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• Response to "How to Recognise encephalopathy earlier?"
  Corline E.J. Parmentier, Sylke J. Steggerda, Linda S. de Vries and Floris Groenendaal
  Published on: 26 July 2022
• How to Recognise encephalopathy earlier?
  Shabih Manzar
  Published on: 25 June 2022

• Published on: 26 July 2022

  Response to "How to Recognise encephalopathy earlier?"

  • Corline E.J. Parmentier, MD, PhD Candidate Neonatology Department of Neonatology, University Medical Center Utrecht, Utrecht, The Netherlands
  • Other Contributors:
    • Sylke J. Steggerda, MD, PhD
    • Linda S. de Vries, MD, PhD
    • Floris Groenendaal, MD, PhD

  We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the...

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  We have read with interest the response by Dr. Shabih Manzar on our article. The Thompson score is a clinical score consisting of nine items that are associated with neurologic dysfunction to assess the severity of neonatal encephalopathy (NE) in infants with perinatal asphyxia.[1] There are indeed important limitations that need to be considered; the assessment of infants by use of the Thompson score requires interpretation from the examiner, and the degree of NE may change over time.[2] It should be noted that these limitations are also applicable to other clinical grading tools, such as the modified Sarnat score, which is being widely applied to select infants for therapeutic hypothermia.[2,3] We would like to emphasize that the majority of the infants described in this study was born in a level-II-hospital. Amplitude-integrated electroencephalography (aEEG), another tool to select infants for therapeutic hypothermia, allows continuous monitoring, expert revision and the detection of subclinical seizures, but also requires well-trained staff for correct interpretation and is often not available in these hospitals. By design, the Thompson score did not require extensive training of the observer, which is why it is suitable to be used in smaller hospitals.[1] In a previous study, our study group demonstrated that the Thompson score and aEEG had a similar predictive value for an adverse outcome.[4] We however completely agree with Dr. Manzar that it is of concern that the Thompson score was not available in more than half of our study population, although this could have been the result of a lack of documentation.

  Seven infants in our study developed moderate NE <6 hours after birth, and therefore indeed qualified for therapeutic hypothermia.[5] Three of these infants showed a rapid cardiorespiratory recovery after birth, i.e. they were cardiorespiratory stable with a minimal amount of oxygen support after resuscitation and only a short period of ventilation. All three were born in a level-II-hospital without access to aEEG. Although one of these infants had a Thompson score of 13 at 1 hour after birth, hypothermia was not started because of a low Thompson score (1) at 3 hours after birth on arrival at the NICU. In the other two cases, the first signs of NE were recognized around 4-5 hours after birth, but hypothermia was not started because the infants arrived at respectively 8 hours and 11 hours after birth at the NICU.

  As mentioned in our discussion, the large trials on therapeutic hypothermia used different eligibility criteria for this intervention, including various thresholds for Apgar scores and pH.[6] Some trials indeed included infants using a pH <7.0 and 10-minute Apgar score ≤5,[7,8] while others included infants with a pH <7.1 [9,10] or 5-minute Apgar score <7.[9] The systematic review by Jacobs et al. used a cord or arterial pH <7.1 within 60 minutes of birth as criterium for peripartum asphyxia.[6] We were interested whether the infants in our study population would have been eligible for hypothermia using different thresholds, and therefore separately reported the proportion of infants with and without a pH <7.0.

  To conclude, we would like to emphasize that selection of infants for therapeutic hypothermia is difficult, especially as most infants are born in level-II-hospitals with different levels of clinical experience and often no access to aEEG. Even though seven infants in our study should have received hypothermia, the proportion of infants who developed an adverse outcome remains high (16/32, 50%) when these seven infants are excluded. Both clinical grading tools as well as aEEG have limitations in clinical practice, which is why further studies on optimizing the selection of infants for therapeutic hypothermia are needed. Until a better tool to select infants for therapeutic hypothermia becomes available, structural use of the Thompson score and early referral of infants with perinatal asphyxia for neuromonitoring, including those who seem to recover quickly from a perinatal insult, remains of great importance.

  References
  [1]. Thompson, CM, Outerman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997 Jul;86(7):757-61.
  [2]. Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976 Oct;33(10):696-705.
  [3]. Mrelashvili A, Russ JB, Ferriero DM, Wusthoff CJ. The Sarnat score for neonatal encephalopathy: looking back and moving forward. Pediatr Res. 2020 Dec;88(6):824-825.
  [4]. Weeke LC, Vilan A, Toet MC, van Haastert IC, de Vries LS, Groenendaal F. A Comparison of the Thompson encephalopathy score and amplitude-integrated electroencephalography in infants with perinatal asphyxia and therapeutic hypothermia. Neonatology. 2017;112(1):24–9.
  [5]. Groenendaal F, Casaer A, Dijkman KP, Gavilanes AWD, de Haan TR, ter Horst HJ, et al. Introduction of Hypothermia for Neonates with Perinatal Asphyxia in the Netherlands and Flanders. Neonatology. 2013;104(1):15-21.
  [6]. Jacobs SE, Berg M, Hunt R, Tarnow-Mordi WO, Inder TE, Davis PG. Cooling for newborns with hypoxic ischaemic encephalopathy. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003311.
  [7]. Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD Ferriero DM, et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005;365(9460):663‐70.
  [8]. Jacobs SE, Morley CJ, Inder TE, Stewart MJ, Smith KR, McNamara PJ, et al. Whole‐body hypothermia for term and near‐term newborns with hypoxic‐ischemic encephalopathy: a randomized controlled trial. Archives of Pediatrics and Adolescent Medicine 2011;165(8):692‐700.
  [9]. Gunn AJ, Gluckman PD, Gunn TR. Selective head cooling in newborn infants after perinatal asphyxia: a safety study. Pediatrics 1998;102(4 Pt 1):885‐92.
  [10]. Lin Z, Yu H, Lin J, Chen S, Liang Z, Zhang Z. Mild hypothermia via selective head cooling as neuroprotective therapy in term neonates with perinatal asphyxia: an experience from a single neonatal intensive care unit. Journal of Perinatology 2006;26(3):180‐4.

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  Conflict of Interest:
  None declared.

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• Published on: 25 June 2022

  How to Recognise encephalopathy earlier?

  • Shabih Manzar, Neonatologist Ochsner LSU Health, Shreveport, LA, USA

  The article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.

  It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].

  The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].

  References:

  1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants w...

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  The article by Parmentier et al [1] highlights the role of Amplitude-integrated electroencephalography (aEEG) and early biomarkers in selecting infants for therapeutic hypothermia (TH). They also suggested the role of the Thompson score (TS) in asphyxiated infants. The problem with TS is that it is subjective. It consists of nine clinical signs: tone, level of consciousness, fits, posture, moro reflex, grasp, suck, respiration, and fontanelle, which could change over time [2]. Also, in the data presented by Parmentier et al [1], twenty-one (53%) infants did not have TS performed.

  It was surprising to note that four cases that had moderate neonatal encephalopathy (NE) were not treated with TH despite having seizures within the first 6 hours. The reason for not treatment was rapid recovery. What was the definition of rapid recovery? According to the published flow diagram for NE, the onset of seizure within 6 hours warrants TH [3].

  The definition of perinatal asphyxia used by Parmentier et al [1] was from a study in 2003 [4]. It was defined as an arterial cord blood pH <7.1, Apgar Score <7 at 5 min, or need for neonatal resuscitation. While the analysis was done with pH of < 7 and > 7 [(Table 1) 1]. A pH of 7.1 and Apgar of 7 at 5 min is higher than the definition/criteria used in the TH trial [5].

  References:

  1. Parmentier CEJ, Steggerda SJ, Weeke LC, Rijken M, De Vries LS, Groenendaal F. Outcome of non-cooled asphyxiated infants with under-recognised or delayed-onset encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2022;107(4):364-370. doi:10.1136/archdischild-2020-321331

  2. Thompson CM, Puterman AS, Linley LL, et al. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757-761. doi:10.1111/j.1651-2227.1997.tb08581.x

  3. Chiang MC, Jong YJ, Lin CH. Therapeutic hypothermia for neonates with hypoxic ischemic encephalopathy. Pediatr Neonatol. 2017;58(6):475-483. doi:10.1016/j.pedneo.2016.11.001

  4. Cowan F, Rutherford M, Groenendaal F, et al. Origin and timing of brain lesions in term infants with neonatal encephalopathy. Lancet. 2003;361(9359):736-742. doi:10.1016/S0140-6736(03)12658-X

  5. Shankaran S, Laptook AR, Ehrenkranz RA, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574-1584. doi:10.1056/NEJMcps050929

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  Conflict of Interest:
  None declared.

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