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  • Print publication year: 2012
  • Online publication date: February 2013

Chapter 16.1 - Neural tube defects

from Section 2 - Fetal disease


Open neural tube defects (NTDs) result from failure of the embryonic process of neural tube closure. This chapter discusses pathophysiology and preventative strategies within each of these recognized subgroups: folate, chromosomal, single gene defects, genetic syndromes, diabetes and obesity, medications and smoking, hyperthermia, amniotic bands, twinning, genes and environment. The greatest success story in NTD prevention is folate supplementation. Through individual supplementation and population-based strategies such as food fortification there has been between a 20% and 70% reduction in NTDs reported across all countries actively supplementing. Diabetes and obesity are potentially modifiable risk factors for NTDs; however, despite general health campaigns regarding the health risks of obesity it remains an ever increasing problem amongst reproductive aged women. Medication and smoking exposures are amenable to prevention with health education advice and further research into safer medication use in pregnancy.

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Copp, A, Greene, N. Genetics and development of neural tube defects. J Pathol 2010;220(2):217–30
Smithells, RW, Sheppard, S, Schorah, C. Possible prevention of neural tube defects by periconceptional vitamin supplementation. Lancet 1980;1(8164);339–40.
MRC, VSRG. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338:131–7.
Czeizel, AE, Ducas, I. Prevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementation. N Engl J Med 1992;327:1832–5.
Berry, RJ, Erickson, JD, Moore, CA. Prevention of neural tube defects with folic acid in China. China-US collaborative project for neural tube defect prevention. N Engl J Med 1999;341(20):1485–90.
De-Regil, LM, Fernández-Gaxiola, AC, Dowswell, T, Peña-Rosas, JP. Effects and safety of periconceptional folate supplementation for preventing birth defects. Cochrane Database Syst Rev 2010; (10)CD007950.
Stockley, L, Lund, V. Use of folic acid supplements, particularly by low-income and young women: a series of systematic reviews to inform public health policy in the UK. Public Health Nutr 2008;11:807–21.
Mandatory folic acid fortification in Australia. Food Standards Australia New Zealand, 2009.
Honein, MA, Paulozzi, LJ, Mathews, TJ, Erickson, JD, Wong, LY. Impact of folic acid fortification of the US food supply on the occurrence of neural tube defects. JAMA 2001;285:2981–6.
Joint SOGC-Motherisk clinical practice guideline. Pre-conceptional Vitamin/Folic Acid Supplementation 2007: The Use of Folic Acid in Combination with a Multivitamin Supplement for the Prevention of Neural Tube Defects and Other Congenital Anomalies. No. 201 (Replaces guideline No. 138), December 2007.
Royal College of Obstetricians and Gynaecologists. Periconceptional folic acid and food fortification in the prevention of neural tube defects. Scientific Advisory Committee Opinion Paper 4 April 2003.
Whitehead, AS, Gallagher, P, Mills, JL, et al. A genetic defect in 5, 10 methylenetetrahydrofolate reductase in neural tube defects. QJM 1995;88:763–6.
Shaer, CM, Chescheir, N, Schulkin, J. Myelomeningocele: a review of the epidemiology, genetics, risk factors for conception, prenatal diagnosis and prognosis for affected individuals. Obstet Gynecol Surv 2007;62(7):471–79.
Hume, RF Jr, Drugan, A, Reichler, A, et al. Aneuploidy among prenatally detected neural tube defects. Am J Med Genet 1996;61(2):171–3.
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;77:317–21.
Babcook, CJ, Goldstein, RB, Filly, RA. Prenatally detected fetal myelomeningocele: is karyotype analysis warranted? Radiology 1995;194(2):491–4.
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(4):352–6.
Hunter, AGW. Brain and spinal cord. In: Stevenson, RE, Hall, JG, Goodman, RM, eds. Human Malformations and Related Anomalies, Vol. 11. New York, Oxford University Press, 1993; 116.
Hunter, AGW. Neural tube defects in Eastern Ontario and Western Quebec; demography and family data. Am J Med Genet 1984;19:45–63.
Chen, CP. Syndromes, disorders and maternal risk factors associated with neural tube defects (I-VII). Taiwan J Obstet Gynecol 2008;47(1):1–17. 47(2):131–49. 47(3):267–82.
Rasmussen, SA, Chu, SY, Kim, SY, Schmid, CH. Maternal obesity and risk of neural tube defects: a metaanalysis. Am J Obstet Gynecol 2008;198(6):611–19.
Stothard, K, Tennant, P, Bell, R, Rankin, J. Maternal overweight and obesity and the risk of congenital anomalies; a systematic review and meta-analysis. JAMA 2009;301(6):636–50.
Salbaum, JM, Kappen, C. Neural tube defect genes and maternal diabetes during pregnancy. Birth Defects Res A 2010;88:601–11.
Ray, JG, Vermeulen, MJ, Meier, C. Risk of congenital anomalies detected during antenatal serum screening in women with pregestational diabetes. QJM 2004;97:651–3.
Shaw, G, Velie, E, Schaffer, D. Risk of neural tube defect-affected pregnancies among obese women. JAMA 1996;275:1093–6.
Mojtabai, R. Body mass index and serum folate in childbearing women. Eur J Epidemiol 2004;19:1029–36.
Carmichael, S, Rasmussen, S, Shaw, G. Prepregnancy obesity: a complex risk factor for selected birth defects. Birth Defects Res A 2010;88:804–10.
Valproic acid. Reprotox, Micromedex database, 2011.
Carbamazepine. Reprotox, Micromedex database 2011.
Hunt, S, Russell, A. Topiramate in pregnancy: preliminary experience from the UK Epilepsy and Pregnancy Register. Neurology 2008;71:272–6.
Methotrexate. Reprotox, Micromedex database, 2011.
Suarez, L, Frelkner, M, Brender, J. Maternal exposures to cigarette smoke, alcohol, and street drugs and neural tube defect occurrence in offspring. Matern Child Health J 2008;12:394–401.
Graham, JM. Edwards, MJ. Discoverer of maternal hyperthermia as a human teratogen. Birth Defects Res A 2005;73(11):857–64.
Milunsky, A. Genetic Disorders and the Fetus: Diagnosis, Prevention and Treatment, 3rd edn. Baltimore, Johns Hopkins University Press. 1992; 1.
Bulman, MC, Hodgson, AJ, Sadler, TW. Hyperthermia-induced neural tube defects: the protective effect of folic acid. International Thermal Physiology Symposium, August 2001. 32(2) Supplement 1.
Moretti, ME, Bar-Oz, B, Fried, S, Koren, G. Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiology 2005;16:216–19.
Zhiwen, L, Aiguo, R, Le, Z, Zhanying, G. A population-based case–control study of risk factors for neural tube defects in four high-prevalence areas of Shanxi province, China. Paediatr Perinat Ep 2006;20(1):43–53.
Milunsky, A, Ulcickas, M, Rothman, KJ, et al. Maternal heat exposure and neural tube defects. JAMA 1992;268:882–5.
Karaman, A, Kahveci, H, Tos, T. Amniotic band sequence associated with fronto-ethmoidal meningoencephalocele: case report. Clin Genet 2010;78(Suppl 1):17.
Donkelaara, HJ, Hamelb, BCJ, Hartmanc, E. Intestinal mucosa on top of a rudimentary occipital meningocele in amniotic rupture sequence: disorganization-like syndrome, homeotic transformation, abnormal surface encounter or endoectodermal adhesion? Clin Dysmorphol 2002;11:9–13.
Jackson, T. Open thoracic meningocele associated with amniotic band syndrome. Pediatr Neurosurg 2001;34:252–4.
Eren, E, Buyukyavuz, I, Ayata, A. Amniotic band syndrome associated with sacral meningocele and anal atresia. Pediatr Int 2010;52(3):505–6.
Morovic, CG, Berwart, F, Varas, J. Craniofacial anomalies of the amniotic band syndrome in serial clinical cases. Plast Reconstr Surg 2004;113(6):1556–62.
Hay, S, Wehrung, DA. Congenital malformations in twins. Am J Hum Genet 1970;22:662–78.
Etiology, Padmanabhan R., pathogenesis and prevention of neural tube defects. Congenit Anom (Kyoto) 2006;46(2):55–67.
Windham, GC, Sever, LE. Neural tube defects among twin births. Am J Hum Genet 1982;34:988–98.
Kallen, B. Congenital malformations in twins. A population study. Acta Genet Med Gemellol (Roma), 1986;35:167–78.
Kallen B, Cocchi G. International study of sex ratio and twining of neural tube defects. Teratology 1994;50(5):322–31.
Luke B, Keith L. Monozygotic twinning as a congenital defect and congenital defects in monozygotic twins. Fetal Diagn Ther 1990;5(2):61.
James, W. Twinning and anencephaly. Ann Hum Biol 1976;3(5):401–9.
Syndromes, Chen C., disorders and maternal risk factors associated with neural tube defects (v). Taiwan J Obstet Gynecol 2008;47(3):259–66.
Au, KS, Ashley-Koch, A. Epidemiologic and genetic aspects of spina bifida and other neural tube defects. Dev Disabil Res Rev 2010;16(1):6–15.
Deak, K, Siegel, D, George, S. Further evidence for a maternal genetic effect and a sex-influenced effect contributing to risk for human neural tube defects. Birth Defects Res A 2008;82(10):662–9.
Detrait, E, George, T, Etchevers, J. Human neural tube defects: developmental biology, epidemiology and genetics. Neurotoxicol Teratol 2005;27(3):515–24.