Pediatric Surgery International

, Volume 23, Issue 5, pp 425–429 | Cite as

The effect of prenatal treatment with steroids and preterm delivery in a model of myelomeningocele on the rabbit foetus

  • César G. FontechaEmail author
  • Jose L. PeiróEmail author
  • Marius Aguirre
  • Francesc Soldado
  • Patricia Paz
  • Marc Oria
  • Núria Torán
  • Vicenç Martinez-Ibáñez
Original Article


Damage of neural elements (spinal cord and encephalus) in myelomeningocele (MMC) seems to be progressive during gestation because of amniotic fluid chemical contact and continuous leakage of CSF. We studied the effect of preterm delivery and steroid treatment in a model of MMC in the rabbit foetus. Twelve New Zealand White rabbits underwent laparotomy and hysterotomy at 23 days of gestation. Fifty-nine out of 107 foetuses underwent lumbar laminectomy (three to four levels). Dura was opened to expose the neural elements to the amniotic fluid. Six rabbits underwent caesarean section on gestational day 31 for fetal harvest; three of them had no treatment (group T) and three received corticosteroid treatment (group TC). The other six rabbits underwent caesarean section on gestational day 29 for fetal harvest (preterm delivery); three of them had no treatment (group P) and three received corticosteroid treatment (group PC). Alive newborns were clinically, neurophysiologically and histologically analysed. None of mothers died during the procedure. After birth, animals in group preterm showed statistically significant less deformity than animals in group at term. Lower kyphosis was observed in group PC (preterm and steroids). Pain related and spontaneous mobility of lower extremities was higher in groups treated with corticosteroids (TC and PC). Only newborns at term (T and TC groups) showed response to evoked potentials (CMEPs). The response was earlier and higher in group treated with steroids (TC). Histologically, we observed progressive lesion of the spinal cord. Groups treated with steroids (TC and PC) show less inflammatory response. Arnold–Chiari malformation was present in all groups. Animals in group preterm with steroids show statistically significant less herniation than those group at term. Preterm delivery and prenatal steroid therapy seem to be an effective treatment to get less neural injury (spinal cord and encephalus) in myelomeningocele foetuses.


Neural tube defect Myelomeningocele Arnold–Chiari malformation Fetal treatment Steroids 


  1. 1.
    Hirose S, Meuli-Simmen C, Meuli M (2003) Fetal surgery for myelomeningocele: panacea or peril? World J Surg 27(1):87–94PubMedCrossRefGoogle Scholar
  2. 2.
    Shaw GM, Jensvold NG, Wasserman CR, Lammer EJ (1994) Epidemiologic characteristics of phenotypically distinct neural tube defects among 0.7 million California births, 1983–1987. Teratology 49(2):143–149PubMedCrossRefGoogle Scholar
  3. 3.
    Gilbert JN, Jones KL, Rorke LB, Chernoff GF, James HE (1986) Central nervous system anomalies associated with meningomyelocele, hydrocephalus, and the Arnold–Chiari malformation: reappraisal of theories regarding the pathogenesis of posterior neural tube closure defects. Neurosurgery 18(5):559–564PubMedCrossRefGoogle Scholar
  4. 4.
    McLaughlin JF, Shurtleff DB, Lamers JY, Stuntz JT, Hayden PW, Kropp RJ (1985) Influence of prognosis on decisions regarding the care of newborns with myelodysplasia. N Engl J Med 312(25):1589–1594PubMedCrossRefGoogle Scholar
  5. 5.
    Shurtleff DB, Hayden PW, Loeser JD, Kronmal RA (1974) Myelodysplasia: decision for death or disability. N Engl J Med 291(19):1005–1011PubMedCrossRefGoogle Scholar
  6. 6.
    McLone DG, Knepper PA (1989) The cause of Chiari II malformation: a unified theory. Pediatr Neurosci 15(1):1–12PubMedGoogle Scholar
  7. 7.
    Cochrane DD, Adderley R, White CP, Norman M, Steinbok P (1990) Apnea in patients with myelomeningocele. Pediatr Neurosurg 16(4–5):232–239PubMedCrossRefGoogle Scholar
  8. 8.
    Bell JE, Gordon A, Maloney AF (1980) The association of hydrocephalus and Arnold–Chiari malformation with spina bifida in the fetus. Neuropathol Appl Neurobiol 6(1):29–39PubMedGoogle Scholar
  9. 9.
    McCullough DC, Johnson DL (1994) Myelomeningocele repair: technical considerations and complications 1988. Pediatr Neurosurg 21(1):83–89PubMedGoogle Scholar
  10. 10.
    Meuli M, Meuli-Simmen C, Yingling CD, Hutchins GM, Hoffman KM, Harrison MR, Adzick NS (1995) Creation of myelomeningocele in utero: a model of functional damage from spinal cord exposure in fetal sheep. J Pediatr Surg 30(7):1028–1032PubMedCrossRefGoogle Scholar
  11. 11.
    Farmer DL, von Koch CS, Peacock WJ, Danielpour M, Gupta N, Lee H, Harrison MR (2003) In utero repair of myelomeningocele: experimental pathophysiology, initial clinical experience, and outcomes. Arch Surg 138(8):872–878PubMedCrossRefGoogle Scholar
  12. 12.
    Drewek MJ, Bruner JP, Whetsell WO, Tulipan N (1997) Quantitative analysis of the toxicity of human amniotic fluid to cultured rat spinal cord. Pediatr Neurosurg 27(4):190–193PubMedGoogle Scholar
  13. 13.
    Api A, Olguner M, Hakguder G, Ates O, Ozer E, Akgur FM (2001) Intestinal damage in gastroschisis correlates with the concentration of intraamniotic meconium. J Pediatr Surg 36(12):1811–1815PubMedCrossRefGoogle Scholar
  14. 14.
    Olguner M, Akgur FM, Ozdemir T, Aktug T, Ozer E (2000) Amniotic fluid exchange for the prevention of neural tissue damage in myelomeningocele: an alternative minimally invasive method to open in utero surgery. Pediatr Neurosurg 33(5):252–256PubMedCrossRefGoogle Scholar
  15. 15.
    Meuli M, Meuli-Simmen C, Hutchins GM, Yingling CD, Hoffman KM, Harrison MR, Adzick NS (1995) In utero surgery rescues neurological function at birth in sheep with spina bifida. Nat Med 1(4):342–347PubMedCrossRefGoogle Scholar
  16. 16.
    Heffez DS, Aryanpur J, Rotellini NA, Hutchins GM, Freeman JM (1993) Intrauterine repair of experimental surgically created dysraphism. Neurosurgery 32(6):1005–1010PubMedCrossRefGoogle Scholar
  17. 17.
    Heffez DS, Aryanpur J, Hutchins GM, Freeman JM (1990) The paralysis associated with myelomeningocele: clinical and experimental data implicating a preventable spinal cord injury. Neurosurgery 26(6):987–992PubMedCrossRefGoogle Scholar
  18. 18.
    Michejda M (1984) Intrauterine treatment of spina bifida: primate model. Z Kinderchir 39(4):259–261PubMedGoogle Scholar
  19. 19.
    Housley HT, Graf JL, Lipshultz GS, Calvano CJ, Harrison MR, Farmer DL, Jennings RW (2000) Creation of myelomeningocele in the fetal rabbit. Fetal Diagn Ther 15(5):275–279PubMedCrossRefGoogle Scholar
  20. 20.
    Paek BW, Farmer DL, Wilkinson CC, Albanese CT, Peacock W, Harrison MR, Jennings RW (2000) Hindbrain herniation develops in surgically created myelomeningocele but is absent after repair in fetal lambs. Am J Obstet Gynecol 183(5):1119–1123PubMedCrossRefGoogle Scholar
  21. 21.
    Bruner JP, Tulipan NB, Richards WO, Walsh WF, Boehm FH, Vrabcak EK (2000) In utero repair of myelomeningocele: a comparison of endoscopy and hysterotomy. Fetal Diagn Ther 15(2):83–88PubMedCrossRefGoogle Scholar
  22. 22.
    Adzick NS, Sutton LN, Crombleholme TM, Flake AW (1998) Successful fetal surgery for spina bifida. Lancet 352(9141):1675–1666PubMedCrossRefGoogle Scholar
  23. 23.
    Sutton LN, Adzick NS, Bilaniuk LT, Johnson MP, Crombleholme TM, Flake AW (1999) Improvement in hindbrain herniation demonstrated by serial fetal magnetic resonance imaging following fetal surgery for myelomeningocele. JAMA 282(19):1826–1831PubMedCrossRefGoogle Scholar
  24. 24.
    Langer JC, Bell JG, Castillo RO, Crombleholme TM, Longaker MT, Duncan BW, Bradley SM, Finkbeiner WE, Verrier ED, Harrison MR (1990) Etiology of intestinal damage in gastroschisis, II timing and reversibility of histological changes, mucosal function, and contractility. J Pediatr Surg 25(11):1122–1126PubMedCrossRefGoogle Scholar
  25. 25.
    Tibboel D, Raine P, McNee M, Azmy A, Kluck P, Young D, Molenaar JC (1986) Developmental aspects of gastroschisis. J Pediatr Surg 21(10):865–869PubMedGoogle Scholar
  26. 26.
    Yu J, Gonzalez-Reyes S, Diez-Pardo JA, Tovar JA (2003) Effects of prenatal dexamethasone on the intestine of rats with gastroschisis. J Pediatr Surg 38(7):1032–1035PubMedCrossRefGoogle Scholar
  27. 27.
    Peiró JL, Guindos S, Lloret J, Marhuenda C, Toran N, Castillo F, Martinez-Ibanez V (2005) New surgical strategy in gastroschisis: treatment simplification according to its physiopathology. Cir Pediatr 18(4):182–187PubMedGoogle Scholar
  28. 28.
    Pedreira DA, Valente PR, Abou-Jamra RC, Pelarigo CL, Silva LM, Goldenberg SA (2002) Different technique to create a ‘myelomeningocele-like’ defect in the fetal rabbit. Fetal Diagn Ther 17(6):372–376PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • César G. Fontecha
    • 1
    Email author
  • Jose L. Peiró
    • 1
    Email author
  • Marius Aguirre
    • 1
  • Francesc Soldado
    • 1
  • Patricia Paz
    • 1
  • Marc Oria
    • 1
  • Núria Torán
    • 1
  • Vicenç Martinez-Ibáñez
    • 1
  1. 1.Fetal and Neonatal Surgery Unit and Pediatric Orthopedics Unit, Pediatric Surgery DepartmentVall d’Hebron Universitary HospitalBarcelonaSpain

Personalised recommendations