Original article
Clinical and epidemiological aspects of microcephaly in the state of Piauí, northeastern Brazil, 2015–2016
Aspectos clínicos e epidemiológicos da microcefalia no Estado do Piauí, Nordeste do Brasil, 2015-2016
Isabel Marlúcia Lopes Moreira de Almeidaa, Carmen Viana Ramosa, Danielle Carvalho Rodriguesb, Amanda Carvalho de Sousaa, Maria de Lourdes Cristina Alcântara Paz Carvalho do Nascimentoa, Marcos Vilhena Bittencourt da Silvaa, Francisca Miriane Araújo Batistaa, Jéssica Pereira dos Santosb,c, Roselane Sampaio de Oliveirad, Filipe Augusto de Freitas Soaresb, Samanta Cristina das Chagas Xavierb, Filipe Anibal Carvalho-Costab,c,
Corresponding author
a Centro Regional de Referência Regional em Microcefalia/Governo do Estado do Piauí, Teresina, PI, Brazil
b Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil
c Escritório Regional Fiocruz Piauí, Teresina, PI, Brazil
d Universidade Federal Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Calcificações na interface entre a substância branca e cinza e nas regiões do núcleo da base. Ectasia ventricular moderada associada a paralelismo dos ventrículos laterais, sugere disgenesia do corpo caloso; 1; Deformidade do esqueleto e redução do volume do cerebelo devido a atrofia, com aumento do espaço do fluido cerebrospinal da fossa posterior.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">B. Pequenas calcificações no intervalo entre a substância branca e cinza; 1; Escassez dos sulcos corticais, configura alteração do espectro de lisencefalia.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">C. Pequenas calcificações no intervalo entre a substância branca e cinza, linear e puntiforme; 1; Escassez dos sulcos corticais, configura alteração do espectro de lisencefalia.</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">D. Pequenas calcificações no intervalo entre as substâncias branca e cinza, linear e puntiforme; 1;1; Assimetria dos hemisférios cerebrais com acentuação dos sulcos corticais e redução do volume do hemisfério esquerdo devido a atrofia, com ectasia compensatória consequente do ventrículo lateral.</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">E. Leve paralelismo dos ventrículos laterais, sugere disgenesia do corpo caloso.</p> <p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">F. Pequenas calcificações puntiformes na interface entre a substância branca e cinza e calcificação grosseira no lóbulo frontal esquerdo. Escassez dos sulcos corticais com poucos sulcos rasos, configura alteração do espectro de lisencefalia. Leve paralelismo dos ventrículos laterais, sugere disgenesia do corpo caloso; 1; Deformidade do esqueleto na região frontal alta.</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">G. Pequenas calcificações puntiformes no intervalo entre a substância branca e cinza e a região periventricular. Escassez dos sulcos corticais, configura alteração do espectro de lisencefalia. Redução volumétrica do cerebelo; 1; Deformidade do esqueleto.</p> <p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">H. Pequenas calcificações puntiformes na interface entre a substância branca no lobo frontal esquerdo. Escassez dos sulcos corticais, além dos sulcos rasos, configura alteração do espectro de lisencefalia. Expansão dos espaços de fluido extra‐axial, mais evidente nas fossas temporais. 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"aff0010" ] ] ] 11 => array:4 [ "nombre" => "Filipe Anibal" "apellidos" => "Carvalho-Costa" "email" => array:1 [ 0 => "guaratiba@ioc.fiocruz.br" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Centro Regional de Referência Regional em Microcefalia/Governo do Estado do Piauí, Teresina, PI, Brazil" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Instituto Oswaldo Cruz, Fundação Oswaldo Cruz, Rio de Janeiro, RJ, Brazil" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Escritório Regional Fiocruz Piauí, Teresina, PI, Brazil" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Universidade Federal Rio de Janeiro, Rio de Janeiro, RJ, Brazil" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Aspectos clínicos e epidemiológicos da microcefalia no Estado do Piauí, Nordeste do Brasil, 2015-2016" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2321 "Ancho" => 3167 "Tamanyo" => 899407 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Head computer tomography scans of confirmed microcephaly cases in the state of Piauí, Brazil, 2015–2016.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">(A) Calcifications at the interface between white and gray matter and in the core-capsular regions. Moderate ventricular ectasia associated with parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum. Deformity of the skull and volume reduction of the cerebellum due to atrophy, with enlargement of the cerebrospinal fluid space of the posterior fossa.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">(B) Small calcifications at the interface between white and gray matter. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">(C) Small calcifications at the interface between white and gray matter, linear and punctiform. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly.</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">(D) Small calcifications at the interface between white and gray substances, linear and punctiform. Asymmetry of the cerebral hemispheres with accentuation of the cortical sulci and volumetric reduction of the left hemisphere due to atrophy, with consequent compensatory ectasia of the lateral ventricle.</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">(E) Slight parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum.</p> <p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">(F) Small punctate calcifications at the interface between white and gray matter, and gross calcification in the left frontal lobe. Scarcity of cortical sulci with few shallow sulci, configuring an alteration of the spectrum of lissencephaly. Slight parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum. Deformity of the skull in high frontal region.</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">(G) Small punctate calcifications at the interface between white and gray matter and periventricular region. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly. Volumetric reduction of the cerebellum. Deformity of the skull.</p> <p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">(H) Small punctate calcifications at the interface between white and gray matter in the right frontal lobe. Scarcity of cortical sulci, in addition to shallow sulci, configuring an alteration of the spectrum of lissencephaly. Expansion of the extra-axial fluidic spaces, more evident in the temporal fossae. Reduction of right hemisphere volume with compensatory ectasia of the right lateral ventricle.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">From mid-2015, a significant increase in the incidence of microcephaly and other central nervous system (CNS) malformations was observed in Brazil, mainly in the northeast region.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">In 2015, Zika virus (ZIKV) was identified by PCR in patients with rash, fever, conjunctivitis, and arthralgia in northeastern Brazil, during the epidemic of an exanthematic disease.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">2</span></a> An association between congenital infection with ZIKV and microcephaly was proposed. The causality was elucidated in several steps: (i) PCR-identification of ZIKV in the amniotic fluid of pregnant women who gave birth to babies with microcephaly<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">3</span></a>; (ii) the identification of ZIKV nucleic acids by PCR and arbovirus-like particles by electron microscopy in the brain of an aborted microcephalic fetus<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">4</span></a>; (iii) a case-control study in the state of Pernambuco showing a higher proportion of ZIKV-infection among children with microcephaly when compared to the controls.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">5</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Microcephaly is defined by a head circumference (HC) more than two standard deviations (a <span class="elsevierStyleItalic">z</span>-score<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−2) below the mean for gestational age, and severe microcephaly is defined as a HC <span class="elsevierStyleItalic">z</span>-score<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−3.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">6</span></a> Microcephaly is a clinical manifestation representing disruption in neurogenesis and death of neuronal progenitors.<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">7</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The most well recognized causes of microcephaly include genetic alterations, congenital infections (such as cytomegalovirus [CMV], herpes simplex virus [HSV], rubella virus, <span class="elsevierStyleItalic">Toxoplasma gondii</span>, and syphilis), or embryonic exposure to teratogenic substances.<a class="elsevierStyleCrossRefs" href="#bib0165"><span class="elsevierStyleSup">8–10</span></a> Congenital Zika is a syndrome characterized by severe microcephaly, decreased brain tissue with a specific pattern of damage, including subcortical calcifications, damage to the back of the eye, congenital contractures, and hypertonia.<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">11</span></a> From November 2015 to December 2016, 10,867 cases of congenital microcephaly were investigated in Brazil. Of those, 2366 were confirmed, 49 were classified as probable, 5,269 were found to be non-microcephalic (discarded), and, as of 31 December 2016, 3183 cases remained under investigation. The criteria for confirmation included typical findings of congenital infection, such as cerebral calcifications or ventricular and posterior fossa alterations, among other clinical signs observed by any imaging method or ZIKV-positivity in laboratory tests.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Of the total number of confirmed cases, 100 were reported in Piauí, northeastern Brazil. The present study aims to describe the clinical, radiological, and epidemiological characteristics of microcephaly cases in the state of Piauí during the 2015–2016 epidemic.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients and methods</span><p id="par0030" class="elsevierStylePara elsevierViewall">The state of Piauí has an area of 251,577.738<span class="elsevierStyleHsp" style=""></span>km<span class="elsevierStyleSup">2</span>. It has a population of 3,194,718 inhabitants; 847,430 of which live in the state's capital, Teresina. Piauí is the second poorest state in Brazil, with a per capita gross domestic product of 3777.60 USD, and it has the fourth lowest human development index in the country (0.646).</p><p id="par0035" class="elsevierStylePara elsevierViewall">A case series study was performed. All cases of congenital microcephaly confirmed in the state of Piauí between 8 November 2015 and 31 December 2016 were included. Inclusion was contingent on the newborn being submitted to the investigation protocol of the Regional Reference Center for Microcephaly (RRCM) established during the epidemic. At the end of the mentioned period, RRCM investigated 188 newborns; 88 cases were discarded. The RRCM's criteria for case confirmation were the presence of clinical, laboratory, and radiological findings compatible with CNS malformation.<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">12</span></a> Monthly incidence rates were calculated as the number of confirmed microcephaly cases<span class="elsevierStyleHsp" style=""></span>×<span class="elsevierStyleHsp" style=""></span>1000/number of live births in the month. Sixty-three of the discarded cases had available data. Discarded cases were used as a comparison group to evaluate some associations between clinical and epidemiological variables and the presence of microcephaly. HC <span class="elsevierStyleItalic">z</span>-scores were calculated for gestational ages with the software Intergrowth-21st, available in <a href="http://intergrowth21.ndog.ox.ac/pt/ManualEntry">http://intergrowth21.ndog.ox.ac/pt/ManualEntry</a>. Fisher's test was employed to compare the frequencies of the categorical variables, and the Kruskal–Wallis test used to compare the medians of the continuous variables. For each comparison, the numbers of confirmed and discarded cases varied, according to the existence of information for each variable.</p><p id="par0040" class="elsevierStylePara elsevierViewall">For geospatial analyses, the base map was acquired from the Brazilian Institute of Geography and Statistics (IBGE). Google Earth® was used to determine the address coordinates of all confirmed and discarded cases. Coordinates were recorded in the WGS 84 Datum (World Geodetic System 1984) geodetic coordinate system. Spatial data were analyzed in a GIS platform using ArcGis 9.3 software (Environmental Systems Research Institute, Redlands, CA, USA). With this analysis, the goal was to describe the geographical distribution of microcephaly cases and show areas with high concentrations of cases or high intensity of cases per unit area. The kernel density technique was applied in order to assess the intensity of incidence per unit area. This technique produces a non-topographical surface displaying the distribution of the disease.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The Research Ethics Committee of the Instituto Oswaldo Cruz/Fundação Oswaldo Cruz approved this study (protocol # 2.121.367).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Results</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Spatiotemporal distribution of microcephaly cases</span><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>A demonstrates the epidemic curve of microcephaly, including the initially suspected and subsequently discarded cases. The number of cases increased from September 2015, with 4 cases confirmed. The epidemic peak was observed in November 2015, when 25 infants with confirmed microcephaly were born in the state of Piauí (1/4 of the total confirmations). In 2015, in October, November, and December, almost 60% of the confirmed cases were born. The epidemic has declined since April 2016. During the pre-epidemic period (January to August 2015), the average monthly incidence rate of congenital microcephaly in the state of Piauí was 0.18 cases/1000 live births. In September 2015, the monthly incidence increased five-fold compared to the pre-epidemic period, reaching 0.89/1000 live births. In October, November, and December 2015 there was a highly significant increase, with monthly incidence rates of 4.46, 6.33, and 3.86/1000 live births respectively. During the peak of the epidemic, in November 2015, confirmation rate reached 89%.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">The map in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a> depicts the spatial distribution of microcephaly cases. Almost half of the cases (44/100 [44%]) were reported in the state capital, the city of Teresina; 46 (20.5%) of the 224 municipalities in the state of Piauí registered at least one confirmed case. Except for Teresina, the maximum number of cases per municipality was 3. Teresina thus represented the most intense area of epidemic development in the state of Piauí. Georeferencing of the confirmed and discarded cases and the kernel density analysis revealed a clustered pattern of confirmed cases in the municipality of Teresina.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Obstetric and childbirth data</span><p id="par0060" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> presents obstetric and childbirth data. Maternal age was slightly, but significantly, higher in the group of confirmed cases. The median gestational age of 38 weeks at birth shows that, in both groups, term pregnancies predominated, with a small proportion of preterm deliveries. In addition, the birth weight medians were similar between confirmed and discarded cases, with a similar low birth weight frequency and a small proportion of very low birth weight. Perinatal asphyxia was a rare condition among both infants born with microcephaly and discarded cases, as demonstrated by high Apgar scores in the 1st and 5th minutes after childbirth in both groups.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Exposure to vaccines routinely offered to pregnant women was evaluated. There were no significant differences in vaccination rates for influenza, diphtheria-tetanus-acellular pertussis (DTaP) and hepatitis B in either group. Indeed, the rate of immunization coverage was high both in mothers who gave birth to infants with microcephaly and those of discarded cases.</p><p id="par0070" class="elsevierStylePara elsevierViewall">Among mothers of infants with confirmed microcephaly, 50/97 (51.5%) reported the presence of a skin rash during pregnancy. This number is significantly higher than that observed among mothers of discarded cases (8/51 [15.7%]; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001).</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Clinical and radiological characteristics of confirmed and discarded microcephaly cases</span><p id="par0075" class="elsevierStylePara elsevierViewall">Among the confirmed cases in which it was possible to recover the exact values of HC (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>92), it was observed that 33 infants (35.9%) had a HC <span class="elsevierStyleItalic">z</span>-score between −2 and −3, 23 (25%) had <span class="elsevierStyleItalic">z</span>-scores between −3 and −4, and 8 (8.7%) had <span class="elsevierStyleItalic">z</span>-scores less than −4. Fifteen children were born with normal HC (z-score<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>−2). The median HC among confirmed children was 30<span class="elsevierStyleHsp" style=""></span>cm (interquartile range [IQR]<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>29–31<span class="elsevierStyleHsp" style=""></span>cm; range [<span class="elsevierStyleItalic">R</span>]<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>26–36<span class="elsevierStyleHsp" style=""></span>cm), while among discarded cases the median was 31<span class="elsevierStyleHsp" style=""></span>cm (IQR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>30.5–32<span class="elsevierStyleHsp" style=""></span>cm; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>27.5–36<span class="elsevierStyleHsp" style=""></span>cm), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 (Kruskal–Wallis test). <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>B presents the correlation between gestational age and HC of confirmed and discarded cases, discriminating the sex of the newborn. A large proportion of confirmed cases had a HC <span class="elsevierStyleItalic">z</span>-score below −2 for the gestational age. Median HC <span class="elsevierStyleItalic">z</span>-scores among confirmed and discarded cases were −2.51 (IQR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−3.19 to −1.63; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−5.22 to 1.43) and −1.49 (IQR<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−2.01 to −0.91; <span class="elsevierStyleItalic">R</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>−3.45 to 2), <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001 (Kruskal–Wallis test), respectively.</p><p id="par0080" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> summarizes clinical and radiological findings. It was possible to access head computer tomography (CT) scans of 95 infants confirmed with microcephaly and 21 discarded cases. Some radiological findings are presented in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>. CT scans revealed intracranial calcifications in 78/95 (82.1%) confirmed microcephaly cases and in 1/25 (4.8%) of discarded cases (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001). Among confirmed cases with calcifications, two children had calcifications on basal nuclei (not shown). Ten (10.5%) confirmed cases presented lissencephaly-pachygyria spectrum alterations, 7 (7.4%) presented hydrocephalus, and 5 (5.3%) presented agenesis of the corpus callosum. In addition, 40 infants underwent transfontanelar ultrasound (US) (20 confirmed and 20 discarded cases). Among infants with confirmed microcephaly, 11 (55%) presented dilated cerebral ventricles and 3 (15%) presented a sonographic diagnosis of hydrocephalus. Transfontanelar US detected 6 (30%) children with calcifications.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0085" class="elsevierStylePara elsevierViewall">In this series, 87 newborns were submitted to ophthalmologic evaluation (67 confirmed cases and 20 discarded cases). The most frequent fundoscopic findings in confirmed cases were retinal pigment epithelium rarefaction (9/67 [13.4%]), retinal pigment epithelial atrophy (6/67 [9%]), and papillary pallor (3/67 [4.8%]). All examinations of discarded cases were normal. With the objective of neonatal screening for deafness, RRCM evaluated otoacoustic emissions in 91 newborns in the first week of life (70 confirmed and 21 discarded cases). The frequency of absence of otoacoustic emissions was 21/70 (30%) among the confirmed cases and 2/21 (9.5%) among the discarded cases (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.051).</p><p id="par0090" class="elsevierStylePara elsevierViewall">Two newborns with microcephaly also presented musculoskeletal involvement and alterations in extremities, including one with lower limb muscle atrophy associated with hip dislocation and one with overlapping fingers. Echocardiography detected cardiac malformations in 2 infants; 1 with patent foramen ovale and ventricular septal defect and 1 with patent foramen ovale and mild pulmonary hypertension.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Serological data related to other congenital infections</span><p id="par0095" class="elsevierStylePara elsevierViewall">Eleven confirmed cases had serological evidence (IgM-positivity) of infection with other teratogenic pathogens, including CMV, herpes and syphilis. Frequencies of IgM-reactivity for rubella, cytomegalovirus, toxoplasmosis, herpes, dengue and chikungunya among confirmed cases were 0/74 (0%), 5/89 (5.6%), 0/81 (0%), 5/79 (6.3%), 8/76 (10.5%), and 6/62 (9.7%), respectively. Among discarded cases, these frequencies were 0/29 (0%), 1/30 (3.3%), 0/31 (0%), 0/22 (0%), 3/23 (13%), and 1/14 (7.1%), respectively. VDRL-positivity among confirmed and discarded cases was 3/84 (3.6%) and 0/28 (0%), respectively. Among CMV-positive microcephaly cases, two had hepatosplenomegaly, jaundice, anemia, and thrombocytopenia.</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Discussion</span><p id="par0100" class="elsevierStylePara elsevierViewall">The present study describes the putative ZIKV-related microcephaly epidemic in the state of Piauí. The epidemic curve shows a concentration of cases during the 8-month period from September 2015 to April 2016. The epidemic peaked in November 2015 when the incidence rate increased almost 15-fold in relation to the pre-epidemic average incidence. This period also corresponds to the highest number of reported cases for all northeastern states. None of the reported cases presented laboratory confirmation for ZIKV infection. It is important to note that, at the time of the epidemic, there were no specific serological tests for ZIKV that could be used to detect IgG or IgM immunoglobulins in newborns or in mothers. Therefore, during the epidemic, laboratory confirmations were based on molecular tests (PCR), which, however, depend heavily on the presence of viremia (i.e. viral nucleic acids), and are therefore not very useful for the diagnosis of infection in the infant after birth, considering that viral infection and replication occur during pregnancy. Among the confirmed cases in the state of Piauí, 68 had blood samples sent for PCR to ZIKV, but all showed negative results. No cerebrospinal fluid sample from affected infants was sent for laboratory testing of viral infections.</p><p id="par0105" class="elsevierStylePara elsevierViewall">It is noteworthy that presumed Zika-related microcephaly exhibited an epidemic behavior pattern, which stands in contrast to the endemic agents with which microcephaly is associated, such as CMV, herpes, and <span class="elsevierStyleItalic">Toxoplasma gondii</span>, which exist in a non-epidemic relationship with the human population. Brazil has a high rubella-vaccine coverage for women, which has thus substantially reduced the incidence of congenital rubella.<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">13</span></a> Currently, Brazil experiences an increasing incidence of congenital syphilis.<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">14</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">The kernel density map shows that the municipality most affected by the Zika outbreak in Piauí throughout the study period was Teresina. Teresina concentrates more than 1/4 of the population of the state and presents serious problems of sanitation, infrastructure, waste management and, consequently, vector control. Another arthropod-borne disease, visceral leishmaniasis, is endemic in the city. From 2007 to 2012, an annual average of 3745 cases of dengue (approximately 50% of cases in the state) has been reported in Teresina, which highlights the local difficulties with mosquito control. On the other hand, the occurrence of microcephaly cases in other municipalities of Piauí illustrates the spread of the microcephaly epidemic in the Brazilian semiarid region, as observed in other states. In northeastern Brazil, the prolonged drought in the 4 years prior to the microcephaly epidemic has led to an increase in sub-standard potable water storage systems, the use of which may have contributed to an increase in mosquito density.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Regarding maternal and obstetric data, full term children predominated among the cases, but with relatively low birth weight for gestational ages. In general, they were children without perinatal asphyxia and therefore unexposed to hypoxia. Consequently, hypoxia cannot serve to explain the neurological impairment of the infants. The vaccination schedule for pregnant women in Brazil includes two doses of the diphtheria-tetanus vaccine (dT), one dose of diphtheria-tetanus-acellular pertussis vaccine (dTaP), two doses of the influenza vaccine, and three doses of the hepatitis B vaccine. Our data demonstrate that the frequency of maternal vaccination with these vaccines was similar among confirmed and discarded cases.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Regarding the clinical presentation, it was observed that the majority of the children had a HC <span class="elsevierStyleItalic">z</span>-score<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−2, with about a quarter of cases exhibiting severe microcephaly (HC <span class="elsevierStyleItalic">z</span>-score<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>−3). Some affected infants had normal HC. The most frequent clinical-radiological picture was microcrania associated with cerebral calcifications, with frequent presentation of ex-vacuo ventricular dilatation, sometimes constituting hydrocephalus and lissencephaly. A more detailed assessment of CNS images of infants with presumed Zika-related microcephaly demonstrated poor gyral development with irregular “beaded” cortex, more consistent with polymicrogyria.<a class="elsevierStyleCrossRef" href="#bib0200"><span class="elsevierStyleSup">15</span></a> A small proportion of cases presented musculoskeletal changes, but arthrogryposis did not occur, as observed in other states of the Brazilian northeast.<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">16</span></a> The frequency of associated cardiac malformations was also low.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Regarding ocular impairment, more than a quarter of affected newborns presented alterations in the fundoscopic examination consistent with retinal epithelial lesions, which is approximately the same proportion reported in a case series in the state of Bahia, Brazil.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">17</span></a> It was recently demonstrated that congenital ZIKV infection is associated with central retinal degeneration with loss of ganglion cell layer, inner nuclear layer thinning, and photoreceptor loss.<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">18</span></a> Screening for hearing loss through otoacoustic emissions has shown that almost 1/3 of affected infants are potentially hearing-impaired. A more detailed audiological evaluation in microcephalic babies born during the epidemic in the state of Pernambuco demonstrated that almost 1/4 failed the first screening test in at least one ear.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">19</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Other congenital infections that could explain the clinical findings were identified in a small number of cases, which were IgM-positive in serological testing for CMV, herpes, and syphilis. In this sense, it is possible that a small proportion of the cases were not caused by congenital infection with ZIKV.</p><p id="par0135" class="elsevierStylePara elsevierViewall">It is interesting to note the explosive nature of the microcephaly epidemic in Brazil and in the state of Piauí. The number of confirmed cases has significantly reduced as of the first half of 2016. The number of cases of Zika fever have also declined throughout Brazil. Thus, the great question as of now is whether congenital Zika syndrome will assume the same epidemiological pattern of other teratogenic infections (such as CMV, toxoplasmosis, and herpes), which produce cases in a more or less stable and endemic way. The probability of Zika fever (and consequently of congenital infections by ZIKV) becoming endemic in Latin America was assessed through mathematical modeling, which has proposed that there is indeed risk that the infection will establish an endemic profile.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">20</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">However, the transmission dynamics – and consequently the basic reproduction number – of ZIKV infections are very different from those observed in other arboviruses, due to some biological characteristics: (i) ZIKV can be transmitted directly, person-to-person, sexually and perhaps through saliva<a class="elsevierStyleCrossRefs" href="#bib0230"><span class="elsevierStyleSup">21,22</span></a>; (ii) It is possible that other species of mosquito, such as <span class="elsevierStyleItalic">Culex quinquefasciatus</span> (which has a very high density in practically all urban areas of Brazil), transmit ZIKV<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">23</span></a>; (iii) ZIKV has only one serotype<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">24</span></a>; and (iv) The majority of ZIKV infections is asymptomatic.<a class="elsevierStyleCrossRef" href="#bib0250"><span class="elsevierStyleSup">25</span></a> These characteristics can lead to a faster induction of herd immunization by natural infection and reduction of the susceptible pool. Thus, the renewal of the population susceptible to ZIKV would require more time, so that the disease would not behave in an endemic manner in the coming years.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In Brazil, ZIKV infections dropped from 170,535 cases in 2016 to 7,911 in 2017. In May 2017, the Brazilian Ministry of Health declared the end of the national emergency for Zika. Currently, the lack of availability of a specific serological test impairs the massive screening of pregnant women in primary health care within the Unified Health System for the congenital infection by Zika. Thus, only pregnant women with a suggestive clinical presentation of ZIKV infection are submitted to molecular testing by PCR.</p><p id="par0150" class="elsevierStylePara elsevierViewall">Current challenges in Brazil include the improvement of vector control (including definition of the role of other mosquito species in transmission), intensification of research to characterize mosquito-independent transmission pathways, development and scaling-up of effective serological diagnostic tools for pre-natal screening, development of vaccines, and improving health care for the affected children.</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Funding</span><p id="par0155" class="elsevierStylePara elsevierViewall">This research was supported by funds from the Fundação Oswaldo Cruz (Fiocruz).</p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Conflicts of interest</span><p id="par0160" class="elsevierStylePara elsevierViewall">The authors declare no conflicts of interest.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres1236151" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1147563" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1236152" "titulo" => "Resumo" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1147562" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Patients and methods" ] 6 => array:3 [ "identificador" => "sec0015" "titulo" => "Results" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0020" "titulo" => "Spatiotemporal distribution of microcephaly cases" ] 1 => array:2 [ "identificador" => "sec0025" "titulo" => "Obstetric and childbirth data" ] 2 => array:2 [ "identificador" => "sec0030" "titulo" => "Clinical and radiological characteristics of confirmed and discarded microcephaly cases" ] 3 => array:2 [ "identificador" => "sec0035" "titulo" => "Serological data related to other congenital infections" ] ] ] 7 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0045" "titulo" => "Funding" ] 9 => array:2 [ "identificador" => "sec0050" "titulo" => "Conflicts of interest" ] 10 => array:2 [ "identificador" => "xack423184" "titulo" => "Acknowledgments" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-01-31" "fechaAceptado" => "2018-04-18" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1147563" "palabras" => array:4 [ 0 => "Microcephaly" 1 => "Infants" 2 => "Zika" 3 => "State of Piauí" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec1147562" "palabras" => array:4 [ 0 => "Microcefalia" 1 => "Neonatos" 2 => "Zika" 3 => "Estado do Piauí" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">To describe aspects of the microcephaly epidemic in the state of Piauí.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">All cases of congenital microcephaly confirmed in the state between 2015 and 2016 were included (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>100). Investigation forms of the Regional Reference Center for Microcephaly were reviewed. Discarded cases (<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>63) were used as a comparison group.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">In October, November, and December 2015 incidence rates reached 4.46, 6.33 and 3.86/1000 live births, respectively; 44 cases were reported in the state capital. Among the mothers of confirmed and discarded cases, the frequency of skin rash during pregnancy was 50/97 (51.5%) and 8/51 (15.7%), respectively (<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.001); 33 confirmed cases (35.9%) had a head circumference <span class="elsevierStyleItalic">z</span>-score between −2 and −3, 23 (25%) between −3 and −4, and 8 (8.7%) had a <span class="elsevierStyleItalic">z</span>-score of less than −4. Head computer tomography scans revealed calcifications in 78/95 (82.1%) cases. Lissencephaly, hydrocephalus and agenesis of the corpus callosum were also frequently observed. Ophthalmic findings included retinal pigment epithelium rarefaction and atrophy. Absence of otoacoustic emissions was observed in 21/70 cases. One newborn also presented lower limb muscle atrophy. There were no significant differences in vaccination rates for influenza, diphtheria-tetanus-acellular pertussis, and hepatitis B in either group.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The state of Piauí, like others in the northeastern region, faced an epidemic of congenital microcephaly between 2015 and 2016, presumably related to congenital Zika virus infection, more intense in the capital. Current challenges include the improvement of vector control, basic research, scaling-up of diagnostic tools for pre-natal screening of Zika virus, vaccines, and health care for affected children.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "pt" => array:3 [ "titulo" => "Resumo" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Objetivos</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Descrever os aspectos da epidemia de microcefalia no Estado do Piauí.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Foram incluídos todos os casos de microcefalia congênita confirmados no estado entre 2015-2016 (n = 100). Os formulários de investigação do Centro Regional de Referência em Microcefalia foram analisados. Os casos descartados (n = 63) foram usados como grupo de comparação.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Em outubro, novembro e dezembro de 2015, as taxas de incidência atingiram 4,46, 6,33 e 3,86/1.000 nascidos vivos, respectivamente; 44 casos foram relatados na capital do estado. Entre as mães de casos confirmados e descartados, a frequência de erupção cutânea durante a gravidez foi 50/97 (51,5%) e 8/51 (15,7%), respectivamente (p < 0,001); 33 casos confirmados (35,9%) apresentaram um escore z de perímetro cefálico entre -2 e -3, 23 (25%) entre -3 e -4 e 8 (8,7%) apresentaram escore z inferior a -4. As tomografias computadorizadas cerebrais revelaram calcificações em 78/95 (82,1%) dos casos. Lisencefalia, hidrocefalia e agenesia do corpo caloso também foram observadas com mais frequência. Os achados oftalmológicos incluíram rarefação e atrofia do epitélio pigmentar da retina. Foram observadas ausência de emissões otoacústicas em 21/70 casos. Um recém-nascido também apresentou atrofia muscular dos membros inferiores. Não houve diferenças significativas nas taxas de vacinação para gripe, vacina difteria tétano e coqueluche acelular e hepatite B em qualquer grupo.</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusões</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">O Estado do Piauí, como outros na região Nordeste, enfrentou, entre 2015 e 2016, uma epidemia de microcefalia congênita, supostamente relacionada à infecção congênita pelo vírus Zika, mais intensa na capital. Os desafios atuais incluem melhora do controle de vetores, pesquisa básica, ampliação de ferramentas de diagnóstico para exame pré-natal do vírus Zika, vacinas e cuidados de saúde para crianças afetadas.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Objetivos" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusões" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Almeida IM, Ramos CV, Rodrigues DC, Sousa AC, Nascimento ML, Silva MV, et al. Clinical and epidemiological aspects of microcephaly in the state of Piauí, northeastern Brazil, 2015–2016. J Pediatr (Rio J). 2019;95:466–74.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 896 "Ancho" => 2568 "Tamanyo" => 180321 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">(A) Gestational age and head circumference of confirmed and discarded microcephaly cases by sex in the state of Piauí, Brazil, 2015–2016. (B) Monthly distribution of confirmed and discarded microcephaly cases and monthly incidence rates in the state of Piauí, Brazil, 2015–2016.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 1468 "Ancho" => 2161 "Tamanyo" => 257588 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">(A) Hotspot map of the confirmed microcephaly cases in the state of Piauí, Brazil, 2015–2016. (B) Map of the spatial distribution of the confirmed and discarded microcephaly cases: pie chart size varies using the sum of the field values by municipalities.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Figure 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 2321 "Ancho" => 3167 "Tamanyo" => 899407 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Head computer tomography scans of confirmed microcephaly cases in the state of Piauí, Brazil, 2015–2016.</p> <p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">(A) Calcifications at the interface between white and gray matter and in the core-capsular regions. Moderate ventricular ectasia associated with parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum. Deformity of the skull and volume reduction of the cerebellum due to atrophy, with enlargement of the cerebrospinal fluid space of the posterior fossa.</p> <p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">(B) Small calcifications at the interface between white and gray matter. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly.</p> <p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">(C) Small calcifications at the interface between white and gray matter, linear and punctiform. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly.</p> <p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">(D) Small calcifications at the interface between white and gray substances, linear and punctiform. Asymmetry of the cerebral hemispheres with accentuation of the cortical sulci and volumetric reduction of the left hemisphere due to atrophy, with consequent compensatory ectasia of the lateral ventricle.</p> <p id="spar0080" class="elsevierStyleSimplePara elsevierViewall">(E) Slight parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum.</p> <p id="spar0085" class="elsevierStyleSimplePara elsevierViewall">(F) Small punctate calcifications at the interface between white and gray matter, and gross calcification in the left frontal lobe. Scarcity of cortical sulci with few shallow sulci, configuring an alteration of the spectrum of lissencephaly. Slight parallelism of the lateral ventricles, suggesting dysgenesis of the corpus callosum. Deformity of the skull in high frontal region.</p> <p id="spar0090" class="elsevierStyleSimplePara elsevierViewall">(G) Small punctate calcifications at the interface between white and gray matter and periventricular region. Scarcity of cortical sulci, configuring an alteration of the spectrum of lissencephaly. Volumetric reduction of the cerebellum. Deformity of the skull.</p> <p id="spar0095" class="elsevierStyleSimplePara elsevierViewall">(H) Small punctate calcifications at the interface between white and gray matter in the right frontal lobe. Scarcity of cortical sulci, in addition to shallow sulci, configuring an alteration of the spectrum of lissencephaly. Expansion of the extra-axial fluidic spaces, more evident in the temporal fossae. Reduction of right hemisphere volume with compensatory ectasia of the right lateral ventricle.</p>" ] ] 3 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black"> \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">Confirmed cases \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">Discarded cases \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"><span class="elsevierStyleItalic">p</span>-Value \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Childbirth characteristics</span></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">Gestational age at birth (weeks)Median (interquartile range [range]) \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 (37–40 [30–42]) \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 (37–39 [29–41]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.154 \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">Birth weight (grams)Median (interquartile range [range]) \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">2748 (2325–2986 [1075–4000]) \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">2635 (2300–2950 [1215–3500]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.313 \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">Apgar score in the 1st minuteMedian (interquartile range [range]) \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">9 (8–9 [1–10]) \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">9 (8–9 [3–10]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.479 \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">Apgar score in the 5th minuteMedian (interquartile range [range]) \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 (9–10 [5–10]) \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 (9–10 [4–10]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.608 \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">Cesarean section \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">52/96 (54.2%) \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">27/59 (45.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.325 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Drugs and vaccines used during pregnancy</span></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"><span class="elsevierStyleHsp" style=""></span>Methyldopa \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">5/53 (9.4%) \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">4/31 (12.9%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.719 \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"><span class="elsevierStyleHsp" style=""></span>Thyroid hormone \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">2/53 (3.8%) \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">0/31 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.528 \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"><span class="elsevierStyleHsp" style=""></span>Paracetamol \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">4/53 (7.5%) \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">1/31 (3.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.647 \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"><span class="elsevierStyleHsp" style=""></span>Dipyrone \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">3/53 (5.7%) \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">1/31 (3.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Nifedipine \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">1/53 (1.9%) \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">0/31 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Influenza vaccine \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">49/53 (92.5%) \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">26/26 (100%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.297 \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"><span class="elsevierStyleHsp" style=""></span>Diphtheria-tetanus-acellular pertussis vaccine \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">53/59 (94.9%) \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">38/38 (100%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.278 \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"><span class="elsevierStyleHsp" style=""></span>Hepatitis B vaccine \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">54/56 (96.4%) \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">31/31 (100%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.536 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Maternal sociodemographic characteristics</span></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"><span class="elsevierStyleHsp" style=""></span>Maternal age (years)Median (interquartile range [range]) \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">25.5 (20–30 [14–45]) \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">22 (18–28 [15–40]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.028 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Education</span></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"><span class="elsevierStyleHsp" style=""></span>Basic education \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">24/92 (26.1%) \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">21/57 (36.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.142 \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"><span class="elsevierStyleHsp" style=""></span>Secondary education \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">52/92 (56.5%) \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">36/57 (63.2%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.312 \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"><span class="elsevierStyleHsp" style=""></span>College education \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">16/92 (17.4%) \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">0/57 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Occupation</span></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"><span class="elsevierStyleHsp" style=""></span>Administrative \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">7/95 (7.4%) \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">2/57 (3.5%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.484 \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"><span class="elsevierStyleHsp" style=""></span>Agriculture \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">14/95 (14.7%) \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">11/57 (19.3%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.502 \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"><span class="elsevierStyleHsp" style=""></span>Commerce \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">9/95 (9.5%) \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">0/57 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.014 \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"><span class="elsevierStyleHsp" style=""></span>Student \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">7/95 (7.4%) \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">6/57 (10.5%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.555 \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"><span class="elsevierStyleHsp" style=""></span>Industry \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">1/95 (1.1%) \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">0/57 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Home \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">51/95 (53.7%) \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">37/57 (64.9%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.029 \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"><span class="elsevierStyleHsp" style=""></span>Teacher \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">2/95 (2.1%) \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">1/57 (1.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Health System \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">4/95 (4.2%) \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">0/57 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.297 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></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"><span class="elsevierStyleItalic">Monthly income (USD)</span>Median (interquartile range [range]) \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">271 (123–370 [31–3086]) \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">271 (77–271 [31–864]) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.083 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Symptoms during pregnancy</span></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"><span class="elsevierStyleHsp" style=""></span>Rash \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">50/97 (51.5%) \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">8/51 (15.7%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Cerebral CT scan alterations</span></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"><span class="elsevierStyleHsp" style=""></span>Calcifications \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">78/95 (82.1%) \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">1/21 (4.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \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"><span class="elsevierStyleHsp" style=""></span>Lissencephaly \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">11/95 (11.6%) \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">0/21 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.210 \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"><span class="elsevierStyleHsp" style=""></span>Hydrocephalus \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">7/95 (7.4%) \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">0/21 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.374 \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"><span class="elsevierStyleHsp" style=""></span>Agenesis of corpus calosum \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">5/95 (5.3%) \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">0/21 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.583 \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"><span class="elsevierStyleHsp" style=""></span>Ventricular dilatation \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">18/95 (18.9%) \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">1/21 (4.8%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.189 \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"><span class="elsevierStyleHsp" style=""></span>Brain volumetric reduction/microcrania \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">52/95 (54.7%) \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">10/21 (47.6%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.632 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Transfontanelar US alterations</span></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"><span class="elsevierStyleHsp" style=""></span>Ventricular dilation \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">11/20 (55%) \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">1/20 (5%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.001 \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"><span class="elsevierStyleHsp" style=""></span>Hydrocephalus \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">3/20 (15%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.230 \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"><span class="elsevierStyleHsp" style=""></span>Calcifications \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">6/20 (30%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.020 \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"><span class="elsevierStyleHsp" style=""></span>Brain volumetric reduction \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">5/20 (25%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.047 \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"><span class="elsevierStyleHsp" style=""></span>Porencephalic cyst \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">1/20 (5%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Hemorrhage \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">1/20 (5%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="4" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">Retinal alterations</span></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"><span class="elsevierStyleHsp" style=""></span>Retinal pigment epithelium rarefaction \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">9/67 (13.4%) \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">0/20 (0%) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.110 \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"><span class="elsevierStyleHsp" style=""></span>Papillary pallor \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">3/67 (4.8%) \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">0/20 (0% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \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"><span class="elsevierStyleHsp" style=""></span>Retinal pigment epithelial atrophy \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">6/67 (9%) \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">0/20 (0% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.329 \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"><span class="elsevierStyleHsp" style=""></span>Chorioretinitis \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">2/67 (3%) \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">0/20 (0% \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1.000 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2111233.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0100" class="elsevierStyleSimplePara elsevierViewall">Childbirth, pregnancy and maternal characteristics, radiological findings and retinal (fundoscopic) alterations in confirmed and discarded microcephaly cases in the state of Piauí, Brazil, 2015–2016.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:25 [ 0 => array:3 [ "identificador" => "bib0130" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Increased hospitalizations for neuropathies as indicators of Zika virus infection, according to health information system data, Brazil" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 7 | 3 | 10 |
| 2024 October | 31 | 30 | 61 |
| 2024 September | 34 | 25 | 59 |
| 2024 August | 50 | 53 | 103 |
| 2024 July | 72 | 54 | 126 |
| 2024 June | 22 | 17 | 39 |
| 2024 May | 22 | 12 | 34 |
| 2024 April | 26 | 30 | 56 |
| 2024 March | 24 | 19 | 43 |
| 2024 February | 22 | 29 | 51 |
| 2024 January | 22 | 29 | 51 |
| 2023 December | 25 | 29 | 54 |
| 2023 November | 31 | 34 | 65 |
| 2023 October | 21 | 34 | 55 |
| 2023 September | 25 | 39 | 64 |
| 2023 August | 19 | 25 | 44 |
| 2023 July | 22 | 22 | 44 |
| 2023 June | 20 | 17 | 37 |
| 2023 May | 24 | 16 | 40 |
| 2023 April | 20 | 11 | 31 |
| 2023 March | 38 | 29 | 67 |
| 2023 February | 23 | 13 | 36 |
| 2023 January | 18 | 15 | 33 |
| 2022 December | 43 | 25 | 68 |
| 2022 November | 23 | 25 | 48 |
| 2022 October | 43 | 37 | 80 |
| 2022 September | 43 | 26 | 69 |
| 2022 August | 52 | 36 | 88 |
| 2022 July | 61 | 36 | 97 |
| 2022 June | 33 | 27 | 60 |
| 2022 May | 39 | 25 | 64 |
| 2022 April | 27 | 29 | 56 |
| 2022 March | 34 | 44 | 78 |
| 2022 February | 25 | 21 | 46 |
| 2022 January | 35 | 15 | 50 |
| 2021 December | 30 | 24 | 54 |
| 2021 November | 28 | 15 | 43 |
| 2021 October | 17 | 18 | 35 |
| 2021 September | 17 | 5 | 22 |
| 2021 August | 20 | 9 | 29 |
| 2021 July | 18 | 6 | 24 |
| 2021 June | 20 | 5 | 25 |
| 2021 May | 36 | 16 | 52 |
| 2021 April | 60 | 8 | 68 |
| 2021 March | 31 | 19 | 50 |
| 2021 February | 14 | 6 | 20 |
| 2021 January | 29 | 18 | 47 |
| 2020 December | 19 | 10 | 29 |
| 2020 November | 34 | 11 | 45 |
| 2020 October | 17 | 12 | 29 |
| 2020 September | 50 | 16 | 66 |
| 2020 August | 11 | 1 | 12 |
| 2020 July | 11 | 10 | 21 |
| 2020 June | 15 | 4 | 19 |
| 2020 May | 30 | 14 | 44 |
| 2020 April | 18 | 23 | 41 |
| 2020 March | 17 | 18 | 35 |
| 2020 February | 17 | 11 | 28 |
| 2020 January | 24 | 19 | 43 |
| 2019 December | 18 | 9 | 27 |
| 2019 November | 8 | 4 | 12 |
| 2019 October | 23 | 22 | 45 |
| 2019 September | 18 | 47 | 65 |
| 2019 August | 27 | 18 | 45 |
| 2019 July | 18 | 10 | 28 |
| 2019 June | 26 | 11 | 37 |
| 2019 May | 11 | 9 | 20 |
| 2019 April | 30 | 12 | 42 |
| 2019 March | 13 | 13 | 26 |
| 2019 February | 17 | 9 | 26 |
| 2019 January | 21 | 7 | 28 |
| 2018 December | 21 | 13 | 34 |
| 2018 November | 10 | 4 | 14 |
| 2018 October | 30 | 19 | 49 |
| 2018 September | 8 | 4 | 12 |
| 2018 August | 7 | 7 | 14 |
| 2018 July | 5 | 1 | 6 |
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