Febrile Seizures: An Updated Narrative Review for Pediatric Ambulatory
Care Providers

James   Sze-Chuck   Leung
Abstract

Background: While generally self-limited, febrile seizures result in significant familial distress. Ambulatory pediatric care providers must be prepared to counsel families on the causes, risk factors, management principles, and prognosis of children with febrile seizures.
Objective: To provide an updated, evidence-based review of febrile seizures focused on the needs of an ambulatory pediatric care provider.
Methods: A narrative review of the literature prioritizing landmark articles, metanalyses, longitudinal population longitudinal cohort studies and national level guidelines.
Results: Febrile seizures are aberrant physiological responses to fever in children caused by complex interactions of cytokine mediated neuroinflammation, environmental triggers, and genetic predisposition. Other than investigations to determine fever etiology, routine bloodwork, lumbar punctures, neuroimaging and electroencephalograms are low yield. The general prognosis is excellent, however, clinicians should be aware of long-term outcomes including: cognitive impairment with non-simple febrile seizures; neuropsychiatric associations; recurrent febrile seizure and epilepsy risk factors; and the association between complex febrile seizures and sudden unexpected death. Children with a high risk of recurrence, complex febrile seizures, limited access to care, or extreme parental anxiety may benefit from intermittent oral diazepam prophylaxis.
Conclusion: Clinicians should consider four management priorities: 1) terminating the seizure; 2) excluding critical differential diagnoses; 3) investigating fever etiology; and 4) providing adequate counselling to families. The clinical approach and prognosis of febrile seizure can be based on subtype. Children with non-simple (i.e. complex or febrile status epilepticus) febrile seizures require closer care than the vast majority of children with simple febrile seizures, who have excellent outcomes.
Keywords: Febrile Seizures, Febrile Convulsions, Status Epilepticus, Prognosis, Counseling, Recurrence, Epilepsy
Graphical Abstract

[1]
Rice SA, Müller RM, Jeschke S, Herziger B, Bertsche T, Neininger MP. Febrile seizures: perceptions and knowledge of parents of affected and unaffected children. Eur J Pediatr  2022; 181(4): 1487-95.
 [PMID:  34873647]

[2]
Shinnar RC, Shinnar S, Hesdorffer DC, et al. Parental stress, pediatric quality of life, and behavior at baseline and one-year follow-up: Results from the FEBSTAT study. Epilepsy Behav  2017; 69: 95-9.
 [http://dx.doi.org/10.1016/j.yebeh.2017.01.024] [PMID:  28236729]

[3]
Mewasingh LD, Chin RFM, Scott RC. Current understanding of febrile seizures and their long‐term outcomes. Dev Med Child Neurol  2020; 62(11): 1245-9.
 [http://dx.doi.org/10.1111/dmcn.14642] [PMID:  32748466]

[4]
Subcommittee on Febrile Seizures; American Academy of Pediatrics. Neurodiagnostic evaluation of the child with a simple febrile seizure. Pediatrics  2011; 127(2): 389-94.
 [http://dx.doi.org/10.1542/peds.2010-3318] [PMID:  21285335]

[5]
Wilmshurst JM, Gaillard WD, Vinayan KP, et al. Summary of recommendations for the management of infantile seizures: Task Force Report for the ILAE Commission of Pediatrics. Epilepsia  2015; 56(8): 1185-97.
 [http://dx.doi.org/10.1111/epi.13057] [PMID:  26122601]

[6]
Nelson KB, Ellenberg JH. Predictors of epilepsy in children who have experienced febrile seizures. N Engl J Med  1976; 295(19): 1029-33.
 [http://dx.doi.org/10.1056/NEJM197611042951901] [PMID:  972656]

[7]
Leung AKC, Hon KL, Leung TNH. Febrile seizures: An overview. Drugs Context  2018; 7: 1-12.
 [http://dx.doi.org/10.7573/dic.212536] [PMID:  30038660]

[8]
Mewasingh LD. Febrile seizures. BMJ Clin Evid  2014; 2014: 0324.

[9]
Hauser WA. The prevalence and incidence of convulsive disorders in children. Epilepsia  1994; 35 (Suppl. 2): S1-6.
 [http://dx.doi.org/10.1111/j.1528-1157.1994.tb05932.x] [PMID:  8275976]

[10]
Veisani Y, Delpisheh A, Sayehmiri K. Familial history and recurrence of febrile seizures; A systematic review and meta-analysis. Iran J Pediatr  2013; 23(4): 389-95.
 [PMID:  24427491]

[11]
Choi YJ, Jung JY, Kim JH, et al. Febrile seizures: Are they truly benign? Longitudinal analysis of risk factors and future risk of afebrile epileptic seizure based on the national sample cohort in South Korea, 2002-2013. Seizure  2019; 64: 77-83.
 [http://dx.doi.org/10.1016/j.seizure.2018.12.004] [PMID:  30594055]

[12]
Ogihara M, Shirakawa S, Miyajima T, Takekuma K, Hoshika A. Diurnal variation in febrile convulsions. Pediatr Neurol  2010; 42(6): 409-12.
 [http://dx.doi.org/10.1016/j.pediatrneurol.2010.02.011] [PMID:  20472192]

[13]
Sugai K. Current management of febrile seizures in Japan: An overview. Brain Dev  2010; 32(1): 64-70.
 [http://dx.doi.org/10.1016/j.braindev.2009.09.019] [PMID:  19853393]

[14]
Vestergaard M, Christensen J. Register-based studies on febrile seizures in Denmark. Brain Dev  2009; 31(5): 372-7.
 [http://dx.doi.org/10.1016/j.braindev.2008.11.012] [PMID:  19203855]

[15]
Millichap JJ, Millichap JG. Methods of investigation and management of infections causing febrile seizures. Pediatr Neurol  2008; 39(6): 381-6.
 [http://dx.doi.org/10.1016/j.pediatrneurol.2008.07.017] [PMID:  19027582]

[16]
Sharafi R, Hassanzadeh RA, Aminzadeh V. Circadian rhythm and the seasonal variation in childhood febrile seizure. Iran J Child Neurol  2017; 11(3): 27-30.
 [PMID:  28883873]

[17]
Mikkonen K, Uhari M, Pokka T, Rantala H. Diurnal and seasonal occurrence of febrile seizures. Pediatr Neurol  2015; 52(4): 424-7.
 [http://dx.doi.org/10.1016/j.pediatrneurol.2015.01.001] [PMID:  25682483]

[18]
Chung S. Febrile seizures. Korean J Pediatr  2014; 57(9): 384-95.
 [http://dx.doi.org/10.3345/kjp.2014.57.9.384] [PMID:  25324864]

[19]
Hall CB, Long CE, Schnabel KC, et al. Human herpesvirus-6 infection in children. A prospective study of complications and reactivation. N Engl J Med  1994; 331(7): 432-8.
 [http://dx.doi.org/10.1056/NEJM199408183310703] [PMID:  8035839]

[20]
Chiu SS, Tse CYC, Lau YL, Peiris ML. A infection is an important cause of febrile seizures. Pediatrics  2001; 108(4): e63.
 [http://dx.doi.org/10.1542/peds.108.4.e63] [PMID:  11581471]

[21]
Millichap JG, Millichap JJ. Role of viral infections in the etiology of febrile seizures. Pediatr Neurol  2006; 35(3): 165-72.
 [http://dx.doi.org/10.1016/j.pediatrneurol.2006.06.004] [PMID:  16939854]

[22]
Li X, Lin Y, Yao G, Wang Y. The influence of vaccine on febrile seizure. Curr Neuropharmacol  2018; 16(1): 59-65.
 [PMID:  28745219]

[23]
Barlow WE, Davis RL, Glasser JW, et al. The risk of seizures after receipt of whole-cell pertussis or measles, mumps, and rubella vaccine. N Engl J Med  2001; 345(9): 656-61.
 [http://dx.doi.org/10.1056/NEJMoa003077] [PMID:  11547719]

[24]
Klein NP, Lewis E, Fireman B, et al. Safety of measles-containing vaccines in 1-year-old children. Pediatrics  2015; 135(2): e321-9.
 [http://dx.doi.org/10.1542/peds.2014-1822] [PMID:  25560438]

[25]
Marin M, Broder KR, Temte JL, Snider DE, Seward JF. Use of combination measles, mumps, rubella, and varicella vaccine: Recommendations of the Advisory Committee on Immunization Practices (ACIP). MMWR Recomm Rep  2010; 59(RR-3): 1-12.
 [PMID:  20448530]

[26]
Kawai AT, Martin D, Kulldorff M, et al. Febrile seizures after 2010-2011 trivalent inactivated influenza vaccine. Pediatrics  2015; 136(4): e848-55.
 [http://dx.doi.org/10.1542/peds.2015-0635] [PMID:  26371192]

[27]
Martin D, Menschik D, Bryant-Genevier M, Ball R. Data mining for prospective early detection of safety signals in the Vaccine Adverse Event Reporting System (VAERS): A case study of febrile seizures after a 2010-2011 seasonal influenza virus vaccine. Drug Saf  2013; 36(7): 547-56.
 [http://dx.doi.org/10.1007/s40264-013-0051-9] [PMID:  23657824]

[28]
Baker MA, Jankosky C, Yih WK, et al. The risk of febrile seizures following influenza and 13-valent pneumococcal conjugate vaccines. Vaccine  2020; 38(9): 2166-71.
 [http://dx.doi.org/10.1016/j.vaccine.2020.01.046] [PMID:  32019703]

[29]
Sun Y, Christensen J, Hviid A, et al. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B. JAMA  2012; 307(8): 823-31.
 [http://dx.doi.org/10.1001/jama.2012.165] [PMID:  22357833]

[30]
Duffy J, Weintraub E, Hambidge SJ, et al. Febrile seizure risk after vaccination in children 6 to 23 months. Pediatrics  2016; 138(1): e20160320.
 [http://dx.doi.org/10.1542/peds.2016-0320] [PMID:  27273711]

[31]
Rosenthal S, Chen R, Hadler S. The safety of acellular pertussis vaccine vs whole-cell pertussis vaccine. A postmarketing assessment. Arch Pediatr Adolesc Med  1996; 150(5): 457-60.
 [http://dx.doi.org/10.1001/archpedi.1996.02170300011001] [PMID:  8620224]

[32]
Rowhani-Rahbar A, Fireman B, Lewis E, et al. Effect of age on the risk of Fever and seizures following immunization with measles-containing vaccines in children. JAMA Pediatr  2013; 167(12): 1111-7.
 [http://dx.doi.org/10.1001/jamapediatrics.2013.2745] [PMID:  24126936]

[33]
Sawyer MH, Simon G, Byington C. Vaccines and febrile seizures: Quantifying the risk. Pediatrics  2016; 138(1): e20160976.
 [http://dx.doi.org/10.1542/peds.2016-0976] [PMID:  27273713]

[34]
 Canada PHA of. Contraindications and precautions: Canadian Immunization Guide. 2007. Available from: https://www.canada.ca/en/public-health/services/publications/healthy-living/canadian-immunization-guide-part-2-vaccine-safety/page-3-contraindications-precautions-concerns.html

[35]
Ray P, Hayward J, Michelson D, et al. Encephalopathy after whole-cell pertussis or measles vaccination: Lack of evidence for a causal association in a retrospective case-control study. Pediatr Infect Dis J  2006; 25(9): 768-73.
 [http://dx.doi.org/10.1097/01.inf.0000234067.84848.e1] [PMID:  16940831]

[36]
Reyes IS, Hsieh DT, Laux LC, Wilfong AA. Alleged cases of vaccine encephalopathy rediagnosed years later as Dravet syndrome. Pediatrics  2011; 128(3): e699-702.
 [http://dx.doi.org/10.1542/peds.2010-0887] [PMID:  21844054]

[37]
Brown NJ, Berkovic SF, Scheffer IE. Vaccination, seizures and ‘vaccine damage’. Curr Opin Neurol  2007; 20(2): 181-7.
 [http://dx.doi.org/10.1097/WCO.0b013e3280555160] [PMID:  17351489]

[38]
Bartolini L, Moran MP, Norato G, et al. Differential activation of neuroinflammatory pathways in children with seizures: A cross-sectional study. Seizure  2021; 91: 150-8.
 [http://dx.doi.org/10.1016/j.seizure.2021.05.022] [PMID:  34161903]

[39]
Mosili P, Maikoo S, Mabandla MV, Qulu L. The pathogenesis of fever-induced febrile seizures and its current state. Neuroscience Insights  2020; 15: 2633105520956973.
 [http://dx.doi.org/10.1177/2633105520956973] [PMID:  33225279]

[40]
Vezzani A, French J, Bartfai T, Baram TZ. The role of inflammation in epilepsy. Nat Rev Neurol  2011; 7(1): 31-40.
 [http://dx.doi.org/10.1038/nrneurol.2010.178] [PMID:  21135885]

[41]
Kwon A, Kwak BO, Kim K, et al. Cytokine levels in febrile seizure patients: A systematic review and meta-analysis. Seizure  2018; 59: 5-10.
 [http://dx.doi.org/10.1016/j.seizure.2018.04.023] [PMID:  29727742]

[42]
Iwasaki N, Nakayama J, Hamano K, Matsui A, Arinami T. Molecular genetics of febrile seizures. Epilepsia  2002; 43 (Suppl. 9): 32-5.
 [http://dx.doi.org/10.1046/j.1528-1157.43.s.9.8.x] [PMID:  12383277]

[43]
Nakayama J. Progress in searching for the febrile seizure susceptibility genes. Brain Dev  2009; 31(5): 359-65.
 [http://dx.doi.org/10.1016/j.braindev.2008.11.014] [PMID:  19201561]

[44]
Bethune P, Gordon K, Dooley J, Camfield C, Camfield P. Which child will have a febrile seizure? Am J Dis Child  1960; 147(1): 35-9.

[45]
Berg AT, Shinnar S, Shapiro ED, Salomon ME, Crain EF, Hauser WA. Risk factors for a first febrile seizure: A matched case-control study. Epilepsia  1995; 36(4): 334-41.
 [http://dx.doi.org/10.1111/j.1528-1157.1995.tb01006.x] [PMID:  7541745]

[46]
Berg AT. Are febrile seizures provoked by a rapid rise in temperature? Am J Dis Child  1960; 147(10): 1101-3.

[47]
Christensen KJ, Dreier JW, Skotte L, et al. Birth characteristics and risk of febrile seizures. Acta Neurol Scand  2021; 144(1): 51-7.
 [http://dx.doi.org/10.1111/ane.13420] [PMID:  33822360]

[48]
Tu YF, Wang LW, Wang ST, Yeh TF, Huang CC. Postnatal steroids and febrile seizure susceptibility in preterm children. Pediatrics  2016; 137(4): e20153404.
 [http://dx.doi.org/10.1542/peds.2015-3404] [PMID:  27012746]

[49]
Vestergaard M, Wisborg K, Henriksen TB, Secher NJ, Østergaard JR, Olsen J. Prenatal exposure to cigarettes, alcohol, and coffee and the risk for febrile seizures. Pediatrics  2005; 116(5): 1089-94.
 [http://dx.doi.org/10.1542/peds.2004-2210] [PMID:  16263994]

[50]
Gholipoor P, Saboory E, Ghazavi A, et al. Prenatal stress potentiates febrile seizure and leads to long-lasting increase in cortisol blood levels in children under 2 years old. Epilepsy Behav  2017; 72: 22-7.
 [http://dx.doi.org/10.1016/j.yebeh.2017.04.021] [PMID:  28570964]

[51]
Hjortebjerg D, Nybo AAM, Ketzel M, Raaschou-Nielsen O, Sørensen M. Exposure to traffic noise and air pollution and risk for febrile seizure: A cohort study. Scand J Work Environ Health  2018; 44(5): 539-46.
 [http://dx.doi.org/10.5271/sjweh.3724] [PMID:  29574476]

[52]
Kwak BO, Kim K, Kim SN, Lee R. Relationship between iron deficiency anemia and febrile seizures in children: A systematic review and meta-analysis. Seizure  2017; 52: 27-34.
 [http://dx.doi.org/10.1016/j.seizure.2017.09.009] [PMID:  28957722]

[53]
Heydarian F, Nakhaei AA, Majd HM, Bakhtiari E. Zinc deficiency and febrile seizure: A systematic review and meta-analysis. Turk J Pediatr  2020; 62(3): 347-58.
 [http://dx.doi.org/10.24953/turkjped.2020.03.001] [PMID:  32558408]

[54]
Foster M, Samman S. Zinc and regulation of inflammatory cytokines: Implications for cardiometabolic disease. Nutrients  2012; 4(7): 676-94.
 [http://dx.doi.org/10.3390/nu4070676] [PMID:  22852057]

[55]
Patel AD, Vidaurre J. Complex febrile seizures: A practical guide to evaluation and treatment. J Child Neurol  2013; 28(6): 762-7.
 [http://dx.doi.org/10.1177/0883073813483569] [PMID:  23576415]

[56]
Annegers JF, Hauser WA, Shirts SB, Kurland LT. Factors prognostic of unprovoked seizures after febrile convulsions. N Engl J Med  1987; 316(9): 493-8.
 [http://dx.doi.org/10.1056/NEJM198702263160901] [PMID:  3807992]

[57]
Verity CM, Ross EM, Golding J. Outcome of childhood status epilepticus and lengthy febrile convulsions: Findings of national cohort study. BMJ  1993; 307(6898): 225-8.
 [http://dx.doi.org/10.1136/bmj.307.6898.225] [PMID:  8369681]

[58]
Patterson KP, Baram TZ, Shinnar S. Origins of temporal lobe epilepsy: Febrile seizures and febrile status epilepticus. Neurotherapeutics  2014; 11(2): 242-50.
 [http://dx.doi.org/10.1007/s13311-014-0263-4] [PMID:  24604424]

[59]
Hesdorffer DC, Shinnar S, Lewis DV, et al. Risk factors for febrile status epilepticus: A case-control study. J Pediatr  2013; 163(4): 1147-51.e1.
 [http://dx.doi.org/10.1016/j.jpeds.2013.05.038] [PMID:  23809042]

[60]
Loddenkemper T. Febrile status epilepticus: Time is of the essence. Epilepsy Curr  2014; 14(6): 345-7.
 [http://dx.doi.org/10.5698/1535-7597-14.6.345] [PMID:  25678870]

[61]
Korff CM, Nordli DR Jr. Diagnosis and management of nonconvulsive status epilepticus in children. Nat Clin Pract Neurol  2007; 3(9): 505-16.
 [http://dx.doi.org/10.1038/ncpneuro0605] [PMID:  17805245]

[62]
Hirsch LJ, Gaspard N, van Baalen A, et al. Proposed consensus definitions for new-onset refractory status epilepticus (NORSE), febrile infection-related epilepsy syndrome (FIRES), and related conditions. Epilepsia  2018; 59(4): 739-44.
 [http://dx.doi.org/10.1111/epi.14016] [PMID:  29399791]

[63]
Smith DK, Sadler KP, Benedum M. Febrile seizures: Risks, evaluation, and prognosis. Am Fam Physician  2019; 99(7): 445-50.
 [PMID:  30932454]

[64]
Baumer JH. Evidence based guideline for post-seizure management in children presenting acutely to secondary care. Arch Dis Child  2004; 89(3): 278-80.
 [http://dx.doi.org/10.1136/adc.2003.044743] [PMID:  14977713]

[65]
Trainor JL, Hampers LC, Krug SE, Listernick R. Children with first-time simple febrile seizures are at low risk of serious bacterial illness. Acad Emerg Med  2001; 8(8): 781-7.
 [http://dx.doi.org/10.1111/j.1553-2712.2001.tb00207.x] [PMID:  11483452]

[66]
Shaikh N, Morone NE, Bost JE, Farrell MH. Prevalence of urinary tract infection in childhood: A meta-analysis. Pediatr Infect Dis J  2008; 27(4): 302-8.
 [http://dx.doi.org/10.1097/INF.0b013e31815e4122] [PMID:  18316994]

[67]
Mahyar A, Ayazi P, Azimi E, Dalirani R, Barikani A, Esmaeily S. The relation between urinary tract infection and febrile seizure. Iran J Child Neurol  2018; 12(4): 120-6.
 [PMID:  30279715]

[68]
Najaf-Zadeh A, Dubos F, Hue V, Pruvost I, Bennour A, Martinot A. Risk of bacterial meningitis in young children with a first seizure in the context of fever: A systematic review and meta-analysis. PLoS One  2013; 8(1): e55270.
 [http://dx.doi.org/10.1371/journal.pone.0055270] [PMID:  23383133]

[69]
Boyle DA, Sturm JJ. Clinical factors associated with invasive testing and imaging in patients with complex febrile seizures. Pediatr Emerg Care  2013; 29(4): 430-4.
 [http://dx.doi.org/10.1097/PEC.0b013e318289e8f1] [PMID:  23528503]

[70]
 Choosing Wisely. AAP - Neuroimaging for Febrile Seizure. 2013. Available from: https://www.choosingwisely.org/clinician-lists/american-academy-pediatrics-neuroimaging-for-simple-febrile-seizure/

[71]
Kimia A, Ben-Joseph EP, Rudloe T, et al. Yield of lumbar puncture among children who present with their first complex febrile seizure. Pediatrics  2010; 126(1): 62-9.
 [http://dx.doi.org/10.1542/peds.2009-2741] [PMID:  20566610]

[72]
Kimia AA, Ben-Joseph E, Prabhu S, et al. Yield of emergent neuroimaging among children presenting with a first complex febrile seizure. Pediatr Emerg Care  2012; 28(4): 316-21.
 [http://dx.doi.org/10.1097/PEC.0b013e31824d8b0b] [PMID:  22453723]

[73]
Harini C, Nagarajan E, Kimia AA, de Carvalho RM, An S, Bergin AM. Utility of initial EEG in first complex febrile seizure. Epilepsy Behav EB  2015; 52(Pt A): 200-4.
 [http://dx.doi.org/10.1016/j.yebeh.2015.09.003]

[74]
Shah PB, James S, Elayaraja S. EEG for children with complex febrile seizures. Cochrane Libr  2020; 2020(4): CD009196.
 [http://dx.doi.org/10.1002/14651858.CD009196.pub5] [PMID:  32270497]

[75]
Baumer JH, David TJ, Valentine SJ, Roberts JE, Hughes BR. Many parents think their child is dying when having a first febrile convulsion. Dev Med Child Neurol  1981; 23(5): 462-4.
 [http://dx.doi.org/10.1111/j.1469-8749.1981.tb02019.x] [PMID:  7274593]

[76]
Shuper A, Gabbay U, Mimouni M. Parental anxiety in febrile convulsions. Isr J Med Sci  1996; 32(12): 1282-5.
 [PMID:  9007172]

[77]
Wirrell E, Turner T. Parental anxiety and family disruption following a first febrile seizure in childhood. Paediatr Child Health  2001; 6(3): 139-43.
 [http://dx.doi.org/10.1093/pch/6.3.139] [PMID:  20084226]

[78]
Huang MC, Liu CC, Huang CC. Effects of an educational program on parents with febrile convulsive children. Pediatr Neurol  1998; 18(2): 150-5.
 [http://dx.doi.org/10.1016/S0887-8994(97)00171-9] [PMID:  9535301]

[79]
Capovilla G, Mastrangelo M, Romeo A, Vigevano F. Recommendations for the management of “febrile seizures” Ad hoc Task Force of LICE Guidelines Commission. Epilepsia  2009; 50 (Suppl. 1): 2-6.
 [http://dx.doi.org/10.1111/j.1528-1167.2008.01963.x] [PMID:  19125841]

[80]
Natsume J, Hamano S, Iyoda K, et al. New guidelines for management of febrile seizures in Japan. Brain Dev  2017; 39(1): 2-9.
 [http://dx.doi.org/10.1016/j.braindev.2016.06.003] [PMID:  27613077]

[81]
 Canadian Paediatric Society. Emergency management of the paediatric patient with convulsive status epilepticus. 2021, Available from: https://www.cps.ca/en/documents//position//emergency-man-agement-of-the-paediatric-patient-with-convulsive-status-epilepticus/

[82]
 Febrile Status Epilepticus. 2021. Available from: https://trekk.ca/resources?tag_id=D003294

[83]
Olson H, Rudloe T, Loddenkemper T, Harper MB, Kimia AA. Should patients with complex febrile seizure be admitted for further management? Am J Emerg Med  2018; 36(8): 1386-90.
 [http://dx.doi.org/10.1016/j.ajem.2017.12.059] [PMID:  29317153]

[84]
Mccrorie K, Thorburn J, Symonds J, Turner SW. Falling admissions to hospital with febrile seizures in the UK. Arch Dis Child  2019; 104(8): 750-4.
 [http://dx.doi.org/10.1136/archdischild-2018-316228] [PMID:  30926585]

[85]
Kannikeswaran N, Sivaswamy L, Farooqi A, Sethuraman U. Children with complex febrile seizures: Is hospital admission necessary? Clin Pediatr  2021; 60(8): 363-9.
 [http://dx.doi.org/10.1177/00099228211017702] [PMID:  34014115]

[86]
Kanemura H, Sano F, Mizorogi S, Tando T, Sugita K, Aihara M. Parental thoughts and actions regarding their child’s first febrile seizure. Pediatr Int  2013; 55(3): 315-9.
 [http://dx.doi.org/10.1111/ped.12058] [PMID:  23360347]

[87]
 OCEBM Levels of Evidence Working Group. The Oxford 2011 Levels of Evidence. 2011. Available from: https://www.cebm.ox.ac.uk/resources/levels-of-evidence/ocebm-levels-of-evidence

[88]
Rosenbloom E, Finkelstein Y, Adams-Webber T, Kozer E. Do antipyretics prevent the recurrence of febrile seizures in children? A systematic review of randomized controlled trials and meta-analysis. Eur J Paediatr Neurol  2013; 17(6): 585-8.
 [http://dx.doi.org/10.1016/j.ejpn.2013.04.008] [PMID:  23702315]

[89]
Hashimoto R, Suto M, Tsuji M, et al. Use of antipyretics for preventing febrile seizure recurrence in children: A systematic review and meta-analysis. Eur J Pediatr  2021; 180(4): 987-97.
 [http://dx.doi.org/10.1007/s00431-020-03845-8] [PMID:  33125519]

[90]
Offringa M, Newton R, Cozijnsen MA, Nevitt SJ. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev  2017; 2(2): CD003031.
 [http://dx.doi.org/10.1002/14651858.CD003031.pub3] [PMID:  28225210]

[91]
Offringa M, Newton R, Nevitt SJ, Vraka K. Prophylactic drug management for febrile seizures in children. Cochrane Database Syst Rev  2021; 6: CD003031.
 [http://dx.doi.org/10.1002/14651858.CD003031.pub4] [PMID:  34131913]

[92]
Verity CM, Greenwood R, Golding J. Long-term intellectual and behavioral outcomes of children with febrile convulsions. N Engl J Med  1998; 338(24): 1723-8.
 [http://dx.doi.org/10.1056/NEJM199806113382403] [PMID:  9624192]

[93]
Chungath M, Shorvon S. The mortality and morbidity of febrile seizures. Nat Clin Pract Neurol  2008; 4(11): 610-21.
 [http://dx.doi.org/10.1038/ncpneuro0922] [PMID:  18978801]

[94]
Sillanpää M, Camfield P, Camfield C, et al. Incidence of febrile seizures in Finland: prospective population-based study. Pediatr Neurol  2008; 38(6): 391-4.
 [http://dx.doi.org/10.1016/j.pediatrneurol.2008.02.006] [PMID:  18486819]

[95]
Nishiyama M, Yamaguchi H, Ishida Y, et al. Seizure prevalence in children aged up to 3 years: A longitudinal population-based cohort study in Japan. BMJ Open  2020; 10(9): e035977.
 [http://dx.doi.org/10.1136/bmjopen-2019-035977] [PMID:  32912975]

[96]
Lee WL. Long-term outcome of children with febrile seizures. Ann Acad Med Singap  1989; 18(1): 32-4.
 [PMID:  2653172]

[97]
Chang YC, Guo NW, Huang CC, Wang ST, Tsai JJ. Neurocognitive attention and behavior outcome of school-age children with a history of febrile convulsions: A population study. Epilepsia  2000; 41(4): 412-20.
 [http://dx.doi.org/10.1111/j.1528-1157.2000.tb00182.x] [PMID:  10756406]

[98]
Leaffer EB, Hinton VJ, Hesdorffer DC. Longitudinal assessment of skill development in children with first febrile seizure. Epilepsy Behav  2013; 28(1): 83-7.
 [http://dx.doi.org/10.1016/j.yebeh.2013.03.034] [PMID:  23669493]

[99]
Shinnar S, Pellock JM, Berg AT, et al. Short-term outcomes of children with febrile status epilepticus. Epilepsia  2001; 42(1): 47-53.
 [http://dx.doi.org/10.1046/j.1528-1157.2001.10000.x] [PMID:  11207784]

[100]
Scott RC, King MD, Gadian DG, Neville BGR, Connelly A. Hippocampal abnormalities after prolonged febrile convulsion: A longitudinal MRI study. Brain  2003; 126(11): 2551-7.
 [http://dx.doi.org/10.1093/brain/awg262] [PMID:  12937081]

[101]
Lewis DV, Shinnar S, Hesdorffer DC, et al. Hippocampal sclerosis after febrile status epilepticus: The FEBSTAT study. Ann Neurol  2014; 75(2): 178-85.
 [http://dx.doi.org/10.1002/ana.24081] [PMID:  24318290]

[102]
Martinos MM, Yoong M, Patil S, et al. Early developmental outcomes in children following convulsive status epilepticus: A longitudinal study. Epilepsia  2013; 54(6): 1012-9.
 [http://dx.doi.org/10.1111/epi.12136] [PMID:  23566067]

[103]
Martinos MM, Pujar S, O’Reilly H, et al. Intelligence and memory outcomes within 10 years of childhood convulsive status epilepticus. Epilepsy Behav  2019; 95: 18-25.
 [http://dx.doi.org/10.1016/j.yebeh.2019.03.039] [PMID:  31009825]

[104]
Nilsson G, Westerlund J, Fernell E, Billstedt E, Miniscalco C, Arvidsson T. Neurodevelopmental problems should be considered in children with febrile seizures. Acta Paediatr Oslo Nor  1992; 108(8): 1507-14.

[105]
Billstedt E, Nilsson G, Leffler L, Carlsson L, Olsson I, Fernell E. Cognitive functioning in a representative cohort of preschool children with febrile seizures. Acta Paediatr Oslo Nor  1992; 109(5): 989-94.

[106]
Tsai ML, Hung KL, Tsan YY, Tung WTH. Long-term neurocognitive outcome and auditory event-related potentials after complex febrile seizures in children. Epilepsy Behav  2015; 47: 55-60.
 [http://dx.doi.org/10.1016/j.yebeh.2015.04.067] [PMID:  26043164]

[107]
Sheppard E, Lalancette E, Thébault-Dagher F, et al. Cognitive and behavioural development in children presenting with complex febrile seizures: At onset and school age. Epileptic Disord  2021; 23(2): 325-36.
 [http://dx.doi.org/10.1684/epd.2021.1260] [PMID:  33814363]

[108]
Adachi S, Inoue M, Kawakami I, Koga H. Short-term neurodevelopmental outcomes of focal febrile seizures. Brain Dev  2020; 42(4): 342-7.
 [http://dx.doi.org/10.1016/j.braindev.2020.01.005] [PMID:  32019687]

[109]
Vestergaard M, Pedersen CB, Christensen J, Madsen KM, Olsen J, Mortensen PB. Febrile seizures and risk of schizophrenia. Schizophr Res  2005; 73(2-3): 343-9.
 [http://dx.doi.org/10.1016/j.schres.2004.07.004] [PMID:  15653280]

[110]
Dreier JW, Li J, Sun Y, Christensen J. Evaluation of long-term risk of epilepsy, psychiatric disorders, and mortality among children with recurrent febrile seizures. JAMA Pediatr  2019; 173(12): 1164-70.
 [http://dx.doi.org/10.1001/jamapediatrics.2019.3343] [PMID:  31589251]

[111]
Offringa M, Bossuyt PMM, Lubsen J, et al. Risk factors for seizure recurrence in children with febrile seizures: A pooled analysis of individual patient data from five studies. J Pediatr  1994; 124(4): 574-84.
 [http://dx.doi.org/10.1016/S0022-3476(05)83136-1] [PMID:  8151472]

[112]
Berg AT, Shinnar S, Hauser WA, et al. A prospective study of recurrent febrile seizures. N Engl J Med  1992; 327(16): 1122-7.
 [http://dx.doi.org/10.1056/NEJM199210153271603] [PMID:  1528207]

[113]
Berg AT, Shinnar S, Hauser WA, Leventhal JM. Predictors of recurrent febrile seizures: A metaanalytic review. J Pediatr  1990; 116(3): 329-37.
 [http://dx.doi.org/10.1016/S0022-3476(05)82816-1] [PMID:  2137875]

[114]
Berg AT, Shinnar S, Darefsky AS, et al. Predictors of recurrent febrile seizures. A prospective cohort study. Arch Pediatr Adolesc Med  1997; 151(4): 371-8.
 [http://dx.doi.org/10.1001/archpedi.1997.02170410045006] [PMID:  9111436]

[115]
Berg AT, Berkovic SF, Brodie MJ, et al. Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005-2009. Epilepsia  2010; 51(4): 676-85.
 [http://dx.doi.org/10.1111/j.1528-1167.2010.02522.x] [PMID:  20196795]

[116]
Fisher RS, Acevedo C, Arzimanoglou A, et al. ILAE Official Report: A practical clinical definition of epilepsy. Epilepsia  2014; 55(4): 475-82.
 [http://dx.doi.org/10.1111/epi.12550] [PMID:  24730690]

[117]
Sapir D, Leitner Y, Harel S, Kramer U. Unprovoked seizures after complex febrile convulsions. Brain Dev  2000; 22(8): 484-6.
 [http://dx.doi.org/10.1016/S0387-7604(00)00187-X] [PMID:  11111061]

[118]
Berg AT, Shinnar S. Unprovoked seizures in children with febrile seizures. Neurology  1996; 47(2): 562-8.
 [http://dx.doi.org/10.1212/WNL.47.2.562] [PMID:  8757039]

[119]
Tsai ML, Hung KL. Risk factors for subsequent epilepsy after febrile convulsions. J Formos Med Assoc  1995; 94(6): 327-31.
 [PMID:  7549552]

[120]
Chiang LM, Huang GS, Sun CC, Hsiao YL, Hui CK, Hu MH. Association of developing childhood epilepsy subsequent to febrile seizure: A population-based cohort study. Brain Dev  2018; 40(9): 775-80.
 [http://dx.doi.org/10.1016/j.braindev.2018.05.006] [PMID:  29801922]

[121]
Mathern GW, Pretorius JK, Babb TL. Influence of the type of initial precipitating injury and at what age it occurs on course and outcome in patients with temporal lobe seizures. J Neurosurg  1995; 82(2): 220-7.
 [http://dx.doi.org/10.3171/jns.1995.82.2.0220] [PMID:  7815149]

[122]
Li Y, Wang C, Wang P, Li X, Zhou L. Effects of febrile seizures in mesial temporal lobe epilepsy with hippocampal sclerosis on gene expression using bioinformatical analysis. Acta Epileptologica  2020; 2(1): 20.
 [http://dx.doi.org/10.1186/s42494-020-00027-9]

[123]
Pujar SS, Neville BGR, Scott RC, Chin RFM. Death within 8 years after childhood convulsive status epilepticus: A population-based study. Brain  2011; 134(10): 2819-27.
 [http://dx.doi.org/10.1093/brain/awr239] [PMID:  21914715]

[124]
Dlouhy BJ, Ciliberto MA, Cifra CL, et al. Unexpected death of a child with complex febrile seizures-pathophysiology similar to sudden unexpected death in epilepsy? Front Neurol  2017; 8: 21.
 [http://dx.doi.org/10.3389/fneur.2017.00021] [PMID:  28203222]

[125]
Vestergaard M, Pedersen MG, Østergaard JR, Pedersen CB, Olsen J, Christensen J. Death in children with febrile seizures: A population-based cohort study. Lancet  2008; 372(9637): 457-63.
 [http://dx.doi.org/10.1016/S0140-6736(08)61198-8] [PMID:  18692714]

[126]
Crandall LG, Lee JH, Stainman R, Friedman D, Devinsky O. Potential role of febrile seizures and other risk factors associated with sudden deaths in children. JAMA Netw Open  2019; 2(4): e192739.
 [http://dx.doi.org/10.1001/jamanetworkopen.2019.2739] [PMID:  31026025]
Cite As
Current Pediatric Reviews

Febrile Seizures: An Updated Narrative Review for Pediatric Ambulatory Care Providers

Abstract

Graphical Abstract
