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

Interpreting changes in the epidemiology of anencephaly and spina bifida following folic acid fortification of the U.S. grain supply

Besser LM, Williams LJ, Cragan JD. Interpreting changes in the epidemiology of anencephaly and spina bifida following folic acid fortification of the U.S. grain supply in the setting of long-term trends, Atlanta, Georgia, 1968-2003. Birth Defects Research. Part A: Clinical Molecular Teratology . 2007 Nov;79(11):730-6.

BACKGROUND:: The prevalence of anencephaly (AN) and spina bifida (SB) was declining long before fortification of enriched grains in the U.S. with folic acid. We examined whether changes in these defects surrounding fortification could be distinguished from preexisting trends.

METHODS:: We used data from the Metropolitan Atlanta Congenital Defects Program to identify three ascertainment periods: Period 1 (1968-1981), prenatal diagnoses rarely made; Period 2 (1981-1993), prenatal diagnoses made but not ascertained; Period 3 (1994-2003), prenatal diagnoses ascertained. We compared the annual percent change (APC) in AN and SB for each period using Poisson regression, then compared prevalences during each period for categories of pregnancy outcome, sex, race, gravidity, and maternal age.

RESULTS:: The prevalence of AN (N = 434) and SB (N = 663) declined during 1968-2003. The APCs in Periods 1, 2, and 3, respectively, were -6.9%, -2.9%, and -6.8% for AN, and -7.1%, -7.0%, and -6.2% for SB; 95% confidence intervals around the APCs for Periods 2 and 3 overlapped for both defects. Prevalence ratios (PRs) for females relative to males decreased for AN (2.3 in Period 1; 1.2 in Period 3); PRs for whites relative to blacks or African Americans decreased for both AN (2.7 in Period 1; 1.2 in Period 3) and SB (2.5 in Period 1; 1.1 in Period 3).

CONCLUSIONS:: Our analysis suggests that changes in AN and SB surrounding folic acid fortification (Period 3) could be part of preexisting trends. This must be considered when evaluating prevention efforts. Birth Defects Research (Part A) 79:730-736, 2007. (c) 2007 Wiley-Liss, Inc.

PMID: 17990332