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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect9060">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Autism spectrum disorder &#40;ASD&#41; is a complex neurodevelopmental condition&#46; Based on the 5th edition of Diagnostic Statistical Manual of Mental Disorders &#40;DSM-5&#41;&#44; specific diagnostic criteria for childhood autism include social skills and communication deficit associated with restrictive and repetitive behaviors&#44; interests&#44; or activities&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a> ASD is currently one of the most common childhood morbidities&#44; presenting in various degrees of severity&#46; The most recent global prevalence of autism was estimated at 0&#46;62&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">2</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">This disorder has grown into a constant challenge for many countries such as Tunisia&#44; as it has a severe impact on both the affected individuals and their families&#46; The financial burden&#44; which has become more acute since the Tunisian revolution&#44; along with the lack of scientific knowledge about the epidemiology&#44; etiology&#44; and natural course of this condition&#44; have rendered the situation more complex&#46;<a class="elsevierStyleCrossRefs" href="#bib0155"><span class="elsevierStyleSup">3&#8211;5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The spectrum of symptoms and the extreme complexity in the developmental and associated medical conditions within ASD do not necessarily mean a single etiology&#46; Several hypotheses concerning the pathogenesis have been proposed&#44; including the interaction of environmental factors and various genetic predispositions&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;6</span></a> Studies based on concordance rates among monozygotic twins and families suggest a possible role of both genetic and environmental factors in the etiology of ASD&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">A recent study suggests that genetic factors account for only 35&#8211;40&#37; of the contributing elements&#46;<a class="elsevierStyleCrossRefs" href="#bib0180"><span class="elsevierStyleSup">8&#44;9</span></a> The remaining 60&#8211;65&#37; are likely due to other factors&#44; such as prenatal&#44; perinatal&#44; and postnatal environmental factors&#46; Since ASDs are neurodevelopmental disorders&#44; neonatally-observed complications that are markers of events or processes that emerge early during the perinatal period may be particularly important to consider&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">8</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">To the best of our knowledge&#44; in Tunisia&#44; there are no studies that have considered the relationship between prenatal&#44; perinatal&#44; and postnatal risk factors and ASD&#46;</p><p id="par0030" class="elsevierStylePara elsevierViewall">Thus&#44; the aim of the present study was to identify the pre-&#44; peri-&#44; and postnatal factors associated to ASD by comparing children with ASD to their siblings who do not present any autistic disorders&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Study</span><p id="par0035" class="elsevierStylePara elsevierViewall">This was a cross sectional and comparative study&#46; It was conducted over a period of three months from July to September 2014&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Population</span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Participants</span><p id="par0040" class="elsevierStylePara elsevierViewall">The sample included 101 children divided into two groups&#58;<ul class="elsevierStyleList" id="lis0005"><li class="elsevierStyleListItem" id="lsti0005"><span class="elsevierStyleLabel">1&#46;</span><p id="par0045" class="elsevierStylePara elsevierViewall">The first group was composed of 50 autistic children previously identified and followed regularly in the child and adolescent psychiatry department of the Hedi CHAKER Hospital of Sfax &#40;Tunisia&#41;&#46; These patients came from different regions of Tunisia&#44; as there are only three child psychiatry departments in the entire country&#46; Subject ages ranged between 3 and 7 years&#46;</p></li><li class="elsevierStyleListItem" id="lsti0010"><span class="elsevierStyleLabel">2&#46;</span><p id="par0050" class="elsevierStylePara elsevierViewall">The second group was composed of 51 non-autistic children&#44; aged between 3 and 12 years&#46;</p></li></ul></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Inclusion and exclusion criteria</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Inclusion criteria</span><p id="par0055" class="elsevierStylePara elsevierViewall"><ul class="elsevierStyleList" id="lis0010"><li class="elsevierStyleListItem" id="lsti0015"><span class="elsevierStyleLabel">-</span><p id="par0060" class="elsevierStylePara elsevierViewall">For the first group&#44; the study included children who both met the DSM-5 criteria for ASD and whose score at the Child Autistic Rating Scale &#40;CARS&#41; was &#8805;30&#46;</p></li><li class="elsevierStyleListItem" id="lsti0020"><span class="elsevierStyleLabel">-</span><p id="par0065" class="elsevierStylePara elsevierViewall">For the second group&#44; the unaffected siblings were included as controls&#46;</p></li></ul></p><p id="par0070" class="elsevierStylePara elsevierViewall">In both groups&#44; the children were aged at least 3 years&#46; This criterion for age selection is based on the fact that ASD is identified with a high degree of certainty at the age of 3&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Exclusion criteria</span><p id="par0075" class="elsevierStylePara elsevierViewall">Exclusion criteria&#58; known neurogenetic conditions &#40;<span class="elsevierStyleItalic">e&#46;g&#46;</span>&#44; tuberous sclerosis&#44; neurofibromatosis&#44; fragile X syndrome&#44; Down syndrome&#41;&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The control group shared the same exclusion criteria&#46;</p></span></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Tools</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">DSM-5 diagnostic criteria for ASD</span><p id="par0085" class="elsevierStylePara elsevierViewall">In DSM-5&#44; ASD encompasses the previous DSM-IV autistic disorder &#40;autism&#41;&#44; Asperger&#39;s disorder&#44; childhood disintegrative disorder&#44; and pervasive developmental disorder not otherwise specified&#46;<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">1</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">CARS</span><p id="par0335" class="elsevierStylePara elsevierViewall">CARS assesses the intensity of ASD symptomatology&#46; It evaluates the severity of autistic behaviors in 14 functional areas by assigning a score from 1 to 4&#46; An overall score is calculated by adding all the grades&#44; to stratify patients into three levels&#58; &#8220;severely autistic&#8221; &#40;score between 37 and 60&#41;&#44; &#8220;mildly to moderately autistic&#8221; &#40;score between 30 and 36&#46;5&#41;&#44; and &#8220;absence of ASD&#8221; &#40;score less than 30&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">10</span></a> The time for administering this questionnaire is around 20&#8211;30<span class="elsevierStyleHsp" style=""></span>min&#46;</p></span></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Procedures</span><p id="par0095" class="elsevierStylePara elsevierViewall">All study procedures were approved by the local Research Ethics Committee&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Informal consent from parents or legal guardians of participants was obtained after the nature of the procedures had been fully explained&#46;</p><p id="par0105" class="elsevierStylePara elsevierViewall">The interviews were conducted with mothers in 78&#37; of the cases&#44; with fathers in 4&#37; of the cases&#44; and with both parents in 18&#37; of the cases&#44; by a properly trained child psychiatrist&#46;</p><p id="par0110" class="elsevierStylePara elsevierViewall">Parents completed a medical history questionnaire with a combination of closed and open-ended questions regarding pregnancy&#44; labor&#44; and complications during and after birth&#46; Additionally&#44; data were collected with reference to medical record and medical birth book&#46;</p><p id="par0115" class="elsevierStylePara elsevierViewall">The studied variables were designed according to the probable risk factors of ASD from existing literature&#46; The following variables&#44; which were considered for both groups&#44; were classified as parental factors&#44; pre-&#44; peri-&#44; and postnatal characteristics and were codified as binary variables &#40;yes&#47;no&#41;&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Parental factors</span>&#58; Advanced maternal and paternal age at the time of childbirth &#40;&#8805;35 years&#41;&#44; consanguinity&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Prenatal factors</span>&#58; These consisted of conditions that arose during pregnancy&#44; such as gestational diabetes&#44; which usually develops in the second half of pregnancy&#59; high and low blood pressure&#59; gestational infections&#59; and fetal distress inducing threatened abortion conditions&#44; such as amniotic fluid loss&#44; bleeding during gestation&#44; and suboptimal intrauterine conditions&#46; <span class="elsevierStyleItalic">Perinatal factors</span>&#58; delivery characteristics&#44; such as term birth &#40;premature or post-term birth&#41;&#59; delivery types&#44; including forceps or cesarean section&#59; acute fetal distress&#59; and birth weight &#40;low birth weight &#91;&#60;2500<span class="elsevierStyleHsp" style=""></span>g&#93; and macrosomia &#91;&#62;4000<span class="elsevierStyleHsp" style=""></span>g&#93;&#41;</p><p id="par0130" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Postnatal factors</span>&#58; All conditions occurring in the first six weeks after birth&#44; such as respiratory and urinary infections&#59; auditory deficit &#40;a loss of 30<span class="elsevierStyleHsp" style=""></span>dB&#41;&#59; and blood disorders such as anemia and thrombopenia&#46;</p><p id="par0135" class="elsevierStylePara elsevierViewall">The diagnosis of respiratory and urinary infections was achieved during hospitalizations in pediatric services&#46;</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Statistical analysis</span><p id="par0140" class="elsevierStylePara elsevierViewall">Statistical analysis was done using SPSS software for Windows&#44; release 20&#46;0 &#40;IBM Corp&#46; Released 2011&#46; IBM SPSS Statistics for Windows&#44; version 20&#46;0&#44; USA&#41;&#46; The analysis included a descriptive study&#44; observing the frequencies for the quantitative variables and means and standard deviations for the qualitative variables&#44; as well as an analytical study&#44; using Pearson&#39;s correlation coefficient to establish correlations between the two groups&#46; The level of statistical significance was set at <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;05 &#40;alpha level of 5&#37;&#41;&#46;</p><p id="par0145" class="elsevierStylePara elsevierViewall">In the multivariable analysis&#44; logistic regression was performed to identify risk factors for autism&#44; taking into account confounding factors and using the down method of Wald&#46;</p><p id="par0150" class="elsevierStylePara elsevierViewall">Initially&#44; all the variables significantly associated with autism were included in the univariable analysis&#44; as well as those found as risk factors in the literature&#46; The significance level was set at 20&#37;&#46; The final model accuracy was verified and calculated according to the Hosmer and Lemeshow test&#46; The results were expressed by the adjusted odds ratio &#40;OR<span class="elsevierStyleInf">a</span>&#41; with their confidence intervals&#44; 95&#37; CI &#40;OR<span class="elsevierStyleInf">a</span>&#41;&#46;</p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Results</span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Clinical profile of children with ASD</span><p id="par0155" class="elsevierStylePara elsevierViewall">This study included 50 children&#46; A male predominance &#40;37 boys and 13 girls&#41; was observed&#44; as well as a moderate socioeconomic level in 90&#37; of cases&#44; and a predominance of the mild to moderate form of ASD at the CARS &#40;62&#37; <span class="elsevierStyleItalic">vs&#46;</span> 38&#37; for the severe form&#41;&#46;</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Parental factors</span><p id="par0160" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the distribution of parental age at the moment of conception in both groups&#46; It indicates that the rate of advanced age &#40;&#8805;35 years&#41; among parents at the moment of conception was higher in children with ASD than in their siblings &#40;66&#37; <span class="elsevierStyleItalic">vs</span>&#46; 49&#46;01&#37; for fathers and 24&#37; <span class="elsevierStyleItalic">vs</span>&#46; 19&#46;6&#37; for mothers&#41;&#44; but the difference was statistically non-significant&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0165" class="elsevierStylePara elsevierViewall">In the present study&#44; the rate of consanguinity was 28&#37; &#40;first degree in 31&#37; of cases&#44; second degree in 26&#37; of cases&#44; and third degree in 43&#37; of cases&#41;&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Prenatal&#44; perinatal&#44; and postnatal factors &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;</span><p id="par0170" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> displays a comparison of prenatal&#44; perinatal&#44; and postnatal factors between both groups&#46; Despite the fact that no statistically significant differences were observed between prenatal factors in the groups &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;13&#41;&#44; the prevalence was higher in the first group &#40;50&#37; <span class="elsevierStyleItalic">vs</span>&#46; 35&#46;3&#37;&#41;&#46; <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows that perinatal factors were more frequent in the first group&#44; with a rate of 60&#37; <span class="elsevierStyleItalic">vs</span>&#46; 11&#46;8&#37; in the second group&#44; a statistically significant difference &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; The most frequent perinatal factors found in the ASD group were acute fetal distress &#40;26&#37;&#41;&#44; prematurity&#44; and difficult labor observed in 18&#37; in each case&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0175" class="elsevierStylePara elsevierViewall">As for postnatal factors&#44; they were associated with ASD &#40;40&#37; in the first group <span class="elsevierStyleItalic">vs</span>&#46; 9&#46;8&#37; in the second group&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#41;&#59; these postnatal factors were primarily a type of respiratory infection &#40;24&#37; of the cases in the first group&#41;&#46;</p><p id="par0180" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a> shows that after logistic regression&#44; the risk factors for autism that remained in the final model were&#58; male gender&#44; prenatal urinary tract infection&#44; acute fetal distress&#44; difficult labor&#44; and respiratory infection&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0185" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the distribution of prenatal&#44; perinatal&#44; and postnatal factors according to the severity of autism&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0190" class="elsevierStylePara elsevierViewall">No association was observed between the severity of autism and the prenatal&#44; perinatal&#44; and postnatal factors&#46;</p></span></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Discussion</span><p id="par0195" class="elsevierStylePara elsevierViewall">The present study discusses prenatal&#44; perinatal&#44; and postnatal complications&#44; as well as some parental characteristics&#44; that could be considered as risk factors for ASD&#46;</p><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0150">Parental factors</span><p id="par0200" class="elsevierStylePara elsevierViewall">Previous studies have linked advanced maternal and paternal age to increased risk for ASDs&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;12</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">In the present study&#44; the chose 35 years as the age cut-off for both parents&#46; This choice was based the recommendations of many authors&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#8211;13</span></a> Despite the fact that a correlation between advanced age at the moment of the conception of both parents and ASD was not observed&#44; the frequency of parents aged over 35 years was higher in children with ASD than their siblings &#40;respectively 24&#37; <span class="elsevierStyleItalic">vs</span>&#46; 19&#46;6&#37; for maternal age and two-thirds <span class="elsevierStyleItalic">vs</span>&#46; almost 50&#37; for paternal age&#41;&#46;</p><p id="par0210" class="elsevierStylePara elsevierViewall">Theories advocating the association between parental age and increased risk for ASDs include the potential for more genetic mutations in the gametes of older fathers and mothers&#44; as well as a less favorable <span class="elsevierStyleItalic">in utero</span> environment in older mothers&#44; with more obstetrical complications such as low birth weight&#44; prematurity&#44; and cerebral hypoxia&#46;<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">11</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Moreover&#44; according to some studies&#44; high prevalence of chronic diseases among older women could contribute to expand the risk of adverse birth outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0200"><span class="elsevierStyleSup">12&#44;14</span></a> Data from the literature trying to explain the increased risk for ASD&#39;s among older mothers have incriminated the high risk of obstetric complications observed in these mothers&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">11&#44;12&#44;14</span></a></p><p id="par0220" class="elsevierStylePara elsevierViewall">Furthermore&#44; congenital anomalies are also more common in the fetuses and infants of older mothers&#44; and these conditions contribute in increasing the risk of ASD&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">In the present study&#44; a rate of 28&#37; of consanguinity was observed&#46; In the literature&#44; it is stated that consanguinity increases the chances of inheriting a bad DNA fit&#44; which will definitely result in a birth defect&#46; Inbred disorders may cause other abnormalities&#44; and ASD can also be brought on by other conditions&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a> Since the control group&#44; in the present study&#44; was represented by the siblings conceived and born from the same biological parents&#44; consanguinity could not be evaluated as a risk factor for ASD&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0155">Prenatal&#44; perinatal and postnatal factors</span><p id="par0230" class="elsevierStylePara elsevierViewall">In the present survey&#44; no correlation was observed between the severity of ASD and prenatal&#44; perinatal&#44; and postnatal factors&#46; The present results are in agreement with some recent studies&#46;<a class="elsevierStyleCrossRefs" href="#bib0220"><span class="elsevierStyleSup">16&#44;17</span></a> Conversely&#44; some hypothesis have been raised&#44; indicating that the light form of autism would show weaker or no association with obstetric risk factors&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0160">Prenatal factors</span><p id="par0235" class="elsevierStylePara elsevierViewall">In the present study&#44; the occurrence of maternal infection was higher among cases when compared to controls &#40;12&#37; for the first group <span class="elsevierStyleItalic">vs</span>&#46; 3&#46;9&#37; for controls&#41;&#46;</p><p id="par0240" class="elsevierStylePara elsevierViewall">According to many studies&#44; adverse intrauterine environment resulting from maternal bacterial and viral infections during pregnancy is a significant risk factor for several neuropsychiatric disorders including ASD&#46;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">15</span></a> The association between intrauterine inflammation&#44; infection&#44; and ASD is based on both epidemiological studies and case reports&#46; This association is apparently related to maternal inflammatory process&#59; hence&#44; maternal immune activation may play a role in neuro-developmental perturbation&#46;</p><p id="par0245" class="elsevierStylePara elsevierViewall">In large population studies&#44; researchers have not identified a specific infection&#44; but rather an increased rate of ASD&#44; especially when the maternal infection is rather severe and requires hospitalization&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#44;18</span></a></p><p id="par0250" class="elsevierStylePara elsevierViewall">Among the prenatal factors identified in this study&#44; exposure to cigarette tobacco &#40;passive smoking&#41; was noted in 22&#37; of cases&#46; Retrospective epidemiological studies have observed&#44; among mothers of children with ASD&#44; a significantly increased percentage of women who were exposed to tobacco during the conception of the child&#46; Therefore&#44; maternal smoking was considered as a potential maternal confounding factor&#44; as well as other toxic chemicals&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">6</span></a></p><p id="par0255" class="elsevierStylePara elsevierViewall">Some authors have demonstrated that maternal cigarette smoking during pregnancy may have a commutative impact on the lineage of her reproductive cells&#59; it is also associated with an increased rate of spontaneous abortions&#44; preterm delivery&#44; reduced birth weight&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">19</span></a> The findings regarding its relation with ASD are still controversial&#46;<a class="elsevierStyleCrossRefs" href="#bib0240"><span class="elsevierStyleSup">20&#8211;22</span></a></p><p id="par0260" class="elsevierStylePara elsevierViewall">The present study showed that the frequency of gestational diabetes was higher in the first group &#40;8&#37; <span class="elsevierStyleItalic">vs</span>&#46; 2&#37; in the second group&#41;&#46;</p><p id="par0265" class="elsevierStylePara elsevierViewall">According to some authors&#44; gestational diabetes is mainly associated with disturbed fetal growth and increased rate of a variety of pregnancy complications&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a> It also affects fine and gross motor development and increases the rate of learning difficulties and of attention deficit hyperactivity disorder&#44; a common comorbid neurobehavioral problem in ASD&#46; The negative effects of maternal diabetes on the brain may result from intrauterine increased fetal oxidative stress and epigenetic changes in the expression of several genes&#46; The increased risk observed might be related to other pregnancy complications that are common in diabetes&#44; or to effects on fetal growth rather than to complications of hyperglycemia&#46; It is also unknown whether optimal control of diabetes will further decrease this association&#46;<a class="elsevierStyleCrossRef" href="#bib0255"><span class="elsevierStyleSup">23</span></a></p><p id="par0270" class="elsevierStylePara elsevierViewall">Because of its rising incidence&#44; maternal diabetes has been considered&#44; by several studies&#44; as an obvious candidate to be associated with ASD&#44; whereas others have failed to demonstrate such associations&#46;<a class="elsevierStyleCrossRefs" href="#bib0215"><span class="elsevierStyleSup">15&#44;20&#44;23</span></a></p><p id="par0275" class="elsevierStylePara elsevierViewall">In the current survey&#44; hypertension&#44; hypotension&#44; and threatened abortion were more frequent in the first group &#40;respectively 10&#37; <span class="elsevierStyleItalic">vs</span>&#46; 5&#46;9&#37;&#44; 2&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#37;&#44; and 10&#37; <span class="elsevierStyleItalic">vs</span>&#46; 5&#46;9&#37; in the second group&#41;&#46; These conditions are generally related to fetal loss and adverse infant outcomes&#44; such as prematurity&#44; intrauterine growth retardation&#44; still birth&#44; and neonatal death indicating fetal distress&#46; Likewise&#44; fetal hypoxia is one of the manifestations of fetal distress and has been reported to induce conditions such as placental abruption&#44; threatened premature delivery&#44; emergency cesarean section&#44; forceps delivery&#44; spontaneous abortion&#44; and varying degrees of cerebral damage&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#44;5</span></a> Accordingly&#44; ASD was linked to fetal distress&#58; oxygen deprivation could damage vulnerable regions in the brain&#44; such as the basal ganglia&#44; hippocampus&#44; and lateral ventricles&#46; Some neuroimaging studies have demonstrated abnormalities in these regions among patients with ASD compared with controls&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;14</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0165">Perinatal factors</span><p id="par0280" class="elsevierStylePara elsevierViewall">In the present series&#44; perinatal factors were very significantly associated with ASD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03&#41;&#46; This result is consistent with the literature&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#44;24</span></a> In fact&#44; complications occurring during labor affect the neurodevelopment of the fetus and infant in later stages&#44; and can contribute toward the risk of ASD&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">The current research also suggests that obstetric factors occur more frequently in ASD children than in their unaffected siblings&#46; The present results corroborate other studies reporting an association between perinatal factors and ASD&#46;</p><p id="par0290" class="elsevierStylePara elsevierViewall">Perinatal factors were represented by a long duration of delivery and prematurity in 18&#37; of the cases each one and suffering acute fetal in 26&#37; of the cases&#46; Therefore&#44; it is admitted that these conditions may lead to fetal distress and asphyxia&#44; resulting in brain damage&#46; Fetal oxygen deprivation has been proposed to increase the risk for ASD&#46; Recently&#44; research has highlighted the occurrence of ASDs in very preterm infants&#44; in addition to already identified developmental disorders&#46;<a class="elsevierStyleCrossRefs" href="#bib0160"><span class="elsevierStyleSup">4&#44;14&#44;24</span></a></p></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0170">Postnatal factors</span><p id="par0295" class="elsevierStylePara elsevierViewall">The present findings are in agreement with previous studies suggesting that postnatal events may increase the risk for ASDs in some children&#46;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">4</span></a> In fact&#44; a significant association between postnatal factors and ASD &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#41; has been observed&#46;</p><p id="par0300" class="elsevierStylePara elsevierViewall">In the present study&#44; an association was observed between both urinary and respiratory infections and ASD&#46; These findings could be explained by the release of cytokines as immune responses of the baby to these infections&#44; which can affect neural cell proliferation and differentiation&#46; These impairments are known to be associated with ASD&#46;<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">5&#44;25</span></a></p><p id="par0305" class="elsevierStylePara elsevierViewall">Hearing deficits were more common in the first group &#40;4&#37; <span class="elsevierStyleItalic">vs</span>&#46; 0&#37; in the second group&#41;&#46; The present results corroborate those of Fombonne&#44;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">26</span></a> who reported&#44; in a meta-analysis&#44; that the prevalence of sensory deficits in autism vary from 0&#46;9&#37; to 5&#46;9&#37;&#46;</p><p id="par0310" class="elsevierStylePara elsevierViewall">Rosenhall et al&#46;&#44;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">27</span></a> in a study conducted on 199 children and adolescents with ASD&#44; estimated that the prevalence of hearing impairment in autism is ten times higher than in general population &#40;11&#37;&#41;&#46; They also observed that 7&#46;9&#37; of the patients had an moderate hearing loss&#44; 3&#46;5&#37; were profoundly deaf&#44; and 18&#37; had hyperacusis in the audiogram&#44; even after controlling for the age factor&#46; More recently&#44; Kielinen et al&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">28</span></a> observed&#44; in a population of children with autism&#44; that 8&#46;6&#37; had a mild hearing loss&#44; 7&#37; a moderate deficit&#44; and 1&#46;6&#37; severe deficiency &#40;hearing loss in more than 60<span class="elsevierStyleHsp" style=""></span>dB at audiometry&#41;&#46;</p><p id="par0315" class="elsevierStylePara elsevierViewall">The strength of the present study lies in its precise confirmation of the ASD&#44; the active participation of parents&#44; and resorting to unaffected siblings as controls&#46; This last feature may help to identify risk factors and to control for hereditary background&#44; family environment&#44; and maternal predisposition to complications in pregnancy or birth&#46; Nonetheless&#44; there are some limitations&#44; namely the limited number of samples&#46; Therefore&#44; the present results should be completed by epidemiological studies with a larger scale and in larger populations&#46; To face the issue of ASD and consanguinity&#44; a larger population with and without consanguinity should be evaluated&#46;</p><p id="par0320" class="elsevierStylePara elsevierViewall">In the present study&#44; no individual factor in the prenatal period was consistently significant as a risk factor for ASD&#46; In the literature&#44; some of these factors were associated with autism&#59; therefore&#44; they should be considered as potential risk factors&#44; as well as perinatal and postnatal events&#46;</p><p id="par0325" class="elsevierStylePara elsevierViewall">Prenatal&#44; perinatal&#44; and postnatal factors for ASD should be considered in the broadest sense&#58; these events of the fetal&#44; newborn&#44; and infant environment could interact or contribute in combination with other co-factors &#40;environmental and genetic&#44; among others&#41; to characterize ASD&#46; Scores indicate that rather than focusing on a single factor&#44; future studies should investigate the combination of several factors&#46;</p></span></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0175">Conflicts of interest</span><p id="par0330" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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            0 => "Autism spectrum disorder"
            1 => "Child"
            2 => "Risk factors"
            3 => "Prenatal"
            4 => "Perinatal"
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            0 => "Transtorno do espectro do autismo"
            1 => "Crian&#231;a"
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            3 => "Pr&#233;-natal"
            4 => "Perinatal"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To identify prenatal&#44; perinatal and postnatal risk factors in children with autism spectrum disorder &#40;ASD&#41; by comparing them to their siblings without autistic disorders&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">The present study is cross sectional and comparative&#46; It was conducted over a period of three months &#40;July&#8211;September 2014&#41;&#46; It included 101 children&#58; 50 ASD&#39;s children diagnosed according to DSM-5 criteria and 51 unaffected siblings&#46; The severity of ASD was assessed by the CARS&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Our study revealed a higher prevalence of prenatal&#44; perinatal and postnatal factors in children with ASD in comparison with unaffected siblings&#46; It showed also a significant association between perinatal and postnatal factors and ASD &#40;respectively <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;03 and <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;042&#41;&#46; In this group&#44; perinatal factors were mainly as type of suffering acute fetal &#40;26&#37; of cases&#41;&#44; long duration of delivery and prematurity &#40;18&#37; of cases for each factor&#41;&#44; while postnatal factors were represented principally by respiratory infections &#40;24&#37;&#41;&#46; As for parental factors&#44; no correlation was found between advanced age of parents at the moment of the conception and ASD&#46; Likewise&#44; no correlation was observed between the severity of ASD and different factors&#46; After logistic regression&#44; the risk factors retained for autism in the final model were&#58; male gender&#44; prenatal urinary tract infection&#44; acute fetal distress&#44; difficult labor and respiratory infection&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">The present survey confirms the high prevalence of prenatal&#44; perinatal and postnatal factors in children with ASD and suggests the intervention of some of these factors &#40;acute fetal distress and difficult labor&#44; among others&#41;&#44; as determinant variables for the genesis of ASD&#46;</p></span>"
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        "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivo</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Identificar fatores de risco pr&#233;-natal&#44; perinatal e p&#243;s-natal em crian&#231;as com transtorno do espectro do autismo &#40;TEA&#41; ao compar&#225;-las a irm&#227;os sem transtornos de autismo&#46;</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">M&#233;todo</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Este estudo &#233; transversal e comparativo&#46; Ele foi conduzido em um per&#237;odo de tr&#234;s meses &#40;julho a setembro de 2014&#41;&#46; Incluiu 101 crian&#231;as&#58; 50 crian&#231;as com TEAs diagnosticadas de acordo com os crit&#233;rios do DSM-5 e 51 irm&#227;os n&#227;o afetados&#46; A gravidade do TEA foi avaliada pela Escala de Avalia&#231;&#227;o do Autismo na Inf&#226;ncia &#40;CARS&#41;&#46;</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Nosso estudo revelou uma preval&#234;ncia maior de fatores pr&#233;-natais&#44; perinatais e p&#243;s-natais em crian&#231;as com TEA em compara&#231;&#227;o a irm&#227;os n&#227;o afetados&#46; Tamb&#233;m mostrou uma associa&#231;&#227;o significativa entre fatores perinatais e p&#243;s-natais e TEA &#40;respectivamente p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;03 e p<span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#44;042&#41;&#46; Nesse grupo&#44; os fatores perinatais foram principalmente do tipo sofrimento fetal agudo &#40;26&#37; dos casos&#41;&#44; longa dura&#231;&#227;o do parto e prematuridade &#40;18&#37; dos casos em cada fator&#41;&#44; ao passo que fatores p&#243;s-natais foram representados principalmente por infec&#231;&#245;es respirat&#243;rias &#40;24&#37;&#41;&#46; No que diz respeito a fatores dos pais&#44; nenhuma correla&#231;&#227;o foi encontrada entre a idade avan&#231;ada dos pais no momento da concep&#231;&#227;o e o TEA&#46; Da mesma forma&#44; nenhuma correla&#231;&#227;o foi estabelecida entre a gravidade do TEA e fatores diferentes&#46;</p><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Ap&#243;s regress&#227;o log&#237;stica&#44; os fatores de risco de autismo encontrados no modelo final foram&#58; sexo masculino&#44; infec&#231;&#227;o pr&#233;-natal do trato urin&#225;rio&#44; sofrimento fetal agudo&#44; parto dif&#237;cil e infec&#231;&#227;o respirat&#243;ria&#46;</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclus&#245;es</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Esta pesquisa confirma a alta preval&#234;ncia de fatores pr&#233;-natais&#44; perinatais e p&#243;s-natais em crian&#231;as com TEA e sugere a interven&#231;&#227;o de alguns desses fatores &#40;sofrimento fetal agudo&#44; parto dif&#237;cil&#8230;&#41; como vari&#225;veis determinantes para a g&#234;nese do TEA&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0025">Please cite this article as&#58; Hadjkacem I&#44; Ayadi H&#44; Turki M&#44; Yaich S&#44; Khemekhem K&#44; Walha A&#44; et al&#46; Prenatal&#44; perinatal and postnatal factors associated with autism spectrum disorder&#46; J Pediatr &#40;Rio J&#41;&#46; 2016&#59;92&#58;595&#8211;601&#46;</p>"
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          "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Distribution of prenatal&#44; perinatal&#44; and postnatal factors according to the severity of ASD &#40;a total of 50 cases&#41;&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">80&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;59&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>&#8805;35 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">19&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="" valign="top">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab1254030.png"
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        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Parental age at the time of conception in both groups&#46;</p>"
        ]
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        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
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        "tabla" => array:2 [
          "tablatextoimagen" => array:1 [
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              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 1 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>50&#41;</th><th class="td" title="table-head  " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Group 2 &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>51&#41;</th><th class="td" title="table-head  " align="left" valign="top" scope="col"><span class="elsevierStyleItalic">p</span>-Value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr><tr title="table-row"><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">N</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">&#37;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th><th class="td" title="table-head  " align="" valign="top" scope="col" style="border-bottom: 2px solid black">&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Prenatal factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">50&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">35&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exposure to cigarette smoking&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">22&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urinary infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypertension in pregnancy&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Threatened abortion&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;48&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Gestational diabetes&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Hypotension&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;49&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Perinatal factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">60&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">11&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Acute fetal distress&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">13&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;006&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Prematurity&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Exceeding the term&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Difficult labor&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">18&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Low birth weight<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Macrosomia<a class="elsevierStyleCrossRef" href="#tblfn0010"><span class="elsevierStyleSup">b</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry  " colspan="6" align="left" valign="top"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleItalic">Postnatal factors</span>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">20&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">9&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">&#60;0&#46;01&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Respiratory infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">12&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Urinary infection&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;36&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Auditory deficit<a class="elsevierStyleCrossRef" href="#tblfn0015"><span class="elsevierStyleSup">c</span></a>&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="table-entry  " align="char" valign="top">0&#46;24&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top"><span class="elsevierStyleHsp" style=""></span>Blood disease<a class="elsevierStyleCrossRef" href="#tblfn0020"><span class="elsevierStyleSup">d</span></a>&nbsp;\t\t\t\t\t\t\n
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                  "comentario" => "Available from&#58; <a class="elsevierStyleInterRef" id="intr0010" href="http://www.dsm5.org/Documents/Autism%20Spectrum%20Disorder%20Fact%20Sheet.pdf">http&#58;&#47;&#47;www&#46;dsm5&#46;org&#47;Documents&#47;Autism&#37;20Spectrum&#37;20Disorder&#37;20Fact&#37;20Sheet&#46;pdf</a> &#91;cited 05&#46;12&#46;13&#93;"
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                      "doi" => "10.1002/aur.239"
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