{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,11]],"date-time":"2026-06-11T20:54:38Z","timestamp":1781211278951,"version":"3.54.1"},"reference-count":65,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2022,12,13]],"date-time":"2022-12-13T00:00:00Z","timestamp":1670889600000},"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":["Birth Defects Research"],"published-print":{"date-parts":[[2023,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Zika virus (ZIKV) was identified as a teratogen in 2016 when an increase in severe microcephaly and other brain defects was observed in fetuses and newborns following outbreaks in French Polynesia (2013\u20132014) and Brazil (2015\u20132016) and among travelers to other countries experiencing outbreaks. Some have questioned why ZIKV was not recognized as a teratogen before these outbreaks: whether novel genetic changes in ZIKV had increased its teratogenicity or whether its association with birth defects had previously been undetected. Here we examine the evidence for these two possibilities. We describe evidence for specific mutations that arose before the French Polynesia outbreak that might have increased ZIKV teratogenicity. We also present information on children born with findings consistent with congenital Zika syndrome (CZS) as early as 2009 and epidemiological evidence that suggests increases in CZS\u2010type birth defects before 2013. We also explore reasons why a link between ZIKV and birth defects might have been missed, including issues with surveillance of ZIKV infections and of birth defects, challenges to ZIKV diagnostic testing, and the susceptibility of different populations to ZIKV infection at the time of pregnancy. Although it is not possible to prove definitively that ZIKV had teratogenic properties before 2013, several pieces of evidence support the hypothesis that its teratogenicity had been missed in the past. These findings emphasize the need for further investments in global surveillance for emerging infections and for birth defects so that infectious teratogens can be identified more expeditiously in the future.<\/jats:p>","DOI":"10.1002\/bdr2.2134","type":"journal-article","created":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T03:25:08Z","timestamp":1670988308000},"page":"265-274","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Zika virus as a cause of birth defects: Were the teratogenic effects of Zika virus missed for decades?"],"prefix":"10.1002","volume":"115","author":[{"given":"Rachel K.","family":"Gilbert","sequence":"first","affiliation":[{"name":"University of Florida College of Medicine  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyle R.","family":"Petersen","sequence":"additional","affiliation":[{"name":"Division of Vector\u2010Borne Diseases Centers for Disease Control and Prevention  Fort Collins Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret A.","family":"Honein","sequence":"additional","affiliation":[{"name":"Division of Preparedness and Emerging Infections National Center for Emerging and Zoonotic Infectious Diseases, Centers for Disease Control and Prevention  Atlanta Georgia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4224-2692","authenticated-orcid":false,"given":"Cynthia A.","family":"Moore","sequence":"additional","affiliation":[{"name":"National Center on Birth Defects and Developmental Disabilities Centers for Disease Control and Prevention  Atlanta Georgia USA"},{"name":"Goldbelt Professional Services, LLC  Chesapeake Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0574-4928","authenticated-orcid":false,"given":"Sonja A.","family":"Rasmussen","sequence":"additional","affiliation":[{"name":"Departments of Pediatrics and Obstetrics and Gynecology College of Medicine, University of Florida  Gainesville Florida USA"},{"name":"Department of Epidemiology, College of Medicine and College of Public Health and Health Professions University of Florida  Gainesville Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,12,13]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6641a1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12889-015-2223-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21199-z"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(17)31450-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1602412"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2019.01.005"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.20533"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(16)00651-6"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.40378"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ccr3.1810"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.02220-20"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6703a2"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(52)90042-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1898"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1701-2163(16)32740-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMc1609015"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1601824"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0805715"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.4269\/ajtmh.17-0263"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaf5036"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0002636"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdr2.1945"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.2147\/tacg.s8794"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pmed.1002726"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jix396"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe1613368"},{"key":"e_1_2_9_28_1","unstructured":"Instituto Nacional de Estadistica e Informatica (INEI)\u2014Peru: Encuesta Demogr\u00e1fica y de Salud Familiar 2018\u2014Nacional y Regional. 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