{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,14]],"date-time":"2025-11-14T17:32:08Z","timestamp":1763141528652,"version":"3.41.2"},"reference-count":27,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T00:00:00Z","timestamp":1611878400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R03AG067064","R01ES031259"],"award-info":[{"award-number":["R03AG067064","R01ES031259"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,1,29]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Zika virus (ZIKV)-associated congenital microcephaly is an important contributor to pediatric death, and more robust pediatric mortality risk metrics are needed to help guide life plans and clinical decision making for these patients. Although common etiologies of pediatric and adult mortality differ, early life health can impact adult outcomes\u2014potentially through DNA methylation. Hence, in this pilot study, we take an early step in identifying pediatric mortality risk metrics by examining associations of ZIKV infection and associated congenital microcephaly with existing adult DNA methylation-based mortality biomarkers: GrimAge and Zhang\u2019s mortality score (ZMS).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Mortality measures were calculated from previously published HumanMethylationEPIC BeadChip data from 44 Brazilian children aged 5\u201340\u2009months (18 with ZIKV-associated microcephaly; 7 normocephalic, exposed to ZIKV in utero; and 19 unexposed controls). We used linear models adjusted for chronological age, sex, methylation batch and white blood cell proportions to evaluate ZIKV and mortality marker relationships.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We observed significant decreases in GrimAge-component plasminogen activator inhibitor-1 [PAI-1; \u03b2\u2009=\u2009\u22122453.06\u2009pg\/ml, 95% confidence interval (CI) \u22123652.96, \u22121253.16, p\u2009=\u20090.0002], and ZMS-site cg14975410 methylation (\u03b2\u2009=\u2009\u22120.06, 95% CI \u22120.09, \u22120.03, p\u2009=\u20090.0003) among children with microcephaly compared to controls. PAI-1 (\u03b2\u2009=\u2009\u22122448.70\u2009pg\/ml, 95% CI \u22124384.45, \u2212512.95, p\u2009=\u20090.01) and cg14975410 (\u03b2\u2009=\u20090.01, 95% CI \u22120.04, 0.06, p\u2009=\u20090.64) results in comparisons of normocephalic, ZIKV-exposed children to controls were not statistically significant.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our results suggest that elements of previously-identified adult epigenetic markers of mortality risk are associated with ZIKV-associated microcephaly, a known contributor to pediatric mortality risk. These findings may provide insights for efforts aimed at developing pediatric mortality markers.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/tropej\/fmab020","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T20:10:31Z","timestamp":1615493431000},"source":"Crossref","is-referenced-by-count":5,"title":["Associations of DNA Methylation Mortality Risk Markers with Congenital Microcephaly from Zika Virus: A Study of Brazilian Children Less than 4 Years of Age"],"prefix":"10.1093","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0356-4867","authenticated-orcid":false,"given":"Jamaji C","family":"Nwanaji-Enwerem","sequence":"first","affiliation":[{"name":"Department of Environmental Health, Harvard T.H. Chan School of Public Health, and MD\/PhD Program, Harvard Medical School, Boston, MA, USA"},{"name":"Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars Van Der","family":"Laan","sequence":"additional","affiliation":[{"name":"Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA Berkeley"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elorm F","family":"Avakame","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children\u2019s National Medical Center, Washington, DC, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristan A","family":"Scott","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Boston Children\u2019s Hospital, Boston, MA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Heather H","family":"Burris","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Children's Hospital of Philadelphia, Philadelphia, PA, USA"},{"name":"Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA"},{"name":"Department of Neonatology, Beth Israel Deaconess Medical Center, Boston, MA, USA"},{"name":"Maternal & Child Health Research Center, Center for Research on Reproduction & Women's Health, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andres","family":"Cardenas","sequence":"additional","affiliation":[{"name":"Division of Environmental Health Sciences, School of Public Health and Center for Computational Biology, University of California, Berkeley, CA, USA 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