{"paper_id":"2522f853-35c3-4ed9-9b4d-543f8ebcb884","body_text":"Reducing the Percent of Surviving Infants with Acute Symptomatic Seizures Discharged on Anti-Seizure Medication | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Article Reducing the Percent of Surviving Infants with Acute Symptomatic Seizures Discharged on Anti-Seizure Medication Elizabeth Sewell, Anne Marie Nangle, Zhulin He, Sonam Bhalla, and 7 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4356197/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 23 Jul, 2024 Read the published version in Journal of Perinatology → Version 1 posted 9 You are reading this latest preprint version Abstract Objective: To evaluate the impact of inclusion of an ASM weaning protocol in a neonatal seizure pathway on the percent of infants discharged on ASMs. Study Design: This cohort study included surviving infants with acute symptomatic seizures treated with ASMs. We evaluated infants in 2 epochs, pre- and post-implementation of the ASM weaning protocol. The primary outcome was discharge on ASM. Results: Of 116 included infants, the percent of infants discharged on ASMs was 69% in epoch 1 versus 34% in epoch 2 (p<0.001). There was no significant difference between epochs in recurrence of seizures after discharge by 1 year of age (p=0.125). There was an annual decrease in the percent of infants discharged on ASM for both delivery and referral NICUs. Conclusion: Inclusion of a formal ASM weaning protocol as part of an institutional seizure pathway reduced percent of infants with acute symptomatic seizures discharged on ASM. Health sciences/Diseases/Neurological disorders/Brain injuries Health sciences/Health care/Therapeutics/Drug therapy Health sciences/Diseases/Neurological disorders/Paediatric neurological disorders Figures Figure 1 Figure 2 BACKGROUND Gestational age and brain injury impacts neurodevelopmental outcome in neonates with seizures, but seizure burden has also been independently associated with worse neurodevelopmental outcomes.( 1 , 2 ) The standard of care is to treat seizures in neonates with anti-seizure medications (ASMs),( 3 ) however commonly used ASMs, such as Phenobarbitol, have also been associated with neurotoxicity in animal models and neurodevelopmental impairment in some infant studies.( 4 – 9 ) Continuation of ASM at discharge may be associated with increased neurodevelopmental impairment.( 10 ) While higher than the average population, epilepsy risk in neonates following acute symptomatic seizures remains relatively low and seizures often do not present until months to years after discharge.( 11 – 13 ) Continuation of ASM after discharge does not decrease the risk of epilepsy.( 14 ) Despite the 2011 World Health Organization’s recommendations to discontinue ASM after 72 hours of seizure freedom in neonates with a normal neurological exam and electroencephalogram, continuation of ASM at discharge remains common in many centers.( 15 ) A recent review of this practice at various centers showed that ASMs were continued at discharge in 73% of those with acute symptomatic seizures.( 16 ) In 2021, Glass et al. expanded on these guidelines and recommended discontinuation of ASM at discharge in most infants with acute symptomatic seizures.( 14 ) Subsequently, the International League Against Epilepsy published a consensus recommendation to discontinue ASM before discharge following resolution of acute symptomatic seizures in infants, regardless of MRI or EEG findings.( 3 ) Our primary aim was to evaluate the impact of an inpatient ASM weaning protocol on the percent of infants discharged on ASMs. METHODS This retrospective cohort study included infants from one referral hospital and two delivery hospitals covered by a single practice group born from January 1, 2018 to November 30, 2023. Infants were screened for study inclusion if they had seizures treated with ASM, but only infants with electroencephalogram (EEG) confirmed seizures and were discharged from our hospitals were included in the cohort. Infants were excluded if they died before discharge. Seizure etiology was determined by chart review and the population was further stratified? to infants with acute symptomatic seizures. For the purposes of this study, acute symptomatic seizures were defined as seizures provoked by hypoxia ischemic encephalopathy, stroke, hemorrhage, meningitis, or transient metabolic disturbances such as sodium or glucose abnormalities. For subset analyses, infants were categorized by type of hospital of discharge, delivery versus referral; infants born at delivery hospital and transferred to referral center were included one time under referral hospital. The Emory University Institutional Review Board approved this study with waiver of consent. An evidence-based ASM weaning protocol was added to the Neonatal Seizure Pathway in October 2020. This pathway was designed through a multidisciplinary collaboration including members from Neonatology and Pediatric Neurology. The pathway was formally presented to both divisions with subsequent feedback incorporated into the final pathway (Supplementary Fig. 1). We evaluated infants in two epochs, pre- and post-implementation of the ASM weaning protocol. The primary outcome was discharge on ASM. The primary outcome was also analyzed based on hospital type at discharge (delivery vs referral center). Additional secondary outcomes included whether or not ASM weaning was initiated prior to discharge, the number of ASMs at discharge per patient, and percent of infants with seizure post-discharge up to one year of age. Seizure post-discharge was included for infants with follow-up data available and determined by chart review of notes from neurology and developmental follow-up visits. Demographic and clinical measurements were summarized using descriptive statistics. To compare between epoch 1 and epoch 2, Welch two-sample t-test was used for continuous data, and Pearson’s Chi-squared test and Fisher’s exact test was used for categorical data. P-values less or equal to 0.05 was considered as statistically significant. All statistical analyses were performed using R software v 4.3.2. RESULTS Study Population One hundred ninety-three (193) infants had electrographic seizures and were discharged from our centers. Of these, 38 (?X%) infants died prior to discharge and 39 (?X%) infants did not have acute symptomatic seizures, leaving 116 infants in our final cohort (Fig. 1 ). Of these, 52 were in epoch 1 and 64 were in epoch 2. Demographic characteristics and underlying brain injury were similar between epoch groups (Table 1 ). Ninety-six infants (83%) of infants had a follow-up visit in our hospital system. Table 1 Demographic and Neonatal Characteristics Variable Total (N = 116) Epoch 1 (N = 52) Epoch 2 (N = 64) Gestational age, mean (SD) 37.5 (3.9) 37.3 (4.0) 37.7 (3.9) Birth weight in grams, mean (SD) 3 030 (883) 2 997 (853) 3 057 (912) Male sex, N (%) 60 (52%) 30 (58%) 30 (47%) Discharge hospital type, N(%) Delivery Referral 49 (42%) 67 (58%) 23 (44%) 29 (56%) 26 (41%) 38 (59%) Days of age at seizure diagnosis, median (IQR) 1 1 [0–2] 1 [0–2] 1 [0–3] Etiology Hypoxic-ischemic encephalopathy Stroke Intracranial hemorrhage Meningitis or brain abscess Transient metabolic disturbances 82 (71%) 14 (12%) 10 (8.6%) 5 (4.3%) 5 (4.3%) 34 (65%) 8 (15%) 3 (5.8%) 3 (5.8%) 4 (7.7%) 48 (75%) 6 (9.4%) 7 (11%) 2 (3.1%) 1 (1.6%) 1 Fourteen missing variables (N = 102) Outcomes The percent of infants discharged on ASMs was 69% in epoch 1 versus 34% in epoch 2 (p < 0.001); The difference in infants discharged on ASMs between epoch 1 and epoch 2 was larger in infants discharged from delivery NICUs versus the referral NICU. There was an annual decrease in the percent of infants discharged on ASM for both delivery and referral NICUs (Fig. 2 ). There was no significant difference between epochs in seizures after discharge by 1 year of age (p = 0.125). The percent of infants with ASM wean initiated prior to discharge and the total number of ASM at discharge also decreased across epochs (Table 2 ). Table 2 Short-term Outcomes Variable Total (N = 116) Epoch 1 (N = 52) Epoch 2 (N = 64) P-value Primary Outcome Discharged on ASM – yes, N (%) 58 (50%) 36 (69%) 22 (34%) < 0.001 Secondary Outcomes Discharged on ASM – yes, N (%) Delivery hospital Referral hospital 26 (53%) 32 (48%) 18 (78%) 18 (62%) 8 (31%) 14 (37%) < 0.001 0.041 Seizure after discharge, N (%) 1 24/96 (25%) 15/47 (32%) 9/49 (18%) 0.125 Number of ASM at discharge per patient, N (%) 2 0.7 (0.9) 1.0 (0.9) 0.4 (0.7) < 0.001 ASM wean initiated among infants discharged on ASM, N (%) 33/58 (57%) 16/36 (44%) 17/22 (77%) 0.014 1 Twenty missing variables (N = 96) 2 One missing variable (N = 115) Supplementary Fig. 1 Summary : Neonatal seizure pathway with inclusion of anti-seizure medication weaning protocol. Reflects most current version following three revisions. DISCUSSION Among infants with acute symptomatic seizures in three local hospitals cared for by one provider group, we found that inclusion of an ASM wean protocol in the neonatal seizure pathway decreased the number of infants discharged on ASM, regardless of type of NICU. There was no difference in seizures after discharge between epochs. Among infants with acute symptomatic seizures who were maintained on ASM at discharge, we found more infants had a wean of ASM initiated prior to hospital discharge in epoch 2. Previous studies have shown variation by center in the percent of infants with acute symptomatic seizures discharged on ASM.( 10 , 17 , 18 ) Historically our academic provider group working in three local hospitals, or has had a high proportion of infants with seizures discharged on ASM. This was compounded by challenges in obtaining neurology follow-up in a timely manner after discharge, resulting in infants being exposed to prolonged duration of ASM. There was initial hesitation about discontinuing ASM prior to discharge in infants with acute symptomatic seizures due to concerns for risk of seizure recurrence. Our original ASM weaning protocol consisted of a slow wean and repeat EEG, which was necessary to gain support from some of our pediatric neurologists. However, the subsequent publication in 2021 of the comparative effectiveness study from the Neonatal Seizure Registry demonstrating no difference in epilepsy at 24 months among children whose ASM was maintained or discontinued at discharge provided more support to our efforts.( 14 ) Our current study also did not find an increase in seizure after discharge between epochs, although this was limited by loss to follow-up. We subsequently revised our ASM weaning protocol to be more efficient and not reliant upon repeat EEG in October of 2022. In parallel to the inclusion of the ASM weaning protocol in our seizure pathway, neurology also worked to increase clinic capacity to see NICU graduates within one month of discharge . Previous work has shown that the development of a neurocritical care program can decrease the percent of infants discharged on ASM.( 19 , 20 ) Unfortunately these specialized programs are not available at the majority of hospitals caring for infants with seizures. Lack of consultation by pediatric neurologists and limited availability of technical resources further restrict wide-spread applicability of neurocritical care programs.( 21 ) Our study demonstrates that decreasing ASM at discharge does not rely solely on a formal neurocritical care program. Inpatient neurology consults are not available at our delivery hospitals at the time of this publication, yet, through collaboration between divisions and buy-in from key stakeholders, we were still able to improve care for these high-risk infants. The strength of this study is the impact of the implementation of an ASM weaning protocol on the evolution of ASM discontinuation at discharge in infants with acute symptomatic seizures across local hospitals managed by one academic group. Our work highlights opportunities for similar NICUs who may frequently discharge infants with acute symptomatic seizures on ASM. This study has some limitations. Generalizability may be limited as it was a retrospective cohort study across three hospitals covered by the same neonatology and neurology physicians. Additionally, we were not able to control for other factors that may have impacted whether an infant was continued on ASM at discharge. Our study was also limited by loss to follow-up in 17% of our cohort. In conclusion, we found that inclusion of an ASM weaning protocol in a neonatal seizure pathway reduced the percent of infants with acute symptomatic seizures discharged on ASM. This difference was seen at delivery hospitals, in addition to a referral hospital, where inpatient neurology consults were not routinely available. This protocol highlights an opportunity for all NICUs to reduce the percentage of infants discharged on ASM. Declarations Conflicts of Interest: Elizabeth Sewell has received consultant fees from Hospicom and Sun Pharmaceutical Industries, Inc. The remaining authors have no conflicts of interest to disclose directly related to this study. Funding: There were no external sources of funding for this study. Author contributions: AMN contributed to the data curation, investigation, and writing of the original manuscript. ZH contributed to the formal analysis and critical review of the final manuscript. ES contributed to the conceptualization, data curation, investigation, methodology, and drafting of the original manuscript. MD, SB, SH, AP, AC, AV, JB, and PJ contributed to the investigation and critical review of the final manuscript. References Kharoshankaya L, Stevenson NJ, Livingstone V, Murray DM, Murphy BP, Ahearne CE, et al. Seizure burden and neurodevelopmental outcome in neonates with hypoxic–ischemic encephalopathy. Developmental Medicine & Child Neurology. 2016;58(12):1242–8. McBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology. 2000;55(4):506–13. Pressler RM, Abend NS, Auvin S, Boylan G, Brigo F, Cilio MR, et al. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations—Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia. 2023;64(10):2550–70. Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002;99(23):15089–94. Forcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug–induced cell death in limbic regions of the neonatal rat brain. Epilepsia. 2011;52(12):e207-e11. Kaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug–induced cell death in the developing white matter of the rodent brain. Epilepsia. 2016;57(5):727–34. Farwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures–effects on intelligence and on seizure recurrence. N Engl J Med. 1990;322(6):364–9. Sulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clinical pediatrics. 1999;38(7):387–94. Maitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. Journal of Perinatology. 2013;33(11):841–6. Sewell EK, Shankaran S, McDonald SA, Hamrick S, Wusthoff CJ, Adams-Chapman I, et al. Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study. Arch Dis Child Fetal Neonatal Ed. 2023. Camfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disorders. 2015;17(2):117–23. Shellhaas RA, Wusthoff CJ, Numis AL, Chu CJ, Massey SL, Abend NS, et al. Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study. Epilepsia. 2021;62(8):1871–82. Pisani F, Facini C, Pavlidis E, Spagnoli C, Boylan G. Epilepsy after neonatal seizures: literature review. Eur J Paediatr Neurol. 2015;19(1):6–14. Glass HC, Soul JS, Chang T, Wusthoff CJ, Chu CJ, Massey SL, et al. Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures. JAMA Neurol. 2021;78(7):817–25. World Health Organization. Guidelines on Neonatal Seizures.; 2011. Shellhaas RA, Chang T, Wusthoff CJ, Soul JS, Massey SL, Chu CJ, et al. Treatment duration after acute symptomatic seizures in neonates: a multicenter cohort study. The Journal of pediatrics. 2017;181:298–301. e1. Shellhaas RA, Chang T, Wusthoff CJ, Soul JS, Massey SL, Chu CJ, et al. Treatment Duration After Acute Symptomatic Seizures in Neonates: A Multicenter Cohort Study. J Pediatr. 2017;181:298–301.e1. Dizon MLV, Rao R, Hamrick SE, Zaniletti I, DiGeronimo R, Natarajan G, et al. Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs. BMC Pediatr. 2019;19(1):67. Bashir RA, Espinoza L, Vayalthrikkovil S, Buchhalter J, Irvine L, Bello-Espinosa L, et al. Implementation of a Neurocritical Care Program: Improved Seizure Detection and Decreased Antiseizure Medication at Discharge in Neonates With Hypoxic-Ischemic Encephalopathy. Pediatr Neurol. 2016;64:38–43. Wietstock SO, Bonifacio SL, McCulloch CE, Kuzniewicz MW, Glass HC. Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication. J Child Neurol. 2015;30(9):1135–41. Boylan G, Burgoyne L, Moore C, O'Flaherty B, Rennie J. An international survey of EEG use in the neonatal intensive care unit. Acta Paediatr. 2010;99(8):1150–5. Additional Declarations Yes there is potential conflict of interest. Supplementary Files SuppFig1.pdf Supplementary Figure 1 Summary: Neonatal seizure pathway with inclusion of anti-seizure medication weaning protocol. Reflects most current version following three revisions. Cite Share Download PDF Status: Published Journal Publication published 23 Jul, 2024 Read the published version in Journal of Perinatology → Version 1 posted Editorial decision: revise 24 May, 2024 Review # 2 received at journal 23 May, 2024 Review # 1 received at journal 23 May, 2024 Reviewer # 2 agreed at journal 15 May, 2024 Reviewer # 1 agreed at journal 05 May, 2024 Reviewers invited by journal 03 May, 2024 Submission checks completed at journal 02 May, 2024 Editor assigned by journal 01 May, 2024 First submitted to journal 01 May, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {\"props\":{\"pageProps\":{\"initialData\":{\"identity\":\"rs-4356197\",\"acceptedTermsAndConditions\":true,\"allowDirectSubmit\":false,\"archivedVersions\":[],\"articleType\":\"Article\",\"associatedPublications\":[],\"authors\":[{\"id\":298380075,\"identity\":\"8b26a417-ae30-47b5-a0b9-81c98b11d59a\",\"order_by\":0,\"name\":\"Elizabeth 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year.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"Figure2.jpg\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4356197/v1/a1b0aa68f348682d260970ef.jpg\"},{\"id\":60970946,\"identity\":\"b937bc17-b859-4569-9813-683842199f07\",\"added_by\":\"auto\",\"created_at\":\"2024-07-24 07:07:46\",\"extension\":\"pdf\",\"order_by\":0,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"manuscript-pdf\",\"size\":490863,\"visible\":true,\"origin\":\"\",\"legend\":\"\",\"description\":\"\",\"filename\":\"manuscript.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4356197/v1/8e1c6b4c-d4da-4f84-a49a-a7732ec9d6f3.pdf\"},{\"id\":56281925,\"identity\":\"6438fd11-78c0-45a9-8bac-b19d4cbd3b7b\",\"added_by\":\"auto\",\"created_at\":\"2024-05-10 21:20:43\",\"extension\":\"pdf\",\"order_by\":1,\"title\":\"\",\"display\":\"\",\"copyAsset\":false,\"role\":\"supplement\",\"size\":197339,\"visible\":true,\"origin\":\"\",\"legend\":\"\\u003cp\\u003e\\u003cstrong\\u003eSupplementary Figure 1 Summary:\\u003c/strong\\u003e\\u003c/p\\u003e\\n\\u003cp\\u003eNeonatal seizure pathway with inclusion of anti-seizure medication weaning protocol. Reflects most current version following three revisions.\\u003c/p\\u003e\",\"description\":\"\",\"filename\":\"SuppFig1.pdf\",\"url\":\"https://assets-eu.researchsquare.com/files/rs-4356197/v1/760f78b5a72c110c08055661.pdf\"}],\"financialInterests\":\"\\u003cb\\u003eYes\\u003c/b\\u003e there is potential conflict of interest.\",\"formattedTitle\":\"Reducing the Percent of Surviving Infants with Acute Symptomatic Seizures Discharged on Anti-Seizure Medication\",\"fulltext\":[{\"header\":\"BACKGROUND\",\"content\":\"\\u003cp\\u003eGestational age and brain injury impacts neurodevelopmental outcome in neonates with seizures, but seizure burden has also been independently associated with worse neurodevelopmental outcomes.(\\u003cspan citationid=\\\"CR1\\\" class=\\\"CitationRef\\\"\\u003e1\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR2\\\" class=\\\"CitationRef\\\"\\u003e2\\u003c/span\\u003e) The standard of care is to treat seizures in neonates with anti-seizure medications (ASMs),(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) however commonly used ASMs, such as Phenobarbitol, have also been associated with neurotoxicity in animal models and neurodevelopmental impairment in some infant studies.(\\u003cspan additionalcitationids=\\\"CR5 CR6 CR7 CR8\\\" citationid=\\\"CR4\\\" class=\\\"CitationRef\\\"\\u003e4\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR9\\\" class=\\\"CitationRef\\\"\\u003e9\\u003c/span\\u003e) Continuation of ASM at discharge may be associated with increased neurodevelopmental impairment.(\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e) While higher than the average population, epilepsy risk in neonates following acute symptomatic seizures remains relatively low and seizures often do not present until months to years after discharge.(\\u003cspan additionalcitationids=\\\"CR12\\\" citationid=\\\"CR11\\\" class=\\\"CitationRef\\\"\\u003e11\\u003c/span\\u003e\\u0026ndash;\\u003cspan citationid=\\\"CR13\\\" class=\\\"CitationRef\\\"\\u003e13\\u003c/span\\u003e) Continuation of ASM after discharge does not decrease the risk of epilepsy.(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e)\\u003c/p\\u003e \\u003cp\\u003eDespite the 2011 World Health Organization\\u0026rsquo;s recommendations to discontinue ASM after 72 hours of seizure freedom in neonates with a normal neurological exam and electroencephalogram, continuation of ASM at discharge remains common in many centers.(\\u003cspan citationid=\\\"CR15\\\" class=\\\"CitationRef\\\"\\u003e15\\u003c/span\\u003e) A recent review of this practice at various centers showed that ASMs were continued at discharge in 73% of those with acute symptomatic seizures.(\\u003cspan citationid=\\\"CR16\\\" class=\\\"CitationRef\\\"\\u003e16\\u003c/span\\u003e) In 2021, Glass et al. expanded on these guidelines and recommended discontinuation of ASM at discharge in most infants with acute symptomatic seizures.(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e) Subsequently, the International League Against Epilepsy published a consensus recommendation to discontinue ASM before discharge following resolution of acute symptomatic seizures in infants, regardless of MRI or EEG findings.(\\u003cspan citationid=\\\"CR3\\\" class=\\\"CitationRef\\\"\\u003e3\\u003c/span\\u003e) Our primary aim was to evaluate the impact of an inpatient ASM weaning protocol on the percent of infants discharged on ASMs.\\u003c/p\\u003e \"},{\"header\":\"METHODS\",\"content\":\"\\u003cp\\u003eThis retrospective cohort study included infants from one referral hospital and two delivery hospitals covered by a single practice group born from January 1, 2018 to November 30, 2023. Infants were screened for study inclusion if they had seizures treated with ASM, but only infants with electroencephalogram (EEG) confirmed seizures and were discharged from our hospitals were included in the cohort. Infants were excluded if they died before discharge. Seizure etiology was determined by chart review and the population was further stratified? to infants with acute symptomatic seizures. For the purposes of this study, acute symptomatic seizures were defined as seizures provoked by hypoxia ischemic encephalopathy, stroke, hemorrhage, meningitis, or transient metabolic disturbances such as sodium or glucose abnormalities. For subset analyses, infants were categorized by type of hospital of discharge, delivery versus referral; infants born at delivery hospital and transferred to referral center were included one time under referral hospital. The Emory University Institutional Review Board approved this study with waiver of consent.\\u003c/p\\u003e \\u003cp\\u003eAn evidence-based ASM weaning protocol was added to the Neonatal Seizure Pathway in October 2020. This pathway was designed through a multidisciplinary collaboration including members from Neonatology and Pediatric Neurology. The pathway was formally presented to both divisions with subsequent feedback incorporated into the final pathway (Supplementary Fig.\\u0026nbsp;1). We evaluated infants in two epochs, pre- and post-implementation of the ASM weaning protocol. The primary outcome was discharge on ASM. The primary outcome was also analyzed based on hospital type at discharge (delivery vs referral center). Additional secondary outcomes included whether or not ASM weaning was initiated prior to discharge, the number of ASMs at discharge per patient, and percent of infants with seizure post-discharge up to one year of age. Seizure post-discharge was included for infants with follow-up data available and determined by chart review of notes from neurology and developmental follow-up visits.\\u003c/p\\u003e \\u003cp\\u003eDemographic and clinical measurements were summarized using descriptive statistics. To compare between epoch 1 and epoch 2, Welch two-sample t-test was used for continuous data, and Pearson\\u0026rsquo;s Chi-squared test and Fisher\\u0026rsquo;s exact test was used for categorical data. P-values less or equal to 0.05 was considered as statistically significant. All statistical analyses were performed using R software v 4.3.2.\\u003c/p\\u003e\"},{\"header\":\"RESULTS\",\"content\":\"\\u003cdiv id=\\\"Sec3\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eStudy Population\\u003c/h2\\u003e \\u003cp\\u003eOne hundred ninety-three (193) infants had electrographic seizures and were discharged from our centers. Of these, 38 (?X%) infants died prior to discharge and 39 (?X%) infants did not have acute symptomatic seizures, leaving 116 infants in our final cohort (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Of these, 52 were in epoch 1 and 64 were in epoch 2. Demographic characteristics and underlying brain injury were similar between epoch groups (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab1\\\" class=\\\"InternalRef\\\"\\u003e1\\u003c/span\\u003e). Ninety-six infants (83%) of infants had a follow-up visit in our hospital system.\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab1\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 1\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eDemographic and Neonatal Characteristics\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"4\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVariable\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eTotal\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;116)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eEpoch 1\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;52)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eEpoch 2\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;64)\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eGestational age, mean (SD)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e37.5 (3.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e37.3 (4.0)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e37.7 (3.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eBirth weight in grams, mean (SD)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e3 030 (883)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e2 997 (853)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e3 057 (912)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eMale sex, N (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e60 (52%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e30 (58%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e30 (47%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDischarge hospital type, N(%)\\u003c/p\\u003e \\u003cp\\u003eDelivery\\u003c/p\\u003e \\u003cp\\u003eReferral\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e49 (42%)\\u003c/p\\u003e \\u003cp\\u003e67 (58%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e23 (44%)\\u003c/p\\u003e \\u003cp\\u003e29 (56%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e26 (41%)\\u003c/p\\u003e \\u003cp\\u003e38 (59%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDays of age at seizure diagnosis, median (IQR)\\u003csup\\u003e1\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e1 [0\\u0026ndash;2]\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1 [0\\u0026ndash;2]\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e1 [0\\u0026ndash;3]\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eEtiology\\u003c/p\\u003e \\u003cp\\u003eHypoxic-ischemic encephalopathy\\u003c/p\\u003e \\u003cp\\u003eStroke\\u003c/p\\u003e \\u003cp\\u003eIntracranial hemorrhage\\u003c/p\\u003e \\u003cp\\u003eMeningitis or brain abscess\\u003c/p\\u003e \\u003cp\\u003eTransient metabolic disturbances\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e82 (71%)\\u003c/p\\u003e \\u003cp\\u003e14 (12%)\\u003c/p\\u003e \\u003cp\\u003e10 (8.6%)\\u003c/p\\u003e \\u003cp\\u003e5 (4.3%)\\u003c/p\\u003e \\u003cp\\u003e5 (4.3%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e34 (65%)\\u003c/p\\u003e \\u003cp\\u003e8 (15%)\\u003c/p\\u003e \\u003cp\\u003e3 (5.8%)\\u003c/p\\u003e \\u003cp\\u003e3 (5.8%)\\u003c/p\\u003e \\u003cp\\u003e4 (7.7%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e48 (75%)\\u003c/p\\u003e \\u003cp\\u003e6 (9.4%)\\u003c/p\\u003e \\u003cp\\u003e7 (11%)\\u003c/p\\u003e \\u003cp\\u003e2 (3.1%)\\u003c/p\\u003e \\u003cp\\u003e1 (1.6%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"4\\\"\\u003e\\u003csup\\u003e1\\u003c/sup\\u003eFourteen missing variables (N\\u0026thinsp;=\\u0026thinsp;102)\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e \\u003cdiv id=\\\"Sec4\\\" class=\\\"Section2\\\"\\u003e \\u003ch2\\u003eOutcomes\\u003c/h2\\u003e \\u003cp\\u003eThe percent of infants discharged on ASMs was 69% in epoch 1 versus 34% in epoch 2 (p\\u0026thinsp;\\u0026lt;\\u0026thinsp;0.001); The difference in infants discharged on ASMs between epoch 1 and epoch 2 was larger in infants discharged from delivery NICUs versus the referral NICU. There was an annual decrease in the percent of infants discharged on ASM for both delivery and referral NICUs (Fig.\\u0026nbsp;\\u003cspan refid=\\\"Fig2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e). There was no significant difference between epochs in seizures after discharge by 1 year of age (p\\u0026thinsp;=\\u0026thinsp;0.125). The percent of infants with ASM wean initiated prior to discharge and the total number of ASM at discharge also decreased across epochs (Table\\u0026nbsp;\\u003cspan refid=\\\"Tab2\\\" class=\\\"InternalRef\\\"\\u003e2\\u003c/span\\u003e).\\u003c/p\\u003e \\u003cp\\u003e \\u003c/p\\u003e \\u003cp\\u003e \\u003cdiv class=\\\"gridtable\\\"\\u003e\\u003ctable float=\\\"Yes\\\" id=\\\"Tab2\\\" border=\\\"1\\\"\\u003e \\u003ccaption language=\\\"En\\\"\\u003e \\u003cdiv class=\\\"CaptionNumber\\\"\\u003eTable 2\\u003c/div\\u003e \\u003cdiv class=\\\"CaptionContent\\\"\\u003e \\u003cp\\u003eShort-term Outcomes\\u003c/p\\u003e \\u003c/div\\u003e \\u003c/caption\\u003e \\u003ccolgroup cols=\\\"5\\\"\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c1\\\" colnum=\\\"1\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c2\\\" colnum=\\\"2\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c3\\\" colnum=\\\"3\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c4\\\" colnum=\\\"4\\\"\\u003e\\u003c/div\\u003e \\u003cdiv align=\\\"left\\\" class=\\\"colspec\\\" colname=\\\"c5\\\" colnum=\\\"5\\\"\\u003e\\u003c/div\\u003e \\u003cthead\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eVariable\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003eTotal\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;116)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003eEpoch 1\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;52)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003eEpoch 2\\u003c/p\\u003e \\u003cp\\u003e(N\\u0026thinsp;=\\u0026thinsp;64)\\u003c/p\\u003e \\u003c/th\\u003e \\u003cth align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003eP-value\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003cth align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003ePrimary Outcome\\u003c/p\\u003e \\u003c/th\\u003e \\u003c/tr\\u003e \\u003c/thead\\u003e \\u003ctbody\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDischarged on ASM \\u0026ndash; yes, N (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e58 (50%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e36 (69%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e22 (34%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colspan=\\\"5\\\" nameend=\\\"c5\\\" namest=\\\"c1\\\"\\u003e \\u003cp\\u003e\\u003cb\\u003eSecondary Outcomes\\u003c/b\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eDischarged on ASM \\u0026ndash; yes, N (%)\\u003c/p\\u003e \\u003cp\\u003eDelivery hospital\\u003c/p\\u003e \\u003cp\\u003eReferral hospital\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e26 (53%)\\u003c/p\\u003e \\u003cp\\u003e32 (48%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e18 (78%)\\u003c/p\\u003e \\u003cp\\u003e18 (62%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e8 (31%)\\u003c/p\\u003e \\u003cp\\u003e14 (37%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/p\\u003e \\u003cp\\u003e0.041\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eSeizure after discharge, N (%)\\u003csup\\u003e1\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e24/96 (25%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e15/47 (32%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e9/49 (18%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.125\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eNumber of ASM at discharge per\\u003c/p\\u003e \\u003cp\\u003epatient, N (%)\\u003csup\\u003e2\\u003c/sup\\u003e\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e0.7 (0.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e1.0 (0.9)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e0.4 (0.7)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e\\u0026lt;\\u0026thinsp;0.001\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003ctr\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c1\\\"\\u003e \\u003cp\\u003eASM wean initiated among infants\\u003c/p\\u003e \\u003cp\\u003edischarged on ASM, N (%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c2\\\"\\u003e \\u003cp\\u003e33/58 (57%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c3\\\"\\u003e \\u003cp\\u003e16/36 (44%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c4\\\"\\u003e \\u003cp\\u003e17/22 (77%)\\u003c/p\\u003e \\u003c/td\\u003e \\u003ctd align=\\\"left\\\" colname=\\\"c5\\\"\\u003e \\u003cp\\u003e0.014\\u003c/p\\u003e \\u003c/td\\u003e \\u003c/tr\\u003e \\u003c/tbody\\u003e \\u003c/colgroup\\u003e \\u003ctfoot\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e\\u003csup\\u003e1\\u003c/sup\\u003eTwenty missing variables (N\\u0026thinsp;=\\u0026thinsp;96)\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e\\u003csup\\u003e2\\u003c/sup\\u003eOne missing variable (N\\u0026thinsp;=\\u0026thinsp;115)\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003e\\u003cb\\u003eSupplementary Fig.\\u0026nbsp;1 Summary\\u003c/b\\u003e:\\u003c/td\\u003e\\u003c/tr\\u003e \\u003ctr\\u003e\\u003ctd colspan=\\\"5\\\"\\u003eNeonatal seizure pathway with inclusion of anti-seizure medication weaning protocol. Reflects most current version following three revisions.\\u003c/td\\u003e\\u003c/tr\\u003e \\u003c/tfoot\\u003e \\u003c/table\\u003e\\u003c/div\\u003e \\u003c/p\\u003e \\u003c/div\\u003e\"},{\"header\":\"DISCUSSION\",\"content\":\"\\u003cp\\u003eAmong infants with acute symptomatic seizures in three local hospitals cared for by one provider group, we found that inclusion of an ASM wean protocol in the neonatal seizure pathway decreased the number of infants discharged on ASM, regardless of type of NICU. There was no difference in seizures after discharge between epochs. Among infants with acute symptomatic seizures who were maintained on ASM at discharge, we found more infants had a wean of ASM initiated prior to hospital discharge in epoch 2.\\u003c/p\\u003e \\u003cp\\u003ePrevious studies have shown variation by center in the percent of infants with acute symptomatic seizures discharged on ASM.(\\u003cspan citationid=\\\"CR10\\\" class=\\\"CitationRef\\\"\\u003e10\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR17\\\" class=\\\"CitationRef\\\"\\u003e17\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR18\\\" class=\\\"CitationRef\\\"\\u003e18\\u003c/span\\u003e) Historically our academic provider group working in three local hospitals, or has had a high proportion of infants with seizures discharged on ASM. This was compounded by challenges in obtaining neurology follow-up in a timely manner after discharge, resulting in infants being exposed to prolonged duration of ASM. There was initial hesitation about discontinuing ASM prior to discharge in infants with acute symptomatic seizures due to concerns for risk of seizure recurrence. Our original ASM weaning protocol consisted of a slow wean and repeat EEG, which was necessary to gain support from some of our pediatric neurologists. However, the subsequent publication in 2021 of the comparative effectiveness study from the Neonatal Seizure Registry demonstrating no difference in epilepsy at 24 months among children whose ASM was maintained or discontinued at discharge provided more support to our efforts.(\\u003cspan citationid=\\\"CR14\\\" class=\\\"CitationRef\\\"\\u003e14\\u003c/span\\u003e) Our current study also did not find an increase in seizure after discharge between epochs, although this was limited by loss to follow-up. We subsequently revised our ASM weaning protocol to be more efficient and not reliant upon repeat EEG in October of 2022. In parallel to the inclusion of the ASM weaning protocol in our seizure pathway, neurology also worked to increase clinic capacity to see NICU graduates within one month of discharge .\\u003c/p\\u003e \\u003cp\\u003e Previous work has shown that the development of a neurocritical care program can decrease the percent of infants discharged on ASM.(\\u003cspan citationid=\\\"CR19\\\" class=\\\"CitationRef\\\"\\u003e19\\u003c/span\\u003e, \\u003cspan citationid=\\\"CR20\\\" class=\\\"CitationRef\\\"\\u003e20\\u003c/span\\u003e) Unfortunately these specialized programs are not available at the majority of hospitals caring for infants with seizures. Lack of consultation by pediatric neurologists and limited availability of technical resources further restrict wide-spread applicability of neurocritical care programs.(\\u003cspan citationid=\\\"CR21\\\" class=\\\"CitationRef\\\"\\u003e21\\u003c/span\\u003e) Our study demonstrates that decreasing ASM at discharge does not rely solely on a formal neurocritical care program. Inpatient neurology consults are not available at our delivery hospitals at the time of this publication, yet, through collaboration between divisions and buy-in from key stakeholders, we were still able to improve care for these high-risk infants.\\u003c/p\\u003e \\u003cp\\u003eThe strength of this study is the impact of the implementation of an ASM weaning protocol on the evolution of ASM discontinuation at discharge in infants with acute symptomatic seizures across local hospitals managed by one academic group. Our work highlights opportunities for similar NICUs who may frequently discharge infants with acute symptomatic seizures on ASM. This study has some limitations. Generalizability may be limited as it was a retrospective cohort study across three hospitals covered by the same neonatology and neurology physicians. Additionally, we were not able to control for other factors that may have impacted whether an infant was continued on ASM at discharge. Our study was also limited by loss to follow-up in 17% of our cohort.\\u003c/p\\u003e \\u003cp\\u003eIn conclusion, we found that inclusion of an ASM weaning protocol in a neonatal seizure pathway reduced the percent of infants with acute symptomatic seizures discharged on ASM. This difference was seen at delivery hospitals, in addition to a referral hospital, where inpatient neurology consults were not routinely available. This protocol highlights an opportunity for all NICUs to reduce the percentage of infants discharged on ASM.\\u003c/p\\u003e\"},{\"header\":\"Declarations\",\"content\":\"\\u003cp\\u003e \\u003ch2\\u003eConflicts of Interest:\\u003c/h2\\u003e \\u003cp\\u003eElizabeth Sewell has received consultant fees from Hospicom and Sun Pharmaceutical Industries, Inc. The remaining authors have no conflicts of interest to disclose directly related to this study.\\u003c/p\\u003e \\u003c/p\\u003e\\u003ch2\\u003eFunding:\\u003c/h2\\u003e \\u003cp\\u003eThere were no external sources of funding for this study.\\u003c/p\\u003e\\u003ch2\\u003eAuthor contributions:\\u003c/h2\\u003e \\u003cp\\u003eAMN contributed to the data curation, investigation, and writing of the original manuscript. ZH contributed to the formal analysis and critical review of the final manuscript. ES contributed to the conceptualization, data curation, investigation, methodology, and drafting of the original manuscript. MD, SB, SH, AP, AC, AV, JB, and PJ contributed to the investigation and critical review of the final manuscript.\\u003c/p\\u003e\"},{\"header\":\"References\",\"content\":\"\\u003col\\u003e\\u003cli\\u003e\\u003cspan\\u003eKharoshankaya L, Stevenson NJ, Livingstone V, Murray DM, Murphy BP, Ahearne CE, et al. Seizure burden and neurodevelopmental outcome in neonates with hypoxic\\u0026ndash;ischemic encephalopathy. Developmental Medicine \\u0026amp; Child Neurology. 2016;58(12):1242\\u0026ndash;8.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMcBride MC, Laroia N, Guillet R. Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology. 2000;55(4):506\\u0026ndash;13.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePressler RM, Abend NS, Auvin S, Boylan G, Brigo F, Cilio MR, et al. Treatment of seizures in the neonate: Guidelines and consensus-based recommendations\\u0026mdash;Special report from the ILAE Task Force on Neonatal Seizures. Epilepsia. 2023;64(10):2550\\u0026ndash;70.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002;99(23):15089\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eForcelli PA, Kim J, Kondratyev A, Gale K. Pattern of antiepileptic drug\\u0026ndash;induced cell death in limbic regions of the neonatal rat brain. Epilepsia. 2011;52(12):e207-e11.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eKaushal S, Tamer Z, Opoku F, Forcelli PA. Anticonvulsant drug\\u0026ndash;induced cell death in the developing white matter of the rodent brain. Epilepsia. 2016;57(5):727\\u0026ndash;34.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eFarwell JR, Lee YJ, Hirtz DG, Sulzbacher SI, Ellenberg JH, Nelson KB. Phenobarbital for febrile seizures\\u0026ndash;effects on intelligence and on seizure recurrence. N Engl J Med. 1990;322(6):364\\u0026ndash;9.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSulzbacher S, Farwell JR, Temkin N, Lu AS, Hirtz DG. Late cognitive effects of early treatment with phenobarbital. Clinical pediatrics. 1999;38(7):387\\u0026ndash;94.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eMaitre NL, Smolinsky C, Slaughter JC, Stark AR. Adverse neurodevelopmental outcomes after exposure to phenobarbital and levetiracetam for the treatment of neonatal seizures. Journal of Perinatology. 2013;33(11):841\\u0026ndash;6.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eSewell EK, Shankaran S, McDonald SA, Hamrick S, Wusthoff CJ, Adams-Chapman I, et al. Antiseizure medication at discharge in infants with hypoxic-ischaemic encephalopathy: an observational study. Arch Dis Child Fetal Neonatal Ed. 2023.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eCamfield P, Camfield C. Incidence, prevalence and aetiology of seizures and epilepsy in children. Epileptic Disorders. 2015;17(2):117\\u0026ndash;23.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShellhaas RA, Wusthoff CJ, Numis AL, Chu CJ, Massey SL, Abend NS, et al. Early-life epilepsy after acute symptomatic neonatal seizures: A prospective multicenter study. Epilepsia. 2021;62(8):1871\\u0026ndash;82.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003ePisani F, Facini C, Pavlidis E, Spagnoli C, Boylan G. Epilepsy after neonatal seizures: literature review. Eur J Paediatr Neurol. 2015;19(1):6\\u0026ndash;14.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eGlass HC, Soul JS, Chang T, Wusthoff CJ, Chu CJ, Massey SL, et al. Safety of Early Discontinuation of Antiseizure Medication After Acute Symptomatic Neonatal Seizures. JAMA Neurol. 2021;78(7):817\\u0026ndash;25.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWorld Health Organization. Guidelines on Neonatal Seizures.; 2011.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShellhaas RA, Chang T, Wusthoff CJ, Soul JS, Massey SL, Chu CJ, et al. Treatment duration after acute symptomatic seizures in neonates: a multicenter cohort study. The Journal of pediatrics. 2017;181:298\\u0026ndash;301. e1.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eShellhaas RA, Chang T, Wusthoff CJ, Soul JS, Massey SL, Chu CJ, et al. Treatment Duration After Acute Symptomatic Seizures in Neonates: A Multicenter Cohort Study. J Pediatr. 2017;181:298\\u0026ndash;301.e1.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eDizon MLV, Rao R, Hamrick SE, Zaniletti I, DiGeronimo R, Natarajan G, et al. Practice variation in anti-epileptic drug use for neonatal hypoxic-ischemic encephalopathy among regional NICUs. BMC Pediatr. 2019;19(1):67.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBashir RA, Espinoza L, Vayalthrikkovil S, Buchhalter J, Irvine L, Bello-Espinosa L, et al. Implementation of a Neurocritical Care Program: Improved Seizure Detection and Decreased Antiseizure Medication at Discharge in Neonates With Hypoxic-Ischemic Encephalopathy. Pediatr Neurol. 2016;64:38\\u0026ndash;43.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eWietstock SO, Bonifacio SL, McCulloch CE, Kuzniewicz MW, Glass HC. Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication. J Child Neurol. 2015;30(9):1135\\u0026ndash;41.\\u003c/span\\u003e\\u003c/li\\u003e \\u003cli\\u003e\\u003cspan\\u003eBoylan G, Burgoyne L, Moore C, O'Flaherty B, Rennie J. An international survey of EEG use in the neonatal intensive care unit. Acta Paediatr. 2010;99(8):1150\\u0026ndash;5.\\u003c/span\\u003e\\u003c/li\\u003e\\u003c/ol\\u003e\"}],\"fulltextSource\":\"\",\"fullText\":\"\",\"funders\":[],\"hasAdminPriorityOnWorkflow\":false,\"hasManuscriptDocX\":true,\"hasOptedInToPreprint\":true,\"hasPassedJournalQc\":\"\",\"hasAnyPriority\":false,\"hideJournal\":false,\"highlight\":\"\",\"institution\":\"\",\"isAcceptedByJournal\":true,\"isAuthorSuppliedPdf\":false,\"isDeskRejected\":\"\",\"isHiddenFromSearch\":false,\"isInQc\":false,\"isInWorkflow\":false,\"isPdf\":false,\"isPdfUpToDate\":true,\"isWithdrawnOrRetracted\":false,\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"journal-of-perinatology\",\"isNatureJournal\":false,\"hasQc\":false,\"allowDirectSubmit\":false,\"externalIdentity\":\"jp\",\"sideBox\":\"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)\",\"snPcode\":\"41372\",\"submissionUrl\":\"https://mts-jper.nature.com/cgi-bin/main.plex\",\"title\":\"Journal of Perinatology\",\"twitterHandle\":\"@jperinatology\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"ejp\",\"reportingPortfolio\":\"Nature AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false},\"keywords\":\"\",\"lastPublishedDoi\":\"10.21203/rs.3.rs-4356197/v1\",\"lastPublishedDoiUrl\":\"https://doi.org/10.21203/rs.3.rs-4356197/v1\",\"license\":{\"name\":\"CC BY 4.0\",\"url\":\"https://creativecommons.org/licenses/by/4.0/\"},\"manuscriptAbstract\":\"\\u003cp\\u003e\\u003cstrong\\u003eObjective:\\u003c/strong\\u003e To evaluate the impact of inclusion of an ASM weaning protocol in a neonatal seizure pathway on the percent of infants discharged on ASMs.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eStudy Design:\\u003c/strong\\u003e This cohort study included surviving infants with acute symptomatic seizures treated with ASMs. We evaluated infants in 2 epochs, pre- and post-implementation of the ASM weaning protocol. The primary outcome was discharge on ASM.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eResults:\\u003c/strong\\u003e Of 116 included infants, the percent of infants discharged on ASMs was 69% in epoch 1 versus 34% in epoch 2 (p\\u0026lt;0.001). There was no significant difference between epochs in recurrence of seizures after discharge by 1 year of age (p=0.125). There was an annual decrease in the percent of infants discharged on ASM for both delivery and referral NICUs.\\u003c/p\\u003e\\n\\u003cp\\u003e\\u003cstrong\\u003eConclusion:\\u003c/strong\\u003e Inclusion of a formal ASM weaning protocol as part of an institutional seizure pathway reduced percent of infants with acute symptomatic seizures discharged on ASM.\\u003c/p\\u003e\",\"manuscriptTitle\":\"Reducing the Percent of Surviving Infants with Acute Symptomatic Seizures Discharged on Anti-Seizure Medication\",\"msid\":\"\",\"msnumber\":\"\",\"nonDraftVersions\":[{\"code\":1,\"date\":\"2024-05-10 21:02:06\",\"doi\":\"10.21203/rs.3.rs-4356197/v1\",\"editorialEvents\":[{\"type\":\"communityComments\",\"content\":0},{\"type\":\"decision\",\"content\":\"revise\",\"date\":\"2024-05-24T12:31:59+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorInvitedReview\",\"content\":\"This content is not available.\",\"date\":\"2024-05-23T19:36:29+00:00\",\"index\":2,\"fulltext\":\"This content is not available.\"},{\"type\":\"editorInvitedReview\",\"content\":\"This content is not available.\",\"date\":\"2024-05-23T19:35:42+00:00\",\"index\":1,\"fulltext\":\"This content is not available.\"},{\"type\":\"reviewerAgreed\",\"content\":\"This content is not available.\",\"date\":\"2024-05-15T13:18:38+00:00\",\"index\":2,\"fulltext\":\"This content is not available.\"},{\"type\":\"reviewerAgreed\",\"content\":\"This content is not available.\",\"date\":\"2024-05-05T15:16:53+00:00\",\"index\":1,\"fulltext\":\"This content is not available.\"},{\"type\":\"reviewersInvited\",\"content\":\"\",\"date\":\"2024-05-03T12:14:40+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"checksComplete\",\"content\":\"\",\"date\":\"2024-05-02T09:42:48+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"editorAssigned\",\"content\":\"\",\"date\":\"2024-05-02T00:02:15+00:00\",\"index\":\"\",\"fulltext\":\"\"},{\"type\":\"submitted\",\"content\":\"Journal of Perinatology\",\"date\":\"2024-05-02T00:02:14+00:00\",\"index\":\"\",\"fulltext\":\"\"}],\"status\":\"published\",\"journal\":{\"display\":true,\"email\":\"info@researchsquare.com\",\"identity\":\"journal-of-perinatology\",\"isNatureJournal\":false,\"hasQc\":false,\"allowDirectSubmit\":false,\"externalIdentity\":\"jp\",\"sideBox\":\"Learn more about [Journal of Perinatology](http://www.nature.com/jp/)\",\"snPcode\":\"41372\",\"submissionUrl\":\"https://mts-jper.nature.com/cgi-bin/main.plex\",\"title\":\"Journal of Perinatology\",\"twitterHandle\":\"@jperinatology\",\"acdcEnabled\":true,\"dfaEnabled\":true,\"editorialSystem\":\"ejp\",\"reportingPortfolio\":\"Nature AJ\",\"inReviewEnabled\":true,\"inReviewRevisionsEnabled\":false}}],\"origin\":\"\",\"ownerIdentity\":\"fa762fec-5783-45df-846b-d8f33924a43a\",\"owner\":[],\"postedDate\":\"May 10th, 2024\",\"published\":true,\"recentEditorialEvents\":[],\"rejectedJournal\":[],\"revision\":\"\",\"amendment\":\"\",\"status\":\"published-in-journal\",\"subjectAreas\":[{\"id\":31479164,\"name\":\"Health sciences/Diseases/Neurological disorders/Brain injuries\"},{\"id\":31479165,\"name\":\"Health sciences/Health care/Therapeutics/Drug therapy\"},{\"id\":31479167,\"name\":\"Health sciences/Diseases/Neurological disorders/Paediatric neurological disorders\"}],\"tags\":[],\"updatedAt\":\"2024-07-24T07:07:41+00:00\",\"versionOfRecord\":{\"articleIdentity\":\"rs-4356197\",\"link\":\"https://doi.org/10.1038/s41372-024-02044-9\",\"journal\":{\"identity\":\"journal-of-perinatology\",\"isVorOnly\":false,\"title\":\"Journal of Perinatology\"},\"publishedOn\":\"2024-07-23 04:00:00\",\"publishedOnDateReadable\":\"July 23rd, 2024\"},\"versionCreatedAt\":\"2024-05-10 21:02:06\",\"video\":\"\",\"vorDoi\":\"10.1038/s41372-024-02044-9\",\"vorDoiUrl\":\"https://doi.org/10.1038/s41372-024-02044-9\",\"workflowStages\":[]},\"version\":\"v1\",\"identity\":\"rs-4356197\",\"journalConfig\":\"researchsquare\"},\"__N_SSP\":true},\"page\":\"/article/[identity]/[[...version]]\",\"query\":{\"redirect\":\"/article/rs-4356197\",\"identity\":\"rs-4356197\",\"version\":[\"v1\"]},\"buildId\":\"8U1c8b4HqxoKbykW_rLl7\",\"isFallback\":false,\"isExperimentalCompile\":false,\"dynamicIds\":[84888],\"gssp\":true,\"scriptLoader\":[]}","source_license":"CC-BY-4.0","license_restricted":false}