Skip to main content
Top
Published in: BMC Pediatrics 1/2021

Open Access 01-12-2021 | Magnetic Resonance Imaging | Research article

Short‐term outcomes in infants with mild neonatal encephalopathy: a retrospective, observational study

Authors: Yoshinori Aoki, Tatsuo Kono, Mikako Enokizono, Kaoru Okazaki

Published in: BMC Pediatrics | Issue 1/2021

Login to get access

Abstract

Background

Neonatal encephalopathy due to acute perinatal asphyxia is a major cause of perinatal brain damage. Moderate to severe neonatal encephalopathy is associated with high mortality and morbidity rates. However, the neurodevelopmental outcomes in neonates with mild neonatal encephalopathy are unclear. The primary aim of this single-center observational study was to assess the short-term outcomes in term neonates with mild neonatal encephalopathy due to perinatal asphyxia. A secondary aim was to identify predictors of poor prognosis by identifying the characteristics of these infants according to their short-term outcomes.

Methods

We retrospectively investigated all infants with perinatal asphyxia at Tokyo Metropolitan Children’s Medical Center from January 2014 to December 2019. An abnormal short-term outcome was defined as any one of the following: seizures or abnormal electroencephalography, abnormal brain magnetic resonance imaging obtained within the first 4 weeks of life, and abnormal neurological examination findings at discharge.

Results

In total, 110 term infants with perinatal asphyxia during the study period were screened and 61 were diagnosed with mild neonatal encephalopathy. Eleven (18 %) of these infants had an abnormal short-term outcome. The median Thompson score at admission was significantly higher in infants with abnormal short-term outcomes than in those with normal short-term outcomes (5 [interquartile range, 4-5.5] vs. 2 [interquartile range, 1–3], p < 0.01). Receiver operating characteristic curve analysis showed that a cutoff value of 4 had high sensitivity and specificity (90.9 and 83.0 %, respectively) for prediction of an abnormal short-term outcome.

Conclusions

18 % of infants with mild encephalopathy had an abnormal short-term outcome, such as abnormal brain magnetic resonance imaging findings. The Thompson score at admission may be a useful predictor of an abnormal short-term outcome in infants with mild neonatal encephalopathy.
Appendix
Available only for authorised users
Literature
1.
2.
go back to reference Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72:156–66.CrossRef Volpe JJ. Neonatal encephalopathy: an inadequate term for hypoxic-ischemic encephalopathy. Ann Neurol. 2012;72:156–66.CrossRef
3.
go back to reference Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169:397–403.CrossRef Douglas-Escobar M, Weiss MD. Hypoxic-ischemic encephalopathy: a review for the clinician. JAMA Pediatr. 2015;169:397–403.CrossRef
4.
go back to reference Pierrat V, Haouari N, Liska A, Thomas D, Subtil D, Truffert P, Groupe d’Etudes en Epidemiologie P. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study. Arch Dis Child Fetal Neonatal Ed. 2005;90(3):F257-61.CrossRef Pierrat V, Haouari N, Liska A, Thomas D, Subtil D, Truffert P, Groupe d’Etudes en Epidemiologie P. Prevalence, causes, and outcome at 2 years of age of newborn encephalopathy: population based study. Arch Dis Child Fetal Neonatal Ed. 2005;90(3):F257-61.CrossRef
5.
go back to reference Lee ACC, Kozuki N, Blencowe H, Vos T, Bahalim A, Darmstadt GL, Niermeyer S, Ellis M, Robertson NJ, Cousens S et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74 Suppl 1:50–72.CrossRef Lee ACC, Kozuki N, Blencowe H, Vos T, Bahalim A, Darmstadt GL, Niermeyer S, Ellis M, Robertson NJ, Cousens S et al. Intrapartum-related neonatal encephalopathy incidence and impairment at regional and global levels for 2010 with trends from 1990. Pediatr Res. 2013;74 Suppl 1:50–72.CrossRef
6.
go back to reference Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365(9460):663–70.CrossRef Gluckman PD, Wyatt JS, Azzopardi D, Ballard R, Edwards AD, Ferriero DM, Polin RA, Robertson CM, Thoresen M, Whitelaw A et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet. 2005;365(9460):663–70.CrossRef
7.
go back to reference Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.CrossRef Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, Fanaroff AA, Poole WK, Wright LL, Higgins RD et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.CrossRef
8.
go back to reference Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361(14):1349–58.CrossRef Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, Kapellou O, Levene M, Marlow N, Porter E et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361(14):1349–58.CrossRef
9.
go back to reference Nolan JP, Hazinski MF, Billi JE, Boettiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2010;81 Suppl 1:e1-25.PubMed Nolan JP, Hazinski MF, Billi JE, Boettiger BW, Bossaert L, de Caen AR, Deakin CD, Drajer S, Eigel B, Hickey RW et al. Part 1: Executive summary: 2010 International Consensus on Cardiopulmonary Resuscitation and Emergency Cardiovascular Care Science With Treatment Recommendations. Resuscitation. 2010;81 Suppl 1:e1-25.PubMed
10.
go back to reference 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;2013(1):Cd003311.PubMedCentral 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;2013(1):Cd003311.PubMedCentral
11.
go back to reference Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696–705.CrossRef Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol. 1976;33(10):696–705.CrossRef
12.
go back to reference Robertson CM, Finer NN, Grace MG. School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr. 1989;114(5):753–60.CrossRef Robertson CM, Finer NN, Grace MG. School performance of survivors of neonatal encephalopathy associated with birth asphyxia at term. J Pediatr. 1989;114(5):753–60.CrossRef
13.
go back to reference DuPont TL, Chalak LF, Morriss MC, Burchfield PJ, Christie L, Sanchez PJ. Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. J Pediatr. 2013;162(1):35–41.CrossRef DuPont TL, Chalak LF, Morriss MC, Burchfield PJ, Christie L, Sanchez PJ. Short-term outcomes of newborns with perinatal acidemia who are not eligible for systemic hypothermia therapy. J Pediatr. 2013;162(1):35–41.CrossRef
14.
go back to reference Murray DM, O’Connor CM, Ryan CA, Korotchikova I, Boylan GB. Early EEG Grade and Outcome at 5 Years After Mild Neonatal Hypoxic Ischemic Encephalopathy. Pediatrics. 2016;138(4):doi:10.1542. Murray DM, O’Connor CM, Ryan CA, Korotchikova I, Boylan GB. Early EEG Grade and Outcome at 5 Years After Mild Neonatal Hypoxic Ischemic Encephalopathy. Pediatrics. 2016;138(4):doi:10.1542.
15.
go back to reference Chalak LF, Nguyen KA, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L et al. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18–22 months. Pediatr Res. 2018;84(6):861–8.CrossRef Chalak LF, Nguyen KA, Prempunpong C, Heyne R, Thayyil S, Shankaran S, Laptook AR, Rollins N, Pappas A, Koclas L et al. Prospective research in infants with mild encephalopathy identified in the first six hours of life: neurodevelopmental outcomes at 18–22 months. Pediatr Res. 2018;84(6):861–8.CrossRef
16.
go back to reference Conway JM, Walsh BH, Boylan GB, Murray DM. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review. Early Hum Dev. 2018;120:80–7.CrossRef Conway JM, Walsh BH, Boylan GB, Murray DM. Mild hypoxic ischaemic encephalopathy and long term neurodevelopmental outcome - A systematic review. Early Hum Dev. 2018;120:80–7.CrossRef
17.
go back to reference Massaro AN, Murthy K, Zaniletti I, Cook N, DiGeronimo R, Dizon M, Hamrick SE, McKay VJ, Natarajan G, Rao R et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group. J Perinatol. 2015;35(4):290–6.CrossRef Massaro AN, Murthy K, Zaniletti I, Cook N, DiGeronimo R, Dizon M, Hamrick SE, McKay VJ, Natarajan G, Rao R et al. Short-term outcomes after perinatal hypoxic ischemic encephalopathy: a report from the Children’s Hospitals Neonatal Consortium HIE focus group. J Perinatol. 2015;35(4):290–6.CrossRef
18.
go back to reference Oliveira V, Singhvi DP, Montaldo P, Lally PJ, Mendoza J, Manerkar S, Shankaran S, Thayyil S. Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK. Arch Dis Child Fetal Neonatal Ed. 2018;103(4):F388-90.CrossRef Oliveira V, Singhvi DP, Montaldo P, Lally PJ, Mendoza J, Manerkar S, Shankaran S, Thayyil S. Therapeutic hypothermia in mild neonatal encephalopathy: a national survey of practice in the UK. Arch Dis Child Fetal Neonatal Ed. 2018;103(4):F388-90.CrossRef
19.
go back to reference Thompson CM, Puterman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, Malan AF. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757–61.CrossRef Thompson CM, Puterman AS, Linley LL, Hann FM, van der Elst CW, Molteno CD, Malan AF. The value of a scoring system for hypoxic ischaemic encephalopathy in predicting neurodevelopmental outcome. Acta Paediatr. 1997;86(7):757–61.CrossRef
20.
go back to reference Murray DM, Boylan GB, Ryan CA, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009;124(3):e459-67.CrossRef Murray DM, Boylan GB, Ryan CA, Connolly S. Early EEG findings in hypoxic-ischemic encephalopathy predict outcomes at 2 years. Pediatrics. 2009;124(3):e459-67.CrossRef
21.
go back to reference Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2015;57 Suppl 3:8–16.CrossRef Merchant N, Azzopardi D. Early predictors of outcome in infants treated with hypothermia for hypoxic-ischaemic encephalopathy. Dev Med Child Neurol. 2015;57 Suppl 3:8–16.CrossRef
22.
go back to reference Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial. The Lancet Neurology. 2010;9(1):39–45.CrossRef Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, Strohm B, Thoresen M, Whitelaw A, Azzopardi D. Assessment of brain tissue injury after moderate hypothermia in neonates with hypoxic–ischaemic encephalopathy: a nested substudy of a randomised controlled trial. The Lancet Neurology. 2010;9(1):39–45.CrossRef
23.
go back to reference Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, Pappas A, Higgins RD. Eunice Kennedy Shriver National Institute of Child H, Human Development Neonatal Research N: Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2015;167(5):987–93.CrossRef Shankaran S, McDonald SA, Laptook AR, Hintz SR, Barnes PD, Das A, Pappas A, Higgins RD. Eunice Kennedy Shriver National Institute of Child H, Human Development Neonatal Research N: Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. J Pediatr. 2015;167(5):987–93.CrossRef
24.
go back to reference Murray DM, Bala P, O’Connor CM, Ryan CA, Connolly S, Boylan GB. The predictive value of early neurological examination in neonatal hypoxic-ischaemic encephalopathy and neurodevelopmental outcome at 24 months. Dev Med Child Neurol. 2010;52(2):e55-9.CrossRef Murray DM, Bala P, O’Connor CM, Ryan CA, Connolly S, Boylan GB. The predictive value of early neurological examination in neonatal hypoxic-ischaemic encephalopathy and neurodevelopmental outcome at 24 months. Dev Med Child Neurol. 2010;52(2):e55-9.CrossRef
25.
go back to reference Chalak L, Latremouille S, Mir I, Sanchez PJ, Sant’Anna G. A review of the conundrum of mild hypoxic-ischemic encephalopathy: Current challenges and moving forward. Early Hum Dev. 2018;120:88–94.CrossRef Chalak L, Latremouille S, Mir I, Sanchez PJ, Sant’Anna G. A review of the conundrum of mild hypoxic-ischemic encephalopathy: Current challenges and moving forward. Early Hum Dev. 2018;120:88–94.CrossRef
26.
go back to reference van Kooij BJ, van Handel M, Nievelstein RA, Groenendaal F, Jongmans MJ, de Vries LS. Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy. J Pediatr. 2010;157(2):221–7.CrossRef van Kooij BJ, van Handel M, Nievelstein RA, Groenendaal F, Jongmans MJ, de Vries LS. Serial MRI and neurodevelopmental outcome in 9- to 10-year-old children with neonatal encephalopathy. J Pediatr. 2010;157(2):221–7.CrossRef
27.
go back to reference de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010;95(3):F220-4.CrossRef de Vries LS, Jongmans MJ. Long-term outcome after neonatal hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2010;95(3):F220-4.CrossRef
28.
go back to reference van Handel M, Swaab H, de Vries LS, Jongmans MJ. Behavioral outcome in children with a history of neonatal encephalopathy following perinatal asphyxia. J Pediatr Psychol. 2010;35(3):286–95.CrossRef van Handel M, Swaab H, de Vries LS, Jongmans MJ. Behavioral outcome in children with a history of neonatal encephalopathy following perinatal asphyxia. J Pediatr Psychol. 2010;35(3):286–95.CrossRef
29.
go back to reference van Handel M, de Sonneville L, de Vries LS, Jongmans MJ, Swaab H. Specific memory impairment following neonatal encephalopathy in term-born children. Dev Neuropsychol. 2012;37(1):30–50.CrossRef van Handel M, de Sonneville L, de Vries LS, Jongmans MJ, Swaab H. Specific memory impairment following neonatal encephalopathy in term-born children. Dev Neuropsychol. 2012;37(1):30–50.CrossRef
30.
go back to reference Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005;90(5):F380-7.CrossRef Marlow N, Rose AS, Rands CE, Draper ES. Neuropsychological and educational problems at school age associated with neonatal encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2005;90(5):F380-7.CrossRef
31.
go back to reference Negro S, Benders M, Tataranno ML, Coviello C, de Vries LS, van Bel F, Groenendaal F, Longini M, Proietti F, Belvisi E et al. Early Prediction of Hypoxic-Ischemic Brain Injury by a New Panel of Biomarkers in a Population of Term Newborns. Oxid Med Cell Longev. 2018;2018:7608108.CrossRef Negro S, Benders M, Tataranno ML, Coviello C, de Vries LS, van Bel F, Groenendaal F, Longini M, Proietti F, Belvisi E et al. Early Prediction of Hypoxic-Ischemic Brain Injury by a New Panel of Biomarkers in a Population of Term Newborns. Oxid Med Cell Longev. 2018;2018:7608108.CrossRef
32.
go back to reference Thorsen P, Jansen-van der Weide MC, Groenendaal F, Onland W, van Straaten HL, Zonnenberg I, Vermeulen JR, Dijk PH, Dudink J, Rijken M et al. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia. Pediatr Neurol. 2016;60:49–53.CrossRef Thorsen P, Jansen-van der Weide MC, Groenendaal F, Onland W, van Straaten HL, Zonnenberg I, Vermeulen JR, Dijk PH, Dudink J, Rijken M et al. The Thompson Encephalopathy Score and Short-Term Outcomes in Asphyxiated Newborns Treated With Therapeutic Hypothermia. Pediatr Neurol. 2016;60:49–53.CrossRef
33.
go back to reference Chalak LF, Adams-Huet B, Sant’Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019;214:217–21.CrossRef Chalak LF, Adams-Huet B, Sant’Anna G. A Total Sarnat Score in Mild Hypoxic-ischemic Encephalopathy Can Detect Infants at Higher Risk of Disability. J Pediatr. 2019;214:217–21.CrossRef
34.
go back to reference Montaldo P, Lally PJ, Oliveira V, Swamy R, Mendoza J, Atreja G, Kariholu U, Shivamurthappa V, Liow N, Teiserskas J et al. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study. Arch Dis Child Fetal Neonatal Ed. 2019;104(5):F515-20.CrossRef Montaldo P, Lally PJ, Oliveira V, Swamy R, Mendoza J, Atreja G, Kariholu U, Shivamurthappa V, Liow N, Teiserskas J et al. Therapeutic hypothermia initiated within 6 hours of birth is associated with reduced brain injury on MR biomarkers in mild hypoxic-ischaemic encephalopathy: a non-randomised cohort study. Arch Dis Child Fetal Neonatal Ed. 2019;104(5):F515-20.CrossRef
35.
go back to reference Goswami IR, Whyte H, Wintermark P, Mohammad K, Shivananda S, Louis D, Yoon EW, Shah PS. Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia. J Perinatol. 2020;40(2):275–83.CrossRef Goswami IR, Whyte H, Wintermark P, Mohammad K, Shivananda S, Louis D, Yoon EW, Shah PS. Characteristics and short-term outcomes of neonates with mild hypoxic-ischemic encephalopathy treated with hypothermia. J Perinatol. 2020;40(2):275–83.CrossRef
36.
go back to reference Kariholu U, Montaldo P, Markati T, Lally PJ, Pryce R, Teiserskas J, Liow N, Oliveira V, Soe A, Shankaran S et al. Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020;105(2):225–28.CrossRef Kariholu U, Montaldo P, Markati T, Lally PJ, Pryce R, Teiserskas J, Liow N, Oliveira V, Soe A, Shankaran S et al. Therapeutic hypothermia for mild neonatal encephalopathy: a systematic review and meta-analysis. Arch Dis Child Fetal Neonatal Ed. 2020;105(2):225–28.CrossRef
Metadata
Title
Short‐term outcomes in infants with mild neonatal encephalopathy: a retrospective, observational study
Authors
Yoshinori Aoki
Tatsuo Kono
Mikako Enokizono
Kaoru Okazaki
Publication date
01-12-2021
Publisher
BioMed Central
Published in
BMC Pediatrics / Issue 1/2021
Electronic ISSN: 1471-2431
DOI
https://doi.org/10.1186/s12887-021-02688-y

Other articles of this Issue 1/2021

BMC Pediatrics 1/2021 Go to the issue