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Open Access 01-12-2019 | Magnetic Resonance Imaging | Research article

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study

Authors: Andrea Lakatos, Márton Kolossváry, Miklós Szabó, Ágnes Jermendy, Hajnalka Barta, Gyula Gyebnár, Gábor Rudas, Lajos R. Kozák

Published in: BMC Pediatrics | Issue 1/2019

Abstract

Background

Identification of early signs of hypoxic ischemic encephalopathy (HIE) with magnetic resonance imaging (MRI) has proven of prognostic significance. Yet, the importance of intracranial hemorrhage (ICH), being present concomitantly had not been investigated yet, despite the known influence of hypothermia on hemostasis. We aimed to determine whether presence of ICH on MRI alongside the signs of HIE have an impact on prognosis in neonates with the clinical diagnosis of HIE.

Methods

A retrospective study of consecutively sampled 108 asphyxiated term infants admitted to a tertiary neonatal intensive care unit (between 2007 and 2016), treated with whole body hypothermia and having brain MRI within 1 week of life was conducted. Presence or absence of HIE signs on MRI (basal ganglia-thalamus, watershed pattern and total brain injury) and on MR spectroscopy (lactate peak with decreased normal metabolites measured by Lac/NAA ratio) and/or of the five major types of ICH were recorded. Neurodevelopmental outcome was measured with Bayley Scales of Infant Development-II (BSID-II) test. Death or abnormal neurodevelopment (BSID-II score < 85) was defined as poor outcome in Chi-square test. Multivariate logistic regression analysis was performed on survivors.

Results

MRI and MR-spectroscopy (MRS) signs of HIE were present in 72% (n = 78). 36% (n = 39) of neonates had ICH, being mainly small in size. Chi-square test showed a relationship between neurodevelopmental outcome and initial MRI. Unadjusted logistic regression showed that neonates presenting MRI and MRS signs of HIE have 6.23 times higher odds for delayed mental development (OR = 6.2292; CI95% = [1.2642; 30.6934], p = 0.0246), than infants without imaging alterations; with no ICH effect on outcome. Adjustment for clinical and imaging parameters did not change the pattern of results, i.e. HIE remained an independent risk factor for delayed neurodevelopment (OR = 6.2496; CI95% = [1.2018; 32.4983], p = 0.0294), while ICH remained to have no significant effect.

Conclusion

HIE related MRI abnormalities proved to be important prognostic factors of poor outcome in cooled asphyxiated infants when present, suggesting that early MRI with MRS is beneficial for prognostication. Interestingly, ICHs present in about one third of all cases had no significant effect on neurodevelopmental outcome, despite the known hemostasis altering effects of hypothermia.

Available only for authorised users

The MR Research Center has been reorganized and renamed to Department of Neuroradiology, Medical Imaging Centre, Semmelweis University on August 29, 2019.

Shroff MM, Soares-Fernandes JP, Whyte H, Raybaud C. MR imaging for diagnostic evaluation of encephalopathy in the newborn. Radiographics. 2010;30(3):763–80.PubMedCrossRef

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.PubMedCrossRef

Shankaran S, Laptook AR, Ehrenkranz RA, Tyson JE, McDonald SA, Donovan EF, et al. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med. 2005;353(15):1574–84.PubMedCrossRef

Azzopardi DV, Strohm B, Edwards AD, Dyet L, Halliday HL, Juszczak E, et al. Moderate hypothermia to treat perinatal asphyxial encephalopathy. N Engl J Med. 2009;361(14):1349–58.PubMedCrossRef

Edwards AD, Brocklehurst P, Gunn AJ, Halliday H, Juszczak E, Levene M, et al. Neurological outcomes at 18 months of age after moderate hypothermia for perinatal hypoxic ischaemic encephalopathy: synthesis and meta-analysis of trial data. BMJ. 2010;340:c363.PubMedPubMedCentralCrossRef

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. Arch Pediatr Adolesc Med. 2011;165(8):692–700.PubMedCrossRef

Cheong JL, Coleman L, Hunt RW, Lee KJ, Doyle LW, Inder TE, et al. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch Pediatr Adolesc Med. 2012;166(7):634–40.PubMedCrossRef

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;1:CD003311.

Forman KR, Diab Y, Wong EC, Baumgart S, Luban NL, Massaro AN. Coagulopathy in newborns with hypoxic ischemic encephalopathy (HIE) treated with therapeutic hypothermia: a retrospective case-control study. BMC Pediatr. 2014;14:277.PubMedPubMedCentralCrossRef

10.

Massaro AN, Jeromin A, Kadom N, Vezina G, Hayes RL, Wang KK, et al. Serum biomarkers of MRI brain injury in neonatal hypoxic ischemic encephalopathy treated with whole-body hypothermia: a pilot study. Pediatr Crit Care Med. 2013;14(3):310–7.PubMedPubMedCentralCrossRef

11.

Laptook AR, Corbett RJ. The effects of temperature on hypoxic-ischemic brain injury. Clin Perinatol 2002;29(4):623–649, vi.PubMedCrossRef

12.

Gorelik N, Faingold R, Daneman A, Epelman M. Intraventricular hemorrhage in term neonates with hypoxic-ischemic encephalopathy: a comparison study between neonates treated with and without hypothermia. Quant Imaging Med Surg. 2016;6(5):504–9.PubMedPubMedCentralCrossRef

13.

Goergen SK, Ang H, Wong F, Carse EA, Charlton M, Evans R, et al. Early MRI in term infants with perinatal hypoxic-ischaemic brain injury: Interobserver agreement and MRI predictors of outcome at 2 years. Clin Radiol. 2014;69(1):72–81.PubMedCrossRef

14.

Ghei SK, Zan E, Nathan JE, Choudhri A, Tekes A, Huisman TAGM, et al. MR imaging of hypoxic-ischemic injury in term neonates: pearls and pitfalls. Radiographics. 2014;34(4):1047–61.PubMedCrossRef

15.

Cavalleri F, Lugli L, Pugliese M, D'Amico R, Todeschini A, Della Casa E, et al. Prognostic value of diffusion-weighted imaging summation scores or apparent diffusion coefficient maps in newborns with hypoxic-ischemic encephalopathy. Pediatr Radiol. 2014;44(9):1141–54.PubMedCrossRef

16.

Xu D, Mukherjee P, Barkovich AJ. Pediatric brain injury: can DTI scalars predict functional outcome? Pediatr Radiol. 2013;43(1):55–9.PubMedPubMedCentralCrossRef

17.

Sugiura H, Kouwaki M, Kato T, Ogata T, Sakamoto R, Ieshima A, et al. Magnetic resonance imaging in neonates with total asphyxia. Brain and Development. 2013;35(1):53–60.PubMedCrossRef

18.

Lee ECC, Kwatra NS, Vezina G, Khademian ZP. White matter integrity on fractional anisotropy maps in encephalopathic neonates post hypothermia therapy with normal-appearing MR imaging. Pediatr Radiol. 2013;43(6):709–15.PubMedCrossRef

19.

Harteman JC, Groenendaal F, Toet MC, Benders MJNL, Van Haastert IC, Nievelstein RAJ, et al. Diffusion-weighted imaging changes in cerebral watershed distribution following neonatal encephalopathy are not invariably associated with an adverse outcome. Dev Med Child Neurol. 2013;55(7):642–53.PubMedCrossRef

20.

Gano D, Chau V, Poskitt KJ, Hill A, Roland E, Brant R, et al. Evolution of pattern of injury and quantitative MRI on days 1 and 3 in term newborns with hypoxic-ischemic encephalopathy. Pediatr Res. 2013;74(1):82–7.PubMedCrossRef

21.

Wintermark P, Hansen A, Soul J, Labrecque M, Robertson RL, Warfield SK. Early versus late MRI in asphyxiated newborns treated with hypothermia. Arch Dis Child Fetal Neonatal Ed. 2011;96(1):F36–44.PubMedCrossRef

22.

Thayyil S, Chandrasekaran M, Taylor A, Bainbridge A, Cady EB, Chong WK, et al. Cerebral magnetic resonance biomarkers in neonatal encephalopathy: a meta-analysis. Pediatrics. 2010;125(2):e382–95.PubMedCrossRef

23.

Rutherford M, Martinez Biarge M, Allsop J, Counsell S, Cowan F. MRI of perinatal brain injury. Pediatr Radiol. 2010;40(6):819–33.PubMedCrossRef

24.

Barkovich AJ, Westmark K, Partridge C, Sola A, Ferriero DM. Perinatal asphyxia: MR findings in the first 10 days. AJNR Am J Neuroradiol. 1995;16(3):427–38.PubMedPubMedCentral

25.

Azzopardi D, Strohm B, Marlow N, Brocklehurst P, Deierl A, Eddama O, et al. Effects of hypothermia for perinatal asphyxia on childhood outcomes. N Engl J Med. 2014;371(2):140–9.PubMedCrossRef

26.

Ancora G, Testa C, Grandi S, Tonon C, Sbravati F, Savini S, et al. Prognostic value of brain proton MR spectroscopy and diffusion tensor imaging in newborns with hypoxic-ischemic encephalopathy treated by brain cooling. Neuroradiology. 2013;55(8):1017–25.PubMedCrossRef

27.

Martinez-Biarge M, Diez-Sebastian J, Kapellou O, Gindner D, Allsop JM, Rutherford MA, et al. Predicting motor outcome and death in term hypoxic-ischemic encephalopathy. Neurology. 2011;76(24):2055–61.PubMedPubMedCentralCrossRef

28.

Pappas A, Shankaran S, Laptook AR, Langer JC, Bara R, Ehrenkranz RA, et al. Hypocarbia and adverse outcome in neonatal hypoxic-ischemic encephalopathy. J Pediatr. 2011;158(5):752–8 e1.PubMedCrossRef

29.

Lingappan K, Kaiser JR, Srinivasan C, Gunn AJ. Relationship between PCO2 and unfavorable outcome in infants with moderate-to-severe hypoxic ischemic encephalopathy. Pediatr Res. 2016;80(2):204–8.PubMedCrossRef

30.

Klinger G, Beyene J, Shah P, Perlman M. Do hyperoxaemia and hypocapnia add to the risk of brain injury after intrapartum asphyxia? Arch Dis Child Fetal Neonatal Ed. 2005;90(1):F49–52.PubMedPubMedCentralCrossRef

31.

Luttikhuizen dos Santos ES, de Kieviet JF, Konigs M, van Elburg RM, Oosterlaan J. Predictive value of the Bayley scales of infant development on development of very preterm/very low birth weight children: a meta-analysis. Early Hum Dev. 2013;89(7):487–96.PubMedCrossRef

32.

Bayley N. Bayley Scales of Infant Development. Second Edition ed: San Antonio,The Psychological Corporation; 1993.

33.

Lakatos A, Kolossvary M, Szabo M, Jermendy A, Bagyura Z, Barsi P, et al. Novel structured MRI reporting system in neonatal hypoxic-ischemic encephalopathy - issues of development and first use experiences. Ideggyogy Sz. 2018;71(7–08):265–76.PubMedCrossRef

34.

Alderliesten T, de Vries LS, Staats L, van Haastert IC, Weeke L, Benders MJ, et al. MRI and spectroscopy in (near) term neonates with perinatal asphyxia and therapeutic hypothermia. Arch Dis Child Fetal Neonatal Ed. 2017;102(2):F147–F52.PubMedCrossRef

35.

Barta H, Jermendy A, Kolossvary M, Kozak LR, Lakatos A, Meder U, et al. Prognostic value of early, conventional proton magnetic resonance spectroscopy in cooled asphyxiated infants. BMC Pediatr. 2018;18(1):302.PubMedPubMedCentralCrossRef

36.

de Vries LS, Groenendaal F. Patterns of neonatal hypoxic-ischaemic brain injury. Neuroradiology. 2010;52(6):555–66.PubMedPubMedCentralCrossRef

37.

Barkovich AJ, Hajnal BL, Vigneron D, Sola A, Partridge JC, Allen F, et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol. 1998;19(1):143–9.PubMedPubMedCentral

38.

Guo L, Wang D, Bo G, Zhang H, Tao W, Shi Y. Early identification of hypoxic-ischemic encephalopathy by combination of magnetic resonance (MR) imaging and proton MR spectroscopy. Exp Ther Med. 2016;12(5):2835–42.PubMedPubMedCentralCrossRef

39.

Brouwer AJ, Groenendaal F, Koopman C, Nievelstein RJ, Han SK, de Vries LS. Intracranial hemorrhage in full-term newborns: a hospital-based cohort study. Neuroradiology. 2010;52(6):567–76.PubMedPubMedCentralCrossRef

40.

Charon V, Proisy M, Bretaudeau G, Bruneau B, Pladys P, Beuchee A, et al. Early MRI in neonatal hypoxic-ischaemic encephalopathy treated with hypothermia: prognostic role at 2-year follow-up. Eur J Radiol. 2016;85(8):1366–74.PubMedCrossRef

41.

Chakkarapani E, Poskitt KJ, Miller SP, Zwicker JG, Xu Q, Wong DS, et al. Reliability of early magnetic resonance imaging (MRI) and necessity of repeating MRI in noncooled and cooled infants with neonatal encephalopathy. J Child Neurol. 2016;31(5):553–9.PubMedCrossRef

42.

Charon V, Proisy M, Ferre JC, Bruneau B, Treguier C, Beuchee A, et al. Comparison of early and late MRI in neonatal hypoxic-ischemic encephalopathy using three assessment methods. Pediatr Radiol. 2015;45(13):1988–2000.PubMedCrossRef

43.

Looney CB, Smith JK, Merck LH, Wolfe HM, Chescheir NC, Hamer RM, et al. Intracranial hemorrhage in asymptomatic neonates: prevalence on MR images and relationship to obstetric and neonatal risk factors. Radiology. 2007;242(2):535–41.PubMedCrossRef

44.

Gupta SN, Kechli AM, Kanamalla US. Intracranial hemorrhage in term newborns: management and outcomes. Pediatr Neurol. 2009;40(1):1–12.PubMedCrossRef

45.

Chaturvedi A, Chaturvedi A, Stanescu AL, Blickman JG, Meyers SP. Mechanical birth-related trauma to the neonate: an imaging perspective. Insights into imaging. 2018;9(1):103–18.PubMedPubMedCentralCrossRef

46.

Bos AF. Bayley-II or Bayley-III: what do the scores tell us? Dev Med Child Neurol. 2013;55(11):978–9.PubMedCrossRef

47.

Liauw L, Palm-Meinders IH, van der Grond J, Leijser LM, le Cessie S, Laan LA, et al. Differentiating normal myelination from hypoxic-ischemic encephalopathy on T1-weighted MR images: a new approach. AJNR Am J Neuroradiol. 2007;28(4):660–5.PubMedPubMedCentral

48.

Kitamura G, Kido D, Wycliffe N, Jacobson JP, Oyoyo U, Ashwal S. Hypoxic-ischemic injury: utility of susceptibility-weighted imaging. Pediatr Neurol. 2011;45(4):220–4.PubMedCrossRef

49.

Weeke LC, Groenendaal F, Mudigonda K, Blennow M, Lequin MH, Meiners LC, et al. A novel magnetic resonance imaging score predicts neurodevelopmental outcome after perinatal asphyxia and therapeutic hypothermia. J Pediatr. 2018;192:33–40 e2.PubMedPubMedCentralCrossRef

50.

Colbourne F, Corbett D. Delayed postischemic hypothermia: a six month survival study using behavioral and histological assessments of neuroprotection. J Neurosci. 1995;15(11):7250–60.PubMedPubMedCentralCrossRef

51.

Taylor DL, Mehmet H, Cady EB, Edwards AD. Improved neuroprotection with hypothermia delayed by 6 hours following cerebral hypoxia-ischemia in the 14-day-old rat. Pediatr Res. 2002;51(1):13–9.PubMedCrossRef

52.

Gunn AJ, Thoresen M. Hypothermic neuroprotection. NeuroRx. 2006;3(2):154–69.PubMedPubMedCentralCrossRef

53.

Drury PP, Bennet L, Gunn AJ. Mechanisms of hypothermic neuroprotection. Semin Fetal Neonatal Med. 2010;15(5):287–92.PubMedCrossRef

54.

Executive summary. Neonatal encephalopathy and neurologic outcome, second edition. Report of the American College of Obstetricians and Gynecologists’ task force on neonatal encephalopathy. Obstet Gynecol. 2014;123(4):896–901.CrossRef

55.

Rutherford M, Ramenghi LA, Edwards AD, Brocklehurst P, Halliday H, Levene M, et al. 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.PubMedPubMedCentralCrossRef

56.

Boudes E, Tan X, Saint-Martin C, Shevell M, Wintermark P. MRI obtained during versus after hypothermia in asphyxiated newborns. Arch Dis Child Fetal Neonatal Ed. 2015;100(3):F238–42.PubMedCrossRef

Title: Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study
Authors: Andrea Lakatos
Márton Kolossváry
Miklós Szabó
Ágnes Jermendy
Hajnalka Barta
Gyula Gyebnár
Gábor Rudas
Lajos R. Kozák
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Magnetic Resonance Imaging
Magnetic Resonance Imaging
Published in: BMC Pediatrics / Issue 1/2019
Electronic ISSN: 1471-2431
DOI: https://doi.org/10.1186/s12887-019-1777-z

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Neurodevelopmental effect of intracranial hemorrhage observed in hypoxic ischemic brain injury in hypothermia-treated asphyxiated neonates - an MRI study

Abstract

Background

Methods

Results

Conclusion

Keynote webinar | Spotlight on sleep in brain health

Springer Medicine

Abstract

Background

Methods

Results

Conclusion

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