Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects

Honein, Margaret A.

doi:10.1001/jama.285.23.2981

Cited by 923 publications

(545 citation statements)

References 35 publications

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“…The smallest decrease occurred in the state of California in the USA (15?5 %) (23) . Twenty-one articles reported on the prevalence of spina bifida before and after flour fortification (15,16,19,(21)(22)(23)25,26,28,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) . The largest reductions reported were in Costa Rica (61 %) (28) , Canada (55 %) (21) and Chile (55 %) (25) The latter study examined the number of NTD cases between the years 1998 and 2007.…”

Section: Resultsmentioning

confidence: 99%

Impact of folic acid fortification of flour on neural tube defects: a systematic review

Castillo-Lancellotti

Tur

Uauy

2012

Public Health Nutr.

188

141

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Objective: To review the impact of folic acid fortification of flour on the prevalence of neural tube defects (NTD). Design: Systematic review of the literature on MEDLINE via PubMed, Scopus, OvidSP and LILACS (Latin American and Caribbean Health Sciences Literature) reporting the impact of folic acid fortification of flour on the prevalence of NTD in 2000-2011. Focusing on Santiago of Chile's birth defects registry (1999)(2000)(2001)(2002)(2003)(2004)(2005)(2006)(2007)(2008)(2009) and the monitoring of flour fortification, we analysed the prevalence (NTD cases/ 10 000 births) pre and post flour fortification and the percentile distribution of folic acid content in flour (2005)(2006)(2007)(2008)(2009). We explored the potential association between median folic acid in flour (mg/kg) and the prevalence of NTD. Setting: Chile, Argentina, Brazil, Canada, Costa Rica, Iran, Jordan, South Africa and the USA. Subjects: Live births and stillbirths. Results: Twenty-seven studies that met inclusion criteria were evaluated. Costa Rica showed a significant reduction in NTD ( , 60 %). Prevalence in Chile decreased from 18?6 to 7?3/10 000 births from 1999 to 2007 and showed a slight increase to 8?5 in 2008-2009, possibly due to changes in fortification limits. When we related the prevalence of NTD with levels of flour fortification, the lowest prevalence was observed at a folic acid level of 1?5 mg/kg. Conclusions: Fortification of flour with folic acid has had a major impact on NTD in all countries where this has been reported. Chile showed a 55 % reduction in NTD prevalence between 1999 and 2009. There is a need to constantly monitor the levels of flour fortification to maximize benefits and prevent the potential risk of folic acid excess, moreover to be vigilant for any new adverse effects associated with excess. Keywords Folic acid Neural tube defects Spinal dysraphism Food fortification Systematic reviewThe importance of nutrition in the aetiology of neural tube defects (NTD) was suggested by Hibbard and Smithells, who found that women deficient in folate had an increased number of abortions, placental abruptions and fetal malformations and intra-uterine growth retardation (1) . The first reports on folate deficiency and NTD, published by Smithells et al. (2,3) , showed the protective effect of folic acid on the recurrence of NTD. A randomised study by Czeizel and Dudas (4) showed a decrease in first NTD occurrence in women supplemented with twelve vitamins containing 0?8 mg of folic acid, but not in women supplemented with trace elements and a very low dose of vitamin C. A rigorous double-blind randomised controlled trial supported by the UK Medical Research Council showed that supplementing women who had a history of children with NTD with 4 mg of folic acid daily decreased recurrence by 72 % (5) . Although some studies were retrospective, their results revealed an inverse relationship between NTD and folic acid consumption of 100-400 mg/d (6,7) . Based on this information, in 1992 the US Public Health Service r...

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Section: Resultsmentioning

confidence: 99%

Impact of folic acid fortification of flour on neural tube defects: a systematic review

Castillo-Lancellotti

Tur

Uauy

2012

Public Health Nutr.

188

141

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“…The level of fortification differs among countries; however, in all cases, these programs are designed to reduce the prevalence of pregnancies with NTDs. In the USA and Canada, these folic supplementation programs were thought to be successful because the population folate status was improved (Ray et al 2002) and reduced rates of NTDs were noted (Honein et al 2001; Williams et al 2002), although the results varied depending on ethnicity (Williams et al 2005). Data from the USA reported from the NHANES trial (Pfeiffer et al 2012) showed that the mean concentration of serum and RBC folate increased dramatically from the prefortification period (1988–1994) to the postfortification period (1990–2010), from 16.7 ± 0.5 to 41.0 ± 0.3 nM and from 747 ± 10 to 1120 ± 7 nM, respectively, resulting in a 31% reduction in the occurrence of NTDs (Williams et al 2002).…”

Section: Response Of Folate Status To Folate Intake and Supplementationmentioning

confidence: 99%

Genetic polymorphisms and folate status

Hiraoka

Kagawa

2017

Congenital Anomalies

136

102

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Moderate hyperhomocysteinemia‐induced low folate status is an independent risk factor for cardiovascular disease, dementia, and depression. Folate is an essential cofactor in the one‐carbon metabolism pathway and is necessary in amino acid metabolism, purine and thymidylate synthesis, and DNA methylation. In the folate cycle and homocysteine metabolism, folate, vitamin B12, vitamin B6, and vitamin B2 are important cofactors. Many enzymes are involved in folate transport and uptake, the folate pathway, and homocysteine (Hcy) metabolism, and various polymorphisms have been documented in these enzymes. Serum folate and total Hcy (tHcy) levels are influenced by folate intake and genetic polymorphisms in 5,10‐methylenetertahydrofolate reductase (MTHFR) such as C677T. The prevalence of the MTHFR 677TT genotype varies across ethnic groups and regions, with a frequency of approximately 15% in Japanese populations. Individuals with the TT genotype have significantly higher tHcy levels and lower folate levels in serum than those with the CT and TT genotypes. However, administration of folic acid has been shown to eliminate these differences. Moreover, data have suggested that interventions based on genotype may be effective for motivating individuals to change their lifestyle and improve their nutrition status. Accordingly, in this review, we discuss the effects of MTHFR C677T polymorphisms on serum tHcy and folate levels with folic acid intervention and evaluate approaches for overcoming folic acid deficiency and related symptoms.

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“…8,9 Indeed, studies in the United States have suggested a significant decrease in the prevalence of spina bifida and anencephaly as the Food and Drug Administration (FDA) mandated the addition of folic acid to all enriched cereal grain products by January 1998. [10][11][12] Cancer Low-plasma folate levels have been associated with an increased incidence of a number of types of cancer. Folate deficiency seems to predispose normal tissue to neoplastic transformation, and folate supplementation can suppress the development of tumors in normal tissue.…”

Section: Neural Tubule Defectsmentioning

confidence: 99%

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

2009

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Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects

Abstract: A 19% reduction in NTD birth prevalence occurred following folic acid fortification of the US food supply. However, factors other than fortification may have contributed to this decline.

Cited by 923 publications

References 35 publications

Impact of folic acid fortification of flour on neural tube defects: a systematic review

Impact of folic acid fortification of flour on neural tube defects: a systematic review

Genetic polymorphisms and folate status

Investigation of inter-individual variability of the one-carbon folate pathway: a bioinformatic and genetic review

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