{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T22:50:21Z","timestamp":1785797421165,"version":"3.56.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T00:00:00Z","timestamp":1526342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Reviews in Medical Virology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>Much progress with respect to congenital Zika virus (ZIKV) pathogenesis has been achieved after the 2015 outbreak in Brazil. It is now accepted that ZIKV is vertically transmitted, infects cells of the developing central nervous system and the placenta, yet it is unclear to what extent placental affection contributes to the development of congenital ZIKV. The association between fulminant villitis and severe fetal involvement emerges as a possibility. ZIKV is unique among the Flaviviruses in its ability to be sexually transmitted, possibly responsible for its teratogenicity. Furthermore, there is controversy over the participation of antibody dependent enhancement (ADE) in patients with non\u2010neutralizing anti\u2010Flavivirus antibodies, a phenomenon previously recognized in serious DENV infections. Our aim was to analyze information regarding the contribution of the placental barrier as an actual player in neonatal ZIKV. Therefore, we underwent a systematic review with keywords \u201cZika virus\u201d and \u201cZIKV\u201d. Articles were screened for relevance concerning the topics of microcephaly, transplacental transmission, sexual transmission, and ADE. We identified variables that affect the severity of congenital Zika syndrome: age of gestation at maternal infection, the extent of placental disruption (villitis), sexual transmission, initial viral replication at the uterine wall, anti\u2010DENV antibodies, and the possibility of antibody\u2010mediated transcytosis of ZIKV through the placenta. These questions may not seem relevant when Zika becomes endemic, and we are no longer witness to the extreme clinical sequelae seen when the virus moves through an immunologically na\u00efve population; however, characterizing the pathogenesis of congenital Zika syndrome will continue to further our understanding.<\/jats:p>","DOI":"10.1002\/rmv.1985","type":"journal-article","created":{"date-parts":[[2018,5,15]],"date-time":"2018-05-15T08:05:45Z","timestamp":1526371545000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Congenital Zika syndrome: Pitfalls in the placental barrier"],"prefix":"10.1002","volume":"28","author":[{"given":"Nia","family":"Robinson","sequence":"first","affiliation":[{"name":"International Program of Medicine Universidad Autonoma de Guadalajara  Zapopan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evangelina E.","family":"Mayorquin Galvan","sequence":"additional","affiliation":[{"name":"Immunology Research Laboratory, International Program of Medicine Universidad Aut\u00f3noma de Guadalajara  Zapopan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isidro G.","family":"Zavala Trujillo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Division Hospital Dr. Angel Lea\u00f1o, Universidad Autonoma de Guadalajara  Zapopan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6508-9657","authenticated-orcid":false,"given":"Maria G.","family":"Zavala\u2010Cerna","sequence":"additional","affiliation":[{"name":"Immunology Research Laboratory, International Program of Medicine Universidad Aut\u00f3noma de Guadalajara  Zapopan Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,5,15]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4"},{"issue":"2","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"223","DOI":"10.4049\/jimmunol.69.2.223","article-title":"Neutralizing antibodies against certain recently isolated viruses in the sera of human beings residing in East Africa","volume":"69","author":"Smithburn KC","year":"1952","journal-title":"J Immunol"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805715"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.2471\/BLT.16.171082"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1590\/0074-02760150192"},{"key":"e_1_2_11_7_1","unstructured":"Pan American Health Organization.Epidemiological alert: increase of microcephaly in the northeast of Brazil.2015 November 17."},{"key":"e_1_2_11_8_1","unstructured":"Brazilian Ministry of Health.Ministry of Health investigates 3 852 suspected cases of microcephaly in the country.2016 February 2;http:\/\/portalsaude.saude.gov.br\/index.php\/cidadao\/principal\/agencia\u2010saude\/22145\u2010ministerio\u2010da\u2010saude\u2010investiga\u20103\u2010852\u2010casossuspeitos\u2010de\u2010microcefalia\u2010no\u2010pais. Accessed July 5 2017."},{"key":"e_1_2_11_9_1","unstructured":"World Health Organization.WHO statement on the first meeting of the International Health Regulations (2005) (IHR 2005) Emergency Committee on Zika virus and observed increase in neurological disorders and neonatal malformations.2016 February 1;http:\/\/www.who.int\/mediacentre\/news\/statements\/2016\/1st\u2010emergency\u2010committee\u2010zika\/en\/. Accessed July 5 2017."},{"key":"e_1_2_11_10_1","unstructured":"World Health Organization.Screening assessment and management of neonates and infants with complications associated with Zika virus exposure in utero.2016 August 30."},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0004877"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6506e1"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2016.02.016"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature18296"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002203"},{"key":"e_1_2_11_16_1","article-title":"Ocular findings in infants with microcephaly associated with presumed Zika virus congenital infection in Salvador, Brazil","author":"Paula Freitas B","year":"2016","journal-title":"JAMA 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