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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Congenital microcephaly is a clinical condition where the head circumference &#40;HC&#41; is smaller than expected&#46; It is defined as an HC equal to or less than two standard deviations &#40;SDs&#41; below the expected mean for a given gestational age and sex&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> It is a scenario that affects both the newborn &#40;reducing its quality of life and life expectancy&#41; and the family &#40;economic burdens and parental stress&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Microcephaly is an adverse manifestation with multiple etiologies&#46; There is now a consensus on the association between Zika virus &#40;ZIKV&#41; infection during pregnancy and microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Many recent studies from South America have cited a lower prevalence of microcephaly &#40;1&#8211;12 per 10&#44;000 children&#41; but the frequency in Brazil is reportedly higher&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the presence of microcephaly is not difficult to identify using standard criteria&#44; several factors can affect the accuracy of its detection&#44; such as the time between delivery and the HC measurement&#44; the type of instrument used to measure the HC&#44; the shape of the baby&#8217;s skull&#44; and the accuracy of the gestational age determination&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The present cross-sectional study aimed to determine the most sensitive cutoff point by comparing different cutoff points to diagnose microcephaly&#44; compared to the INTERGROWTH-21st curve &#40;IG&#41;&#44; and to identify the etiology of the microcephalies observed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This retrospective observational cross-sectional study was performed using data obtained from the Jundia&#237; Zika Cohort study&#44; which was previously published&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> This is a maternal-infant cohort&#44; with patients both positive and negative for Zika virus&#46; Most of these study patients were negative for Zika virus&#46; All live newborn participants were born in the region of Jundia&#237; and followed at the Hospital Universit&#225;rio da Faculdade de Medicina de Jundia&#237; &#40;HUJ&#41; in the city of Jundia&#237;&#44; S&#227;o Paulo&#44; Brazil&#44; from March 2016 to August 2018&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The inclusion criteria were&#58; &#40;1&#41; gestational age &#8804;13 weeks and 6 days determined by obstetric ultrasound in the first trimester&#44; or &#40;2&#41; gestational age between 14&#8211;20 weeks and a difference &#60;1 week between the estimates based on the date of the last menstrual period and ultrasound examination&#46; These criteria were based on guidelines from the Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists &#40;ACOG&#41; and the Brazilian Pediatrics Society &#40;SBP&#41; to increase accuracy&#44; since gestational age is a dependent variable of the curves used in this study&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> Newborns with incomplete anthropometric and&#47;or sex data were excluded from the study&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the process of patient selection&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical considerations</span><p id="par0030" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of the Jundia&#237; School of Medicine &#40;CAAE 53248616&#46;2&#46;0000&#46;5412&#59; legal opinion number 1&#46;446&#46;577&#41;&#46; Research participation was only accepted after mothers or legal guardians provided written informed consent&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Data collection</span><p id="par0035" class="elsevierStylePara elsevierViewall">During the cohort study period&#44; maternal data on general health and pregnancy were collected directly from the mothers&#46; The neonatology team &#40;composed of pediatricians and neonatologists&#41; underwent specific training on accurate anthropometric measurement offered by the JZC group&#46; At birth&#44; all newborns underwent a complete physical examination&#44; weight determination on a digital scale&#44; length measurement with a stainless steel anthropometer&#44; and HC measurement with a non-elastic tape measure &#40;presented in centimeters and millimeters&#41; following the guidelines by the Brazilian Ministry of Health &#40;MoH&#41; and the Brazilian Pediatrics Society&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Peripheral blood&#44; saliva&#44; and urine samples from pregnant women and babies were collected&#44; transported at 2&#8211;6<span class="elsevierStyleHsp" style=""></span>&#176;C for a maximum of 5<span class="elsevierStyleHsp" style=""></span>hours&#44; and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Serum samples were stored after collection by centrifugation at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Detection of IgM and IgG antibodies for Dengue virus&#44; Chikungunya virus&#44; Parvovirus B19 virus&#44; STORCH&#44; and ZIVK was performed using a commercial ELISA kit &#40;Euroimmun&#8482;&#44; Euroimmun&#44; Lubeck&#44; Germany&#41; following the manufacturer&#8217;s recommendations&#46; The ELISA utilized to detect viral antibodies did not completely eliminate the possibility of cross-reactivity between the three arboviruses&#46; The detection of Dengue virus&#44; ZIKV&#44; and Chikungunya virus by real-time quantitative polymerase chain reaction &#40;RT-qPCR&#41; in blood&#44; saliva&#44; and urine utilized a published protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">HC was classified by the z-score according to the Fenton curves for preterm newborns and IG for all term babies&#46; Microcephaly was diagnosed when the z-score was equal to or below two standard deviations of the expected mean&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> Additionally&#44; in cases of microcephaly&#44; the difference in the weight and HC z-scores was calculated for proportionality assessment&#44; according to Noyola et al&#46;&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> who found that in infants with congenital cytomegalovirus infection&#44; a difference &#8805;2 was associated with adverse neurodevelopmental outcomes&#46; Microcephalic newborns underwent transfontanellar ultrasound and&#47;or non-contrast-enhanced computed tomography&#44; and the results were verified by a team of radiologists&#46; Newborns were then divided into 10 groups for comparisons based on HC&#44; IG z-scores&#44; and sex &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; according to the different cutoff points established by the Brazilian MoH to simulate the different situations during the ZIKV epidemic&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using the 12&#46;7 version of the SPSS software &#40;SPSS&#8482; South America&#59; SPSS Inc&#46;&#44; Chicago&#44; IL&#41;&#46; Cutoff points were determined using receiver operating characteristic curves&#44; finding the most appropriate balance between the sensitivity and specificity of the indicators and considering the Youden index&#46; In addition&#44; the Kappa index was calculated to describe the agreement between the diagnostic methods for microcephaly&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the characteristics of the study population&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Microcephaly prevalence</span><p id="par0065" class="elsevierStylePara elsevierViewall">The prevalence of microcephaly&#44; calculated according to the established HC cutoff points&#44; was 4&#46;1&#37;&#46; This translated to 3&#46;2&#37; for term births and 4&#46;3&#37; for babies delivered preterm&#46; The results for microcephaly prevalence in each group&#44; as well as the comparison between the HC cutoff points and standard IG curve&#44; are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Groups 8 and 9 had only one case each&#44; which ruled out statistical analysis&#46; In the remaining groups&#44; the percentage varied from 4&#46;3&#8211;29&#37;&#44; specificity varied from 71&#46;7&#8211;100&#37;&#44; and sensitivity ranged from 57&#46;1&#8211;100&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Utilizing a cutoff value of 33<span class="elsevierStyleHsp" style=""></span>cm resulted in increased reporting of suspected microcephaly cases&#46; We identified 106 babies with an HC<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>33<span class="elsevierStyleHsp" style=""></span>cm compared to 12 cases when using the reference standard&#46; Therefore&#44; 84 cases &#40;79&#46;2&#37;&#41; were presumptive false positives&#46; When the cutoff was subsequently changed to 32<span class="elsevierStyleHsp" style=""></span>cm&#44; 41 babies &#40;38&#46;7&#37;&#41; were defined as having microcephaly&#44; and of them&#44; only 12 were true positives&#46; The accuracy for detecting infants who were truly positive for microcephaly increased further when different cutoffs were used for each sex&#46; It is also worth noting that as the groups were stratified&#44; the number of cases sampled decreased&#44; which reduced the statistical power of the tests performed&#46; The utilization of the World Health Organization &#40;WHO&#41; curve resulted in a further increase in specificity&#46; In addition&#44; it is noteworthy that for male babies the accuracy in detecting those who were indeed positive for microcephaly was very high &#40;100&#37; sensitivity and 98&#37; specificity&#41; in relation to the standard curve &#40;IG&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">From the 19 cases of microcephaly&#44; only 16 were available for analysis due to the loss of three cases to follow-up&#46; In terms of etiology &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; there were three &#40;15&#46;8&#37;&#41; positive cases for ZIKV&#44; three cases &#40;15&#46;8&#37;&#41; with other congenital anomalies &#40;one case each of trisomy 21&#44; band heterotopia&#44; and an unknown congenital syndrome still under diagnostic investigation&#41;&#44; and nine cases &#40;47&#46;4&#37;&#41; of intrauterine growth restriction with no other determined cause&#46; Lastly&#44; there was one case &#40;5&#46;2&#37;&#41; of a twin born to a ZIKV-positive mother who had microcephaly and intrauterine growth restriction and tested negative for ZIKV at birth&#46; All cases were negative for Dengue virus&#44; Chikungunya virus&#44; Parvovirus B19&#44; and STORCH&#46; Of the three microcephalic newborns with ZIKV infection at birth&#44; two were positive by PCR in urine and the third was positive for IgG antibodies to ZIKV&#44; but negative by PCR&#46; One PCR-positive newborn&#44; delivered at term&#44; had a z-score difference of 0&#46;82 between HC and weight&#44; with no additional findings on examination&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The baby went on to have HC catch-up growth and normal neurodevelopment&#46; The other PCR-positive baby had an imaging examination that showed lissencephaly&#44; ventriculomegaly&#44; and agenesis of the corpus callosum&#44; as well as clinical arthrogryposis and dysphagia&#46; The z-score difference between HC and weight was 3&#46;21&#46; The ZIKV IgG-positive newborn had altered visual acuity&#44; without any other clinical alterations&#44; and the z-score difference between HC and weight was not significant at birth but increased to 4&#46;10 during follow-up &#40;increased over time&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In this study&#44; the prevalence of microcephaly was 4&#46;1&#37;&#46; In the literature&#44; the reported prevalence of microcephaly varies widely&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The Latin American Collaborative Study of Congenital Malformations <span class="elsevierStyleItalic">&#40;ECLAMC&#41;</span> group conducted a study on microcephaly from 2005 to 2014&#44; including 10 Latin American countries &#40;including Brazil&#41; before the ZIKV epidemic&#44; which considered microcephaly as an HC less than or equal to three standard deviations below the reference according to the IG curve&#46; During this period&#44; the prevalence of microcephaly was 4&#46;4 per 10&#44;000 live births &#40;5&#46;4 cases per 10&#44;000 live births in Brazil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Other studies utilizing the same diagnostic criteria as the present study have also been reported&#46; In the United States&#44; one population-based survey conducted from 2009 to 2013 reported 9&#44;678 cases of microcephaly with a prevalence of 8&#46;7 cases per 10&#44;000 live births&#44; and 95&#37; of these cases had a definite diagnosis of microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A Brazilian study using population-based data showed differences in the prevalence of microcephaly between the cities of S&#227;o Luis &#40;state of Maranh&#227;o&#44; Northeast region of Brazil&#59; 3&#46;5&#37;&#41; and Ribeir&#227;o Preto &#40;state of S&#227;o Paulo&#44; Southeast region of Brazil&#59; 2&#46;5&#37;&#41; in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">During the ZIKV epidemic&#44; a study from the SINASC &#40;&#8220;Sistema de Informa&#231;&#245;es sobre Nascidos Vivos&#8221; &#8211; Information System about Livebirths&#41; reported a nine-fold increase in the prevalence of microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Also during the same period in Southern Brazil&#44; in a study with a large number of newborns&#44; microcephaly was detected in 9&#46;6 per 10&#44;000 live births &#40;from the initial sample&#44; 60&#46;8&#37; were &#8220;non-confirmed&#8221; microcephaly&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In Brazil&#44; those differences in the prevalence of microcephaly may also have occurred because of the different cutoff points established by the Brazilian MoH from November 2015 to August 2016&#46; During this period&#44; four different cutoff points were considered &#40;for term babies&#58; 33<span class="elsevierStyleHsp" style=""></span>cm in November 2015&#44; 32<span class="elsevierStyleHsp" style=""></span>cm in December 2015&#44; WHO curve in March 2016&#44; and IG curve in August 2016&#59; for preterm babies&#58; Fenton curve from November 2015 to March 2016&#44; and then the IG curve&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;23</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Considering the IG curve as the gold-standard and comparing the different cutoff points previously established by the MoH&#44; we observed that the sensitivity was 100&#37; but the specificity was low&#44; especially with the first two cutoff points&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In addition to increasing sensitivity&#44; the use of a more stringent cutoff point for reporting suspected cases of microcephaly has an economic impact by reducing the number of babies who require additional screening&#46; In a country with low to moderate health resources such as Brazil&#44; this cost impact must be seriously considered&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">A strength of our study was the inclusion of newborns with a very well-defined gestational age&#44; which increased accuracy since age was a dependent variable in the IG curve &#40;the standard curve for this study&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The limitations of our study should also be mentioned&#46; Firstly&#44; most of our study sample were the offspring of high-risk pregnant women&#46; Six of the nineteen microcephaly cases were from pregnant women with hypertension &#40;chronic and&#47;or gestational&#41;&#59; one had diabetes&#59; and another had thrombophilia&#46; In these high-risk women&#44; there is a known association between maternal pathology and intrauterine growth restriction&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> A second limitation was that 20&#37; of our subjects were preterm newborns&#46; This varies from the rates &#40;7&#46;5&#8211;11&#37;&#41; observed in countries such as France and the United States&#46; This difference may have increased the number of small-for-gestational-age newborns in our study&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> Lastly&#44; although newborns were tested for both viral antibodies and ZIKV by gene amplification&#44; there remains a small possibility that a variable number of ZIKV-negative babies with microcephaly were actually infected with this virus&#46; Inadequacies of the testing protocols have been previously reported&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the etiology of microcephaly&#44; it is noteworthy that although ZIKV infection was a primary motivator for recent microcephaly-based studies in Brazil&#44; it was only one of several etiological factors identified&#46; Thus&#44; even in the periods of a particular outbreak&#44; multiple etiologies must be considered&#46; However&#44; when HC was adjusted for weight &#40;by the difference in z-score&#41; a greater disproportion was noticed in two of the three cases with ZIKV infection&#46; Microcephaly in relation to birth weight predicts adverse neurological outcomes in infants with congenital infection&#44; and the disproportion between them suggests a higher risk of developmental disability&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">We conclude that the WHO cutoff point was almost as sensitive as the INTERGROWTH-21st curve to diagnose microcephaly in our study&#46; Despite the ZIKV epidemic being the trigger of this study&#44; it was not the main cause of microcephaly&#46; For the majority of patients other causes were found&#44; thus emphasizing the importance of screening and follow-up to facilitate individual approaches and to maximize their developmental potential&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0145" class="elsevierStylePara elsevierViewall">This work and this manuscript were supported by the <span class="elsevierStyleGrantSponsor" id="gs0005">Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0005">2016&#47;08578-0</span>&#41;&#44; the <span class="elsevierStyleGrantSponsor" id="gs0010">Brazilian Ministry of Health</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0010">861306&#47;2017</span> and <span class="elsevierStyleGrantNumber" refid="gs0010">861307&#47;2017</span>&#41;&#44; and the <span class="elsevierStyleGrantSponsor" id="gs0015">London School of Hygiene and Tropical Medicine</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0015">PC0002&#47;16</span>&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic&#46; As a secondary aim&#44; we investigated the possible etiology of the microcephaly&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This retrospective study utilized newborn participants in the Zika Cohort Study Jundia&#237;&#46; Newborns from the Zika Cohort Study Jundia&#237; with an accurate gestational age determination and complete anthropometric data were analyzed&#44; and microcephaly was diagnosed according to the INTERGROWTH-21<span class="elsevierStyleSup">st</span> curve&#46; At delivery&#44; fluids were tested for specific antibodies and for viruses&#46; Brain images were evaluated for microcephaly&#46; Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Of 462 eligible newborns&#44; 19 &#40;4&#46;1&#37;&#41; were positive for microcephaly&#46; Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity&#46; Three of the microcephaly cases &#40;15&#46;8&#37;&#41; were positive for Zika virus infections&#59; nine &#40;47&#46;4&#37;&#41; had intrauterine growth restriction&#59; one had intrauterine growth restriction and was exposed to Zika virus&#59; three had a genetic syndrome &#40;15&#46;8&#37;&#41;&#59; and three had causes that had not been determined &#40;15&#46;8&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Microcephaly prevalence was 4&#46;1&#37; in this study&#46; Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve&#46; The main reason for microcephaly was intrauterine growth restriction&#46; All possible causes of microcephaly must be investigated to allow the best development of an affected baby&#46;</p></span>"
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                  \t\t\t\t">&#8804;32<span class="elsevierStyleHsp" style=""></span>cm&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="left" valign="\n
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                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -2&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\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8805;37 weeks&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</td><td class="td" title="\n
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                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">M&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\ttable-entry\n
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                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&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</td><td class="td" title="\n
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                  \t\t\t\t">IG zs &#8804; -3&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">7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&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">IG zs &#8804; -3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&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
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M&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</td><td class="td" title="\n
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                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\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">10&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&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="left" valign="\n
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                  \t\t\t\t">Fenton zs &#8804; -3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;37 weeks&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">N&#44; number of cases&#59; g&#44; grams&#59; cm&#44; centimeters&#59; HC&#44; head circumference&#59; CA&#44; congenital anomalies&#59; IUGR&#44; intrauterine growth restriction&#59; ZIKV&#44; Zika virus&#59; ZIKV exp&#44; Zika virus exposition&#46;</p>"
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">462&nbsp;\t\t\t\t\t\t\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">Term birth&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\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\ttop\n
                  \t\t\t\t">369 &#40;80&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm birth&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">40 &#40;19&#46;9&#37;&#41;&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">53 &#40;22&#46;2&#37;&#41;&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\ttop\n
                  \t\t\t\t">93 &#40;20&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG &#40;weeks&#47;days&#41;&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 6&#47;7&#8211;42 3&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 3&#47;7&#8211;41 5&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">23 6&#47;7&#8211;42 3&#47;7&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
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Median&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">38 2&#47;7&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 2&#47;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 2&#47;7&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3049<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>613&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2894<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>660&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2969<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>643&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3190<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>470&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3090<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>494&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3141<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>489&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2427<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>697&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2204<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>704&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2285<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>719&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">46&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">45&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">43&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">44&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcephalies &#8211; Term births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;63&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcephalies &#8211; Preterm births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;37&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology &#8211; Term births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 IUGR 1 ZIKV&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 IUGR 2 CA 2 ZIKV 1 ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;63&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology &#8211; Preterm births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1IUGR 1 ND&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">2 IUGR 1 CA 1ZIKV exp<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IUGR 1 ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Sensitivity &#40;&#37;&#41; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Specificity &#40;&#37;&#41; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">PPV &#40;&#37;&#41; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NPV &#40;&#37;&#41; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">AUC &#40;&#37;&#41; CI &#40;&#37;&#41; <span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kappa &#40;&#37;&#41; CI &#40;95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 73&#46;5&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">73&#46;7 68&#46;8&#8211;78&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&#46;3 9&#46;7&#8211;13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;8 83&#8211;90&#46;1 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;154 0&#46;075&#8211;0&#46;233&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 73&#46;5&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">91&#46;9 88&#46;5&#8211;94&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&#46;3 22&#46;6&#8211;37&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">95&#46;9 93&#46;4&#8211;97&#46;7 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;424 0&#46;259&#8211;0&#46;589&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#46;7 42&#46;1&#8211;99&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">92&#46;7 87&#46;9&#8211;96&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;6 20&#46;1&#8211;45&#46;8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">99&#46;4 96&#46;4&#8211;99&#46;9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#46;2 83&#46;9&#8211;93&#46;3 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;430 0&#46;913&#8211;0&#46;669&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 47&#46;8&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">97&#46;8 94&#46;3&#8211;99&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55&#46;6 32&#46;2&#8211;76&#46;7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">98&#46;9 96&#46;1&#8211;99&#46;9 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;704 0&#46;430&#8211;0&#46;978&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">57&#46;1 18&#46;4&#8211;90&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 95&#46;8&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">96&#46;6 92&#46;4&#8211;98&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78&#46;6 68&#46;8&#8211;86&#46;4 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;711 0&#46;404&#8211;1&#46;0&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 15&#46;8&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">71&#46;7 66&#46;8&#8211;76&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1&#46;9 1&#46;6&#8211;2&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">85&#46;8 81&#46;8&#8211;89&#46;2 &#60; 0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;025 -0&#46;01&#8211;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="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100 15&#46;8&#8211;100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">89&#46;4 85&#46;8&#8211;92&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4&#46;9 3&#46;7&#8211;6&#46;5&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">100&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">94&#46;7 91&#46;9&#8211;96&#46;7 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;084 -0&#46;0025&#8211;0&#46;192&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">-&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;091 -0&#46;07&#8211;0&#46;25&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
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        "texto" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The authors want to acknowledge all the patients that participated at this study&#44; as well as all the volunteers&#44; researchers&#44; and professionals involved in this project&#46; We acknowledge the researchers team&#44; named &#8220;Cohort Zika Jundia&#237; Consortium&#8221;&#44; which includes&#44; in addition to the authors of this paper&#44; Rita de C&#225;ssia Aguirre Dezena&#44; Andrea Cristina Botelho Silva&#44; Alexandra Siqueira Mello&#44; Clovis Antonio Lopes Pinto&#44; Dora Fix Ventura&#44; Danielle Bruna Leal de Oliveira&#44; Danilla Soares Tambalo&#44; Diego da Silva Lima&#44; Dirce Takako Fujiwara&#44; Edison Luiz Durigon&#44; Eduardo Roberto Bagne&#44; Fernanda Guerra Velasco&#44; Fernando Novo Arita&#44; Francisco Del Moral Hernandez&#44; Geovane Ribeiro dos Santos&#44; Juliana Paula Gomes de Almeida&#44; Karen Richter Camandulli&#44; Lucas Pires de Castro&#44; Luiz C P Baran&#44; M&#225;rcia Borges Machado&#44; Mayana Zatz&#44; Maria Manoela Duarte Rodrigues&#44; Maria de F&#225;tima Valente Rizzo&#44; Maria Am&#233;lia Farr&#227;o&#44; Raquel Prestes&#44; Sandra Helena A Bonom&#44; Sergio Vranjac&#44; S&#233;rgio Rosemberg&#44; Tathiana Ghisi de Souza&#44; Viviane Cristina Martori Pandini&#44; and Viviam Paschoarelli Paiva&#46;</p>"
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Original article
Prevalence and diagnostic accuracy of microcephaly in a pediatric cohort in Brazil: a retrospective cross-sectional study
Ana Paula Antunes Pascalicchio Bertozzia,
Corresponding author
bertozzianap@gmail.com

Corresponding author.
, Rosa Estela Gazetaa, Thamirys Cosmo Gillo Fajardob, Antonio Fernandes Moronc, Antoni Soriano-Arandesd, Ana Alarcone, Alfredo Garcia-Alixf, Alify Bertoldo da Silvaa, Nemésio Florence Filhoa, Stephanno Gomes Pereira Sarmentog, Steven S. Witkinc,h,i, Saulo Duarte Passosa
a Faculdade de Medicina de Jundiaí, Departamento de Pediatria, Jundiaí, SP, Brazil
b Faculdade de Medicina de Jundiaí, Laboratório de Infectologia Pediátrica, Jundiaí, SP, Brazil
c Universidade de São Paulo (USP), Instituto de Medicina Tropical, São Paulo, SP, Brazil
d Hospital Universitari Vall d’Hebron, Paediatric Infectious Diseases and Immunodeficiencies Unit, Unit of International Health-Tuberculosis Vall Hebron Drassanes, Barcelona, Spain
e Hospital Universitari Sant Joan de Déu, Institut de Recerca Sant Joan de Déu, Department of Neonatology, Esplugues de Llobregat, Spain
f University of Barcelona, Institut de Recerca Sant Joan de Déu, Fundación NeNe, Esplugues de Llobregat, Spain
g Faculdade de Medicina de Jundiaí, Departamento de Ginecologia e Obstetrícia, Jundiaí, SP, Brazil
h Weill Cornell Medicine, Department of Obstetrics and Gynecology, New York, United States
i Faculdade de Medicina de Jundiaí, Jundiaí, SP, Brazil
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          "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Inclusion and exclusion criteria&#46;</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">LMP&#44; Last Menstrual Period&#46;</p>"
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    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Congenital microcephaly is a clinical condition where the head circumference &#40;HC&#41; is smaller than expected&#46; It is defined as an HC equal to or less than two standard deviations &#40;SDs&#41; below the expected mean for a given gestational age and sex&#46;<a class="elsevierStyleCrossRefs" href="#bib0005"><span class="elsevierStyleSup">1&#44;2</span></a> It is a scenario that affects both the newborn &#40;reducing its quality of life and life expectancy&#41; and the family &#40;economic burdens and parental stress&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> Microcephaly is an adverse manifestation with multiple etiologies&#46; There is now a consensus on the association between Zika virus &#40;ZIKV&#41; infection during pregnancy and microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> Many recent studies from South America have cited a lower prevalence of microcephaly &#40;1&#8211;12 per 10&#44;000 children&#41; but the frequency in Brazil is reportedly higher&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">Although the presence of microcephaly is not difficult to identify using standard criteria&#44; several factors can affect the accuracy of its detection&#44; such as the time between delivery and the HC measurement&#44; the type of instrument used to measure the HC&#44; the shape of the baby&#8217;s skull&#44; and the accuracy of the gestational age determination&#44; among others&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The present cross-sectional study aimed to determine the most sensitive cutoff point by comparing different cutoff points to diagnose microcephaly&#44; compared to the INTERGROWTH-21st curve &#40;IG&#41;&#44; and to identify the etiology of the microcephalies observed&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Methods</span><p id="par0020" class="elsevierStylePara elsevierViewall">This retrospective observational cross-sectional study was performed using data obtained from the Jundia&#237; Zika Cohort study&#44; which was previously published&#46;<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> This is a maternal-infant cohort&#44; with patients both positive and negative for Zika virus&#46; Most of these study patients were negative for Zika virus&#46; All live newborn participants were born in the region of Jundia&#237; and followed at the Hospital Universit&#225;rio da Faculdade de Medicina de Jundia&#237; &#40;HUJ&#41; in the city of Jundia&#237;&#44; S&#227;o Paulo&#44; Brazil&#44; from March 2016 to August 2018&#46;</p><p id="par0025" class="elsevierStylePara elsevierViewall">The inclusion criteria were&#58; &#40;1&#41; gestational age &#8804;13 weeks and 6 days determined by obstetric ultrasound in the first trimester&#44; or &#40;2&#41; gestational age between 14&#8211;20 weeks and a difference &#60;1 week between the estimates based on the date of the last menstrual period and ultrasound examination&#46; These criteria were based on guidelines from the Committee on Obstetric Practice of the American College of Obstetricians and Gynecologists &#40;ACOG&#41; and the Brazilian Pediatrics Society &#40;SBP&#41; to increase accuracy&#44; since gestational age is a dependent variable of the curves used in this study&#46;<a class="elsevierStyleCrossRefs" href="#bib0050"><span class="elsevierStyleSup">10&#44;11</span></a> Newborns with incomplete anthropometric and&#47;or sex data were excluded from the study&#46; <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a> shows the process of patient selection&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Ethical considerations</span><p id="par0030" class="elsevierStylePara elsevierViewall">The study was approved by the Ethics Committee of the Jundia&#237; School of Medicine &#40;CAAE 53248616&#46;2&#46;0000&#46;5412&#59; legal opinion number 1&#46;446&#46;577&#41;&#46; Research participation was only accepted after mothers or legal guardians provided written informed consent&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Data collection</span><p id="par0035" class="elsevierStylePara elsevierViewall">During the cohort study period&#44; maternal data on general health and pregnancy were collected directly from the mothers&#46; The neonatology team &#40;composed of pediatricians and neonatologists&#41; underwent specific training on accurate anthropometric measurement offered by the JZC group&#46; At birth&#44; all newborns underwent a complete physical examination&#44; weight determination on a digital scale&#44; length measurement with a stainless steel anthropometer&#44; and HC measurement with a non-elastic tape measure &#40;presented in centimeters and millimeters&#41; following the guidelines by the Brazilian Ministry of Health &#40;MoH&#41; and the Brazilian Pediatrics Society&#46;</p><p id="par0040" class="elsevierStylePara elsevierViewall">Peripheral blood&#44; saliva&#44; and urine samples from pregnant women and babies were collected&#44; transported at 2&#8211;6<span class="elsevierStyleHsp" style=""></span>&#176;C for a maximum of 5<span class="elsevierStyleHsp" style=""></span>hours&#44; and stored at &#8722;80<span class="elsevierStyleHsp" style=""></span>&#176;C&#46; Serum samples were stored after collection by centrifugation at &#8722;20<span class="elsevierStyleHsp" style=""></span>&#176;C&#46;</p><p id="par0045" class="elsevierStylePara elsevierViewall">Detection of IgM and IgG antibodies for Dengue virus&#44; Chikungunya virus&#44; Parvovirus B19 virus&#44; STORCH&#44; and ZIVK was performed using a commercial ELISA kit &#40;Euroimmun&#8482;&#44; Euroimmun&#44; Lubeck&#44; Germany&#41; following the manufacturer&#8217;s recommendations&#46; The ELISA utilized to detect viral antibodies did not completely eliminate the possibility of cross-reactivity between the three arboviruses&#46; The detection of Dengue virus&#44; ZIKV&#44; and Chikungunya virus by real-time quantitative polymerase chain reaction &#40;RT-qPCR&#41; in blood&#44; saliva&#44; and urine utilized a published protocol&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">HC was classified by the z-score according to the Fenton curves for preterm newborns and IG for all term babies&#46; Microcephaly was diagnosed when the z-score was equal to or below two standard deviations of the expected mean&#46;<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">13&#44;14</span></a> Additionally&#44; in cases of microcephaly&#44; the difference in the weight and HC z-scores was calculated for proportionality assessment&#44; according to Noyola et al&#46;&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a> who found that in infants with congenital cytomegalovirus infection&#44; a difference &#8805;2 was associated with adverse neurodevelopmental outcomes&#46; Microcephalic newborns underwent transfontanellar ultrasound and&#47;or non-contrast-enhanced computed tomography&#44; and the results were verified by a team of radiologists&#46; Newborns were then divided into 10 groups for comparisons based on HC&#44; IG z-scores&#44; and sex &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#41;&#44; according to the different cutoff points established by the Brazilian MoH to simulate the different situations during the ZIKV epidemic&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Statistical analysis</span><p id="par0055" class="elsevierStylePara elsevierViewall">Statistical analyses were performed using the 12&#46;7 version of the SPSS software &#40;SPSS&#8482; South America&#59; SPSS Inc&#46;&#44; Chicago&#44; IL&#41;&#46; Cutoff points were determined using receiver operating characteristic curves&#44; finding the most appropriate balance between the sensitivity and specificity of the indicators and considering the Youden index&#46; In addition&#44; the Kappa index was calculated to describe the agreement between the diagnostic methods for microcephaly&#46;</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a> shows the characteristics of the study population&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Microcephaly prevalence</span><p id="par0065" class="elsevierStylePara elsevierViewall">The prevalence of microcephaly&#44; calculated according to the established HC cutoff points&#44; was 4&#46;1&#37;&#46; This translated to 3&#46;2&#37; for term births and 4&#46;3&#37; for babies delivered preterm&#46; The results for microcephaly prevalence in each group&#44; as well as the comparison between the HC cutoff points and standard IG curve&#44; are shown in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>&#46; Groups 8 and 9 had only one case each&#44; which ruled out statistical analysis&#46; In the remaining groups&#44; the percentage varied from 4&#46;3&#8211;29&#37;&#44; specificity varied from 71&#46;7&#8211;100&#37;&#44; and sensitivity ranged from 57&#46;1&#8211;100&#37;&#46;</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">Utilizing a cutoff value of 33<span class="elsevierStyleHsp" style=""></span>cm resulted in increased reporting of suspected microcephaly cases&#46; We identified 106 babies with an HC<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>33<span class="elsevierStyleHsp" style=""></span>cm compared to 12 cases when using the reference standard&#46; Therefore&#44; 84 cases &#40;79&#46;2&#37;&#41; were presumptive false positives&#46; When the cutoff was subsequently changed to 32<span class="elsevierStyleHsp" style=""></span>cm&#44; 41 babies &#40;38&#46;7&#37;&#41; were defined as having microcephaly&#44; and of them&#44; only 12 were true positives&#46; The accuracy for detecting infants who were truly positive for microcephaly increased further when different cutoffs were used for each sex&#46; It is also worth noting that as the groups were stratified&#44; the number of cases sampled decreased&#44; which reduced the statistical power of the tests performed&#46; The utilization of the World Health Organization &#40;WHO&#41; curve resulted in a further increase in specificity&#46; In addition&#44; it is noteworthy that for male babies the accuracy in detecting those who were indeed positive for microcephaly was very high &#40;100&#37; sensitivity and 98&#37; specificity&#41; in relation to the standard curve &#40;IG&#41;&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">From the 19 cases of microcephaly&#44; only 16 were available for analysis due to the loss of three cases to follow-up&#46; In terms of etiology &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#41;&#44; there were three &#40;15&#46;8&#37;&#41; positive cases for ZIKV&#44; three cases &#40;15&#46;8&#37;&#41; with other congenital anomalies &#40;one case each of trisomy 21&#44; band heterotopia&#44; and an unknown congenital syndrome still under diagnostic investigation&#41;&#44; and nine cases &#40;47&#46;4&#37;&#41; of intrauterine growth restriction with no other determined cause&#46; Lastly&#44; there was one case &#40;5&#46;2&#37;&#41; of a twin born to a ZIKV-positive mother who had microcephaly and intrauterine growth restriction and tested negative for ZIKV at birth&#46; All cases were negative for Dengue virus&#44; Chikungunya virus&#44; Parvovirus B19&#44; and STORCH&#46; Of the three microcephalic newborns with ZIKV infection at birth&#44; two were positive by PCR in urine and the third was positive for IgG antibodies to ZIKV&#44; but negative by PCR&#46; One PCR-positive newborn&#44; delivered at term&#44; had a z-score difference of 0&#46;82 between HC and weight&#44; with no additional findings on examination&#46;</p><p id="par0080" class="elsevierStylePara elsevierViewall">The baby went on to have HC catch-up growth and normal neurodevelopment&#46; The other PCR-positive baby had an imaging examination that showed lissencephaly&#44; ventriculomegaly&#44; and agenesis of the corpus callosum&#44; as well as clinical arthrogryposis and dysphagia&#46; The z-score difference between HC and weight was 3&#46;21&#46; The ZIKV IgG-positive newborn had altered visual acuity&#44; without any other clinical alterations&#44; and the z-score difference between HC and weight was not significant at birth but increased to 4&#46;10 during follow-up &#40;increased over time&#41;&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">In this study&#44; the prevalence of microcephaly was 4&#46;1&#37;&#46; In the literature&#44; the reported prevalence of microcephaly varies widely&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">The Latin American Collaborative Study of Congenital Malformations <span class="elsevierStyleItalic">&#40;ECLAMC&#41;</span> group conducted a study on microcephaly from 2005 to 2014&#44; including 10 Latin American countries &#40;including Brazil&#41; before the ZIKV epidemic&#44; which considered microcephaly as an HC less than or equal to three standard deviations below the reference according to the IG curve&#46; During this period&#44; the prevalence of microcephaly was 4&#46;4 per 10&#44;000 live births &#40;5&#46;4 cases per 10&#44;000 live births in Brazil&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Other studies utilizing the same diagnostic criteria as the present study have also been reported&#46; In the United States&#44; one population-based survey conducted from 2009 to 2013 reported 9&#44;678 cases of microcephaly with a prevalence of 8&#46;7 cases per 10&#44;000 live births&#44; and 95&#37; of these cases had a definite diagnosis of microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">17</span></a></p><p id="par0100" class="elsevierStylePara elsevierViewall">A Brazilian study using population-based data showed differences in the prevalence of microcephaly between the cities of S&#227;o Luis &#40;state of Maranh&#227;o&#44; Northeast region of Brazil&#59; 3&#46;5&#37;&#41; and Ribeir&#227;o Preto &#40;state of S&#227;o Paulo&#44; Southeast region of Brazil&#59; 2&#46;5&#37;&#41; in 2010&#46;<a class="elsevierStyleCrossRef" href="#bib0030"><span class="elsevierStyleSup">6</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">During the ZIKV epidemic&#44; a study from the SINASC &#40;&#8220;Sistema de Informa&#231;&#245;es sobre Nascidos Vivos&#8221; &#8211; Information System about Livebirths&#41; reported a nine-fold increase in the prevalence of microcephaly&#46;<a class="elsevierStyleCrossRef" href="#bib0090"><span class="elsevierStyleSup">18</span></a> Also during the same period in Southern Brazil&#44; in a study with a large number of newborns&#44; microcephaly was detected in 9&#46;6 per 10&#44;000 live births &#40;from the initial sample&#44; 60&#46;8&#37; were &#8220;non-confirmed&#8221; microcephaly&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">In Brazil&#44; those differences in the prevalence of microcephaly may also have occurred because of the different cutoff points established by the Brazilian MoH from November 2015 to August 2016&#46; During this period&#44; four different cutoff points were considered &#40;for term babies&#58; 33<span class="elsevierStyleHsp" style=""></span>cm in November 2015&#44; 32<span class="elsevierStyleHsp" style=""></span>cm in December 2015&#44; WHO curve in March 2016&#44; and IG curve in August 2016&#59; for preterm babies&#58; Fenton curve from November 2015 to March 2016&#44; and then the IG curve&#41;&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#8211;23</span></a></p><p id="par0115" class="elsevierStylePara elsevierViewall">Considering the IG curve as the gold-standard and comparing the different cutoff points previously established by the MoH&#44; we observed that the sensitivity was 100&#37; but the specificity was low&#44; especially with the first two cutoff points&#46;</p><p id="par0120" class="elsevierStylePara elsevierViewall">In addition to increasing sensitivity&#44; the use of a more stringent cutoff point for reporting suspected cases of microcephaly has an economic impact by reducing the number of babies who require additional screening&#46; In a country with low to moderate health resources such as Brazil&#44; this cost impact must be seriously considered&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">A strength of our study was the inclusion of newborns with a very well-defined gestational age&#44; which increased accuracy since age was a dependent variable in the IG curve &#40;the standard curve for this study&#41;&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">The limitations of our study should also be mentioned&#46; Firstly&#44; most of our study sample were the offspring of high-risk pregnant women&#46; Six of the nineteen microcephaly cases were from pregnant women with hypertension &#40;chronic and&#47;or gestational&#41;&#59; one had diabetes&#59; and another had thrombophilia&#46; In these high-risk women&#44; there is a known association between maternal pathology and intrauterine growth restriction&#46;<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">24&#44;25</span></a> A second limitation was that 20&#37; of our subjects were preterm newborns&#46; This varies from the rates &#40;7&#46;5&#8211;11&#37;&#41; observed in countries such as France and the United States&#46; This difference may have increased the number of small-for-gestational-age newborns in our study&#46;<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">26&#44;27</span></a> Lastly&#44; although newborns were tested for both viral antibodies and ZIKV by gene amplification&#44; there remains a small possibility that a variable number of ZIKV-negative babies with microcephaly were actually infected with this virus&#46; Inadequacies of the testing protocols have been previously reported&#46;<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">28</span></a></p><p id="par0135" class="elsevierStylePara elsevierViewall">Regarding the etiology of microcephaly&#44; it is noteworthy that although ZIKV infection was a primary motivator for recent microcephaly-based studies in Brazil&#44; it was only one of several etiological factors identified&#46; Thus&#44; even in the periods of a particular outbreak&#44; multiple etiologies must be considered&#46; However&#44; when HC was adjusted for weight &#40;by the difference in z-score&#41; a greater disproportion was noticed in two of the three cases with ZIKV infection&#46; Microcephaly in relation to birth weight predicts adverse neurological outcomes in infants with congenital infection&#44; and the disproportion between them suggests a higher risk of developmental disability&#46;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;16</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">We conclude that the WHO cutoff point was almost as sensitive as the INTERGROWTH-21st curve to diagnose microcephaly in our study&#46; Despite the ZIKV epidemic being the trigger of this study&#44; it was not the main cause of microcephaly&#46; For the majority of patients other causes were found&#44; thus emphasizing the importance of screening and follow-up to facilitate individual approaches and to maximize their developmental potential&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Funding</span><p id="par0145" class="elsevierStylePara elsevierViewall">This work and this manuscript were supported by the <span class="elsevierStyleGrantSponsor" id="gs0005">Funda&#231;&#227;o de Amparo &#224; Pesquisa do Estado de S&#227;o Paulo</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0005">2016&#47;08578-0</span>&#41;&#44; the <span class="elsevierStyleGrantSponsor" id="gs0010">Brazilian Ministry of Health</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0010">861306&#47;2017</span> and <span class="elsevierStyleGrantNumber" refid="gs0010">861307&#47;2017</span>&#41;&#44; and the <span class="elsevierStyleGrantSponsor" id="gs0015">London School of Hygiene and Tropical Medicine</span> &#40;SDP&#35;grant <span class="elsevierStyleGrantNumber" refid="gs0015">PC0002&#47;16</span>&#41;&#46;</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Conflicts of interest</span><p id="par0150" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest&#46;</p></span></span>"
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        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objective</span><p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">We sought to describe the prevalence of microcephaly and to compare the different cutoff points established by the Brazilian Ministry of Health at various times during a Zika virus epidemic&#46; As a secondary aim&#44; we investigated the possible etiology of the microcephaly&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Method</span><p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">This retrospective study utilized newborn participants in the Zika Cohort Study Jundia&#237;&#46; Newborns from the Zika Cohort Study Jundia&#237; with an accurate gestational age determination and complete anthropometric data were analyzed&#44; and microcephaly was diagnosed according to the INTERGROWTH-21<span class="elsevierStyleSup">st</span> curve&#46; At delivery&#44; fluids were tested for specific antibodies and for viruses&#46; Brain images were evaluated for microcephaly&#46; Receiver Operating Characteristic curves were plotted to define the accuracy of different cutoff points for microcephaly diagnosis&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Of 462 eligible newborns&#44; 19 &#40;4&#46;1&#37;&#41; were positive for microcephaly&#46; Cutoff points corresponding to the curves of the World Health Organization yielded the best sensitivity and specificity&#46; Three of the microcephaly cases &#40;15&#46;8&#37;&#41; were positive for Zika virus infections&#59; nine &#40;47&#46;4&#37;&#41; had intrauterine growth restriction&#59; one had intrauterine growth restriction and was exposed to Zika virus&#59; three had a genetic syndrome &#40;15&#46;8&#37;&#41;&#59; and three had causes that had not been determined &#40;15&#46;8&#37;&#41;&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Microcephaly prevalence was 4&#46;1&#37; in this study&#46; Cutoff values determined by the World Health Organization had the highest sensitivity and specificity in relation to the standard IG curve&#46; The main reason for microcephaly was intrauterine growth restriction&#46; All possible causes of microcephaly must be investigated to allow the best development of an affected baby&#46;</p></span>"
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                  \t\t\t\t">1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">M and F&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8804;33<span class="elsevierStyleHsp" style=""></span>cm&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">&#8805;37 weeks&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">M and F&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8804;32<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8805;37 weeks&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">IG zs &#8804; -2&nbsp;\t\t\t\t\t\t\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">3&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">&#8804;31&#46;5<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">IG zs &#8804; -2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">4&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  " align="left" valign="\n
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                  \t\t\t\t">&#8804;31&#46;9<span class="elsevierStyleHsp" style=""></span>cm&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">&#8805;37 weeks&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="left" valign="\n
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                  \t\t\t\t">IG zs &#8804; -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="\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">5&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="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fenton zs &#8804; -2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -2&nbsp;\t\t\t\t\t\t\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  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">&#8804;33<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8804;32<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8804;31&#46;5<span class="elsevierStyleHsp" style=""></span>cm&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8804;31&#46;9<span class="elsevierStyleHsp" style=""></span>cm&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#8805;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">M and F&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Fenton zs &#8804; -3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;37 weeks&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG zs &#8804; -3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
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          "leyenda" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">N&#44; number of cases&#59; g&#44; grams&#59; cm&#44; centimeters&#59; HC&#44; head circumference&#59; CA&#44; congenital anomalies&#59; IUGR&#44; intrauterine growth restriction&#59; ZIKV&#44; Zika virus&#59; ZIKV exp&#44; Zika virus exposition&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Variables&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t">462&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Term birth&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</td><td class="td" title="\n
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                  \t\t\t\t">186 &#40;77&#46;8&#37;&#41;&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">369 &#40;80&#37;&#41;&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">Preterm birth&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">40 &#40;19&#46;9&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">93 &#40;20&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">IG &#40;weeks&#47;days&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">23 6&#47;7&#8211;42 3&#47;7&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">26 3&#47;7&#8211;41 5&#47;7&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">23 6&#47;7&#8211;42 3&#47;7&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">Median&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  " align="left" valign="\n
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                  \t\t\t\t">38 2&#47;7&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">38 2&#47;7&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2894<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>660&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3190<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>470&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\ttop\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">3141<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>489&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm Mean Weight &#40;g&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t\ttop\n
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                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2285<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>719&nbsp;\t\t\t\t\t\t\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">Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">47&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">46&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;4&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">47&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;6<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">47&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Preterm Mean Length &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">45&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">43&#46;5<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;3&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">44&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>4&#46;5&nbsp;\t\t\t\t\t\t\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">Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34&#46;0<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;1&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">33&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;3&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">33&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>2&#46;2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Term Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">34&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;5&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">33&#46;9<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">34&#46;1<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>1&#46;6&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Preterm Mean HC &#40;cm&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">32&#46;2<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">31&#46;7<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>3&#46;1&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcephalies &#8211; Term births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">5&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">7&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">12 &#40;63&#37;&#41;&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
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Microcephalies &#8211; Preterm births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">5&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">7 &#40;37&#37;&#41;&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
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology &#8211; Term births&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 IUGR 1 ZIKV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2 IUGR 2 CA 2 ZIKV 1 ND&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="left" valign="\n
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                  \t\t\t\t">12 &#40;63&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Etiology &#8211; Preterm births&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="left" valign="\n
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                  \t\t\t\t">1IUGR 1 ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">2 IUGR 1 CA 1ZIKV exp<span class="elsevierStyleHsp" style=""></span>&#43;<span class="elsevierStyleHsp" style=""></span>IUGR 1 ND&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">7 &#40;37&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  """
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          "leyenda" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">CI&#44; confidence interval&#59; PPV&#44; positive predictive value&#59; NPV&#44; negative predictive value&#59; AUC&#44; area under the curve&#46;</p>"
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">NPV &#40;&#37;&#41; CI &#40;&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-head\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Kappa &#40;&#37;&#41; CI &#40;95&#37;&#41;&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">100 73&#46;5&#8211;100&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">11&#46;3 9&#46;7&#8211;13&#46;2&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
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                  \t\t\t\t">100&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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">86&#46;8 83&#8211;90&#46;1 &#60; 0&#46;0001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
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                  \t\t\t\t">0&#46;154 0&#46;075&#8211;0&#46;233&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\ttop\n
                  \t\t\t\t">2&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttable-entry\n
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        "texto" => "<p id="par0155" class="elsevierStylePara elsevierViewall">The authors want to acknowledge all the patients that participated at this study&#44; as well as all the volunteers&#44; researchers&#44; and professionals involved in this project&#46; We acknowledge the researchers team&#44; named &#8220;Cohort Zika Jundia&#237; Consortium&#8221;&#44; which includes&#44; in addition to the authors of this paper&#44; Rita de C&#225;ssia Aguirre Dezena&#44; Andrea Cristina Botelho Silva&#44; Alexandra Siqueira Mello&#44; Clovis Antonio Lopes Pinto&#44; Dora Fix Ventura&#44; Danielle Bruna Leal de Oliveira&#44; Danilla Soares Tambalo&#44; Diego da Silva Lima&#44; Dirce Takako Fujiwara&#44; Edison Luiz Durigon&#44; Eduardo Roberto Bagne&#44; Fernanda Guerra Velasco&#44; Fernando Novo Arita&#44; Francisco Del Moral Hernandez&#44; Geovane Ribeiro dos Santos&#44; Juliana Paula Gomes de Almeida&#44; Karen Richter Camandulli&#44; Lucas Pires de Castro&#44; Luiz C P Baran&#44; M&#225;rcia Borges Machado&#44; Mayana Zatz&#44; Maria Manoela Duarte Rodrigues&#44; Maria de F&#225;tima Valente Rizzo&#44; Maria Am&#233;lia Farr&#227;o&#44; Raquel Prestes&#44; Sandra Helena A Bonom&#44; Sergio Vranjac&#44; S&#233;rgio Rosemberg&#44; Tathiana Ghisi de Souza&#44; Viviane Cristina Martori Pandini&#44; and Viviam Paschoarelli Paiva&#46;</p>"
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Article information
ISSN: 00217557
Original language: English
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