Modeling anterior development in mice: Diet as modulator of risk for neural tube defects.

Kappen C. (2013). Modeling anterior development in mice: Diet as modulator of risk for neural tube defects.  American Journal of Medical Genetics Part C Seminars in Medical Genetics. 163(4):333-56. doi: 10.1002/ajmg.c.31380. Epub 2013 Oct 4.

Abstract

Head morphogenesis is a complex process that is controlled by multiple signaling centers. The most common defects of cranial development are craniofacial defects, such as cleft lip and cleft palate, and neural tube defects, such as anencephaly and encephalocoele in humans. More than 400 genes that contribute to proper neural tube closure have been identified in experimental animals, but only very few causative gene mutations have been identified in humans, supporting the notion that environmental influences are critical. The intrauterine environment is influenced by maternal nutrition, and hence, maternal diet can modulate the risk for cranial and neural tube defects. This article reviews recent progress toward a better understanding of nutrients during pregnancy, with particular focus on mouse models for defective neural tube closure. At least four major patterns of nutrient responses are apparent, suggesting that multiple pathways are involved in the response, and likely in the underlying pathogenesis of the defects. Folic acid has been the most widely studied nutrient, and the diverse responses of the mouse models to folic acid supplementation indicate that folic acid is not universally beneficial, but that the effect is dependent on genetic configuration. If this is the case for other nutrients as well, efforts to prevent neural tube defects with nutritional supplementation may need to become more specifically targeted than previously appreciated. Mouse models are indispensable for a better understanding of nutrient-gene interactions in normal pregnancies, as well as in those affected by metabolic diseases, such as diabetes and obesity. © 2013 Wiley Periodicals, Inc.

 

PMID:24124024

Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects.

Tinker SC, Devine O, Mai C, Hamner HC, Reefhuis J, Gilboa SM, Dowling NF, Honein MA. (2013) Estimate of the potential impact of folic acid fortification of corn masa flour on the prevention of neural tube defects. Birth Defects Res A Clin Mol Teratol.  97(10):649-57. doi: 10.1002/bdra.23158.

Abstract

BACKGROUND:

Hispanics in the US have a higher prevalence of neural tube defect (NTD) -affected pregnancies than non-Hispanic whites, and lower median total folic acid (FA) intake. FA fortification of corn masa flour (CMF) is a policy-level intervention for NTD prevention; however, the impact on NTD prevalence has not been estimated.

METHODS:

We developed a model to estimate the percentage reduction in prevalence of spina bifida and anencephaly (NTDs) that could occur with FA fortification of CMF. Model inputs included estimates of the percentage reduction in United States NTD prevalence attributed to FA fortification of enriched cereal grain products (1995-1996 vs. 1998-2002), the increase in median FA intake after enriched cereal grain product fortification, and the estimated increase in median FA intake that could occur with CMF fortification at the same level as enriched cereal grain products (140 μg/100 g). We used Monte Carlo simulation to quantify uncertainty. We stratified analyses by racial/ethnic group and rounded results to the nearest 10.

RESULTS:

We estimated CMF fortification could prevent 30 Hispanic infants from having spina bifida (95% uncertainty interval: 0, 80) and 10 infants from having anencephaly (95% uncertainty interval: 0, 40) annually. The estimated impact among non-Hispanic whites and blacks was smaller.

CONCLUSION:

CMF fortification with FA could prevent from 0 to 120 infants, with the most likely value of approximately 40, from having spina bifida or anencephaly among Hispanics, the population most likely to benefit from the proposed intervention. While this estimated reduction is unlikely to be discernible using current birth defect surveillance methods, it still suggests an important benefit to the target population. Birth Defects Research (Part A) 97:649-657, 2013. © 2013 Wiley Periodicals, Inc.

PMID:24142499

http://onlinelibrary.wiley.com/doi/10.1002/bdra.23158/full

Neural tube defects and maternal intake of micronutrients related to one-carbon metabolism or antioxidant activity.

Chandler AL, Hobbs CA, Mosley BS, Berry RJ, Canfield MA, Qi YP, Siega-Riz AM, Shaw GM; National Birth Defects Prevention Study. (2012) Neural tube defects and maternal intake of micronutrients related to one-carbon metabolism or antioxidant activity. Birth defects research. Part A, Clinical and molecular teratology. 2012 Aug 29.

BACKGROUND:

Maternal nutritional status has been evaluated to clarify its role in development of neural tube defects (NTDs). Maternal folate intake during pregnancy has been closely evaluated for its association with NTDs. The study objective was to examine associations between NTDs and other dietary periconceptional micronutrient intake, particularly nutrients involved in one-carbon metabolism or antioxidant activity.

METHODS:

Using data from the National Birth Defects Prevention Study, 1997-2005, logistic regression models were used to estimate the relative risk of NTDs based on maternal micronutrient intake.

RESULTS:

Results were stratified according to folic acid supplement use, race/ethnicity, and maternal body mass index. Analyses included 954 cases (300 with anencephaly, 654 with spina bifida) and 6268 controls. Higher intakes of folate, thiamin, betaine, iron, and vitamin A were associated with decreased risk of anencephaly among some ethnic and clinical groups. In some groups, higher intakes of thiamin, riboflavin, vitamin B(6) , vitamin C, vitamin E, niacin, and retinol were associated with decreased risk of spina bifida.

CONCLUSION:

In addition to folic acid, other micronutrients, including thiamin, betaine, riboflavin, vitamin B(6) , vitamin C, vitamin E, niacin, iron, retinol, and vitamin A, may decrease the risk of NTD occurrence. Birth Defects Research (Part A) 2012. © 2012 Wiley Periodicals, Inc.

PMID: 22933447

The changing incidence of myelomeningocele and its impact on pediatric neurosurgery: a review from the Children's Memorial Hospital.

Bowman RM, Boshnjaku V, McLone DG. (2009) The changing incidence of myelomeningocele and its impact on pediatric neurosurgery: a review from the Children's Memorial Hospital. Child's Nervous System. Jul;25(7):801-6.

Division of Neurosurgery, Children's Memorial Hospital, 2300 Children's Plaza, P. O. Box 28, Chicago, IL 60614, USA. RBowman@childrensmemorial.org

INCIDENCE: Worldwide, the incidence of neural tube defects (NTDs) varies from 0.17 to 6.39 per 1,000 live births. The declining prevalence of myelomeningocele, the most common NTD, is secondary to several factors including folic acid fortification, prenatal diagnosis with termination of affected fetuses, and unknown factors.

IMPACT OF CHANGES: Of those born with myelomeningocele, survival during infancy and preschool years has improved over the last 25 years (Bowman et al., Pediatr Neurosurg 34:114-120). Fewer newborns today require shunt placement, which will hopefully improve the long-term mortality associated with this disease (Chakraborty et al., J Neurosurg Pediatr 1(5):361-365, unpublished data). Of a cohort born in 1975-1979 and treated at a single US institution, 74% have survived into young adulthood.

CLINICAL IMPLICATIONS: One of the greatest challenges facing these young adults is the transitioning of their medical care into an adult medical community.

PMID: 19326126

Mouse models of neural tube defects: investigating preventive mechanisms.

Greene ND, Copp AJ. Mouse models of neural tube defects: investigating preventive mechanisms. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics. 2005 May 15;135C(1):31-41. Review.

Neural Development Unit, Institute of Child Health, University College London, UK. n.greene@ich.ucl.ac.uk

Neural tube defects (NTD), including anencephaly and spina bifida, are a group of severe congenital abnormalities in which the future brain and/or spinal cord fail to close. In mice, NTD may result from genetic mutations or knockouts, or from exposure to teratogenic agents, several of which are known risk factors in humans. Among the many mouse NTD models that have been identified to date, a number have been tested for possible primary prevention of NTD by exogenous agents, such as folic acid. In genetic NTD models such as Cart1, splotch, Cited2, and crooked tail, and NTD induced by teratogens including valproic acid and fumonisins, the incidence of defects is reduced by maternal folic acid supplementation. These folate-responsive models provide an opportunity to investigate the possible mechanisms underlying prevention of NTD by folic acid in humans. In another group of mouse models, that includes curly tail, axial defects, and the Ephrin-A5 knockout, NTD are not preventable by folic acid, reflecting the situation in humans in which a subset of NTD appear resistant to folic acid therapy. In this group of mutants alternative preventive agents, including inositol and methionine, have been shown to be effective. Overall, the data from mouse models suggests that a broad-based in utero therapy may offer scope for prevention of a greater proportion of NTD than is currently possible. Copyright 2005 Wiley-Liss, Inc

PMID: 15800852