{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T03:32:17Z","timestamp":1769052737590,"version":"3.49.0"},"reference-count":40,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,4,5]],"date-time":"2025-04-05T00:00:00Z","timestamp":1743811200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000038","name":"U.S. Food and Drug Administration","doi-asserted-by":"publisher","award":["RO1FD004147"],"award-info":[{"award-number":["RO1FD004147"]}],"id":[{"id":"10.13039\/100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Epilepsia Open"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>To study the relationship between the delay in treatment and the efficacy of phenobarbital in neonates, we re\u2010analyzed data from the NEOLEV2 study. Continuous video EEG (cEEG) from patients treated with phenobarbital was reviewed by neurophysiologists who marked each seizure. The time from seizure onset to phenobarbital, total seizure burden pre\u2010phenobarbital, and maximum seizure density (summed seizure burden per hour) pre\u2010phenobarbital were calculated and correlated with phenobarbital efficacy at 20\u2009mg\/kg and at 40\u2009mg\/kg. The time between seizure onset and phenobarbital treatment did <jats:bold>not<\/jats:bold> predict refractoriness to phenobarbital. However, the maximum seizure density per hour and total seizure burden before phenobarbital treatment were strongly correlated with efficacy. ROC curve analysis showed cut\u2010offs of maximum seizure density pre\u2010phenobarbital of 10 \u00bd\u2009min\/h and total seizure burden pre\u2010phenobarbital of 36 \u00bc\u2009min had excellent discriminatory ability in separating patients in whom phenobarbital would be effective from patients in whom it would not be effective (AUC 0.84, <jats:italic>p<\/jats:italic>\u2009=\u20090.0002 and AUC 0.85, <jats:italic>p<\/jats:italic>\u2009=\u20090.0051). These data suggest that whereas neonates with high seizure density must be treated as an emergency, mild\u2010to\u2010moderate seizures remain responsive to phenobarbital if treated within a time frame of several hours.<\/jats:p><\/jats:sec><jats:sec><jats:title>Plain Language Summary<\/jats:title><jats:p>Phenobarbital is very effective at stopping seizures in newborns. But if phenobarbital is given after many hours of seizures, it becomes less effective. We do not know how quickly this happens. Our study found that it does not happen over the short term (&lt;4\u2009h). It is more difficult to stop seizures that cumulatively last more than 10\u2009min\/h.<\/jats:p><\/jats:sec>","DOI":"10.1002\/epi4.70020","type":"journal-article","created":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T01:05:14Z","timestamp":1743901514000},"page":"948-956","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Efficacy of phenobarbital is maintained after exposure to mild\u2010to\u2010moderate seizures in neonates"],"prefix":"10.1002","volume":"10","author":[{"given":"Cynthia","family":"Sharpe","sequence":"first","affiliation":[{"name":"Department of Paediatric Neurology Starship Children's Health  Auckland New Zealand"},{"name":"Department of Neurosciences University of California San Diego, Rady Children's Hospital San Diego  San Diego California USA"},{"name":"Department of Paediatrics University of Auckland  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charlotte\u2010Rose","family":"Rennie\u2010Younger","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Starship Children's Health  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dug Yeo","family":"Han","sequence":"additional","affiliation":[{"name":"Starship Research and Innovation Starship Foundation  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Suzanne L.","family":"Davis","sequence":"additional","affiliation":[{"name":"Department of Paediatric Neurology Starship Children's Health  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark","family":"Nespeca","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego, Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesco","family":"Pisani","sequence":"additional","affiliation":[{"name":"Department of Neuroscience Sapienza University  Rome Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey J.","family":"Gold","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego, Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gail E.","family":"Reiner","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego, Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sonya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology University of Minnesota School of Medicine  Minneapolis Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Haas","sequence":"additional","affiliation":[{"name":"Department of Neurosciences University of California San Diego, Rady Children's Hospital San Diego  San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,4,5]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.17745"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582\u2010022\u201000664\u20103"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/epi.13354"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yebeh.2008.02.008"},{"key":"e_1_2_12_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clp.2009.08.001"},{"key":"e_1_2_12_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrn919"},{"key":"e_1_2_12_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2017.03.006"},{"key":"e_1_2_12_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2016.03.035"},{"key":"e_1_2_12_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamanetworkopen.2021.39604"},{"key":"e_1_2_12_11_1","unstructured":"HuntRW.Email regarding efficacy of phenobarbital in NEST. 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