Original Article

Neural Tube Defects in South Carolina 1992–2019: A Review of Risk Factors

Authors: Lucy Pulliam, PhD, Stephanie Trammel, PhD, APRN, FNP-BC, Jane H. Dean, RN, Natallia Sianko, PhD

Abstract

Objectives: Neural tube defects (NTDs) are one of the most common major birth defects, yet the reasons for occurrence of many NTDs are still not well understood. This study sought to determine the presence of seven specific NTD risk factors in a sample of 515 isolated NTD cases that occurred in South Carolina between 1992 and 2019.

Methods: A total of 1351 NTD cases were ascertained in the state between 1992 and 2019 using data from the South Carolina NTD Surveillance and Prevention Program. Medical and pregnancy data were available for 723 of the children, whose mothers chose to enroll in the prevention portion of the program. This study focused on examining the presence of seven NTD risk factors in 515 (71.2%) of these 723 cases in which the NTDs were isolated birth defects and had no identified probable cause, such as a chromosome abnormality.

Results: Of the 515 isolated NTD cases examined in this study, 26.3% had mothers with maternal obesity, 24.0% had exposure to maternal hyperthermia, 7.6% had Hispanic race/ethnicity, 4.7% were the product of a twin or multiple pregnancy, 4.1% had mothers with pregestational diabetes mellitus, and 1.4% had maternal exposure to drugs that affect folate metabolism. In addition, 12.2% of the mothers and 12.1% of the infants were homozygous for the MTHFR C677T variant allele. Of the NTD cases under review, 57.0% had one or more of the risk factors and 15.2% had two or more risk factors.

Conclusions: These findings on NTD risk factors may provide focus areas for continued efforts to reduce preventable NTDs.

Full Article

Having trouble viewing the article content below? Click here to open it directly.

Images

Download Image

Download Image

Download Image

Download Image

Download Image

References

1. Cordero A, Mullinare J, Berry R, et al. CDC grand rounds: additional opportunities to prevent neural tube defects with folic acid fortification. MMWR Morb Mortal Wkly Rep 2010;59: 980–984.
 
2. Greenberg F, James LM, Oakley GP. Estimates of birth prevalence rates of spina bifida in the United States from computer-generated maps. Am J Obstet Gynecol 1983;145:570–573.
 
3. Dean JH, Pauly R, Stevenson RE. Neural tube defects and associated anomalies before and after folic acid fortification. J Pediatr 2020;226:186–194.
 
4. Smithells RW, Sheppard S, Schorah CJ, et al. Possible prevention of neural-tube defects by periconceptional vitamin supplementation. Lancet 1980;315:339–340.
 
5. Laurence KM, James N, Miller MH, et al. Double-blind randomised controlled trial of folate treatment before conception to prevent recurrence of neural-tube defects. Br Med J 1981;282: 1509–1511.
 
6. MRC Vitamin Study Research Group. Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. Lancet 1991;338:131–137.
 
7. Centers for Disease Control and Prevention. Spina bifida and anencephaly before and after folic acid mandate–United States, 1995-1996 and 1999-2000. https://www.cdc.gov/mmwr/preview/mmwrhtml/mm5317a3.htm. Published May 7, 2004. Accessed August 3, 2023.
 
8. Bupp CP, Sarasua SM, Dean JH, et al. When folic acid fails: insights from 20 years of neural tube defect surveillance in South Carolina. Am J Med Genet A 2015;167A:2244–2250.
 
9. Collins JS, Atkinson KK, Dean JH, et al. Long term maintenance of neural tube defects prevention in a high prevalence state. J Pediatr 2011;159:143–149.e2.
 
10. Correa A, Marcinkevage J. Prepregnancy obesity and the risk of birth defects: an update. Nutr Rev 2013;71:S68–S77.
 
11. Cadenas-Benitez NM, Yanes-Sosa F, Gonzalez-Meneses A, et al. Association of neural tube defects in children of mothers with MTHFR 677TT genotype and abnormal carbohydrate metabolism risk: a case-control study. Genet Mol Res 2014;13:2200–2207.
 
12. Williams LJ, Rasmussen SA, Flores A, et al. Decline in the prevalence of spina bifida and anencephaly by race/ethnicity: 1995–2002. Pediatrics 2005;116:580–586.
 
13. Yan L, Zhao L, Long Y, et al. Association of the maternal MTHFR C677T polymorphism with susceptibility to neural tube defects in offspring: evidence from 25 case-control studies. PLoS One 2012;7:e41689.
 
14. Windham GC, Sever LE. Neural tube defects among twin births. Am J Hum Genet 1982;34: 988–998.
 
15. Hernández-Díaz S, Werler MM, Walker AM, et al. Neural tube defects in relation to use of folic acid antagonists during pregnancy. Am J Epidemiol 2001;153:961–968.
 
16. Moretti ME, Bar-Oz B, Fried S, et al. Maternal hyperthermia and the risk for neural tube defects in offspring: systematic review and meta-analysis. Epidemiology 2005;16: 216–219.
 
17. South Carolina Community Assessment Network. Births (1990 – 2022). https://apps.dhec.sc.gov/Health/SCAN_BDP/tables/birthtable.aspx. Accessed April 26, 2023.
 
18. Murad H, Fleischman A, Sadetzki S, et al. Small samples and ordered logistic regression: does it help to collapse categories of outcome? Am Stat 2003;57:155–160.
 
19. Molloy AM. Neural tube defects: mechanisms of folate. In: Karakochuk CD, Whitfield KC, Green TJ, et al, eds. The Biology of the First 1,000 Days. Boca Raton, FL: CRC Press; 2017: 123–136.
 
20. Liu J, Li Z, Ye R, et al. Periconceptional folic acid supplementation and sex difference in prevention of neural tube defects and their subtypes in China: results from a large prospective cohort study. Nutr J 2018;17:1–7.
 
21. Miller P, Smith D, Shepard T. Maternal hyperthermia as a possible cause of anencephaly. Lancet 1978;311:519–521.
 
22. Layde PM, Edmonds LD, Erickson JD. Maternal fever and neural tube defects. Teratology 1980;21:105–108.
 
23. Corona-Rivera JR, Olvera-Molina S, Pérez-Molina JJ, et al. Prevalence of open neural tube defects and risk factors related to isolated anencephaly and spina bifida in live births from the “Dr. Juan I. Menchaca” Civil Hospital of Guadalajara (Jalisco, Mexico). Congenit Anom 2020;61:46–54.
 
24. Bailey LB, Gregory JF. Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement. J Nutr 1999;129: 919–922.
 
25. Rozen R. Genetic predisposition to hyperhomocysteinemia: deficiency of methylenetetrahydrofolate reductase (MTHFR). Thromb Haemostasis 1997;78:523–526.
 
26. Osterman MJ, Hamilton BE, Martin JA, et al. Births: final data for 2021. https://www.cdc.gov/nchs//data/nvsr/nvsr72/nvsr72-01.pdf. Published January 31, 2023. Accessed August 3, 2023.
 
27. Driscoll AK, Gregory EC. Increases in prepregnancy obesity: United States, 2016-2019. https://www.cdc.gov/nchs/products/databriefs/db392.htm. Published November 25, 2020. Accessed August 3, 2023.