{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T17:08:35Z","timestamp":1781716115692,"version":"3.54.5"},"reference-count":37,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,5,27]],"date-time":"2020-05-27T00:00:00Z","timestamp":1590537600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>The global epidemic of Zika virus has been a major public health problem affecting pregnant women and their infants. Zika virus causes a viral disease transmitted to humans mainly by the infected Aedes mosquito bite. The infection is not severe in most cases; however, there is evidence that infection during pregnancy may be associated with fetal genetic abnormalities (including microcephaly). In addition to microcephaly and other malformations, some specific lesions in the central nervous system have been reported. The aim of this systematic review was to determine the risk of developing microcephaly in infants whose mothers were infected with Zika virus in pregnancy. Epidemiological studies and case reports were incorporated in our review, finally including 15 articles from an initial pool of 355 related papers. Most studies have linked maternal infection during pregnancy to the development of neonatal microcephaly. The period considered most dangerous is the first trimester and the beginning or the whole of the second trimester. In order to understand the relationship between Zika virus and microcephaly in infants, a cohort study will be able to estimate the time from the onset of Zika infection and the full spectrum of adverse pregnancy outcomes.<\/jats:p>","DOI":"10.3390\/ijerph17113806","type":"journal-article","created":{"date-parts":[[2020,5,28]],"date-time":"2020-05-28T10:02:45Z","timestamp":1590660165000},"page":"3806","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":68,"title":["Zika Virus and the Risk of Developing Microcephaly in Infants: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4494-3089","authenticated-orcid":false,"given":"Evangelia","family":"Antoniou","sequence":"first","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7458-7500","authenticated-orcid":false,"given":"Eirini","family":"Orovou","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-4627","authenticated-orcid":false,"given":"Angeliki","family":"Sarella","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0891-040X","authenticated-orcid":false,"given":"Maria","family":"Iliadou","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaos","family":"Rigas","sequence":"additional","affiliation":[{"name":"Department of Health Management, Greek Open University, 26335 Patra, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ermioni","family":"Palaska","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgios","family":"Iatrakis","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4871-999X","authenticated-orcid":false,"given":"Maria","family":"Dagla","sequence":"additional","affiliation":[{"name":"Department of Midwifery, University of West Attica, 12243 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,5,27]]},"reference":[{"key":"ref_1","unstructured":"Division of Vector-Borne Diseases (DVBD) (2020, March 31). Division of Vector-Borne Diseases. NCEZID. CDC, Available online: https:\/\/www.cdc.gov\/ncezid\/dvbd\/index.html."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"523","DOI":"10.4103\/2249-4863.197256","article-title":"Zika Virus: An Overview","volume":"5","author":"Rawal","year":"2016","journal-title":"J. Fam. Med. Prim. Care"},{"key":"ref_3","unstructured":"(2020, February 13). CDC Press Releases, Available online: https:\/\/www.cdc.gov\/media\/releases\/2016\/p0729-zika-infections-puerto-rico.html."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"116","DOI":"10.3855\/jidc.8217","article-title":"Zika Virus Outbreak in Brazil","volume":"10","author":"Heukelbach","year":"2016","journal-title":"J. Infect. Dev. Ctries."},{"key":"ref_5","unstructured":"CDC (2020, March 31). Facts about Microcephaly. Birth Defects. NCBDDD. CDC, Available online: https:\/\/www.cdc.gov\/ncbddd\/birthdefects\/microcephaly.html."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1001\/jamapediatrics.2016.2974","article-title":"Estimating the Number of Pregnant Women Infected With Zika Virus and Expected Infants With Microcephaly Following the Zika Virus Outbreak in Puerto Rico, 2016","volume":"170","author":"Ellington","year":"2016","journal-title":"JAMA Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"26","DOI":"10.5858\/arpa.2016-0382-RA","article-title":"Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know","volume":"141","author":"Alvarado","year":"2017","journal-title":"Arch. Pathol. Lab. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1126\/science.aaf6116","article-title":"Zika Virus Impairs Growth in Human Neurospheres and Brain Organoids","volume":"352","author":"Garcez","year":"2016","journal-title":"Science"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1016\/j.stem.2016.02.016","article-title":"Zika Virus Infects Human Cortical Neural Progenitors and Attenuates Their Growth","volume":"18","author":"Tang","year":"2016","journal-title":"Cell Stem Cell"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e1914061","DOI":"10.1001\/jamanetworkopen.2019.14061","article-title":"Cognitive Development of Infants Exposed to the Zika Virus in Puerto Rico","volume":"2","author":"Valdes","year":"2019","journal-title":"JAMA Netw. Open"},{"key":"ref_11","unstructured":"(2020, February 14). Phylogeny of Zika Virus in Western Hemisphere, Available online: https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4861537\/."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Agumadu, V.C., and Ramphul, K. (2018). Zika Virus: A Review of Literature. Cureus, 10.","DOI":"10.7759\/cureus.3025"},{"key":"ref_13","unstructured":"Birth Defects (2020, February 14). Zika Virus. CDC, Available online: https:\/\/www.cdc.gov\/zika\/healtheffects\/birth_defects.html."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1056\/NEJMra1602113","article-title":"Zika Virus","volume":"374","author":"Petersen","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_15","unstructured":"CDC (2020, February 13). Zika Outcomes Investigation (ZODIAC). CDC, Available online: https:\/\/www.cdc.gov\/pregnancy\/zika\/research\/zodiac.html."},{"key":"ref_16","unstructured":"(2020, February 05). Zika Virus, Available online: https:\/\/www.cdc.gov\/zika\/fs-posters\/index.html."},{"key":"ref_17","unstructured":"(2020, May 07). Zika Virus Outbreak and the Risk to Europe. Available online: http:\/\/www.euro.who.int\/en\/health-topics\/health-emergencies\/zika-virus\/zika-virus-outbreak-and-the-risk-to-europe2."},{"key":"ref_18","unstructured":"(2020, February 13). Communicable Disease Threats Report, 27 October\u20132 November 2019, Week 44. Available online: https:\/\/www.ecdc.europa.eu\/en\/publications-data\/communicable-disease-threats-report-27-october-2-november-2019-week-44."},{"key":"ref_19","unstructured":"Wilkinson, R., and Weltgesundheitsorganisation (2003). The Solid Facts: Social Determinants of Health, WHO Regional Office for Europe. [2nd ed.]."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1356","DOI":"10.1016\/S1473-3099(16)30318-8","article-title":"Association between Zika Virus Infection and Microcephaly in Brazil, January to May, 2016: Preliminary Report of a Case-Control Study","volume":"16","author":"Rodrigues","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.tmaid.2016.09.006","article-title":"Trends of the Microcephaly and Zika Virus Outbreak in Brazil, January-July 2016","volume":"14","author":"Robaina","year":"2016","journal-title":"Travel Med. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1002\/uog.15831","article-title":"Zika Virus Intrauterine Infection Causes Fetal Brain Abnormality and Microcephaly: Tip of the Iceberg?","volume":"47","author":"Melo","year":"2016","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"717","DOI":"10.1002\/uog.17303","article-title":"Progressive Lesions of Central Nervous System in Microcephalic Fetuses with Suspected Congenital Zika Virus Syndrome","volume":"50","author":"Sarno","year":"2017","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1016\/S0140-6736(16)30902-3","article-title":"Congenital Zika Virus Syndrome in Brazil: A Case Series of the First 1501 Livebirths with Complete Investigation","volume":"388","author":"Oliveira","year":"2016","journal-title":"Lancet Lond. Engl."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1056\/NEJMoa1601824","article-title":"Zika Virus Infection with Prolonged Maternal Viremia and Fetal Brain Abnormalities","volume":"374","author":"Driggers","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sarno, M., Sacramento, G.A., Khouri, R., do Ros\u00e1rio, M.S., Costa, F., Archanjo, G., Santos, L.A., Nery, N., Vasilakis, N., and Ko, A.I. (2016). Zika Virus Infection and Stillbirths: A Case of HydropsFetalis, Hydranencephaly and Fetal Demise. PLoSNegl. Trop. Dis., 10.","DOI":"10.1371\/journal.pntd.0004517"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"159","DOI":"10.15585\/mmwr.mm6506e1","article-title":"Notes from the Field: Evidence of Zika Virus Infection in Brain and Placental Tissues from Two Congenitally Infected Newborns and Two Fetal Losses-Brazil, 2015","volume":"65","author":"Martines","year":"2016","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_28","unstructured":"Pacheco, O., Beltr\u00e1n, M., Nelson, C.A., Valencia, D., Tolosa, N., Farr, S.L., Padilla, A.V., Tong, V.T., Cuevas, E.L., and Espinosa-Bode, A. (2016). Zika Virus Disease in Colombia\u2014Preliminary Report. N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1016\/S1473-3099(16)00095-5","article-title":"Detection and Sequencing of Zika Virus from Amniotic Fluid of Fetuses with Microcephaly in Brazil: A Case Study","volume":"16","author":"Calvet","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1001\/jamaneurol.2016.3720","article-title":"Congenital Zika Virus Infection: Beyond Neonatal Microcephaly","volume":"73","author":"Melo","year":"2016","journal-title":"JAMA Neurol."},{"key":"ref_31","first-page":"858","article-title":"Vital Signs: Zika-Associated Birth Defects and Neurodevelopmental Abnormalities Possibly Associated with Congenital Zika Virus Infection\u2014U.S. Territories and Freely Associated States, 2018","volume":"67","author":"Rice","year":"2018","journal-title":"Morb. Mortal. Wkly. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"985","DOI":"10.1056\/NEJMoa1709481","article-title":"Pregnancy Outcomes after ZIKV Infection in French Territories in the Americas","volume":"378","author":"Hoen","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.cell.2016.05.008","article-title":"Zika Virus Infection during Pregnancy in Mice Causes Placental Damage and Fetal Demise","volume":"165","author":"Miner","year":"2016","journal-title":"Cell"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1145","DOI":"10.1523\/JNEUROSCI.1376-19.2019","article-title":"Zika Virus Infection in the Developing Mouse Produces Dramatically Different Neuropathology Dependent on Viral Strain","volume":"40","author":"Noguchi","year":"2020","journal-title":"J. Neurosci."},{"key":"ref_35","unstructured":"(2020, May 08). Zika Virus\u2014Prevention and Transmission, Available online: https:\/\/www.cdc.gov\/zika\/prevention\/index.html."},{"key":"ref_36","unstructured":"(2020, March 24). Top 10 Facts on Zika Virus. Available online: https:\/\/www.medindia.net\/health_statistics\/health_facts\/top10-facts-on-zika-virus.htm."},{"key":"ref_37","unstructured":"WHO (2020, March 24). World Health Organization. Available online: http:\/\/www.who.int\/emergencies\/diseases\/zika\/en\/."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/11\/3806\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T09:33:03Z","timestamp":1760175183000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/17\/11\/3806"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,5,27]]},"references-count":37,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,6]]}},"alternative-id":["ijerph17113806"],"URL":"https:\/\/doi.org\/10.3390\/ijerph17113806","relation":{},"ISSN":["1660-4601"],"issn-type":[{"value":"1660-4601","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,5,27]]}}}