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Prenatal screening and diagnosis of neural tube defects

Authors
Lauri Hochberg, MD
Joanne Stone, MD
Section Editors
Louise Wilkins-Haug, MD, PhD
Deborah Levine, MD
Deputy Editor
Vanessa A Barss, MD, FACOG

INTRODUCTION

Neural tube defects (NTD) are the second most prevalent congenital anomaly worldwide, second only to cardiac malformations [1]. Three factors have played a significant role in the assessment and prevention of NTDs:

Widespread use of maternal screening programs to identify affected pregnancies

Sonographic imaging with or without amniotic fluid testing for diagnosis of affected fetuses

Food fortification and periconceptional administration of folic acid for prevention

Prenatal screening and diagnosis of NTDs will be reviewed here. Prevention of NTDs is discussed separately. (See "Folic acid supplementation in pregnancy".)

                                    

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Literature review current through: Nov 2016. | This topic last updated: Mon Jul 11 00:00:00 GMT+00:00 2016.
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References
Top
  1. The March of Dimes Global Report on Birth Defects: The Hidden Toll of Dying and Disabled Children. 2006. http://www.marchofdimes.com/glue/files/BirthDefectsExecutiveSummary.pdf (Accessed on July 24, 2013).
  2. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group. Lancet 1991; 338:131.
  3. Czeizel AE, Dudás I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992; 327:1832.
  4. Morris JK, Wald NJ. Quantifying the decline in the birth prevalence of neural tube defects in England and Wales. J Med Screen 1999; 6:182.
  5. Centers for Disease Control and Prevention (CDC). Neural tube defect surveillance and folic acid intervention--Texas-Mexico border, 1993-1998. MMWR Morb Mortal Wkly Rep 2000; 49:1.
  6. Murphy M, Whiteman D, Stone D, et al. Dietary folate and the prevalence of neural tube defects in the British Isles: the past two decades. BJOG 2000; 107:885.
  7. Klusmann A, Heinrich B, Stöpler H, et al. A decreasing rate of neural tube defects following the recommendations for periconceptional folic acid supplementation. Acta Paediatr 2005; 94:1538.
  8. Berry RJ, Li Z, Erickson JD, et al. Prevention of neural-tube defects with folic acid in China. China-U.S. Collaborative Project for Neural Tube Defect Prevention. N Engl J Med 1999; 341:1485.
  9. Martin, JA, Hamilton, BE, Ventura SJ, et al. Births: Final data for 2009. Natl Vital Stat Rep 2009. http://www.cdc.gov/nchs/data/nvsr/nvsr60/nvsr60_01.pdf (Accessed on November 29, 2011).
  10. ACOG Committee on Practice Bulletins. ACOG practice bulletin. Clinical management guidelines for obstetrician-gynecologists. Number 44, July 2003. (Replaces Committee Opinion Number 252, March 2001). Obstet Gynecol 2003; 102:203.
  11. Shaw GM, Todoroff K, Velie EM, Lammer EJ. Maternal illness, including fever and medication use as risk factors for neural tube defects. Teratology 1998; 57:1.
  12. Mitchell LE. Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet 2005; 135C:88.
  13. Nau H. Valproic acid-induced neural tube defects. Ciba Found Symp 1994; 181:144.
  14. Watkins ML, Rasmussen SA, Honein MA, et al. Maternal obesity and risk for birth defects. Pediatrics 2003; 111:1152.
  15. Rasmussen SA, Chu SY, Kim SY, et al. Maternal obesity and risk of neural tube defects: a metaanalysis. Am J Obstet Gynecol 2008; 198:611.
  16. Sukanya S, Bay BH, Tay SS, Dheen ST. Frontiers in research on maternal diabetes-induced neural tube defects: Past, present and future. World J Diabetes 2012; 3:196.
  17. Benedum CM, Yazdy MM, Mitchell AA, Werler MM. Impact of Periconceptional Use of Nitrosatable Drugs on the Risk of Neural Tube Defects. Am J Epidemiol 2015; 182:675.
  18. Reefhuis J, Honein MA, Schieve LA, et al. Use of clomiphene citrate and birth defects, National Birth Defects Prevention Study, 1997-2005. Hum Reprod 2011; 26:451.
  19. Benedum CM, Yazdy MM, Parker SE, et al. Association of Clomiphene and Assisted Reproductive Technologies With the Risk of Neural Tube Defects. Am J Epidemiol 2016; 183:977.
  20. Wu YW, Croen LA, Henning L, et al. Potential association between infertility and spinal neural tube defects in offspring. Birth Defects Res A Clin Mol Teratol 2006; 76:718.
  21. Greenland S, Ackerman DL. Clomiphene citrate and neural tube defects: a pooled analysis of controlled epidemiologic studies and recommendations for future studies. Fertil Steril 1995; 64:936.
  22. De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon P. Effects and safety of periconceptional oral folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2015; :CD007950.
  23. Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA. Folic acid antagonists during pregnancy and the risk of birth defects. N Engl J Med 2000; 343:1608.
  24. Wald NJ, Hackshaw AD, Stone R, Sourial NA. Blood folic acid and vitamin B12 in relation to neural tube defects. Br J Obstet Gynaecol 1996; 103:319.
  25. van der Put NM, van Straaten HW, Trijbels FJ, Blom HJ. Folate, homocysteine and neural tube defects: an overview. Exp Biol Med (Maywood) 2001; 226:243.
  26. Steegers-Theunissen RP, Boers GH, Blom HJ, et al. Neural tube defects and elevated homocysteine levels in amniotic fluid. Am J Obstet Gynecol 1995; 172:1436.
  27. Rothenberg SP, da Costa MP, Sequeira JM, et al. Autoantibodies against folate receptors in women with a pregnancy complicated by a neural-tube defect. N Engl J Med 2004; 350:134.
  28. Molloy AM, Quadros EV, Sequeira JM, et al. Lack of association between folate-receptor autoantibodies and neural-tube defects. N Engl J Med 2009; 361:152.
  29. Li DK, Janevic T, Odouli R, Liu L. Hot tub use during pregnancy and the risk of miscarriage. Am J Epidemiol 2003; 158:931.
  30. Edwards MJ. Review: Hyperthermia and fever during pregnancy. Birth Defects Res A Clin Mol Teratol 2006; 76:507.
  31. Dreier JW, Andersen AM, Berg-Beckhoff G. Systematic review and meta-analyses: fever in pregnancy and health impacts in the offspring. Pediatrics 2014; 133:e674.
  32. Edwards MJ. Hyperthermia as a teratogen: a review of experimental studies and their clinical significance. Teratog Carcinog Mutagen 1986; 6:563.
  33. Graham JM Jr, Edwards MJ, Edwards MJ. Teratogen update: gestational effects of maternal hyperthermia due to febrile illnesses and resultant patterns of defects in humans. Teratology 1998; 58:209.
  34. Feldkamp ML, Meyer RE, Krikov S, Botto LD. Acetaminophen use in pregnancy and risk of birth defects: findings from the National Birth Defects Prevention Study. Obstet Gynecol 2010; 115:109.
  35. Windham GC, Bjerkedal T, Sever LE. The association of twinning and neural tube defects: studies in Los Angeles, California, and Norway. Acta Genet Med Gemellol (Roma) 1982; 31:165.
  36. Kibar Z, Torban E, McDearmid JR, et al. Mutations in VANGL1 associated with neural-tube defects. N Engl J Med 2007; 356:1432.
  37. Wang XW, Luo YL, Wang W, et al. Association between MTHFR A1298C polymorphism and neural tube defect susceptibility: a metaanalysis. Am J Obstet Gynecol 2012; 206:251.e1.
  38. Copp AJ, Stanier P, Greene ND. Neural tube defects: recent advances, unsolved questions, and controversies. Lancet Neurol 2013; 12:799.
  39. Kirke PN, Mills JL, Molloy AM, et al. Impact of the MTHFR C677T polymorphism on risk of neural tube defects: case-control study. BMJ 2004; 328:1535.
  40. Yang Y, Chen J, Wang B, et al. Association between MTHFR C677T Polymorphism and NeuralTube Defect Risks: A Comprehensive Evaluation in ThreeGroups of NTD Patients, Mothers, and Fathers. Birth Defects Res A Clin Mol Teratol 2015; 103:488.
  41. James SJ, Pogribna M, Pogribny IP, et al. Abnormal folate metabolism and mutation in the methylenetetrahydrofolate reductase gene may be maternal risk factors for Down syndrome. Am J Clin Nutr 1999; 70:495.
  42. O'Leary VB, Parle-McDermott A, Molloy AM, et al. MTRR and MTHFR polymorphism: link to Down syndrome? Am J Med Genet 2002; 107:151.
  43. Hobbs CA, Sherman SL, Yi P, et al. Polymorphisms in genes involved in folate metabolism as maternal risk factors for Down syndrome. Am J Hum Genet 2000; 67:623.
  44. Barkai G, Arbuzova S, Berkenstadt M, et al. Frequency of Down's syndrome and neural-tube defects in the same family. Lancet 2003; 361:1331.
  45. Hollis ND, Allen EG, Oliver TR, et al. Preconception folic acid supplementation and risk for chromosome 21 nondisjunction: a report from the National Down Syndrome Project. Am J Med Genet A 2013; 161A:438.
  46. Brody LC, Conley M, Cox C, et al. A polymorphism, R653Q, in the trifunctional enzyme methylenetetrahydrofolate dehydrogenase/methenyltetrahydrofolate cyclohydrolase/formyltetrahydrofolate synthetase is a maternal genetic risk factor for neural tube defects: report of the Birth Defects Research Group. Am J Hum Genet 2002; 71:1207.
  47. Parle-McDermott A, Pangilinan F, O'Brien KK, et al. A common variant in MTHFD1L is associated with neural tube defects and mRNA splicing efficiency. Hum Mutat 2009; 30:1650.
  48. Shaw GM, Lu W, Zhu H, et al. 118 SNPs of folate-related genes and risks of spina bifida and conotruncal heart defects. BMC Med Genet 2009; 10:49.
  49. Parle-McDermott A, Kirke PN, Mills JL, et al. Confirmation of the R653Q polymorphism of the trifunctional C1-synthase enzyme as a maternal risk for neural tube defects in the Irish population. Eur J Hum Genet 2006; 14:768.
  50. De Marco P, Merello E, Calevo MG, et al. Evaluation of a methylenetetrahydrofolate-dehydrogenase 1958G>A polymorphism for neural tube defect risk. J Hum Genet 2006; 51:98.
  51. Boyd PA, Devigan C, Khoshnood B, et al. Survey of prenatal screening policies in Europe for structural malformations and chromosome anomalies, and their impact on detection and termination rates for neural tube defects and Down's syndrome. BJOG 2008; 115:689.
  52. Norem CT, Schoen EJ, Walton DL, et al. Routine ultrasonography compared with maternal serum alpha-fetoprotein for neural tube defect screening. Obstet Gynecol 2005; 106:747.
  53. Racusin D, Stevens B, Campbell G, Aagaard KM. Obesity and the risk and detection of fetal malformations. Semin Perinatol 2012; 36:213.
  54. Cameron M, Moran P. Prenatal screening and diagnosis of neural tube defects. Prenat Diagn 2009; 29:402.
  55. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 101: Ultrasonography in pregnancy. Obstet Gynecol 2009; 113:451.
  56. Gitlin D, Perricelli A, Gitlin GM. Synthesis of -fetoprotein by liver, yolk sac, and gastrointestinal tract of the human conceptus. Cancer Res 1972; 32:979.
  57. Driscoll DA, Gross SJ, Professional Practice Guidelines Committee. Screening for fetal aneuploidy and neural tube defects. Genet Med 2009; 11:818.
  58. Bredaki FE, Poon LC, Birdir C, et al. First-trimester screening for neural tube defects using alpha-fetoprotein. Fetal Diagn Ther 2012; 31:109.
  59. Aitken DA, McCaw G, Crossley JA, et al. First-trimester biochemical screening for fetal chromosome abnormalities and neural tube defects. Prenat Diagn 1993; 13:681.
  60. Bernard JP, Cuckle HS, Bernard MA, et al. Combined screening for open spina bifida at 11-13 weeks using fetal biparietal diameter and maternal serum markers. Am J Obstet Gynecol 2013; 209:223.e1.
  61. Sebire NJ, Spencer K, Noble PL, et al. Maternal serum alpha-fetoprotein in fetal neural tube and abdominal wall defects at 10 to 14 weeks of gestation. Br J Obstet Gynaecol 1997; 104:849.
  62. Spencer K, Khalil A, Brown L, et al. First trimester maternal serum alpha-fetoprotein is not raised in pregnancies with open spina bifida. Prenat Diagn 2014; 34:168.
  63. Wald NJ, Cuckle H, Brock JH, et al. Maternal serum-alpha-fetoprotein measurement in antenatal screening for anencephaly and spina bifida in early pregnancy. Report of U.K. collaborative study on alpha-fetoprotein in relation to neural-tube defects. Lancet 1977; 1:1323.
  64. Wang ZP, Li H, Hao LZ, Zhao ZT. The effectiveness of prenatal serum biomarker screening for neural tube defects in second trimester pregnant women: a meta-analysis. Prenat Diagn 2009; 29:960.
  65. Evans MI, Llurba E, Landsberger EJ, et al. Impact of folic acid fortification in the United States: markedly diminished high maternal serum alpha-fetoprotein values. Obstet Gynecol 2004; 103:474.
  66. Wald N, Cuckle H, Boreham J, et al. The effect of maternal weight on maternal serum alpha-fetoprotein levels. Br J Obstet Gynaecol 1981; 88:1094.
  67. Reichler A, Hume RF Jr, Drugan A, et al. Risk of anomalies as a function of level of elevated maternal serum alpha-fetoprotein. Am J Obstet Gynecol 1994; 171:1052.
  68. Morrow RJ, Whittle MJ, McNay MB, et al. Prenatal diagnosis and management of anterior abdominal wall defects in the west of Scotland. Prenat Diagn 1993; 13:111.
  69. Wald N, Cuckle H, Nanchahal K. Amniotic fluid acetylcholinesterase measurement in the prenatal diagnosis of open neural tube defects. Second report of the Collaborative Acetylcholinesterase Study. Prenat Diagn 1989; 9:813.
  70. Flick A, Krakow D, Martirosian A, et al. Routine measurement of amniotic fluid alpha-fetoprotein and acetylcholinesterase: the need for a reevaluation. Am J Obstet Gynecol 2014; 211:139.e1.
  71. Sepulveda W, Donaldson A, Johnson RD, et al. Are routine alpha-fetoprotein and acetylcholinesterase determinations still necessary at second-trimester amniocentesis? Impact of high-resolution ultrasonography. Obstet Gynecol 1995; 85:107.
  72. Saleem SN, Said AH, Abdel-Raouf M, et al. Fetal MRI in the evaluation of fetuses referred for sonographically suspected neural tube defects (NTDs): impact on diagnosis and management decision. Neuroradiology 2009; 51:761.
  73. Zugazaga Cortazar A, Martín Martinez C, Duran Feliubadalo C, et al. Magnetic resonance imaging in the prenatal diagnosis of neural tube defects. Insights Imaging 2013; 4:225.
  74. Chao TT, Dashe JS, Adams RC, et al. Fetal spine findings on MRI and associated outcomes in children with open neural tube defects. AJR Am J Roentgenol 2011; 197:W956.
  75. Loft AG, Høgdall E, Larsen SO, Nørgaard-Pedersen B. A comparison of amniotic fluid alpha-fetoprotein and acetylcholinesterase in the prenatal diagnosis of open neural tube defects and anterior abdominal wall defects. Prenat Diagn 1993; 13:93.
  76. Stoll C, Dott B, Alembik Y, Roth MP. Associated malformations among infants with neural tube defects. Am J Med Genet A 2011; 155A:565.
  77. Rossi AC, Prefumo F. Additional value of fetal magnetic resonance imaging in the prenatal diagnosis of central nervous system anomalies: a systematic review of the literature. Ultrasound Obstet Gynecol 2014; 44:388.
  78. Kennedy D, Chitayat D, Winsor EJ, et al. Prenatally diagnosed neural tube defects: ultrasound, chromosome, and autopsy or postnatal findings in 212 cases. Am J Med Genet 1998; 77:317.
  79. Hume RF Jr, Drugan A, Reichler A, et al. Aneuploidy among prenatally detected neural tube defects. Am J Med Genet 1996; 61:171.
  80. Sepulveda W, Corral E, Ayala C, et al. Chromosomal abnormalities in fetuses with open neural tube defects: prenatal identification with ultrasound. Ultrasound Obstet Gynecol 2004; 23:352.
  81. Drugan A, Johnson MP, Dvorin E, et al. Aneuploidy with neural tube defects: another reason for complete evaluation in patients with suspected ultrasound anomalies or elevated maternal serum alpha-fetoprotein. Fetal Ther 1989; 4:88.
  82. Warner AA, Pettenati MJ, Burton BK. Risk of fetal chromosomal anomalies in patients with elevated maternal serum alpha-fetoprotein. Obstet Gynecol 1990; 75:64.
  83. Barth WH Jr, Frigoletto FD Jr, Krauss CM, et al. Ultrasound detection of fetal aneuploidy in patients with elevated maternal serum alpha-fetoprotein. Obstet Gynecol 1991; 77:897.
  84. Megerian G, Godmilow L, Donnenfeld AE. Ultrasound-adjusted risk and spectrum of fetal chromosomal abnormality in women with elevated maternal serum alpha-fetoprotein. Obstet Gynecol 1995; 85:952.
  85. Johnson CY, Honein MA, Dana Flanders W, et al. Pregnancy termination following prenatal diagnosis of anencephaly or spina bifida: a systematic review of the literature. Birth Defects Res A Clin Mol Teratol 2012; 94:857.
  86. Practice bulletin no. 145: antepartum fetal surveillance. Obstet Gynecol 2014; 124:182.
  87. Frey HA, Odibo AO, Dicke JM, et al. Stillbirth risk among fetuses with ultrasound-detected isolated congenital anomalies. Obstet Gynecol 2014; 124:91.
  88. Wilson RD, SOGC Genetics Committee, Wilson RD, et al. Prenatal screening, diagnosis, and pregnancy management of fetal neural tube defects. J Obstet Gynaecol Can 2014; 36:927.
  89. Cowchock S, Ainbender E, Prescott G, et al. The recurrence risk for neural tube defects in the United States: a collaborative study. Am J Med Genet 1980; 5:309.
  90. Toriello HV, Higgins JV. Occurrence of neural tube defects among first-, second-, and third-degree relatives of probands: results of a United States study. Am J Med Genet 1983; 15:601.
  91. Seller MJ. Recurrence risks for neural tube defects in a genetic counseling clinic population. J Med Genet 1981; 18:245.
  92. Czeizel A, Métneki J. Recurrence risk after neural tube defects in a genetic counselling clinic. J Med Genet 1984; 21:413.
  93. Koch M, Fuhrmann W. Sibs of probands with neural tube defects--a study in the Federal Republic of Germany. Hum Genet 1985; 70:74.
  94. Nussbaum, R, McInnes, et al. Genetics of disorders with complex inheritance. In: Thompson & Thompson Genetics in Medicine, 6th, WB Saunders Co, Philadelphia 2001. p.289.
  95. MacCarthy PA, Dalrymple IJ, Duignan NM, et al. Recurrence rates of neural tube defects in Dublin maternity hospitals. Ir Med J 1983; 76:78.
  96. The infant with anencephaly. The Medical Task Force on Anencephaly. N Engl J Med 1990; 322:669.