-1 and C-reactive protein (CRP) concentrations were determined in the blood sample before supplementation with retinyl palmitate (A0). For the determination of serum IGF-1 concentrations, the blood samples were centrifuged at 2500 rpm for 15 minutes and the serum was stored at -70°C until the time for determination in the Endocrinology Laboratory, Department of Internal Medicine (Ribeirão Preto Medical School, University of São Paulo). Serum IGF-1 concentration was determined by solid-phase immunometric immunoassay labeled by chemoluminescence using the commercial kit IMMULITE 2000 SIEMENS® (UK) for IGF-1. Serum IGF-1 concentrations below the 3rd percentile for sex and age were considered deficient.For CRP determination the blood samples were centrifuged at 2500 rpm and serum was stored at -70°C until the time for analysis in the biochemistry laboratory of the university. CRP was determined by turbidimetric immunoassay and serum concentrations above 0.5 mg/dL were considered abnormal.The nutritional status of the participants was determined by measuring weight and height at the beginning of the study and classified according to the growth curves for children with DS. A socioeconomic questionnaire was applied to determine family income, number of household residents and parents’ schooling.The occurrence of fever and diarrhea was considered a clinical marker of infection/inflammation. The parents/guardians of the children were asked if the child had experienced at least one episode of axillary temperature higher than 37°C measured with a thermometer during a period of 15 days prior to entering the study. Similarly, the parents/guardians of the children were asked if the child had shown a pattern of evacuation characterized by three or more episodes of the passage of liquid or semi-liquid feces over a period of 24 hours, or passage of liquid feces with blood visible to the naked eye at least once during 15 days prior to entering the study.Statistical analysisAs described, there is no sample size calculation in this study because the authors reached the whole eligible population, except those who did not agree to participate. Confidence intervals (95%CI) for the prevalence of VAD among the whole population and in subgroups of children were calculated by the Clopper-Pearson exact method. The difference in mean serum retinol concentrations before and after supplementation was determined by the Student t-test for paired data. Mean serum IGF-1 concentrations were compared between children with and without VAD by multiple linear regression, with adjustment for age and serum retinol concentrations before supplementation. Residual analysis was used to examine the assumptions of this regression model, including checks for linearity, normality, and homoscedasticity of the residuals. Spearman correlation coefficient was used to determine the correlation of pre-supplementation serum retinol concentrations with serum IGF-1 concentrations. The statistical analyses were carried out using SAS 9.2 and R 2.15.10 software, with the level of significance set at 5%.ResultsThe mean age of the participants was 42.8 [Standard Deviation (SD) 14.9] months (range 25-69 months) and 55.3% (n = 26) were females. Only one child was above the 95th percentile in the weight/age indicator. This child had no VAD and had adequate serum IGF-1 concentrations. All the other children (n = 46) were classified between the 5th and 95th percentile for weight/age and height/age. The parents of most of the children had an education of over eight years, an income of less than three Brazilian minimum wages, and the children lived in a household with less than four people. <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a> shows the socioeconomic characteristics of the study population and prevalence of VAD (determined by the RDR test) for each class category of these variables.<elsevierMultimedia ident="tbl0001"></elsevierMultimedia>The prevalence of VAD determined by the RDR test was 25.5% (n = 12; 95%CI: 13.9-40.3). The mean age of the children with and without VAD was 47.0 (SD 16.8) and 41.4 (SD 14.2) months, respectively. Mean pre- (A0) and post-supplementation (A5) retinol concentrations were 0.64 µmol/l (SD 0.24) and 0.70 µmol/L (SD 0.24), respectively, with a significant difference between them (mean difference: 0.06; 95%CI: 0.02-0.10; p-value < 0.01). 74.5% (n = 35; 95%CI: 42.3-89.1) of the children had pre-supplementation serum retinol concentrations below 0.70 µmol/l. After intervention with the oral administration of 600 µg retinol palmitate for the RDR test, 57.4% (n = 27; 95%CI: 34.2-76.3) of the children still had serum retinol concentrations below 0.70 µmol/L.It was observed that 27.6% (n = 13) of the children studied had serum CRP concentrations considered to be high, with only three of these children (23%) having VAD. There was no association between pre-supplementation serum retinol and CRP concentrations (p-value = 0.99).Mean serum IGF-1 concentrations among children with and without VAD were 103.5 ng/mL and 116.3 ng/mL, respectively, with no significant difference between them after adjustment for age and for pre-supplementation serum retinol concentrations (p-value = 0.78) (<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0002">Fig. 2</a>).<elsevierMultimedia ident="tbl0002"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia>Only four children had IGF-1 deficiency (< 3rd percentile), although without VAD. Thus, the presence of VAD was not associated with IGF-1 deficiency (p-value = 0.56). However, all children with serum IGF-1 concentrations below the 25th percentile for sex and age had retinol values below 0.55 µmol/L. A moderate and significant positive correlation was observed between pre-supplementation serum retinol and IGF-1 concentrations (ρ = 0.34; p-value = 0.019; <a class="elsevierStyleCrossRef" href="#fig0003">Fig. 3</a>).<elsevierMultimedia ident="fig0003"></elsevierMultimedia>DiscussionThe present study was the first to investigate the prevalence of VAD and its association with serum IGF-1 concentrations in a population of preschoolers with DS. The prevalence of VAD among children with DS has been little investigated. Some studies have detected the presence of VAD in children with DS, but have not investigated its prevalence,<a class="elsevierStyleCrossRef" href="#bib0016">16</a> while other studies did not even demonstrate the presence of VAD among these children.<a class="elsevierStyleCrossRef" href="#bib0017">17</a> A prevalence of VAD of 25.5% was detected by the RDR test. Furthermore, 74.5% of the children had deficient serum retinol concentrations before the intervention (pre-supplementation – A0) required for the RDR test, i.e., oral supplementation with 600 µg retinol palmitate. In a study of Venezuelan children with DS aged 4 to 12 years, Chávez et al.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> detected an 18.4% prevalence of retinol concentrations < 0.70 µmol/L. However, it should be pointed that the study by Chávez et al.<a class="elsevierStyleCrossRef" href="#bib0008">8</a> included older children and not simply preschoolers – an age range at higher risk for VAD -, a fact that may have contributed to a lower prevalence of deficient serum retinol concentrations compared to the present study. It is interesting to point out that, in the cited study, children with DS aged two to six years had significantly lower mean retinol concentrations than older children. It is known that serum retinol concentrations are not necessarily consistent with hepatic vitamin A reserves and may be normal even when liver reserves are extremely low.<a class="elsevierStyleCrossRef" href="#bib0018">18</a> In addition, due to homeostatic control, serum retinol concentrations remain constant within a broad range of hepatic reserves. And they may be influenced by some factors such as infection, inflammation and obesity.<a class="elsevierStyleCrossRef" href="#bib0019">19</a> The most sensitive method for the assessment of vitamin A status in relation to the hepatic reserves is the isotope dilution method; however, this method is too expensive for the population assessment.<a class="elsevierStyleCrossRef" href="#bib0019">19</a> Moreover, the changes in serum retinol concentrations due to a standard oral dose of vitamin A reflect the fact that when the hepatic reserves of vitamin A are reduced, the retinol-binding protein (RBP) accumulates in the liver before the retinol concentrations decrease. Thus, when a standard vitamin A dose is administered, retinol binds to the accumulated RBP and is rapidly released into the serum, a phenomenon that causes an increase in serum retinol concentrations.<a class="elsevierStyleCrossRef" href="#bib0019">19</a> The RDR test is based on this physiological response of the RBP-retinol complex to identify persons with low hepatic reserves. Since the authors used a different method for the classification of vitamin A status (RDR) compared to the Venezuelan study, it is difficult to compare the observed prevalence. However, so far, no studies have been published in the literature regarding the determination of VAD prevalence among children with DS using the RDR test.Studies have shown that children with DS are more susceptible to infections.<a class="elsevierStyleCrossRef" href="#bib0011">11</a> In the present study, although the children were apparently healthy without acute febrile or diarrheic episodes, more than one-quarter of them had high CRP concentrations. However, only three children with VAD had high CRP serum concentrations. Subclinical infectious or inflammatory processes may reduce serum retinol concentrations in the organism in a transitory manner, leading to an overestimate of the prevalence of values considered deficient. In response to inflammation or tissue injury, CRP concentrations increase within six to eight hours after the insult, peaking within 48 hours.<a class="elsevierStyleCrossRef" href="#bib0020">20</a> Thus, children with infections or inflammatory processes during the period of incubation may not show increased serum CRP concentrations. It is also known that in infectious or inflammatory processes the serum concentrations of retinol start to decline before the occurrence of high increases in CRP.<a class="elsevierStyleCrossRef" href="#bib0008">8</a>,<a class="elsevierStyleCrossRef" href="#bib0011">11</a>. Finally, since RBP is a negative acute-phase protein, subclinical infectious or inflammatory processes may interfere with the release of the retinol-RBP complex by the liver even after supplementation with retinol palmitate, possibly influencing the RDR results. These phenomena, in addition to strict homeostatic control of serum retinol concentrations, even when liver stores are extremely low, may explain the difference in prevalence detected by RDR and by serum retinol concentrations.The prevalence of deficient serum retinol concentration detected in the present population was higher than that observed in studies conducted on children without DS of similar age ranges when compared with Brazilian data<a class="elsevierStyleCrossRef" href="#bib0021">21</a> and international data.<a class="elsevierStyleCrossRef" href="#bib0022">22</a> On the other hand, two studies using tests of the response of the serum concentrations to a standard dose of vitamin A have reported a higher VAD prevalence than observed in the present study. Samba et al.,<a class="elsevierStyleCrossRef" href="#bib0023">23</a> using the modified dose-response test (MRDR), observed a 30% VAD prevalence and a 50% prevalence of deficient serum retinol concentrations among preschoolers of sub-Saharan Africa. In two studies, conducted with healthy individuals in the same community investigated by the present study, there was a 74.5% prevalence of VAD among preschoolers without DS, as determined by the + S30DR method<a class="elsevierStyleCrossRef" href="#bib0024">24</a> and, recently, insufficient concentrations of vitamin A were observed in breastmilk of lactating women.<a class="elsevierStyleCrossRef" href="#bib0025">25</a>Inadequate vitamin A intake in response to the demands of the organism represents a common pathway towards the development of deficiency.<a class="elsevierStyleCrossRef" href="#bib0001">1</a> On the other hand, in Brazil DS children receive periodic assistance since the first months of life in specialized institutions, as well as multidisciplinary medical monitoring with physiotherapists and nutritionists for the treatment of their complications. Furthermore, in some cases, their parents or tutors spend greater care on the diet and hygiene of these children. These observations may explain in part the differences in VAD prevalence detected in the present study compared to the values reported by other authors who studied children without the trisomy.In the present study, children without VAD had higher mean serum IGF-1 concentrations than children with VAD, but the difference was not significant. The relatively small number of individuals studied could explain this finding. However, a moderate positive correlation was observed between the serum retinol and IGF-1 concentrations. Similar results were found among pregnant Nepalese women and healthy Japanese adults.<a class="elsevierStyleCrossRef" href="#bib0005">5</a> Regarding children, Dijkhuizen et al.<a class="elsevierStyleCrossRef" href="#bib0007">7</a> have also found a moderate correlation between the plasma concentration of retinol and IGF-1 among healthy infants in Indonesia. Du et al.<a class="elsevierStyleCrossRef" href="#bib0006">6</a> also observed a moderate positive correlation between serum retinol and IGF-1 concentrations in Canadian newborn girls but not in boys. Although some studies have shown that vitamin A supplementation may improve the growth of children with VAD<a class="elsevierStyleCrossRef" href="#bib0026">26</a> and associated with zinc supplementation, increase the serum concentrations of IGF-1,<a class="elsevierStyleCrossRef" href="#bib0027">27</a> no studies of this kind have been conducted on children with DS. Thus, whether an improvement of serum retinol concentrations in populations with a high prevalence of deficiency might lead to an increase in IGF-1 concentrations of some clinical relevance in children with DS is a question proposed by the present study. All children of the present study who presented with serum IGF-1 concentrations below the 25th percentile for sex and age had serum retinol concentrations below 0.55 µmol/L. Despite the high proportion of deficient retinol values detected, only four children had deficient serum IGF-1 concentrations.The present study has some limitations. Although the study group practically included the entire population of preschoolers with DS in the city, the number of subjects studied was relatively small, a fact that may have reduced the power of some analyses. Since it was a cross-sectional study, changes along time that might have occurred in the relationship between retinol and IGF-1 concentrations, especially during or in the absence of infectious episodes or inflammatory processes, could not be detected. Finally, another limitation was the lack of information about vitamin A intake that might have helped explain some findings.ConclusionThe present population-based study detected an elevated prevalence of VAD among preschoolers with DS using the RDR method, as well as a high proportion of deficient serum retinol concentrations. A small proportion of children had deficient IGF-1 concentrations. No difference in mean IGF concentrations was observed between children with and without VAD. However, a positive correlation was observed between serum retinol and IGF-1." "textoCompletoSecciones" => array:1 [ "secciones" => array:8 [ 0 => array:3 [ "identificador" => "xres1653745" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1470027" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0001" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0002" "titulo" => "Subjects and methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0003" "titulo" => "Study design and population" ] 1 => array:2 [ "identificador" => "sec0004" "titulo" => "Data collection and analysis" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Statistical analysis" ] ] ] 4 => array:2 [ "identificador" => "sec0006" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0007" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0008" "titulo" => "Conclusion" ] 7 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2021-02-10" "fechaAceptado" => "2021-04-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1470027" "palabras" => array:5 [ 0 => "Vitamin A deficiency" 1 => "Insulin-like growth factor I" 2 => "Child" 3 => "Down syndrome" 4 => "Growth" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "ObjectiveTo determine the prevalence of vitamin A deficiency (VAD) and serum concentrations of retinol, correlating them with IGF-1 concentrations in preschoolers with DS. MethodsCross-sectional study was conducted on 47 children with DS aged 24 to 72 months, in Ribeirão Preto, Brazil. VAD was determined by the relative dose-response (RDR) test. Retinol serum concentration ≤ 0.70 µmol/L and IGF-1 serum concentration below the 3rd percentile for sex and age were considered to represent deficiency. C-reactive protein (CRP) was determined at the beginning of the study. Weight, height, and information about fever and/or diarrhea were obtained at the beginning of the study. ResultsVAD prevalence was 25.5% (12/47), and 74.5% (35/47) of the children had deficient retinol before the intervention. CRP was not associated with VAD. Mean IGF-1 were 103.5 ng/mL (SD = 913) for the group with VAD and 116.3 ng/mL (SD = 54.9) for the group with no VAD (p-value = 0.85); 8.5% (4/47) of the children showed deficient IGF-1, but without VAD. No association was observed between VAD and IGF-1 deficiency. A moderate positive correlation was observed between pre-intervention retinol and IGF-1 (ρ = 0.37; p-value = 0.01). Conclusiona high prevalence of VAD and deficient retinol was observed and there was a positive correlation between serum retinol and IGF-1." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abss0001" "titulo" => "Objective" ] 1 => array:2 [ "identificador" => "abss0002" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abss0003" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abss0004" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:5 [ 0 => array:8 [ "identificador" => "fig0001" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1475 "Ancho" => 2473 "Tamanyo" => 204791 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0001" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Flow diagram of the inclusion of preschool children with Down Syndrome." ] ] 1 => array:8 [ "identificador" => "fig0002" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2741 "Ancho" => 2690 "Tamanyo" => 187299 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0002" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Mean serum IGF-1 concentrations between children with and without Vitamin A Deficiency. Ribeirão Preto 2009-2011. Brazil. VAD, vitamin A deficiency." ] ] 2 => array:8 [ "identificador" => "fig0003" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2145 "Ancho" => 3002 "Tamanyo" => 188784 ] ] "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0003" "detalle" => "Figure " "rol" => "short" ] ] "descripcion" => array:1 [ "en" => "Dispersion graph representing the correlation between serum IGF-1 concentrations (ng/mL) and pre-supplementation (A0) retinol concentrations among preschoolers with Down Syndrome. Ribeirão Preto 2009-2011. Brazil." ] ] 3 => array:8 [ "identificador" => "tbl0001" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0004" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "VAD, vitamin A deficiency; RDR, relative dose-response; 95%CI, 95% confidence interval." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0001"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variables \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0002"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">n \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0003"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">% \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0004"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Prevalence of VAD (95%CI) \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0005"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Sex \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0006"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0007"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0008"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Female \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26.9 (11.5 – 47.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Male \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">44.7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">23.8 (8.2 – 47.2) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Age (months) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">< 40 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">23 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">48.9 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">17.4 (4.9 – 38.8) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≥ 40 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">24 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">51.1 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">33.3 (15.6 – 55.3) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Maternal schooling(years of study successfully completed) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">< 8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">12.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">16.7 (0.4 – 64.1) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≥ 8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">41 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">87.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26.8 (14.2 – 42.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Paternal schooling(years of study successfully completed) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">< 8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">10.0 (0.2 – 44.5) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≥ 8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">37 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">78.7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">29.7 (15.8 – 46.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">Monthly family income(Brazilian minimum wages) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≤ 3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">26 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">55.3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">15.4 (4.4 – 34.9) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">˃ 3 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">21 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">44.7 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">38.1 (18.1 – 61.6) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0065"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">N° of household persons \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top"> \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">≤ 4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">63.8 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">30.0 (14.7 – 49.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0073"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">˃ 4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">17 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">36.2 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">17.6 (3.8 – 43.4) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810663.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Socioeconomic characteristics of preschoolers with Down Syndrome, and prevalence of VAD determined by the RDR test. Ribeirão Preto 2009-2011. Brazil." ] ] 4 => array:8 [ "identificador" => "tbl0002" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "alt0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "SD, standard deviation; VAD, vitamin A deficiency." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><a name="en0077"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0078"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Mean (SD) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0079"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">p-value<a class="elsevierStyleCrossRef" href="#tb2fn1">a</a> \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0080"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Minimum \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0081"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">1st quartile \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0082"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Median \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0083"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">3rd quartile \t\t\t\t\t\t\n \t\t\t\t\t\t</th><a name="en0084"></a><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Maximum \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><a name="en0085"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">Without VAD (n = 35) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0086"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">116.3 (92.2) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0087"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowgroup " rowspan="2" align="left" valign="top">0.780</td><a name="en0088"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">25.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0089"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">40.4 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0090"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">102.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0091"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">170.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0092"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">440.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><a name="en0093"></a><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="" valign="top">VAD (n = 12) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0094"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">103.5 (54.9) \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0096"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">35.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0097"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">65.6 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0098"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">99.0 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0099"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">112.5 \t\t\t\t\t\t\n \t\t\t\t</td><a name="en0100"></a><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="" valign="top">238.0 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2810662.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tb2fn1" "etiqueta" => "a" "nota" => "significance of the effect of VAD obtained from multiple linear regression, with log transformation for serum IGF-1 and adjustment for age, sex and for serum retinol concentrations before supplementation." ] ] ] "descripcion" => array:1 [ "en" => "Means, medians, and quartile distributions of serum IGF-1 concentrations (ng/mL) among preschool children with Down syndrome, according to vitamin A deficiency. Ribeirão Preto 2009-2011. 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Ivan Savioli Ferraza, Débora Mônica Costa Vieiraa, Luiz Antonio Del Ciampo Jr.a,

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delciamp@fmrp.usp.br

Corresponding author.

, Fábio da Veiga Uedb, Ane Cristina Fayão Almeidaa, Alceu Afonso Jordão Jr.b, Davi Casale Aragona, Edson Zangiacomi Martinezc, Carlos Eduardo Martinelli Jr.a, Carlos Alberto Nogueira-de-Almeidad

a Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Pediatria, Ribeirão Preto, SP, Brazil

b Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Ciências da Saúde, Ribeirão Preto, SP, Brazil

c Universidade de São Paulo, Faculdade de Medicina de Ribeirão Preto, Departamento de Medicina Social, Ribeirão Preto, SP, Brazil

d Universidade Federal de São Carlos, Departamento de Medicina, São Carlos, SP, Brazil

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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0007">Introduction</span><p id="para0005" class="elsevierStylePara elsevierViewall">Vitamin A deficiency &#40;VAD&#41; represents a global public health problem&#44; affecting 190 million preschoolers each year in the world&#44; and 4&#46;4 million children have a diagnosis of xerophthalmia&#44; mainly in developing countries&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Subclinical VAD starts before the onset of ocular clinical signs and leads to a reduction of immune response and cell differentiation and multiplication&#46; Thus&#44; VAD has negative effects on the immunological response and is associated with greater morbidity-mortality due to infections&#44; in addition to interfering with the processes of child growth and development&#46;<a class="elsevierStyleCrossRef" href="#bib0002"><span class="elsevierStyleSup">2</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0003"><span class="elsevierStyleSup">3</span></a></p><p id="para0006" class="elsevierStylePara elsevierViewall">Retinoic acid can stimulate the secretion of growth hormone &#40;GH&#41; <span class="elsevierStyleItalic">in vitro</span> in rat pituitary cells&#46;<a class="elsevierStyleCrossRef" href="#bib0004"><span class="elsevierStyleSup">4</span></a> In humans&#44; serum retinol concentrations are positively correlated with nocturnal GH secretion&#46; In addition&#44; some studies have observed a positive correlation between the serum concentrations of retinol and insulin-like growth factor 1 &#40;IGF-1&#41;&#44; including in newborns and infants&#44;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> whose production is influenced by GH and by nutritional status&#46; These components of the GH-IGF system axis&#44; together with genetic inheritance&#44; directly determine growth and development&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a></p><p id="para0007" class="elsevierStylePara elsevierViewall">The nutritional status related to vitamin A needs to be screened and monitored&#44; especially in populations at higher risk of VAD&#44; such as preschoolers and pregnant and nursing women&#44; because of the greater nutrient demand&#44;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> so that preventive and early diagnosis strategies may be effective&#46; Children with Down Syndrome &#40;DS&#41; are also at a higher risk to develop VAD&#46; In a Venezuelan study&#44; Ch&#225;vez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> observed an 18&#46;4&#37; prevalence of VAD in preschoolers with DS aged 2 to 6 years&#44; as opposed to a prevalence of 4&#37; among children without the syndrome&#46; Several hypotheses have been raised regarding VAD in children with DS&#46; The increased gene expression of the enzyme superoxide dismutase &#40;SOD&#41; due to the third chromosome 21 increases the production of oxygen free radicals&#44; which represents a risk factor for the reduction of serum retinol concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0009"><span class="elsevierStyleSup">9</span></a> Children with DS have orofacial muscle hypotonia and oral motor dysfunction which impairs the mandibular movements&#46; In addition&#44; a narrow palate and tongue protrusion also cause suction&#44; chew and swallowing difficulties&#44; possibly contributing to a low intake of micronutrients&#44; among them vitamin A&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">10</span></a> In parallel&#44; children with DS have more infectious episodes than persons without the trisomy&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> VAD may increase the severity of the infection&#44; which in turn may reduce the intake and accelerate the body losses of vitamin A&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> Also&#44; an increase in acute phase proteins&#44; a phenomenon commonly occurring during infectious episodes&#44; reduces the serum concentrations of retinol&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a></p><p id="para0008" class="elsevierStylePara elsevierViewall">Short stature and delayed growth are some of the main characteristics of persons with DS and it seems to be associated with disorders of GH secretion and IGF-1&#46;<a class="elsevierStyleCrossRef" href="#bib0012"><span class="elsevierStyleSup">12</span></a> There are scarce literature reports about the prevalence of this nutritional deficiency among children with DS and its relationship with IGF-1&#46; The objectives of the present study were 1&#41; to determine the prevalence of VAD and serum concentrations of retinol and IGF-1 among preschoolers with DS&#44; and 2&#41; to verify the correlation between serum concentrations of retinol and IGF-1 and to compare the mean serum concentrations of IGF-1 between the groups with and without VAD&#46;</p></span><span id="sec0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0008">Subjects and methods</span><span id="sec0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0009">Study design and population</span><p id="para0009" class="elsevierStylePara elsevierViewall">This was a cross-sectional&#44; observational&#44; and analytical study of prevalence&#46; All preschool children with DS aged 24 to 72 months&#44; living in the city of Ribeir&#227;o Preto &#40;S&#227;o Paulo&#44; Brazil&#41; during the period from November 2009 to December 2011 were eligible for the study&#46; To estimate the study population&#44; the number of live-born infants registered in Ribeir&#227;o Preto in the year 2009&#44; a total of 10&#46;744&#44; was obtained&#46; Based on the proportion of one baby born with the trisomy per 700 live births and considering the babies born in the city but no longer living in it&#44; as well as babies that might have died due to comorbidities linked to the trisomy&#44; the authors estimated a population of approximately 60 children with DS aged two to six years during the study period&#46; An active search was conducted in genetics and cardiology outpatient clinics and in institutions dedicated to the care of children with developmental delay in the city&#46; This process permitted us to locate 55 subjects eligible for the study&#46; On this basis&#44; the authors estimate that they could have possibly contemplated the entire population of children with DS aged two to six years living in the city of Ribeir&#227;o Preto during the period from November 2009 to December 2011&#46; The parents or guardians of six children did not permit their inclusion in the study&#46; Two children did not participate in the blood collection to complete the relative dose-response &#40;RDR&#41; test and were excluded from the study&#46; Thus&#44; 47 children participated in the present investigation&#46; The flow diagram of subject inclusion in the study is presented in <a class="elsevierStyleCrossRef" href="#fig0001">Fig&#46; 1</a>&#46;</p><elsevierMultimedia ident="fig0001"></elsevierMultimedia><p id="para0010" class="elsevierStylePara elsevierViewall">The research protocol followed the Declaration of Helsinki and was approved by the Research Ethics Committee of Hospital das Cl&#237;nicas da Faculdade de Medicina de Ribeir&#227;o Preto da Universidade de S&#227;o Paulo &#40;HCRP n&#176;&#46; 9573&#47;2009&#41; and persons responsible for the participants gave written informed consent to participate in the study&#46;</p></span><span id="sec0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0010">Data collection and analysis</span><p id="para0011" class="elsevierStylePara elsevierViewall">Data were collected at an academic primary health care center &#40;&#8220;Vila Lobato&#8221; Community Social Medical Center &#8211; Ribeir&#227;o Preto&#44; SP&#44; Brazil&#41;&#46; Vitamin A was determined using the relative dose-response &#40;RDR&#41; test&#46; For the test&#44; a venous blood sample was obtained from each child after a six-hour fast &#40;A<span class="elsevierStyleInf">0</span>&#41;&#46; Children with fever and&#47;or diarrhea at the time of collection were sent home and invited to return two weeks after the end of the episode to start participating in the study&#46; Immediately after blood collection &#40;A<span class="elsevierStyleInf">0</span>&#41; the child received an oral solution containing 600 &#956;g retinyl palmitate and a new blood sample was obtained five hours after this intervention &#40;A<span class="elsevierStyleInf">5</span>&#41;&#46; At each collection &#40;A<span class="elsevierStyleInf">0</span> and A<span class="elsevierStyleInf">5</span>&#41;&#44; the tubes for the determination of serum retinol concentration were protected from light with aluminum foil to minimize vitamin A photodegradation&#46; The samples were then taken to the laboratory&#44; where they were centrifuged at 2500 rpm for 15 minutes&#46; Serum was stored at -70&#176;C in Eppendorf&#174; tubes also protected from light until the time for analysis in the Nutrition and Metabolism Laboratory&#44; Department of Internal Medicine &#40;Ribeir&#227;o Preto Medical School&#44; University of S&#227;o Paulo&#41;&#46; Serum retinol concentration was determined by high-performance liquid chromatography &#40;HPLC&#41; before &#40;A<span class="elsevierStyleInf">0</span>&#41; and after &#40;A<span class="elsevierStyleInf">5</span>&#41; supplementation according to a standard technique of the laboratory itself based on the method of Arnaud et al&#46;&#46;<a class="elsevierStyleCrossRef" href="#bib0013"><span class="elsevierStyleSup">13</span></a> The detection limits of the method are 0&#46;016 and 13&#46;7 &#181;mol&#47;l&#46; RDR was calculated by the formula &#40;A<span class="elsevierStyleInf">5</span>-A<span class="elsevierStyleInf">0</span>&#47;A<span class="elsevierStyleInf">5</span>&#41; x 100&#46; Individual results of 20&#37; or more are indicative of low hepatic reserves of vitamin A&#44;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> i&#46;e&#46;&#44; VAD&#46; The adoption of a serum retinol concentration of 1&#46;05 &#181;mol&#47;l as the cut-off value to consider a child as having VAD would result in a high proportion of deficiency even in a population of well-nourished preschoolers&#59;<a class="elsevierStyleCrossRef" href="#bib0014"><span class="elsevierStyleSup">14</span></a> therefore&#44; in the present study&#44; the authors used the cutoff point recommended by the WHO as indicative of VAD&#44; that is&#44; &#8804; 0&#46;70 &#181;mol&#47;L&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">15</span></a></p><p id="para0012" class="elsevierStylePara elsevierViewall">Serum IGF-1 and C-reactive protein &#40;CRP&#41; concentrations were determined in the blood sample before supplementation with retinyl palmitate &#40;A<span class="elsevierStyleInf">0</span>&#41;&#46; For the determination of serum IGF-1 concentrations&#44; the blood samples were centrifuged at 2500 rpm for 15 minutes and the serum was stored at -70&#176;C until the time for determination in the Endocrinology Laboratory&#44; Department of Internal Medicine &#40;Ribeir&#227;o Preto Medical School&#44; University of S&#227;o Paulo&#41;&#46; Serum IGF-1 concentration was determined by solid-phase immunometric immunoassay labeled by chemoluminescence using the commercial kit IMMULITE 2000 SIEMENS&#174; &#40;UK&#41; for IGF-1&#46; Serum IGF-1 concentrations below the 3rd percentile for sex and age were considered deficient&#46;</p><p id="para0013" class="elsevierStylePara elsevierViewall">For CRP determination the blood samples were centrifuged at 2500 rpm and serum was stored at -70&#176;C until the time for analysis in the biochemistry laboratory of the university&#46; CRP was determined by turbidimetric immunoassay and serum concentrations above 0&#46;5 mg&#47;dL were considered abnormal&#46;</p><p id="para0014" class="elsevierStylePara elsevierViewall">The nutritional status of the participants was determined by measuring weight and height at the beginning of the study and classified according to the growth curves for children with DS&#46; A socioeconomic questionnaire was applied to determine family income&#44; number of household residents and parents&#8217; schooling&#46;</p><p id="para0015" class="elsevierStylePara elsevierViewall">The occurrence of fever and diarrhea was considered a clinical marker of infection&#47;inflammation&#46; The parents&#47;guardians of the children were asked if the child had experienced at least one episode of axillary temperature higher than 37&#176;C measured with a thermometer during a period of 15 days prior to entering the study&#46; Similarly&#44; the parents&#47;guardians of the children were asked if the child had shown a pattern of evacuation characterized by three or more episodes of the passage of liquid or semi-liquid feces over a period of 24 hours&#44; or passage of liquid feces with blood visible to the naked eye at least once during 15 days prior to entering the study&#46;</p></span><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0011">Statistical analysis</span><p id="para0016" class="elsevierStylePara elsevierViewall">As described&#44; there is no sample size calculation in this study because the authors reached the whole eligible population&#44; except those who did not agree to participate&#46; Confidence intervals &#40;95&#37;CI&#41; for the prevalence of VAD among the whole population and in subgroups of children were calculated by the Clopper-Pearson exact method&#46; The difference in mean serum retinol concentrations before and after supplementation was determined by the Student <span class="elsevierStyleItalic">t</span>-test for paired data&#46; Mean serum IGF-1 concentrations were compared between children with and without VAD by multiple linear regression&#44; with adjustment for age and serum retinol concentrations before supplementation&#46; Residual analysis was used to examine the assumptions of this regression model&#44; including checks for linearity&#44; normality&#44; and homoscedasticity of the residuals&#46; Spearman correlation coefficient was used to determine the correlation of pre-supplementation serum retinol concentrations with serum IGF-1 concentrations&#46; The statistical analyses were carried out using SAS 9&#46;2 and R 2&#46;15&#46;10 software&#44; with the level of significance set at 5&#37;&#46;</p></span></span><span id="sec0006" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0012">Results</span><p id="para0017" class="elsevierStylePara elsevierViewall">The mean age of the participants was 42&#46;8 &#91;Standard Deviation &#40;SD&#41; 14&#46;9&#93; months &#40;range 25-69 months&#41; and 55&#46;3&#37; &#40;n&#8239;&#61;&#8239;26&#41; were females&#46; Only one child was above the 95th percentile in the weight&#47;age indicator&#46; This child had no VAD and had adequate serum IGF-1 concentrations&#46; All the other children &#40;n&#8239;&#61;&#8239;46&#41; were classified between the 5th and 95th percentile for weight&#47;age and height&#47;age&#46; The parents of most of the children had an education of over eight years&#44; an income of less than three Brazilian minimum wages&#44; and the children lived in a household with less than four people&#46; <a class="elsevierStyleCrossRef" href="#tbl0001">Table 1</a> shows the socioeconomic characteristics of the study population and prevalence of VAD &#40;determined by the RDR test&#41; for each class category of these variables&#46;</p><elsevierMultimedia ident="tbl0001"></elsevierMultimedia><p id="para0018" class="elsevierStylePara elsevierViewall">The prevalence of VAD determined by the RDR test was 25&#46;5&#37; &#40;n&#8239;&#61;&#8239;12&#59; 95&#37;CI&#58; 13&#46;9-40&#46;3&#41;&#46; The mean age of the children with and without VAD was 47&#46;0 &#40;SD 16&#46;8&#41; and 41&#46;4 &#40;SD 14&#46;2&#41; months&#44; respectively&#46; Mean pre- &#40;A0&#41; and post-supplementation &#40;A5&#41; retinol concentrations were 0&#46;64 &#181;mol&#47;l &#40;SD 0&#46;24&#41; and 0&#46;70 &#181;mol&#47;L &#40;SD 0&#46;24&#41;&#44; respectively&#44; with a significant difference between them &#40;mean difference&#58; 0&#46;06&#59; 95&#37;CI&#58; 0&#46;02-0&#46;10&#59; p-value &#60; 0&#46;01&#41;&#46; 74&#46;5&#37; &#40;n&#8239;&#61;&#8239;35&#59; 95&#37;CI&#58; 42&#46;3-89&#46;1&#41; of the children had pre-supplementation serum retinol concentrations below 0&#46;70 &#181;mol&#47;l&#46; After intervention with the oral administration of 600 &#181;g retinol palmitate for the RDR test&#44; 57&#46;4&#37; &#40;n&#8239;&#61;&#8239;27&#59; 95&#37;CI&#58; 34&#46;2-76&#46;3&#41; of the children still had serum retinol concentrations below 0&#46;70 &#181;mol&#47;L&#46;</p><p id="para0019" class="elsevierStylePara elsevierViewall">It was observed that 27&#46;6&#37; &#40;n&#8239;&#61;&#8239;13&#41; of the children studied had serum CRP concentrations considered to be high&#44; with only three of these children &#40;23&#37;&#41; having VAD&#46; There was no association between pre-supplementation serum retinol and CRP concentrations &#40;p-value&#8239;&#61;&#8239;0&#46;99&#41;&#46;</p><p id="para0020" class="elsevierStylePara elsevierViewall">Mean serum IGF-1 concentrations among children with and without VAD were 103&#46;5 ng&#47;mL and 116&#46;3 ng&#47;mL&#44; respectively&#44; with no significant difference between them after adjustment for age and for pre-supplementation serum retinol concentrations &#40;p-value&#8239;&#61;&#8239;0&#46;78&#41; &#40;<a class="elsevierStyleCrossRef" href="#tbl0002">Table 2</a> and <a class="elsevierStyleCrossRef" href="#fig0002">Fig&#46; 2</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0002"></elsevierMultimedia><elsevierMultimedia ident="fig0002"></elsevierMultimedia><p id="para0021" class="elsevierStylePara elsevierViewall">Only four children had IGF-1 deficiency &#40;&#60; 3rd percentile&#41;&#44; although without VAD&#46; Thus&#44; the presence of VAD was not associated with IGF-1 deficiency &#40;p-value&#8239;&#61;&#8239;0&#46;56&#41;&#46; However&#44; all children with serum IGF-1 concentrations below the 25th percentile for sex and age had retinol values below 0&#46;55 &#181;mol&#47;L&#46; A moderate and significant positive correlation was observed between pre-supplementation serum retinol and IGF-1 concentrations &#40;&#961;&#8239;&#61;&#8239;0&#46;34&#59; p-value&#8239;&#61;&#8239;0&#46;019&#59; <a class="elsevierStyleCrossRef" href="#fig0003">Fig&#46; 3</a>&#41;&#46;</p><elsevierMultimedia ident="fig0003"></elsevierMultimedia></span><span id="sec0007" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0013">Discussion</span><p id="para0022" class="elsevierStylePara elsevierViewall">The present study was the first to investigate the prevalence of VAD and its association with serum IGF-1 concentrations in a population of preschoolers with DS&#46; The prevalence of VAD among children with DS has been little investigated&#46; Some studies have detected the presence of VAD in children with DS&#44; but have not investigated its prevalence&#44;<a class="elsevierStyleCrossRef" href="#bib0016"><span class="elsevierStyleSup">16</span></a> while other studies did not even demonstrate the presence of VAD among these children&#46;<a class="elsevierStyleCrossRef" href="#bib0017"><span class="elsevierStyleSup">17</span></a> A prevalence of VAD of 25&#46;5&#37; was detected by the RDR test&#46; Furthermore&#44; 74&#46;5&#37; of the children had deficient serum retinol concentrations before the intervention &#40;pre-supplementation &#8211; A<span class="elsevierStyleInf">0</span>&#41; required for the RDR test&#44; i&#46;e&#46;&#44; oral supplementation with 600 &#181;g retinol palmitate&#46; In a study of Venezuelan children with DS aged 4 to 12 years&#44; Ch&#225;vez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> detected an 18&#46;4&#37; prevalence of retinol concentrations &#60; 0&#46;70 &#181;mol&#47;L&#46; However&#44; it should be pointed that the study by Ch&#225;vez et al&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a> included older children and not simply preschoolers &#8211; an age range at higher risk for VAD -&#44; a fact that may have contributed to a lower prevalence of deficient serum retinol concentrations compared to the present study&#46; It is interesting to point out that&#44; in the cited study&#44; children with DS aged two to six years had significantly lower mean retinol concentrations than older children&#46; It is known that serum retinol concentrations are not necessarily consistent with hepatic vitamin A reserves and may be normal even when liver reserves are extremely low&#46;<a class="elsevierStyleCrossRef" href="#bib0018"><span class="elsevierStyleSup">18</span></a> In addition&#44; due to homeostatic control&#44; serum retinol concentrations remain constant within a broad range of hepatic reserves&#46; And they may be influenced by some factors such as infection&#44; inflammation and obesity&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> The most sensitive method for the assessment of vitamin A status in relation to the hepatic reserves is the isotope dilution method&#59; however&#44; this method is too expensive for the population assessment&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> Moreover&#44; the changes in serum retinol concentrations due to a standard oral dose of vitamin A reflect the fact that when the hepatic reserves of vitamin A are reduced&#44; the retinol-binding protein &#40;RBP&#41; accumulates in the liver before the retinol concentrations decrease&#46; Thus&#44; when a standard vitamin A dose is administered&#44; retinol binds to the accumulated RBP and is rapidly released into the serum&#44; a phenomenon that causes an increase in serum retinol concentrations&#46;<a class="elsevierStyleCrossRef" href="#bib0019"><span class="elsevierStyleSup">19</span></a> The RDR test is based on this physiological response of the RBP-retinol complex to identify persons with low hepatic reserves&#46; Since the authors used a different method for the classification of vitamin A status &#40;RDR&#41; compared to the Venezuelan study&#44; it is difficult to compare the observed prevalence&#46; However&#44; so far&#44; no studies have been published in the literature regarding the determination of VAD prevalence among children with DS using the RDR test&#46;</p><p id="para0023" class="elsevierStylePara elsevierViewall">Studies have shown that children with DS are more susceptible to infections&#46;<a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a> In the present study&#44; although the children were apparently healthy without acute febrile or diarrheic episodes&#44; more than one-quarter of them had high CRP concentrations&#46; However&#44; only three children with VAD had high CRP serum concentrations&#46; Subclinical infectious or inflammatory processes may reduce serum retinol concentrations in the organism in a transitory manner&#44; leading to an overestimate of the prevalence of values considered deficient&#46; In response to inflammation or tissue injury&#44; CRP concentrations increase within six to eight hours after the insult&#44; peaking within 48 hours&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">20</span></a> Thus&#44; children with infections or inflammatory processes during the period of incubation may not show increased serum CRP concentrations&#46; It is also known that in infectious or inflammatory processes the serum concentrations of retinol start to decline before the occurrence of high increases in CRP&#46;<a class="elsevierStyleCrossRef" href="#bib0008"><span class="elsevierStyleSup">8</span></a><span class="elsevierStyleSup">&#44;</span><a class="elsevierStyleCrossRef" href="#bib0011"><span class="elsevierStyleSup">11</span></a>&#46; Finally&#44; since RBP is a negative acute-phase protein&#44; subclinical infectious or inflammatory processes may interfere with the release of the retinol-RBP complex by the liver even after supplementation with retinol palmitate&#44; possibly influencing the RDR results&#46; These phenomena&#44; in addition to strict homeostatic control of serum retinol concentrations&#44; even when liver stores are extremely low&#44; may explain the difference in prevalence detected by RDR and by serum retinol concentrations&#46;</p><p id="para0024" class="elsevierStylePara elsevierViewall">The prevalence of deficient serum retinol concentration detected in the present population was higher than that observed in studies conducted on children without DS of similar age ranges when compared with Brazilian data<a class="elsevierStyleCrossRef" href="#bib0021"><span class="elsevierStyleSup">21</span></a> and international data&#46;<a class="elsevierStyleCrossRef" href="#bib0022"><span class="elsevierStyleSup">22</span></a> On the other hand&#44; two studies using tests of the response of the serum concentrations to a standard dose of vitamin A have reported a higher VAD prevalence than observed in the present study&#46; Samba et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0023"><span class="elsevierStyleSup">23</span></a> using the modified dose-response test &#40;MRDR&#41;&#44; observed a 30&#37; VAD prevalence and a 50&#37; prevalence of deficient serum retinol concentrations among preschoolers of sub-Saharan Africa&#46; In two studies&#44; conducted with healthy individuals in the same community investigated by the present study&#44; there was a 74&#46;5&#37; prevalence of VAD among preschoolers without DS&#44; as determined by the&#8239;&#43;&#8239;S30DR method<a class="elsevierStyleCrossRef" href="#bib0024"><span class="elsevierStyleSup">24</span></a> and&#44; recently&#44; insufficient concentrations of vitamin A were observed in breastmilk of lactating women&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">25</span></a></p><p id="para0025" class="elsevierStylePara elsevierViewall">Inadequate vitamin A intake in response to the demands of the organism represents a common pathway towards the development of deficiency&#46;<a class="elsevierStyleCrossRef" href="#bib0001"><span class="elsevierStyleSup">1</span></a> On the other hand&#44; in Brazil DS children receive periodic assistance since the first months of life in specialized institutions&#44; as well as multidisciplinary medical monitoring with physiotherapists and nutritionists for the treatment of their complications&#46; Furthermore&#44; in some cases&#44; their parents or tutors spend greater care on the diet and hygiene of these children&#46; These observations may explain in part the differences in VAD prevalence detected in the present study compared to the values reported by other authors who studied children without the trisomy&#46;</p><p id="para0026" class="elsevierStylePara elsevierViewall">In the present study&#44; children without VAD had higher mean serum IGF-1 concentrations than children with VAD&#44; but the difference was not significant&#46; The relatively small number of individuals studied could explain this finding&#46; However&#44; a moderate positive correlation was observed between the serum retinol and IGF-1 concentrations&#46; Similar results were found among pregnant Nepalese women and healthy Japanese adults&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">5</span></a> Regarding children&#44; Dijkhuizen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0007"><span class="elsevierStyleSup">7</span></a> have also found a moderate correlation between the plasma concentration of retinol and IGF-1 among healthy infants in Indonesia&#46; Du et al&#46;<a class="elsevierStyleCrossRef" href="#bib0006"><span class="elsevierStyleSup">6</span></a> also observed a moderate positive correlation between serum retinol and IGF-1 concentrations in Canadian newborn girls but not in boys&#46; Although some studies have shown that vitamin A supplementation may improve the growth of children with VAD<a class="elsevierStyleCrossRef" href="#bib0026"><span class="elsevierStyleSup">26</span></a> and associated with zinc supplementation&#44; increase the serum concentrations of IGF-1&#44;<a class="elsevierStyleCrossRef" href="#bib0027"><span class="elsevierStyleSup">27</span></a> no studies of this kind have been conducted on children with DS&#46; Thus&#44; whether an improvement of serum retinol concentrations in populations with a high prevalence of deficiency might lead to an increase in IGF-1 concentrations of some clinical relevance in children with DS is a question proposed by the present study&#46; All children of the present study who presented with serum IGF-1 concentrations below the 25th percentile for sex and age had serum retinol concentrations below 0&#46;55 &#181;mol&#47;L&#46; Despite the high proportion of deficient retinol values detected&#44; only four children had deficient serum IGF-1 concentrations&#46;</p><p id="para0027" class="elsevierStylePara elsevierViewall">The present study has some limitations&#46; Although the study group practically included the entire population of preschoolers with DS in the city&#44; the number of subjects studied was relatively small&#44; a fact that may have reduced the power of some analyses&#46; Since it was a cross-sectional study&#44; changes along time that might have occurred in the relationship between retinol and IGF-1 concentrations&#44; especially during or in the absence of infectious episodes or inflammatory processes&#44; could not be detected&#46; Finally&#44; another limitation was the lack of information about vitamin A intake that might have helped explain some findings&#46;</p></span><span id="sec0008" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0014">Conclusion</span><p id="para0028" class="elsevierStylePara elsevierViewall">The present population-based study detected an elevated prevalence of VAD among preschoolers with DS using the RDR method&#44; as well as a high proportion of deficient serum retinol concentrations&#46; A small proportion of children had deficient IGF-1 concentrations&#46; No difference in mean IGF concentrations was observed between children with and without VAD&#46; However&#44; a positive correlation was observed between serum retinol and IGF-1&#46;</p></span></span>"
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    "fechaRecibido" => "2021-02-10"
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            0 => "Vitamin A deficiency"
            1 => "Insulin-like growth factor I"
            2 => "Child"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abss0001" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0002">Objective</span><p id="spara008" class="elsevierStyleSimplePara elsevierViewall">To determine the prevalence of vitamin A deficiency &#40;VAD&#41; and serum concentrations of retinol&#44; correlating them with IGF-1 concentrations in preschoolers with DS&#46;</p></span> <span id="abss0002" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0003">Methods</span><p id="spara009" class="elsevierStyleSimplePara elsevierViewall">Cross-sectional study was conducted on 47 children with DS aged 24 to 72 months&#44; in Ribeir&#227;o Preto&#44; Brazil&#46; VAD was determined by the relative dose-response &#40;RDR&#41; test&#46; Retinol serum concentration &#8804; 0&#46;70 &#181;mol&#47;L and IGF-1 serum concentration below the 3rd percentile for sex and age were considered to represent deficiency&#46; C-reactive protein &#40;CRP&#41; was determined at the beginning of the study&#46; Weight&#44; height&#44; and information about fever and&#47;or diarrhea were obtained at the beginning of the study&#46;</p></span> <span id="abss0003" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0004">Results</span><p id="spara010" class="elsevierStyleSimplePara elsevierViewall">VAD prevalence was 25&#46;5&#37; &#40;12&#47;47&#41;&#44; and 74&#46;5&#37; &#40;35&#47;47&#41; of the children had deficient retinol before the intervention&#46; CRP was not associated with VAD&#46; Mean IGF-1 were 103&#46;5 ng&#47;mL &#40;SD&#8239;&#61;&#8239;913&#41; for the group with VAD and 116&#46;3 ng&#47;mL &#40;SD&#8239;&#61;&#8239;54&#46;9&#41; for the group with no VAD &#40;p-value&#8239;&#61;&#8239;0&#46;85&#41;&#59; 8&#46;5&#37; &#40;4&#47;47&#41; of the children showed deficient IGF-1&#44; but without VAD&#46; No association was observed between VAD and IGF-1 deficiency&#46; A moderate positive correlation was observed between pre-intervention retinol and IGF-1 &#40;&#961;&#8239;&#61;&#8239;0&#46;37&#59; p-value&#8239;&#61;&#8239;0&#46;01&#41;&#46;</p></span> <span id="abss0004" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="cesectitle0005">Conclusion</span><p id="spara011" class="elsevierStyleSimplePara elsevierViewall">a high prevalence of VAD and deficient retinol was observed and there was a positive correlation between serum retinol and IGF-1&#46;</p></span>"
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          "en" => "<p id="spara002" class="elsevierStyleSimplePara elsevierViewall">Mean serum IGF-1 concentrations between children with and without Vitamin A Deficiency&#46; Ribeir&#227;o Preto 2009-2011&#46; Brazil&#46; VAD&#44; vitamin A deficiency&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "fig0003"
        "etiqueta" => "Figure 3"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr3.jpeg"
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          0 => array:3 [
            "identificador" => "alt0003"
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          "en" => "<p id="spara003" class="elsevierStyleSimplePara elsevierViewall">Dispersion graph representing the correlation between serum IGF-1 concentrations &#40;ng&#47;mL&#41; and pre-supplementation &#40;A<span class="elsevierStyleInf">0</span>&#41; retinol concentrations among preschoolers with Down Syndrome&#46; Ribeir&#227;o Preto 2009-2011&#46; Brazil&#46;</p>"
        ]
      ]
      3 => array:8 [
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        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
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          "leyenda" => "<p id="spara005" class="elsevierStyleSimplePara elsevierViewall">VAD&#44; vitamin A deficiency&#59; RDR&#44; relative dose-response&#59; 95&#37;CI&#44; 95&#37; confidence interval&#46;</p>"
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                  \t\t\t\t\tvoid\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">Prevalence of VAD &#40;95&#37;CI&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0009"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Female&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0010"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0011"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">55&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0012"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#46;9 &#40;11&#46;5 &#8211; 47&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0013"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">Male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0014"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0015"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">44&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0016"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">23&#46;8 &#40;8&#46;2 &#8211; 47&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0017"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">Age &#40;months&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0018"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0019"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0020"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0021"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0022"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">23&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0023"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">48&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0024"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17&#46;4 &#40;4&#46;9 &#8211; 38&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0025"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8805; 40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0026"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0027"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">51&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0028"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">33&#46;3 &#40;15&#46;6 &#8211; 55&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0029"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">Maternal schooling</span><span class="elsevierStyleBold">&#40;years of study successfully completed&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0030"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0031"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0032"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0033"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0034"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0035"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">12&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0036"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">16&#46;7 &#40;0&#46;4 &#8211; 64&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0037"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8805; 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0038"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">41&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0039"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">87&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0040"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&#46;8 &#40;14&#46;2 &#8211; 42&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0041"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">Paternal schooling</span><span class="elsevierStyleBold">&#40;years of study successfully completed&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0042"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0043"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0044"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0045"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#60; 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0046"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0047"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0048"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">10&#46;0 &#40;0&#46;2 &#8211; 44&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0049"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8805; 8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0050"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0051"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">78&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0052"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">29&#46;7 &#40;15&#46;8 &#8211; 46&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0053"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">Monthly family income</span><span class="elsevierStyleBold">&#40;Brazilian minimum wages&#41;</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0054"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0055"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0056"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0057"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8804; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0058"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0059"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">55&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0060"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">15&#46;4 &#40;4&#46;4 &#8211; 34&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0061"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#707; 3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0062"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0063"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">44&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0064"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">38&#46;1 &#40;18&#46;1 &#8211; 61&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0065"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top"><span class="elsevierStyleBold">N&#176; of household persons</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0066"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0067"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0068"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0069"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#8804; 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0070"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0071"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">63&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0072"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">30&#46;0 &#40;14&#46;7 &#8211; 49&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><a name="en0073"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">&#707; 4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0074"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0075"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">36&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><a name="en0076"></a><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="" valign="top">17&#46;6 &#40;3&#46;8 &#8211; 43&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
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        "descripcion" => array:1 [
          "en" => "<p id="spara004" class="elsevierStyleSimplePara elsevierViewall">Socioeconomic characteristics of preschoolers with Down Syndrome&#44; and prevalence of VAD determined by the RDR test&#46; Ribeir&#227;o Preto 2009-2011&#46; Brazil&#46;</p>"
        ]
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      4 => array:8 [
        "identificador" => "tbl0002"
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          "en" => "<p id="spara006" class="elsevierStyleSimplePara elsevierViewall">Means&#44; medians&#44; and quartile distributions of serum IGF-1 concentrations &#40;ng&#47;mL&#41; among preschool children with Down syndrome&#44; according to vitamin A deficiency&#46; Ribeir&#227;o Preto 2009-2011&#46; Brazil&#46;</p>"
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Article information

ISSN: 00217557
Original language: English

DOI:10.1016/j.jped.2021.04.003

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Year/Month	Html	Pdf	Total

2024 November	5	6	11
2024 October	89	31	120
2024 September	83	47	130
2024 August	133	59	192
2024 July	152	45	197
2024 June	97	32	129
2024 May	59	20	79
2024 April	77	26	103
2024 March	81	23	104
2024 February	77	29	106
2024 January	61	27	88
2023 December	82	24	106
2023 November	68	33	101
2023 October	81	43	124
2023 September	58	36	94
2023 August	57	18	75
2023 July	50	14	64
2023 June	43	11	54
2023 May	37	22	59
2023 April	34	22	56
2023 March	46	31	77
2023 February	52	27	79
2023 January	64	34	98
2022 December	97	54	151
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2022 October	100	36	136
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2022 August	85	44	129
2022 July	64	60	124
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2022 May	107	38	145
2022 April	87	51	138
2022 March	164	91	255
2022 February	140	56	196
2022 January	109	53	162
2021 December	21	21	42
2021 November	10	18	28
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