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<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Malnutrition in children under five years of age is one of the leading health problems in all countries.<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">1</span></a> In addition, malnutrition is the leading cause of death, estimated to be about 45% of deaths in children aged 0–59 months.<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Nutritional problems in Indonesia are one of the main problems in human development. As one of the countries with a very diverse population complexity, Indonesia is faced with the dynamics of malnutrition. Although Indonesia's development process has been able to overcome the problem of nutrition, if seen from the trend of statistical data, there are still many problems that need to be assessed and resolved, especially those concerning under-nutrition.<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">3</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Malnutrition is a medical condition caused by insufficient intake, and this condition is often associated with malnutrition due to lack of food consumption, low absorption, or excessive loss of nutrients.<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">4</span></a> Another impact of malnutrition is that apart from causing death, it also disrupts intelligence growth and development, where everyone who experiences malnutrition is reported to have a risk of losing IQ by 10–13 points.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">5</span></a> If the food intake for toddlers is insufficient, it will cause malnutrition. The toddler period is a period of very rapid growth and development. Toddlers over one year old have started to understand language and have a powerful sense of curiosity.</p><p id="par0020" class="elsevierStylePara elsevierViewall">Lack of food or nutritional intake in children under five is caused by factors such as economic factors, education, knowledge, and food security. The family's economic status, classified as weak, causes a lack of community ability to provide nutritious food. If this continues for a long time, there will be chronic malnutrition in children, which will result in stunting. In addition, the education and knowledge of parents or caregivers greatly influence parenting styles. Good parenting can meet all toddlers to cause them to grow and develop optimally; on the other hand, poor parenting will interfere with toddlers’ growth and development.<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">6</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Average growth and development in children also depend on hormonal factors. Normal nutritional status is required for linear growth.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">7</span></a> Nutritional status plays an essential role in controlling GH and IGF-1 in circulation, regulating their work and delivery in body fluids and tissues. GH mediates growth, and IGF-1 as a mediator of GH action, bioavailability, and bioactivity of IGF-1 is modulated by the binding protein IGFBP-3.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Nutritional deficiencies can affect GH signaling and lead to a state of GH resistance, resulting in higher systemic growth hormone levels and decreased IGF-1 and IGFBP-3 production. IGFBP-3 is the primary protein binding to IGF in serum and functions as a circulating IGF reserve. IGFBP-3 carries IGF-1 in the blood circulation, directs it to target tissues, protects it from proteolytic degradation, and regulates its interaction with IGF-1R. About 99% of IGF-1 in the blood circulation is mainly bound to IGFBP-3.<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">8,9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The identification of the nutritional status of toddlers by examining the hormones involved in growth is still rarely used, and there is still a lack of knowledge and research on the examination of hormones involved in growth, even though the examination of the hormones involved in growth is an accurate test to determine the level of nutritional status.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Research methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Location and research design</span><p id="par0040" class="elsevierStylePara elsevierViewall">This study used a cross-sectional study method, which is a design by measuring or observing variables simultaneously. This study aimed to determine the levels of IGFBP-3 in malnourished toddlers aged 36–60 months. This research was carried out by the Bara-Baraya Health Center in Makassar City, South Sulawesi, Indonesia.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Population and subject</span><p id="par0045" class="elsevierStylePara elsevierViewall">The population of this study was all toddlers aged 36–60 months. The sampling technique used in this study was simple random sampling with the subject in this study was 41 people consisting of well-nourished and malnourished toddlers aged 36–60 months. This study has received a recommendation of approval from the Ethical Commission for Health Research of Medical Faculty, Hasanuddin University Makassar with number 420/UN4.6.4.5.31/PP36/2020 and Protocol Number UH20050223.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Method and data analysis</span><p id="par0050" class="elsevierStylePara elsevierViewall">The instruments used in this study were questionnaires and measuring levels of IGFBP-3. The questionnaire is data collection by providing a list of questions to the respondent to provide answers to all the questions listed. Measurement of levels of IGFBP-3 (Insulin-Like Growth Factor Binding Protein-3) using ELISA (Enzyme-Linked Immunosorbent Assay) at the Hasanuddin University RSP Research Laboratory Unit. Then, data analyzed using the Fisher exact and Mann–Whitney statistical test.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0055" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the number of maternal education is low; family income is at most \n
<umr, family="" members="">\n
4, ownership of latrines, in this case, is more likely to be without a private latrine. More birth history with birth weight 2500–4000\n
</umr,><span class="elsevierStyleHsp" style=""></span>g, birth length >48<span class="elsevierStyleHsp" style=""></span>cm, and exclusive breastfeeding.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">To find out the differences in IGFBP-3 levels in malnourished and normal under-five children is essential; the Mann–Whitney statistical test was used because the data on IGFBP-3 levels were not normally distributed. The results of statistical tests showed that there were differences in IGFBP-3 levels in malnourished and typical toddlers (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). This indicates that Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) levels are low in malnourished toddlers.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Discussion</span><p id="par0065" class="elsevierStylePara elsevierViewall">Based on the results of the Mann-Whitney test, it shows that there are differences in levels of Insulin-like Growth Factor Binding Protein-3 (IGFBP-3) in toddlers with normal nutritional status and toddlers with malnutrition nutritional status.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Toddler time needs adequate nutrition because the Toddler period is a golden period. A period of life that is very important for physical and mental development is when toddlers begin to do a lot and discover new things. In this case, good nutrition plays an important role.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">10</span></a> Regarding individual nutritional status, the GH and IGF-1 axis are the endocrine system principles that regulate linear growth in children. GH is a stimulator of IGF-I secretion and action<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a> and a significant regulator of IGFBP-3 production in humans. Apart from GH regulation, nutrition and age also play a role in regulating IGFBP-3 production.<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">IGF-1 and IGFBP-3 serve as primary mediators of GH action and as GH-independent growth factors. Many studies have shown that GH and IGF-1 concentrations are responsive to nutritional status changes.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> IGFBP-3 is an IGF-1 carrier protein and regulates the bioavailability of IGF-1 so that it has a very close relationship.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">14</span></a> The function of IGF-1 is to metabolize food protein, energy, and carbohydrates<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> and the growth of cartilage. When the amount of Insulin-Like Growth Factor-1 (IGF-1) secreted increases in response to Growth Hormone (GH) stimulation, there will be an increase in Insulin-Like Growth Factor Binding Protein-3 (IGFBP-3) to absorb it in the circulation. Low concentrations of IGF and IGFBP-3 can inhibit linear growth until body weight and height are stopped.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Weight gain and linear growth were associated with IGF-1 and IGFBP-3.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">13</span></a> Malnutrition has a strong effect on IGF-I, IGFBP-3, and ALS,<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">15</span></a> and reduced serum concentrations are influenced by nutritional status. Examination of serum levels of Insulin-Like Growth Factor-1 (IGF-1) and IGF-binding protein, namely IGFBP-3, can complement the growth status assessment to predict growth response.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">11</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Adequate dietary intake is essential to maintain normal circulating levels of IGF-1 and IGFBP-3 in serum. Energy and protein restriction in children leads to decreased IGF-1 and IGFBP-3 levels. Smith et al. observed that calorie restriction led to decreased IGF-1 and IGFBP-3 in both adults and children. After nutritional rehabilitation, there was an increase in IGF-1 and IGFBP-3, but the increase was not significant or did not reach baseline levels.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">16</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">This study showed that the levels of IGFBP-3 in malnourished children were low, with a median (minimum–maximum) value of 0.35 (0.04–1.27)<span class="elsevierStyleHsp" style=""></span>mcg/mL. This is in line with previous studies that have also shown that malnutrition decreases IGFBP-3 production. IGFBP-3 has been intensively studied in light of this protein's physiological role in acute changes in plasma glucose, IGF, and insulin levels. Secretion of IGF-1 is GH dependent and stimulated by an increase in blood glucose after feeding. The biological effects of IGF-1 are regulated by IGFBP-3, which is responsible for its transport in the blood.<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">17</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Conclusion</span><p id="par0095" class="elsevierStylePara elsevierViewall">A cross-sectional study has been conducted, and after statistical analysis, it can be concluded that IGFBP-3 levels are low in malnourished children under five and can be used as a parameter to assess nutritional status.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Conflicts of interest</span><p id="par0100" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interest.</p></span></span>
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"resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">This study aimed to compare serum levels of Insulin-like Growth Factor Binding Protein-3 in children with malnutrition and good nutritional status.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">This cross-sectional study included 41 participants consisting of 31 malnourished, 10 well-nourished children aged between 36 and 60 months. Demographic data of participants were obtained utilizing a questionnaire. Nutritional status was determined by calculating the <span class="elsevierStyleItalic">Z</span>-score of body weight for age, height for age, and body weight for height indices using the WHO classification. IGFBP-3 levels were determined by the Enzyme-Linked Immunosorbent Assay (ELISA) method.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Result</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Median serum IGFBP-3 levels in malnourished children were found to be lower i.e. 0.35<span class="elsevierStyleHsp" style=""></span>mcg/mL (minimum–maximum: 0.04–1.52<span class="elsevierStyleHsp" style=""></span>mcg/mL) compared to well-nourished children 1.52<span class="elsevierStyleHsp" style=""></span>ng/mL (minimum–maximum 0.47–3.17<span class="elsevierStyleHsp" style=""></span>mcg/mL).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Serum IGFBP-3 levels can be used as indicators to assess nutritional status.</p></span>"
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\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">1 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t">10.00 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t " align="char" valign="\n
\t\t\t\t\ttop\n
\t\t\t\t">18 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t">58.06 \t\t\t\t\t\t\n
\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t</td><td class="td" title="\n
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\t\t\t\t">13 \t\t\t\t\t\t\n
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