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Hemodynamics in infants with hypoxemic ischemic encephalopathy: pathophysiology and beyond

Journal of Perinatology (2025)Cite this article

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Abstract

Perinatal asphyxia is a critical event causing variable degrees of multiorgan dysfunction. Hypoxemic ischemic encephalopathy (HIE) features the brain exposure to asphyxia, and most of the underlying pathophysiology is a related to impaired blood flow and oxygen delivery to the brain. Cardiovascular compromise is common in this context and often necessitates initiation of inotropic support. In this article, we highlight the neonatal hemodynamics and its derangements, following asphyxia, and we highlight the pitfalls in the current hemodynamic approach.

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Fig. 1: Complexity of hemodynamics following perinatal asphyxia.
Fig. 2: Different types of hemodynamic compromise following asphyxia.

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References

  1. Kurinczuk JJ, White-Koning M, Badawi N. Epidemiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy. Early Human Dev. 2010;86:329–38.

  2. Schiariti V, Klassen AF, Houbé JS, Synnes A, Lisonkova S, Lee SK. Perinatal characteristics and parents’ perspective of health status of NICU graduates born at term. J Perinatol. 2008;28:368–76.

    Article  CAS  PubMed  Google Scholar 

  3. Erecinska M, Thoresen M, Silver IA. Effects of hypothermia on energy metabolism in mammalian central nervous system. J Cereb Blood Flow Metab. 2003;23:513–30.

    Article  CAS  PubMed  Google Scholar 

  4. Natarajan G, Pappas A, Shankaran S. Outcomes in childhood following therapeutic hypothermia for neonatal hypoxic-ischemic encephalopathy (HIE). Semin Perinatol. 2016;40:549–55.

    Article  PubMed  PubMed Central  Google Scholar 

  5. 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:CD003311.

  6. Goh D, Minns RA, Hendry GMA, Thambyayah M, Steers AJW. Cerebrovascular resistive index assessed by Duplex Doppler sonography and its relationship to intracranial pressure in infantile hydrocephalus. Pediatr Radio. 1992;22:246–50.

    Article  CAS  Google Scholar 

  7. Wood T, Thoresen M. Physiological responses to hypothermia. Semin Fetal Neonatal Med. 2015;20:87–96.

  8. 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;365:663–70.

    Article  PubMed  Google Scholar 

  9. Thoresen M. Supportive care during neuroprotective hypothermia in the term newborn: adverse effects and their prevention. Clin Perinatol. 2008;35:749–63.

    Article  PubMed  Google Scholar 

  10. Dill DB, Forbes WH. Respiratory and metabolic effects of hypothermia. Am J Physiol Legacy Content. 1941;132:685–97.

  11. Bacher A. Effects of body temperature on blood gases. Intensive Care Med. 2005;31:24–7.

  12. Bisson J, Younker J. Correcting arterial blood gases for temperature: (when) is it clinically significant? Nurs Crit Care. 2006;11:232–8.

  13. Cotten CM, Shankaran S. Hypothermia for hypoxic-ischemic encephalopathy. Expert Rev Obstet Gynecol. 2010;5:227–39.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Wassink G, Davidson JO, Dhillon SK, Zhou K, Bennet L, Thoresen M, et al. Therapeutic Hypothermia in Neonatal Hypoxic-Ischemic Encephalopathy. Curr Neurol Neurosci Rep. 2019;19:2.

    Article  PubMed  Google Scholar 

  15. Ristovska S, Stomnaroska O, Danilovski D. Hypoxic ischemic encephalopathy (HIE) in term and preterm infants. Prilozi. 2022;43:77–84.

    PubMed  Google Scholar 

  16. Silveira RC, Procianoy RS. Hypothermia therapy for newborns with hypoxic ischemic encephalopathy. J de Pediatr. 2015;91:S78–S83.

    Article  Google Scholar 

  17. Wang Z, Zhang D, Zhang P, Zhou W, Hu L, Wang L, et al. Safety and efficacy of therapeutic hypothermia in neonates with mild hypoxic-ischemic encephalopathy. BMC Pediatr. 2023;23:530.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Chong WH, Ong HY, Ooi JS, Eleen Khaw YY, Lim LM, Tew MM, et al. The effect of hypoxic ischemic encephalopathy towards multi-organ complications and its early outcome at a Malaysian district hospital. Med J Malays. 2024;79:184–90.

    CAS  Google Scholar 

  19. 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.

    Article  PubMed  PubMed Central  Google Scholar 

  20. Basiri B, Sabzehei M, Sabahi M. Predictive factors of death in neonates with hypoxic-ischemic encephalopathy receiving selective head cooling. Clin Exp Pediatr. 2021;64:180–7.

    Article  CAS  PubMed  Google Scholar 

  21. Kumar C, Peruri G, Plakkal N, Oleti TP, Aradhya AS, Tandur B, et al. Short-term outcome and predictors of survival among neonates with moderate or severe hypoxic ischemic encephalopathy: data from the Indian Neonatal Collaborative. Indian Pediatr. 2022;59:21–24.

    Article  PubMed  Google Scholar 

  22. Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Arch Dis Child Fetal Neonatal Ed. 2004;89:F152–F155.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Hankins GD. Neonatal organ system injury in acute birth asphyxia sufficient to result in neonatal encephalopathy. Obstet Gynecol. 2002;99:688–91.

    PubMed  Google Scholar 

  24. Martín-Ancel A, García-Alix A, Cabañas FGF, Burgueros M, Quero J. Multiple organ involvement in perinatal asphyxia. J Pediatr. 1995;127:786–93.

    Article  PubMed  Google Scholar 

  25. Michniewicz B, Al Saad SR, Karbowski LM, Gadzinowski J, Szymankiewicz M, Szpecht D. Organ complications of infants with hypoxic ischemic encephalopathy before. Ther Hypothermia Temp Manag. 2021;11:58–63.

    Article  PubMed  Google Scholar 

  26. Sweetman DU, Strickland T, Isweisi E, Kelly L, Slevin MT, Donoghue V, et al. Multi-organ dysfunction scoring in neonatal encephalopathy (MODE Score) and neurodevelopmental outcomes. Acta Paediatr Int J Paediatr. 2022;111:93–98.

    Article  Google Scholar 

  27. Bozkurt O, Yucesoy E. Acute kidney injury in neonates with perinatal asphyxia receiving therapeutic hypothermia. Am J Perinatol. 2021;38:922–9.

    Article  PubMed  Google Scholar 

  28. Chaudhari T, McGuire W. Allopurinol for preventing mortality and morbidity in newborn infants with suspected hypoxic-ischaemic encephalopathy. Cochrane Database Syst Rev. 2012;2012:CD006817.

  29. Armour EA, Curcio AM, Fryer RH. Neonatal hypoxic ischemic encephalopathy: an updated preclinical and clinical review. OBM Neurobiol. 2020;04:1–15.

    Article  Google Scholar 

  30. Allen KA, Brandon DH. Hypoxic Ischemic Encephalopathy: Pathophysiology and Experimental Treatments. Newborn Infant Nurs Rev. 2011;11:125–33.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Dumbuya JS, Chen L, Wu JY, Wang B. The role of G-CSF neuroprotective effects in neonatal hypoxic-ischemic encephalopathy (HIE): current status. J Neuroinflammation. 2021;18:55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Shalak L, Perlman JM. Hypoxic-ischemic brain injury in the term infant-current concepts. Early Hum Dev. 2004;80:125–41.

    Article  PubMed  Google Scholar 

  33. Perlman JM. Brain injury in the term infant. Semin Perinatol. 2004;28:415–24.

    Article  PubMed  Google Scholar 

  34. Grow J, Barks JDE. Pathogenesis of hypoxic-ischemic cerebral injury in the term infant: current concepts. Clin Perinatol. 2002;29:585–602.

    Article  PubMed  Google Scholar 

  35. Peeters LLH, Sheldon RE, Jones MD, Makowski EL, Meschia G. Blood flow to fetal organs as a function of arterial oxygen content. Am J Obstet Gynecol. 1979;135:637–46.

    Article  CAS  PubMed  Google Scholar 

  36. Cohn HE, Sacks EJ, Heymann MA, Rudolph AM. Cardiovascular responses to hypoxemia and acidemia in fetal lambs. Am J Obstet Gynecol. 1974;120:817–24.

    Article  CAS  PubMed  Google Scholar 

  37. Rudolph AM. Distribution and regulation of blood flow in the fetal and neonatal lamb. Circ Res. 1985;57:811–21.

    Article  CAS  PubMed  Google Scholar 

  38. Jensen A, Roman C, Rudolph AM. Effects of reducing uterine blood flow on fetal blood flow distribution and oxygen delivery. J Dev Physiol. 1991;15:309–23.

    CAS  PubMed  Google Scholar 

  39. Pedroso FS, Riesgo RS, Gatiboni T, Rotta NT. The diving reflex in healthy infants in the first year of life. J Child Neurol. 2012;27:168–71.

    Article  PubMed  Google Scholar 

  40. Heusser K, Dzamonja G, Tank J, Palada I, Valic Z, Bakovic D, et al. Cardiovascular regulation during apnea in elite divers. Hypertension. 2009;53:719–24.

    Article  CAS  PubMed  Google Scholar 

  41. Campbell LB, Gooden BA, Horowitz JD. Cardiovascular responses to partial and total immersion in man. J Physiol. 1969;202:239–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Panneton WM. The mammalian diving response: an enigmatic reflex to preserve life? Physiology. 2013;28:284–97.

  43. Graves B. Challenges of neonatal resuscitation for nurse-midwives. J Nurse Midwifery. 1988;33:217–24.

    Article  CAS  PubMed  Google Scholar 

  44. Manning FA, Platt LD, Sipos L, Keegan KA. Fetal breathing movements and the nonstress test in high-risk pregnancies. Am J Obstet Gynecol. 1979;135:511–5.

    Article  CAS  PubMed  Google Scholar 

  45. Ovali F. Hemodynamic changes and evaluation during hypoxic-ischemic encephalopathy and therapeutic hypothermia. Early Hum Dev. 2022;167:105563.

    Article  PubMed  Google Scholar 

  46. Habib S, Saini J, Amendoeira S, McNair C. Hemodynamic instability in hypoxic ischemic encephalopathy: more than just brain injury—understanding physiology, assessment, and management. Neonatal Netw. 2020;39:129–36.

    PubMed  Google Scholar 

  47. Wang J, Li J, Yin X, Zhou H, Zheng Y, Liu H. Cerebral hemodynamics of hypoxic-ischemic encephalopathy neonates at different ages detected by arterial spin labeling imaging. Clin Hemorheol Microcirc. 2022;81:271–9.

    Article  CAS  PubMed  Google Scholar 

  48. Rios DR, Lapointe A, Schmolzer GM, Mohammad K, VanMeurs KP, Keller RL, et al. Hemodynamic optimization for neonates with neonatal encephalopathy caused by a hypoxic ischemic event: physiological and therapeutic considerations. Semin Fetal Neonatal Med. 2021;26:101277.

    Article  PubMed  Google Scholar 

  49. Rubini A. Effect of perfusate temperature on pulmonary vascular resistance and compliance by arterial and venous occlusion in the rat. Eur J Appl Physiol. 2005;93:435–9.

    Article  PubMed  Google Scholar 

  50. Vasquez AM, Bischoff AR, Giesinger RE, McNamara PJ. Impact of therapeutic hypothermia (TH) on echocardiography indices of pulmonary hemodynamics among neonates with hypoxic ischemic encephalopathy (HIE). J Perinatol. 2024;44:1212–5. https://doi.org/10.1038/s41372-024-01958-8.

    Article  PubMed  Google Scholar 

  51. Bamber AR, Pryce J, Cook A, Ashworth M, Sebire NJ. Myocardial necrosis and infarction in newborns and infants. Forensic Sci Med Pathol. 2013;9:521–7.

    Article  PubMed  Google Scholar 

  52. Jedelkin R, Primhak A, Shennan AT, Swyer PR, Rowe RD. Serial electrocardiographic changes in healthy and stressed neonates. Arch Dis Child. 1983;58:605–11.

  53. Hamm CW. Troponin t: a new marker for myocardial cell injury. Ann Med. 1994;26:319–20.

    Article  CAS  PubMed  Google Scholar 

  54. Mair J, Dienstl F, Puschendorf B. Cardiac troponin t in the diagnosis of myocardial injury. Crit Rev Clin Lab Sci. 1992;29:31–57.

    Article  CAS  PubMed  Google Scholar 

  55. Abiramalatha T, Kumar M, Chandran S, Sudhakar Y, Thenmozhi M, Thomas N. Troponin-T as a biomarker in neonates with perinatal asphyxia. J Neonatal Perinat Med. 2017;10:275–80.

    Article  CAS  Google Scholar 

  56. Donnelly WH, Bucciarelli RL, Nelson RM. Ischemic papillary muscle necrosis in stressed newborn infants. J Pediatr. 1980;96:295–300.

    Article  CAS  PubMed  Google Scholar 

  57. Al Balushi A, Barbosa Vargas S, Maluorni J, Sanon PN, Rampakakis E, Saint-Martin C, et al. Hypotension and brain injury in asphyxiated newborns treated with hypothermia. Am J Perinatol. 2018;35:031–8.

    Article  Google Scholar 

  58. Siefkes HM, Lakshminrusimha S. Management of systemic hypotension in term infants with persistent pulmonary hypertension of the newborn: An illustrated review. Arch Dis Childhood. 2021;106:446–55.

  59. Lee JK, Wang B, Reyes M, Armstrong JS, Kulikowicz E, Santos PT, et al. Hypothermia and rewarming activate a macroglial unfolded protein response independent of hypoxic-ischemic brain injury in neonatal piglets. Dev Neurosci. 2016;38:277–94.

    Article  CAS  PubMed  Google Scholar 

  60. Howlett JA, Northington FJ, Gilmore MM, Tekes A, Huisman TAGM, Parkinson C, et al. Cerebrovascular autoregulation and neurologic injury in neonatal hypoxic-ischemic encephalopathy. Pediatr Res. 2013;74:525–35.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Massaro AN, Govindan RB, Vezina G, Chang T, Andescavage NN, Wang Y, et al. Impaired cerebral autoregulation and brain injury in newborns with hypoxic-ischemic encephalopathy treated with hypothermia. J Neurophysiol. 2015;114:818–24.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Chen MW, Lee JK, Vezina G, Tekes A, Perin J, Li R, et al. The utility of cerebral autoregulation indices in detecting severe brain injury varies by cooling treatment phase in neonates with hypoxic-ischemic encephalopathy. Dev Neurosci. 2022;44:363–72.

    Article  CAS  PubMed  Google Scholar 

  63. Carrasco M, Perin J, Jennings JM, Parkinson C, Gilmore MM, Chavez-Valdez R, et al. Cerebral autoregulation and conventional and diffusion tensor imaging magnetic resonance imaging in neonatal hypoxic-ischemic encephalopathy. Pediatr Neurol. 2018;82:36–43.

    Article  PubMed  PubMed Central  Google Scholar 

  64. Lee JK, Poretti A, Perin J, Huisman TAGM, Parkinson C, Chavez-Valdez R, et al. Optimizing cerebral autoregulation may decrease neonatal regional hypoxic-ischemic brain injury. Dev Neurosci. 2017;39:248–56.

    Article  PubMed  Google Scholar 

  65. Yoon JH, Lee E, Yum SK, Moon C, Youn YA, Kwun YJ, et al. Impacts of therapeutic hypothermia on cardiovascular hemodynamics in newborns with hypoxic-ischemic encephalopathy: a case control study using echocardiography. J Matern Fetal Neonatal Med. 2018;31:2175–82.

    Article  PubMed  Google Scholar 

  66. More K, Sakhuja P, Giesinger R, Ting J, Keyzers M, Sheth J, et al. Cardiovascular associations with abnormal brain magnetic resonance imaging in neonates with hypoxic ischemic encephalopathy undergoing therapeutic hypothermia and rewarming. Am J Perinatol. 2018;35:979–89.

    Article  PubMed  Google Scholar 

  67. Forman E, Breatnach CR, Ryan S, Semberova J, Miletin J, Foran A, et al. Noninvasive continuous cardiac output and cerebral perfusion monitoring in term infants with neonatal encephalopathy: assessment of feasibility and reliability. Pediatr Res. 2017;82:789–95.

    Article  PubMed  Google Scholar 

  68. Montaldo P, Cuccaro P, Caredda E, Pugliese U, De Vivo M, Orbinato F, et al. Electrocardiographic and echocardiographic changes during therapeutic hypothermia in encephalopathic infants with long-term adverse outcome. Resuscitation. 2018;130:99–104.

    Article  PubMed  Google Scholar 

  69. Ilves P, Lintrop M, Talvik I, Muug K, Maipuu L. Changes in cerebral and visceral blood flow velocities in asphyxiated term neonates with hypoxic-ischemic encephalopathy. J Ultrasound Med. 2009;28:1471–80.

    Article  PubMed  Google Scholar 

  70. 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 Pediatrics. 2014;164:999–1004.e1.

    Article  Google Scholar 

  71. Osborn DA, Evans N, Kluckow M. Clinical detection of low upper body blood flow in very premature infants using blood pressure, capillary refill time, and central-peripheral temperature difference. Arch Dis Child Fetal Neonatal Ed. 2004;89:F168–F173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Kluckow M, Evans N. Low superior vena cava flow and intraventricular haemorrhage in preterm infants. Arch Dis Child Fetal Neonatal Ed. 2000;82:188F–194.

    Article  Google Scholar 

  73. Osborn DA, Evans N, Kluckow M. Hemodynamic and antecedent risk factors of early and late periventricular/intraventricular hemorrhage in premature infants. Pediatrics. 2003;112:33–39.

    Article  PubMed  Google Scholar 

  74. Osborn DA, Evans N, Kluckow M. Effect of early targeted indomethacin on the ductus arteriosus and blood flow to the upper body and brain in the preterm infant. Arch Dis Child Fetal Neonatal Ed. 2003;88:F477–F482.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. McGovern M, Miletin J. A review of superior vena cava flow measurement in the neonate by functional echocardiography. Acta Paediatr Int J Paediatr. 2017;106:22–29.

    Article  Google Scholar 

  76. Shimada S, Kasai T, Hoshi A, Murata A, Chida S. Cardiocirculatory effects of patent ductus arteriosus in extremely low-birth-weight infants with respiratory distress syndrome. Pediatr Int. 2003;45:255–62.

    Article  PubMed  Google Scholar 

  77. Surak A, Bischoff A. Should SVC flow be a routine measure when performing targeted neonatal echocardiography? A narrative review. Pediatr Neonatol. 2024;65:323–7.

    Article  PubMed  Google Scholar 

  78. Gautam B, Surak A, Campbell SM, Kumar M. Superior Vena Cava flow in preterm infants and neonatal outcomes: a systematic review. Am J Perinatol. 2023. http://www.thieme-connect.de/DOI/DOI?10.1055/a-2113-8621.

  79. Thewissen L, Caicedo A, Lemmers P, Van Bel F, Van Huffel S, Naulaers G. Measuring near-infrared spectroscopy derived cerebral autoregulation in neonates: From research tool toward bedside multimodal monitoring. Front Pediatr. 2018;6:117.

  80. Alderliesten T, Dix L, Baerts W, Caicedo A, Van Huffel S, Naulaers G, et al. Reference values of regional cerebral oxygen saturation during the first 3 days of life in preterm neonates. Pediatr Res. 2016;79:55–64.

    Article  CAS  PubMed  Google Scholar 

  81. Wijbenga RG, Lemmers PMA, Van Bel F. Cerebral oxygenation during the first days of life in preterm and term neonates: Differences between different brain regions. Pediatr Res. 2011;70:389–94.

    Article  CAS  PubMed  Google Scholar 

  82. Van Vonderen JJ, Roest AAW, Siew ML, Walther FJ, Hooper SB, Te Pas AB. Measuring physiological changes during the transition to life after birth. Neonatology. 2014;105:230–42.

    Article  PubMed  Google Scholar 

  83. Lemmers PMA, Zwanenburg RJ, Benders MJNL, De Vries LS, Groenendaal F, Van Bel F, et al. Cerebral oxygenation and brain activity after perinatal asphyxia: Does hypothermia change their prognostic value?. Pediatr Res. 2013;74:180–5.

    Article  CAS  PubMed  Google Scholar 

  84. Arriaga-Redondo M, Arnaez J, Benavente-Fernández I, Lubián-López S, Hortigüela M, Vega-Del-Val C, et al. Lack of variability in cerebral oximetry tendency in infants with severe hypoxic-ischemic encephalopathy under hypothermia. Ther Hypothermia Temp Manag. 2019;9:243–50.

    Article  PubMed  Google Scholar 

  85. Ancora G, Maranella E, Grandi S, Sbravati F, Coccolini E, Savini S, et al. Early predictors of short term neurodevelopmental outcome in asphyxiated cooled infants. A combined brain amplitude integrated electroencephalography and near infrared spectroscopy study. Brain Dev. 2013;35:26–31.

    Article  PubMed  Google Scholar 

  86. Zaramella P, Saraceni E, Freato F, Falcon E, Suppiej A, Milan A, et al. Can tissue oxygenation index (TOI) and cotside neurophysiological variables predict outcome in depressed/asphyxiated newborn infants?. Early Hum Dev. 2007;83:483–9.

    Article  PubMed  Google Scholar 

  87. Bale G, Mitra S, de Roever I, Sokolska M, Price D, Bainbridge A, et al. Oxygen dependency of mitochondrial metabolism indicates outcome of newborn brain injury. J Cereb Blood Flow Metab. 2019;39:2035–47.

    Article  CAS  PubMed  Google Scholar 

  88. Mitra S, Bale G, Meek J, Tachtsidis I, Robertson NJ. Cerebral near infrared spectroscopy monitoring in term infants with hypoxic ischemic encephalopathy—a systematic review. Front Neurol. 2020;11:393.

  89. Rusin CG, Acosta SI, Brady KM, Vu E, Scahill C, Fonseca B, et al. Automated prediction of cardiorespiratory deterioration in patients with single-ventricle parallel circulation: a multicenter validation study. JTCVS Open. 2023;15:406–11.

    Article  PubMed  PubMed Central  Google Scholar 

  90. 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;90:247–52.

    Article  PubMed  Google Scholar 

  91. Sehgal A, Wong F, Menahem S. Speckle tracking derived strain in infants with severe perinatal asphyxia: a comparative case control study. Cardiovasc Ultrasound. 2013;11:34.

    Article  PubMed  PubMed Central  Google Scholar 

  92. Smolich J. Ultrastructural and functional features of the developing mammalian heart: a brief overview. Reprod Fertil Dev. 1995;7:451–61.

    Article  CAS  PubMed  Google Scholar 

  93. Arrigo M, Huber LC, Winnik S, Mikulicic F, Guidetti F, Frank M, et al. Right ventricular failure: pathophysiology, diagnosis and treatment. Card Fail Rev. 2019;5:140–6.

    Article  PubMed  PubMed Central  Google Scholar 

  94. Pinson CW, Morton MJ, Thornburg KL. An anatomic basis for fetal right ventricular dominance and arterial pressure sensitivity. J Dev Physiol. 1987;9:253–69.

    CAS  PubMed  Google Scholar 

  95. Patel PA, Malkin CJ, Ali N. Assessment of coronary physiology – the evidence and implications. Clin Med. 2019;19:364–68.

  96. Duncker DJ, Bache RJ. Regulation of coronary blood flow during exercise. Physiological Rev. 2008;88:1009–86.

    Article  CAS  Google Scholar 

  97. Konstam MA, Kiernan MS, Bernstein D, Bozkurt B, Jacob M, Kapur NK, et al. Evaluation and management of right-sided heart failure: a scientific statement from the American Heart Association. Circulation. 2018 May 15;137:e578–e622.

  98. James TN. Effective coronary perfusion pressure. Am Heart J. 1961;62:427–9.

    Article  CAS  PubMed  Google Scholar 

  99. Crystal GJ, Pagel PS. Right ventricular perfusion: physiology and clinical implications. Anesthesiology. 2018;128:202–18.

    Article  PubMed  Google Scholar 

  100. Ryan JJ, Huston J, Kutty S, Hatton ND, Bowman L, Tian L, et al. Right ventricular adaptation and failure in pulmonary arterial hypertension. Can J Cardiol. 2015;31:391–406.

    PubMed  Google Scholar 

  101. Giesinger RE, El Shahed AI, Castaldo MP, Breatnach CR, Chau V, Whyte HE, et al. Impaired right ventricular performance is associated with adverse outcome after hypoxic ischemic encephalopathy. Am J Respir Crit Care Med. 2019;200:1294–305.

    Article  CAS  PubMed  Google Scholar 

  102. Giesinger RE, El Shahed AI, Castaldo MP, Bischoff AR, Chau V, Whyte HEA, et al. Neurodevelopmental outcome following hypoxic ischaemic encephalopathy and therapeutic hypothermia is related to right ventricular performance at 24-hour postnatal age. Arch Dis Child Fetal Neonatal Ed. 2022;107:70–75.

    Article  PubMed  Google Scholar 

  103. Altit G, Bonifacio SL, Guimaraes CV, Bhombal S, Sivakumar G, Yan B, et al. Cardiac dysfunction in neonatal HIE is associated with increased mortality and brain injury by MRI. Am J Perinatol. 2023;40:1336–44.

    Article  PubMed  Google Scholar 

  104. Elias P, Lapointe A, Wintermark P, Moore SS, Villegas Martinez D, Simoneau J, et al. Left ventricular function and dimensions are altered early in infants developing brain injury in the setting of neonatal encephalopathy. J Pediatrics. 2023;261:113585.

    Article  Google Scholar 

  105. Agarwal P, Shankaran S, Laptook AR, Chowdhury D, Lakshminrusimha S, Bonifacio SL, et al. Outcomes of infants with hypoxic ischemic encephalopathy and persistent pulmonary hypertension of the newborn: results from three NICHD studies. J Perinatol. 2021;41:502–11.

    Article  PubMed  PubMed Central  Google Scholar 

  106. Obolonska O, Mavropulo T, Vakulenko L, Borysova T, Obolonskyi O. Diagnostic value of additional markers for acute kidney injury in preterm neonates with patent ductus arteriosus. Neonatol Surg Perinatal Med. 2023;3:26–35.

  107. Levene MI, Grindulis H, Sands C, Moore JR. Comparison of two methods of predicting outcome in perinatal asphyxia. Lancet. 1986;327:67–69.

    Article  Google Scholar 

  108. Lowe LH, Bailey Z. State-of-the-art cranial sonography: Part 1, Modern techniques and image interpretation. Am J Roentgenol. 2011;196:1028–33.

    Article  Google Scholar 

  109. Allison JW, Faddis LA, Kinder DL, Roberson PK, Glasier CM, Seibert JJ. Intracanial resistive index (RI) values in normal term infants during the first day of life. Pediatr Radio. 2000;30:618–20.

    Article  CAS  Google Scholar 

  110. Ecury-Goossen GM, Raets MMA, Camfferman FA, Vos RHJ, van Rosmalen J, Reiss IKM, et al. Resistive indices of cerebral arteries in very preterm infants: values throughout stay in the neonatal intensive care unit and impact of patent ductus arteriosus. Pediatr Radio. 2016;46:1291–1300.

    Article  Google Scholar 

  111. Stark JE, Seibert JJ. Cerebral artery Doppler ultrasonography for prediction of outcome after perinatal asphyxia. J Ultrasound Med. 1994;13:595–600.

    Article  CAS  PubMed  Google Scholar 

  112. Seibert JJ, McCowan TC, Chadduck WM, Adametz JR, Glasier CM, Williamson SL, et al. Duplex pulsed Doppler US versus intracranial pressure in the neonate: clinical and experimental studies. Radiology. 1989;171:155–9.

    Article  CAS  PubMed  Google Scholar 

  113. Petty GW, Mohr JP, Pedley TA, Tatemichi TK, Lennihan L, Duterte DI, et al. The role of transcranial Doppler in confirming brain death: sensitivity, specificity, and suggestions for performance and interpretation. Neurology. 1990;40:300.

    Article  CAS  PubMed  Google Scholar 

  114. Shiogai T, Sato E, Tokitsu M, Hara M, Takeuchi K. Transcranial Doppler monitoring in severe brain damage: relationships between intracranial haemodynamics, brain dysfunction and outcome. Neurol Res. 1990;12:205–13.

    Article  CAS  PubMed  Google Scholar 

  115. 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;53:351–4.

    Article  PubMed  Google Scholar 

  116. 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;27:955–60.

    Article  PubMed  Google Scholar 

  117. Skranes JH, Elstad M, Thoresen M, Cowan FM, Stiris T, Fugelseth D. Hypothermia makes cerebral resistance index a poor prognostic tool in encephalopathic newborns. Neonatology. 2014;106:17–23.

    Article  CAS  PubMed  Google Scholar 

  118. Jain SV, Pagano L, Gillam-Krakauer M, Slaughter JC, Pruthi S, Engelhardt B. Cerebral regional oxygen saturation trends in infants with hypoxic-ischemic encephalopathy. Early Hum Dev. 2017;113:55–61.

    Article  CAS  PubMed  Google Scholar 

  119. Marwick TH. Measurement of strain and strain rate by echocardiography: Ready for prime time?. J Am Coll Cardiol. 2006;47:1313–27.

    Article  PubMed  Google Scholar 

  120. Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography - basic concepts and clinical applicability. Curr Cardiol Rev. 2009;5:133–48.

    Article  PubMed  PubMed Central  Google Scholar 

  121. Hoit BD. Strain and strain rate echocardiography and coronary artery disease. Circ Cardiovasc Imaging. 2011;4:179–90.

    Article  PubMed  Google Scholar 

  122. Yamada KP, Kariya T, Aikawa T, Ishikawa K. Effects of therapeutic hypothermia on normal and ischemic heart. Front Cardiovasc Med. 2021;8:642843.

  123. Yang X, Liu Y, Yang XM, Hu F, Cui L, Swingle MR, et al. Cardioprotection by mild hypothermia during ischemia involves preservation of ERK activity. Basic Res Cardiol. 2011;106:421–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Mochizuki T, Yu S, Katoh T, Aoki K, Sato S. Cardioprotective effect of therapeutic hypothermia at 34°C against ischaemia/reperfusion injury mediated by PI3K and nitric oxide in a rat isolated heart model. Resuscitation. 2012;83:238–42.

    Article  CAS  PubMed  Google Scholar 

  125. Shao ZH, Sharp WW, Wojcik KR, Li CQ, Han M, Chang WT, et al. Therapeutic hypothermia cardioprotection via Akt- and nitric oxide-mediated attenuation of mitochondrial oxidants. Am J Physiol Heart Circ Physiol. 2010;298:H2164–H2173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Ning XH, Chi EY, Buroker NE, Chen SH, Xu CS, Tien YT, et al. Moderate hypothermia (30°C) maintains myocardial integrity and modifies response of cell survival proteins after reperfusion. Am J Physiol Heart Circ Physiol. 2007;293:H2119–H2128.

    Article  CAS  PubMed  Google Scholar 

  127. Joseph S, Kumar S, Ahamed M Z, Lakshmi S. Cardiac troponin-T as a marker of myocardial dysfunction in term neonates with perinatal asphyxia. Indian J Pediatr. 2018;85:877–84.

    Article  PubMed  Google Scholar 

  128. Tapia-Rombo CA, Carpio-Hernández JC, Salazar-Acuña AH, Alvarez-Vázquez E, Mendoza-Zanella R, Pérez-Olea V, et al. Detection of transitory myocardial ischemia secondary to perinatal asphyxia. Arch Med Res. 2000;31:377–83.

    Article  CAS  PubMed  Google Scholar 

  129. Rodriguez MJ, Martinez-Orgado J, Corredera A, Serrano I, Arruza L. Diastolic dysfunction in neonates with hypoxic-ischemic encephalopathy during therapeutic hypothermia: a tissue Doppler study. Front Pediatr. 2022;10:880786.

  130. Bhasin H, Kohli C. Myocardial dysfunction as a predictor of the severity and mortality of hypoxic ischaemic encephalopathy in severe perinatal asphyxia: a case–control study. Paediatr Int Child Health. 2019;39:259–64.

    Article  PubMed  Google Scholar 

  131. Liu J, Li J, Gu M. The correlation between myocardial function and cerebral hemodynamics in term infants with hypoxic-ischemic encephalopathy. J Trop Pediatr. 2006;53:44–48.

    Article  PubMed  Google Scholar 

  132. Kovacs K, Giesinger RE, Lakatos A, Szabo AJ, Szabo M, Jermendy A, et al. Comparative evaluation of approach to cardiovascular care in neonatal encephalopathy undergoing therapeutic hypothermia. J Perinatol. 2022;42:1637–43.

    Article  PubMed  Google Scholar 

  133. Giesinger RE, Levy PT, Ruoss JL, El Dib M, Mohammad K, Wintermark P, et al. Cardiovascular management following hypoxic–ischemic encephalopathy in North America: need for physiologic consideration. Pediatr Res. 2021;90:600–7.

    Article  PubMed  Google Scholar 

  134. Giesinger RE, Bailey LJ, Deshpande P, McNamara PJ. Hypoxic-ischemic encephalopathy and therapeutic hypothermia: the hemodynamic perspective. J Pediatrics. 2017;180:22–30.e2. https://doi.org/10.1016/j.jpeds.2016.09.009.

    Article  Google Scholar 

  135. Surak A, Lalitha R, Bitar E, Hyderi A, Hicks M, Cheung PY, et al. Multimodal assessment of systemic blood flow in infants. Neoreviews. 2022;23:e486–96.

    Article  PubMed  Google Scholar 

  136. Giesinger RE, McNamara PJ. Hemodynamic instability in the critically ill neonate: an approach to cardiovascular support based on disease pathophysiology. Semin Perinatol. 2016;40:174–88.

    Article  PubMed  Google Scholar 

  137. Eriksen VR, Trautner S, Hahn GH, Greisen G. Lactate acidosis and cardiac output during initial therapeutic cooling in asphyxiated newborn infants. PLoS One. 2019;14:e0213537.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Bhayat SI, Gowda HM, Eisenhut M. Should dopamine be the first line inotrope in the treatment of neonatal hypotension? Review of the evidence. World J Clin Pediatr. 2016;5:212.

    Article  PubMed  PubMed Central  Google Scholar 

  139. Dempsey E, Rabe H. The use of cardiotonic drugs in neonates. Clin Perinatol. 2019;46:273–90.

    Article  PubMed  Google Scholar 

  140. Prins I, Plötz FB, Uiterwaal CSPM, Van Vught HJ. Low-dose dopamine in neonatal and pediatric intensive care: a systematic review. Intensive Care Med. 2001;27:206–10.

    Article  CAS  PubMed  Google Scholar 

  141. DiSessa TG, Leitner M, Ti CC, Gluck L, Coen R, Friedman WF. The cardiovascular effects of dopamine in the severely asphyxiated neonate. J Pediatr. 1981;99:772–6.

    Article  CAS  PubMed  Google Scholar 

  142. Pazandak C, McPherson C, Abubakar M, Zanelli S, Fairchild K, Vesoulis Z. Blood pressure profiles in infants with hypoxic ischemic encephalopathy (HIE), response to dopamine, and association with brain injury. Front Pediatr. 2020;8:512.

  143. Manouchehri N, Bigam DL, Churchill T, Rayner D, Joynt C, Cheung PY. A comparison of combination dopamine and epinephrine treatment with high-dose dopamine alone in asphyxiated newborn piglets after resuscitation. Pediatr Res. 2013;73:435–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. James AT, Corcoran JD, McNamara PJ, Franklin O, El-Khuffash AF. The effect of milrinone on right and left ventricular function when used as a rescue therapy for term infants with pulmonary hypertension. Cardiol Young. 2016;26:90–99.

    Article  PubMed  Google Scholar 

  145. Bischoff AR, Habib S, McNamara PJ, Giesinger RE. Hemodynamic response to milrinone for refractory hypoxemia during therapeutic hypothermia for neonatal hypoxic ischemic encephalopathy. J Perinatol. 2021;41:2345–54.

    Article  CAS  PubMed  Google Scholar 

  146. Smith A, Purna JR, Castaldo MP, Ibarra-Rios D, Giesinger RE, Rios DR, et al. Accuracy and reliability of qualitative echocardiography assessment of right ventricular size and function in neonates. Echocardiography. 2019;36:1346–52.

    Article  PubMed  PubMed Central  Google Scholar 

  147. Guillet R, Edwards AD, Thoresen M, Ferriero DM, Gluckman PD, Whitelaw A, et al. Seven-to eight-year follow-up of the CoolCap trial of head cooling for neonatal encephalopathy. Pediatr Res. 2012;71:205–9.

    Article  PubMed  Google Scholar 

  148. 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;371:140–9.

    Article  CAS  PubMed  Google Scholar 

  149. Natarajan G, Pappas A, Shankaran S, Laptook AR, Walsh M, McDonald SA, et al. Effect of inborn vs. outborn delivery on neurodevelopmental outcomes in infants with hypoxic-ischemic encephalopathy: Secondary analyses of the NICHD whole-body cooling trial. Pediatr Res. 2012;72:414–9.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Alammary D, Narvey M, Soni R, Elsayed Y, Louis D. Targeted neonatal echocardiography service in neonatal intensive care in Manitoba, Canada. J Perinatol. 2022;42:655–9.

    Article  PubMed  Google Scholar 

  151. Makoni M, Chatmethakul T, Giesinger R, McNamara PJ. Hemodynamic precision in the neonatal intensive care unit using targeted neonatal echocardiography. J Vis Exp. 2023. https://doi.org/10.3791/64257.

  152. Giesinger RE, Rios DR, Chatmethakul T, Bischoff AR, Sandgren JA, Cunningham A, et al. Impact of early hemodynamic screening on extremely preterm outcomes in a high-performance center. Am J Respir Crit Care Med. 2023;208:290–300.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Giesinger RE, Hobson AA, Bischoff AR, Klein JM, McNamara PJ. Impact of early screening echocardiography and targeted PDA treatment on neonatal outcomes in “22-23” week and “24-26” infants. Semin Perinatol. 2023;47:151721. https://doi.org/10.1016/j.semperi.2023.151721.

    Article  CAS  PubMed  Google Scholar 

  154. Bischoff AR, Bhombal S, Altman CA, Fraga M V., Punn R, Rohatgi RK, et al. Targeted neonatal echocardiography in patients with hemodynamic instability. Pediatrics. 2022;150:e2022056415I.

  155. Goldsmith JP, Keels E. Recognition and management of cardiovascular insufficiency in the very low birth weight newborn. Pediatrics. 2022;149:e2021056051.

  156. Pang R, Mintoft A, Crowley R, Sellwood M, Mitra S, Robertson NJ. Optimizing hemodynamic care in neonatal encephalopathy. Neonatology. 2020;25:101139.

  157. Engdahl RK, Opperman K, Yerrum S, Monroy A, Daly J. Epinephrine regulation of pro-inflammatory and anti-inflammatory macrophage cytokine expression. J Am Coll Surg. 2007;205:S35.

    Article  Google Scholar 

  158. Beck GC, Brinkkoetter P, Hanusch C, Schulte J, van Ackern K, van der Woude FJ, et al. Clinical review: Immunomodulatory effects of dopamine in general inflammation, Critical Care. 2004;8:485–91.

  159. Kovacs K, Szakmar E, Meder U, Szakacs L, Cseko A, Vatai B, et al. A randomized controlled study of low-dose hydrocortisone versus placebo in dopamine-treated hypotensive neonates undergoing hypothermia treatment for hypoxic−ischemic encephalopathy. J Pediatrics. 2019;211:13–19.e3.

    Article  CAS  Google Scholar 

  160. Qamar S, Ansari M, Mohapatra J, Khan S. Correlation of umbilical cord blood pH, base deficit, and lactate levels with outcomes of hypoxic newborns: a prospective study. J Acute Dis. 2023;12:114.

    Article  Google Scholar 

  161. Olofsson P. Umbilical cord pH, blood gases, and lactate at birth: normal values, interpretation, and clinical utility. Am J Obstet Gynecol. 2023;228:S1222–S1240.

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Division of Neonatology, University of Alberta, Edmonton, AB, Canada

    Aimann Surak, Georg M. Schmölzer & Joseph Y. Ting

  2. Centre for the Studies of Asphyxia and Resuscitation, Royal Alexandra Hospital, Edmonton, AB, Canada

    Georg M. Schmölzer

  3. Division of Neonatology, Department of Pediatrics, University of Iowa, Iowa City, IA, USA

    Patrick J. McNamara

  4. Division of Neonatology, Alberta Children’s Hospital Research Institute, Calgary, AB, Canada

    Musab Alshareef & Khorshid Mohammad

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  1. Aimann Surak
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  2. Georg M. Schmölzer
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  6. Khorshid Mohammad
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AS, MA conceptualized, designed and drafted the initial manuscript. GS, PM, JT, KM reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

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Surak, A., Schmölzer, G.M., McNamara, P.J. et al. Hemodynamics in infants with hypoxemic ischemic encephalopathy: pathophysiology and beyond. J Perinatol (2025). https://doi.org/10.1038/s41372-025-02516-6

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