Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada

Wals, Philippe De; Tairou, Fassiatou; Allen, Margot I. Van; Uh, Soo Hong; Lowry, R. Brian; Sibbald, Barbara; Evans, Jane; Hof, Michiel C. Van den; Zimmer, Pamela; Crowley, Marian; Fernandez, Bridget A.; Lee, Nora S.; Niyonsenga, Théophile

doi:10.1056/nejmoa067103

Cited by 675 publications

(244 citation statements)

References 21 publications

Supporting

Mentioning

216

Contrasting

Unclassified

Order By: Relevance

“…These ground-breaking randomised controlled trials provided the evidence base for national-scale public health interventions, initially in the USA and Canada, which require the mandatory fortification of flour with 140 µg folic acid per 100 g flour. This fortification programme, which began in 1996 and became mandatory from January 1998, has been highly effective in raising the folate status of the whole population (8) and has been associated with a substantial fall in NTD prevalence (9) . Several other countries, excluding those in the European Union, have implemented similar folic acid fortification policies.…”

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Maternal folate deficiency and metabolic dysfunction in offspring

McKay

Mathers

2015

Proc. Nutr. Soc.

View full text Add to dashboard Cite

Conference on 'Diet, gene regulation and metabolic disease' Symposium 3: Nutrition, epigenetics and the fetal origins of metabolic disease Maternal folate deficiency and metabolic dysfunction in offspring The importance of folate during pregnancy was established more than 80 years ago by Lucy Wills' ground-breaking studies of tropical macrocytic anaemia. More recently, it has become apparent that the adverse consequences of inadequate nutrient supply during early developmental may be exacerbated by over-nutrition postnatally. The present paper aims to review recent evidence that maternal methyl donor (notably folate) supply peri-conceptually and during pregnancy has long-term effects on offspring (metabolic) health. In addition, we propose the hypothesis that epigenetic mechanisms, especially DNA methylation, may mediate the effects of these early life nutritional insults. We discuss evidence from a natural experiment in human subjects which provides proof of principle for the hypothesis. We describe an attempt to test this hypothesis using a mouse model in which female C57Bl/6 mice were randomised to low or normal folate diets prior to, and during, pregnancy and lactation. Low maternal folate supply resulted in offspring that were more susceptible to detrimental metabolic effects of a high-fat diet fed from weaning, manifested as increased circulating TAG concentration. Interestingly, this metabolic phenotype in adult offspring occurred without any detectable change in adiposity, suggesting a different aetiological origin from the more commonly reported observation that maternal undernutrition leads to increased offspring adiposity and to symptoms of the Metabolic Syndrome. The widespread prevalence of overweight and obesity and of folate deficiency among women of child-bearing age highlights the possibility that this double nutritional insult may exacerbate the risk of metabolic disease in their offspring.

show abstract

Section: Proceedings Of the Nutrition Societymentioning

confidence: 99%

Maternal folate deficiency and metabolic dysfunction in offspring

McKay

Mathers

2015

Proc. Nutr. Soc.

View full text Add to dashboard Cite

show abstract

“…NTDs are now the leading cause of infant mortality and inflict a large economic burden on society and families Table 3 Distribution of rs4816 and association with NTD subtypes Genotypes Control (n = 141), n (%) Anencephaly (n = 50), n (%) Spina bifida (n = 55), n (%) Encephalocele (n = 11), n (%) (Davidoff et al 2002). It has been reported that NTDs can be prevented with periconceptional folic acid supplementation (Czeizel and Dudas 1992;De Wals et al 2007). Actions have been taken by the Chinese Ministry of Health to reduce the incidence of NTDs in China since 2009.…”

Section: Discussionmentioning

confidence: 99%

“…NTDs include a range of malformations (e.g., spina bifida, anencephaly), which further complicates the identification of risk factors. Periconceptional folic acid supplementation has been reported to prevent 50-70 % of NTDs (Czeizel and Dudas 1992;De Wals et al 2007). We previously demonstrated that nutrient deficiency is an important independent risk factor for birth defects (Zhang et al 2008a), and lower plasma concentrations of folate and vitamin B12 are related to an increased risk of NTDs in high-risk populations (Zhang et al 2009).…”

Section: Introductionmentioning

confidence: 99%

PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

Wang

Guo

et al. 2013

Genes Nutr

View full text Add to dashboard Cite

The PCMT1 gene encodes the protein repair enzyme protein-L-isoaspartate (D-aspartate) O-methyltransferase, which is known to protect certain neural cells against Bax-induced apoptosis. Previous studies have produced inconsistent results regarding the effects of PCMT1 (rs4816 and rs4552) polymorphisms on neural tube defects (NTDs). Reduced maternal plasma folate levels and/or elevated homocysteine (Hcy) levels are considered to be risk factors for NTDs. In order to clarify the key factors contributing to the apparent discrepancy and investigate gene-environment interaction, we conducted a case-control study including 121 cases and 146 matched controls to investigate the association between the two PCMT1 polymorphisms in fetuses and the risk of NTDs in the Chinese population of Lvliang, which has low folate intake. Maternal plasma folate and Hcy levels were also measured, and the interaction between fetal PCMT1 gene status and maternal folate metabolites was assessed. Maternal plasma folate concentrations in the NTD group were lower than in controls (10.23 vs. 13.08 nmol/L, adjusted P = 0.059), and Hcy concentrations were significantly higher (14.46 vs. 11.65 lmol/L, adjusted P = 0.026). Fetuses carrying the rs4816 AG ? GG genotype, combined with higher maternal plasma Hcy, had a 6.46-fold (95 % CI 1.15-36.46) increased risk of anencephaly. The results of this study imply that the fetal PCMT1 rs4816 polymorphism may play only a weak role in NTD formation and that gene-environment interactions might be more significant.

show abstract

“…Implementation of food fortification with folic acid in 1998 in USA and Canada caused a significant decrease of NTDs. The incidence of spina bifida decreased by 31% and 53% in the USA and Canada, respectively [27,28]. A study conducted by Ionescu-Ittu et al showed a significant drop in incidence of congenital heart defects in Quebec province in Canada after implementation of mandatory food fortification [29].…”

Section: Discussionmentioning

confidence: 99%

Intake of folic acid by Polish women with higher education — a survey research: can we do more?

Pietrzykowska-Kuncman¹,

Zasina-Olaszek

Łukasz

et al. 2017

Ginekol Pol

View full text Add to dashboard Cite

Objectives: The objective of the study is to determine efficacy of the Primary Prevention Program of Neural Tube Defects in Polish women with higher education in 5-year interval. Material and methods:Survey research was conducted twice (in 2008 and 2013) in 630 female students of universities: 305 female medical students and 325 female non-medical students. The survey was also done among women aged 27--35 who graduated from medical or non-medical universities and have at least one child. Questions concerned knowledge about prophylaxis and periconceptional folic acid intake. Chi square test was used to assess the significance. There was no significant difference in preconceptional folic acid intake among mothers with medical and non-medical education (53.3% vs. 45% p = 0.4). However, the highest folic acid intake was among mothers -medical doctors who treat children with neural tube defect. Conclusions:Difference between medical and non-medical students shows that better educational programs may improve knowledge about prophylaxis. Aside from knowledge, compliance with recommendations of Primary Prevention Program of Neural Tube Defects is unsatisfactory.

show abstract

Reduction in Neural-Tube Defects after Folic Acid Fortification in Canada

Abstract: Food fortification with folic acid was associated with a significant reduction in the rate of neural-tube defects in Canada. The decrease was greatest in areas in which the baseline rate was high.

Cited by 675 publications

References 21 publications

Maternal folate deficiency and metabolic dysfunction in offspring

Maternal folate deficiency and metabolic dysfunction in offspring

PCMT1 gene polymorphisms, maternal folate metabolism, and neural tube defects: a case–control study in a population with relatively low folate intake

Intake of folic acid by Polish women with higher education — a survey research: can we do more?

Contact Info

Product

Resources

About