Skip to main content
SpringerLink
Log in

Pediatric Age and the Ontogeny of the Brain and Heart Connection

  • Living reference work entry
  • First Online:
Brain and Heart Dynamics

  • 190 Accesses

Abstract

During development individuals change enormously, and so does the main structure devoted to control their internal organ functioning, the autonomic nervous system (ANS). The connection between the brain and heart starts with few cells from the neural crest exchanging chemical signals with the dorsal aorta and progressively develops into a complex neural network. This network receives afferent inputs from structures such as the carotid sinus and body; it is under the control of higher-order regulatory neural structures and instantly responds, adjusting the heart chronotropism and inotropism and providing a progressively more refined control during its maturation. The acquired flexibility makes the organism capable to adapt to the different environmental conditions that an individual experiences from fetal life until adulthood, with the postnatal development of reflexes and maturation of central regulating areas proceeding until adolescence. One key moment of this maturational process is the shift from sympathetic to parasympathetic balance that occurs during infancy, when the myelinated fibers subserving vagal tone become strong enough to determine the resting heart rate. This maturational process is extremely important for the acquirement of social skills but also leads to periods of developmental instability that could play a significant role in the pathogenesis of either benign conditions such as breath-holding spells or extreme outcomes such as sudden infant death syndrome (SIDS). Conversely, the presence of congenital heart disease may affect deeply brain development, ultimately resulting in a worse neurological outcome in adulthood.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Institutional subscriptions

Similar content being viewed by others

References

  1. Belich AI, Konstantinova NN. Formation of Coordinational function of the central nervous System: Phylo and ontogenetic aspects. J Evol Biochem Physiol. 2003;39(3):375–87.

    Article  Google Scholar 

  2. Schmidt A, Schukat-Talamazzini EG, Zöllkau J, Pytlik A, Leibl S, Kumm K, et al. Universal characteristics of evolution and development are inherent in fetal autonomic brain maturation. Auton Neurosci. 2018;212:32–41. Available from: https://doi.org/10.1016/j.autneu.2018.02.004

    Article  PubMed  Google Scholar 

  3. Mcquillen PS, Miller SP. Congenital heart disease and brain development. Ann N Y Acad Sci. 2010;1184:68–86.

    Article  CAS  PubMed  Google Scholar 

  4. Taylor EW, Leite CAC, Sartori MR, Wang T, Abe AS, Crossley DA. The phylogeny and ontogeny of autonomic control of the heart and cardiorespiratory interactions in vertebrates. J Exp Biol. 2014;217(5):690–703. Available from: http://jeb.biologists.org/cgi/doi/10.1242/jeb.086199

    Article  PubMed  Google Scholar 

  5. Vincentz JW, Rubart M, Firulli AB. Ontogeny of cardiac sympathetic innervation and its implications for cardiac disease. Pediatr Cardiol. 2013;33(6):923–8.

    Article  Google Scholar 

  6. Smith J. Ontogeny of the autonomic nervous System. In: Gootman PM, editor. Developmental neurobiology of the autonomic nervous System. New York: Springer Science; 1987. p. 18–37. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC469751/.

    Google Scholar 

  7. Kim C-H, Kim K-S. Development and differentiation of autonomic neurons. In: Robertson D, Biaggioni I, Burnstock G, Low PA, JFR P, editors. Primer on the autonomic nervous system. 3rd ed. Amsterdam: Elsevier; 2012. p. 10–6.

    Google Scholar 

  8. Ieda M, Fukuda K. Cardiac innervation and sudden cardiac death. Curr Cardiol Rev. 2009;5(4):289–95. Available from: http://openurl.ingenta.com/content/xref?genre=article&issn=1573-403X&volume=5&issue=4&spage=289

    Article  PubMed  PubMed Central  Google Scholar 

  9. Rubart M, Zipes DP. Mechanisms of sudden cardiac death. J Cllinical Investig. 2005;115(9):2305–15.

    Article  CAS  Google Scholar 

  10. Gordon L, Polak JM, Moscoso GJ, Smith A, Kuhn DM, Wharton J. Development of the peptidergic innervation of human heart. J Anat. 1993;183(Pt 1):131–40.

    CAS  PubMed  PubMed Central  Google Scholar 

  11. Navaratnam V. Development of the nerve supply to the human heart. Br Heart J. 1965;27(5):640–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Pappano AJ. Ontogenetic development of autonomic neuroeffector transmission and transmitter reactivity in embryonic and fetal hearts. Pharmacol Rev. 1977;29(1):3–33.

    CAS  PubMed  Google Scholar 

  13. Schneider U, Bode F, Schmidt A, Nowack S, Hoyer D, Rudolph A, et al. Developmental milestones of the autonomic nervous system revealed via longitudinal monitoring of fetal heart rate variability. PLoS One. 2018;13(7):1–13.

    Article  Google Scholar 

  14. Gagnon R, Campbell K, Ph D, Hunse C, Patrick J. Patterns of human fetal heart rate accelerations from 26 weeks to term. Am J Obstet Gynecol. 1987;157(3):743–8.

    Article  CAS  PubMed  Google Scholar 

  15. Bartolome J, Mills E, Lau C, Slotkin AT. Maturation of sympathetic neurotransmission in the rat heart. V. Development of baroreceptor control of sympathetic. J Pharmacol Exp Ther. 1980;215(3):596–600.

    CAS  PubMed  Google Scholar 

  16. Segar JL, Hajduczok G, Smith BA, Merrill DC, Merrill C, Hajduczok G, et al. Ontogeny of baroreflex control of renal sympathetic nerve activity and heart rate. Am J Physiol Heart Circ Physiol. 1992;263(6):H1819–6.

    Article  CAS  Google Scholar 

  17. Hempleman SC, Warburton SJ. Comparative embryology of the carotid body. Respir Physiol Neurobiol. 2013;185(1):3–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S156990481200225X

    Article  PubMed  Google Scholar 

  18. Zhu Y. Shan, Szeto HH. Cyclic variation in fetal heart rate and sympathetic activity. Am J Obstet Gynecol. 1987;156(4):1001–5.

    Article  CAS  PubMed  Google Scholar 

  19. Karin J, Hirsch M, Akselrod S. An estimate of fetal autonomic state by spectral analysis of fetal heart rate fluctuations. Pediatr Res. 1993;34(2):3–7.

    Article  Google Scholar 

  20. Koutcherov Y, Mai JK, Paxinos G. Hypothalamus of the human fetus. J Chem Neuroanat. 2003;26:253–70.

    Article  CAS  PubMed  Google Scholar 

  21. Sachis PN, Armstrong DL, Becker LAE, Bryan C. Myelination of the human Vagus nerve from 24 weeks postconceptional age to adolescence. J Exp Neurobiol. 1982;41(4):466–72.

    CAS  Google Scholar 

  22. Lagercrantz H. Catecholamine release in the newborn infant at birth. Pediatr Res. 1977;11(8):889–93.

    Article  CAS  PubMed  Google Scholar 

  23. Ogundipe OA, Kullama LK, Stein H, Nijland MJ, Ervin MG, Padbury J, et al. Fetal endocrine and renal responses to in utero ventilation and umbilical cord occlusion. Am J Obstet Gynecol. 1993;169(6):1479–86. Available from: https://doi.org/10.1016/0002-9378(93)90422-F

    Article  CAS  PubMed  Google Scholar 

  24. Inwald D, Hathorn MKS, Costeloe K. The deep breath vasoconstriction reflex – a new tool for autonomic assessment in infancy? David Early Hum Dev. 1996;45:55–61.

    Article  CAS  Google Scholar 

  25. Grieve PG, Stark RI, Isler JR, Housman SL, Fifer WP, Myers MM. Electrocortical functional connectivity in infancy: response to body tilt. Pediatr Neurol. 2007;37(2):91–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0887899407001543

    Article  PubMed  Google Scholar 

  26. Carroll JL, Kim I. Postnatal development of carotid body glomus cell O2 sensitivity. Respir Physiol Neurobiol. 2005;149(1–3):201–15. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1569904805001187

    Article  PubMed  Google Scholar 

  27. Chow LT, Chow SS, Anderson RH, Gosling JA, Elizabeth Q. Innervation of the human cardiac conduction system at birth. Br Heart J. 1993;69:430–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Chow LT, Chow SS, Anderson RH, Gosling JA. The innervation of the human myocardium at birth. J Anat. 1995;187:107–14.

    PubMed  PubMed Central  Google Scholar 

  29. Ziyatdinova NI, Dement RE, Khisamieva LI, Ze TL. Age-related peculiarities of adrenergic regulation of cardiac chronotropic action after I f blockage. Bull Exp Biol Med. 2013;156(1):7–9.

    Article  CAS  Google Scholar 

  30. Porges SW, Furman SA. The early development of the autonomic nervous system provides a neural platform for social behaviour: a polyvagal perspective. Infant Child Dev. 2011;20(1):106–18. Available from: http://doi.wiley.com/10.1002/icd.688

    Article  PubMed  PubMed Central  Google Scholar 

  31. Hunt CE. Ontogeny of autonomic regulation in late preterm infants born at 34-37 weeks postmenstrual age. Semin Perinatol. 2006;30(2):73–6. Available from: http://linkinghub.elsevier.com/retrieve/pii/S0146000506000310

    Article  PubMed  Google Scholar 

  32. Massin M. Normal ranges of heart rate variability during infancy and childhood. Pediatr Cardiol. 1997;18(4):297–302.

    Article  CAS  PubMed  Google Scholar 

  33. Cohen HL. Development of autonomic innervation in mammalian myocardium. In: Gootman PM, editor. Neurobiology of the autonomic nervous system: Springer Science; 1987. p. 159–91. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC469751/.

  34. Kirjavainen J, Jahnukainen T, Huhtala V, Lehtonen L, Kirjavainen T, Korvenranta H, et al. The balance of the autonomic nervous system is normal in colicky infants. Acta Paediatr. 2001;15:250–4.

    Article  Google Scholar 

  35. Stifter CA, Dollar JM, Cipriano EA. Temperament and emotion regulation: the role of autonomic nervous System reactivity. Dev Psichobiology. 2013;53(3):266–79.

    Article  Google Scholar 

  36. Tsun L, Chow C, Sau S, Chow M, Anderson RH, Gosling JA. Autonomic innervation of the human cardiac conduction System: changes from infancy to senility — an Immunohistochemical and. Anat Rec. 2001;182(February):169–82.

    Google Scholar 

  37. Bernstein D. Developmental biology of the cardiovascular system. In: Nelson textbook of pediatrics. Philadelphia: W.B. Saunders Co; 2011. p. 1527–36.

    Chapter  Google Scholar 

  38. Giardino ND, Glenny RW, Borson S, Chan L. Respiratory sinus arrhythmia is associated with efficiency of pulmonary gas exchange in healthy humans. Am J Physiol Circ Physiol. 2003;284(5):H1585–91. Available from: http://www.physiology.org/doi/10.1152/ajpheart.00893.2002

    Article  CAS  Google Scholar 

  39. Quigley KS, Stifter CA. A comparative validation of sympathetic reactivity in children and adults. Psychophysiology. 2006;43(4):357–65. Available from: http://doi.wiley.com/10.1111/j.1469-8986.2006.00405.x

    Article  PubMed  Google Scholar 

  40. Bush NR, Caron ZK, Blackburn KS, Alkon A. Measuring cardiac autonomic nervous System (ANS) activity in toddlers – resting and developmental challenges. J Vis Exp. 2016;25(108):1–12. Available from: http://www.jove.com/video/53652/measuring-cardiac-autonomic-nervous-system-ans-activity-toddlers

    Google Scholar 

  41. Alkon A, Lippert S, Vujan N, Rodriquez ME, Boyce WT, Eskenazi B. The ontogeny of autonomic measures in 6- and 12-month-old infants. Dev Psychobiol. 2006;48(3):197–208. Available from: http://doi.wiley.com/10.1002/dev.20129

    Article  PubMed  Google Scholar 

  42. Salomon K, Matthews KA, Allen MT. Patterns of sympathetic and parasympathetic reactivity in a sample of children and adolescents. Psychophysiology. 2000;37:842–9.

    Article  CAS  PubMed  Google Scholar 

  43. Fox NA, Porges SW. The relation between neonatal heart period patterns and developmental outcome author (s): Nathan a. Fox and Stephen W. Porges published by: Wiley on behalf of the Society for Research in child development stable. Child Dev. 1985;56(1):28–37.. http://www.jstor.org/stable/1130

    Article  CAS  PubMed  Google Scholar 

  44. Alkon A, Boyce WT, Davis NV, Eskenazi B. Developmental changes in autonomic nervous System resting and reactivity measures in Latino children from 6 to 60 months of age. J Dev Behav Pediatr. 2011;32(9):668–77.

    Article  PubMed  Google Scholar 

  45. Snidman N, Kagan J, Riordan L, Shannon DC. Cardiac function and behavioral reactivity during infancy. Psychophysiology. 1995;32:199–207.

    Article  CAS  PubMed  Google Scholar 

  46. Bar-Haim Y, Marshall PJ, Fox NA. Developmental changes in heart period and high- frequency heart period variability from 4 months to 4 years of age. Dev Psychobiol. 2000;37(1):44–56.

    Article  CAS  PubMed  Google Scholar 

  47. Marshall PJ, Stevenson-Hinde J. Behavioral inhibition, heart period, and respiratory sinus arrhythmia in young children. Dev Psychobiol. 1998;33(3):283–92.

    Article  CAS  PubMed  Google Scholar 

  48. Korkushko OV, Shatilo VB, Plachinda YI, Shatilo TV. Autonomic control of cardiac chronotropic function in man as a function of age: assessment by power spectral analysis of heart rate variability. J Auton Nerv Syst. 1991;32:191–8.

    Article  CAS  PubMed  Google Scholar 

  49. Finley John P, System NSTAN. Heart rate variability in infants, children and young adults. J Auton Nerv Syst. 1995;51(2):103–8.

    Article  Google Scholar 

  50. Yiallourou SR, Sands SA, Walker AM, Horne RSC. Postnatal development of baroreflex sensitivity in infancy. J Physiol. 2010;588(12):2193–203. Available from: http://doi.wiley.com/10.1113/jphysiol.2010.187070

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Dergachevaa O, Batemana R, Byrnea P, Mendelowitza D. Orexinergic modulation of GABAergic neurotransmission to cardiac vagal neurons in the brainstem nucleus ambiguus changes during development. Neuroscience. 2013;202:12–20.

    Google Scholar 

  52. Horne RSC. Cardio-respiratory control during sleep in infancy. Paediatr Respir Rev. 2014;15(2):163–9. Available from: https://doi.org/10.1016/j.prrv.2013.02.012

    PubMed  Google Scholar 

  53. Yiallourou SR, Sands SA, Walker AM, Horne RSC. Maturation of heart rate and blood pressure variability during sleep in term-born infants. Sleep. 2012;35:177–86. Available from: https://academic.oup.com/sleep/article-lookup/doi/10.5665/sleep.1616

    PubMed  PubMed Central  Google Scholar 

  54. Schechtman VL, Henslee JA, Harper RM. Developmental patterns of heart rate and variability in infants with persistent apnea of infancy. Early Hum Dev. 1998;50:251–62.

    Article  CAS  PubMed  Google Scholar 

  55. Thayer JF, Brosschot JF. Psychosomatics and psychopathology: looking up and down from the brain. Psychoneuroendocrinology. 2005;30(10):1050–8. Available from: http://linkinghub.elsevier.com/retrieve/pii/S030645300500106X

    Article  PubMed  Google Scholar 

  56. DiFrancesco MW, Shamsuzzaman A, McConnell KB, Ishman SL, Zhang N, Huang G, et al. Age-related changes in baroreflex sensitivity and cardiac autonomic tone in children mirrored by regional brain gray matter volume trajectories. Pediatr Res. 2018;83(2):498–505. Available from: http://www.nature.com/doifinder/10.1038/pr.2017.273

    Article  PubMed  Google Scholar 

  57. Huang C, Sandroni P, Sletten DM. Effect of age on adrenergic and vagal baroreflex sensitivity in normal subjects. Muscle Nerve. 2007;36:637–42.

    Article  PubMed  Google Scholar 

  58. Harper RM, Macey PM, Henderson LA, Woo MA, Macey KE, Frysinger RC, et al. fMRI responses to cold pressor challenges in control and obstructive sleep apnea subjects. Brain Behav. 2018;8(6):1583–95.

    Google Scholar 

  59. Richardson HL, Macey PM, Kumar R, Valladares EM, Woo MA, Harper RM. Neural and physiological responses to a cold pressor challenge in healthy adolescents. J Neurosci Res. 2013;91(12):1618–27. Available from: http://doi.wiley.com/10.1002/jnr.23283

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Yoshinaga M, Kucho Y, Ushinohama H, Ishikawa Y, Ohno S, Ogata H. Autonomic function and QT interval during night-time sleep in infant long QT syndrome. Circ J. 2018;82(8):2152–9. Available from: https://www.jstage.jst.go.jp/article/circj/82/8/82_CJ-18-0048/_article

    Article  PubMed  Google Scholar 

  61. Tomoum H, Habeeb N, Elagouza I, Mobarez H. Paediatric breath-holding spells are associated with autonomic dysfunction and iron deficiency may play a role. Acta Paediatr. 2018;107:653–7.

    Article  CAS  PubMed  Google Scholar 

  62. Calik M, Dokumaci DS, Demir M, Isik I, Kazanasmaz H, Kandemir H. Brain metabolite values in children with breath- holding spells. Neuropsychiatr Dis Treat. 2017;13:1655–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Vurucu S, Karaoglu A, Paksu SM, Oz O, Yaman H, Gulgun M, et al. Breath-holding spells may be associated with maturational delay in myelination of brain stem. J Clin Neurophysiol. 2014;31(1):99–101.

    Article  PubMed  Google Scholar 

  64. Orii KE, Kato Z, Osamu F, Funato M, Kubodera K, Inoue R, et al. Changes of autonomic nervous system function in patients with breath-holding spells treated with iron. J Child Neurol. 2002;17(5):337–40.

    Article  PubMed  Google Scholar 

  65. Moon RY, Horne RSC, Hauck FR. Sudden infant death syndrome. The Lancet. 2007;370:1578–87.

    Article  Google Scholar 

  66. Harper RM, Leake B, Hodgman E. Developmental patterns of heart rate and heart rate variability during sleep and waking in normal infants and infants at risk for the sudden infant death syndrome. Sleep. 1982;5:28–38.

    Article  CAS  PubMed  Google Scholar 

  67. Grieve PG, Myers MM, Stark RI, Housman S, Fifer WP. Topographic localization of electrocortical activation in newborn and two- to four-month-old infants in response to head-up tilting. Acta Paediatr Int J Paediatr. 2005;94(12):1756–63.

    Article  Google Scholar 

  68. Bornstein MH, Suess PE. Physiological self-regulation and information processing in infancy: cardiac vagal tone and habituation. Child Dev. 2000;71(2):273–87.

    Article  CAS  PubMed  Google Scholar 

  69. Richards JE, Cameron D. Infant heart rate variability and behavioral developmental status. Infant Behav Dev. 1989;12:42–58.

    Google Scholar 

  70. Burgess KB, Marshall PJ, Rubin KH, Fox NA. Infant attachment and temperament as predictors of subsequent externalizing problems and cardiac physiology. J Psychol Psychiatry. 2003;6:819–31.

    Article  Google Scholar 

  71. Izard CE, Porges SW, Simons RF, Haynes OM, et al. Infant cardiac activity: developmental changes and relations with attachment. Dev Psychol. 1991;27(3):432–9. Available from: http://doi.apa.org/getdoi.cfm?doi=10.1037/0012-1649.27.3.432

    Article  Google Scholar 

  72. Kagan J, Reznick JS, Snidman N, Kagan J, Reznick JS, Snidman N. The physiology and psychology of behavioral inhibition in children. Child Dev. 1987;58(6):1459–73.

    Article  CAS  PubMed  Google Scholar 

  73. Porges SW, Doussard-Roosevelt JA, Maiti AK. Vagal tone and the physiological regulation of emotion. Monogr Soc Res Child Dev. 1994;59:167–86.

    Article  CAS  PubMed  Google Scholar 

  74. Calkins SD, Keane SP. Cardiac vagal regulation across the preschool period: stability, continuity, and implications for childhood adjustment. Dev Psychobiol. 2004;45(3):101–12. Available from: http://doi.wiley.com/10.1002/dev.20020

    Article  PubMed  Google Scholar 

  75. Moore GA. Parent conflict predicts infants’ vagal regulation in social interaction. Dev Psychopathol. 2010;22(1):23–33.

    Article  PubMed  PubMed Central  Google Scholar 

  76. Chugani HT, Behen ME, Muzik O, Juha C. Local brain functional activity following early deprivation: a study of Postinstitutionalized Romanian orphans. NeuroImage. 2001;14(6):1290–301.

    Article  CAS  PubMed  Google Scholar 

  77. Eluvathingal TJ, Chugani HT, Behen ME, Juhász C, Maqbool M, Chugani DC, et al. Abnormal brain connectivity in children after early severe socioemotional deprivation: a diffusion. Pediatrics. 2006;117(6):2093–100.

    Article  PubMed  Google Scholar 

  78. Lehman BJ, Taylor SE, Kiefe CI, Seeman TE. Relationship of early life stress and psychological functioning to blood pressure in the CARDIA study. Health Psychol. 2009;28(3):338–46. Available from: http://doi.apa.org/getdoi.cfm?doi=10.1037/a0013785

    Article  PubMed  PubMed Central  Google Scholar 

  79. Evans S, Tsao JCI, Lung KC, Zeltzer LK, Naliboff BD. Heart rate variability as a biomarker for autonomic nervous system response differences between children with chronic pain and healthy control children. J Pain Res. 2013;2013:449–57.

    Google Scholar 

  80. Limperopoulos C, Tworetzky W, McElhinney DB, Newburger JW, Brown DW, Robertson RL, et al. Brain volume and metabolism in fetuses with congenital heart disease: evaluation with quantitative magnetic resonance imaging and spectroscopy. Circulation. 2010;121(1):26–33. Available from: http://circ.ahajournals.org/cgi/doi/10.1161/CIRCULATIONAHA.109.865568

    Article  CAS  PubMed  Google Scholar 

  81. Dimitropoulos A, Xu D, Brant R, Azakie A, Campbell A, Barkovich AJ, et al. Brain injury and development in newborns with critical congenital heart disease. Am Acad Neurol. 2013;81(3):241–8.

    Google Scholar 

  82. Miller SP, McQuillen PS, Hamrick S, Xu D, Glidden DV, Charlton N, et al. Abnormal brain development in newborns with congenital heart disease. N Engl J Med. 2007;357(19):1928–38. Available from: http://www.nejm.org/doi/abs/10.1056/NEJMoa067393

    Article  CAS  PubMed  Google Scholar 

  83. Prsa M, Sun L, Van Amerom J, Yoo S. Reference ranges of blood flow in the major vessels of the normal human fetal circulation at term by phase-contrast magnetic resonance imaging. Circ Cardiovasc Imaging. 2014;7(4):663–70.

    Article  PubMed  Google Scholar 

  84. Kinney HC, Brody BANN, Ph D, Kloman AS, Gilles FH. Sequence of central nervous System myelination in human infancy II. Patterns of myelination in autopsied infants. J Neuropathol Exp Neurol. 1988;47(3):217–34.

    Article  CAS  PubMed  Google Scholar 

  85. Claessens NHP, Kelly CJ, Counsell SJ, Benders MJNL. Neuroimaging, cardiovascular physiology, and functional outcomes in infants with congenital heart disease. Dev Med Child Neurol. 2017;59(9):894–902. Available from: http://doi.wiley.com/10.1111/dmcn.13461

    Article  PubMed  Google Scholar 

  86. Menteer J, Macey PM, Woo MA, Panigrahy A, Harper RM. Central nervous System changes in pediatric heart failure: a volumetric study. Pediatr Cardiol. 2010;31(7):969–76. Available from: http://link.springer.com/10.1007/s00246-010-9730-9

    Article  PubMed  PubMed Central  Google Scholar 

  87. Licht DJ, Shera DM, Clancy RR, Wernovsky G, Montenegro LM. Brain maturation is delayed in infants with complex congenital heart defects. J Thorac Cardiovasc Surg. 2008;137(3):529–37. Available from: https://doi.org/10.1016/j.jtcvs.2008.10.025

    Article  Google Scholar 

  88. Owen M, Shevell M, Donofrio M, Majnemer A, Mccarter R, Vezina G, et al. Brain volume and Neurobehavior in newborns with complex congenital heart defects. J Pediatr. 2014;164(5):1121–1127.e1. Available from: https://doi.org/10.1016/j.jpeds.2013.11.033

    Article  PubMed  Google Scholar 

  89. Morton PD, Ishibashi N, Jonas RA. Neurodevelopmental abnormalities and congenital heart disease. Circ Res. 2017;120(6):960–77. Available from: http://circres.ahajournals.org/lookup/doi/10.1161/CIRCRESAHA.116.309048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Scuola Superiore Sant’Anna, Pisa, Italy

    Lorenzo Mangone

  2. Neuroscience Department, Children’s Hospital Anna Meyer – University of Florence, Florence, Italy

    Renzo Guerrini

  3. Institute of Life Science, Scuola Superiore Sant’Anna, Pisa, Italy

    Michele Emdin

  4. Division of Cardiology and Cardiovascular Medicine, Fondazione Toscana Gabriele Monasterio, Pisa, Italy

    Michele Emdin

Authors
  1. Lorenzo Mangone
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renzo Guerrini
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Michele Emdin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Renzo Guerrini .

Editor information

Editors and Affiliations

  1. Dept of Drug Sciences, Pharmacology Sect, University of Pavia, Dept of Drug Sciences, Pharmacology Sect, Pavia, Pavia, Italy

    Stefano Govoni

  2. Dept of Brain and Behavioural Sciences, University of Pavia Dept of Brain and Behavioural Sciences, Pavia, Pavia, Italy

    Pierluigi Politi

  3. Department of Molecular Medicine, University of Pavia, Department of Molecular Medicine, Pavia, Pavia, Italy

    Emilio Vanoli

Section Editor information

  1. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy

    Niccolò Marchionni

  2. Dipartimento di Medicina Sperimentale e Clinica, Università degli Studi di Firenze, Florence, Italy

    Enrico Mossello

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this entry

Check for updates. Verify currency and authenticity via CrossMark

Cite this entry

Mangone, L., Guerrini, R., Emdin, M. (2019). Pediatric Age and the Ontogeny of the Brain and Heart Connection. In: Govoni, S., Politi, P., Vanoli, E. (eds) Brain and Heart Dynamics. Springer, Cham. https://doi.org/10.1007/978-3-319-90305-7_60-1

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-90305-7_60-1

  • Received:

  • Accepted:

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-90305-7

  • Online ISBN: 978-3-319-90305-7

  • eBook Packages: Springer Reference MedicineReference Module Medicine

Publish with us

Policies and ethics

Search

Navigation