Neural Tube Defects, Folate, and Immune Modulation

Overview

Journal Birth Defects Res A Clin Mol Teratol

Publisher Wiley

Date 2013 Oct 1

PMID 24078477

Citations 13

Authors

Kerina J Denny

Angela Jeanes

Kristin Fathe

Richard H Finnell

Stephen M Taylor

Trent M Woodruff

Affiliations

Soon will be listed here.

Abstract

Periconceptional supplementation with folic acid has led to a significant worldwide reduction in the incidence of neural tube defects (NTDs). However, despite increasing awareness of the benefits of folic acid supplementation and the implementation of food fortification programs in many countries, NTDs continue to be a leading cause of perinatal morbidity and mortality worldwide. Furthermore, there exists a significant subgroup of women who appear to be resistant to the protective effects of folic acid supplementation. The following review addresses emerging clinical and experimental evidence for a role of the immune system in the etiopathogenesis of NTDs, with the aim of developing novel preventative strategies to further reduce the incidence of NTD-affected pregnancies. In particular, recent studies demonstrating novel roles and interactions between innate immune factors such as the complement cascade, neurulation, and folate metabolism are explored.

Citing Articles

Fetal spina bifida associates with dysregulation in nutrient-sensitive placental gene networks: Findings from a matched case-control study.

White M, Arif-Pardy J, Van Mieghem T, Connor K Clin Transl Sci. 2024; 17(1):e13710.

PMID: 38226444 PMC: 10804907. DOI: 10.1111/cts.13710.

Determinants of neural tube defects among newborns in public referral hospitals in Eastern Ethiopia.

Mohamed F, Dheresa M, Raru T, Yusuf N, Hassen T, Mehadi A BMC Nutr. 2023; 9(1):93.

PMID: 37491389 PMC: 10369744. DOI: 10.1186/s40795-023-00752-7.

Identification of immune-related biomarkers in embryos with neural tube defects via a bioinformatics analysis.

Huang Q, Yang L, Nong B, Gan H, Wu H, Li M Ann Transl Med. 2022; 10(9):521.

PMID: 35928755 PMC: 9347061. DOI: 10.21037/atm-22-1273.

Biology of Perseverative Negative Thinking: The Role of Timing and Folate Intake.

Eszlari N, Bruncsics B, Millinghoffer A, Hullam G, Petschner P, Gonda X Nutrients. 2021; 13(12).

PMID: 34959947 PMC: 8703428. DOI: 10.3390/nu13124396.

Systems biology analysis of human genomes points to key pathways conferring spina bifida risk.

Aguiar-Pulido V, Wolujewicz P, Martinez-Fundichely A, Elhaik E, Thareja G, Abdel Aleem A Proc Natl Acad Sci U S A. 2021; 118(51).

PMID: 34916285 PMC: 8713748. DOI: 10.1073/pnas.2106844118.

References

Wu M, Brennan F, Lynch J, Mantovani S, Phipps S, Wetsel R . The receptor for complement component C3a mediates protection from intestinal ischemia-reperfusion injuries by inhibiting neutrophil mobilization. Proc Natl Acad Sci U S A. 2013; 110(23):9439-44. PMC: 3677481. DOI: 10.1073/pnas.1218815110. View

Woodruff T, Pollitt S, Proctor L, Stocks S, Manthey H, Williams H . Increased potency of a novel complement factor 5a receptor antagonist in a rat model of inflammatory bowel disease. J Pharmacol Exp Ther. 2005; 314(2):811-7. DOI: 10.1124/jpet.105.086835. View

Torchinsky A, Toder V, Savion S, Shepshelovich J, Orenstein H, Fein A . Immunostimulation increases the resistance of mouse embryos to the teratogenic effect of diabetes mellitus. Diabetologia. 1997; 40(6):635-40. DOI: 10.1007/s001250050727. View

Yadav A, Saini V, Arora S . MCP-1: chemoattractant with a role beyond immunity: a review. Clin Chim Acta. 2010; 411(21-22):1570-9. DOI: 10.1016/j.cca.2010.07.006. View

Undas A, Perla J, Lacinski M, Trzeciak W, Kazmierski R, Jakubowski H . Autoantibodies against N-homocysteinylated proteins in humans: implications for atherosclerosis. Stroke. 2004; 35(6):1299-304. DOI: 10.1161/01.STR.0000128412.59768.6e. View

Botto L, Moore C, Khoury M, Erickson J . Neural-tube defects. N Engl J Med. 1999; 341(20):1509-19. DOI: 10.1056/NEJM199911113412006. View

Attilakos A, Papakonstantinou E, Schulpis K, Voudris K, Katsarou E, Mastroyianni S . Early effect of sodium valproate and carbamazepine monotherapy on homocysteine metabolism in children with epilepsy. Epilepsy Res. 2006; 71(2-3):229-32. DOI: 10.1016/j.eplepsyres.2006.06.015. View

Finnell R, Gelineau-van Waes J, Bennett G, Barber R, Wlodarczyk B, Shaw G . Genetic basis of susceptibility to environmentally induced neural tube defects. Ann N Y Acad Sci. 2000; 919:261-77. DOI: 10.1111/j.1749-6632.2000.tb06886.x. View

Saitsu H, Ishibashi M, Nakano H, Shiota K . Spatial and temporal expression of folate-binding protein 1 (Fbp1) is closely associated with anterior neural tube closure in mice. Dev Dyn. 2003; 226(1):112-7. DOI: 10.1002/dvdy.10203. View

10.

Shaw G, Quach T, Nelson V, Carmichael S, Schaffer D, Selvin S . Neural tube defects associated with maternal periconceptional dietary intake of simple sugars and glycemic index. Am J Clin Nutr. 2003; 78(5):972-8. DOI: 10.1093/ajcn/78.5.972. View

11.

Lomaga M, Henderson J, Elia A, Robertson J, Noyce R, Yeh W . Tumor necrosis factor receptor-associated factor 6 (TRAF6) deficiency results in exencephaly and is required for apoptosis within the developing CNS. J Neurosci. 2000; 20(19):7384-93. PMC: 6772765. View

12.

Da Costa M, Sequeira J, Rothenberg S, Weedon J . Antibodies to folate receptors impair embryogenesis and fetal development in the rat. Birth Defects Res A Clin Mol Teratol. 2004; 67(10):837-47. DOI: 10.1002/bdra.10088. View

13.

Kieffer E, Martin J, Herman W . Impact of maternal nativity on the prevalence of diabetes during pregnancy among U.S. ethnic groups. Diabetes Care. 1999; 22(5):729-35. DOI: 10.2337/diacare.22.5.729. View

14.

Copp A, Greene N . Neural tube defects: prevention by folic acid and other vitamins. Indian J Pediatr. 2001; 67(12):915-21. DOI: 10.1007/BF02723958. View

15.

Copp A, Greene N, Murdoch J . The genetic basis of mammalian neurulation. Nat Rev Genet. 2003; 4(10):784-93. DOI: 10.1038/nrg1181. View

16.

Shim J, Xiao C, Paschal A, Bailey S, Rao P, Hayden M . TAK1, but not TAB1 or TAB2, plays an essential role in multiple signaling pathways in vivo. Genes Dev. 2005; 19(22):2668-81. PMC: 1283960. DOI: 10.1101/gad.1360605. View

17.

Hammons A, Summers C, Woodside J, McNulty H, Strain J, Young I . Folate/homocysteine phenotypes and MTHFR 677C>T genotypes are associated with serum levels of monocyte chemoattractant protein-1. Clin Immunol. 2009; 133(1):132-7. PMC: 4402225. DOI: 10.1016/j.clim.2009.06.008. View

18.

Kalter H . Folic acid and human malformations: a summary and evaluation. Reprod Toxicol. 2000; 14(5):463-76. DOI: 10.1016/s0890-6238(00)00093-9. View

19.

Lake B, Ford R, Kao K . Xrel3 is required for head development in Xenopus laevis. Development. 2000; 128(2):263-73. DOI: 10.1242/dev.128.2.263. View

20.

Boulet S, Yang Q, Mai C, Kirby R, Collins J, Robbins J . Trends in the postfortification prevalence of spina bifida and anencephaly in the United States. Birth Defects Res A Clin Mol Teratol. 2008; 82(7):527-32. DOI: 10.1002/bdra.20468. View