{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T00:16:49Z","timestamp":1778717809255,"version":"3.51.4"},"reference-count":34,"publisher":"BMJ","issue":"8","license":[{"start":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T00:00:00Z","timestamp":1691452800000},"content-version":"unspecified","delay-in-days":7,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","award":["001"],"award-info":[{"award-number":["001"]}],"id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"published-print":{"date-parts":[[2023,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Although adverse drug reactions (ADRs) are quite common in hospitalised neonates, pharmacovigilance activities in this public are still incipient. This study aims to characterise ADRs in neonates in a neonatal intensive care unit (NICU), identifying causative drugs, temporal profile and associated factors.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Prospective observational study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>NICU of a public maternity hospital in Natal\/Brazil.<\/jats:p><\/jats:sec><jats:sec><jats:title>Participants<\/jats:title><jats:p>All neonates admitted to the NICU for more than 24 hours and using at least one medication were followed up during the time of hospitalisation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Primary outcome measures<\/jats:title><jats:p>Incidence rate and risk factors for ADRs. The ADRs were detected by an active search in electronic medical records and analysis of spontaneous reports in the hospital pharmacovigilance system.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Six hundred neonates were included in the study, where 118 neonates had a total of 186 ADRs. The prevalence of ADRs at the NICU was 19.7% (95% CI 16.7% to 23.0%). The most common ADRs were tachycardia (30.6%), polyuria (9.1%) and hypokalaemia (8.6%). Tachycardia (peak incidence rate: 57.1 ADR\/1000 neonates) and hyperthermia (19.1 ADR\/1000 neonates) predominated during the first 5\u2009days of hospitalisation. The incidence rate of polyuria and hypokalaemia increased markedly after the 20th day, with both reaching a peak of 120.0 ADR\/1000 neonates. Longer hospitalisation time (OR 0.018, 95% CI 0.007 to 0.029; p&lt;0.01) and number of prescribed drugs (OR 0.127, 95% CI 0.075 to 0.178; p&lt;0.01) were factors associated with ADRs.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ADRs are very common in NICU, with tachycardia and hyperthermia predominant in the first week of hospitalisation and polyuria and hypokalaemia from the third week onwards.<\/jats:p><\/jats:sec>","DOI":"10.1136\/bmjopen-2023-073304","type":"journal-article","created":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T15:22:30Z","timestamp":1691508150000},"page":"e073304","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["Temporal profile of adverse drug reactions and associated clinical factors: a prospective observational study in a neonatal intensive care unit"],"prefix":"10.1136","volume":"13","author":[{"given":"Ramon Weyler Duarte","family":"Leopoldino","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel Paiva","family":"Marques","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luan Carvalho","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Flavia Evelyn Medeiros","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9103-6532","authenticated-orcid":false,"given":"Antonio Gouveia","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9668-0482","authenticated-orcid":false,"given":"Rand Randall","family":"Martins","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[2023,8,8]]},"reference":[{"key":"2023080808051780000_13.8.e073304.1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(20)31977-2"},{"key":"2023080808051780000_13.8.e073304.2","doi-asserted-by":"crossref","first-page":"S10","DOI":"10.1002\/jcph.1284","article-title":"Developmental changes in pharmacokinetics and pharmacodynamics","volume":"58 Suppl 10","author":"van den Anker","year":"2018","journal-title":"J Clin Pharmacol"},{"key":"2023080808051780000_13.8.e073304.3","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1007\/s40262-015-0298-7","article-title":"Effect of kidney function on drug Kinetics and dosing in neonates, infants, and children","volume":"54","author":"Rodieux","year":"2015","journal-title":"Clin Pharmacokinet"},{"key":"2023080808051780000_13.8.e073304.4","doi-asserted-by":"crossref","first-page":"S141","DOI":"10.1002\/jcph.1884","article-title":"Considerations for drug dosing in premature infants","volume":"61","author":"Anker","year":"2021","journal-title":"The Journal of Clinical Pharmacology"},{"key":"2023080808051780000_13.8.e073304.5","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.166"},{"key":"2023080808051780000_13.8.e073304.6","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12430"},{"key":"2023080808051780000_13.8.e073304.7","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1159\/000480994","article-title":"Epidemiology of adverse drug reactions in the newborn","volume":"5","author":"Aranda","year":"1982","journal-title":"Dev Pharmacol Ther"},{"key":"2023080808051780000_13.8.e073304.8","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2015-309396"},{"key":"2023080808051780000_13.8.e073304.9","doi-asserted-by":"crossref","first-page":"1541","DOI":"10.1111\/bcp.14485","article-title":"Prospective identification and causality evaluation of suspected adverse drug reactions in neonates","volume":"87","author":"Roberts","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"2023080808051780000_13.8.e073304.10","first-page":"33","article-title":"Adverse drug reactions in neonates hospitalized in neonatal intensive care units in Barranquilla, Colombia","volume":"37","author":"De las Salas","year":"2017","journal-title":"Biomedica"},{"key":"2023080808051780000_13.8.e073304.11","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-011-1183-4"},{"key":"2023080808051780000_13.8.e073304.12","doi-asserted-by":"publisher","DOI":"10.1002\/jcph.75"},{"key":"2023080808051780000_13.8.e073304.13","unstructured":"ICH Guideline E2D . Post-approval safety data management: definitions and standards for expedited reporting. 2004. Available: http:\/\/www.ich.org\/fileadmin\/Public_Web_Site\/ICH_Products\/Guidelines\/Efficacy\/E2D\/Step4\/E2D_Guideline.pdf"},{"key":"2023080808051780000_13.8.e073304.14","doi-asserted-by":"crossref","unstructured":"Al-Turkait A , Szatkowski L , Choonara I , et al . Review of drug utilization studies in neonatal units: A global perspective. Int J Environ Res Public Health 2020;17:5669. doi:10.3390\/ijerph17165669","DOI":"10.3390\/ijerph17165669"},{"key":"2023080808051780000_13.8.e073304.15","doi-asserted-by":"publisher","DOI":"10.1111\/jcpt.12440"},{"key":"2023080808051780000_13.8.e073304.16","unstructured":"Griffin FA , Resar RK . IHI Global Trigger Tool for Measuring Adverse Events (Second Edition). IHI Innovation Series white paper. Cambridge, Massachusetts: Institute for Healthcare Improvement, 2009."},{"key":"2023080808051780000_13.8.e073304.17","doi-asserted-by":"publisher","DOI":"10.7861\/clinmedicine.16-5-481"},{"key":"2023080808051780000_13.8.e073304.18","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(05)83390-6"},{"key":"2023080808051780000_13.8.e073304.19","doi-asserted-by":"publisher","DOI":"10.1159\/000014189"},{"key":"2023080808051780000_13.8.e073304.20","doi-asserted-by":"crossref","unstructured":"Aranda JV , Beharry KD . Pharmacokinetics, pharmacodynamics and metabolism of caffeine in newborns. Semin Fetal Neonatal Med 2020;25:S1744-165X(20)30108-6. doi:10.1016\/j.siny.2020.101183","DOI":"10.1016\/j.siny.2020.101183"},{"key":"2023080808051780000_13.8.e073304.21","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1111\/bcp.14483","article-title":"Developmental population pharmacokinetics of caffeine in Chinese premature infants with apnoea of Prematurity: A post-marketing study to support Paediatric labelling in China","volume":"87","author":"Gao","year":"2021","journal-title":"Br J Clin Pharmacol"},{"key":"2023080808051780000_13.8.e073304.22","unstructured":"Hew MR , Gerriets V . Prostaglandin E1. In: StatPearls [online]. Treasure Island, FL: StatPearls Publishing, 2022."},{"key":"2023080808051780000_13.8.e073304.23","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1016\/j.pedneo.2012.10.007","article-title":"Reappraisal of the prostaglandin E1 dose for early newborns with patent Ductus Arteriosus-dependent pulmonary circulation","volume":"54","author":"Huang","year":"2013","journal-title":"Pediatr Neonatol"},{"key":"2023080808051780000_13.8.e073304.24","doi-asserted-by":"crossref","unstructured":"Pacifici GM . n.d. Clinical pharmacology of furosemide in neonates: A review [pharmaceuticals 2013;6:1094\u2013129]. Pharmaceuticals;6:1094\u2013129. doi:10.3390\/ph6091094","DOI":"10.3390\/ph6091094"},{"key":"2023080808051780000_13.8.e073304.25","doi-asserted-by":"crossref","unstructured":"Okazaki K , Fukuoka N , Kuboi T , et al . Furosemide clearance in very Preterm neonates early in life: A pilot study using Scavenged samples. Pediatr Int 2022;64:e14735. doi:10.1111\/ped.14735","DOI":"10.1111\/ped.14735"},{"key":"2023080808051780000_13.8.e073304.26","doi-asserted-by":"crossref","first-page":"2085","DOI":"10.1007\/s00467-013-2666-6","article-title":"Developmental changes in renal tubular transport-an overview","volume":"30","author":"Gattineni","year":"2015","journal-title":"Pediatr Nephrol"},{"key":"2023080808051780000_13.8.e073304.27","doi-asserted-by":"publisher","DOI":"10.1186\/s12967-018-1417-7"},{"key":"2023080808051780000_13.8.e073304.28","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1016\/j.clp.2014.05.007","article-title":"Electrolyte disorders","volume":"41","author":"Bockenhauer","year":"2014","journal-title":"Clin Perinatol"},{"key":"2023080808051780000_13.8.e073304.29","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1007\/s00246-015-1263-9","article-title":"A literature review of the pharmacokinetics and pharmacodynamics of dobutamine in neonates","volume":"37","author":"Mahoney","year":"2016","journal-title":"Pediatr Cardiol"},{"key":"2023080808051780000_13.8.e073304.30","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.clp.2011.12.013","article-title":"Anesthesia and analgesia in the NICU","volume":"39","author":"Hall","year":"2012","journal-title":"Clin Perinatol"},{"key":"2023080808051780000_13.8.e073304.31","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.pedneo.2014.06.002","article-title":"Clinical pharmacology of fentanyl in Preterm infants. A review","volume":"56","author":"Pacifici","year":"2015","journal-title":"Pediatr Neonatol"},{"key":"2023080808051780000_13.8.e073304.32","doi-asserted-by":"publisher","DOI":"10.1136\/archdischild-2018-315920"},{"key":"2023080808051780000_13.8.e073304.33","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/j.clp.2019.08.005","article-title":"Assessment of pain in the newborn: an update","volume":"46","author":"Maxwell","year":"2019","journal-title":"Clin Perinatol"},{"key":"2023080808051780000_13.8.e073304.34","doi-asserted-by":"crossref","unstructured":"Thiesen S , Conroy EJ , Bellis JR , et al . Incidence, characteristics and risk factors of adverse drug reactions in hospitalized children \u2013 a prospective observational cohort study of 6,601 admissions. BMC Med 2013;11:237. doi:10.1186\/1741-7015-11-237","DOI":"10.1186\/1741-7015-11-237"}],"container-title":["BMJ Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/bmjopen-2023-073304","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,8]],"date-time":"2023-08-08T15:22:51Z","timestamp":1691508171000},"score":1,"resource":{"primary":{"URL":"https:\/\/bmjopen.bmj.com\/lookup\/doi\/10.1136\/bmjopen-2023-073304"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8]]},"references-count":34,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2023,8,8]]},"published-print":{"date-parts":[[2023,8]]}},"alternative-id":["10.1136\/bmjopen-2023-073304"],"URL":"https:\/\/doi.org\/10.1136\/bmjopen-2023-073304","relation":{},"ISSN":["2044-6055","2044-6055"],"issn-type":[{"value":"2044-6055","type":"print"},{"value":"2044-6055","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8]]}}}