{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T15:54:17Z","timestamp":1783698857149,"version":"3.55.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T00:00:00Z","timestamp":1697155200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003243","name":"Ministerstvo Zdravotnictv\u00ed Cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["Conceptual Development of Research Organization (FNBr 65269705)"],"award-info":[{"award-number":["Conceptual Development of Research Organization (FNBr 65269705)"]}],"id":[{"id":"10.13039\/501100003243","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009553","name":"Agentura Pro Zdravotnick\u00fd V\u00fdzkum \u010cesk\u00e9 Republiky","doi-asserted-by":"publisher","award":["NU21-04-00305"],"award-info":[{"award-number":["NU21-04-00305"]}],"id":[{"id":"10.13039\/501100009553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Our goal was to identify highly accurate empirical models for the prediction of the risk of febrile seizure (FS) and FS recurrence. In a prospective, three-arm, case\u2013control study, we enrolled 162 children (age 25.8\u2009\u00b1\u200917.1\u00a0months old, 71 females). Participants formed one case group (patients with FS) and two control groups (febrile patients without seizures and healthy controls). The impact of blood iron status, peak body temperature, and participants\u2019 demographics on FS risk and recurrence was investigated with univariate and multivariate statistics. Serum iron concentration, iron saturation, and unsaturated iron-binding capacity differed between the three investigated groups (p\n                    <jats:sub>FWE<\/jats:sub>\n                    \u2009&lt;\u20090.05). These serum analytes were key variables in the design of novel multivariate linear mixture models. The models classified FS risk with higher accuracy than univariate approaches. The designed bi-linear classifier achieved a sensitivity\/specificity of 82%\/89% and was closest to the gold-standard classifier. A multivariate model assessing FS recurrence provided a difference (p\n                    <jats:sub>FWE<\/jats:sub>\n                    \u2009&lt;\u20090.05) with a separating sensitivity\/specificity of 72%\/69%. Iron deficiency, height percentile, and age were significant FS risk factors. In addition, height percentile and hemoglobin concentration were linked to FS recurrence. Novel multivariate models utilizing blood iron status and demographic variables predicted FS risk and recurrence among infants and young children with fever.\n                  <\/jats:p>","DOI":"10.1038\/s41598-023-43599-5","type":"journal-article","created":{"date-parts":[[2023,10,13]],"date-time":"2023-10-13T05:01:35Z","timestamp":1697173295000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Multivariate linear mixture models for the prediction of febrile seizure risk and recurrence: a prospective case\u2013control study"],"prefix":"10.1038","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6677-5480","authenticated-orcid":false,"given":"Jan","family":"Pape\u017e","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-1304","authenticated-orcid":false,"given":"Ren\u00e9","family":"Labounek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petr","family":"Jaband\u017eiev","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katar\u00edna","family":"\u010cesk\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate\u0159ina","family":"Slab\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hana","family":"O\u0161lej\u0161kov\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6421-046X","authenticated-orcid":false,"given":"\u0160tefania","family":"Aulick\u00e1","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3833-1484","authenticated-orcid":false,"given":"Igor","family":"Nestra\u0161il","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,10,13]]},"reference":[{"key":"43599_CR1","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1186\/s12887-019-1675-4","volume":"19","author":"HN Jang","year":"2019","unstructured":"Jang, H. N., Yoon, H. S. & Lee, E. H. Prospective case control study of iron deficiency and the risk of febrile seizures in children in South Korea. BMC Pediatr. 19, 309. https:\/\/doi.org\/10.1186\/s12887-019-1675-4 (2019).","journal-title":"BMC Pediatr."},{"key":"43599_CR2","doi-asserted-by":"publisher","first-page":"116682","DOI":"10.1016\/j.jns.2020.116682","volume":"411","author":"J Kubota","year":"2020","unstructured":"Kubota, J. et al. Predictors of recurrent febrile seizures during the same febrile illness in children with febrile seizures. J. Neurol. Sci. 411, 116682. https:\/\/doi.org\/10.1016\/j.jns.2020.116682 (2020).","journal-title":"J. Neurol. Sci."},{"key":"43599_CR3","doi-asserted-by":"publisher","unstructured":"Subcommittee on Febrile Seizures & American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics 127, 389\u2013394 (2011). https:\/\/doi.org\/10.1542\/peds.2010-3318","DOI":"10.1542\/peds.2010-3318"},{"key":"43599_CR4","doi-asserted-by":"publisher","unstructured":"Steering Committee on Quality, Improvement Management, Subcommittee on Febrile Seizures. Febrile seizures: Clinical practice guideline for the long-term management of the child with simple febrile seizures. Pediatrics 121, 1281\u20131286 (2008). https:\/\/doi.org\/10.1542\/peds.2008-0939","DOI":"10.1542\/peds.2008-0939"},{"key":"43599_CR5","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.pediatrneurol.2015.10.008","volume":"55","author":"SA Seinfeld","year":"2016","unstructured":"Seinfeld, S. A., Pellock, J. M., Kjeldsen, M. J., Nakken, K. O. & Corey, L. A. Epilepsy after febrile seizures: Twins suggest genetic influence. Pediatr. Neurol. 55, 14\u201316. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2015.10.008 (2016).","journal-title":"Pediatr. Neurol."},{"key":"43599_CR6","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/S2352-4642(18)30351-1","volume":"3","author":"JW Dreier","year":"2019","unstructured":"Dreier, J. W., Pedersen, C. B., Cotsapas, C. & Christensen, J. Childhood seizures and risk of psychiatric disorders in adolescence and early adulthood: A Danish nationwide cohort study. Lancet Child Adolesc. Health 3, 99\u2013108. https:\/\/doi.org\/10.1016\/S2352-4642(18)30351-1 (2019).","journal-title":"Lancet Child Adolesc. Health"},{"key":"43599_CR7","doi-asserted-by":"publisher","first-page":"292","DOI":"10.1097\/MOP.0000000000000220","volume":"27","author":"AA Kimia","year":"2015","unstructured":"Kimia, A. A., Bachur, R. G., Torres, A. & Harper, M. B. Febrile seizures: Emergency medicine perspective. Curr. Opin. Pediatr. 27, 292\u2013297. https:\/\/doi.org\/10.1097\/MOP.0000000000000220 (2015).","journal-title":"Curr. Opin. Pediatr."},{"key":"43599_CR8","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.seizure.2017.09.009","volume":"52","author":"BO Kwak","year":"2017","unstructured":"Kwak, B. O., Kim, K., Kim, S. N. & Lee, R. Relationship between iron deficiency anemia and febrile seizures in children: A systematic review and meta-analysis. Seizure 52, 27\u201334. https:\/\/doi.org\/10.1016\/j.seizure.2017.09.009 (2017).","journal-title":"Seizure"},{"key":"43599_CR9","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.seizure.2009.01.008","volume":"18","author":"E Bidabadi","year":"2009","unstructured":"Bidabadi, E. & Mashouf, M. Association between iron deficiency anemia and first febrile convulsion: A case-control study. Seizure 18, 347\u2013351. https:\/\/doi.org\/10.1016\/j.seizure.2009.01.008 (2009).","journal-title":"Seizure"},{"key":"43599_CR10","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1177\/088307389501000207","volume":"10","author":"NL Kobrinsky","year":"1995","unstructured":"Kobrinsky, N. L., Yager, J. Y., Cheang, M. S., Yatscoff, R. W. & Tenenbein, M. Does iron deficiency raise the seizure threshold?. J. Child Neurol. 10, 105\u2013109. https:\/\/doi.org\/10.1177\/088307389501000207 (1995).","journal-title":"J. Child Neurol."},{"key":"43599_CR11","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1016\/j.seizure.2012.06.010","volume":"21","author":"S Zareifar","year":"2012","unstructured":"Zareifar, S., Hosseinzadeh, H. R. & Cohan, N. Association between iron status and febrile seizures in children. Seizure 21, 603\u2013605. https:\/\/doi.org\/10.1016\/j.seizure.2012.06.010 (2012).","journal-title":"Seizure"},{"key":"43599_CR12","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1136\/bmj.308.6943.1552","volume":"308","author":"DG Altman","year":"1994","unstructured":"Altman, D. G. & Bland, J. M. Diagnostic tests. 1: Sensitivity and specificity. BMJ 308, 1552. https:\/\/doi.org\/10.1136\/bmj.308.6943.1552 (1994).","journal-title":"BMJ"},{"key":"43599_CR13","doi-asserted-by":"crossref","unstructured":"Haibo, H., Yang, B., Garcia, E. A. & Shutao, L. in 2008 IEEE International Joint Conference on Neural Networks (IEEE World Congress on Computational Intelligence). 1322\u20131328.","DOI":"10.1109\/IJCNN.2008.4633969"},{"key":"43599_CR14","doi-asserted-by":"publisher","first-page":"1263","DOI":"10.1109\/TKDE.2008.239","volume":"21","author":"H He","year":"2009","unstructured":"He, H. & Garcia, E. A. Learning from imbalanced data. IEEE Trans. Knowl. Data Eng. 21, 1263\u20131284. https:\/\/doi.org\/10.1109\/TKDE.2008.239 (2009).","journal-title":"IEEE Trans. Knowl. Data Eng."},{"key":"43599_CR15","doi-asserted-by":"publisher","first-page":"1588S","DOI":"10.3945\/ajcn.117.155846","volume":"106","author":"MK Georgieff","year":"2017","unstructured":"Georgieff, M. K. Iron assessment to protect the developing brain. Am. J. Clin. Nutr. 106, 1588S-1593S. https:\/\/doi.org\/10.3945\/ajcn.117.155846 (2017).","journal-title":"Am. J. Clin. Nutr."},{"key":"43599_CR16","doi-asserted-by":"publisher","first-page":"34","DOI":"10.1301\/nr.2006.may.s34-s43","volume":"64","author":"B Lozoff","year":"2006","unstructured":"Lozoff, B. et al. Long-lasting neural and behavioral effects of iron deficiency in infancy. Nutr. Rev. 64, 34\u201343. https:\/\/doi.org\/10.1301\/nr.2006.may.s34-s43 (2006).","journal-title":"Nutr. Rev."},{"key":"43599_CR17","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/j.spen.2006.08.004","volume":"13","author":"B Lozoff","year":"2006","unstructured":"Lozoff, B. & Georgieff, M. K. Iron deficiency and brain development. Semin. Pediatr. Neurol. 13, 158\u2013165. https:\/\/doi.org\/10.1016\/j.spen.2006.08.004 (2006).","journal-title":"Semin. Pediatr. Neurol."},{"key":"43599_CR18","doi-asserted-by":"publisher","first-page":"493","DOI":"10.1056\/NEJM198702263160901","volume":"316","author":"JF Annegers","year":"1987","unstructured":"Annegers, J. F., Hauser, W. A., Shirts, S. B. & Kurland, L. T. Factors prognostic of unprovoked seizures after febrile convulsions. N. Engl. J. Med. 316, 493\u2013498. https:\/\/doi.org\/10.1056\/NEJM198702263160901 (1987).","journal-title":"N. Engl. J. Med."},{"key":"43599_CR19","doi-asserted-by":"publisher","first-page":"106858","DOI":"10.1016\/j.eplepsyres.2022.106858","volume":"180","author":"S Aulicka","year":"2022","unstructured":"Aulicka, S. et al. Cytokine-chemokine profiles in the hippocampus of patients with mesial temporal lobe epilepsy and hippocampal sclerosis. Epilepsy Res. 180, 106858. https:\/\/doi.org\/10.1016\/j.eplepsyres.2022.106858 (2022).","journal-title":"Epilepsy Res."},{"key":"43599_CR20","doi-asserted-by":"publisher","DOI":"10.1111\/apa.16171","author":"G Nilsson","year":"2021","unstructured":"Nilsson, G., Lundstrom, S., Fernell, E. & Gillberg, C. Neurodevelopmental problems in children with febrile seizures followed to young school age: A prospective longitudinal community-based study in Sweden. Acta Paediatr. https:\/\/doi.org\/10.1111\/apa.16171 (2021).","journal-title":"Acta Paediatr."},{"key":"43599_CR21","doi-asserted-by":"publisher","first-page":"175909141774652","DOI":"10.1177\/1759091417746521","volume":"9","author":"M Rudy","year":"2017","unstructured":"Rudy, M. & Mayer-Proschel, M. Iron deficiency affects seizure susceptibility in a time- and sex-specific manner. ASN Neuro 9, 175909141774652. https:\/\/doi.org\/10.1177\/1759091417746521 (2017).","journal-title":"ASN Neuro"},{"key":"43599_CR22","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1046\/j.1528-1157.2002.32501.x","volume":"43","author":"AS Daoud","year":"2002","unstructured":"Daoud, A. S. et al. Iron status: A possible risk factor for the first febrile seizure. Epilepsia 43, 740\u2013743. https:\/\/doi.org\/10.1046\/j.1528-1157.2002.32501.x (2002).","journal-title":"Epilepsia"},{"key":"43599_CR23","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1097\/MPG.0000000000000206","volume":"58","author":"M Domellof","year":"2014","unstructured":"Domellof, M. et al. Iron requirements of infants and toddlers. J. Pediatr. Gastroenterol. Nutr. 58, 119\u2013129. https:\/\/doi.org\/10.1097\/MPG.0000000000000206 (2014).","journal-title":"J. Pediatr. Gastroenterol. Nutr."},{"key":"43599_CR24","doi-asserted-by":"publisher","first-page":"761","DOI":"10.1038\/sj.ejcn.1602137","volume":"59","author":"BS Gunnarsson","year":"2005","unstructured":"Gunnarsson, B. S., Thorsdottir, I. & Palsson, G. Iron status in 6-y-old children: Associations with growth and earlier iron status. Eur. J. Clin. Nutr. 59, 761\u2013767. https:\/\/doi.org\/10.1038\/sj.ejcn.1602137 (2005).","journal-title":"Eur. J. Clin. Nutr."},{"key":"43599_CR25","doi-asserted-by":"publisher","first-page":"e12458","DOI":"10.1111\/mcn.12458","volume":"14","author":"EK McCarthy","year":"2018","unstructured":"McCarthy, E. K. et al. Iron status, body size, and growth in the first 2 years of life. Matern. Child Nutr. 14, e12458. https:\/\/doi.org\/10.1111\/mcn.12458 (2018).","journal-title":"Matern. Child Nutr."},{"key":"43599_CR26","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/sj.ejcn.1601594","volume":"57","author":"I Thorsdottir","year":"2003","unstructured":"Thorsdottir, I., Gunnarsson, B. S., Atladottir, H., Michaelsen, K. F. & Palsson, G. Iron status at 12 months of age\u2014Effects of body size, growth and diet in a population with high birth weight. Eur. J. Clin. Nutr. 57, 505\u2013513. https:\/\/doi.org\/10.1038\/sj.ejcn.1601594 (2003).","journal-title":"Eur. J. Clin. Nutr."},{"key":"43599_CR27","doi-asserted-by":"publisher","first-page":"760","DOI":"10.1016\/j.bbagen.2010.03.011","volume":"1800","author":"W Wang","year":"2010","unstructured":"Wang, W., Knovich, M. A., Coffman, L. G., Torti, F. M. & Torti, S. V. Serum ferritin: Past, present and future. Biochim. Biophys. Acta 1800, 760\u2013769. https:\/\/doi.org\/10.1016\/j.bbagen.2010.03.011 (2010).","journal-title":"Biochim. Biophys. Acta"},{"key":"43599_CR28","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1542\/peds.110.3.545","volume":"110","author":"M Domellof","year":"2002","unstructured":"Domellof, M. et al. Sex differences in iron status during infancy. Pediatrics 110, 545\u2013552. https:\/\/doi.org\/10.1542\/peds.110.3.545 (2002).","journal-title":"Pediatrics"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-43599-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-43599-5","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-43599-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T15:50:15Z","timestamp":1730303415000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-023-43599-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,10,13]]},"references-count":28,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["43599"],"URL":"https:\/\/doi.org\/10.1038\/s41598-023-43599-5","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-2606721\/v1","asserted-by":"object"}]},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,10,13]]},"assertion":[{"value":"20 February 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2023","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"13 October 2023","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"17372"}}