{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T17:09:54Z","timestamp":1785431394784,"version":"3.56.0"},"reference-count":38,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T00:00:00Z","timestamp":1784073600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill & Melinda Gates Foundation","doi-asserted-by":"crossref","award":["OPP1018614"],"award-info":[{"award-number":["OPP1018614"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"crossref"}]},{"award":["OPP1018614"],"award-info":[{"award-number":["OPP1018614"]}],"id":[{"id":"https:\/\/ror.org\/0456r8d26","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Apnea is a potentially life-threatening complication of severe acute respiratory infection (SARI) in early infancy; however, its determinants remain incompletely understood. Between 2011 and 2013, we conducted a population-based, cross-sectional, multicenter study in Buenos Aires, Argentina. We examined epidemiological, clinical, virological, and immunological factors associated with apnea in a population-based cohort of 2376 infants younger than five months hospitalized due to SARI. Using hierarchical multivariable logistic regression, we identified preterm birth, cesarean section, previous NICU admission, age under two months, and severe household crowding as independent predictors of apnea. RSV infection was inversely associated with apnea, and IL-5 levels in respiratory secretions were significantly lower among infants with apnea, suggesting a qualitatively different immune response in this group. Taken together, these findings indicate that apnea during SARI in early infancy is primarily driven by biological immaturity and adverse environmental conditions.<\/jats:p>","DOI":"10.3390\/v18070778","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T08:08:34Z","timestamp":1784189314000},"page":"778","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biomarkers and Risk Factors Associated with Apnea in Hospitalized Infants with Acute Respiratory Infection"],"prefix":"10.3390","volume":"18","author":[{"given":"Julia","family":"Dvorkin","sequence":"first","affiliation":[{"name":"Centro Infant de Medicina Traslacional (CIMeT), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn (UNSAM), General San Mart\u00edn 1650, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Ciudad Aut\u00f3noma de Buenos Aires 1425, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Pico","sequence":"additional","affiliation":[{"name":"Centro Infant de Medicina Traslacional (CIMeT), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn (UNSAM), General San Mart\u00edn 1650, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3732-674X","authenticated-orcid":false,"given":"Josefina L.","family":"Razzini","sequence":"additional","affiliation":[{"name":"Genetics, Vaccines and Pediatric Infectious Diseases Research Group (GENVIP), Instituto de Investigaci\u00f3n Sanitaria de Santiago de Compostela (IDIS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Galicia, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Libster","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n INFANT, Ciudad Aut\u00f3noma de Buenos Aires 1406, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fernando P.","family":"Polack","sequence":"additional","affiliation":[{"name":"Fundaci\u00f3n INFANT, Ciudad Aut\u00f3noma de Buenos Aires 1406, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4218-5942","authenticated-orcid":false,"given":"Mauricio T.","family":"Caballero","sequence":"additional","affiliation":[{"name":"Centro Infant de Medicina Traslacional (CIMeT), Escuela de Bio y Nanotecnolog\u00edas (EByN), Universidad Nacional de San Mart\u00edn (UNSAM), General San Mart\u00edn 1650, Argentina"},{"name":"Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Ciudad Aut\u00f3noma de Buenos Aires 1425, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of The INFANT Respiratory Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1191","DOI":"10.1016\/S1473-3099(18)30310-4","article-title":"Estimates of the Global, Regional, and National Morbidity, Mortality, and Aetiologies of Lower Respiratory Infections in 195 Countries, 1990\u20132016: A Systematic Analysis for the Global Burden of Disease Study 2016","volume":"18","author":"Troeger","year":"2018","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","article-title":"Global Burden of 369 Diseases and Injuries in 204 Countries and Territories, 1990\u20132019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"396","author":"Vos","year":"2020","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e1194","DOI":"10.1542\/peds.2013-1501","article-title":"Apnea in Children Hospitalized with Bronchiolitis","volume":"132","author":"Schroeder","year":"2013","journal-title":"Pediatrics"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e20153757","DOI":"10.1542\/peds.2015-3757","article-title":"Committee on Fetus and Newborn, American Academy of Pediatrics, Apnea of Prematurity","volume":"137","author":"Eichenwald","year":"2016","journal-title":"Pediatrics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"597","DOI":"10.5664\/jcsm.2172","article-title":"Rules for Scoring Respiratory Events in Sleep: Update of the 2007 AASM Manual for the Scoring of Sleep and Associated Events","volume":"8","author":"Berry","year":"2012","journal-title":"J. Clin. Sleep Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1016\/j.jpeds.2009.04.063","article-title":"Incidence of Apnea in Infants Hospitalized with Respiratory Syncytial Virus Bronchiolitis: A Systematic Review","volume":"155","author":"Ralston","year":"2009","journal-title":"J. Pediatr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1001\/archpedi.1984.02140410027010","article-title":"Respiratory Syncytial Virus\u2014Related Apnea in Infants: Demographics and Outcome","volume":"138","author":"Church","year":"1984","journal-title":"Am. J. Dis. Child."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e20160590","DOI":"10.1542\/peds.2016-0590","article-title":"Brief Resolved Unexplained Events (Formerly Apparent Life-Threatening Events) and Evaluation of Lower-Risk Infants","volume":"137","author":"Tieder","year":"2016","journal-title":"Pediatrics"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1542\/peds.2004-0847","article-title":"Yield of Diagnostic Testing in Infants Who Have Had an Apparent Life-Threatening Event","volume":"115","author":"Brand","year":"2005","journal-title":"Pediatrics"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1007\/s004310050822","article-title":"Risk Factors for Respiratory Syncytial Virus Associated Apnoea","volume":"157","author":"Kneyber","year":"1998","journal-title":"Eur. J. Pediatr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e1474","DOI":"10.1542\/peds.2014-2742","article-title":"Clinical Practice Guideline: The Diagnosis, Management, and Prevention of Bronchiolitis","volume":"134","author":"Ralston","year":"2014","journal-title":"Pediatrics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"351","DOI":"10.1096\/fasebj.10.2.8641570","article-title":"Interleukin-1 Receptors on Rat Brain Endothelial Cells: A Role in Neuroimmune Interaction?","volume":"10","author":"Kuiper","year":"1996","journal-title":"FASEB J."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/j.jpeds.2015.08.053","article-title":"Prostaglandin E2 Mediates Cardiorespiratory Disturbances during Infection in Neonates","volume":"167","author":"Siljehav","year":"2015","journal-title":"J. Pediatr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1164\/rccm.201603-0658OC","article-title":"Mortality Due to Respiratory Syncytial Virus. Burden and Risk Factors","volume":"195","author":"Geoghegan","year":"2017","journal-title":"Am. J. Respir. Crit. Care Med."},{"key":"ref_15","unstructured":"(2026, May 22). Surveillance Case Definitions for ILI and SARI. Available online: https:\/\/www.who.int\/teams\/global-influenza-programme\/surveillance-and-monitoring\/case-definitions-for-ili-and-sari."},{"key":"ref_16","unstructured":"Villatoro, P. (2017). Indicadores no Monetarios de Carencias en las Encuestas de los Pa\u00edses de Am\u00e9rica Latina: Disponibilidad, Comparabilidad y Pertinencia, CEPAL."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1129","DOI":"10.1093\/infdis\/jiaa046","article-title":"Respiratory Failure and Death in Vulnerable Premature Children With Lower Respiratory Tract Illness","volume":"222","author":"Ofman","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1002\/ppul.23998","article-title":"Interleukin-13 Associates with Life-Threatening Rhinovirus Infections in Infants and Young Children","volume":"53","author":"Caballero","year":"2018","journal-title":"Pediatr. Pulmonol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1172\/JCI75183","article-title":"TLR4 Genotype and Environmental LPS Mediate RSV Bronchiolitis through Th2 Polarization","volume":"125","author":"Caballero","year":"2015","journal-title":"J. Clin. Investig."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1111\/j.1651-2227.2008.01208.x","article-title":"Comparison of Cytokine Responses in Nasopharyngeal Aspirates from Children with Viral Lower Respiratory Tract Infections","volume":"98","author":"Byeon","year":"2009","journal-title":"Acta Paediatr."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/ije\/26.1.224","article-title":"The role of conceptual frameworks in epidemiological analysis: A hierarchical approach","volume":"26","author":"Victora","year":"1997","journal-title":"Int. J. Epidemiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1093\/infdis\/jiy517","article-title":"Mortality Associated With Acute Respiratory Infections Among Children at Home","volume":"219","author":"Caballero","year":"2019","journal-title":"J. Infect. Dis."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.ijid.2021.03.002","article-title":"Effect of In-House Crowding on Childhood Hospital Admissions for Acute Respiratory Infection: A Matched Case\u2013Control Study in Bangladesh","volume":"105","author":"Islam","year":"2021","journal-title":"Int. J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Colosia, A.D., Masaquel, A., Hall, C.B., Barrett, A.M., Mahadevia, P.J., and Yogev, R. (2012). Residential Crowding and Severe Respiratory Syncytial Virus Disease among Infants and Young Children: A Systematic Literature Review. BMC Infect. Dis., 12.","DOI":"10.1186\/1471-2334-12-95"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S210","DOI":"10.1093\/cid\/ciab497","article-title":"Community Mortality Due to Respiratory Syncytial Virus in Argentina: Population-Based Surveillance Study","volume":"73","author":"Caballero","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_26","first-page":"100336","article-title":"Caesarean Section and Respiratory System Disorders in Newborns","volume":"23","author":"Yeganegi","year":"2024","journal-title":"Eur. J. Obstet. Gynecol. Reprod. Biol. X"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1111\/j.1651-2227.2004.tb02752.x","article-title":"Breathing Patterns in Term Infants Delivered by Caesarean Section","volume":"93","author":"Bader","year":"2004","journal-title":"Acta Paediatr."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1016\/0031-9384(95)00155-C","article-title":"Simulated Uterine Contractions Facilitate Fetal and Newborn Respiratory Behavior in Rats","volume":"58","author":"Ronca","year":"1995","journal-title":"Physiol. Behav."},{"key":"ref_29","first-page":"CD006614","article-title":"Antenatal Corticosteroids Prior to Planned Caesarean at Term for Improving Neonatal Outcomes","volume":"2021","author":"Sotiriadis","year":"2021","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_30","first-page":"286","article-title":"Epidemiology of Sudden Infant Death Syndrome (SIDS) for Kentucky Infants Born in 1990: Maternal, Prenatal, and Perinatal Risk Factors","volume":"93","author":"Sanghavi","year":"1995","journal-title":"J. Ky. Med. Assoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1128\/CMR.00090-16","article-title":"The Human Immune Response to Respiratory Syncytial Virus Infection","volume":"30","author":"Russell","year":"2017","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Melville, J.M., and Moss, T.J.M. (2013). The Immune Consequences of Preterm Birth. Front. Neurosci., 7.","DOI":"10.3389\/fnins.2013.00079"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/j.anorl.2019.03.001","article-title":"Respiratory Polygraphy in Children: Feasibility in Everyday Practice in an ENT Department and Value of Automatic Detection of Respiratory Events","volume":"136","author":"Blanc","year":"2019","journal-title":"Eur. Ann. Otorhinolaryngol. Head Neck Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1016\/j.sleep.2013.07.016","article-title":"Reference Values for Respiratory Events in Overnight Polygraphy from Infants Aged 1 and 3 months","volume":"14","author":"Brockmann","year":"2013","journal-title":"Sleep Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"710","DOI":"10.1093\/aje\/kwk052","article-title":"Relaxing the rule of ten events per variable in logistic and Cox regression","volume":"165","author":"Vittinghoff","year":"2007","journal-title":"Am. J. Epidemiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"S248","DOI":"10.1093\/cid\/ciab487","article-title":"Challenges of Assessing Community Mortality Due to Respiratory Viruses in Children Aged Less Than 5 Years","volume":"73","author":"Caballero","year":"2021","journal-title":"Clin. Infect. Dis."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1111\/j.1651-2227.2010.02004.x","article-title":"Central Apnoeas in Infants with Bronchiolitis Admitted to the Paediatric Intensive Care Unit","volume":"100","author":"Schiller","year":"2011","journal-title":"Acta. Paediatr."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"983","DOI":"10.1164\/rccm.201301-0016OC","article-title":"Macronutrients during Pregnancy and Life-Threatening Respiratory Syncytial Virus Infections in Children","volume":"187","author":"Ferolla","year":"2013","journal-title":"Am. J. Respir. Crit. Care Med."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/7\/778\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T04:23:41Z","timestamp":1784262221000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/7\/778"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,15]]},"references-count":38,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["v18070778"],"URL":"https:\/\/doi.org\/10.3390\/v18070778","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,15]]}}}