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one of the main factors that determine exercise capacity is the maximum oxygen uptake &#40;VO<span class="elsevierStyleInf">2</span> peak&#41;&#46; Studies on adults and adolescents born extremely preterm have shown that peak VO<span class="elsevierStyleInf">2</span> values may be within the normal range&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;8</span></a> However&#44; some authors have reported that decreased pulmonary diffusion capacity or altered pulmonary function may compromise the aerobic capacity in preterm children and adolescents&#44; with a decreased peak VO<span class="elsevierStyleInf">2</span> or distance covered being observed on the cardiopulmonary exercise test &#40;CPET&#41; that is performed on a treadmill or cycle ergometer&#46;<a class="elsevierStyleCrossRefs" href="#bib0190"><span class="elsevierStyleSup">8&#8211;10</span></a> Hence&#44; the actual aerobic capacity and the associated factors with it in school age preterm children with very low birth weight &#40;VLBW&#41; remain controversial&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Therefore&#44; the present study was conducted to evaluate the aerobic capacity in school age preterm children with VLBW and its associated factors&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">A cross-sectional study was conducted on two groups of 6&#8211;9-year-old children of both sex&#44; recruited between February 2013 and April 2015&#46; The preterm group consisted of children born with gestational age of &#60;37 weeks and birth weight of &#60;1500<span class="elsevierStyleHsp" style=""></span>g&#44; accompanied at the multidisciplinary outpatient follow-up clinic of the institution&#46; Term group consisted of children born with gestational age of &#8805;37 weeks&#44; both sexes&#44; without respiratory impairment or outpatient follow-up&#44; and being relatives or friends of premature children attended in our outpatient clinic&#46; Children with congenital malformations&#59; neuromuscular diseases&#59; neurological&#44; visual&#44; and&#47;or hearing disorders&#59; and&#47;or other problems that may lead to difficulties on the execution of the test were excluded&#46; Children with signs or symptoms of acute or chronic respiratory disease in the last 2 weeks or those with abnormal hemodynamic condition at rest were also excluded&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">11</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">This study followed the declaration of Helsinki&#46; The Ethics and Research Committee of the Institution approved this study &#40;Protocol&#58; 173&#46;275&#47;12&#41;&#46; The consent form was signed by the parents or guardians of the children&#44; and the assent form was signed by the children&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Included children were evaluated according to a clinical questionnaire answered by their parents&#44; and anthropometric variables were evaluated before cardiopulmonary exercise test&#46; Additionally&#44; the clinical records of preterm group during the neonatal period and their clinical status after discharge from the neonatal unit were also collected&#46; In the term group&#44; neonatal data were obtained from the birth card complemented by an interview with parents and&#47;or legal guardians conducted by the researcher&#46; The socioeconomic status and frequency of weekly physical activity of the child were evaluated through a questionnaire answered by the parents or guardians on the scheduled day of the test&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">12</span></a> The child&#39;s Body Mass Index &#40;BMI&#41; during the recruitment was determined according to the recommendations of the World Health Organization&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">13</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">A cardiopulmonary exercise test &#40;CPET&#41; and a symptom-limited treadmill test with a rapid incremental protocol and individualized increase in load was used to evaluate the aerobic capacity&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> The slope was calculated individually<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">15</span></a> based on the fixed velocity of 3&#46;5<span class="elsevierStyleHsp" style=""></span>mph &#40;children aged between 6 and 7 years&#41; and 4&#46;0<span class="elsevierStyleHsp" style=""></span>mph &#40;those aged between 8 and 9 years&#41; and predicted maximum VO<span class="elsevierStyleInf">2</span> &#40;VO<span class="elsevierStyleInf">2</span> max&#41;&#46; For each age group&#44; VO<span class="elsevierStyleInf">2</span> max was calculated according to child&#39;s sex and weight&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">Prior to the test&#44; the child remained seated for 5<span class="elsevierStyleHsp" style=""></span>min&#44; and then vital signs &#40;blood pressure&#44; heart rate&#44; and peripheral oxygen saturation&#41; and degree of dyspnea were evaluated&#46; The non-rebreathing valve face mask &#40;Hans Rudolph&#44; Kansa&#41; of the gas analyzer &#40;K4b2&#44; Cosmed&#44; Pavonadi Albano&#44; It&#225;lia&#41; was placed on the face of the child&#44; and the device analyzer was placed in front of the treadmill in order not to impose a workload during the CPET&#46; The gas analyzer was previously calibrated at the beginning of the tests according to the manufacturer&#39;s recommendations&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">The CPET was started with 3-min warm-up phase<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> maintaining the speed of 1&#46;0<span class="elsevierStyleHsp" style=""></span>mph without grade and during the last minute&#44; the speed was raised according to the child&#39;s age&#46; During the exercise phase&#44; the grade was increased by 2&#37; every minute until a maximum grade of 10&#37;&#46; If at this grade the child did not meet the maximum effort criteria&#44;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;18</span></a> the speed was increased by 0&#46;5<span class="elsevierStyleHsp" style=""></span>mph every minute until meeting the interruption criteria&#46; In the recovery phase&#44; the child remained walking for 5<span class="elsevierStyleHsp" style=""></span>min in the warm-up speed and grade&#46;</p><p id="par0050" class="elsevierStylePara elsevierViewall">During the test&#44; expired gases were collected breath-by-breath&#44; and data recording was filtered every 15<span class="elsevierStyleHsp" style=""></span>s&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">19</span></a> Variables were analyzed for two periods&#58; at rest and at the peak of the CPET&#44; considering the values during the last 15&#8211;30<span class="elsevierStyleHsp" style=""></span>s at the end of the test&#44; based on arithmetic means&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">The anaerobic threshold &#40;AT&#41; was obtained using the V-slope method<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">16</span></a> after the concordance of two previously trained observers&#46; The interpretation of anaerobic threshold of gas exchange &#40;VO<span class="elsevierStyleInf">2</span>&#64;LA&#41; was obtained based on the relationship between anaerobic threshold of gas exchange and percentage of maximum oxygen consumption predicted according to age &#40;VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37; VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46;&#41;&#46;</p><p id="par0060" class="elsevierStylePara elsevierViewall">To assess the aerobic capacity&#44; the following cardiovascular&#44; respiratory&#44; and metabolic variables were analyzed&#58; oxygen pulse &#40;PuO<span class="elsevierStyleInf">2</span>&#41; obtained by the ratio &#916;FC&#47;&#916;VO<span class="elsevierStyleInf">2</span>&#59; &#37;HR max&#59; tidal volume and inspiratory capacity ratio &#40;TV&#47;IC peak&#41;&#59; VO<span class="elsevierStyleInf">2</span> peak&#44; and the relationship between anaerobic threshold of gas exchange and percentage of maximum oxygen consumption predicted according to age &#40;VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37;VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46;&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#44;19&#44;20</span></a></p><p id="par0065" class="elsevierStylePara elsevierViewall">In order to consider the maximum CPET&#44; the child was required to meet three of the following criteria&#58; maximum HR &#8805;90&#37; of the predicted HR according to age&#59; signs of exhaustion&#44; gaseous exchange ratio &#40;<span class="elsevierStyleItalic">R</span>&#41; of &#62;1&#46;0&#44; and VO<span class="elsevierStyleInf">2</span> maximum of &#8805;85&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">14&#44;18</span></a> In addition&#44; CPET was discontinued if some of the following intercurrences were identified&#58; request for discontinuation by the child&#44; failure of the monitoring device&#44; pulse oxygenation decrease of &#8805;4&#37; compared to the resting phase&#46;<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">16&#44;21</span></a></p><p id="par0070" class="elsevierStylePara elsevierViewall">The same protocol was used in all children&#44; and a pulmonologist and&#47;or pediatrician was present in the laboratory during the tests&#44; together with the researchers of the study&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Statistical analysis</span><p id="par0075" class="elsevierStylePara elsevierViewall">Sample size &#40;G-Power 3&#46;0&#46;10&#41; was calculated according to VO<span class="elsevierStyleInf">2</span> difference of 7&#46;3<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">14</span></a> between groups&#44; showed the need of 22 participants in each group&#44; assuming an alpha error of 0&#46;05 and beta of 0&#46;80&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">Numerical variables were compared using Student&#39;s <span class="elsevierStyleItalic">t</span> test &#40;normal distribution&#41; or Mann&#8211;Whitney test &#40;non-normal distribution&#41;&#46; Categorical variables were compared using the chi-square test or Fisher&#39;s exact test&#46; The normality of variables was evaluated using the Kolmogorov&#8211;Smirnov test&#46;</p><p id="par0085" class="elsevierStylePara elsevierViewall">Regarding the analysis of factors associated with children&#39;s aerobic capacity&#44; univariate and multivariate linear regressions were used considering the cardiovascular&#44; respiratory&#44; and metabolic variables related to an individual&#39;s aerobic capacity as dependent variables&#46; Variables with statistical &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;2&#41; and clinical significance in the univariate regression were included in the multiple linear regression models&#44; excluding collinear variables in the same model&#46; Statistical analyses were performed using the SPSS for Win&#47;v&#46;17&#46;0 program &#40;IBM SPSS Statistics&#44; Somers&#44; NY&#41;&#44; and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 was considered statistically significant&#46;</p></span></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Results</span><p id="par0090" class="elsevierStylePara elsevierViewall">During the study period&#44; 95 preterm children were attended in our outpatient clinic&#44; however 33 &#40;34&#46;7&#37;&#41; of them did not meet inclusion criteria&#46; Then&#44; 62 preterm children were eligible and 34 term children &#40;relatives or preterm children&#39;s friends&#41; were invited to the study but at the end of the study 34 preterm and 32 term children finished the exercise test &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0095" class="elsevierStylePara elsevierViewall">The 22 &#40;35&#46;5&#37;&#41; eligible preterm children &#40;but not included&#41; were compared to 34 included preterm children&#44; and no difference in the demographic and clinical characteristics was observed&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">The mean birth weight and gestational age were 3072<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>609<span class="elsevierStyleHsp" style=""></span>g and 38&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;4 weeks in the term group&#44; and 1131<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>228<span class="elsevierStyleHsp" style=""></span>g and 29&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;5 weeks in the preterm group&#46; Clinical and demographic characteristics of both groups were similar&#44; except for the lower <span class="elsevierStyleItalic">Z</span> score height for age and an increased need for hospitalization in the preterm group &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0105" class="elsevierStylePara elsevierViewall">During the CPET&#44; all children reached the maximum speed and grade recommended in the protocol&#44; and in some cases&#44; the speed was also increased meeting all the criteria for the maximum CPET&#46; Despite this&#44; the speed variation of the treadmill was similar between groups &#40;preterm group&#58; 23&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>13&#46;5&#37; vs&#46; term&#58; 26&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>9&#46;6&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;312&#41;&#46; All children presented sinus rhythm on the electrocardiogram from the beginning until the recovery phase&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Aerobic pattern was similar between groups according to cardiovascular&#44; respiratory&#44; and metabolic variables&#44; as described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">Multiple linear regression analyses for possible factors associated with aerobic capacity are shown in <a class="elsevierStyleCrossRefs" href="#tbl0015">Tables 3&#8211;5</a>&#46; The &#37;HR max was positively associated to the dependence of O<span class="elsevierStyleInf">2</span> for more than 28 days and overweight&#47;obesity&#46; Oxygen pulse was positively associated to <span class="elsevierStyleItalic">Z</span> score height&#47;age and negatively to female sex&#46; In the same way&#44; VO<span class="elsevierStyleInf">2</span> peak &#40;mL&#47;kg&#47;min&#41; was negatively associated to female and overweight&#47;obese but positively to birth weight &#60; 1000 g&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><elsevierMultimedia ident="tbl0020"></elsevierMultimedia><elsevierMultimedia ident="tbl0025"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">The following respiratory and metabolic parameters&#44; the relationship between VC&#47;IC peak&#44; VO<span class="elsevierStyleInf">2</span> in absolute values&#44; and VO<span class="elsevierStyleInf">2</span> LA&#47;&#37; VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46;&#44; did not show significant association in the univariate linear regression&#59; thus&#44; they were not included in the multiple regression analysis&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Discussion</span><p id="par0125" class="elsevierStylePara elsevierViewall">The present study showed that children aged between 6 and 9 years with VLBW had similar aerobic capacity to children born at term&#46; Nevertheless&#44; after adjusting the covariates&#44; these parameters were associated with the history of bronchopulmonary dysplasia&#44; birth weight of &#60;1000<span class="elsevierStyleHsp" style=""></span>g&#44; sex and factors related to body growth&#44; such as <span class="elsevierStyleItalic">Z</span> score height for age and overweight&#47;obesity&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The results in the univariate analysis demonstrate that at school age&#44; preterm children had an aerobic capacity similar to that of full-term children&#46; Some hypotheses may explain this similarity as evidenced by the fact that the included preterm children were born after undergoing measures to reduce mortality and neonatal morbidity&#44; such as the use of exogenous surfactant&#44; antenatal corticosteroids&#44; and gentle ventilation modes&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">22</span></a> These measures have certainly improved the development and lung growth of preterm infants&#44; reducing the severity of pulmonary complications such as bronchopulmonary dysplasia&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">23</span></a> Another hypothesis would be the low frequency of physical activity of the children in both groups&#44; which may have influenced their aerobic responses&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> These children had a very low physical activity &#40;approximately 3&#46;5<span class="elsevierStyleHsp" style=""></span>h&#47;week in both groups&#41; when compared to the recommended physical activity for this group age &#40;60<span class="elsevierStyleHsp" style=""></span>min daily&#41; to prevent sedentary lifestyle&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">24</span></a> Additionally&#44; the final hypothesis is the possibility of these preterm children to be like adults with chronic obstructive pulmonary disease&#44; which increases the work of respiratory muscles during exercise to maintain or reach their aerobic capacity&#44; i&#46;e&#46;&#44; within the normal range&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">25</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Although the results of physical capacity seemed similar between groups&#44; other factors were important according to the multivariate regression analysis&#46; The presence of bronchopulmonary dysplasia increased by 3&#37; maximum heart rate for age&#46; This association could be explained by reduced ventilatory reserve and decreased lung diffusion capacity in preterm children&#44; which can be supplied by increased cardiovascular system demand during exercise&#44; represented by the increase in the &#37;HR max&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;10</span></a> Moreover&#44; children with history of pulmonary disease during the neonatal period have greater degree of respiratory impairment&#46; Maybe&#44; if we have had a greater sample of preterm children with bronchopulmonary dysplasia&#44; the difference in cardiopulmonary conditions could possibly be showed&#46;</p><p id="par0140" class="elsevierStylePara elsevierViewall">Other important neonatal variable was associated with physical capacity as lower weight of birth&#46; Birth weight of &#60;1000<span class="elsevierStyleHsp" style=""></span>g increased the VO<span class="elsevierStyleInf">2</span> peak in approximately 4<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min&#46; It is known that preterm infants&#44; especially the extremely ones may present air trapping during exercise&#44; which involves pulmonary mechanics in an indirect way&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">5</span></a> In the present study&#44; premature birth or BPD were not associated with any ventilatory variable&#44; such as VC&#47;IC peak&#44; however&#44; we cannot affirm that preterm infants do not present ventilatory or pulmonary mechanics alterations during exercise&#44; since these variables were not evaluated by spirometry&#44; being a limitation of the present study&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In addition to factors inherent to prematurity&#44; sex and factors related to body growth&#44; such as <span class="elsevierStyleItalic">Z</span>-score for height&#47;age and overweight&#47;obesity seemed to be associated with cardiovascular and metabolic conditions during exercise&#46; The nutritional status&#44; more specifically&#44; being obese or overweight&#44; reduced the VO<span class="elsevierStyleInf">2</span> peak by approximately 6<span class="elsevierStyleHsp" style=""></span>mL&#47;kg&#47;min and increased by about 3&#37; &#37;HR for age&#46; Zwiren<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">26</span></a> describes that the peak VO<span class="elsevierStyleInf">2</span> expectedly increases based on an individual&#39;s growth&#59; however&#44; when excessive body weight gain occurs&#44; as in the case of overweight or obesity&#44; the association may be negative because the percentage of body fat is higher than body growth&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">27</span></a> Our results are consistent with the study of Welsh et al&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">8</span></a> that studied preterm children aged between 10 and 11 years by cycloergometer test&#46; They also showed that impaired body growth was associated with decreased aerobic capacity&#46; Our results show the importance of a good monitoring of nutritional status&#44; especially in relation to obesity and overweight during follow-up of these premature infants during childhood&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Another important factor that presented a positive association was oxygen pulse&#46; Despite this association&#44; it did not clinically alter the PuO<span class="elsevierStyleInf">2</span> behavior in these children&#46; This association was expected as studies had demonstrated the association between increased VO2 peak and body growth&#46; As already known&#44; PuO<span class="elsevierStyleInf">2</span> is dependent on VO<span class="elsevierStyleInf">2</span>&#44; which were expected to increase together&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">26&#44;28</span></a></p><p id="par0155" class="elsevierStylePara elsevierViewall">Finally&#44; the last factor associated with cardiovascular and metabolic parameters was sex&#44; which demonstrated that being female reduced the PuO<span class="elsevierStyleInf">2</span> and VO<span class="elsevierStyleInf">2</span> peak &#40;mL&#47;kg&#47;min&#41;&#46; As previously demonstrated&#44; PuO<span class="elsevierStyleInf">2</span> is dependent on the VO<span class="elsevierStyleInf">2</span> peak&#44; as girls had lesser PuO<span class="elsevierStyleInf">2</span>&#44; may be associated with the lower VO<span class="elsevierStyleInf">2</span> peak presented&#46;<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">26&#44;27</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Ventilatory reserve expressed as TV&#47;IC peak ratio is expected to be associated with some independent variables because of the presence of BPD or prematurity itself&#44; as previously reported in the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;4&#44;8</span></a> This association was expected because preterm infants may present pulmonary hyperinflation&#44; which would reduce the tidal volume and inspiratory capacity to exercise&#46; Then&#44; preterm infants in their study sample possibly did not present significant pulmonary sequelae due to BPD or prematurity per se&#46;</p><p id="par0165" class="elsevierStylePara elsevierViewall">Regarding metabolic parameters&#44; absolute values of VO<span class="elsevierStyleInf">2</span> and VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37;VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46; ratio<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> studies had shown controversial results&#44; which were expected to be not associated with preterm parameters&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">2&#44;28&#44;29</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">The varied results presented in our study and the literature can be explained by the inclusion criteria&#46; Most studies included heterogeneous population<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">4</span></a> and different types of protocols and ergometers that could also influence the results&#46;<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">4&#44;9</span></a> Thus&#44; including children with homogeneous age group and similar growth and developmental characteristics as in our study could increase the internal validity and reliability of the presented data&#44; because studies have shown that sexual maturation may play an important role in the performance of exercise capacity in preterm children&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">30</span></a> Although the groups presenting statistical difference in the <span class="elsevierStyleItalic">Z</span> score height&#47;age ratio&#44; their mean values are within normal limits&#44; showing the similarity of growth and development between groups&#46; The application of an individualized CPET loading protocol in the treadmill also favored the validity of results&#44; because this type of ergometer protocol can better identify the peak VO<span class="elsevierStyleInf">2</span> in children&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">17</span></a> Aside from this factor&#44; controlling the weekly physical activity of children&#44; which would be a possible confounding factor&#44; increased the quality of results in this study&#46;</p><p id="par0175" class="elsevierStylePara elsevierViewall">The percentage of loss and the number of children that had not met criteria to participate to the study could be a limitation in this study and it is possible that if we had a larger sample we could reach more precise conclusions&#46; However&#44; the analysis of the main demographic and clinical characteristics comparing the included and not included preterm children showed no significant difference&#44; especially in relation to variables that could be biased&#44; such as BPD and VLBW&#46; Another limitation was the inclusion of a convenience sample&#44; excluding preterm children with severe motor and cognitive sequelae&#46; Those with severe neurodevelopmental impairments are also possibly the extremely preterm ones and with higher occurrence of bronchopulmonary dysplasia&#44; and thus they could show a decreased aerobic capacity&#46; However&#44; these patients cannot be included due to the characteristics required in the protocol&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Conclusions</span><p id="par0180" class="elsevierStylePara elsevierViewall">Preterm children with VLBW at school age showed aerobic capacity similar to that of full-term children&#46; However&#44; the intensity of responses during the cardiopulmonary exercise test was associated with sex&#44; BPD&#44; lower birth weight and factors related to body growth&#44; demonstrating the influence of neonatal factors and body growth on the aerobic capacity in these children&#46;</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Funding</span><p id="par0185" class="elsevierStylePara elsevierViewall">This work was supported by the <span class="elsevierStyleGrantSponsor" id="gs1">Brazilian Government Scholarship&#8212;CAPES&#8212;Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior</span>&#44; in which Sabrina Pinheiro Tsopanoglou was supported by as a postgraduate student&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Authorship</span><p id="par0190" class="elsevierStylePara elsevierViewall">Tsopanoglou S&#46;P&#46;&#44; Davidson J&#46;&#44; Dourado V&#46;Z&#46;&#44; Goulart A&#46;L&#46;&#44; Barros M&#46;C&#46;M&#46;&#44; Santos A&#46;M&#46;N&#46;&#58; the conception and design of the study&#59; acquisition of data&#59; analysis and interpretation of data&#59; drafting the article&#59; revising it critically for important intellectual content and final approval of the version to be submitted&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflict of interests</span><p id="par0195" class="elsevierStylePara elsevierViewall">The authors declare no conflict of interests&#46;</p></span></span>"
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    "fechaRecibido" => "2019-03-13"
    "fechaAceptado" => "2019-05-26"
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          "palabras" => array:3 [
            0 => "Preterm children"
            1 => "Very low birth weight"
            2 => "Aerobic capacity"
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          "clase" => "keyword"
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          "palabras" => array:3 [
            0 => "Ni&#241;os prematuros"
            1 => "Muy bajo peso al nacer"
            2 => "Capacidad aer&#243;bica"
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    "resumen" => array:2 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Respiratory morbidities of preterm infants can cause significant ventilatory impairment thus compromising the aerobic capacity in childhood and adolescence&#46; Therefore&#44; the present study was conducted to evaluate the aerobic capacity in school age preterm children with VLBW and its associated factors&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was conducted among preterm born with VLBW and term children&#44; both aged 6&#8211;9 years&#46; An individualized symptom-limited treadmill testing protocol performed aerobic capacity&#46; Measured variables&#58; oxygen pulse &#40;PuO<span class="elsevierStyleInf">2</span>&#41;&#44; percentage of maximum heart rate for age &#40;&#37;HR max&#41;&#44; tidal volume&#47;inspiratory capacity ratio &#40;TV&#47;IC&#41;&#44; oxygen consumption &#40;VO<span class="elsevierStyleInf">2</span>&#41; peak&#44; and the ratio of the anaerobic threshold of gas exchange to the predicted percentage of maximum VO<span class="elsevierStyleInf">2</span> &#40;VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37;VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46;&#41; were compared between groups&#46; Univariate and multiple linear regression analyses were used to determine the factors associated with aerobic capacity&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Thirty-four preterm and 32 term children were included&#46; Similar VO<span class="elsevierStyleInf">2</span> peak and the other variables were observed&#46; The development of bronchopulmonary dysplasia &#40;BPD&#41; and being obese&#47;overweight was positively associated with &#37;HR max&#46; The <span class="elsevierStyleItalic">Z</span>-score for height&#47;age and birth weight &#60;1000<span class="elsevierStyleHsp" style=""></span>g was positively associated with PuO<span class="elsevierStyleInf">2</span> and peak VO<span class="elsevierStyleInf">2</span>&#44; and negatively associated with overweight&#47;obesity and female sex&#46;</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Aerobic capacity was similar in both groups&#46; Sex&#44; development of BPD&#44; birth weight &#60;1000<span class="elsevierStyleHsp" style=""></span>g and factors related to body growth&#44; such as <span class="elsevierStyleItalic">Z</span>-score for height&#47;age and overweight&#47;obesity&#44; were associated with aerobic capacity in preterm children with VLBW&#46;</p></span>"
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            "identificador" => "abst0010"
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        "resumen" => "<span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introducci&#243;n</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Las enfermedades respiratorias de los ni&#241;os prematuros pueden causar importantes impedimentos ventilatorios que comprometen la capacidad aer&#243;bica en la infancia y en la adolescencia&#46; El presente estudio se llev&#243; a cabo para evaluar la capacidad aer&#243;bica de ni&#241;os prematuros en edad escolar de muy bajo peso al nacer &#40;BPN&#41; y los factores asociados&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">M&#233;todos</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Se llev&#243; a cabo un estudio transversal con ni&#241;os prematuros de muy BPN y con ni&#241;os a t&#233;rmino&#44; ambos grupos con edades comprendidas entre los 6 y 9 a&#241;os&#46; Las siguientes variables se compararon entre los 2 grupos&#58; el pulso de ox&#237;geno &#40;PuO<span class="elsevierStyleInf">2</span>&#41;&#44; el porcentaje de frecuencia card&#237;aca m&#225;xima &#40;&#37;FC m&#225;x&#46;&#41;&#44; la relaci&#243;n entre el volumen corriente y la capacidad inspiratoria &#40;TV&#47;IC&#41;&#44; el consumo pico de ox&#237;geno &#40;VO<span class="elsevierStyleInf">2</span>&#41; y la relaci&#243;n entre el umbral anaer&#243;bico de intercambio de gas y el porcentaje estimado de VO<span class="elsevierStyleInf">2</span> m&#225;ximo &#40;VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37;VO<span class="elsevierStyleInf">2</span> m&#225;x&#46; pred&#46;&#41;&#46; Se llevaron a cabo an&#225;lisis de regresi&#243;n lineal univariante y multivariante para determinar los factores asociados con la capacidad aer&#243;bica&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Se incluyeron 34 ni&#241;os prematuros y 32 ni&#241;os a t&#233;rmino&#46; Se registraron valores similares de VO<span class="elsevierStyleInf">2</span> pico y de otras variables&#46; El desarrollo de displasia broncopulmonar &#40;BPD&#41; y de obesidad&#47;sobrepeso mostr&#243; una asociaci&#243;n positiva con el &#37;FC m&#225;x&#46; El <span class="elsevierStyleItalic">Z-score</span> para la altura&#47;edad y el peso al nacer &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;000<span class="elsevierStyleHsp" style=""></span>g se asoci&#243; positivamente con la SaO<span class="elsevierStyleInf">2</span> y el VO<span class="elsevierStyleInf">2</span> y negativamente con el sobrepeso&#47;obesidad y el sexo femenino&#46;</p></span> <span id="abst0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Conclusiones</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">La capacidad aer&#243;bica fue similar entre los 2 grupos&#46; El sexo&#44; el desarrollo de BPD&#44; peso al nacer &#60;<span class="elsevierStyleHsp" style=""></span>1&#46;000<span class="elsevierStyleHsp" style=""></span>g y factores relacionados con el crecimiento corporal&#44; tales como el <span class="elsevierStyleItalic">Z-score</span> para la altura&#47;edad y para el sobrepeso&#47;obesidad se asociaron con la capacidad aer&#243;bica en ni&#241;os prematuros de muy BPN&#46;</p></span>"
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                  \t\t\t\t">17&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">17&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;8&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">BMI &#40;<span class="elsevierStyleItalic">Z</span>-score&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">0&#46;40<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Hospitalization after NICU discharge&#44; <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \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  " align="char" valign="\n
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                  \t\t\t\t">Physical activity &#40;h&#47;week&#41;<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;735&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">VO<span class="elsevierStyleInf">2</span> peak &#40;mL&#47;kg&#47;min&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;541&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">VO<span class="elsevierStyleInf">2</span>&#64;LA&#47;&#37;VO<span class="elsevierStyleInf">2</span> max&#46;pred&#46; &#40;&#37;&#41;<a class="elsevierStyleCrossRef" href="#tblfn0025"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8722;4&#46;326&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">0&#46;003&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t</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  " align="char" valign="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                  \t\t\t\t">&#8722;5&#46;624&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8722;0&#46;409 to &#8722;3&#46;837&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="char" valign="\n
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                      "titulo" => "Differential effects of immaturity and neonatal lung disease on the lung function of very low birth weight infants at 48&#8211;52 postconceptional weeks"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
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                            0 => "G&#46; Schmalisch"
                            1 => "S&#46; Wilitzki"
                            2 => "C&#46;C&#46; Roehr"
                            3 => "H&#46; Proquitt&#233;"
                            4 => "C&#46; B&#252;hrer"
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                      "Revista" => array:5 [
                        "tituloSerie" => "Pediatr Pulmonol"
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                        "volumen" => "48"
                        "paginaInicial" => "1214"
                        "paginaFinal" => "1223"
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                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Exercise capacity after extremely preterm birth&#46; Development from adolescence to adulthood"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "H&#46;H&#46; Clemm"
                            1 => "M&#46; Volls&#230;ter"
                            2 => "O&#46;D&#46; R&#248;ksund"
                            3 => "G&#46;E&#46; Eide"
                            4 => "T&#46; Markestad"
                            5 => "T&#46; Halvorsen"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1513/AnnalsATS.201309-311OC"
                      "Revista" => array:6 [
                        "tituloSerie" => "Ann Am Thorac Soc"
                        "fecha" => "2014"
                        "volumen" => "11"
                        "paginaInicial" => "537"
                        "paginaFinal" => "545"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24502400"
                            "web" => "Medline"
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              "etiqueta" => "3"
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                  "contribucion" => array:1 [
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                      "titulo" => "Evaluation of lung function on impulse oscillometry in preschool children born late preterm"
                      "autores" => array:1 [
                        0 => array:2 [
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