{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T00:22:11Z","timestamp":1793838131021,"version":"4.6.1"},"reference-count":33,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T00:00:00Z","timestamp":1680825600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Cnpq","award":["442873\/2019-0"],"award-info":[{"award-number":["442873\/2019-0"]}]},{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["401739\/2015-5"],"award-info":[{"award-number":["401739\/2015-5"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["202912\/Z\/16\/Z"],"award-info":[{"award-number":["202912\/Z\/16\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["213589\/Z\/18\/Z"],"award-info":[{"award-number":["213589\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Congenital syphilis (CS) is a major and avoidable cause of neonatal death worldwide. In this study, we aimed to estimate excess all-cause mortality in children under 5 years with CS compared to those without CS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>In this population-based cohort study, we used linked, routinely collected data from Brazil from January 2011 to December 2017. Cox survival models were adjusted for maternal region of residence, maternal age, education, material status, self-declared race and newborn sex, and year of birth and stratified according to maternal treatment status, non-treponemal titers and presence of signs and symptoms at birth. Over 7 years, a total of 20 057 013 live-born children followed up (through linkage) to 5 years of age, 93 525 were registered with CS, and 2 476 died. The all-cause mortality rate in the CS group was 7\u00b784\/1 000 person-years compared with 2\u00b792\/1 000 person-years in children without CS, crude hazard ratio (HR) = 2\u00b741 (95% CI 2\u00b731 to 2\u00b750). In the fully adjusted model, the highest under-five mortality risk was observed among children with CS from untreated mothers HR = 2\u00b782 (95% CI 2\u00b763 to 3\u00b702), infants with non-treponemal titer higher than 1:64 HR = 8\u00b787 (95% CI 7\u00b770 to 10\u00b722), and children with signs and symptoms at birth HR = 7\u00b710 (95% CI 6\u00b760 to 7\u00b763). Among children registered with CS, CS was recorded as the underlying cause of death in 33% (495\/1 496) of neonatal, 11% (85\/770) of postneonatal, and 2\u00b79% (6\/210) of children 1 year of age. The main limitations of this study were the use of a secondary database without additional clinical information and the potential misclassification of exposure status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study showed an increased mortality risk among children with CS that goes beyond the first year of life. It also reinforces the importance of maternal treatment that infant non-treponemal titers and the presence of signs and symptoms of CS at birth are strongly associated with subsequent mortality.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Trial registration<\/jats:title>\n                    <jats:p>Observational study.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004209","type":"journal-article","created":{"date-parts":[[2023,4,7]],"date-time":"2023-04-07T13:23:12Z","timestamp":1680873792000},"page":"e1004209","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":28,"title":["Mortality in children under 5 years of age with congenital syphilis in Brazil: A nationwide cohort study"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4797-908X","authenticated-orcid":true,"given":"Enny S.","family":"Paixao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00eaa JF","family":"Ferreira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0466-2733","authenticated-orcid":true,"given":"Id\u00e1lia Oliveira","family":"dos Santos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura C.","family":"Rodrigues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosemeire","family":"Fiaccone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonardo","family":"Salvi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3220-6356","authenticated-orcid":true,"given":"Guilherme Lopes","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Guilherme","family":"Santana","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7591-7791","authenticated-orcid":true,"given":"Andrey Moreira","family":"Cardoso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos Ant\u00f4nio de S. S.","family":"Teles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3338-6045","authenticated-orcid":true,"given":"Maria Auxiliadora","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliana","family":"Amaral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Smeeth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio L.","family":"Barreto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Yury","family":"Ichihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,4,7]]},"reference":[{"key":"pmed.1004209.ref001","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1186\/s12884-020-03314-y","article-title":"Maternal syphilis treatment and pregnancy outcomes: a retrospective study in Jiangxi Province, China.","volume":"20","author":"Z Wan","year":"2020","journal-title":"BMC Pregnancy Childbirth"},{"key":"pmed.1004209.ref002","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1097\/OLQ.0000000000001277","article-title":"A Narrative Review of the Epidemiology of Congenital Syphilis in the United States From 1980 to 2019.","volume":"48","author":"C Smullin","year":"2021","journal-title":"Sex Transm Dis."},{"key":"pmed.1004209.ref003","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1093\/pch\/5.8.463","article-title":"Congenital syphilis: A guide to diagnosis and management.","volume":"5","author":"SR Arnold","year":"2000","journal-title":"Paediatr Child Health"},{"key":"pmed.1004209.ref004","volume-title":"With rising trends of syphilis and congenital syphilis in some countries in the Americas","author":"PAHO","year":"2022"},{"key":"pmed.1004209.ref005","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1016\/S2666-5247(22)00041-6","article-title":"Congenital syphilis increases in the USA","volume":"3","author":"R. 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