Neural Tube Defects: Prenatal Diagnosis and Genetic Counseling

  • Giovanni Neri
Part of the Principles of Pediatric Neurosurgery book series (PRINCPEDIATR)


The practice of genetic counseling for neural tube defects (NTD) has changed substantially over the past 15 years with the advent of three major developments, i.e., second-trimester prenatal diagnosis, mass screening of pregnant women for elevated serum α-fetoprotein levels, and vitamin supplementation around the time of conception. On the other hand, the principles on which recurrence risk estimates are based have changed little, the multifactorial model of inheritance being the one that still fits best the epidemiologic data.


Amniotic Fluid Prenatal Diagnosis Spina Bifida Neural Tube Defect Maternal Serum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Elwood JH, Nevin NC: Factors associated with anencephalus and spina bifida in Belfast. Br J Prey Soc Med 27: 73–80, 1973.Google Scholar
  2. 2.
    Laurence KM, Carter CO, David PA: The central nervous system malformations in South Wales. I. Incidence, local variations and geographical factors. Br J Prey Soc Med 22: 146–152, 1968.Google Scholar
  3. 3.
    Carter CO, Evans KA: Spina bifida and anencephalus in Greater London. J Med Genet 10: 209–234, 1973.PubMedCrossRefGoogle Scholar
  4. 4.
    Mastroiacovo P: Epidemiologia dei difetti del tubo neurale. Giorn Neurops Eta Evol 4: 207–222, 1984.Google Scholar
  5. 5.
    Granroth G, Hakama M, Saxén L: Defects of the central nervous system in Finland: I. Variations in time and space, sex distribution, and parental age. Br J Prey Soc Med 31: 164–170, 1977.Google Scholar
  6. 6.
    Emanuel I, Huang SW, Gutman LT, Yu FC, Lin CC: The incidence of congenital malformations in a Chinese population. Teratology 5: 159–170, 1972.PubMedCrossRefGoogle Scholar
  7. 7.
    Ogbalu MM, Leck I, Hillier VF: The prevalence of malformations at birth in Southern Nigeria. Paper presented at the Fifth International Conference on Birth Defects, Montreal, Canada, 1977.Google Scholar
  8. 8.
    Laurence KM: Prevention of neural tube malformations by genetic counselling and prenatal diagnostic surveillance. J Genet Hum 27: 289–299, 1979.PubMedGoogle Scholar
  9. 9.
    Laurence KM: The recurrence risk in spina bifida cystica and anencephaly. Dev Med Child Neurol 11 (Suppl 20): 23–30, 1969.Google Scholar
  10. 10.
    Lalouel JM, Morton NE, Jackson J: Neural tube malformations: complex segregation analysis and calculation of recurrence risks. J Med Genet 16: 8–13, 1979.PubMedCrossRefGoogle Scholar
  11. 11.
    Carter CO, Evans K: Children of adult survivors with spina bifida cystica. Lancet 1: 924–926, 1973.CrossRefGoogle Scholar
  12. 12.
    Laurence KM, Beresford A: Fifty-one adults with spina bifida; continence, friends, marriage and children. Dev Med Child Neurol 17 (Suppl 35): 123–128, 1975Google Scholar
  13. 13.
    WHO Scientific Group on Genetic Factors in Congenital Malformations: Genetic factors in congenital malformations. WHO Tech Rep Sery No 438, 1970.Google Scholar
  14. 14.
    Carter CO: Clues to the aetiology of neural tube malformations. Dev Med Child Neurol 16(Suppl 32 ): 3–15.Google Scholar
  15. 15.
    Brock DJH, Scrimgeour JB: Early prenatal diagnosis of anencephaly. Lancet 11: 1252–1253, 1972.CrossRefGoogle Scholar
  16. 16.
    Brock DJH, Sutcliffe RG: Alpha fetoprotein in the antenatal diagnosis of anencephaly and spina bifida. Lancet 11: 197–199, 1972.CrossRefGoogle Scholar
  17. 17.
    Brock DJH: Amniotic fluid tests for fetal neural tube defects. Br Med Bull 39: 373–377, 1983.PubMedGoogle Scholar
  18. 18.
    Gitlin D, Boesman M: Sites of serum alphafetoprotein synthesis in the human and in the rat. J Clin Invest 45: 1826–1834, 1966.PubMedCrossRefGoogle Scholar
  19. 19.
    Brock DJH: The molecular character of alphafetoprotein in C.N.S. malformations. Clin Chim Acta 87: 315–320, 1974.CrossRefGoogle Scholar
  20. 20.
    Laurence KM, Turnbull AC, Harris R, Jennison RF, Ruoslathi E, Seppala M: Antenatal diagnosis of spina bifida. Lancet 11: 860, 1973.CrossRefGoogle Scholar
  21. 21.
    Adinolfi M: Human alphafetoprotein 1956–1978. Adv Hum Genet 9: 165–228, 1979.PubMedGoogle Scholar
  22. 22.
    Second Report of the UK Collaborative Study on Alpha-fetoprotein in Relation to Neural-tube Defects: amniotic-fluid alpha-fetoprotein measurement in antenatal diagnosis of anencephaly and open spina bifida in early pregnancy. Lancet 11:651–662, 1979.Google Scholar
  23. 23.
    Brock DJH: The use of amniotic fluid AFP action limits in diagnosing open neural tube defects. Prenat Diagn 1: 11–16, 1981.PubMedCrossRefGoogle Scholar
  24. 24.
    Kleijer WJ, De Bruijn HWA, Leschot NJ: Amniotic fluid alpha-fetoprotein levels and prenatal diagnosis of neural tube defects: a collaborative study of 2180 pregnancies in the Netherlands. Br J Obstet Gynecol 85: 512–517, 1978.CrossRefGoogle Scholar
  25. 25.
    Duncan SLB, Ginz B, Ward AM, Hingley SM: Amniotic fluid AFP in multiple pregnancy. Br Med J 1: 1354, 1977.PubMedCrossRefGoogle Scholar
  26. 26.
    Seppala M, Ranta T, Aula P, Ruoslathi E: Alpha-fetoprotein in normal and abnormal pregnancy. In Lehmann FG (ed): Carcino-Embryonic Proteins. Vol 1, Elsevier, Amsterdam, 1979, pp 191–197.Google Scholar
  27. 27.
    Brock DJH: Neural tube defects (AFP-analysis) in amniotic fluid and maternal serum. In Murken JD, Stengel-Rutkowski S, Schwinger E (eds): Proceedings of the Third European Conference on Prenatal Diagnosis of Genetic Disorders. Ferdinand Enke, Stuttgart, 1979, pp 87–93.Google Scholar
  28. 28.
    Wald NJ, Cuckte HS, Barlow RD, Smith AD, Stirrat GM, Turnbull AC, Bobrow M, Brock DJH, Stein SM: Early antenatal diagnosis of exomphalos. Lancet 1: 1368–1369, 1980.PubMedCrossRefGoogle Scholar
  29. 29.
    Smith AD, Wald NJ, Cuckle HS, Stirrat GM, Bobrow M, Lagercrantz H: Amniotic fluid acetylcholinesterase as a possible diagnostic test for neural tube defects in early pregnancy. Lancet 11: 685–688, 1979.CrossRefGoogle Scholar
  30. 30.
    Wyvill PC, Hullin DA, Elder GH, Laurence KM: A prospective study of amniotic fluid cholinesterases: comparison of quantitative and qualitative methods for detection of open spina bifida in early pregnancy. Prenat Diagn 4: 319–327, 1984.PubMedCrossRefGoogle Scholar
  31. 31.
    Report of the Collaborative Acetylcholinesterase Study: Amniotic fluid acetyl-cholinesterase electrophoresis as a secondary test in the diagnosis of anencephaly and open spina bifida in early pregnancy. Lancet 11: 321–324, 1981.Google Scholar
  32. 32.
    Aitken DA, Morrison NM, Ferguson-Smith MA: Predictive value of amniotic acetyl-cholinesterase analysis in the diagnosis of fetal abnormality in 3700 pregnancies. Prenat Diagn 4: 329–340, 1984.PubMedCrossRefGoogle Scholar
  33. 33.
    Seller MJ, Cole KJ, Merritt BL: Alphafetoprotein, cholinesterases and rapidly adhering cells in the prenatal diagnosis of neural tube defects. Prenat Diagn 1: 7–10, 1981.PubMedCrossRefGoogle Scholar
  34. 34.
    Brock DJH, Hayward C, Seppala M: Distinguishing neural tube defects and congenital nephrosis by amniotic fluid assay. Lancet 1: 773, 1980.PubMedCrossRefGoogle Scholar
  35. 35.
    Sutherland GR, Brock DJH, Scrimgeour JB: Amniotic fluid macrophages and anencephaly. Lancet 11: 1098–1099, 1973.CrossRefGoogle Scholar
  36. 36.
    Gosden CM, Brock DJH: Morphology of rapidly adhering amniotic fluid cells as an aid to the diagnosis of neural tube defects. Lancet 1: 919–922, 1977.PubMedCrossRefGoogle Scholar
  37. 37.
    Gosden CM, Brock DJH, Eason RI: The origin of the rapidly adhering cells found in amniotic fluids from foetuses with neural tube defects. Clin Genet 12: 193–201, 1977.PubMedCrossRefGoogle Scholar
  38. 38.
    Bobrow M, Evans CJ, Noble J, Patel C: Cellular content of amniotic fluid as predictor of central nervous system malformations. J Med Genet 15: 97–100, 1978.PubMedCrossRefGoogle Scholar
  39. 39.
    Cantuaria AA, Jones AL: Immunoglobulin M in human amniotic fluid and its possible association with neural tube malformations. Br J Obstet Gynecol 82: 262–264, 1975.CrossRefGoogle Scholar
  40. 40.
    Brock DJH: Amniotic fluid alpha-2-macroglobulin and the antenatal diagnosis of spina bifida and anencephaly. Clin Genet 8: 297–301, 1975.PubMedCrossRefGoogle Scholar
  41. 41.
    Purdie DW, Howie PW, Edgar W, Forbes CD, Prentice CRM: Raised amniotic fluid fibrinogen degradation products in fetal neural tube anomalies. Lancet 1: 1013–1014, 1975.PubMedCrossRefGoogle Scholar
  42. 42.
    Sindic CJM, Freund M, Van Regemorter N, Verellen-Demoulin C, Masson PL: S-100 protein in amniotic fluid of anencephalic fetuses. Prenat Diagn 4: 297–302, 1984.PubMedCrossRefGoogle Scholar
  43. 43.
    Albrechtsen M, Bock E: Glial fibrillary acidic protein in amniotic fluids from pregnancies with neural tube defects. Prenat Diagn 4: 405–410, 1984.PubMedCrossRefGoogle Scholar
  44. 44.
    Persson PH, Kullander S, Gennser G, Grennert L, Laurell CS: Screening for fetal malformations using ultrasound and measurement of alpha-fetoprotein in maternal serum. Br Med J 286: 747–749, 1983.CrossRefGoogle Scholar
  45. 45.
    Roberts CJ, Evans KT, Hibbard BM, Laurence KM, Roberts EE, Robertson IB: Diagnostic effectiveness of ultrasound in detection of neural tube defects. Lancet 11: 1068–1069, 1983.CrossRefGoogle Scholar
  46. 46.
    Brock DJH, Bolton AE, Monaghan JM: Prenatal diagnosis of anencephaly through maternal serum alphafetoprotein measurement. Lancet 11: 923–924, 1973.CrossRefGoogle Scholar
  47. 47.
    Leek AE, Ruoss CF, Kitau MJ, Chard T: Raised alpha-fetoprotein in maternal serum with anencephalic pregnancy. Lancet 11: 385, 1973.CrossRefGoogle Scholar
  48. 48.
    Report of UK Collaborative Study on Alpha-fetoprotein in Relation to Neural-tube Defects: maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Lancet 1:1323–1332, 1977.Google Scholar
  49. 49.
    Ferguson-Smith MA: The reduction of anencephalic and spina bifida births by maternal serum alpha-fetoprotein screening. Br Med Bull 39: 365–372, 1983.PubMedGoogle Scholar
  50. 50.
    Ghosh A, Woo JSK, Rawlinson HA, Ferguson-Smith MA: Prognostic significance of raised serum alpha-fetoprotein levels in twin pregnancies. Br J Obstet Gynecol 89: 817–820, 1982.CrossRefGoogle Scholar
  51. 51.
    Special Report: Maternal serum alpha-fetoprotein screening for neural tube defects. Results of a consensus meeting. Prenat Diagn 5: 77–83, 1985.CrossRefGoogle Scholar
  52. 52.
    Bennet MJ: Fetal loss after second-trimester amniocentesis in women with raised serum-alpha-fetoprotein. Lancet 11: 987, 1978.CrossRefGoogle Scholar
  53. 53.
    Ferguson-Smith MA, Gibson AAM, Whitfield CR, Ratcliffe JG: Amniocentesis and the alpha-fetoprotein screening programme. Lancet 1: 39–40, 1979.CrossRefGoogle Scholar
  54. 54.
    Roberts CJ, Hibbard BM, Elder GH, Evans KT, Laurence KM, Roberts A, Woodhead JS, Robertson IB, Hoole M: The efficacy of a serum screening service for neural tube defects: the South Wales experience. Lancet 1: 1315–1318, 1983.PubMedCrossRefGoogle Scholar
  55. 55.
    Hagard S, Carter F, Milne RG: Screening for spina bifida cystica-a cost benefit analysis. Br J Soc Prey Med 30: 40–53, 1976.Google Scholar
  56. 56.
    Sadovnick AD, Baird PA: A cost-benefit analysis of a population screening programme for neural tube defects. Prenat Diagn 3: 117–126, 1983.PubMedCrossRefGoogle Scholar
  57. 57.
    Chamberlain J: Human benefits and costs of a national screening programme for neural-tube defects. Lancet 11: 1293–1296, 1978.CrossRefGoogle Scholar
  58. 58.
    Laurence KM, James N, Miller M, Campbell H: Increased risk of recurrence of neural tube defects to mothers on poor diets and the possible benefit of dietary counselling. Br Med J 281: 1542–1544, 1980.CrossRefGoogle Scholar
  59. 59.
    James N, Laurence KM, Miller M: Diet as a factor in the aetiology of neural tube malformations. Zeit Kinderchir 31: 302–307, 1980.Google Scholar
  60. 60.
    Laurence KM, James N, Miller M, Tennant GP, Campbell H: Double-blind randomised controlled trial of folate treatment before conception to prevent recurrences in neural tube defects. Br Med J 282: 1509–1511, 1981.CrossRefGoogle Scholar
  61. 61.
    Smithells RW, Sheppard S, Schorah CJ, Seller MJ, Nevin NC, Harris R, Read AP, Fielding DW: Apparent prevention of neural tube defects by periconceptional vitamin supplementation. Arch Dis Child 56: 911–918, 1981.PubMedCrossRefGoogle Scholar
  62. 62.
    Dobbing J: Prevention of Spina Bifida and Other Neural Tube Defects. Academic Press, London, 1983.Google Scholar
  63. 63.
    Morris J, Laurence KM: The effectiveness of genetic counselling for neural tube malformations. Dev Med Child Neurol 18 (Suppl 37): 157–163, 1976.Google Scholar
  64. 64.
    Laurence KM, Morris J: The effect of the introduction of prenatal diagnosis in the reproductive history of women at increased risk from neural tube defects. Prenat Diagn 1: 51–60, 1981.PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York Inc. 1989

Authors and Affiliations

  • Giovanni Neri

There are no affiliations available

Personalised recommendations