Skip to main content

Aetiological Factors

  • Chapter
  • First Online:
Cerebral Palsy

Abstract

The aetiology of cerebral palsy (CP) is heterogeneous, multifactorial and only partially understood. The brain development begins with neurulation (3 weeks of gestation) and makes further important steps during the first 2 years of life, in particular in the first 12–15 months. CP can result from brain injury occurring during the prenatal, perinatal or postnatal periods. This chapter discusses the aetiological mechanisms that underpin the development of CP. For some, e.g. iodine, perinatal arterial ischaemic stroke (maternal, placental, fetal, neonatal), head injury, coagulation defects and haemorrhage, the relationship with the development of disability is clear. But for others, sometimes considered risk factors rather than aetiological factors, for example, premature birth, small for gestational age, and multiple pregnancies, despite strong evidence of an association, the aetiological mechanisms remain obscure. The potential mechanisms underlying the relationship between hypoxia and the role of neonatal encephalopathy in the development of CP are explored, and the role of genetic and familiar factors associated with CP is identified and discussed. In summary, the aetiological factors associated with CP are complex and diverse, and the precise causal mechanisms underpinning the development of CP for several of the associated risk factors are still unknown.

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

Access this chapter

Institutional subscriptions

References

  1. Huitfeldt A. Is caviar a risk factor for being a millionaire? BMJ. 2016;355:i6536.

    Article  PubMed  Google Scholar 

  2. Nelson K. Causative factors in cerebral palsy. Clin Obstet Gynecol. 2008;51:749–62.

    Article  PubMed  Google Scholar 

  3. Krägeloh-Mann I, Hagberg G, Meisner C, et al. Bilateral spastic cerebral palsy- a comparative study between south West Germany and West Sweden III. Etiology. Dev Med Child Neurol. 1995;37:191–203.

    Article  PubMed  Google Scholar 

  4. Panteliadis CP, Korinthenberg R, editors. Paediatric neurology - theory and practice. Stuttgart: Thieme; 2005. p. 14–28. and p. 311-355

    Google Scholar 

  5. Little WJ. On the influence of abnormal parturition, difficult labours, premature birth and asphyxia neonatorum on the mental and physical condition of the child, especially in relation to deformities. Trans Obstet Soc London. 1961;3:244–93.

    Google Scholar 

  6. Odding E, Roebroeck ME, Stam HJ. The epidemiology of cerebral palsy: incidence, impairments and risk factors. Disabil Rehabil. 2006;28:183–91.

    Article  PubMed  Google Scholar 

  7. Sellier E, Platt MJ, Andersen GL, et al. Decreasing prevalence in cerebral palsy: a multi-site European population-based study, 1980-2003. Dev Med Child Neurol. 2015;58:85–92.

    Article  PubMed  Google Scholar 

  8. Jarvis S, Glinianaia SV, Torrioli MG, et al. Surveillance of cerebral palsy in Europe (SCPE) collaboration of European cerebral palsy registers. Cerebral palsy and intrauterine growth in single births: European collaborative study. Lancet. 2003;362:1089–90.

    Article  Google Scholar 

  9. Hong T, Paneth N. Maternal and infant thyroid disorders and cerebral palsy. Semin Perinatol. 2008;32:438–45.

    Article  PubMed  Google Scholar 

  10. Pharoah PO, Connolly KJ. A controlled trial of iodinated oil for the prevention of endemic cretinism: a long term follow-up. Int J Epidemiol. 1987;16:68–73.

    Article  CAS  PubMed  Google Scholar 

  11. O’Leary CM, Watson L, D’Antoine H, et al. Heavy maternal alcohol consumption and cerebral palsy in the offspring. Dev Med Child Neurol. 2012;54:224–30.

    Article  PubMed  Google Scholar 

  12. Mamunes P, Prince PE, Thornton NH, et al. Intellectual deficits after transient tyrosinemia in the term neonate. Pediatrics. 1976;57:675–80.

    CAS  PubMed  Google Scholar 

  13. Peterson B, Nelson KB, Watson L, et al. Twins, triplets and cerebral palsy in births in Western Australia in the 1980s. BMJ. 1993;307:1239–43.

    Article  Google Scholar 

  14. Scheller JM, Nelson KB. Does cesarean delivery prevent cerebral palsy or other neurologic problems of childhood? Obstet Gynaecol. 1994;83:624–30.

    Article  CAS  Google Scholar 

  15. Smithers-Sheedy H, McIntyre S, Gibson C, et al. A special supplement: findings from the Australian cerebral palsy register, birth years1993-2006. Dev Med Child Neurol. 2016;58(Suppl. 2):5–10.

    Article  PubMed  Google Scholar 

  16. Stromberg B, Dahlquist G, Ericson A, et al. Neurological sequelae in children born after in-vitro fertilization: a population-based study. Lancet. 2002;65:232–42.

    Google Scholar 

  17. Grether JK, Nelson KB, Cummins SK. Twinning and cerebral palsy: experience in four northern California countries, births 1983 through 1985. Pediatrics. 1993;92:854–8.

    CAS  PubMed  Google Scholar 

  18. Hughes I, Newton R. Genetic aspects of cerebral palsy. Dev Med Child Neurol. 1992;34:80–6.

    Article  CAS  PubMed  Google Scholar 

  19. Pharoah PO, Cooke RWI. A hypothesis for the aetiology of spastic cerebral palsy – the vanishing twin. Dev Med Child Neurol. 1997;39:202–6.

    Google Scholar 

  20. Newton R, Casabonne D, Johnson A, et al. A case-control study of vanishing twin as a risk factor for cerebral palsy. Twin Res. 2003;6:83–4.

    Article  PubMed  Google Scholar 

  21. Panteliadis CP, Hagel C, Karch D, Heinemann K. Cerebral palsy: a lifelong challenge asks for early intervention. Open Neurol J. 2015;9:45–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Blumenthal I. Periventricular leucomalacia: a review. Eur J Pediatr. 2004;163:435–42.

    Article  PubMed  Google Scholar 

  23. Ness JK, Romanko MJ, Rothstein RP, et al. Perinatal hypoxia-ischaemia induces apoptotic and excitotox death of periventricular white matter oligodendrocyte progenitors. Dev Neurosci. 2001;23:203–8.

    Article  CAS  PubMed  Google Scholar 

  24. Volpe JJ. Cerebral white matter injury of the premature infant – more common than you think. Pediatrics. 2003;112:176–80.

    Article  PubMed  Google Scholar 

  25. Limperopoulos C. Advanced neuroimaging techniques: their role in the development of future fetal and neonatal neuroprotection. Semin Perinatol. 2010;34:93–101.

    Article  PubMed  Google Scholar 

  26. Babcock MA, Kostoa FV, Ferriero DM, et al. Injury to the pre-term brain and cerebral palsy. J Child Neurol. 2009;24:1064–84.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Takahashi R, Yamada M, Takahashi T, et al. Risk factors for cerebral palsy in preterm infants. Early Hum Dev. 2005;81:545–53.

    Article  PubMed  Google Scholar 

  28. Bax M, Tydeman C, Flodmark O. Clinical and MRI correlates of cerebral palsy. The European cerebral palsy study. JAMA. 2006;296:1602–8.

    Article  CAS  PubMed  Google Scholar 

  29. Hansen-Pupp I, Hallin AL, Hellsröm-Westas L, et al. Inflammation at birth is associated with subnormal development in very preterm infants. Pediatr Res. 2008;64:183–8.

    Article  PubMed  Google Scholar 

  30. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;67:1–8.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Juliet PA, Mao X, DelBigio M. Proinflammatory cytokine production by cultured neonatal rat microglia after exposure to blood products. Brain Res. 2008;19:230–9.

    Article  Google Scholar 

  32. Vasileiadis GT, Gelman N, Victor KM. Uncomplicated intraventricular hemorrhage is followed by reduced cortical volume at near-term age. Pediatrics. 2004;114:e367–72.

    Article  PubMed  Google Scholar 

  33. Graham EM, Ruis KA, Hartman AL, et al. A systematic review of the role of intrapartum hypoxia-ischemia in the causation of neonatal encephalopathy. Am J Obstet Gynecol. 2008;199:587–95.

    Article  CAS  PubMed  Google Scholar 

  34. Blair E, Stanley FJ. Intrapartum asphyxia: a rare cause of cerebral palsy. J Pediatr. 1998;112:515–9.

    Article  Google Scholar 

  35. Leijser LM, Vein AA, Liauw L, et al. Prediction of short-term neurological outcome in full-term neonates with hypoxic-ischaemic encephalopathy based on combined use of electroencephalogram and neuroimaging. Neuropediatrics. 2007;38:219–27.

    Article  CAS  PubMed  Google Scholar 

  36. Pschirrer ER, Yeomans ER. Does asphyxia cause cerebral palsy? Semin Perinatol. 2000;24:215–20.

    Article  CAS  PubMed  Google Scholar 

  37. MacLennan A. A for the international cerebral palsy task force. A template for defining a causal relationship between acute intrapartum events and cerebral palsy: international consensus statement. BMJ. 1999;319:1054–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Ellenberg JH, Nelson KB. The association of cerebral palsy with birth asphyxia: a definitional quagmire. Dev Med Child Neurol. 2013;55:210–6.

    Article  PubMed  Google Scholar 

  39. Badawi N, Kurinczuk JJ, Keogh JM, et al. Intrapartum risk factors for newborn encephalopathy: the western Australian case control study. BMJ. 1998;317:1554–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Perlman JM. Summary proceedings from the neurology group on hypoxic-ischemic encephalopathy. Pediatrics. 2006;117:S28–33.

    Article  PubMed  Google Scholar 

  41. Task Force on Neonatal Encephalopathy. Neonatal encephalopathy and neurological outcome, second edition. Pediatrics. 2014;133:1483–8.

    Google Scholar 

  42. Mcintyre S, Badawi N, Blair E, Nelson KB. Does aetiology of neonatal encephalopathy and hypoxic-ischaemic encephalopathy influence the outcome of treatment. Dev Med Child Neurol. 2015;57(Suppl 3):2–7.

    Article  PubMed  Google Scholar 

  43. Beligere N, Rao N. Neurodevelopmental outcome in infants with meconium aspiration syndrome: report of a study and literature review. J Perinatol. 2008;28:S93–S101.

    Article  PubMed  Google Scholar 

  44. Govaert P, Ramenghi L, Taal R, et al. Diagnosis of perinatal stroke 1: definitions, differential diagnosis and registration. Acta Paediatr. 2009;98:1556–67.

    Article  CAS  PubMed  Google Scholar 

  45. Lehman LL, Rivkin MJ. Perinatal arterial ischemic stroke: presentation, risk factors, evaluation, and outcome. Pediatr Neurol. 2014;51:760–8.

    Article  PubMed  Google Scholar 

  46. Fluss J, Dinomais M, Kossorotoff M, et al. Perspectives in neonatal and childhood arterial ischemic stroke. Expert Rev Neurother. 2017;17:135–42.

    Article  CAS  PubMed  Google Scholar 

  47. Fluss J, Garcia-Tarodo S, Granier M, et al. Perinatal arterial ischemic stroke related to caroid artery occlusion. Eur J Paediatr Neurol. 2016;20:639–48.

    Article  PubMed  Google Scholar 

  48. Hartemann JC, Groenendaal F, Kwee A, et al. Risk factors for perinatal arterial ischaemic stroke in full term infants : a case-control study. Arch Dis Child Fetal Neonatal. 2012;97:F411–2.

    Article  Google Scholar 

  49. Rutherford MA, Ramenghi LA, Cowan FM. Neonatal stroke. Arch Dis Child Fetal Neonatal Ed. 2012;97:F377–84.

    Article  CAS  PubMed  Google Scholar 

  50. Nelson KB, Lynch JK. Stroke in newborn infants. Lancet Neurol. 2004;3:216–24.

    Google Scholar 

  51. Roach ES, Colomb MR, Adams R, et al. Management of stroke in infants and children: a scientific statement from a special writing Group of the American Heart Association. Stroke. 2008;39:2644–91.

    Article  PubMed  Google Scholar 

  52. Wasay M, Dai AI, Ansari M, et al. Cerebral venous sinus thrombosis in children: a multicenter cohort from the United States. J Child Neurol. 2008;23:26–31.

    Article  PubMed  Google Scholar 

  53. Hayashi T, Hashimotot T, Fukuda S, et al. Neonatal subdural hematoma secondary to birth injury. Clinical analysis of 48 survivors. Childs Nerv Syst. 1987;3:23–9.

    Article  CAS  PubMed  Google Scholar 

  54. Loh JK, Lin CL, Kwan AL, et al. Acute subdural hematoma in infancy. Surg Neurol. 2002;58:218–24.

    Article  PubMed  Google Scholar 

  55. Sandberg DI, Lamberti-Pasculli M, Drake JM, et al. Spontaneous intraparenchymal hemorrhage in full-term neonates. Neurosurgery. 2001;48:1042–8.

    CAS  PubMed  Google Scholar 

  56. Sutor AH. Vitamin K deficiency bleeding in infants and children. Semin Thromb Hemost. 1995;21:317–29.

    Article  CAS  PubMed  Google Scholar 

  57. Vinchon M, Pierrat V, Tchofo J, et al. Traumatic intracranial hemorrhage in newborns. Childs Nerv Syt. 2005;21:1042–8.

    Article  Google Scholar 

  58. Cans C, McManua V, Crowley M, et al. Cerebral palsy of post neonatal origin: characteristics and risk factors. Paediatr Perinat Epidemiol. 2004;18:214–20.

    Article  PubMed  Google Scholar 

  59. Germany L, Ehlinger V, Klapouszczak D, et al. Trends in prevalence and characteristics of post-neonatal cerebral palsy cases : a European registry study. Res Dev Disabil. 2013;34:1669–77.

    Article  PubMed  Google Scholar 

  60. Reid SM, Lanigan A, Reddihough DS. Post-natally acquired cerebral palsy in Victoria, Australia. 1970-1999. J Paediatr Child Health. 2003;42:606–11.

    Article  Google Scholar 

  61. Blair E, Watson L. Epidemiology of cerebral palsy. Semin Fetal Neonatal Med. 2006;11:117–25.

    Article  PubMed  Google Scholar 

  62. Barkovich AJ. MR and CT evaluation of profound neonatal and infantile asphyxia. Am J Neuroradiol. 1992;13:959–72.

    CAS  PubMed  Google Scholar 

  63. Tollanes MC, Wilcox AJ, Lie RT, et al. Familial risk of cerebral palsy: population based cohort study. BMJ. 2014;346:4294–9.

    Article  Google Scholar 

  64. Garne E, Dolk H, Krägeloh-Mann I, et al. Cerebral palsy and congenital malformations. Eur J Paediatr Neurol. 2008;12:82–8.

    Article  PubMed  Google Scholar 

  65. O'Driscoll MC, Daly SB, Urquhart JE, et al. Pilz recessive mutations in the gene encoding the tight junction protein occludin cause band-like calcification with simplified gyration and polymicrogyria. Am J Hum Genet. 2010;87:354–64.

    Article  PubMed  PubMed Central  Google Scholar 

  66. Gibson CS, MacLennan AH, Dekker GA, et al. Genetic polymorphisms and spontaneous preterm birth. Obstet Gynecol. 2007;109:384–91.

    Article  CAS  PubMed  Google Scholar 

  67. Gibson CS, MacLennan AH, Dekker GA, et al. Candidate genes and cerebral palsy: a population-based study. Pediatrics. 2008;122:1079–85.

    Article  PubMed  Google Scholar 

  68. Kuroda MM, Weck ME, Sarwark JF, et al. Association of apolipoprotein E genotype and cerebral palsy in children. Pediatrics. 2006;118:306–13.

    Google Scholar 

  69. O’Callaghan ME, Mc Lennan AH, Haan EA, et al. The genomic basis of cerebral palsy: a HuGE systematic literature review. Hum Gnet. 2009;126:149–72.

    Article  Google Scholar 

  70. Gibson CS, MacLennan AH, Hague WM, et al. Associations between inherited thrombophilias, gestational age and cerebral palsy. Am J Obstr Gyn. 2005;193:1437el1–1437el12.

    Article  Google Scholar 

  71. Gibson CS, MacLennan AH, Goldwater PN, et al. Antenatal causes of cerebral palsy: associations between inherited thrombophilias, viral and bacterial infection, and inherited susceptibility to infection. Obstet Gynecol Surv. 2003;58:209–20.

    PubMed  Google Scholar 

  72. MacLennan A, Thompson SC, Gecz J. Cerebral palsy: causes, pathways, and the role of genetic variants. AJOG. 2015;213:779–88.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Mary Jane Platt M.B.B.S., M.P.H., M.D. .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG

About this chapter

Cite this chapter

Platt, M.J., Panteliadis, C.P., Häusler, M. (2018). Aetiological Factors. In: Panteliadis, C. (eds) Cerebral Palsy. Springer, Cham. https://doi.org/10.1007/978-3-319-67858-0_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-67858-0_6

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-67857-3

  • Online ISBN: 978-3-319-67858-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics