The estimated prevalence of spina bifida and anencephalus in the US is 3.63 and 2.15, respectively, per 10,000 live births.[3]Mai CT, Isenburg JL, Canfield MA, et al. National population-based estimates for major birth defects, 2010-2014. Birth Defects Res. 2019 Nov 1;111(18):1420-35.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7203968
http://www.ncbi.nlm.nih.gov/pubmed/31580536?tool=bestpractice.com
Incidence and prevalence trends reveal striking differences in racial and ethnic susceptibility, with highest rates noted among Hispanic women and lowest rates noted among African and Asian women.[4]Mitchell LE. Epidemiology of neural tube defects. Am J Med Genet C Semin Med Genet. 2005 May 15;135C(1):88-94.
https://onlinelibrary.wiley.com/doi/10.1002/ajmg.c.30057
http://www.ncbi.nlm.nih.gov/pubmed/15800877?tool=bestpractice.com
[5]Centers for Disease Control and Prevention. Racial/ethnic differences in the birth prevalence of spina bifida - United States, 1995-2005. MMWR Morb Mortal Wkly Rep. 2009 Jan 9;57(53):1409-13.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5753a2.htm
http://www.ncbi.nlm.nih.gov/pubmed/19129744?tool=bestpractice.com
[6]Shin M, Besser LM, Siffel C, et al; Congenital Anomaly Multistate Prevalence and Survival Collaborative. Prevalence of spina bifida among children and adolescents in 10 regions in the United States. Pediatrics. 2010 Aug;126(2):274-9.
http://www.ncbi.nlm.nih.gov/pubmed/20624803?tool=bestpractice.com
Genetic susceptibility is a known factor. The recurrence rate of neural tube defects, for women who have had one previous affected pregnancy, is 3% to 4%.[7]Sebold CD, Melvin EC, Siegel D, et al. Recurrence risks for neural tube defects in siblings of patients with lipomyelomeningocele. Genet Med. 2005 Jan;7(1):64-7.
http://www.ncbi.nlm.nih.gov/pubmed/15654231?tool=bestpractice.com
[8]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(3):309-14.
http://www.ncbi.nlm.nih.gov/pubmed/7405962?tool=bestpractice.com
[9]Copp AJ, Adzick NS, Chitty LS, et al. Spina bifida. Nat Rev Dis Primers. 2015 Apr 30;1:15007.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4898641
http://www.ncbi.nlm.nih.gov/pubmed/27189655?tool=bestpractice.com
If two previous pregnancies have been affected, the recurrence rate is 10% to 20%.[10]Carter CO, Roberts JA. The risk of recurrence after two children with central-nervous-system malformations. Lancet. 1967 Feb 11;1(7485):306-8.
http://www.ncbi.nlm.nih.gov/pubmed/4163511?tool=bestpractice.com
[11]Nevin NC, Johnston WP. Risk of recurrence after two children with central nervous system malformations in an area of high incidence. J Med Genet. 1980 Apr;17(2):87-92.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1048508
http://www.ncbi.nlm.nih.gov/pubmed/6991696?tool=bestpractice.com
However, more than 95% of infants with spina bifida are born to couples without a family history of neural tube defects. Therefore, environmental factors are also implicated.
Geographical variability has been documented, with higher incidence rates noted in Northern China, England and Wales, and along the eastern seaboard in the US. Interaction between environmental and genetic factors is evidenced by temporal trends, seasonal variation, and fluctuations in the incidence of spina bifida with migration.[12]Olney RS, Mulinare J. Trends in neural tube defect prevalence, folic acid supplementation, and vitamin supplement use. Semin Perinatol. 2002 Aug;26(4):277-85.
http://www.ncbi.nlm.nih.gov/pubmed/12211618?tool=bestpractice.com
Spina bifida is 1.2 to 1.7 times more common in girls, except for sacral-level defects, which occur with equal frequency among boys and girls.[13]Lary JM, Edmonds LD. Prevalence of spina bifida at birth - United States, 1983-1990: a comparison of two surveillance systems. MMWR CDC Surveill Summ. 1996 Apr 19;45(2):15-26.
https://www.cdc.gov/mmwr/preview/mmwrhtml/00040954.htm
http://www.ncbi.nlm.nih.gov/pubmed/8602137?tool=bestpractice.com
Thoracic-level spina bifida is less common than lower-level lesions, and disproportionately affects girls.[14]Greene WB, Terry RC, Demasi RA, et al. Effect of race and gender on neurological level in myelomeningocele. Dev Med Child Neurol. 1991 Feb;33(2):110-7.
http://www.ncbi.nlm.nih.gov/pubmed/2015978?tool=bestpractice.com
A worldwide decline in neural tube defect births has occurred over the past half-century.[6]Shin M, Besser LM, Siffel C, et al; Congenital Anomaly Multistate Prevalence and Survival Collaborative. Prevalence of spina bifida among children and adolescents in 10 regions in the United States. Pediatrics. 2010 Aug;126(2):274-9.
http://www.ncbi.nlm.nih.gov/pubmed/20624803?tool=bestpractice.com
[15]Nikkilä A, Rydhström H, Källén B. Incidence of spina bifida in Sweden 1973-2003: the effect of prenatal diagnosis. Eur J Public Health. 2006 Dec;16(6):660-2.
https://academic.oup.com/eurpub/article/16/6/660/587676
http://www.ncbi.nlm.nih.gov/pubmed/16672253?tool=bestpractice.com
Since the advent of alpha-fetoprotein screening and ultrasonography it is estimated that elective termination of pregnancy has diminished the birth incidence of anencephaly by 60% to 70%, and of spina bifida by 20% to 30%.[16]Cragan JD, Robert HE, Edmonds LD, et al. Surveillance for anencephaly and spina bifida and the impact of prenatal diagnosis - United States, 1985-1994. MMWR CDC Surveill Summ. 1995 Aug 25;44(4):1-13.
https://www.cdc.gov/mmwr/preview/mmwrhtml/00038567.htm
http://www.ncbi.nlm.nih.gov/pubmed/7637675?tool=bestpractice.com
Rates of neural tube defects in the US have dropped 35% since the Food and Drug Administration-mandated fortification of enriched cereal grain products in 1998, and the incidence of myelomeningocele has stabilised at 3.4 cases per 10,000 births.[17]Williams J, Mai CT, Mulinare J, et al. Updated estimates of neural tube defects prevented by mandatory folic acid fortification - United States, 1995-2011. MMWR Morb Mortal Wkly Rep. 2015 Jan 16;64(1):1-5.
https://www.cdc.gov/mmwr/preview/mmwrhtml/mm6401a2.htm
http://www.ncbi.nlm.nih.gov/pubmed/25590678?tool=bestpractice.com
[18]De Wals P, Tairou F, Van Allen MI, et al. Reduction in neural-tube defects after folic acid fortification in Canada. N Engl J Med. 2007 Jul 12;357(2):135-42.
https://www.nejm.org/doi/10.1056/NEJMoa067103
http://www.ncbi.nlm.nih.gov/pubmed/17625125?tool=bestpractice.com
[19]Boulet SL, Yang Q, Mai C, et al. Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol. 2008 Jul;82(7):527-32.
http://www.ncbi.nlm.nih.gov/pubmed/18481813?tool=bestpractice.com
However, many countries do not mandate fortification, due to concerns about the risks from high intakes of folic acid.[20]Field MS, Stover PJ. Safety of folic acid. Ann N Y Acad Sci. 2018 Feb;1414(1):59-71.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5849489
http://www.ncbi.nlm.nih.gov/pubmed/29155442?tool=bestpractice.com
[21]Weggemans RM, Schaafsma G, Kromhout D, et al. Toward an optimal use of folic acid: an advisory report of the Health Council of the Netherlands. Eur J Clin Nutr. 2009 Aug;63(8):1034-6.
https://www.nature.com/articles/ejcn20092.pdf
http://www.ncbi.nlm.nih.gov/pubmed/19209186?tool=bestpractice.com
Excess folate may increase the risk of cognitive impairment and anaemia in older adults with vitamin B12 deficiency.[22]Morris MS, Jacques PF, Rosenberg IH, et al. Folate and vitamin B-12 status in relation to anemia, macrocytosis, and cognitive impairment in older Americans in the age of folic acid fortification. Am J Clin Nutr. 2007 Jan;85(1):193-200.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1828842
http://www.ncbi.nlm.nih.gov/pubmed/17209196?tool=bestpractice.com
Concern also exists that folate fortification may increase the risk of colorectal cancers, although studies have been inconclusive.[23]Kennedy DA, Stern SJ, Moretti M, et al. Folate intake and the risk of colorectal cancer: a systematic review and meta-analysis. Cancer Epidemiol. 2011 Feb;35(1):2-10.
http://www.ncbi.nlm.nih.gov/pubmed/21177150?tool=bestpractice.com
It is estimated that current fortification programmes are preventing just 9% of the estimated folic acid-preventable spina bifida and anencephaly cases worldwide.[24]Bell KN, Oakley GP Jr. Update on prevention of folic acid-preventable spina bifida and anencephaly. Birth Defects Res A Clin Mol Teratol. 2009 Jan;85(1):102-7.
http://www.ncbi.nlm.nih.gov/pubmed/19067404?tool=bestpractice.com
In the absence of mandatory fortification, the prevalence of neural tube defects has not decreased in Europe, despite long-standing recommendations aimed at promoting peri-conceptional folic acid supplementation and existence of voluntary folic acid fortification.[25]Khoshnood B, Loane M, de Walle H, et al. Long term trends in prevalence of neural tube defects in Europe: population based study. BMJ. 2015 Nov 24;351:h5949.
https://www.bmj.com/content/351/bmj.h5949.long
http://www.ncbi.nlm.nih.gov/pubmed/26601850?tool=bestpractice.com
In countries where fortification has been implemented, prevention campaigns are increasingly focused on high-risk populations, including Hispanic women, women with diabetes, and women who are obese. These risk factors appear to have a synergistic effect.[26]Moore LL, Singer MR, Bradlee ML, et al. A prospective study of the risk of congenital defects associated with maternal obesity and diabetes mellitus. Epidemiology. 2000 Nov;11(6):689-94.
http://www.ncbi.nlm.nih.gov/pubmed/11055631?tool=bestpractice.com
[27]Farrell T, Neale L, Cundy T. Congenital anomalies in the offspring of women with type 1, type 2 and gestational diabetes. Diab Med. 2002 Apr;19(4):322-6.
http://www.ncbi.nlm.nih.gov/pubmed/11943005?tool=bestpractice.com
For example, maternal obesity is associated with a 3.5-fold excess risk of having a baby with spina bifida.[28]Watkins ML, Rasmussen SA, Honein MA, et al. Maternal obesity and risk for birth defects. Pediatrics. 2003 May;111(5 Pt 2):1152-8.
http://www.ncbi.nlm.nih.gov/pubmed/12728129?tool=bestpractice.com
This risk is increased 8-fold for an obese Hispanic woman, and is even higher if she is also diabetic.[29]Shaw GM, Quach T, Nelson V, et. al. Neural tube defects associated with maternal periconceptional dietary intake of simple sugars and glycemic index. Am J Clin Nutr. 2003 Nov;78(5):972-8.
https://academic.oup.com/ajcn/article/78/5/972/4677507
http://www.ncbi.nlm.nih.gov/pubmed/14594784?tool=bestpractice.com
Despite recommendations for peri-conceptual folic acid fortification, the incidence of neural tube defects has not significantly reduced, largely due to poor adherence.[24]Bell KN, Oakley GP Jr. Update on prevention of folic acid-preventable spina bifida and anencephaly. Birth Defects Res A Clin Mol Teratol. 2009 Jan;85(1):102-7.
http://www.ncbi.nlm.nih.gov/pubmed/19067404?tool=bestpractice.com
[30]Botto LD, Lisi A, Robert-Gnansia E, et al. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? 2005 Mar 12;330(7491):571.
https://www.bmj.com/content/330/7491/571.long
http://www.ncbi.nlm.nih.gov/pubmed/15722368?tool=bestpractice.com
[31]Inskip HM, Crozier SR, Godfrey KM. Women's compliance with nutrition and lifestyle recommendations before pregnancy: general population cohort study. BMJ. 2009 Feb 12;338:b481.
https://www.bmj.com/content/338/bmj.b481.long
http://www.ncbi.nlm.nih.gov/pubmed/19213768?tool=bestpractice.com