Modern Pediatrics.Ukraine.2019.8(104):9-18; doi 10.15574/SP.2019.104.9
Dariia Kostiukova^1,2, Yelyzaveta Shunko², Anastasia Babintseva³, Tetiana Konchakovska^2
1National Children's Specialized Hospital «OKHMATDYT», Kyiv, Ukraine
²Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine
³Higher State Educational Institution of Ukraine «Bukovinian State Medical University», Chernivtsi

For citation: Kostiukova Dariia, Shunko Yelyzaveta, Babintseva Anastasia, Konchakovska Tetiana. (2019). The features of clinical and electroencephalographic diagnosis of seizures in preterm infants. Modern Pediatrics. Ukraine. 8(104): 9-18. doi 10.15574/SP.2019.104.9
Article received: Aug 20, 2019. Accepted for publication: Dec 11, 2019.

Neonatal seizures are the most common emergency paroxysmal conditions in patients of the neonatal intensive care units.
The aim of the study: to determine clinical and electroencephalographic signs of seizures in preterm infants with paroxysmal conditions, taking into account gestational age at birth and post-menstrual age in the dynamics of treatment.
Materials and methods. Complex clinical and neurophysiological examination of 90 premature babies was conducted (group I – 29 children with gestational age 24–28 weeks, group II — 45 children with gestational age 29–32 weeks, group III — 16 children with gestation age 33–36 weeks).
Results. Preterm infants of the study groups had manifestations of combined perinatal pathology, among which the incidence of perinatal CNS lesions was 24.1% in group I, 33.3% in group II and 37.5% in group III. According to neuromonitoring data, electrographic (31%, 42% and 43.6%, p>0.05), clonic (24.1%, 20% and 25%, p>0.05) and sequential (10.3%), seizures predominate (9%, 12.5%, p>0.05). Dynamics of clinical and electroencephalographic examination of preterm infants according to the increase postmenstrual age showed a gradual decrease in the frequency of electroclinic seizures (in group I — from 89.7% to 3.4%, p<0.0001; in group II — from 60% to 7%, p<0.0001; in group III — from 75% to 6.3%, p=0.0001) and an increase in the frequency of electrographic seizures (from 6.9% to 44.9%, p=0.0011; from 15,6% up to 27%, p>0.05; from 6.3% to 44%, p>0.05). At the corrected age of 1.5–3 months postpartum, convulsions persisted only in 24.1% of cases of group I, in 15.5% of cases of group II and in 25% of group III, p>0.05) with the prevalence of electrographic seizures. Dynamic comprehensive neuromonitoring allowed for timely adjustment of anticonvulsant therapy, which increased the proportion of children without convulsions.
Conclusions. High frequency of seizures, as one of the main manifestations of paroxysmal conditions, preterm infants and long-term preservation of electrographic seizures during the first months of postpartum life determine the need for complex neuromonitoring with the inclusion of standard electroencephalography during the first 3 months of corrected age and objective age diagnosis, correction of therapeutic complex.
The children were examined after obtaining the written consent of the parents, following the basic ethical principles of scientific medical research and approval of the research program by the Commission on Biomedical Ethics of the Shupyk National Medical Academy of Postgraduate Education.
No conflict of interest was declared by the authors.
Key words: preterm infants; neonatal seizures; standard electroencephalography.

REFERENCES

1. MOZ Ukrainy. (2014). Unifikovanyi klinichnyi protokol Pochatkova, reanimatsiina i pisliareanimatsiina dopomoha novonarodzhenym v Ukraini. Nakaz No225 vid 28.03.2014. Kyiv: 42.

2. Aicardi J. (2009). Diseases of the Nervous System in Childhood. Part VII. Parohysmal Disorders. Mac Keith Press: 581–697.

3. Al-Muhtasib N, Sepulveda-Rodriguez A, Vicini S et al. (2018). Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons. Epilepsia. 59(2): 333–344. https://doi.org/10.1111/epi.13990; PMid:29315524 PMCid:PMC6364562

4. Als H, McAnulty BG. (2011). The Newborn Individualized Developmental Care and Assessment Program (NIDCAP) with Kangaroo Mother Care (KMC): Comprehensive Care for Preterm Infants. Curr Womens Health Rev. 7(3): 288–301. https://doi.org/10.2174/157340411796355216; PMid:25473384 PMCid:PMC4248304.

5. Behrman RE, Butler AS. (2007). Preterm Birth: Causes, Consequences, and Prevention. Committee on Understanding Premature Birth and Assuring Healthy Outcomes; Washington (DC): National Academies Press: 790.

6. Besag FMC, Hughes EF. (2010). Paroxysmal disorders in infancy: a diagnostic challenge. Dev Med Child Neurol. 52(11): 980–1. https://doi.org/10.1111/j.1469-8749.2010.03725.x; PMid:20584050

7. Bittigau P, Sifringer M, Genz K et al. (2002). Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proceedings of the National Academy of Sciences of the United States of America. 99(23): 15089–15094. https://doi.org/10.1073/pnas.222550499; PMid:12417760 PMCid:PMC137548

8. Boylan GB, Pressler RM, Rennie JM et al. (1999). Outcome of electroclinical, electrographic, and clinical seizures in the newborn infant. Dev Med Child Neurol. 41(12): 819–25. https://doi.org/10.1017/S0012162299001632; PMid:10619280

9. Britton JW, Frey LC, Hopp JL et al. (2016). Electroencephalography (EEG): An Introductory Text and Atlas of Normal and Abnormal Findings in Adults, Children, and Infants. Сhicago: American Epilepsy Society. https://doi.org/10.5698/978-0-9979756-0-4.

10. Celik Y, Resitoglu B, Komur M et al. (2016). Is levetiracetam neuroprotective in neonatal rats with hypoxic ischemic brain injury? Bratislava Medical Journal. 117(12): 730–733. https://doi.org/10.4149/BLL_2016_140; PMid:28127971

11. Davis AS, Hintz SR, Van Meurs KP et al. (2010). Seizures in extremely low birth weight infants are associated with adverse outcome. J Pediatr.157: 720–725. https://doi.org/10.1016/j.jpeds.2010.04.065; PMid:20542294 PMCid:PMC2939969

12. Ellingson RJ. (1982). Development of sleep spindle bursts during the first year of life. Sleep. (1): 39–46. https://doi.org/10.1093/sleep/5.1.39

13. Falsaperla R, Mauceri L, Pavone P et al. (2019). Short-term neurodevelopmental outcome in term neonates treated with phenobarbital versus levetiracetam: a single-center experience. Behavioural Neurology. Available from: https://www.hindawi.com/journals/bn/2019/3683548/ https://doi.org/10.1155/2019/3683548; PMid:31281546 PMCid:PMC6589264

14. Forcelli PA, Janssen MJ, Vicini S et al. (2012). Neonatal exposure to antiepileptic drugs disrupts striatal synaptic development. Annals of Neurology. 72(3): 363–372. https://doi.org/10.1002/ana.23600; PMid:22581672 PMCid:PMC3421036

15. Glass HC, Costarino AT, Stayer SA et al. (2015). Outcomes for extremely premature infants. Anesth Analg. 120(6): 1337–1351. https://doi.org/10.1213/ANE.0000000000000705; PMid:25988638 PMCid:PMC4438860

16. Glass HC, Shellhaas RA, Tsuchida TN et al. (2017). On behalf of the Neonatal Seizure Registry study group. Seizures in Preterm Neonates: A Multicenter Observational Cohort Study. Pediatric Neurology. 72: 19–24. https://doi.org/10.1016/j.pediatrneurol.2017.04.016; PMid:28558955 PMCid:PMC5863228

17. Glass HC, Shellhaas RA, Tsuchida TN et al. (2017). Seizures in preterm neonates: a multicenter observational cohort study. Pediatr Neurol. 72: 19–24. https://doi.org/10.1016/j.pediatrneurol.2017.04.016; PMid:28558955 PMCid:PMC5863228

18. Hellström-Westas L, Boylan G. (2015). Systematic review of neonatal seizure management strategies provides guidance on anti0epileptic treatment. Acta Paediatr. 104(2): 123–129. https://doi.org/10.1111/apa.12812; PMid:25251733

19. Janáčková S, Boyda S, Yozawitz E et al. (2016). Electroencephalographic characteristics of epileptic seizures in preterm neonates. Clinical Neurophysiology. 127(8): 2721–2727. https://doi.org/10.1016/j.clinph.2016.05.006; PMid:27417043

20. Kohelet D, Shochat R, Lusky A et al. (2004). Risk factors for neonatal seizures in very low birthweight infants: population0based survey. J Child Neurol. 19(2): 123–128. https://doi.org/10.1177/08830738040190020701; PMid:15072105

21. Lanska MJ, Lanska DJ, Baumann RJ et al. (1995). A population-based study of neonatal seizures in Fayette County, Kentucky. Neurology. 45(4): 724–32. https://doi.org/10.1212/WNL.45.4.724; PMid:7723962

22. McBride MC, Laroia N, Guillet R. (2000). Electrographic seizures in neonates correlate with poor neurodevelopmental outcome. Neurology. 55: 506–513. https://doi.org/10.1212/WNL.55.4.506; PMid:10953181

23. Miller SP, Weiss J, Barnwell A et al. (2002). Seizure-associated brain injury in term newborns with perinatal asphyxia. Neurology. 58: 542–548. https://doi.org/10.1212/WNL.58.4.542; PMid:11865130

24. Pressler RM, Cilio MR, Mizrahi EM et al. (2017). The ILAE Classification of Seizures & the Epilepsies: Modification for Seizures in the Neonate. Proposal from the ILAE Task Force on Neonatal Seizures, Epilepsia. Available from: https://www.ilae.org/guidelines/definition-and-classification/neonatal-seizure-classification

25. Queensland Clinical Guideline: Neonatal seizures. (2017). Available from: https://www.who.int/mental_health/publications/guidelines_neonatal_seizures/en/

26. Saliba RM, Annegers JF, Waller DK et al. (1999). Incidence of neonatal seizures in Harris County, Texas, 1992–1994. Am J Epidemiol. 150(7): 763–769. https://doi.org/10.1093/oxfordjournals.aje.a010079; PMid:10512430

27. Scher MS, Aso K, Beggarly ME et al. (1993). Electrographic seizures in preterm and full-term neonates: clinical correlates, associated brain lesions, and risk for neurologic sequelae. Pediatrics. 91(1): 128–34.

28. Shah DK, Boylan GB, Rennie JM. (2012). Monitoring of seizures in the newborn. Arch Dis Child Fetal Neonatal Ed. 97(1): 65–69. https://doi.org/10.1136/adc.2009.169508
PMid:20688863

29. Shellhaas RA. (2015). Continuous long-term electroencephalography: the gold standard for neonatal seizure diagnosis. Seminars in Fetal and Neonatal Medicine. 20(3): 149–153. https://doi.org/10.1016/j.siny.2015.01.005; PMid:25660396

30. Sheth RD, Hobbs GR, Mullett M. (1999). Neonatal seizures. J Perinatol. 19(1): 40–43. https://doi.org/10.1038/sj.jp.7200107; PMid:10685200

31. Temko A, Marnane W, Boylan G et al. (2015). Clinical implementation of a neonatal seizure detection algorithm. 70: 86–96. https://doi.org/10.1016/j.dss.2014.12.006; PMid:25892834 PMCid:PMC4394138

32. Tsuchida T, Wusthoff CJ, Shellhaas RA et al. (2013). ACNS standardized EEG terminology and categorization for the description of continuous EEG monitoring in neonates: report of the American Clinical Neurophysiology Society Critical Care Monitoring Committee. J Clin Neurophys. 30(2): 161–173. https://doi.org/10.1097/WNP.0b013e3182872b24; PMid:2354576

33. Vesoulis ZA, Mathur AM. (2014). Advances in management of neonatal seizures. Indian J Pediatr. 81(6): 592–598. https://doi.org/10.1007/s12098-014-1457-9; PMid:24796413 PMCid:PMC4338003

34. Volpe J. (2008). Neurology of the Newborn. Elsevier Sauders: 203.

35. Weiner SP, Painter MJ, Geva D et al. (1991). Neonatal seizures: electroclinical dissociation. Pediatr Neurol. 7(5): 363–368. https://doi.org/10.1016/0887-8994(91)90067-U

36. Zeller B, Giebe J. (2015). Pharmacologic management of neonatal seizures. Neonatal Network. 34(4): 239–244. https://doi.org/10.1891/0730-0832.34.4.239; PMid:26802639