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p&#234;nfigo paraneopl&#225;sico e p&#234;nfigo induzidos por f&#225;rmacos&#46; H&#225; produ&#231;&#227;o de autoanticorpos direcionados contra glicoprote&#237;nas epid&#233;rmicas intercelulares&#46; O segundo grupo&#44; das dermatoses bolhosas subepid&#233;rmicas&#44; tem como principais representantes o penfigoide bolhoso &#40;PB&#41; e epiderm&#243;lise bolhosa adquirida &#40;EBA&#41;&#44; seguidos por condi&#231;&#245;es menos comuns como a dermatose bolhosa por IgA linear &#40;DBAL&#41;&#44; dermatite herpetiforme &#40;DH&#41;&#44; penfigoide das mucosas &#40;PM&#41; e l&#250;pus eritematoso sist&#234;mico bolhoso &#40;LESB&#41;&#46; Esse grupo &#233; definido pela presen&#231;a de autoanticorpos direcionados contra autoant&#237;genos da zona da membrana basal &#40;ZMB&#41;&#44; levando &#224; clivagem subepid&#233;rmica&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">As DBAI podem ocorrer durante a gesta&#231;&#227;o&#44; mas s&#227;o relativamente raras&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a> Existem duas situa&#231;&#245;es cl&#237;nicas distintas&#58; 1&#41;&#160;paciente com DBAI previamente diagnosticada&#44; engravida&#59; 2&#41;&#160;gestante sem hist&#243;rico pr&#233;vio de DBAI desenvolve um surto de bolhas que requer diagn&#243;stico e manejo&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">3</span></a> De acordo com esta revis&#227;o&#44; a primeira situa&#231;&#227;o &#233; a mais frequente&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">O penfigoide gestacional &#40;PG&#41;&#44; uma variante do PB&#44; tem seu in&#237;cio exclusivamente associado &#224; gesta&#231;&#227;o&#44; ao per&#237;odo p&#243;s&#8208;parto&#44; a tumores trofobl&#225;sticos&#44; mola hidatiforme ou coriocarcinoma&#44; e n&#227;o foi inclu&#237;do nesta revis&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">4</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Os autores tiveram como objetivo realizar uma revis&#227;o sobre a ocorr&#234;ncia de DBAI durante a gesta&#231;&#227;o&#44; uma vez que a maioria das publica&#231;&#245;es &#233; baseada em relatos de casos&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Sistema imune e gesta&#231;&#227;o</span><p id="par0025" class="elsevierStylePara elsevierViewall">A resposta imunol&#243;gica existe principalmente para defender o hospedeiro contra pat&#243;genos invasores&#44; e para proporcionar toler&#226;ncia aos autoant&#237;genos&#46; Linf&#243;citos derivados do timo&#44; ou linf&#243;citos&#160;T &#40;LT&#41;&#44; est&#227;o envolvidos com a manuten&#231;&#227;o de tal fun&#231;&#227;o&#46; Assim&#44; LT nativos podem diferenciar&#8208;se em LT com especificidade para responder a ant&#237;genos externos&#44; bem como a autoant&#237;genos&#46; A matura&#231;&#227;o celular dos LT depende essencialmente de intera&#231;&#245;es com o ambiente f&#237;sico&#8208;qu&#237;mico e resulta no desenvolvimento de c&#233;lulas com fun&#231;&#227;o efetora e de mem&#243;ria&#44; ou no desenvolvimento de c&#233;lulas com fun&#231;&#227;o regulat&#243;ria&#46; Linf&#243;citos&#160;T auxiliares exercem um papel na defesa imunol&#243;gica estimulando a s&#237;ntese de anticorpos&#59; e linf&#243;citos&#160;T regulat&#243;rios t&#234;m a&#231;&#227;o anti&#8208;inflamat&#243;ria e desempenham um papel na manuten&#231;&#227;o da toler&#226;ncia aos seus pr&#243;prios componentes celulares&#46; Dados da literatura indicam que&#44; tanto em murinos quanto humanos&#44; a deple&#231;&#227;o dos linf&#243;citos&#160;T regulat&#243;rios est&#225; relacionada ao desenvolvimento de doen&#231;as autoimunes graves&#46;<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">A gesta&#231;&#227;o constitui um estado imunol&#243;gico espec&#237;fico&#44; uma vez que o organismo materno deve equilibrar a toler&#226;ncia fetal com a manuten&#231;&#227;o de seu pr&#243;prio sistema imunol&#243;gico&#46; Altera&#231;&#245;es hormonais relevantes ocorrem na gesta&#231;&#227;o&#44; tanto nos n&#237;veis de progesterona e estrog&#234;nio quanto em cortisol&#44; norepinefrina e deidroepiandrosterona&#46; Os n&#237;veis s&#233;ricos de progesterona e estradiol aumentam de cinco a&#160;10&#160;vezes ao longo da gesta&#231;&#227;o&#44; retornando rapidamente ao n&#237;vel normal no p&#243;s&#8208;parto&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">6</span></a> Sob a influ&#234;ncia desses horm&#244;nios&#44; mudan&#231;as profundas no sistema imunol&#243;gico ocorrem durante toda a gesta&#231;&#227;o&#44; a fim de acomodar o feto alog&#234;nico&#44; que incluem processos imunorregulat&#243;rios e imunossupressores&#46; Esse estado de imunomodula&#231;&#227;o ocorre mais intensamente na interface materno&#8208;fetal&#44; na qual os n&#237;veis de progesterona s&#227;o muito altos em fun&#231;&#227;o da maior produ&#231;&#227;o desse horm&#244;nio pela placenta&#44; e mais sutil no sangue perif&#233;rico materno&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">Na regi&#227;o uterina onde a placenta se desenvolve &#40;dec&#237;dua&#41;&#44; h&#225; supress&#227;o acentuada da citotoxicidade&#44; infiltra&#231;&#227;o de c&#233;lulas <span class="elsevierStyleItalic">natural killer</span> &#40;NK&#41; &#250;tero&#8208;espec&#237;ficas&#44; bloqueio de ant&#237;genos fetais expostos a linfonodos maternos e ac&#250;mulo de c&#233;lulas&#160;T reguladoras &#40;Treg&#41; feto&#8208;espec&#237;ficas&#46; A quantidade de c&#233;lulas Treg est&#225; elevada durante a gesta&#231;&#227;o&#44; inclusive no sangue materno&#59; elas desempenham um papel na supress&#227;o da resposta imune local por meio do fen&#244;meno da supress&#227;o vinculada&#46; Essa supress&#227;o pode explicar os baixos n&#237;veis de autoanticorpos durante a gesta&#231;&#227;o em determinadas doen&#231;as autoimunes e inflamat&#243;rias&#44; levando &#224; remiss&#227;o&#44; seguida de reativa&#231;&#227;o no p&#243;s&#8208;parto como na doen&#231;a de Graves e artrite reumatoide&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">3</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">H&#225; escassez de dados na literatura m&#233;dica que mencionem as importantes mudan&#231;as na popula&#231;&#227;o de c&#233;lulas Treg em gestantes&#46; No entanto&#44; essas c&#233;lulas s&#227;o conhecidas por desempenhar um papel de destaque na promo&#231;&#227;o da sobreviv&#234;ncia fetal&#44; e sugere&#8208;se que seu aumento esteja relacionado ao aumento das c&#233;lulas Th2 efetoras<span class="elsevierStyleItalic">&#46;</span> Estudos <span class="elsevierStyleItalic">in vivo</span> e <span class="elsevierStyleItalic">in vitro</span> mostram que a progesterona tem a capacidade de suprimir a diferencia&#231;&#227;o Th1&#47;Th17 e&#44; em contraste&#44; potencializar a diferencia&#231;&#227;o Th2 e das c&#233;lulas Treg&#46; Al&#233;m disso&#44; citocinas maternas levam &#224; maior diferencia&#231;&#227;o das c&#233;lulas&#160;T nativas em c&#233;lulas Th2&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">8</span></a> O resultado final &#233; um desequil&#237;brio imunol&#243;gico&#44; com aumento da popula&#231;&#227;o celular Th2&#44; em detrimento das c&#233;lulas Th1 e Th17&#46; Sugere&#8208;se que haja maior direcionamento para a popula&#231;&#227;o Th2&#44; essencial para a manuten&#231;&#227;o do estado normal de gesta&#231;&#227;o&#46; &#201; importante ressaltar que um ambiente inicial na predomin&#226;ncia do Th1 &#233; necess&#225;rio para o sucesso da implanta&#231;&#227;o uterina&#46; No entanto&#44; em est&#225;gios posteriores da gesta&#231;&#227;o&#44; a predomin&#226;ncia da resposta linfocit&#225;ria Th2 &#233; necess&#225;ria para um ambiente de toler&#226;ncia transit&#243;ria aos ant&#237;genos fetais &#40;<a class="elsevierStyleCrossRef" href="#fig0005">fig&#46; 1</a>&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0045" class="elsevierStylePara elsevierViewall">Considerando as altera&#231;&#245;es fisiol&#243;gicas na resposta imune durante a gesta&#231;&#227;o&#44; a ocorr&#234;ncia de doen&#231;as autoimunes em gestantes &#233; um fator de alto risco e pode levar a mudan&#231;as no estado de suas doen&#231;as durante esse per&#237;odo&#46;<a class="elsevierStyleCrossRef" href="#bib0265"><span class="elsevierStyleSup">3</span></a></p><p id="par0050" class="elsevierStylePara elsevierViewall">A gesta&#231;&#227;o &#233; marcada pela predomin&#226;ncia da resposta linfocit&#225;ria Th2&#44; um perfil coincidente com o desenvolvimento de dermatoses bolhosas autoimunes&#46; Por causa da redu&#231;&#227;o da resposta Th1 e possivelmente Th17 durante a gesta&#231;&#227;o normal&#44; doen&#231;as cut&#226;neas com predomin&#226;ncia da resposta Th1&#44; como psor&#237;ase&#44; artrite reumatoide e esclerose m&#250;ltipla&#44; apresentam melhora durante a gesta&#231;&#227;o&#46; Por outro lado&#44; doen&#231;as com padr&#227;o de resposta Th2 como p&#234;nfigos&#44; l&#250;pus eritematoso e asma podem n&#227;o se beneficiar dessa mudan&#231;a no padr&#227;o imunol&#243;gico&#44; por causa da predomin&#226;ncia da resposta Th2 na atividade dessas doen&#231;as&#46;<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">2&#44;9</span></a></p><p id="par0055" class="elsevierStylePara elsevierViewall">Assim&#44; a coexist&#234;ncia da dermatose bolhosa autoimune em gestantes precipitaria ou aumentaria a ocorr&#234;ncia de p&#234;nfigos e penfigoides &#40;<a class="elsevierStyleCrossRef" href="#tbl0005">tabela 1</a>&#41;&#46; No entanto&#44; o curso das DBAI tende a flutuar durante a gesta&#231;&#227;o em decorr&#234;ncia das altera&#231;&#245;es imunol&#243;gicas causadas por estrog&#234;nio e progesterona&#44; mas tamb&#233;m por cortisol&#44; norepinefrina e deidroepiandrosterona&#46;<a class="elsevierStyleCrossRef" href="#bib0260"><span class="elsevierStyleSup">2</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Al&#233;m disso&#44; a gesta&#231;&#227;o traz outras exig&#234;ncias no manejo cl&#237;nico usual das DBAI&#58; restri&#231;&#245;es nos m&#233;todos habituais de confirma&#231;&#227;o diagn&#243;stica&#44; limita&#231;&#227;o no uso de determinados medicamentos e escolha da forma de parto&#46; Por essas raz&#245;es&#44; pacientes com DBAI em idade f&#233;rtil e que desejam engravidar devem ser aconselhadas a fazer o planejamento familiar&#44; no intuito de garantir melhores condi&#231;&#245;es de sa&#250;de para ela e o concepto&#46; O uso de um m&#233;todo contraceptivo deve ser institu&#237;do at&#233; que a doen&#231;a esteja bem controlada&#44; de modo que a gesta&#231;&#227;o ocorra durante per&#237;odo com redu&#231;&#227;o na atividade da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">3&#44;10</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Alguns aspectos etiol&#243;gicos e epidemiol&#243;gicos das DBAI</span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">P&#234;nfigo vulgar</span><p id="par0065" class="elsevierStylePara elsevierViewall">No PV&#44; h&#225; predomin&#226;ncia do sexo feminino&#44; evidenciada por raz&#227;o mulher&#58;homem de&#160;1&#46;4&#160;e&#160;2&#46;3&#44; segundo estudos epidemiol&#243;gicos realizados na China e Gr&#233;cia&#46;<a class="elsevierStyleCrossRefs" href="#bib0265"><span class="elsevierStyleSup">3&#44;11</span></a> Um desfecho pior do PV tamb&#233;m tem sido observado em mulheres&#59; an&#225;lise recente mostrou que os alelos HLA DRB1&#42;04&#58;02 e DQB1 &#42;03&#58;02 estavam associados com PV grave&#44; e DQB1&#42;03&#58;02 foi encontrado com maior frequ&#234;ncia em pacientes do sexo feminino&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">Uma revis&#227;o envolvendo&#160;49&#160;gestantes com PV constatou que&#160;37&#37;&#160;apresentavam a doen&#231;a pela primeira vez durante a gesta&#231;&#227;o&#44; e desfechos adversos da gesta&#231;&#227;o &#40;ou seja&#44; p&#234;nfigo neonatal e &#243;bito perinatal&#41; ocorreram em at&#233;&#160;10&#37;&#160;dos casos&#46; O PV tende a melhorar na gesta&#231;&#227;o&#44; ap&#243;s o terceiro trimestre&#44; e reativar no per&#237;odo p&#243;s&#8208;parto&#46; Portanto&#44; a gesta&#231;&#227;o pode precipitar ou agravar o quadro de PV&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">A ocorr&#234;ncia de PV neonatal &#233; transit&#243;ria&#44; e sua resolu&#231;&#227;o tende a ocorrer dentro de tr&#234;s semanas&#59; em geral&#44; deve&#8208;se &#224; transmiss&#227;o transplacent&#225;ria de anticorpos IgG da m&#227;e para o feto&#44; e &#233; facilmente trat&#225;vel&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">13</span></a> Al&#233;m do PV neonatal&#44; outras consequ&#234;ncias para o rec&#233;m&#8208;nascido incluem&#58; restri&#231;&#227;o ao crescimento intrauterino&#44; rec&#233;m&#8208;nascido pr&#233;&#8208;termo e morte fetal&#46; No entanto&#44; &#233; dif&#237;cil distinguir as consequ&#234;ncias decorrentes do tratamento daquelas pr&#243;prias da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">14</span></a> Al&#233;m disso&#44; as diferen&#231;as na express&#227;o da desmogle&#237;na na pele neonatal s&#227;o respons&#225;veis pela diversidade de manifesta&#231;&#245;es cl&#237;nicas entre m&#227;e e filho&#46;<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">13</span></a> Os eventos adversos parecem estar mais correlacionados com mau controle da doen&#231;a materna&#44; maior n&#237;vel s&#233;rico e no cord&#227;o umbilical de anticorpos maternos&#44; do que com medicamentos espec&#237;ficos utilizados para tratar PV materno&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">15</span></a> Portanto&#44; tratamentos que levem &#224; diminui&#231;&#227;o nos n&#237;veis de anticorpos s&#233;ricos maternos&#44; a fim de limitar a passagem transplacent&#225;ria de IgG patog&#234;nica&#44; justificam a terapia imunossupressora&#44; a despeito de essa abordagem durante a gesta&#231;&#227;o ainda n&#227;o ter sido bem estabelecida&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">15</span></a> Deve&#8208;se lembrar que&#44; antes da introdu&#231;&#227;o do uso de corticosteroides sist&#234;micos para PV&#44; a doen&#231;a apresentava elevadas taxas de mortalidade&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">P&#234;nfigo foli&#225;ceo</span><p id="par0080" class="elsevierStylePara elsevierViewall">O PF se apresenta sob duas formas&#58; a cl&#225;ssica &#40;doen&#231;a de Cazenave&#41; e a end&#234;mica&#46; Esta &#250;ltima inclui o fogo selvagem &#40;FS&#41;&#44; que corresponde &#224; forma end&#234;mica sul&#8208;americana&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">16</span></a> N&#227;o h&#225; relato de predomin&#226;ncia de g&#234;nero no PF ou FS&#44; mas as formas end&#234;micas de PF observadas no norte da &#193;frica &#40;Tun&#237;sia&#41; mostram uma predomin&#226;ncia feminina caracter&#237;stica&#44; especialmente entre as mulheres jovens &#40;rela&#231;&#227;o mulher&#58;homem de&#160;4&#58;1&#41;&#46; Em uma s&#233;rie de casos com&#160;23&#160;pacientes tunisianas com p&#234;nfigo&#44; suspeitou&#8208;se do papel provocador da gesta&#231;&#227;o no desenvolvimento dessa doen&#231;a&#44; em fun&#231;&#227;o de ser a Tun&#237;sia um pa&#237;s onde mulheres jovens t&#234;m alta taxa de fecundidade&#46;<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">17</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">O PF pode ter curso vari&#225;vel na gesta&#231;&#227;o&#44; sem efeito sobre o feto&#46; A associa&#231;&#227;o com PF neonatal &#233; extremamente rara no contexto de t&#237;tulos de anticorpos excepcionalmente elevados&#46;<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">18</span></a> A desmogle&#237;na&#160;3 &#233; expressa em toda a epiderme&#44; incluindo as camadas subc&#243;rneas na pele neonatal&#44; e pode ser protetora contra anticorpos antidesmogle&#237;na 1 causadores da doen&#231;a&#46;<a class="elsevierStyleCrossRefs" href="#bib0315"><span class="elsevierStyleSup">13&#44;19</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Um estudo no Brasil com&#160;19&#160;gestantes que apresentavam FS n&#227;o observou nenhuma doen&#231;a cl&#237;nica neonatal&#59; a imunofluoresc&#234;ncia direta foi negativa em&#160;12&#160;dos&#160;17&#160;esp&#233;cimes de pele neonatal&#44; os autoanticorpos IgG estavam presentes em t&#237;tulos baixos &#40;menos de&#160;1&#58;40&#41; e a IgG4 era a subclasse predominante de IgG&#44; em&#160;nove&#160;das&#160;19&#160;amostras de sangue do cord&#227;o umbilical&#46; Os autores sugerem que a placenta possa servir como imunoabsorvente biol&#243;gico de autoanticorpos patog&#234;nicos&#46;<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">20</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Epiderm&#243;lise bolhosa adquirida</span><p id="par0095" class="elsevierStylePara elsevierViewall">A EBA &#233; um subtipo raro&#44; fenotipicamente heterog&#234;neo de DBAI&#44; predominante no sexo feminino e caracterizado por autoanticorpos contra o col&#225;geno tipo VII&#46; Dois trabalhos estudaram EBA e seus dados associados&#44; com um total de 83 casos&#44; revelando que a raz&#227;o mulher&#58;homem &#233; de&#160;1&#44;56&#46;<a class="elsevierStyleCrossRefs" href="#bib0355"><span class="elsevierStyleSup">21&#44;22</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Dermatose por IgA linear</span><p id="par0100" class="elsevierStylePara elsevierViewall">A DBAL &#233; uma doen&#231;a bolhosa autoimune rara com bolhas subepid&#233;rmicas&#44; na qual os autoanticorpos IgA reconhecem como ant&#237;genos os ectodom&#237;nios subepid&#233;rmicos do col&#225;geno tipo&#160;XVII &#40;COL17&#44; BP180&#41; na ZMB&#46; H&#225; escassos dados epidemiol&#243;gicos sobre sua ocorr&#234;ncia por g&#234;nero bem como sua incid&#234;ncia na gesta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0365"><span class="elsevierStyleSup">23</span></a> Os pacientes s&#227;o categorizados em dois grupos&#58; um com in&#237;cio pr&#233;&#8208;puberal e o outro de in&#237;cio posterior &#40;DBAL adulto&#41;&#46; Alguns pacientes com DBAL s&#227;o mulheres jovens que engravidaram&#46; Pouco se sabe sobre o efeito da DBAL e seu tratamento na gesta&#231;&#227;o&#44; ou sobre o efeito da gesta&#231;&#227;o na DBAL&#46; Sabe&#8208;se que seu ant&#237;geno &#233; expresso na membrana basal amni&#243;tica e a deposi&#231;&#227;o do IgA ocorre na zona da membrana basal amni&#243;tica do feto das pacientes afetadas&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">24</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">De acordo com uma s&#233;rie de casos de DBAL na gesta&#231;&#227;o&#44; a doen&#231;a geralmente melhora ao final do primeiro trimestre e normalmente recorre no segundo trimestre&#44; mas pode recair no per&#237;odo p&#243;s&#8208;parto&#46; Por essa raz&#227;o&#44; pode ser poss&#237;vel a suspens&#227;o da dapsona durante a gesta&#231;&#227;o&#46; H&#225; evid&#234;ncias de que os anticorpos IgA tornam&#8208;se glicosilados durante a gesta&#231;&#227;o&#44; o que poderia explicar essa remiss&#227;o&#59; as c&#233;lulas Treg tamb&#233;m exerceriam algum papel&#46; No entanto&#44; os pacientes devem ser aconselhados sobre a possibilidade de uma reca&#237;da p&#243;s&#8208;parto&#46; A doen&#231;a tamb&#233;m pode reativar anos depois&#44; mesmo ap&#243;s um per&#237;odo prolongado de remiss&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Dermatite herpetiforme</span><p id="par0110" class="elsevierStylePara elsevierViewall">A DH est&#225; intimamente associada &#224; doen&#231;a cel&#237;aca&#59; ambas as condi&#231;&#245;es s&#227;o mediadas por autoanticorpos IgA e t&#234;m como alvo o autoant&#237;geno transglutaminase&#46; Em contraste com os p&#234;nfigos e o penfigoide&#44; as evid&#234;ncias de predomin&#226;ncia de g&#234;nero na DH s&#227;o conflitantes&#44; sem conclus&#227;o sobre a preval&#234;ncia em mulheres ou homens&#46;<a class="elsevierStyleCrossRef" href="#bib0380"><span class="elsevierStyleSup">26</span></a> Quanto &#224; sua ocorr&#234;ncia durante a gesta&#231;&#227;o&#44; h&#225; escassez de dados&#44; com apenas dois artigos encontrados na literatura&#46;</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">DBAI e gesta&#231;&#227;o</span><p id="par0115" class="elsevierStylePara elsevierViewall">A presente pesquisa teve como principal foco relatos de casos e estudos retrospectivos&#46; As refer&#234;ncias foram recuperadas em um per&#237;odo de publica&#231;&#227;o de&#160;1979&#160;a&#160;2017 por uma estrat&#233;gia de busca eletr&#244;nica&#58; &#8220;&#40;p&#234;nfigo vulgar &#91;Termos do MeSH&#93;&#41; E &#40;gesta&#231;&#227;o &#91;Termos de MeSH&#93;&#41;&#59; &#40;p&#234;nfigo foli&#225;ceo &#91;Termos de MeSH&#93;&#41; E &#40;gesta&#231;&#227;o&#91;Termos de MeSH&#93;&#41;&#59; &#40;dermatite herpertiforme &#91;Termos MeSH&#93;&#41; E &#40;gesta&#231;&#227;o&#91;Termos de MeSH&#93;&#41;&#59; &#40;epiderm&#243;lise bolhosa adquirida &#91;Termos de MeSH&#93;&#41; E &#40;gesta&#231;&#227;o&#91;Termos de MeSH&#93;&#41;&#59; &#40;dermatose IgA linear &#91;Termos de MeSH&#93;&#41; E &#40;gesta&#231;&#227;o&#91;Termos de MeSH&#93;&#41;&#59; Filtros&#58; relatos de casos&#8221; no PubMed&#46; Foram exclu&#237;dos os artigos n&#227;o publicados em ingl&#234;s e aqueles de penfigoide gestacional e formas cong&#234;nitas de doen&#231;as bolhosas&#46; Foram inclu&#237;dos 56 artigos&#44; de acordo com seus t&#237;tulos e resumos&#46;</p><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">P&#234;nfigos e gesta&#231;&#227;o</span><p id="par0120" class="elsevierStylePara elsevierViewall">Foram inclu&#237;dos&#160;49&#160;artigos &#40;<a class="elsevierStyleCrossRef" href="#sec0145">Ap&#234;ndice A</a>&#41;&#44; que relatavam um total de&#160;57&#160;mulheres com&#160;59&#160;gesta&#231;&#245;es &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">tabela 2</a>&#41;&#59; 31&#160;pacientes&#160;&#40;54&#44;3&#37;&#41; tiveram o diagn&#243;stico de p&#234;nfigo antes da gesta&#231;&#227;o&#44; e 26&#160;&#40;45&#44;6&#37;&#41; durante a gesta&#231;&#227;o&#46; Cinquenta e um pacientes&#160;&#40;89&#44;4&#37;&#41; tiveram o diagn&#243;stico de PV e&#160;seis&#160;&#40;10&#44;5&#37;&#41; de PF&#46; A m&#233;dia de idade no in&#237;cio da doen&#231;a foi de 28&#44;4 anos&#44; e a m&#233;dia das semanas de semana gestacional de in&#237;cio&#47;piora da doen&#231;a foi igual a 16&#46; O comportamento do p&#234;nfigo foi relatado em 50 gesta&#231;&#245;es&#46; Em 33&#47;50 &#40;66&#37;&#41; gesta&#231;&#245;es a doen&#231;a piorou&#44; em 14&#47;50 &#40;28&#37;&#41; a doen&#231;a manteve&#8208;se est&#225;vel&#44; e em 3&#47;50 &#40;6&#37;&#41; a doen&#231;a melhorou&#46; Em 12 das 50 gesta&#231;&#245;es&#160;&#40;24&#37;&#41; houve relato de reativa&#231;&#227;o p&#243;s&#8208;parto&#44; e desfechos adversos da gesta&#231;&#227;o como p&#234;nfigo neonatal&#44; morte perinatal ou aborto foram relatados em 33&#37; dessas gesta&#231;&#245;es&#46; Quanto ao tratamento de p&#234;nfigos durante a gesta&#231;&#227;o&#44; foram identificadas 51 pacientes cujos tratamentos foram descritos&#46; Em 41 deles &#40;80&#44;3&#37;&#41; a monoterapia foi a escolha&#44; e nos outros&#160;10&#160;&#40;19&#44;6&#37;&#41; a terapia combinada foi relatada&#46; Rituximabe foi utilizado em quatro &#40;7&#44;8&#37;&#41;&#59; corticoides sist&#234;micos em todos os 51 &#40;100&#37;&#41;&#59; azatioprina em cinco &#40;9&#44;8&#37;&#41;&#59; micofenolato mofetil em tr&#234;s &#40;5&#44;8&#37;&#41;&#59; dapsona em um &#40;1&#44;9&#37;&#41; e imunoglobulina intravenosa em quatro &#40;7&#44;8&#37;&#41; casos&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Dermatose por IgA linear e gesta&#231;&#227;o</span><p id="par0125" class="elsevierStylePara elsevierViewall">Foram encontrados tr&#234;s artigos sobre DBAL e gesta&#231;&#227;o&#46; Em um deles&#44; 12 pacientes tiveram um total de 19 gesta&#231;&#245;es&#46; A doen&#231;a permaneceu em atividade em 13 de 19 gesta&#231;&#245;es&#44; sofreu remiss&#227;o em quatro e houve recorr&#234;ncia no p&#243;s&#8208;parto em duas&#160;gesta&#231;&#245;es&#46; A idade de in&#237;cio da DBAL variou de 1&#44;5 a 33 anos&#59; tr&#234;s pacientes tinham doen&#231;a bolhosa cr&#244;nica na inf&#226;ncia&#44; e nove tinham DBAL forma do adulto&#46; No geral&#44; a DBAL tende a melhorar durante a gesta&#231;&#227;o&#44; especialmente por volta da&#160;d&#233;cima&#160;semana gestacional&#46; Doze das&#160;19&#160;pacientes receberam tratamento sist&#234;mico &#40;7&#47;12&#160;receberam dapsona&#41;&#44; 4&#47;19&#160;estavam em remiss&#227;o e 1&#47;19&#160;apresentou doen&#231;a m&#237;nima&#44; sem terapia&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">25</span></a></p><p id="par0130" class="elsevierStylePara elsevierViewall">Dois artigos de relatos de caso descreveram DBAL e gesta&#231;&#227;o&#58; um refere&#8208;se a uma mulher de&#160;24&#160;anos diagnosticada com DBAL e mola hidatiforme&#44; excisada em sua terceira gesta&#231;&#227;o&#44; e o outro refere&#8208;se a uma mulher de&#160;29&#160;anos&#44; gr&#225;vida de&#160;38&#160;semanas&#44; com autoanticorpos direcionados contra o dom&#237;nio n&#227;o col&#225;geno&#160;16A &#40;NC16A&#41; de COL17&#46;<a class="elsevierStyleCrossRefs" href="#bib0365"><span class="elsevierStyleSup">23&#44;27</span></a></p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Epiderm&#243;lise bolhosa adquirida e gesta&#231;&#227;o</span><p id="par0135" class="elsevierStylePara elsevierViewall">Foram recuperados tr&#234;s artigos sobre EBA e gesta&#231;&#227;o&#46; Em um deles&#44; uma mulher de&#160;32&#160;anos teve o diagn&#243;stico de EBA e&#44; no momento do parto&#44; tanto a m&#227;e quanto o rec&#233;m&#8208;nascido apresentavam eros&#245;es superficiais e profundas na face&#44; t&#243;rax&#44; abdome e extremidades&#46;<a class="elsevierStyleCrossRef" href="#bib0390"><span class="elsevierStyleSup">28</span></a> O segundo artigo descreve uma paciente que desenvolveu EBA no&#160;segundo dia do p&#243;s&#8208;parto com resolu&#231;&#227;o de bolhas na menopausa&#46;<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">29</span></a> O terceiro artigo relata uma mulher de&#160;26&#160;anos que teve uma reca&#237;da do EBA durante o primeiro m&#234;s de gesta&#231;&#227;o&#46; Por causa de uma resposta insuficiente aos corticosteroides sist&#234;micos&#44; ela sofreu um aborto no segundo m&#234;s de gesta&#231;&#227;o e&#44; em seguida&#44; teve redu&#231;&#227;o significativa do n&#250;mero de bolhas&#46;<a class="elsevierStyleCrossRef" href="#bib0400"><span class="elsevierStyleSup">30</span></a></p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Dermatite herpetiforme e gesta&#231;&#227;o</span><p id="par0140" class="elsevierStylePara elsevierViewall">Apenas um artigo foi recuperado&#46; Uma paciente de&#160;33&#160;anos com quadro de DH grave engravidou&#44; e foi necess&#225;ria dapsona oral &#40;25&#8208;50&#160;mg&#47;dia&#41; para controle da doen&#231;a&#46; A paciente deu &#224; luz um rec&#233;m&#8208;nascido a termo&#44; h&#237;gido&#44; e no p&#243;s&#8208;parto evoluiu com reativa&#231;&#227;o da doen&#231;a&#46;<a class="elsevierStyleCrossRef" href="#bib0405"><span class="elsevierStyleSup">31</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Diagn&#243;stico laboratorial</span><p id="par0145" class="elsevierStylePara elsevierViewall">Para todos os casos com suspeita cl&#237;nica de DBAI&#44; o diagn&#243;stico &#233; confirmado pela realiza&#231;&#227;o de exame citol&#243;gico&#44; bi&#243;psia cut&#226;nea com exame anatomopatol&#243;gico&#44; imunofluoresc&#234;ncia direta e indireta e ELISA&#46; Portanto&#44; uma paciente&#160;com diagn&#243;stico confirmado de DBAI&#160;pr&#233;vio &#224; gesta&#231;&#227;o n&#227;o precisaria ser submetida novamente &#224; proped&#234;utica investigat&#243;ria&#44; salvo se as les&#245;es atuais n&#227;o se apresentam com caracter&#237;sticas t&#237;picas da DBAI previamente diagnosticada&#46; No entanto&#44; nos casos com quadro sugestivo de DBAI pela primeira vez durante a gesta&#231;&#227;o&#44; faz&#8208;se necess&#225;ria a confirma&#231;&#227;o diagn&#243;stica&#46; Com rela&#231;&#227;o&#160;&#224; bi&#243;psia cut&#226;nea&#44; aplica&#231;&#227;o t&#243;pica de clorexidina para antissepsia pode ser usada com seguran&#231;a em gestantes&#46; N&#227;o h&#225; relatos de efeitos teratog&#234;nicos relacionados aos anest&#233;sicos t&#243;picos&#46; No entanto&#44; a bi&#243;psia da pele deve ser realizada com cautela em gestantes em fun&#231;&#227;o do risco de metemoglobinemia fetal associada &#224; priloca&#237;na e da diminui&#231;&#227;o do fluxo uterino secund&#225;rio ao uso de anest&#233;sicos locais&#46;<a class="elsevierStyleCrossRef" href="#bib0410"><span class="elsevierStyleSup">32</span></a> Por esses motivos&#44; m&#233;todos alternativos podem ser &#250;teis e incluem investiga&#231;&#227;o sorol&#243;gica por meio da imunofluoresc&#234;ncia indireta&#44; ELISA e microscopia de imunofluoresc&#234;ncia com <span class="elsevierStyleItalic">biochip</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0415"><span class="elsevierStyleSup">33</span></a></p></span></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Tratamento das DBAI na gesta&#231;&#227;o e durante a lacta&#231;&#227;o</span><p id="par0150" class="elsevierStylePara elsevierViewall">O desafio do tratamento das DBAI durante a gesta&#231;&#227;o refere&#8208;se &#224; escolha do medicamento&#44; tendo como quest&#227;o principal a seguran&#231;a da m&#227;e e do concepto&#46; A dificuldade em avaliar os medicamentos melhores e mais seguros para DBAI em gestantes se deve&#58; 1&#41; &#224; ocorr&#234;ncia rara de DBAI na gesta&#231;&#227;o&#59; 2&#41; &#224; exclus&#227;o de gestantes de estudos cl&#237;nicos sobre medicamentos&#59; e 3&#41; &#224;s altera&#231;&#245;es hormonais associadas &#224; gesta&#231;&#227;o que podem impactar o controle da doen&#231;a&#44; interferindo na resposta imune&#46; Desde que a nova regulamenta&#231;&#227;o para uso de medicamentos na gesta&#231;&#227;o e lacta&#231;&#227;o entrou em vigor&#44; em&#160;30&#160;de junho de&#160;2015&#44; a Federal Drug Administration &#40;FDA&#41; eliminou as letras padr&#227;o da categoria para medicamentos prescritos na gesta&#231;&#227;o &#40;A&#44;&#160;B&#44;&#160;C&#44;&#160;D&#160;e&#160;X&#41;&#46;<a class="elsevierStyleCrossRef" href="#bib0420"><span class="elsevierStyleSup">34</span></a> De acordo com o sistema da categoria anterior&#44; nenhum medicamento para tratamento de DBAI pertencia &#224; classe&#160;A&#44; uma vez que as pacientes gr&#225;vidas n&#227;o podiam participar de ensaios cl&#237;nicos controlados randomizados&#46;</p><p id="par0155" class="elsevierStylePara elsevierViewall">Diversos medicamentos frequentemente utilizados na gesta&#231;&#227;o pertenciam &#224; categoria&#160;C&#44; uma vez que modelos animais evidenciaram efeitos adversos no feto&#46; No entanto&#44; existem diferen&#231;as significativas entre roedores e placenta humana&#44; e&#44; portanto&#44; esses riscos muitas vezes n&#227;o s&#227;o aplic&#225;veis aos seres humanos&#46; Muitos desses medicamentos anteriormente classificados na categoria&#160;C s&#227;o&#44; de fato&#44; boas op&#231;&#245;es para uso na gesta&#231;&#227;o&#44; especialmente quando os riscos da DBAI superam os riscos de utiliza&#231;&#227;o da medica&#231;&#227;o&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;35</span></a></p><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Glicocorticoides t&#243;picos</span><p id="par0160" class="elsevierStylePara elsevierViewall">Glicocorticoides t&#243;picos s&#227;o&#44; frequentemente&#44; tratamentos de primeira linha para DBAI e ainda mostram seguran&#231;a na gesta&#231;&#227;o&#44; com a vantagem de n&#227;o compartilhar os mesmos riscos dos esteroides sist&#234;micos&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">36</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">Os escores de Apgar&#44; anormalidades cong&#234;nitas&#44; incluindo fissuras orofaciais&#44; parto prematuro&#44; tipo de parto e morte fetal n&#227;o mostraram rela&#231;&#227;o com o uso de glicocorticoides t&#243;picos em qualquer pot&#234;ncia&#46; Uma exce&#231;&#227;o foi a associa&#231;&#227;o dose&#8208;resposta entre glicocorticoides t&#243;picos e crescimento intrauterino restrito &#40;CIUR&#41; e rec&#233;m&#8208;nascido de baixo peso ao nascer &#40;RNBP&#41;&#44; especificamente quando aplicado no terceiro trimestre em doses muito altas&#46;<a class="elsevierStyleCrossRef" href="#bib0430"><span class="elsevierStyleSup">36</span></a></p><p id="par0170" class="elsevierStylePara elsevierViewall">Glicocorticoides t&#243;picos s&#227;o seguros durante a lacta&#231;&#227;o&#44; uma vez que a transmiss&#227;o para o leite materno &#233; marginal e os glicocorticoides s&#227;o um elemento natural do leite materno&#46;<a class="elsevierStyleCrossRef" href="#bib0435"><span class="elsevierStyleSup">37</span></a> No entanto&#44; glicocorticoides t&#243;picos de alta pot&#234;ncia n&#227;o devem ser aplicados no mamilo antes da amamenta&#231;&#227;o&#44; em fun&#231;&#227;o do risco de hipertens&#227;o arterial infantil&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Inibidores t&#243;picos da calcineurina</span><p id="par0175" class="elsevierStylePara elsevierViewall">Relatos de casos e um ensaio cl&#237;nico duplo&#8208;cego placebo controlado demonstraram a efic&#225;cia dos inibidores t&#243;picos da calcineurina no tratamento das DBAI&#44; particularmente se a doen&#231;a for leve e localizada&#46;<a class="elsevierStyleCrossRef" href="#bib0445"><span class="elsevierStyleSup">39</span></a> Esses agentes geralmente s&#227;o usados para evitar os efeitos colaterais do uso prolongado de esteroides t&#243;picos&#44; especialmente em &#225;reas como face&#44; pesco&#231;o&#44; dobras e genitais&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">10</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Os efeitos sobre o feto&#44; que podem ser extrapolados a partir de estudos sobre a administra&#231;&#227;o sist&#234;mica de tacrolimo em pacientes transplantados&#44; incluem parto prematuro e RNBP&#46; Embora n&#227;o tenham sido realizados estudos formais em gestantes&#44; especialistas recomendam o uso de no m&#225;ximo&#160;5<span class="elsevierStyleHsp" style=""></span>g&#47;dia&#44; durante&#160;2&#8208;3&#160;semanas&#44; em pequenas &#225;reas&#46;<a class="elsevierStyleCrossRef" href="#bib0450"><span class="elsevierStyleSup">40</span></a></p><p id="par0185" class="elsevierStylePara elsevierViewall">Os dados de recomenda&#231;&#227;o de seguran&#231;a do tacrolimo t&#243;pico durante a lacta&#231;&#227;o s&#227;o limitados&#59; portanto&#44; ele deve ser usado com modera&#231;&#227;o&#44; evitando&#8208;se aplica&#231;&#227;o na &#225;rea do mamilo&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a></p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Glicocorticoides sist&#234;micos</span><p id="par0190" class="elsevierStylePara elsevierViewall">Os esteroides sist&#234;micos ainda s&#227;o considerados uma op&#231;&#227;o de tratamento importante e segura para as DBAI na gesta&#231;&#227;o&#46; Esteroides n&#227;o fluorados como prednisona e hidrocortisona costumam ser as formas preferidas&#44; porque a inativa&#231;&#227;o pela 11&#8208;beta&#8208;hidroxiesteroide&#8208;desidrogenase limita a exposi&#231;&#227;o fetal&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">10</span></a> Os riscos no feto s&#227;o fissuras orofaciais&#44; CIUR&#44; RNBP&#44; ruptura prematura de membranas&#44; atraso do desenvolvimento neuropsicomotor e parto prematuro&#44; e para gestantes&#44; os principais efeitos colaterais incluem pr&#233;&#8208;ecl&#226;mpsia&#44; eclampsia&#44; hipertens&#227;o arterial&#44; diabetes gestacional&#44; osteoporose&#44; m&#225; cicatriza&#231;&#227;o de feridas&#44; forma&#231;&#227;o de estrias e infec&#231;&#245;es puerperais e p&#243;s&#8208;operat&#243;rias&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;40&#44;41</span></a> A dose recomendada n&#227;o deve exceder 20<span class="elsevierStyleHsp" style=""></span>mg&#47;dia de prednisona&#44; evitando o uso a longo prazo&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a> Se forem necess&#225;rias doses mais altas&#44; a op&#231;&#227;o &#233; mudar para um agente poupador de esteroides para o controle da doen&#231;a&#46;</p><p id="par0195" class="elsevierStylePara elsevierViewall">O aleitamento materno deve ocorrer pelo menos&#160;4 horas&#160;ap&#243;s a administra&#231;&#227;o da prednisona&#44; uma vez que sua meia&#8208;vida s&#233;rica &#233; de 60 minutos&#44; com n&#237;veis no leite materno atingindo o pico ap&#243;s&#160;2 horas&#160;de ingest&#227;o e diminuindo rapidamente em seguida&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;40</span></a></p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Azatioprina</span><p id="par0200" class="elsevierStylePara elsevierViewall">Azatioprina &#233; um an&#225;logo sint&#233;tico da base purina de uso <span class="elsevierStyleItalic">off label</span> no tratamento das DBAI&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;40&#44;41</span></a> V&#225;rios estudos cl&#237;nicos e revis&#245;es recomendam a azatioprina como um imunossupressor relativamente seguro para ser usado durante a gesta&#231;&#227;o e lacta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">42</span></a> A placenta pode limitar a entrada de azatioprina e seu metab&#243;lito 6&#8208;mercaptopurina&#46; Linfopenia transit&#243;ria e imunodefici&#234;ncia podem ser evitadas se a dose di&#225;ria n&#227;o exceder 2<span class="elsevierStyleHsp" style=""></span>mg&#47;kg&#47;dia&#46;<a class="elsevierStyleCrossRef" href="#bib0465"><span class="elsevierStyleSup">43</span></a></p><p id="par0205" class="elsevierStylePara elsevierViewall">A European Federation of Crohn&#39;s &#38; Ulcerative Colitis Associations classifica a azatioprina como &#8220;provavelmente segura&#8221; para uso durante a amamenta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0460"><span class="elsevierStyleSup">42</span></a> O aleitamento deve ser feito pelo menos&#160;4 horas&#160;ap&#243;s a &#250;ltima dose&#46;<a class="elsevierStyleCrossRef" href="#bib0470"><span class="elsevierStyleSup">44</span></a></p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Micofenolato de mofetila</span><p id="par0210" class="elsevierStylePara elsevierViewall">Micofenolato de Mofetila &#40;MMF&#41; &#233; um excelente agente poupador de esteroides em doen&#231;as autoimunes&#44; incluindo DBAI&#46; No entanto&#44; &#233; um componente teratog&#234;nico conhecido e n&#227;o deve ser usado durante a gesta&#231;&#227;o&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">45</span></a> Como o metotrexato&#44; MMF inibe a s&#237;ntese de DNA e interrompe a divis&#227;o celular&#44; causando risco aumentado de aborto&#46; MMF tem sido associado a abortos espont&#226;neos &#40;especialmente no primeiro trimestre&#41;&#44; anormalidades de membros e face&#44; defeitos de linha m&#233;dia e outras malforma&#231;&#245;es cong&#234;nitas&#46;<a class="elsevierStyleCrossRef" href="#bib0475"><span class="elsevierStyleSup">45</span></a></p><p id="par0215" class="elsevierStylePara elsevierViewall">Apesar da escassez de dados sobre o uso de MMF durante o aleitamento materno&#44; especialistas atualmente o classificam como contraindicado&#46; O pequeno peso molecular do MMF permite que ele passe em quantidades significativas para o leite materno&#44; o que poderia causar problemas de desenvolvimento e risco de infec&#231;&#227;o no rec&#233;m&#8208;nascido&#46;<a class="elsevierStyleCrossRef" href="#bib0440"><span class="elsevierStyleSup">38</span></a></p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Dapsona</span><p id="par0220" class="elsevierStylePara elsevierViewall">A dapsona &#40;diaminodifenilsulfona&#41; &#233; frequentemente usada como terapia adjuvante para DBAI&#46; Relatos de casos mostraram sua seguran&#231;a na gesta&#231;&#227;o&#44; sem evid&#234;ncia de teratogenicidade&#44; bem como em estudos de gestantes em tratamento de mal&#225;ria&#44; hansen&#237;ase ou pneumonia por <span class="elsevierStyleItalic">Pneumocystis jiroveci</span>&#46;<a class="elsevierStyleCrossRef" href="#bib0455"><span class="elsevierStyleSup">41</span></a> Dapsona&#44; principalmente acima de 50<span class="elsevierStyleHsp" style=""></span>mg&#47;dia&#44; deve ser evitada em m&#227;e ou feto com defici&#234;ncia de glicose&#8208;6&#8208;fosfato desidrogenase &#40;G6PD&#41;&#44; em fun&#231;&#227;o do risco de anemia hemol&#237;tica&#59; todos os pacientes devem ser testados antes do seu uso&#46;<a class="elsevierStyleCrossRef" href="#bib0480"><span class="elsevierStyleSup">46</span></a></p><p id="par0225" class="elsevierStylePara elsevierViewall">A American&#160;Academy&#160;of Pediatrics considera a dapsona compat&#237;vel com o aleitamento materno&#44; uma vez que apenas quantidades pequenas de seus metab&#243;litos s&#227;o excretadas no leite&#46; A icter&#237;cia no beb&#234; deve ser monitorada&#44; se o aleitamento materno ocorrer durante a terapia com dapsona&#44; especialmente em caso de defici&#234;ncia de G6PD diagnosticada no rec&#233;m&#8208;nascido&#46;</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Doxiciclina</span><p id="par0230" class="elsevierStylePara elsevierViewall">Doxiciclina &#233; um antibi&#243;tico com efeitos anti&#8208;inflamat&#243;rios e pode ser &#250;til no tratamento das DBAI&#46;<a class="elsevierStyleCrossRef" href="#bib0485"><span class="elsevierStyleSup">47</span></a> Doxiciclina h&#225; muito tempo tem sido agrupada com outras tetraciclinas e classificadas como n&#227;o seguras durante a gesta&#231;&#227;o&#44; mas esse agrupamento pode n&#227;o estar correto&#44; uma vez que a doxiciclina foi desenvolvida ap&#243;s a toxicidade das outras tetraciclinas ter sido bem estabelecida&#46; &#201; prov&#225;vel que a doxiciclina tenha um perfil de seguran&#231;a diferente das outras tetraciclinas&#44; sem evid&#234;ncias que sustentem uma sobreposi&#231;&#227;o de toxicidades&#46; As tetraciclinas t&#234;m um risco aumentado de teratogenicidade&#44; descolora&#231;&#227;o dent&#225;ria&#44; interrup&#231;&#227;o do crescimento &#243;sseo e hepatotoxicidade materna&#44; mas a doxiciclina parece n&#227;o estar associada a esses riscos&#46; Os dados que diferenciam a doxiciclina das tetraciclinas ainda s&#227;o limitados e&#44; por isso&#44; os m&#233;dicos tendem a evitar a doxiciclina quando h&#225; op&#231;&#227;o de outras subst&#226;ncias com perfil de seguran&#231;a conhecido&#46;<a class="elsevierStyleCrossRef" href="#bib0490"><span class="elsevierStyleSup">48</span></a></p><p id="par0235" class="elsevierStylePara elsevierViewall">O uso de doxiciclina a curto prazo durante a lacta&#231;&#227;o n&#227;o &#233; contraindicado&#44; mas o f&#225;rmaco excreta&#8208;se no leite materno e estudos ainda s&#227;o escassos&#46;<a class="elsevierStyleCrossRef" href="#bib0425"><span class="elsevierStyleSup">35</span></a></p></span><span id="sec0115" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Rituximabe</span><p id="par0240" class="elsevierStylePara elsevierViewall">Rituximabe &#40;RTX&#41; &#233; um anticorpo monoclonal quim&#233;rico anti&#8208;CD20 cujos alvos s&#227;o as c&#233;lulas&#160;B&#44; implicadas na patog&#234;nese das DBAI&#46; O RTX &#233; bem&#8208;sucedido em propiciar remiss&#227;o da doen&#231;a&#44; por&#233;m &#233; contraindicado durante a gesta&#231;&#227;o&#44; por atravessar a placenta&#44; esgotar as c&#233;lulas&#160;B fetais e potencialmente aumentar o risco de infec&#231;&#245;es materno&#8208;fetais e para o rec&#233;m&#8208;nascido&#46; A passagem transplacent&#225;ria do RTX &#233; m&#237;nima no primeiro trimestre&#44; moderada no segundo e mais elevada no terceiro&#46; O RTX permanece no soro por tr&#234;s a seis meses e &#233; capaz de atravessar a placenta&#59; por isso&#44; o planejamento da gesta&#231;&#227;o &#233; essencial e as pacientes s&#227;o aconselhadas a esperar&#160;12&#160;meses ap&#243;s sua &#250;ltima infus&#227;o antes de tentar engravidar&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">10&#44;35</span></a> Em relatos de casos de pacientes que acidentalmente receberam RTX durante a gesta&#231;&#227;o n&#227;o foi observada correla&#231;&#227;o definitiva com eventos adversos&#44; mas os dados sobre o assunto permanecem escassos&#46;<a class="elsevierStyleCrossRef" href="#bib0495"><span class="elsevierStyleSup">49</span></a></p><p id="par0245" class="elsevierStylePara elsevierViewall">O RTX n&#227;o &#233; recomendado durante a lacta&#231;&#227;o devido &#224; falta de evid&#234;ncias sobre o assunto&#46;<a class="elsevierStyleCrossRef" href="#bib0500"><span class="elsevierStyleSup">50</span></a></p></span></span><span id="sec0120" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Considera&#231;&#245;es finais</span><p id="par0250" class="elsevierStylePara elsevierViewall">A gesta&#231;&#227;o constitui um per&#237;odo em que altera&#231;&#245;es imunol&#243;gicas e hormonais intensas ocorrem no organismo materno&#44; a fim de manter o feto halog&#234;nico e a estabilidade de seu pr&#243;prio sistema imunol&#243;gico&#46; Como a gesta&#231;&#227;o &#233; marcada pela predomin&#226;ncia da resposta linfocit&#225;ria Th2&#44; da mesma forma que as DBAI&#44; seria esperada uma piora dessas dermatoses&#46; No entanto&#44; o que se observou nesta revis&#227;o foi o curso vari&#225;vel das DBAI durante a gesta&#231;&#227;o&#46; Com rela&#231;&#227;o aos p&#234;nfigos&#44; o PV tende a piorar&#44; enquanto o PF n&#227;o costuma sofrer altera&#231;&#227;o&#46; Por outro lado&#44; a DBAL apresenta tend&#234;ncia de melhora&#46; Em raz&#227;o do pequeno n&#250;mero de casos estudados&#44; torna&#8208;se dif&#237;cil a an&#225;lise da evolu&#231;&#227;o da DH e da EBA durante a gesta&#231;&#227;o&#46;</p><p id="par0255" class="elsevierStylePara elsevierViewall">De maneira geral&#44; apesar da raridade&#44; a ocorr&#234;ncia das DBAI durante a gesta&#231;&#227;o &#233; situa&#231;&#227;o especial&#44; considerando&#8208;se as peculiaridades da confirma&#231;&#227;o diagn&#243;stica por bi&#243;psia cut&#226;nea e os riscos potenciais de alguns medicamentos para o concepto&#46; Glicocorticoides&#44; azatioprina e dapsona podem ser consideradas op&#231;&#245;es relativamente seguras durante a gesta&#231;&#227;o e o aleitamento&#44; desde que sua prescri&#231;&#227;o e acompanhamento sejam feitos rigorosamente sob supervis&#227;o m&#233;dica&#46; Ao contr&#225;rio&#44; micofenolato de mofetila&#44; doxiciclina e rituximabe&#44; apesar de alternativas eficientes para tratamento das DBAI&#44; t&#234;m seu uso contraindicado na gesta&#231;&#227;o pelos riscos potenciais para o concepto&#46; Exclu&#237;do o penfigoide gestacional&#44; ao conhecimento dos autores&#44; at&#233; o momento n&#227;o h&#225; nenhuma revis&#227;o semelhante de DBAI na gesta&#231;&#227;o&#46;</p></span><span id="sec0125" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Suporte financeiro</span><p id="par0260" class="elsevierStylePara elsevierViewall">FUNADERSP &#40;Fundo de Apoio &#224; Dermatologia do Estado de S&#227;o Paulo&#41; &#8211; projeto 50&#8208;2017&#46;</p></span><span id="sec0130" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Contribui&#231;&#227;o dos autores</span><p id="par0265" class="elsevierStylePara elsevierViewall">Patr&#237;cia Penha Silveira Fagundes&#58; Coleta de dados&#59; concep&#231;&#227;o e desenho do estudo&#59; an&#225;lise dos dados&#59; reda&#231;&#227;o do artigo&#59; revis&#227;o cr&#237;tica do conte&#250;do e aprova&#231;&#227;o da vers&#227;o final&#46;</p><p id="par0270" class="elsevierStylePara elsevierViewall">Claudia Giuli Santi&#58; Concep&#231;&#227;o&#59; revis&#227;o e aprova&#231;&#227;o da vers&#227;o final&#46;</p><p id="par0275" class="elsevierStylePara elsevierViewall">Celina Wakisaka Maruta&#58; Concep&#231;&#227;o&#59; revis&#227;o e aprova&#231;&#227;o da vers&#227;o final&#46;</p><p id="par0280" class="elsevierStylePara elsevierViewall">Denise Miyamoto&#58; Concep&#231;&#227;o&#59; revis&#227;o e aprova&#231;&#227;o da vers&#227;o final&#46;</p><p id="par0285" class="elsevierStylePara elsevierViewall">Valeria Aoki&#58; Concep&#231;&#227;o e desenho do estudo&#59; an&#225;lise dos dados&#59; reda&#231;&#227;o do artigo&#59; revis&#227;o cr&#237;tica do conte&#250;do e aprova&#231;&#227;o da vers&#227;o final&#46;</p></span><span id="sec0135" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflito de interesses</span><p id="par0290" class="elsevierStylePara elsevierViewall">Nenhum&#46;</p></span></span>"
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              "titulo" => "Glicocorticoides sist&#234;micos"
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    "fechaAceptado" => "2020-10-17"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">As dermatoses bolhosas autoimunes s&#227;o um grupo heterog&#234;neo de doen&#231;as com autoanticorpos direcionados contra prote&#237;nas estruturais da pele&#46; Embora a ocorr&#234;ncia das dermatoses bolhosas autoimunes na gesta&#231;&#227;o seja baixa&#44; esse tema merece aten&#231;&#227;o&#44; uma vez que as altera&#231;&#245;es imunol&#243;gicas e hormonais que ocorrem durante esse per&#237;odo podem trazer mudan&#231;as no curso esperado dessas dermatoses&#46; Os autores fazem uma revis&#227;o dos diversos aspectos das dermatoses bolhosas autoimunes que afetam as gestantes&#44; incluindo a abordagem terap&#234;utica durante o per&#237;odo grav&#237;dico e de amamenta&#231;&#227;o&#46; O penfigoide gestacional&#44; doen&#231;a bolhosa espec&#237;fica da gesta&#231;&#227;o&#44; n&#227;o foi objeto de estudo nesta revis&#227;o&#46;</p></span>"
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        "nota" => "<p class="elsevierStyleNotepara" id="npar0010">Como citar este artigo&#58; Fagundes PPS&#44; Santi CG&#44; Maruta CW&#44; Miyamoto D&#44; Aoki V&#46; Autoimmune bullous diseases in pregnancy&#58; clinical and epidemiological characteristics and therapeutic approach&#46; An Bras Dermatol&#46; 2021&#59;96&#58;581&#8211;90&#46;</p>"
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;a&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Curso da doen&#231;a na gesta&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Efeitos adversos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Doen&#231;a bolhosa neonatal&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">P&#234;nfigo vulgar&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Pode melhorar no terceiro trimestre&#44; mas recorrer no p&#243;s&#8208;parto&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">At&#233; 10&#37;&#44; em uma s&#233;rie de casos associados ao mau controle da doen&#231;a&#46; Risco de nascimento prematuro em doen&#231;a grave&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Transit&#243;ria e facilmente tratada&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">P&#234;nfigo foli&#225;ceo&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Curso vari&#225;vel&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">M&#237;nimos&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Extremamente rara&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Raramente visto na gesta&#231;&#227;o&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t\ttop\n
                  \t\t\t\t">N&#227;o relatada&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">Dermatose IgA linear&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">Pode melhorar no segundo trimestre&#44; mas recorrer no p&#243;s&#8208;parto&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&#237;nimos&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">N&#227;o relatada&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">Epiderm&#243;lise bolhosa adquirida&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">Extremamente rara&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">Um caso de exacerba&#231;&#227;o na gesta&#231;&#227;o&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">Um caso descrito&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">Penfigoide gestacional&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">Tende a ocorrer do segundo para o terceiro trimestre&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">Risco aumentado de parto pr&#233;&#8208;termo&#44; rec&#233;m&#8208;nascido pequeno para idade gestacional ou com baixo peso&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">Extremamente rara&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2743972.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "pt" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Curso das doen&#231;as bolhosas autoimunes e efeitos adversos durante a gesta&#231;&#227;o</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Tabela 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Tabela "
            "rol" => "short"
          ]
        ]
        "tabla" => array:3 [
          "leyenda" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">PV&#44; p&#234;nfigo vulgar&#59; PF&#44; p&#234;nfigo foli&#225;ceo&#59; ND&#44; dado n&#227;o dispon&#237;vel&#59; C&#44; corticosteroides&#59; MMF&#44; micofenolato de mofetila&#59; AZA&#44; azatioprina&#59; RTX&#44; rituximabe&#59; IGIV&#44; imunoglobulina intravenosa&#46;</p>"
          "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="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Autores<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a>&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">N&#250;mero de mulheres&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">Diagn&#243;stico antes da gesta&#231;&#227;o&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">Diagn&#243;stico durante a gesta&#231;&#227;o&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">Doen&#231;a&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">Idade do in&#237;cio &#40;anos&#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">Semana da gesta&#231;&#227;o do in&#237;cio ou piora&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">Piora durante gesta&#231;&#227;o&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">Melhora durante gesta&#231;&#227;o&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">Est&#225;vel durante a gesta&#231;&#227;o&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">Piora no p&#243;s&#8208;parto&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">Rec&#233;m&#8208; nascido com bolhas&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">Tratamento&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">Lake et al&#46;&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&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">X&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="" 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">PV&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">24&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">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="" 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="" 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">X&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="" 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="" 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">C&#47;MMF&#47;AZA&#47;IGIV&#47;RTX&nbsp;\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  " align="" 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">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">X&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="" 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">PV&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">19&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">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="" 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="" 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">X&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="" 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="" 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">C&#47;MMF&#47;IGIV&#47;RTX&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">Rangel&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&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="" 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">X&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">PV&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">24&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">X&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="" 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="" 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">X&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="" 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">C&#47;RTX&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">Elmuradi et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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&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">24&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">X&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="" valign="\n
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                  \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="" 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="" valign="\n
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                  \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="" 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">C&#47;MMF&#47;IGIV&#47;RTX&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">&#199;ayirli et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">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">18&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">X&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="" 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="" valign="\n
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                  \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="" valign="\n
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                  \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="" 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">C&#47;AZA&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">Salzberg et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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&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">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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&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">Kodagali et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">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">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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">X&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">C&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">Sol&#237;s&#8208;Arias et al&#46;&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&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">X&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="" 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">PV&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">21&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">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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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">X&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="" valign="\n
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                  \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">C&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">Itsukaichi et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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&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">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">X&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="" valign="\n
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                  \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="" 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">X&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">X&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="" valign="\n
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                  \t\t\t\t">&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">Ibrahim et al&#46;&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&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="" 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">X&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">PV&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&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">22&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">X&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="" 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="" 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="" 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">X&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">C&#47;IGIV&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">Lorente Lavirgen et al&#46;&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&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">X&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="" 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">PF&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&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">24&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">X&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="" 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="" 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="" 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">X&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">C&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">Drenovska et al&#46;&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&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="" 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">X&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">PV&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">27&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">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="" 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="" 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">X&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">X&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="" 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">C&nbsp;\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  " align="" 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">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">X&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="" 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">PV&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">24&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="" 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="" 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="" 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">X&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="" 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="" 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">C&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">Galarza et al&#46;&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&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="" 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">X&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">PF&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">36&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">17&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="" 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="" 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="" 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="" 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="" 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">C&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">Gushi et al&#46;&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&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">X&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="" 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">PV&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&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">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="" 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="" 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">X&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="" 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">X&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">C&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">Lehman et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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&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">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="" valign="\n
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                  \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="" 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">X&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="" 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="" 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="" 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></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">Amer et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">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">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="" 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="" 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">X&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="" 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="" 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">C&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">Ugajin et al&#46;&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&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">X&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="" 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">PV&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">30&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">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">X&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="" 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="" valign="\n
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                  \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">X&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="" valign="\n
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                  \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">C&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">Bonifazi et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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">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">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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">In&#237;cio PV 6 meses p&#243;s&#8208; parto&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">X&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="" valign="\n
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                  \t\t\t\t">&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">Fenniche et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">12&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="" valign="\n
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                  \t\t\t\t">&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">X&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="" valign="\n
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                  \t\t\t\t">&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">X&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="" valign="\n
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                  \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">C&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">L&#243;pez&#8208;Jornet et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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&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">20&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&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">Shieh et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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">16&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">X&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">C&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">Okubo et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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">24&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">18&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="" valign="\n
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                  \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">X&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="" valign="\n
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                  \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">X&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="" valign="\n
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                  \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">C&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">Hirsch et al&#46;&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&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">X&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="" valign="\n
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                  \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">PF&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&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">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="" valign="\n
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                  \t\t\t\t">&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \t\t\t\t">&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">X&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="" valign="\n
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                  \t\t\t\t">&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">Parlowsky et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">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">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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \t\t\t\t">&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
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                  \t\t\t\t</td><td class="td" title="\n
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                  \t\t\t\t  " align="" valign="\n
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                  \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="" valign="\n
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                  \t\t\t\t">&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">Campo&#8208;Voegeli et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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">35&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">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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">X&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">C&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">Kalayciyan et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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&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&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" 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
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                  \t\t\t\t">C&#47;AZA&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  " align="left" valign="\n
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                  \t\t\t\t">PV&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">PV&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 ; entry_with_role_rowhead " align="left" valign="\n
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                  \t\t\t\t">Muhammad et al&#46;&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">PV&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">Masson et al&#46;&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">PV&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">Avalos&#8208;D&#237;az et al&#46;&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">PF&nbsp;\t\t\t\t\t\t\n
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                  \t\t\t\t">ND&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">&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="" 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">X&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">C&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">Piontek et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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">12&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" 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">C&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">Fainaru et al&#46;&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&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">X&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="" 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">PV&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&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">13&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">X&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="" 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="" 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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&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">Kanwar et al&#46;&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&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="" 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">X&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">PV&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&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">24&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">X&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">C&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">Hern et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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&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">14&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&nbsp;\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  " align="" 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">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">X&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="" valign="\n
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                  \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">PV&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&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">14&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">Tratamento sintom&#225;tico&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">Chowdhury et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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&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">18&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="" 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="" 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">X&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="" 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">X&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">C&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">Virgili et al&#46;&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&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="" 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">X&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">PV&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">27&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&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">X&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="" 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="" 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="" 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="" 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">C&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">Tope et al&#46;&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&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">X&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="" 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">PV&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">27&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">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="" 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">X&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="" 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="" 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">X&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">C&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">Goldberg et al&#46;&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&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">X&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="" 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">PV&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">21&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">28&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">X&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="" 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="" 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="" 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="" 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">C&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">Kanwar et al&#46;&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&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="" 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">X&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">PV&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">21&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">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="" 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="" 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">X&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="" 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="" 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">C&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">Moncada et al&#46;&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&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">X&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="" 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">PV&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">28&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">16&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="" 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="" 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">X&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">X&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="" 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">C&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">Kaufman et al&#46;&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&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="" 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">X&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">PF&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">27&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">16&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">X&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="" 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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&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">Eyre et al&#46;&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&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">X&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="" 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">PF&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">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">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">X&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="" 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="" 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="" 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="" 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">C&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">Hup et al&#46;&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&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">X&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="" 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">PV&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">20&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">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="" 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="" 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">X&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="" 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="" 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="" 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></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">Merlob et al&#46;&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&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">X&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="" 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">PV&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">24&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">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="" 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="" 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">X&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="" 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">X&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">C&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">Ross et al&#46;&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&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="" 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">X&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">PV&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">19&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">13&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">X&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="" 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="" 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="" 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">Morte fetal&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">C&#47;AZA&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">Wasserstrum et al&#46;&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&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">X&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="" 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">PV&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">30&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">20&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">X&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="" 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="" 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="" 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">Morte fetal&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">C&#47;AZA&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">Green et al&#46;&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&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">X&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="" 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">PV&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">36&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">28&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">X&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="" 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="" 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="" valign="\n
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                  \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">Morte fetal&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">C&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">Moncada et al&#46;&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&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="" 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">X&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">PV&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">18&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">14&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">X&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="" 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="" 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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&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">Honeyman et al&#46;&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&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="" valign="\n
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                  \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">X&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">PV&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">25&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&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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">C&nbsp;\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  " align="" 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="" 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="" valign="\n
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                  \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">X&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">PV&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">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">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="" valign="\n
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                  \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="" valign="\n
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                  \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">X &#40;p&#243;s aborto&#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">Aborto&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="" valign="\n
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                  \t\t\t\t">&nbsp;\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  " align="" 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="" 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="" 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">X&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">PV&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&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">16&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">X&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="" valign="\n
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                  \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="" valign="\n
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                  \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="" valign="\n
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                  \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="" 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">C&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">Terpstra et al&#46;&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&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="" 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">X&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">PV&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&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&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">X&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="" 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="" 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="" 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">Morte fetal&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">C&#47;DAPSONA&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">Stanoeva et al&#46;&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&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">X&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="" valign="\n
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                  \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">PV&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&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
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Journal Information
Vol. 96. Issue 5.
Pages 581-590 (1 September 2021)
Visits
11995
Vol. 96. Issue 5.
Pages 581-590 (1 September 2021)
Revisão
Open Access
Doenças bolhosas autoimunes na gestação: características clínicas, epidemiológicas e abordagem terapêutica
Visits
11995
Patrícia Penha Silveira Fagundes
Corresponding author
patricia1fagundes@gmail.com

Autor para correspondência.
, Claudia Giuli Santi, Celina Wakisaka Maruta, Denise Miyamoto, Valeria Aoki
Departamento de Dermatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil
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Tables (2)
Tabela 1. Curso das doenças bolhosas autoimunes e efeitos adversos durante a gestação
Tabela 2. Dados clínicos e demográficos de mulheres grávidas com pênfigos
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Resumo

As dermatoses bolhosas autoimunes são um grupo heterogêneo de doenças com autoanticorpos direcionados contra proteínas estruturais da pele. Embora a ocorrência das dermatoses bolhosas autoimunes na gestação seja baixa, esse tema merece atenção, uma vez que as alterações imunológicas e hormonais que ocorrem durante esse período podem trazer mudanças no curso esperado dessas dermatoses. Os autores fazem uma revisão dos diversos aspectos das dermatoses bolhosas autoimunes que afetam as gestantes, incluindo a abordagem terapêutica durante o período gravídico e de amamentação. O penfigoide gestacional, doença bolhosa específica da gestação, não foi objeto de estudo nesta revisão.

Palavras‐chave:
Autoimunidade
Dermatopatias vesiculobolhosas
Epidermólise bolhosa adquirida
Gravidez
Pênfigo
Penfigoide bolhoso
Full Text
Introdução

As doenças bolhosas autoimunes (DBAI) cursam com o surgimento de bolhas na pele e/ou em mucosas, resultantes da ligação de autoanticorpos contra antígenos epidérmicos ou estruturas da junção dermoepidérmica (JDE), relacionados à adesão celular, e são classificadas de acordo com o nível da clivagem epitelial.1 O primeiro grupo, das dermatoses bolhosas intraepidérmicas, tem como principais representantes o pênfigo foliáceo (PF) e o pênfigo vulgar (PV); outras condições incluem pênfigo por IgA, pênfigo paraneoplásico e pênfigo induzidos por fármacos. Há produção de autoanticorpos direcionados contra glicoproteínas epidérmicas intercelulares. O segundo grupo, das dermatoses bolhosas subepidérmicas, tem como principais representantes o penfigoide bolhoso (PB) e epidermólise bolhosa adquirida (EBA), seguidos por condições menos comuns como a dermatose bolhosa por IgA linear (DBAL), dermatite herpetiforme (DH), penfigoide das mucosas (PM) e lúpus eritematoso sistêmico bolhoso (LESB). Esse grupo é definido pela presença de autoanticorpos direcionados contra autoantígenos da zona da membrana basal (ZMB), levando à clivagem subepidérmica.

As DBAI podem ocorrer durante a gestação, mas são relativamente raras.2 Existem duas situações clínicas distintas: 1) paciente com DBAI previamente diagnosticada, engravida; 2) gestante sem histórico prévio de DBAI desenvolve um surto de bolhas que requer diagnóstico e manejo.3 De acordo com esta revisão, a primeira situação é a mais frequente.

O penfigoide gestacional (PG), uma variante do PB, tem seu início exclusivamente associado à gestação, ao período pós‐parto, a tumores trofoblásticos, mola hidatiforme ou coriocarcinoma, e não foi incluído nesta revisão.4

Os autores tiveram como objetivo realizar uma revisão sobre a ocorrência de DBAI durante a gestação, uma vez que a maioria das publicações é baseada em relatos de casos.

Sistema imune e gestação

A resposta imunológica existe principalmente para defender o hospedeiro contra patógenos invasores, e para proporcionar tolerância aos autoantígenos. Linfócitos derivados do timo, ou linfócitos T (LT), estão envolvidos com a manutenção de tal função. Assim, LT nativos podem diferenciar‐se em LT com especificidade para responder a antígenos externos, bem como a autoantígenos. A maturação celular dos LT depende essencialmente de interações com o ambiente físico‐químico e resulta no desenvolvimento de células com função efetora e de memória, ou no desenvolvimento de células com função regulatória. Linfócitos T auxiliares exercem um papel na defesa imunológica estimulando a síntese de anticorpos; e linfócitos T regulatórios têm ação anti‐inflamatória e desempenham um papel na manutenção da tolerância aos seus próprios componentes celulares. Dados da literatura indicam que, tanto em murinos quanto humanos, a depleção dos linfócitos T regulatórios está relacionada ao desenvolvimento de doenças autoimunes graves.5

A gestação constitui um estado imunológico específico, uma vez que o organismo materno deve equilibrar a tolerância fetal com a manutenção de seu próprio sistema imunológico. Alterações hormonais relevantes ocorrem na gestação, tanto nos níveis de progesterona e estrogênio quanto em cortisol, norepinefrina e deidroepiandrosterona. Os níveis séricos de progesterona e estradiol aumentam de cinco a 10 vezes ao longo da gestação, retornando rapidamente ao nível normal no pós‐parto.6 Sob a influência desses hormônios, mudanças profundas no sistema imunológico ocorrem durante toda a gestação, a fim de acomodar o feto alogênico, que incluem processos imunorregulatórios e imunossupressores. Esse estado de imunomodulação ocorre mais intensamente na interface materno‐fetal, na qual os níveis de progesterona são muito altos em função da maior produção desse hormônio pela placenta, e mais sutil no sangue periférico materno.7

Na região uterina onde a placenta se desenvolve (decídua), há supressão acentuada da citotoxicidade, infiltração de células natural killer (NK) útero‐específicas, bloqueio de antígenos fetais expostos a linfonodos maternos e acúmulo de células T reguladoras (Treg) feto‐específicas. A quantidade de células Treg está elevada durante a gestação, inclusive no sangue materno; elas desempenham um papel na supressão da resposta imune local por meio do fenômeno da supressão vinculada. Essa supressão pode explicar os baixos níveis de autoanticorpos durante a gestação em determinadas doenças autoimunes e inflamatórias, levando à remissão, seguida de reativação no pós‐parto como na doença de Graves e artrite reumatoide.3

Há escassez de dados na literatura médica que mencionem as importantes mudanças na população de células Treg em gestantes. No entanto, essas células são conhecidas por desempenhar um papel de destaque na promoção da sobrevivência fetal, e sugere‐se que seu aumento esteja relacionado ao aumento das células Th2 efetoras. Estudos in vivo e in vitro mostram que a progesterona tem a capacidade de suprimir a diferenciação Th1/Th17 e, em contraste, potencializar a diferenciação Th2 e das células Treg. Além disso, citocinas maternas levam à maior diferenciação das células T nativas em células Th2.8 O resultado final é um desequilíbrio imunológico, com aumento da população celular Th2, em detrimento das células Th1 e Th17. Sugere‐se que haja maior direcionamento para a população Th2, essencial para a manutenção do estado normal de gestação. É importante ressaltar que um ambiente inicial na predominância do Th1 é necessário para o sucesso da implantação uterina. No entanto, em estágios posteriores da gestação, a predominância da resposta linfocitária Th2 é necessária para um ambiente de tolerância transitória aos antígenos fetais (fig. 1).

Figura 1.

Supressão da citotoxicidade e o estado de imunomodulação na interface materno‐fetal.

(0.19MB).

Considerando as alterações fisiológicas na resposta imune durante a gestação, a ocorrência de doenças autoimunes em gestantes é um fator de alto risco e pode levar a mudanças no estado de suas doenças durante esse período.3

A gestação é marcada pela predominância da resposta linfocitária Th2, um perfil coincidente com o desenvolvimento de dermatoses bolhosas autoimunes. Por causa da redução da resposta Th1 e possivelmente Th17 durante a gestação normal, doenças cutâneas com predominância da resposta Th1, como psoríase, artrite reumatoide e esclerose múltipla, apresentam melhora durante a gestação. Por outro lado, doenças com padrão de resposta Th2 como pênfigos, lúpus eritematoso e asma podem não se beneficiar dessa mudança no padrão imunológico, por causa da predominância da resposta Th2 na atividade dessas doenças.2,9

Assim, a coexistência da dermatose bolhosa autoimune em gestantes precipitaria ou aumentaria a ocorrência de pênfigos e penfigoides (tabela 1). No entanto, o curso das DBAI tende a flutuar durante a gestação em decorrência das alterações imunológicas causadas por estrogênio e progesterona, mas também por cortisol, norepinefrina e deidroepiandrosterona.2

Tabela 1.

Curso das doenças bolhosas autoimunes e efeitos adversos durante a gestação

Doença  Curso da doença na gestação  Efeitos adversos  Doença bolhosa neonatal 
Pênfigo vulgar  Pode melhorar no terceiro trimestre, mas recorrer no pós‐parto  Até 10%, em uma série de casos associados ao mau controle da doença. Risco de nascimento prematuro em doença grave  Transitória e facilmente tratada 
Pênfigo foliáceo  Curso variável  Mínimos  Extremamente rara 
Penfigoide bolhoso  Raramente visto na gestação  Não relatados  Não relatada 
Dermatose IgA linear  Pode melhorar no segundo trimestre, mas recorrer no pós‐parto  Mínimos  Não relatada 
Epidermólise bolhosa adquirida  Extremamente rara  Um caso de exacerbação na gestação  Um caso descrito 
Penfigoide gestacional  Tende a ocorrer do segundo para o terceiro trimestre  Risco aumentado de parto pré‐termo, recém‐nascido pequeno para idade gestacional ou com baixo peso  Extremamente rara 

Além disso, a gestação traz outras exigências no manejo clínico usual das DBAI: restrições nos métodos habituais de confirmação diagnóstica, limitação no uso de determinados medicamentos e escolha da forma de parto. Por essas razões, pacientes com DBAI em idade fértil e que desejam engravidar devem ser aconselhadas a fazer o planejamento familiar, no intuito de garantir melhores condições de saúde para ela e o concepto. O uso de um método contraceptivo deve ser instituído até que a doença esteja bem controlada, de modo que a gestação ocorra durante período com redução na atividade da doença.3,10

Alguns aspectos etiológicos e epidemiológicos das DBAIPênfigo vulgar

No PV, há predominância do sexo feminino, evidenciada por razão mulher:homem de 1.4 e 2.3, segundo estudos epidemiológicos realizados na China e Grécia.3,11 Um desfecho pior do PV também tem sido observado em mulheres; análise recente mostrou que os alelos HLA DRB1*04:02 e DQB1 *03:02 estavam associados com PV grave, e DQB1*03:02 foi encontrado com maior frequência em pacientes do sexo feminino.

Uma revisão envolvendo 49 gestantes com PV constatou que 37% apresentavam a doença pela primeira vez durante a gestação, e desfechos adversos da gestação (ou seja, pênfigo neonatal e óbito perinatal) ocorreram em até 10% dos casos. O PV tende a melhorar na gestação, após o terceiro trimestre, e reativar no período pós‐parto. Portanto, a gestação pode precipitar ou agravar o quadro de PV.12

A ocorrência de PV neonatal é transitória, e sua resolução tende a ocorrer dentro de três semanas; em geral, deve‐se à transmissão transplacentária de anticorpos IgG da mãe para o feto, e é facilmente tratável.13 Além do PV neonatal, outras consequências para o recém‐nascido incluem: restrição ao crescimento intrauterino, recém‐nascido pré‐termo e morte fetal. No entanto, é difícil distinguir as consequências decorrentes do tratamento daquelas próprias da doença.14 Além disso, as diferenças na expressão da desmogleína na pele neonatal são responsáveis pela diversidade de manifestações clínicas entre mãe e filho.13 Os eventos adversos parecem estar mais correlacionados com mau controle da doença materna, maior nível sérico e no cordão umbilical de anticorpos maternos, do que com medicamentos específicos utilizados para tratar PV materno.15 Portanto, tratamentos que levem à diminuição nos níveis de anticorpos séricos maternos, a fim de limitar a passagem transplacentária de IgG patogênica, justificam a terapia imunossupressora, a despeito de essa abordagem durante a gestação ainda não ter sido bem estabelecida.15 Deve‐se lembrar que, antes da introdução do uso de corticosteroides sistêmicos para PV, a doença apresentava elevadas taxas de mortalidade.

Pênfigo foliáceo

O PF se apresenta sob duas formas: a clássica (doença de Cazenave) e a endêmica. Esta última inclui o fogo selvagem (FS), que corresponde à forma endêmica sul‐americana.16 Não há relato de predominância de gênero no PF ou FS, mas as formas endêmicas de PF observadas no norte da África (Tunísia) mostram uma predominância feminina característica, especialmente entre as mulheres jovens (relação mulher:homem de 4:1). Em uma série de casos com 23 pacientes tunisianas com pênfigo, suspeitou‐se do papel provocador da gestação no desenvolvimento dessa doença, em função de ser a Tunísia um país onde mulheres jovens têm alta taxa de fecundidade.17

O PF pode ter curso variável na gestação, sem efeito sobre o feto. A associação com PF neonatal é extremamente rara no contexto de títulos de anticorpos excepcionalmente elevados.18 A desmogleína 3 é expressa em toda a epiderme, incluindo as camadas subcórneas na pele neonatal, e pode ser protetora contra anticorpos antidesmogleína 1 causadores da doença.13,19

Um estudo no Brasil com 19 gestantes que apresentavam FS não observou nenhuma doença clínica neonatal; a imunofluorescência direta foi negativa em 12 dos 17 espécimes de pele neonatal, os autoanticorpos IgG estavam presentes em títulos baixos (menos de 1:40) e a IgG4 era a subclasse predominante de IgG, em nove das 19 amostras de sangue do cordão umbilical. Os autores sugerem que a placenta possa servir como imunoabsorvente biológico de autoanticorpos patogênicos.20

Epidermólise bolhosa adquirida

A EBA é um subtipo raro, fenotipicamente heterogêneo de DBAI, predominante no sexo feminino e caracterizado por autoanticorpos contra o colágeno tipo VII. Dois trabalhos estudaram EBA e seus dados associados, com um total de 83 casos, revelando que a razão mulher:homem é de 1,56.21,22

Dermatose por IgA linear

A DBAL é uma doença bolhosa autoimune rara com bolhas subepidérmicas, na qual os autoanticorpos IgA reconhecem como antígenos os ectodomínios subepidérmicos do colágeno tipo XVII (COL17, BP180) na ZMB. Há escassos dados epidemiológicos sobre sua ocorrência por gênero bem como sua incidência na gestação.23 Os pacientes são categorizados em dois grupos: um com início pré‐puberal e o outro de início posterior (DBAL adulto). Alguns pacientes com DBAL são mulheres jovens que engravidaram. Pouco se sabe sobre o efeito da DBAL e seu tratamento na gestação, ou sobre o efeito da gestação na DBAL. Sabe‐se que seu antígeno é expresso na membrana basal amniótica e a deposição do IgA ocorre na zona da membrana basal amniótica do feto das pacientes afetadas.24

De acordo com uma série de casos de DBAL na gestação, a doença geralmente melhora ao final do primeiro trimestre e normalmente recorre no segundo trimestre, mas pode recair no período pós‐parto. Por essa razão, pode ser possível a suspensão da dapsona durante a gestação. Há evidências de que os anticorpos IgA tornam‐se glicosilados durante a gestação, o que poderia explicar essa remissão; as células Treg também exerceriam algum papel. No entanto, os pacientes devem ser aconselhados sobre a possibilidade de uma recaída pós‐parto. A doença também pode reativar anos depois, mesmo após um período prolongado de remissão.25

Dermatite herpetiforme

A DH está intimamente associada à doença celíaca; ambas as condições são mediadas por autoanticorpos IgA e têm como alvo o autoantígeno transglutaminase. Em contraste com os pênfigos e o penfigoide, as evidências de predominância de gênero na DH são conflitantes, sem conclusão sobre a prevalência em mulheres ou homens.26 Quanto à sua ocorrência durante a gestação, há escassez de dados, com apenas dois artigos encontrados na literatura.

DBAI e gestação

A presente pesquisa teve como principal foco relatos de casos e estudos retrospectivos. As referências foram recuperadas em um período de publicação de 1979 a 2017 por uma estratégia de busca eletrônica: “(pênfigo vulgar [Termos do MeSH]) E (gestação [Termos de MeSH]); (pênfigo foliáceo [Termos de MeSH]) E (gestação[Termos de MeSH]); (dermatite herpertiforme [Termos MeSH]) E (gestação[Termos de MeSH]); (epidermólise bolhosa adquirida [Termos de MeSH]) E (gestação[Termos de MeSH]); (dermatose IgA linear [Termos de MeSH]) E (gestação[Termos de MeSH]); Filtros: relatos de casos” no PubMed. Foram excluídos os artigos não publicados em inglês e aqueles de penfigoide gestacional e formas congênitas de doenças bolhosas. Foram incluídos 56 artigos, de acordo com seus títulos e resumos.

Pênfigos e gestação

Foram incluídos 49 artigos (Apêndice A), que relatavam um total de 57 mulheres com 59 gestações (tabela 2); 31 pacientes (54,3%) tiveram o diagnóstico de pênfigo antes da gestação, e 26 (45,6%) durante a gestação. Cinquenta e um pacientes (89,4%) tiveram o diagnóstico de PV e seis (10,5%) de PF. A média de idade no início da doença foi de 28,4 anos, e a média das semanas de semana gestacional de início/piora da doença foi igual a 16. O comportamento do pênfigo foi relatado em 50 gestações. Em 33/50 (66%) gestações a doença piorou, em 14/50 (28%) a doença manteve‐se estável, e em 3/50 (6%) a doença melhorou. Em 12 das 50 gestações (24%) houve relato de reativação pós‐parto, e desfechos adversos da gestação como pênfigo neonatal, morte perinatal ou aborto foram relatados em 33% dessas gestações. Quanto ao tratamento de pênfigos durante a gestação, foram identificadas 51 pacientes cujos tratamentos foram descritos. Em 41 deles (80,3%) a monoterapia foi a escolha, e nos outros 10 (19,6%) a terapia combinada foi relatada. Rituximabe foi utilizado em quatro (7,8%); corticoides sistêmicos em todos os 51 (100%); azatioprina em cinco (9,8%); micofenolato mofetil em três (5,8%); dapsona em um (1,9%) e imunoglobulina intravenosa em quatro (7,8%) casos.

Tabela 2.

Dados clínicos e demográficos de mulheres grávidas com pênfigos

Autoresa  Número de mulheres  Diagnóstico antes da gestação  Diagnóstico durante a gestação  Doença  Idade do início (anos)  Semana da gestação do início ou piora  Piora durante gestação  Melhora durante gestação  Estável durante a gestação  Piora no pós‐parto  Recém‐ nascido com bolhas  Tratamento 
Lake et al.    PV  24  ND          C/MMF/AZA/IGIV/RTX 
    PV  19  ND          C/MMF/IGIV/RTX 
Rangel    PV  24  11        C/RTX 
Elmuradi et al.    PV  33  24          C/MMF/IGIV/RTX 
Çayirli et al.    PV  ND  18          C/AZA 
Salzberg et al.    PV  34         
Kodagali et al.    PV  ND  ND         
Solís‐Arias et al.    PV  21       
Itsukaichi et al.    PV  34  ND       
Ibrahim et al.    PV  23  22        C/IGIV 
Lorente Lavirgen et al.    PF  33  24       
Drenovska et al.    PV  27  ND       
    PV  24           
Galarza et al.    PF  36  17           
Gushi et al.    PV  32  ND       
Lehman et al.    PV  32  ND           
Amer et al.    PV  ND  ND         
Ugajin et al.    PV  30  ND       
Bonifazi et al.    PV  ND  ND        Início PV 6 meses pós‐ parto   
Fenniche et al.    PV  29  12       
López‐Jornet et al.    PV  32  20         
Shieh et al.    PV  29  16       
Okubo et al.    PV  24  18       
Hirsch et al.    PF  23  ND           
Parlowsky et al.    PV  ND  ND         
Campo‐Voegeli et al.    PV  35       
Kalayciyan et al.    PV  31  32            C/AZA 
    PV  33           
    PV  32  10           
    PV  30           
Muhammad et al.    PV  28         
Masson et al.    PV  38  12         
Avalos‐Díaz et al.    PF  20  ND       
Piontek et al.    PV  29  12         
Fainaru et al.    PV  32  13         
Kanwar et al.    PV  33  24       
Hern et al.    PV  32  14         
    PV  33  14          Tratamento sintomático 
Chowdhury et al.    PV  31  18       
Virgili et al.    PV  27  26         
Tope et al.    PV  27  ND       
Goldberg et al.    PV  21  28         
Kanwar et al.    PV  21         
Moncada et al.    PV  28  16       
Kaufman et al.    PF  27  16         
Eyre et al.    PF  37  ND         
Hup et al.    PV  20  ND           
Merlob et al.    PV  24  ND       
Ross et al.    PV  19  13        Morte fetal  C/AZA 
Wasserstrum et al.    PV  30  20        Morte fetal  C/AZA 
Green et al.    PV  36  28        Morte fetal 
Moncada et al.    PV  18  14         
Honeyman et al.    PV  25  32         
      PV  29  ND  ND      X (pós aborto)  Aborto   
      PV  33  16         
Terpstra et al.    PV  23  12        Morte fetal  C/DAPSONA 
Stanoeva et al.    PV  33  13         
    PV  28  20       
    PV  29  20         

PV, pênfigo vulgar; PF, pênfigo foliáceo; ND, dado não disponível; C, corticosteroides; MMF, micofenolato de mofetila; AZA, azatioprina; RTX, rituximabe; IGIV, imunoglobulina intravenosa.

a

As referências bibliográficas estão disponíveis como material suplementar (Apêndice A).

Dermatose por IgA linear e gestação

Foram encontrados três artigos sobre DBAL e gestação. Em um deles, 12 pacientes tiveram um total de 19 gestações. A doença permaneceu em atividade em 13 de 19 gestações, sofreu remissão em quatro e houve recorrência no pós‐parto em duas gestações. A idade de início da DBAL variou de 1,5 a 33 anos; três pacientes tinham doença bolhosa crônica na infância, e nove tinham DBAL forma do adulto. No geral, a DBAL tende a melhorar durante a gestação, especialmente por volta da décima semana gestacional. Doze das 19 pacientes receberam tratamento sistêmico (7/12 receberam dapsona), 4/19 estavam em remissão e 1/19 apresentou doença mínima, sem terapia.25

Dois artigos de relatos de caso descreveram DBAL e gestação: um refere‐se a uma mulher de 24 anos diagnosticada com DBAL e mola hidatiforme, excisada em sua terceira gestação, e o outro refere‐se a uma mulher de 29 anos, grávida de 38 semanas, com autoanticorpos direcionados contra o domínio não colágeno 16A (NC16A) de COL17.23,27

Epidermólise bolhosa adquirida e gestação

Foram recuperados três artigos sobre EBA e gestação. Em um deles, uma mulher de 32 anos teve o diagnóstico de EBA e, no momento do parto, tanto a mãe quanto o recém‐nascido apresentavam erosões superficiais e profundas na face, tórax, abdome e extremidades.28 O segundo artigo descreve uma paciente que desenvolveu EBA no segundo dia do pós‐parto com resolução de bolhas na menopausa.29 O terceiro artigo relata uma mulher de 26 anos que teve uma recaída do EBA durante o primeiro mês de gestação. Por causa de uma resposta insuficiente aos corticosteroides sistêmicos, ela sofreu um aborto no segundo mês de gestação e, em seguida, teve redução significativa do número de bolhas.30

Dermatite herpetiforme e gestação

Apenas um artigo foi recuperado. Uma paciente de 33 anos com quadro de DH grave engravidou, e foi necessária dapsona oral (25‐50 mg/dia) para controle da doença. A paciente deu à luz um recém‐nascido a termo, hígido, e no pós‐parto evoluiu com reativação da doença.31

Diagnóstico laboratorial

Para todos os casos com suspeita clínica de DBAI, o diagnóstico é confirmado pela realização de exame citológico, biópsia cutânea com exame anatomopatológico, imunofluorescência direta e indireta e ELISA. Portanto, uma paciente com diagnóstico confirmado de DBAI prévio à gestação não precisaria ser submetida novamente à propedêutica investigatória, salvo se as lesões atuais não se apresentam com características típicas da DBAI previamente diagnosticada. No entanto, nos casos com quadro sugestivo de DBAI pela primeira vez durante a gestação, faz‐se necessária a confirmação diagnóstica. Com relação à biópsia cutânea, aplicação tópica de clorexidina para antissepsia pode ser usada com segurança em gestantes. Não há relatos de efeitos teratogênicos relacionados aos anestésicos tópicos. No entanto, a biópsia da pele deve ser realizada com cautela em gestantes em função do risco de metemoglobinemia fetal associada à prilocaína e da diminuição do fluxo uterino secundário ao uso de anestésicos locais.32 Por esses motivos, métodos alternativos podem ser úteis e incluem investigação sorológica por meio da imunofluorescência indireta, ELISA e microscopia de imunofluorescência com biochip.33

Tratamento das DBAI na gestação e durante a lactação

O desafio do tratamento das DBAI durante a gestação refere‐se à escolha do medicamento, tendo como questão principal a segurança da mãe e do concepto. A dificuldade em avaliar os medicamentos melhores e mais seguros para DBAI em gestantes se deve: 1) à ocorrência rara de DBAI na gestação; 2) à exclusão de gestantes de estudos clínicos sobre medicamentos; e 3) às alterações hormonais associadas à gestação que podem impactar o controle da doença, interferindo na resposta imune. Desde que a nova regulamentação para uso de medicamentos na gestação e lactação entrou em vigor, em 30 de junho de 2015, a Federal Drug Administration (FDA) eliminou as letras padrão da categoria para medicamentos prescritos na gestação (A, B, C, D e X).34 De acordo com o sistema da categoria anterior, nenhum medicamento para tratamento de DBAI pertencia à classe A, uma vez que as pacientes grávidas não podiam participar de ensaios clínicos controlados randomizados.

Diversos medicamentos frequentemente utilizados na gestação pertenciam à categoria C, uma vez que modelos animais evidenciaram efeitos adversos no feto. No entanto, existem diferenças significativas entre roedores e placenta humana, e, portanto, esses riscos muitas vezes não são aplicáveis aos seres humanos. Muitos desses medicamentos anteriormente classificados na categoria C são, de fato, boas opções para uso na gestação, especialmente quando os riscos da DBAI superam os riscos de utilização da medicação.10,35

Glicocorticoides tópicos

Glicocorticoides tópicos são, frequentemente, tratamentos de primeira linha para DBAI e ainda mostram segurança na gestação, com a vantagem de não compartilhar os mesmos riscos dos esteroides sistêmicos.36

Os escores de Apgar, anormalidades congênitas, incluindo fissuras orofaciais, parto prematuro, tipo de parto e morte fetal não mostraram relação com o uso de glicocorticoides tópicos em qualquer potência. Uma exceção foi a associação dose‐resposta entre glicocorticoides tópicos e crescimento intrauterino restrito (CIUR) e recém‐nascido de baixo peso ao nascer (RNBP), especificamente quando aplicado no terceiro trimestre em doses muito altas.36

Glicocorticoides tópicos são seguros durante a lactação, uma vez que a transmissão para o leite materno é marginal e os glicocorticoides são um elemento natural do leite materno.37 No entanto, glicocorticoides tópicos de alta potência não devem ser aplicados no mamilo antes da amamentação, em função do risco de hipertensão arterial infantil.38

Inibidores tópicos da calcineurina

Relatos de casos e um ensaio clínico duplo‐cego placebo controlado demonstraram a eficácia dos inibidores tópicos da calcineurina no tratamento das DBAI, particularmente se a doença for leve e localizada.39 Esses agentes geralmente são usados para evitar os efeitos colaterais do uso prolongado de esteroides tópicos, especialmente em áreas como face, pescoço, dobras e genitais.10

Os efeitos sobre o feto, que podem ser extrapolados a partir de estudos sobre a administração sistêmica de tacrolimo em pacientes transplantados, incluem parto prematuro e RNBP. Embora não tenham sido realizados estudos formais em gestantes, especialistas recomendam o uso de no máximo 5g/dia, durante 2‐3 semanas, em pequenas áreas.40

Os dados de recomendação de segurança do tacrolimo tópico durante a lactação são limitados; portanto, ele deve ser usado com moderação, evitando‐se aplicação na área do mamilo.41

Glicocorticoides sistêmicos

Os esteroides sistêmicos ainda são considerados uma opção de tratamento importante e segura para as DBAI na gestação. Esteroides não fluorados como prednisona e hidrocortisona costumam ser as formas preferidas, porque a inativação pela 11‐beta‐hidroxiesteroide‐desidrogenase limita a exposição fetal.10 Os riscos no feto são fissuras orofaciais, CIUR, RNBP, ruptura prematura de membranas, atraso do desenvolvimento neuropsicomotor e parto prematuro, e para gestantes, os principais efeitos colaterais incluem pré‐eclâmpsia, eclampsia, hipertensão arterial, diabetes gestacional, osteoporose, má cicatrização de feridas, formação de estrias e infecções puerperais e pós‐operatórias.10,40,41 A dose recomendada não deve exceder 20mg/dia de prednisona, evitando o uso a longo prazo.41 Se forem necessárias doses mais altas, a opção é mudar para um agente poupador de esteroides para o controle da doença.

O aleitamento materno deve ocorrer pelo menos 4 horas após a administração da prednisona, uma vez que sua meia‐vida sérica é de 60 minutos, com níveis no leite materno atingindo o pico após 2 horas de ingestão e diminuindo rapidamente em seguida.10,40

Azatioprina

Azatioprina é um análogo sintético da base purina de uso off label no tratamento das DBAI.10,40,41 Vários estudos clínicos e revisões recomendam a azatioprina como um imunossupressor relativamente seguro para ser usado durante a gestação e lactação.42 A placenta pode limitar a entrada de azatioprina e seu metabólito 6‐mercaptopurina. Linfopenia transitória e imunodeficiência podem ser evitadas se a dose diária não exceder 2mg/kg/dia.43

A European Federation of Crohn's & Ulcerative Colitis Associations classifica a azatioprina como “provavelmente segura” para uso durante a amamentação.42 O aleitamento deve ser feito pelo menos 4 horas após a última dose.44

Micofenolato de mofetila

Micofenolato de Mofetila (MMF) é um excelente agente poupador de esteroides em doenças autoimunes, incluindo DBAI. No entanto, é um componente teratogênico conhecido e não deve ser usado durante a gestação.45 Como o metotrexato, MMF inibe a síntese de DNA e interrompe a divisão celular, causando risco aumentado de aborto. MMF tem sido associado a abortos espontâneos (especialmente no primeiro trimestre), anormalidades de membros e face, defeitos de linha média e outras malformações congênitas.45

Apesar da escassez de dados sobre o uso de MMF durante o aleitamento materno, especialistas atualmente o classificam como contraindicado. O pequeno peso molecular do MMF permite que ele passe em quantidades significativas para o leite materno, o que poderia causar problemas de desenvolvimento e risco de infecção no recém‐nascido.38

Dapsona

A dapsona (diaminodifenilsulfona) é frequentemente usada como terapia adjuvante para DBAI. Relatos de casos mostraram sua segurança na gestação, sem evidência de teratogenicidade, bem como em estudos de gestantes em tratamento de malária, hanseníase ou pneumonia por Pneumocystis jiroveci.41 Dapsona, principalmente acima de 50mg/dia, deve ser evitada em mãe ou feto com deficiência de glicose‐6‐fosfato desidrogenase (G6PD), em função do risco de anemia hemolítica; todos os pacientes devem ser testados antes do seu uso.46

A American Academy of Pediatrics considera a dapsona compatível com o aleitamento materno, uma vez que apenas quantidades pequenas de seus metabólitos são excretadas no leite. A icterícia no bebê deve ser monitorada, se o aleitamento materno ocorrer durante a terapia com dapsona, especialmente em caso de deficiência de G6PD diagnosticada no recém‐nascido.

Doxiciclina

Doxiciclina é um antibiótico com efeitos anti‐inflamatórios e pode ser útil no tratamento das DBAI.47 Doxiciclina há muito tempo tem sido agrupada com outras tetraciclinas e classificadas como não seguras durante a gestação, mas esse agrupamento pode não estar correto, uma vez que a doxiciclina foi desenvolvida após a toxicidade das outras tetraciclinas ter sido bem estabelecida. É provável que a doxiciclina tenha um perfil de segurança diferente das outras tetraciclinas, sem evidências que sustentem uma sobreposição de toxicidades. As tetraciclinas têm um risco aumentado de teratogenicidade, descoloração dentária, interrupção do crescimento ósseo e hepatotoxicidade materna, mas a doxiciclina parece não estar associada a esses riscos. Os dados que diferenciam a doxiciclina das tetraciclinas ainda são limitados e, por isso, os médicos tendem a evitar a doxiciclina quando há opção de outras substâncias com perfil de segurança conhecido.48

O uso de doxiciclina a curto prazo durante a lactação não é contraindicado, mas o fármaco excreta‐se no leite materno e estudos ainda são escassos.35

Rituximabe

Rituximabe (RTX) é um anticorpo monoclonal quimérico anti‐CD20 cujos alvos são as células B, implicadas na patogênese das DBAI. O RTX é bem‐sucedido em propiciar remissão da doença, porém é contraindicado durante a gestação, por atravessar a placenta, esgotar as células B fetais e potencialmente aumentar o risco de infecções materno‐fetais e para o recém‐nascido. A passagem transplacentária do RTX é mínima no primeiro trimestre, moderada no segundo e mais elevada no terceiro. O RTX permanece no soro por três a seis meses e é capaz de atravessar a placenta; por isso, o planejamento da gestação é essencial e as pacientes são aconselhadas a esperar 12 meses após sua última infusão antes de tentar engravidar.10,35 Em relatos de casos de pacientes que acidentalmente receberam RTX durante a gestação não foi observada correlação definitiva com eventos adversos, mas os dados sobre o assunto permanecem escassos.49

O RTX não é recomendado durante a lactação devido à falta de evidências sobre o assunto.50

Considerações finais

A gestação constitui um período em que alterações imunológicas e hormonais intensas ocorrem no organismo materno, a fim de manter o feto halogênico e a estabilidade de seu próprio sistema imunológico. Como a gestação é marcada pela predominância da resposta linfocitária Th2, da mesma forma que as DBAI, seria esperada uma piora dessas dermatoses. No entanto, o que se observou nesta revisão foi o curso variável das DBAI durante a gestação. Com relação aos pênfigos, o PV tende a piorar, enquanto o PF não costuma sofrer alteração. Por outro lado, a DBAL apresenta tendência de melhora. Em razão do pequeno número de casos estudados, torna‐se difícil a análise da evolução da DH e da EBA durante a gestação.

De maneira geral, apesar da raridade, a ocorrência das DBAI durante a gestação é situação especial, considerando‐se as peculiaridades da confirmação diagnóstica por biópsia cutânea e os riscos potenciais de alguns medicamentos para o concepto. Glicocorticoides, azatioprina e dapsona podem ser consideradas opções relativamente seguras durante a gestação e o aleitamento, desde que sua prescrição e acompanhamento sejam feitos rigorosamente sob supervisão médica. Ao contrário, micofenolato de mofetila, doxiciclina e rituximabe, apesar de alternativas eficientes para tratamento das DBAI, têm seu uso contraindicado na gestação pelos riscos potenciais para o concepto. Excluído o penfigoide gestacional, ao conhecimento dos autores, até o momento não há nenhuma revisão semelhante de DBAI na gestação.

Suporte financeiro

FUNADERSP (Fundo de Apoio à Dermatologia do Estado de São Paulo) – projeto 50‐2017.

Contribuição dos autores

Patrícia Penha Silveira Fagundes: Coleta de dados; concepção e desenho do estudo; análise dos dados; redação do artigo; revisão crítica do conteúdo e aprovação da versão final.

Claudia Giuli Santi: Concepção; revisão e aprovação da versão final.

Celina Wakisaka Maruta: Concepção; revisão e aprovação da versão final.

Denise Miyamoto: Concepção; revisão e aprovação da versão final.

Valeria Aoki: Concepção e desenho do estudo; análise dos dados; redação do artigo; revisão crítica do conteúdo e aprovação da versão final.

Conflito de interesses

Nenhum.

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Como citar este artigo: Fagundes PPS, Santi CG, Maruta CW, Miyamoto D, Aoki V. Autoimmune bullous diseases in pregnancy: clinical and epidemiological characteristics and therapeutic approach. An Bras Dermatol. 2021;96:581–90.

Trabalho realizado no Departamento de Dermatologia, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP, Brasil.

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