Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming

Kiran S. More; Pankaj Sakhuja; Regan E. Giesinger; Joseph Y. Ting; Matthew Keyzers; Jesal N. Sheth; Anie Lapointe; Amish Jain; Aideen M. Moore; Steven P. Miller; Patrick J. McNamara

doi:10.1055/s-0038-1629900

American Journal of Perinatology, Table of Contents

Am J Perinatol 2018; 35(10): 979-989
DOI: 10.1055/s-0038-1629900

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Cardiovascular Associations with Abnormal Brain Magnetic Resonance Imaging in Neonates with Hypoxic Ischemic Encephalopathy Undergoing Therapeutic Hypothermia and Rewarming

Kiran S. More

¹Department of Neonatology, Christchurch Women's Hospital, Canterbury, New Zealand

,

Pankaj Sakhuja

²Department of Paediatrics, King Hamad University Hospital, Busaiteen, Bahrain

,

Regan E. Giesinger

³Division of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada

⁴Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada

,

Joseph Y. Ting

⁵Children's & Women's Health Centre of British Columbia, Vancouver, British Columbia, Canada

,

Matthew Keyzers

³Division of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada

,

Jesal N. Sheth

⁶Department of Neonatology, Fortis Hospital, Mumbai, Maharashtra, India

,

Anie Lapointe

⁷Department of Neonatology, Sainte-Justine Hospital, Montreal, Canada

,

Amish Jain

⁸Department of Paediatrics, Mount Sinai Hospital, Toronto, Ontario, Canada

⁹Department of Physiology, The University of Toronto, Toronto, Ontario, Canada

,

Aideen M. Moore

³Division of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada

⁴Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada

,

Steven P. Miller

⁴Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada

,

Patrick J. McNamara

³Division of Neonatology, The Hospital for Sick Children, Toronto, Ontario, Canada

⁴Department of Paediatrics, The University of Toronto, Toronto, Ontario, Canada

⁹Department of Physiology, The University of Toronto, Toronto, Ontario, Canada

› Author Affiliations

Abstract

Objective This article compares hemodynamic characteristics of neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia (TH) with normal versus abnormal brain magnetic resonance imaging (MRI).

Methods Serial echocardiography (echo) was performed within 24 hours, after 48 to 72 hours of cooling, within 24 hours of normothermia, and after starting feeds. Pulmonary hemodynamics, cardiac output, and ventricular function were evaluated. All neonates underwent brain MRI (day 4–5), per clinical standard of care. Clinical cardiovascular and echocardiography characteristics were compared between patients with normal versus abnormal MRI. Cardiovascular changes during TH and after rewarming were identified.

Results Twenty neonates at median gestation and birth weight of 40 weeks (interquartile range [IQR]: 39, 41) and 3,410 g (IQR: 2,885, 4,093), respectively, were enrolled. Increased median left ventricular output (LVO) (106–159 mL/kg/min, p < 0.001) and reduced isovolumic relaxation time (IVRT) (48–42 ms, p < 0.001) were seen after rewarming. Echocardiography evidence of pulmonary hypertension (PH) was identified in five neonates. Eight neonates (40%) had brain injury identified on MRI (watershed [n = 4], basal ganglia [n = 4]); this subgroup were more likely to have echo evidence of PH at 24 hours.

Conclusion Longitudinal changes in cardiac output were noted in neonates with HIE during TH and rewarming. Echocardiography evidence of PH, however, was associated with abnormal MRI brain. The prognostic relevance of these physiologic changes requires more comprehensive delineation.

Keywords

hypoxic ischemic encephalopathy - therapeutic hypothermia - myocardial performance and hemodynamics

Full Text

References

References
1 Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Hum Dev 2010; 86 (06) 329-338
2 García-Alix A, Martínez-Biarge M, Diez J, Gayá F, Quero J. Neonatal hypoxic-ischemic encephalopathy: incidence and prevalence in the first decade of the 21st century [in Spanish]. An Pediatr (Barc) 2009; 71 (04) 319-326
3 Mwaniki MK, Atieno M, Lawn JE, Newton CR. Long-term neurodevelopmental outcomes after intrauterine and neonatal insults: a systematic review. Lancet 2012; 379 (9814): 445-452
4 Blanco D, García-Alix A, Valverde E, Tenorio V, Vento M, Cabañas F. ; Comisión de Estándares de la Sociedad Española de Neonatología (SEN). Neuroprotection with hypothermia in the newborn with hypoxic-ischaemic encephalopathy. Standard guidelines for its clinical application [in Spanish]. An Pediatr (Barc) 2011; 75 (05) 341.e1-341.e20
5 Hagmann CF, Brotschi B, Bernet V, Latal B, Berger TM, Robertson NJ. Hypothermia for perinatal asphyxial encephalopathy. Swiss Med Wkly 2011; 141: w13145
6 Jacobs SE, Morley CJ, Inder TE. , et al; Infant Cooling Evaluation Collaboration. Whole-body hypothermia for term and near-term newborns with hypoxic-ischemic encephalopathy: a randomized controlled trial. Arch Pediatr Adolesc Med 2011; 165 (08) 692-700
7 Czernik C, Rhode S, Helfer S, Schmalisch G, Bührer C. Left ventricular longitudinal strain and strain rate measured by 2-D speckle tracking echocardiography in neonates during whole-body hypothermia. Ultrasound Med Biol 2013; 39 (08) 1343-1349
8 Nestaas E, Skranes JH, Støylen A, Brunvand L, Fugelseth D. The myocardial function during and after whole-body therapeutic hypothermia for hypoxic-ischemic encephalopathy, a cohort study. Early Hum Dev 2014; 90 (05) 247-252
9 Liu J, Cao HY, Huang XH, Wang Q. The pattern and early diagnostic value of Doppler ultrasound for neonatal hypoxic-ischemic encephalopathy. J Trop Pediatr 2007; 53 (05) 351-354
10 Nishimaki S, Iwasaki S, Minamisawa S, Seki K, Yokota S. Blood flow velocities in the anterior cerebral artery and basilar artery in asphyxiated infants. J Ultrasound Med 2008; 27 (06) 955-960
11 Hochwald O, Jabr M, Osiovich H, Miller SP, McNamara PJ, Lavoie PM. Preferential cephalic redistribution of left ventricular cardiac output during therapeutic hypothermia for perinatal hypoxic-ischemic encephalopathy. J Pediatr 2014; 164 (05) 999-10041
12 Miller SP, Ramaswamy V, Michelson D. , et al. Patterns of brain injury in term neonatal encephalopathy. J Pediatr 2005; 146 (04) 453-460
13 Cheong JL, Coleman L, Hunt RW. , et al; Infant Cooling Evaluation Collaboration. Prognostic utility of magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy: substudy of a randomized trial. Arch Pediatr Adolesc Med 2012; 166 (07) 634-640
14 Sarnat HB, Sarnat MS. Neonatal encephalopathy following fetal distress. A clinical and electroencephalographic study. Arch Neurol 1976; 33 (10) 696-705
15 Jain A, El-Khuffash AF, Kuipers BCW. , et al. Left ventricular function in healthy term neonates during the transitional period. J Pediatr 2017; 182: 197-203
16 Jain A, Mohamed A, El-Khuffash A. , et al. A comprehensive echocardiographic protocol for assessing neonatal right ventricular dimensions and function in the transitional period: normative data and z scores. J Am Soc Echocardiogr 2014; 27 (12) 1293-1304
17 Barkovich AJ, Hajnal BL, Vigneron D. , et al. Prediction of neuromotor outcome in perinatal asphyxia: evaluation of MR scoring systems. AJNR Am J Neuroradiol 1998; 19 (01) 143-149
18 Chau V, Poskitt KJ, Sargent MA. , et al. Comparison of computer tomography and magnetic resonance imaging scans on the third day of life in term newborns with neonatal encephalopathy. Pediatrics 2009; 123 (01) 319-326
19 Gano D, Chau V, Poskitt KJ. , 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 (01) 82-87
20 Hayes BC, Ryan S, McGarvey C. , et al. Brain magnetic resonance imaging and outcome after hypoxic ischaemic encephalopathy. J Matern Fetal Neonatal Med 2016; 29 (05) 777-782
21 Gluckman PD, Wyatt JS, Azzopardi D. , et al. Selective head cooling with mild systemic hypothermia after neonatal encephalopathy: multicentre randomised trial. Lancet 2005; 365 (9460): 663-670
22 Shankaran S, Laptook AR, Ehrenkranz RA. , et al; National Institute of Child Health and Human Development Neonatal Research Network. Whole-body hypothermia for neonates with hypoxic-ischemic encephalopathy. N Engl J Med 2005; 353 (15) 1574-1584
23 Gagnon M-H, Wintermark P. Effect of persistent pulmonary hypertension on brain oxygenation in asphyxiated term newborns treated with hypothermia. J Matern Fetal Neonatal Med 2016; 29 (13) 2049-2055
24 Thoresen M, Whitelaw A. Cardiovascular changes during mild therapeutic hypothermia and rewarming in infants with hypoxic-ischemic encephalopathy. Pediatrics 2000; 106 (1 Pt 1): 92-99
25 Lapointe A, Barrington KJ. Pulmonary hypertension and the asphyxiated newborn. J Pediatr 2011; 158 (2, Suppl): e19-e24
26 Aaltonen M, Soukka H, Halkola L. , et al. Asphyxia aggravates systemic hypotension but not pulmonary hypertension in piglets with meconium aspiration. Pediatr Res 2003; 53 (03) 473-478
27 Dakshinamurti S. Pathophysiologic mechanisms of persistent pulmonary hypertension of the newborn. Pediatr Pulmonol 2005; 39 (06) 492-503
28 Gersony WM, Morishima HO, Daniel SS. , et al. The hemodynamic effects of intrauterine hypoxia: an experimental model in newborn lambs. J Pediatr 1976; 89 (04) 631-635
29 Gebauer CM, Knuepfer M, Robel-Tillig E, Pulzer F, Vogtmann C. Hemodynamics among neonates with hypoxic-ischemic encephalopathy during whole-body hypothermia and passive rewarming. Pediatrics 2006; 117 (03) 843-850
30 Kluckow M. Functional echocardiography in assessment of the cardiovascular system in asphyxiated neonates. J Pediatr 2011; 158 (2, Suppl) e13-e18
31 Del Toro J, Louis PT, Goddard-Finegold J. Cerebrovascular regulation and neonatal brain injury. Pediatr Neurol 1991; 7 (01) 3-12
32 Firth AL, Yuan JX. Bringing down the ROS: a new therapeutic approach for PPHN. Am J Physiol Lung Cell Mol Physiol 2008; 295 (06) L976-L978
33 Dalen ML, Liu X, Elstad M. , et al. Resuscitation with 100% oxygen increases injury and counteracts the neuroprotective effect of therapeutic hypothermia in the neonatal rat. Pediatr Res 2012; 71 (03) 247-252
34 Kuwagata Y, Oda J, Ninomiya N, Shiozaki T, Shimazu T, Sugimoto H. Changes in left ventricular performance in patients with severe head injury during and after mild hypothermia. J Trauma 1999; 47 (04) 666-672
35 Sehgal A, Wong F, Mehta S. Reduced cardiac output and its correlation with coronary blood flow and troponin in asphyxiated infants treated with therapeutic hypothermia. Eur J Pediatr 2012; 171 (10) 1511-1517
36 Costa S, Zecca E, De Rosa G. , et al. Is serum troponin T a useful marker of myocardial damage in newborn infants with perinatal asphyxia?. Acta Paediatr 2007; 96 (02) 181-184
37 Barberi I, Calabrò MP, Cordaro S. , et al. Myocardial ischaemia in neonates with perinatal asphyxia. Electrocardiographic, echocardiographic and enzymatic correlations. Eur J Pediatr 1999; 158 (09) 742-747
38 Nestaas E, Støylen A, Brunvand L, Fugelseth D. Longitudinal strain and strain rate by tissue Doppler are more sensitive indices than fractional shortening for assessing the reduced myocardial function in asphyxiated neonates. Cardiol Young 2011; 21 (01) 1-7
39 Szymankiewicz M, Matuszczak-Wleklak M, Hodgman JE, Gadzinowski J. Usefulness of cardiac troponin T and echocardiography in the diagnosis of hypoxic myocardial injury of full-term neonates. Biol Neonate 2005; 88 (01) 19-23

References
1 Lang RMBL, Badano LP, Mor-Avi V. , et al. Recommendations for cardiac chamber quantification by echocardiography in adults: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2015; 28 (01) 1-39.e14
2 Slama M, Susic D, Varagic J, Ahn J, Frohlich ED. Echocardiographic measurement of cardiac output in rats. Am J Physiol Heart Circ Physiol 2003; 284 (02) H691-H697
3 Nagueh SF, Smiseth OA, Appleton CP. , et al. Recommendations for the evaluation of left ventricular diastolic function by echocardiography: an update from the American Society of Echocardiography and the European Association of Cardiovascular Imaging. J Am Soc Echocardiogr 2016; 29 (04) 277-314
4 Jain A, Mohamed A, El-Khuffash A. , et al. A comprehensive echocardiographic protocol for assessing neonatal right ventricular dimensions and function in the transitional period: normative data and z scores. J Am Soc Echocardiogr 2014; 27 (12) 1293-1304
5 Yared K, Noseworthy P, Weyman AE, McCabe E, Picard MH, Baggish AL. Pulmonary artery acceleration time provides an accurate estimate of systolic pulmonary arterial pressure during transthoracic echocardiography. J Am Soc Echocardiogr 2011; 24 (06) 687-692