{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T02:49:13Z","timestamp":1777344553370,"version":"3.51.4"},"reference-count":34,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neuropediatrics"],"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>To determine the effects of empiric antibiotic therapy within the first 72\u2009hours after birth, in cases of suspected early-onset sepsis without positive blood cultures, on the neurodevelopment of VLBW infants.<\/jats:p><jats:p>Cohort study conducted from January 2014 to December 2021, included neonates from 24 to 32 weeks' gestation. They were categorized based on receiving early antibiotics. Outcomes measured included neonatal morbidities and scores on the Bayley Scales of Infant Development, Third Edition (BSID-III), at 12 to 36 months corrected age.<\/jats:p><jats:p>Of 261 VLBW infants 52.9% (n\u2009=\u2009138) received empiric antibiotics within the first 72\u2009hours, while 47.1% (n\u2009=\u2009123) did not. Multivariate analysis revealed no association between early antibiotics and neurodevelopmental delay. Severe intraventricular hemorrhage independently correlated with delays, while late-onset sepsis and bronchopulmonary dysplasia contributed to specific motor and cognitive delays. Propensity score matching (PSM) was conducted using various models that included gestational age, late-onset sepsis, severe intraventricular hemorrhage, bronchopulmonary dysplasia, and clinical chorioamnionitis. However, antibiotic use was not independently associated with an increased risk of developmental delay in the applied models.<\/jats:p><jats:p>Although the use of antibiotics did not emerge as an independent factor contributing to developmental delay, VLBW infants who received antibiotics had more morbidities during their NICU stay.<\/jats:p>","DOI":"10.1055\/a-2561-8208","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T19:53:21Z","timestamp":1742414001000},"page":"320-327","source":"Crossref","is-referenced-by-count":1,"title":["Empiric Antibiotic Therapy and Neurodevelopment Outcome of Very Low Birth Weight Infants"],"prefix":"10.1055","volume":"56","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6316-6321","authenticated-orcid":false,"given":"Marina P.","family":"Menegolla","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2982-2652","authenticated-orcid":false,"given":"Rita C.","family":"Silveira","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2013-1027","authenticated-orcid":false,"given":"Ant\u00f4nio R. H.","family":"G\u00f6rgen","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9400-5287","authenticated-orcid":false,"given":"Fernanda E.","family":"Gandolfi","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2111-538X","authenticated-orcid":false,"given":"Carolina","family":"Panceri","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8297-4164","authenticated-orcid":false,"given":"Renato S.","family":"Procianoy","sequence":"additional","affiliation":[{"name":"Newborn Section, Child Health and Adolescent Medicine Graduate Program, Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Hospital de Cl\u00ednicas de Porto Alegre, Porto Alegre, RS, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,3,27]]},"reference":[{"issue":"04","key":"ref1","doi-asserted-by":"crossref","first-page":"e2021052456","DOI":"10.1542\/peds.2021-052456","article-title":"Early-onset sepsis among very preterm infants","volume":"148","author":"D D Flannery","year":"2021","journal-title":"Pediatrics"},{"issue":"07","key":"ref2","doi-asserted-by":"crossref","first-page":"e200593","DOI":"10.1001\/jamapediatrics.2020.0593","article-title":"Early-onset neonatal sepsis 2015 to 2017, the rise of Escherichia coli, and the need for novel prevention strategies","volume":"174","author":"B J Stoll","year":"2020","journal-title":"JAMA Pediatr"},{"issue":"04","key":"ref3","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1016\/j.bjid.2018.07.009","article-title":"Inadequate use of antibiotics and increase in neonatal sepsis caused by resistant bacteria related to health care assistance: a systematic review","volume":"22","author":"A CB Silva","year":"2018","journal-title":"Braz J Infect Dis"},{"issue":"01","key":"ref4","doi-asserted-by":"crossref","first-page":"2423","DOI":"10.1038\/s41467-023-38156-7","article-title":"Less is more: antibiotics at the beginning of life","volume":"14","author":"M Stocker","year":"2023","journal-title":"Nat Commun"},{"issue":"12","key":"ref5","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1001\/jamapediatrics.2016.2132","article-title":"Association between antibiotic use and neonatal mortality and morbidities in very low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis","volume":"170","author":"J Y Ting","year":"2016","journal-title":"JAMA Pediatr"},{"issue":"02","key":"ref6","doi-asserted-by":"publisher","DOI":"10.33552\/GJPNC.2020.02.000532","article-title":"Mismanagement of antibiotics in neonatal medicine","volume":"2","author":"A Sola","year":"2020","journal-title":"Glob J Pediatr Neonatal Care"},{"issue":"10","key":"ref7","doi-asserted-by":"crossref","first-page":"972","DOI":"10.1055\/s-0038-1632390","article-title":"Association of antibiotic utilization and neurodevelopmental outcomes among extremely low gestational age neonates without proven sepsis or necrotizing enterocolitis","volume":"35","author":"J Y Ting","year":"2018","journal-title":"Am J Perinatol"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.jpeds.2020.02.038","article-title":"Impact of early-onset sepsis and antibiotic use on death or survival with neurodevelopmental impairment at 2 years of age among extremely preterm infants","volume":"221","author":"S Mukhopadhyay","year":"2020","journal-title":"J Pediatr"},{"issue":"05","key":"ref9","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1016\/j.jpeds.2011.05.033","article-title":"Prolonged initial empirical antibiotic treatment is associated with adverse outcomes in premature infants","volume":"159","author":"V S Kuppala","year":"2011","journal-title":"J Pediatr"},{"issue":"05","key":"ref10","first-page":"600","article-title":"Tratamiento antibi\u00f3tico emp\u00edrico inicial prolongado y riesgo de morbimortalidad en reci\u00e9n nacidos de muy bajo peso al nacer","volume":"89","author":"D Torres","year":"2018","journal-title":"Rev Chil Pediatr"},{"issue":"04","key":"ref11","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0022-3476(78)80282-0","article-title":"Incidence and evolution of subependymal and intraventricular hemorrhage: a study of infants with birth weights less than 1,500 gm","volume":"92","author":"L A Papile","year":"1978","journal-title":"J Pediatr"},{"issue":"02","key":"ref12","first-page":"180","article-title":"Bayley scales of infant and toddler development","volume":"25","author":"C A Albers","year":"2007","journal-title":"J Psychoeduc Assess"},{"issue":"05","key":"ref13","doi-asserted-by":"crossref","first-page":"670","DOI":"10.1038\/pr.2014.10","article-title":"Using the Bayley-III to assess neurodevelopmental delay: which cut-off should be used?","volume":"75","author":"S Johnson","year":"2014","journal-title":"Pediatr Res"},{"issue":"S 01","key":"ref14","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.jped.2019.10.004","article-title":"The challenges of neonatal sepsis management","volume":"96","author":"R S Procianoy","year":"2020","journal-title":"J Pediatr (Rio J)"},{"issue":"06","key":"ref15","doi-asserted-by":"crossref","first-page":"e2022057442","DOI":"10.1542\/peds.2022-057442","article-title":"Preterm brain injury and neurodevelopmental outcomes: a meta-analysis","volume":"150","author":"P Rees","year":"2022","journal-title":"Pediatrics"},{"issue":"06","key":"ref16","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1542\/peds.2005-0249","article-title":"Validation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia","volume":"116","author":"R A Ehrenkranz","year":"2005","journal-title":"Pediatrics"},{"issue":"02","key":"ref17","doi-asserted-by":"crossref","first-page":"e348","DOI":"10.1542\/peds.2010-3338","article-title":"Impact of sepsis on neurodevelopmental outcome in a Swiss National Cohort of extremely premature infants","volume":"128","author":"L J Schlapbach","year":"2011","journal-title":"Pediatrics"},{"issue":"01","key":"ref18","doi-asserted-by":"crossref","first-page":"15448","DOI":"10.1038\/s41598-019-51617-8","article-title":"Late-onset sepsis as a risk factor for bronchopulmonary dysplasia in extremely low birth weight infants: a nationwide cohort study","volume":"9","author":"E Jung","year":"2019","journal-title":"Sci Rep"},{"issue":"12","key":"ref19","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.1177\/0883073813513335","article-title":"Systemic inflammation and cerebral palsy risk in extremely preterm infants","volume":"29","author":"K C Kuban","year":"2014","journal-title":"J Child Neurol"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.jpeds.2021.11.075","article-title":"Early antibiotic exposure and adverse outcomes in very preterm infants at low risk of early-onset sepsis: the EPIPAGE-2 cohort study","volume":"243","author":"M Letouzey","year":"2022","journal-title":"J Pediatr"},{"issue":"02","key":"ref21","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/j.clp.2017.01.005","article-title":"The microbiota of the extremely preterm infant","volume":"44","author":"M A Underwood","year":"2017","journal-title":"Clin Perinatol"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"100573","DOI":"10.1016\/j.bbih.2022.100573","article-title":"Impact of broad-spectrum antibiotics on the gut-microbiota-spleen-brain axis","volume":"27","author":"X Wan","year":"2022","journal-title":"Brain Behav Immun Health"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1038\/s41586-022-04396-8","article-title":"A gut-derived metabolite alters brain activity and anxiety behaviour in mice","volume":"602","author":"B D Needham","year":"2022","journal-title":"Nature"},{"issue":"01","key":"ref24","doi-asserted-by":"crossref","first-page":"4026","DOI":"10.1038\/s41598-024-54553-4","article-title":"A systematic review and meta-analysis of the effects of long-term antibiotic use on cognitive outcomes","volume":"14","author":"Y Ye","year":"2024","journal-title":"Sci Rep"},{"issue":"08","key":"ref25","doi-asserted-by":"crossref","first-page":"785","DOI":"10.1007\/s12098-021-04023-w","article-title":"Association between antibiotic overexposure and adverse outcomes in very-low-birth-weight infants without culture-proven sepsis or necrotizing enterocolitis: a multicenter prospective study","volume":"89","author":"S Hou","year":"2022","journal-title":"Indian J Pediatr"},{"issue":"06","key":"ref26","doi-asserted-by":"crossref","first-page":"967","DOI":"10.3390\/antibiotics12060967","article-title":"Duration of neonatal antibiotic exposure in preterm infants in association with health and developmental outcomes in early childhood","volume":"12","author":"N Deianova","year":"2023","journal-title":"Antibiotics (Basel)"},{"issue":"14","key":"ref27","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1177\/0883073820946206","article-title":"Neonatal adverse outcomes, neonatal birth risks, and socioeconomic status: combined influence on preterm infants' cognitive, language, and motor development in Brazil","volume":"35","author":"C Panceri","year":"2020","journal-title":"J Child Neurol"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"277","DOI":"10.3389\/fped.2018.00277","article-title":"Predictors of mortality in neonates and infants hospitalized with sepsis or serious infections in developing countries: a systematic review","volume":"6","author":"L D Liang","year":"2018","journal-title":"Front Pediatr"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"105634","DOI":"10.1016\/j.earlhumdev.2022.105634","article-title":"Cognitive and motor development in preterm children from 6 to 36 months of age: trajectories, risk factors and predictability","volume":"172","author":"S J Li","year":"2022","journal-title":"Early Hum Dev"},{"issue":"02","key":"ref30","doi-asserted-by":"crossref","first-page":"e0193406","DOI":"10.1371\/journal.pone.0193406","article-title":"Evaluation of the INTERGROWTH-21st neurodevelopment assessment (INTER-NDA) in 2 year-old children","volume":"13","author":"E Murray","year":"2018","journal-title":"PLoS One"},{"issue":"01","key":"ref31","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/s41390-023-02814-9","article-title":"Neurodevelopmental and behavioral outcomes of very preterm infants: latent profile analysis in the environmental influences on child health outcomes (ECHO) program","volume":"95","author":"M Camerota","year":"2024","journal-title":"Pediatr Res"},{"issue":"03","key":"ref32","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1080\/00273171.2011.568786","article-title":"An introduction to propensity score methods for reducing the effects of confounding in observational studies","volume":"46","author":"P C Austin","year":"2011","journal-title":"Multivariate Behav Res"},{"issue":"12","key":"ref33","doi-asserted-by":"crossref","first-page":"1945","DOI":"10.1017\/ice.2021.379","article-title":"Variation in antibiotic use among neonatal intensive care units in the United States","volume":"43","author":"H JJ Spencer","year":"2022","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"05","key":"ref34","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1001\/jamapediatrics.2020.6087","article-title":"Association between preterm-birth phenotypes and differential morbidity, growth, and neurodevelopment at age 2 years: results from the INTERBIO-21st newborn study","volume":"175","author":"J Villar","year":"2021","journal-title":"JAMA Pediatr"}],"container-title":["Neuropediatrics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.thieme-connect.de\/products\/ejournals\/pdf\/10.1055\/a-2561-8208.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T22:42:00Z","timestamp":1757457720000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.thieme-connect.de\/DOI\/DOI?10.1055\/a-2561-8208"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,19]]},"references-count":34,"journal-issue":{"issue":"05","published-online":{"date-parts":[[2025,9,9]]},"published-print":{"date-parts":[[2025,10]]}},"URL":"https:\/\/doi.org\/10.1055\/a-2561-8208","archive":["Portico","CLOCKSS"],"relation":{},"ISSN":["0174-304X","1439-1899"],"issn-type":[{"value":"0174-304X","type":"print"},{"value":"1439-1899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,3,19]]},"published":{"date-parts":[[2025,3,19]]}}}