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5&#37; to 10&#37; of neonates are SGA&#46; In Spain&#44; the proportion ranges from 3&#37; to 5&#37; of total births&#44; and in the province of Alava&#44; 3&#46;5&#37; of the total&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;6</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The causes of SGA are not well established&#44; but are known to include foetal&#44; maternal&#44; uteroplacental and environmental factors&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3&#44;5</span></a> Several studies have concluded that SGA infants have decreased serum levels of insulin-like growth factors &#40;IGF-1 and IGF-2&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> There is evidence of an association between these decreased levels and defects in the growth hormone receptor in SGA infants&#46;<a class="elsevierStyleCrossRefs" href="#bib0040"><span class="elsevierStyleSup">8&#44;9</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Accurate diagnosis is important due to the increased neonatal morbidity and mortality in this group of infants&#44; in addition to an increased risk of developing certain diseases in childhood as well as adulthood&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> These include metabolic and endocrine disorders such as diabetes mellitus&#44; dyslipidaemia and high blood pressure<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;10</span></a> as well as growth and developmental disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Children born SGA can be classified into different categories&#58; symmetric SGA refers to children in whom both weight and height are affected&#44; while asymmetric SGA refers to children in whom either weight or height are affected&#44; but not both&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> This classification is important&#44; as it can guide the aetiological diagnosis and help predict the future risk of vascular disease<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and the response to growth hormone replacement therapy&#44; with symmetric SGA associated with an increased frequency of short stature in adulthood<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and asymmetric SGA affecting weight associated with an increased frequency of perinatal hypoglycaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">When it comes to the hormone profile of children born SGA&#44; thyroid function is among the least studied axes in this population&#46; Thyroid hormones are essential during the foetal period and in the first months of life for normal development of the nervous system and adequate growth&#46; They also play a key role in bone&#44; heart and lung maturation throughout the foetal period&#46; Therefore&#44; low levels in the first months of life can increase the risk of intellectual disability&#44; short stature and metabolic disorders with irreversible consequences&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However&#44; from a clinical standpoint&#44; there are no specific signs or symptoms at birth that would allow suspicion of thyroid abnormalities&#44; which makes performance of screening tests for early diagnosis essential&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Several studies show that thyroid function in preterm infants is usually altered due to the lower gestational age&#44; resulting in increased requirements of thyroid hormones that in turn lead to higher serum concentrations of thyroid-stimulating hormone &#40;TSH&#41; and lower concentrations of triiodothyronine and thyroxine compared to term neonates&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> This is why monitoring thyroid function is recommended in the first years of life in children born preterm&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">However&#44; few studies have analysed the thyroid hormone profile in SGA infants&#46; Some have found that there are differences compared to children with birth weights appropriate for gestational age &#40;AGA&#41;&#44; but few have focused on the levels of TSH and thyroxine&#44; and the published data are contradictory&#44; so at present there is no indication for specific follow-up or thyroid function monitoring in SGA children&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The aim of our study was to compare thyroid function in a sample of SGA infants with thyroid function in other subsets of infants&#58; AGA infants and preterm infants&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sample and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">For the purpose of sample selection&#44; we defined SGA as a birth weight and&#47;or length 2 or more SDs from the mean&#44; taking as reference the growth charts of the nationwide study of growth conducted in Spain in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The inclusion criteria were&#58; Caucasian infant born between June 1&#44; 2013 and June 1&#44; 2015 in the department of labour and delivery of the Hospital Universitario Araba &#40;HUA&#41; meeting the case definition of SGA&#46; The exclusion criteria were&#58; non-white race&#44; infants product of a multiple pregnancy&#44; severe malformations&#44; death within 24&#8239;hours of birth or not meeting the case definition of SGA&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Recruitment took place by consecutive sampling&#58; any infant born in the labour and delivery department of the HUA in the period under study that met the inclusion criteria was a candidate for participation&#46; We collected data on the following variables&#58; gestational age&#44; birth weight and length&#44; sex&#44; and serum TSH levels in SGA infants at different time points between age 4 months and 2 years&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Subsequently&#44; we excluded cases with incorrectly documented or missing data for the variables under study&#44; and obtained a final sample of 38 infants&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Having obtained the sample&#44; we proceeded to the descriptive analysis of the explanatory variables using the mean&#44; SD and median&#46; We then compared TSH levels based on sex &#40;SGA boys vs SGA girls&#41;&#44; gestational age &#40;SGA infants born at term vs preterm&#44; defined as birth before 37 weeks&#41;&#44; SGA symmetry &#40;defining symmetric SGA as low weight and length and asymmetric SGA as alteration of only one of the two&#41; and by the age of the child born SGA at the time of collection of the blood sample &#40;age &#60; 6 months vs age &#62; 6 months&#41;&#46; We made compared means using 2-tailed tests&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We also calculated the correlation coefficient for gestational age&#44; birth length and weight and age at the time of blood sample collection&#44; as these were quantitative variables&#44; with values close to 1 or &#8722;1 indicating a strong correlation and values nearing 0 a weak correlation&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We also compared the results in our sample with the data published in other studies conducted in different populations&#46; First&#44; we compared our sample to a sample of healthy children born AGA in a study conducted by Cort&#233;s-Blanco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Specifically&#44; we grouped serum TSH values for healthy children from Zaragoza by age group&#58; 1 to 6 months &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;18&#41; and 6 months to 4 years &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;30&#41;&#46; We did the same with a sample of children born preterm in Barcelona in a study conducted by Clemente et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> This study published longitudinal data on serum TSH levels in a sample of healthy children born preterm &#40;between 30 and 35 weeks of gestation&#41;&#46; We compared samples using the Student <span class="elsevierStyleItalic">t</span> test for quantitative variables&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results of the descriptive analysis of the study sample</span><p id="par0085" class="elsevierStylePara elsevierViewall">The TSH levels in SGA children in our sample ranged from 1 to 9&#8239;&#956;U&#47;mL&#46; However&#44; as can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; the sample mean was 3&#46;68 &#956;U&#47;mL&#44; with a SD of 1&#46;88 &#956;U&#47;mL and a median of 3 &#956;U&#47;mL&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> presents the mean serum TSH values in children born SGA categorised based on the variables under study &#40;sex&#44; gestational age&#44; symmetry and age at time of sample collection&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results by sex</span><p id="par0095" class="elsevierStylePara elsevierViewall">The mean TSH level in SGA boys was 4&#46;24 &#956;U&#47;mL&#44; with a SD of 1&#46;79&#8239;&#956;U&#47;mL and a median of 4&#8239;&#956;U&#47;mL&#46; In contrast&#44; the mean TSH values in SGA girls ranged from 1 to 8&#8239;&#956;U&#47;mL&#44; with a mean of 3 &#956;U&#47;mL&#44; a SD of &#177;1&#46;8&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We found statistically significant differences based on sex in the serum TSH levels of children born SGA in the catchment population of the health area of Alava &#40;OSI Araba&#41; aged 3 months to 2 years &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; Thus&#44; we can state that in our sample of children born SGA&#44; boys had higher serum TSH levels compared to girls&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results by gestational age group</span><p id="par0105" class="elsevierStylePara elsevierViewall">The mean TSH level in children born SGA at term was 3&#46;43&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;78&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46; In contrast&#44; children born SGA and preterm had a mean serum TSH level of 4&#46;46&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;86&#8239;&#956;U&#47;mL and a median of 4&#46;5&#8239;&#956;U&#47;mL&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The correlation coefficient for the association between the gestational age of SGA infants and their serum TSH values was &#8722;0&#46;19&#44; indicative of a weak inverse correlation&#46; That is&#44; the lower the gestational age at birth&#44; the higher the serum TSH levels in the first months of life&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results based on anthropometric measurements</span><p id="par0115" class="elsevierStylePara elsevierViewall">The mean TSH level in the symmetric SGA group was 3&#46;88&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;62&#8239;&#956;U&#47;mL and a median of 5&#8239;&#956;U&#47;mL&#46; In contrast&#44; in the asymmetric SGA group the mean was 3&#46;71&#8239;&#956;U&#47;mL&#44; with a SD of 2&#46;02&#8239;&#956;U&#47;mL and a median of 3&#46;5&#8239;&#956;U&#47;mL&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The correlation coefficients for the association between the serum levels of TSH in SGA children and their birth length and weight were &#8722;0&#46;15 and &#8722;0&#46;12&#44; respectively&#46; In other words&#44; a low birth length&#47;weight seems to predispose infants to decreased serum TSH levels in the early months of life&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results based on age of children born SGA</span><p id="par0125" class="elsevierStylePara elsevierViewall">The proportion of children born SGA aged less than 6 months was 58&#37;&#44; compared to 42&#37; of children born SGA aged more than 6 months&#46; The mean TSH level in SGA infants aged less than 6 months was 3&#46;86&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;74&#8239;&#956;U&#47;mL and a median of 4&#8239;&#956;U&#47;mL&#46; The mean TSH level in children born SGA aged more than 6 months was 3&#46;4&#8239;&#956;U&#47;mL&#44; with a SD of 2&#46;16&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in TSH levels between children born SGA aged less than 6 months and those aged more than 6 months at the time of collection of the blood sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46; Nevertheless&#44; the correlation coefficient for the association between the current age of children born SGA and their serum TSH levels was &#8722;0&#46;16&#46; Thus&#44; serum TSH levels in children born SGA tend to decrease with age&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results of comparing TSH levels in the study sample with other paediatric samples</span><p id="par0135" class="elsevierStylePara elsevierViewall">First&#44; we compared the results in our sample with data obtained in healthy children in Zaragoza published by Cort&#233;s-Blanco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> On one hand&#44; we compared serum TSH levels in SGA infants aged less than 6 months in our sample with those of healthy children from Zaragoza aged 1 to 6 months&#44; and on the other&#44; we compared the levels in children born SGA in our sample aged more than 6 months with those in healthy children from Zaragoza aged 6 months to 4 years&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in serum TSH levels in SGA infants in our sample compared to healthy infants aged 1 to 6 months in the Zaragoza sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In contrast&#44; we did find statistically significant differences in serum TSH levels between children born SGA aged more than 6 months in our sample and the healthy children aged 6 months to 4 years in the Zaragoza sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Then&#44; we compared the results in our sample with data obtained in the study of healthy children born preterm conducted in Barcelona by Clemente et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> To do so&#44; we compared the groups of infants aged 4 and 6 months in the Barcelona study to the group of SGA infants aged less than 6 months in our sample&#44; and also the groups aged 9 and 12 months in the Barcelona study with children born SGA aged more than 6 months in our sample&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in TSH levels in the comparison of children in either of these age groups&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">Our study found statistically significant differences in the sample of children born SGA based on sex&#46; It seems that boys born SGA tend to have higher serum levels of TSH compared to girls&#46; This is consistent with the results of several studies that suggest that male infants are at increased risk of transient hyperthyrotropinaemia and transient hypothyroxinaemia in the early years of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">On the other hand&#44; we identified gestational age at birth as a possible predictor of hyperthyrotropinaemia in children born SGA in the OSI Araba&#44; although the association between these variables was weak&#46; This was similar to the results of previous studies that have found differences in TSH levels between term and preterm infants&#44; with a higher risk of hypothyroidism in the latter&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;21&#44;22</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">When it comes to anthropometric values&#44; some studies in the previous literature suggest that low birth weight is a risk factor for thyroid disorders&#44;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;23</span></a> while others did not find an association between anthropometric values at birth and TSH levels in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In our study&#44; we found a weak association between the birth weight and length and TSH values&#44; although we did not find statistically significant differences based on the symmetry of SGA&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">We ought to highlight that TSH values varied between groups&#44; yet they were in the normal range in 50&#37; of the cases&#44; so it may be worth assessing the clinical relevance of the observed differences&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">As for the comparison of our sample to samples in other infant populations&#44; we found that children born SGA in the OSI Araba had higher serum levels of TSH in the first years of life compared to healthy children in Zaragoza&#46; Thus&#44; while serum TSH levels tended to decrease from 6 months of age in children born AGA&#44; they remained elevated for longer in children born SGA in the OSI Araba&#46; The evidence on the association between SGA and thyroid disorders is insufficient&#44; but previous studies have found that a birth weight of less than 2000&#8239;g was associated with an increased risk of hyperthyrotropinaemia in the long term&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24</span></a> an elevation that could in turn increase the risk of developing hypothyroidism and cardiovascular problems at later ages&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">On the other hand&#44; when we compared the sample of SGA infants in our study to the sample of preterm infants&#44; we did not find statistically significant differences at any age&#46; Therefore&#44; we may conclude that the risk of thyroid disorders is similar in SGA infants and in preterm infants&#46; Several studies have found that preterm SGA infants have higher serum TSH levels compared to preterm AGA infants&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and therefore thyroid function in these infants should be monitored in the first months of life&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The main limitation of the study was the lack of a group of AGA infants born in the OSI Araba in the same time interval and with collection of data under the same circumstances for comparison with the SGA sample&#46; Due to this lack&#44; we collected information from studies conducted on AGA children in other regions&#44; which may come from populations whose characteristics differ from the catchment population of the OSI Araba&#46; We also ought to mention that the sample size was small&#44; which may affect the validity of the results&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">As noted above&#44; the factors that seem to have an effect on the development of increased TSH levels in infants born SGA are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Male sex&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Lower gestational age at birth seems to be associated with an increased risk of thyroid disorders&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">A low birth length and&#47;or weight relative to the reference population seems to increase the risk of thyroid disorders in SGA infants&#46;</p></li></ul></p><p id="par0215" class="elsevierStylePara elsevierViewall">The main conclusion of our study is that SGA infants have higher thyroid hormone requirements in the long term&#44; similar to those of preterm infants&#46; That is&#44; our findings suggest that the risk of hyperthyrotropinaemia in SGA infants is similar to the risk in preterm infants&#44; possibly leading to an increased frequency of thyroid abnormalities that may give rise to chronic and irreversible diseases in the future&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Taking these similarities into account&#44; we propose the following&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Screen TSH levels in SGA infants&#44; with monitoring of thyroid function as needed in male infants and infants born at lower gestational ages or with very low birth weight or length&#44; similar to the follow-up performed in preterm infants&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Assess the need for thyroid hormone replacement therapy in SGA infants at increased risk of developing thyroid disorders or those that do not exhibit adequate catch-up growth&#46;</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0235" class="elsevierStylePara elsevierViewall">The study was funded by a global medical grant from <span class="elsevierStyleGrantSponsor" id="gs0005">Pfizer</span>&#44; awarded in 2012&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors received a global grant from Pfizer for performance of this study in year 2012&#46;</p></span></span>"
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    "fechaRecibido" => "2020-06-16"
    "fechaAceptado" => "2020-10-09"
    "PalabrasClave" => array:2 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1439340"
          "palabras" => array:3 [
            0 => "Small for gestational age"
            1 => "Thyrotropin"
            2 => "Premature"
          ]
        ]
      ]
      "es" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Palabras clave"
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          "palabras" => array:3 [
            0 => "Peque&#241;o para la edad gestacional"
            1 => "Tirotropina"
            2 => "Reci&#233;n nacido prematuro"
          ]
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Several studies conclude that small for gestational age &#40;SGA&#41; children have a higher number of comorbidities&#44; as well as a different hormonal profile compared to those with appropriate weight for gestational age &#40;AGA&#41;&#46; Thyroid hormones play an important role in growth and neurocognitive development&#46; Thyroid function in SGA children is still not completely known&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">To compare the thyroid function of SGA children during the first 2 years of life with that in publications on thyroid function in other groups of infants&#44; such as AGA and premature children&#44; using the same methodology&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A cohort of 38 SGA children was obtained&#44; in which the thyrotropin &#40;TSH&#41; values in blood were measured at different points in the development of the SGA child&#46; The results were compared with a population of AGA children from Zaragoza and a population of premature children from Barcelona by comparing the means using a 2-tailed test&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A statistically significant difference &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41; was observed between the SGA children in our study and the AGA children older than 6 months&#44; but not between the SGA children of the study and the population of premature infants&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SGA children have higher TSH values compared to AGA children older than 6 months&#46; Therefore&#44; it seems reasonable to establish a screening and a follow-up protocol in those SGA with high risk to develop thyroid dysfunction&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Objectives"
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          2 => array:2 [
            "identificador" => "abst0015"
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            "titulo" => "Results"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">M&#250;ltiples estudios concluyen que los ni&#241;os peque&#241;os para la edad gestacional &#40;PEG&#41; tienen un n&#250;mero mayor de comorbilidades&#44; as&#237; como un perfil hormonal diferente respecto a los ni&#241;os con un peso adecuado para la edad gestacional &#40;PAEG&#41;&#46; Las hormonas tiroideas juegan un papel importante en el crecimiento y en el desarrollo neurocognitivo&#46; La funci&#243;n tiroidea en los ni&#241;os PEG es&#44; hoy en d&#237;a&#44; incierta&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio es comparar la funci&#243;n tiroidea de los ni&#241;os PEG durante los 2 primeros a&#241;os de vida con publicaciones sobre funci&#243;n tiroidea en otros grupos de lactantes &#40;PAEG y prematuros&#41; que utilicen la misma metodolog&#237;a&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se obtuvo una cohorte de 38 ni&#241;os PEG&#44; en los cuales se midieron los valores de TSH en sangre en distintos momentos del desarrollo del ni&#241;o PEG&#46; Los resultados se compararon con una poblaci&#243;n de ni&#241;os PAEG de Zaragoza y una poblaci&#243;n de ni&#241;os prematuros de Barcelona mediante pruebas de comparaci&#243;n de medias de contraste bilateral&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se ha observado una diferencia estad&#237;sticamente significativa &#40;p&#8239;&#60;&#8239;0&#44;05&#41; entre los ni&#241;os PEG de nuestro estudio y los ni&#241;os PAEG mayores de 6 meses&#44; no as&#237; entre los PEG del estudio y la poblaci&#243;n de prematuros&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Los ni&#241;os PEG tienen valores de TSH superiores respecto a los ni&#241;os PAEG mayores de 6 meses&#46; Por lo tanto&#44; parece razonable establecer un cribado y un protocolo de seguimiento en los PEG de mayor riesgo&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gonz&#225;lez IF&#44; Maeso-M&#233;ndez S&#44; Miranda AS&#44; del Hoyo Moracho M&#44; Bl&#225;zquez IL&#44; L&#243;pez ID&#46; Diferencias en la funci&#243;n tiroidea de los peque&#241;os para la edad gestacional y los de peso adecuado&#46; &#191;Es normal la funci&#243;n tiroidea de los reci&#233;n nacidos peque&#241;os para la edad gestacional&#63; An Pediatr &#40;Barc&#41;&#46; 2021&#59;95&#58;330&#8211;335&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Thyroid-stimulating hormone levels in children born small for gestational age between 4 months and 2 years of life&#46;</p>"
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                            0 => "L&#46; Gal&#225;n Bueno"
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                      "Libro" => array:3 [
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Original Article
Differences in thyroid function between small for gestational age and those with appropriate weight for gestational age. Is thyroid function normal in small for gestational age newborns?
Diferencias en la función tiroidea de los pequeños para la edad gestacional y los de peso adecuado. ¿Es normal la función tiroidea de los recién nacidos pequeños para la edad gestacional?
Iker Fernández Gonzáleza,
Corresponding author
ikerfergon13@gmail.com

Corresponding author.
, Sandra Maeso-Méndezb, Ainhoa Sarasua Mirandac, Marta del Hoyo Morachod, Isabel Lorente Blázquezc, Ignacio Díez Lópeze
a Facultad de Medicina, Universidad del País Vasco (UPV/EHU), Vitoria-Gasteiz, Álava, Spain
b Servicio de Pediatría, Hospital Universitario Araba, Vitoria-Gasteiz, Álava, Spain
c Sección de Endocrinología Infantil, Servicio de Pediatría, Hospital Universitario Araba, Vitoria-Gasteiz, Álava, Spain
d Sección de Neonatología, Servicio de Pediatría, Hospital Universitario Araba, Vitoria-Gasteiz, Álava, Spain
e Sección de Endocrinología Infantil, Servicio de Pediatría, Hospital Universitario Araba, Facultad de Medicina, Universidad del País Vasco (UPV/EHU), Vitoria-Gasteiz, Álava, Spain
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in addition to an increased risk of developing certain diseases in childhood as well as adulthood&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#8211;5</span></a> These include metabolic and endocrine disorders such as diabetes mellitus&#44; dyslipidaemia and high blood pressure<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;10</span></a> as well as growth and developmental disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;4&#44;5</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Children born SGA can be classified into different categories&#58; symmetric SGA refers to children in whom both weight and height are affected&#44; while asymmetric SGA refers to children in whom either weight or height are affected&#44; but not both&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;3</span></a> This classification is important&#44; as it can guide the aetiological diagnosis and help predict the future risk of vascular disease<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> and the response to growth hormone replacement therapy&#44; with symmetric SGA associated with an increased frequency of short stature in adulthood<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> and asymmetric SGA affecting weight associated with an increased frequency of perinatal hypoglycaemia&#46;<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">When it comes to the hormone profile of children born SGA&#44; thyroid function is among the least studied axes in this population&#46; Thyroid hormones are essential during the foetal period and in the first months of life for normal development of the nervous system and adequate growth&#46; They also play a key role in bone&#44; heart and lung maturation throughout the foetal period&#46; Therefore&#44; low levels in the first months of life can increase the risk of intellectual disability&#44; short stature and metabolic disorders with irreversible consequences&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However&#44; from a clinical standpoint&#44; there are no specific signs or symptoms at birth that would allow suspicion of thyroid abnormalities&#44; which makes performance of screening tests for early diagnosis essential&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Several studies show that thyroid function in preterm infants is usually altered due to the lower gestational age&#44; resulting in increased requirements of thyroid hormones that in turn lead to higher serum concentrations of thyroid-stimulating hormone &#40;TSH&#41; and lower concentrations of triiodothyronine and thyroxine compared to term neonates&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a> This is why monitoring thyroid function is recommended in the first years of life in children born preterm&#46;<a class="elsevierStyleCrossRef" href="#bib0065"><span class="elsevierStyleSup">13</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">However&#44; few studies have analysed the thyroid hormone profile in SGA infants&#46; Some have found that there are differences compared to children with birth weights appropriate for gestational age &#40;AGA&#41;&#44; but few have focused on the levels of TSH and thyroxine&#44; and the published data are contradictory&#44; so at present there is no indication for specific follow-up or thyroid function monitoring in SGA children&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">The aim of our study was to compare thyroid function in a sample of SGA infants with thyroid function in other subsets of infants&#58; AGA infants and preterm infants&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Sample and methods</span><p id="par0050" class="elsevierStylePara elsevierViewall">For the purpose of sample selection&#44; we defined SGA as a birth weight and&#47;or length 2 or more SDs from the mean&#44; taking as reference the growth charts of the nationwide study of growth conducted in Spain in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">The inclusion criteria were&#58; Caucasian infant born between June 1&#44; 2013 and June 1&#44; 2015 in the department of labour and delivery of the Hospital Universitario Araba &#40;HUA&#41; meeting the case definition of SGA&#46; The exclusion criteria were&#58; non-white race&#44; infants product of a multiple pregnancy&#44; severe malformations&#44; death within 24&#8239;hours of birth or not meeting the case definition of SGA&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">Recruitment took place by consecutive sampling&#58; any infant born in the labour and delivery department of the HUA in the period under study that met the inclusion criteria was a candidate for participation&#46; We collected data on the following variables&#58; gestational age&#44; birth weight and length&#44; sex&#44; and serum TSH levels in SGA infants at different time points between age 4 months and 2 years&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">Subsequently&#44; we excluded cases with incorrectly documented or missing data for the variables under study&#44; and obtained a final sample of 38 infants&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Having obtained the sample&#44; we proceeded to the descriptive analysis of the explanatory variables using the mean&#44; SD and median&#46; We then compared TSH levels based on sex &#40;SGA boys vs SGA girls&#41;&#44; gestational age &#40;SGA infants born at term vs preterm&#44; defined as birth before 37 weeks&#41;&#44; SGA symmetry &#40;defining symmetric SGA as low weight and length and asymmetric SGA as alteration of only one of the two&#41; and by the age of the child born SGA at the time of collection of the blood sample &#40;age &#60; 6 months vs age &#62; 6 months&#41;&#46; We made compared means using 2-tailed tests&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">We also calculated the correlation coefficient for gestational age&#44; birth length and weight and age at the time of blood sample collection&#44; as these were quantitative variables&#44; with values close to 1 or &#8722;1 indicating a strong correlation and values nearing 0 a weak correlation&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">We also compared the results in our sample with the data published in other studies conducted in different populations&#46; First&#44; we compared our sample to a sample of healthy children born AGA in a study conducted by Cort&#233;s-Blanco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Specifically&#44; we grouped serum TSH values for healthy children from Zaragoza by age group&#58; 1 to 6 months &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;18&#41; and 6 months to 4 years &#40;<span class="elsevierStyleItalic">n</span>&#8239;&#61;&#8239;30&#41;&#46; We did the same with a sample of children born preterm in Barcelona in a study conducted by Clemente et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> This study published longitudinal data on serum TSH levels in a sample of healthy children born preterm &#40;between 30 and 35 weeks of gestation&#41;&#46; We compared samples using the Student <span class="elsevierStyleItalic">t</span> test for quantitative variables&#46;</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results of the descriptive analysis of the study sample</span><p id="par0085" class="elsevierStylePara elsevierViewall">The TSH levels in SGA children in our sample ranged from 1 to 9&#8239;&#956;U&#47;mL&#46; However&#44; as can be seen in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#44; the sample mean was 3&#46;68 &#956;U&#47;mL&#44; with a SD of 1&#46;88 &#956;U&#47;mL and a median of 3 &#956;U&#47;mL&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> presents the mean serum TSH values in children born SGA categorised based on the variables under study &#40;sex&#44; gestational age&#44; symmetry and age at time of sample collection&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Results by sex</span><p id="par0095" class="elsevierStylePara elsevierViewall">The mean TSH level in SGA boys was 4&#46;24 &#956;U&#47;mL&#44; with a SD of 1&#46;79&#8239;&#956;U&#47;mL and a median of 4&#8239;&#956;U&#47;mL&#46; In contrast&#44; the mean TSH values in SGA girls ranged from 1 to 8&#8239;&#956;U&#47;mL&#44; with a mean of 3 &#956;U&#47;mL&#44; a SD of &#177;1&#46;8&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">We found statistically significant differences based on sex in the serum TSH levels of children born SGA in the catchment population of the health area of Alava &#40;OSI Araba&#41; aged 3 months to 2 years &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46; Thus&#44; we can state that in our sample of children born SGA&#44; boys had higher serum TSH levels compared to girls&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Results by gestational age group</span><p id="par0105" class="elsevierStylePara elsevierViewall">The mean TSH level in children born SGA at term was 3&#46;43&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;78&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46; In contrast&#44; children born SGA and preterm had a mean serum TSH level of 4&#46;46&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;86&#8239;&#956;U&#47;mL and a median of 4&#46;5&#8239;&#956;U&#47;mL&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">The correlation coefficient for the association between the gestational age of SGA infants and their serum TSH values was &#8722;0&#46;19&#44; indicative of a weak inverse correlation&#46; That is&#44; the lower the gestational age at birth&#44; the higher the serum TSH levels in the first months of life&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Results based on anthropometric measurements</span><p id="par0115" class="elsevierStylePara elsevierViewall">The mean TSH level in the symmetric SGA group was 3&#46;88&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;62&#8239;&#956;U&#47;mL and a median of 5&#8239;&#956;U&#47;mL&#46; In contrast&#44; in the asymmetric SGA group the mean was 3&#46;71&#8239;&#956;U&#47;mL&#44; with a SD of 2&#46;02&#8239;&#956;U&#47;mL and a median of 3&#46;5&#8239;&#956;U&#47;mL&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">The correlation coefficients for the association between the serum levels of TSH in SGA children and their birth length and weight were &#8722;0&#46;15 and &#8722;0&#46;12&#44; respectively&#46; In other words&#44; a low birth length&#47;weight seems to predispose infants to decreased serum TSH levels in the early months of life&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Results based on age of children born SGA</span><p id="par0125" class="elsevierStylePara elsevierViewall">The proportion of children born SGA aged less than 6 months was 58&#37;&#44; compared to 42&#37; of children born SGA aged more than 6 months&#46; The mean TSH level in SGA infants aged less than 6 months was 3&#46;86&#8239;&#956;U&#47;mL&#44; with a SD of 1&#46;74&#8239;&#956;U&#47;mL and a median of 4&#8239;&#956;U&#47;mL&#46; The mean TSH level in children born SGA aged more than 6 months was 3&#46;4&#8239;&#956;U&#47;mL&#44; with a SD of 2&#46;16&#8239;&#956;U&#47;mL and a median of 3&#8239;&#956;U&#47;mL&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in TSH levels between children born SGA aged less than 6 months and those aged more than 6 months at the time of collection of the blood sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46; Nevertheless&#44; the correlation coefficient for the association between the current age of children born SGA and their serum TSH levels was &#8722;0&#46;16&#46; Thus&#44; serum TSH levels in children born SGA tend to decrease with age&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Results of comparing TSH levels in the study sample with other paediatric samples</span><p id="par0135" class="elsevierStylePara elsevierViewall">First&#44; we compared the results in our sample with data obtained in healthy children in Zaragoza published by Cort&#233;s-Blanco et al&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> On one hand&#44; we compared serum TSH levels in SGA infants aged less than 6 months in our sample with those of healthy children from Zaragoza aged 1 to 6 months&#44; and on the other&#44; we compared the levels in children born SGA in our sample aged more than 6 months with those in healthy children from Zaragoza aged 6 months to 4 years&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in serum TSH levels in SGA infants in our sample compared to healthy infants aged 1 to 6 months in the Zaragoza sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#62;&#8239;0&#46;05&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In contrast&#44; we did find statistically significant differences in serum TSH levels between children born SGA aged more than 6 months in our sample and the healthy children aged 6 months to 4 years in the Zaragoza sample &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41;&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Then&#44; we compared the results in our sample with data obtained in the study of healthy children born preterm conducted in Barcelona by Clemente et al&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a> To do so&#44; we compared the groups of infants aged 4 and 6 months in the Barcelona study to the group of SGA infants aged less than 6 months in our sample&#44; and also the groups aged 9 and 12 months in the Barcelona study with children born SGA aged more than 6 months in our sample&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">We did not find statistically significant differences in TSH levels in the comparison of children in either of these age groups&#46;</p></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Discussion</span><p id="par0160" class="elsevierStylePara elsevierViewall">Our study found statistically significant differences in the sample of children born SGA based on sex&#46; It seems that boys born SGA tend to have higher serum levels of TSH compared to girls&#46; This is consistent with the results of several studies that suggest that male infants are at increased risk of transient hyperthyrotropinaemia and transient hypothyroxinaemia in the early years of life&#46;<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">18&#8211;20</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">On the other hand&#44; we identified gestational age at birth as a possible predictor of hyperthyrotropinaemia in children born SGA in the OSI Araba&#44; although the association between these variables was weak&#46; This was similar to the results of previous studies that have found differences in TSH levels between term and preterm infants&#44; with a higher risk of hypothyroidism in the latter&#46;<a class="elsevierStyleCrossRefs" href="#bib0060"><span class="elsevierStyleSup">12&#44;13&#44;21&#44;22</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">When it comes to anthropometric values&#44; some studies in the previous literature suggest that low birth weight is a risk factor for thyroid disorders&#44;<a class="elsevierStyleCrossRefs" href="#bib0105"><span class="elsevierStyleSup">21&#44;23</span></a> while others did not find an association between anthropometric values at birth and TSH levels in childhood&#46;<a class="elsevierStyleCrossRef" href="#bib0100"><span class="elsevierStyleSup">20</span></a> In our study&#44; we found a weak association between the birth weight and length and TSH values&#44; although we did not find statistically significant differences based on the symmetry of SGA&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">We ought to highlight that TSH values varied between groups&#44; yet they were in the normal range in 50&#37; of the cases&#44; so it may be worth assessing the clinical relevance of the observed differences&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall">As for the comparison of our sample to samples in other infant populations&#44; we found that children born SGA in the OSI Araba had higher serum levels of TSH in the first years of life compared to healthy children in Zaragoza&#46; Thus&#44; while serum TSH levels tended to decrease from 6 months of age in children born AGA&#44; they remained elevated for longer in children born SGA in the OSI Araba&#46; The evidence on the association between SGA and thyroid disorders is insufficient&#44; but previous studies have found that a birth weight of less than 2000&#8239;g was associated with an increased risk of hyperthyrotropinaemia in the long term&#44;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#44;24</span></a> an elevation that could in turn increase the risk of developing hypothyroidism and cardiovascular problems at later ages&#46;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">On the other hand&#44; when we compared the sample of SGA infants in our study to the sample of preterm infants&#44; we did not find statistically significant differences at any age&#46; Therefore&#44; we may conclude that the risk of thyroid disorders is similar in SGA infants and in preterm infants&#46; Several studies have found that preterm SGA infants have higher serum TSH levels compared to preterm AGA infants&#44;<a class="elsevierStyleCrossRef" href="#bib0070"><span class="elsevierStyleSup">14</span></a> and therefore thyroid function in these infants should be monitored in the first months of life&#46;</p><p id="par0190" class="elsevierStylePara elsevierViewall">The main limitation of the study was the lack of a group of AGA infants born in the OSI Araba in the same time interval and with collection of data under the same circumstances for comparison with the SGA sample&#46; Due to this lack&#44; we collected information from studies conducted on AGA children in other regions&#44; which may come from populations whose characteristics differ from the catchment population of the OSI Araba&#46; We also ought to mention that the sample size was small&#44; which may affect the validity of the results&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conclusion</span><p id="par0195" class="elsevierStylePara elsevierViewall">As noted above&#44; the factors that seem to have an effect on the development of increased TSH levels in infants born SGA are&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">-</span><p id="par0200" class="elsevierStylePara elsevierViewall">Male sex&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">-</span><p id="par0205" class="elsevierStylePara elsevierViewall">Lower gestational age at birth seems to be associated with an increased risk of thyroid disorders&#46;</p></li><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0210" class="elsevierStylePara elsevierViewall">A low birth length and&#47;or weight relative to the reference population seems to increase the risk of thyroid disorders in SGA infants&#46;</p></li></ul></p><p id="par0215" class="elsevierStylePara elsevierViewall">The main conclusion of our study is that SGA infants have higher thyroid hormone requirements in the long term&#44; similar to those of preterm infants&#46; That is&#44; our findings suggest that the risk of hyperthyrotropinaemia in SGA infants is similar to the risk in preterm infants&#44; possibly leading to an increased frequency of thyroid abnormalities that may give rise to chronic and irreversible diseases in the future&#46;</p><p id="par0220" class="elsevierStylePara elsevierViewall">Taking these similarities into account&#44; we propose the following&#58;<ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0225" class="elsevierStylePara elsevierViewall">Screen TSH levels in SGA infants&#44; with monitoring of thyroid function as needed in male infants and infants born at lower gestational ages or with very low birth weight or length&#44; similar to the follow-up performed in preterm infants&#46;</p></li><li class="elsevierStyleListItem" id="lsti0025"><span class="elsevierStyleLabel">-</span><p id="par0230" class="elsevierStylePara elsevierViewall">Assess the need for thyroid hormone replacement therapy in SGA infants at increased risk of developing thyroid disorders or those that do not exhibit adequate catch-up growth&#46;</p></li></ul></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Funding</span><p id="par0235" class="elsevierStylePara elsevierViewall">The study was funded by a global medical grant from <span class="elsevierStyleGrantSponsor" id="gs0005">Pfizer</span>&#44; awarded in 2012&#46;</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Conflicts of interest</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors received a global grant from Pfizer for performance of this study in year 2012&#46;</p></span></span>"
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      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Several studies conclude that small for gestational age &#40;SGA&#41; children have a higher number of comorbidities&#44; as well as a different hormonal profile compared to those with appropriate weight for gestational age &#40;AGA&#41;&#46; Thyroid hormones play an important role in growth and neurocognitive development&#46; Thyroid function in SGA children is still not completely known&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Objectives</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">To compare the thyroid function of SGA children during the first 2 years of life with that in publications on thyroid function in other groups of infants&#44; such as AGA and premature children&#44; using the same methodology&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">A cohort of 38 SGA children was obtained&#44; in which the thyrotropin &#40;TSH&#41; values in blood were measured at different points in the development of the SGA child&#46; The results were compared with a population of AGA children from Zaragoza and a population of premature children from Barcelona by comparing the means using a 2-tailed test&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">A statistically significant difference &#40;<span class="elsevierStyleItalic">P</span>&#8239;&#60;&#8239;0&#46;05&#41; was observed between the SGA children in our study and the AGA children older than 6 months&#44; but not between the SGA children of the study and the population of premature infants&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">SGA children have higher TSH values compared to AGA children older than 6 months&#46; Therefore&#44; it seems reasonable to establish a screening and a follow-up protocol in those SGA with high risk to develop thyroid dysfunction&#46;</p></span>"
        "secciones" => array:5 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction"
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          1 => array:2 [
            "identificador" => "abst0010"
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          2 => array:2 [
            "identificador" => "abst0015"
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      "es" => array:3 [
        "titulo" => "Resumen"
        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">M&#250;ltiples estudios concluyen que los ni&#241;os peque&#241;os para la edad gestacional &#40;PEG&#41; tienen un n&#250;mero mayor de comorbilidades&#44; as&#237; como un perfil hormonal diferente respecto a los ni&#241;os con un peso adecuado para la edad gestacional &#40;PAEG&#41;&#46; Las hormonas tiroideas juegan un papel importante en el crecimiento y en el desarrollo neurocognitivo&#46; La funci&#243;n tiroidea en los ni&#241;os PEG es&#44; hoy en d&#237;a&#44; incierta&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Objetivos</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">El objetivo de este estudio es comparar la funci&#243;n tiroidea de los ni&#241;os PEG durante los 2 primeros a&#241;os de vida con publicaciones sobre funci&#243;n tiroidea en otros grupos de lactantes &#40;PAEG y prematuros&#41; que utilicen la misma metodolog&#237;a&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">M&#233;todos</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Se obtuvo una cohorte de 38 ni&#241;os PEG&#44; en los cuales se midieron los valores de TSH en sangre en distintos momentos del desarrollo del ni&#241;o PEG&#46; Los resultados se compararon con una poblaci&#243;n de ni&#241;os PAEG de Zaragoza y una poblaci&#243;n de ni&#241;os prematuros de Barcelona mediante pruebas de comparaci&#243;n de medias de contraste bilateral&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Resultados</span><p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Se ha observado una diferencia estad&#237;sticamente significativa &#40;p&#8239;&#60;&#8239;0&#44;05&#41; entre los ni&#241;os PEG de nuestro estudio y los ni&#241;os PAEG mayores de 6 meses&#44; no as&#237; entre los PEG del estudio y la poblaci&#243;n de prematuros&#46;</p></span> <span id="abst0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Conclusiones</span><p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">Los ni&#241;os PEG tienen valores de TSH superiores respecto a los ni&#241;os PAEG mayores de 6 meses&#46; Por lo tanto&#44; parece razonable establecer un cribado y un protocolo de seguimiento en los PEG de mayor riesgo&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as&#58; Gonz&#225;lez IF&#44; Maeso-M&#233;ndez S&#44; Miranda AS&#44; del Hoyo Moracho M&#44; Bl&#225;zquez IL&#44; L&#243;pez ID&#46; Diferencias en la funci&#243;n tiroidea de los peque&#241;os para la edad gestacional y los de peso adecuado&#46; &#191;Es normal la funci&#243;n tiroidea de los reci&#233;n nacidos peque&#241;os para la edad gestacional&#63; An Pediatr &#40;Barc&#41;&#46; 2021&#59;95&#58;330&#8211;335&#46;</p>"
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          "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Thyroid-stimulating hormone levels in children born small for gestational age between 4 months and 2 years of life&#46;</p>"
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      "titulo" => "References"
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        0 => array:2 [
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ISSN: 23412879
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Anales de Pediatría (English Edition)
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