Impact Of Folic Acid Fortification Research Articles

Low-dose daily folic acid (400 μg) supplementation does not affect regulation of folate transporters found present throughout the terminal ileum and colon of humans: a randomized clinical trial

BackgroundFolic acid supplementation during the periconceptional period reduces the risk of neural tube defects in infants, but concern over chronic folic acid exposure remains. An improved understanding of folate absorption may clarify potential risks. Folate transporters have been characterized in the small intestine, but less so in the colon of healthy, free-living humans. The impact of folic acid fortification or supplementation on regulation of these transporters along the intestinal tract is unknown. ObjectiveThe objective was to characterize expression of folate transporters/receptor (FT/R) and folate hydrolase, glutamate carboxypeptidase II (GCPII), from the terminal ileum and throughout the colon of adults and assess the impact of supplemental folic acid. MethodsIn this 16-wk open-labeled randomized clinical trial, adults consumed a low folic acid-containing diet, a folate-free multivitamin, and either a 400 μg folic acid supplement or no folic acid supplement. Dietary intakes and blood were assessed at baseline, 8 wk, and 16 wk (time of colonoscopy). Messenger RNA (mRNA) expression and protein expression of FT/R and GCPII were assessed in the terminal ileum, cecum, and ascending and descending colon. ResultsAmong 24 randomly assigned subjects, no differences in dietary folate intake or blood folate were observed at baseline. Mean ± SD red blood cell folate at 16 wk was 1765 ± 426 and 911 ± 242 nmol/L in the 400 and 0 μg folic acid group, respectively (P < 0.0001). Reduced folate carrier, proton-coupled folate transporter, and folate-receptor alpha expression were detected in the terminal ileum and colon, as were efflux transporters of breast cancer resistance protein and multidrug resistance protein-3. Other than a higher mRNA expression of FR-alpha and GCPII in the 400 μg supplement group in the ascending colon, no treatment differences were observed (P < 0.02). ConclusionsFolate transporters are present throughout the terminal ileum and colon; there is little evidence that a low dose of folic acid supplementation affects colonic absorption.This trial was registered at clinicaltrials.gov as NCT03421483.

Prevalence of neural tube defects in England prior to the mandatory fortification of non-wholemeal wheat flour with folic acid: a population-based cohort study

ObjectivesTo determine the baseline trends in the total birth prevalence of neural tube defects (NTDs) in England (2000–2019) to enable the impact of folic acid fortification of non-wholemeal wheat flour...

Intended and Unintended Benefits of Folic Acid Fortification-A Narrative Review.

Inadequate folate intake during pregnancy is the leading cause of the development of neural tube defects (NTDs) in newborns. For this reason, mandatory fortification of folic acid, a synthetic, easily bioavailable form, in processed cereals and cereal products has been implemented in the US since 1 January 1998 to reduce the risk of NTD in newborn children. This report aimed to review the literature related to the impact of mandated folic acid fortification on the intended and unintended benefits to health. Potential adverse effects were also discussed. We searched Pubmed, Google Scholar, Embase, SCOPUS, and Cochrane databases for reports. About 60 reports published between January 1998 and December 2022 were reviewed, summarized, and served as background for this review. The intended benefit was decreased prevalence of NTDs, while unintended benefits were reduction in anemia, blood serum homocysteine, and the risk of developing cardiovascular diseases. Potential issues with folic acid fortification are the presence of unmetabolized folic acid in circulation, increased risk of cancer, and the masking of vitamin B-12 deficiency. From a health perspective, it is important to monitor the impact of folic acid fortification periodically.

Low proportions of folic acid deficiency after introduction of mandatory folic acid fortification in remote areas of northern Queensland, Australia: a secondary health data analysis

Background: Australia implemented mandatory folic acid fortification of bread-making flour in 2009.Objective: To assess the impact of folic acid fortification in remote vs. regional urban areas and Indigenous vs. non-Indigenous populations in northern Queensland.Methods: Routinely collected data on folic acid measurements in remote areas and two regional urban centres in northern Queensland between 2004 and 2015 were analysed (n = 13,929) dichotomously (folic deficient vs. non-deficient).Results: Overall prevalence of folic acid deficiency was 3.2% (235/7282) in urban centres compared with 7.2% (480/6647) in remote areas (p < 0.001), and 9.3% (393/4240) in the Indigenous population compared with 3.2% (273/8451) in the non-Indigenous population (p < 0.001). Prevalence of folic acid deficiency dropped from 12.2% (n = 481) in 2004–2008 to 1.5% (n = 126) in 2010–2015 (p < 0.001). This translates into a relative risk reduction (RRR) of 88%. RRR was 79% (7.2% vs. 1.5%) in urban centres, 91% (17.3% vs. 1.5%) in remote areas, 92% (20.5% vs. 1.6%) in the Indigenous population and 80% (7.4% vs. 1.5%) in the non-Indigenous population (p < 0.001 for all).Conclusions: Substantial declines of folic acid deficiency to low and comparable proportions in former high-risk populations indicate that mandatory folic acid fortification of flour has had a population-wide benefit in northern Queensland.

Modeling the impact of folic acid fortification and supplementation on red blood cell folate concentrations and predicted neural tube defect risk in the United States: have we reached optimal prevention?

The US CDC and the Institute of Medicine recommend that women capable of becoming pregnant consume ≥400 µg synthetic folic acid/d to prevent neural tube defects (NTDs). The United States has 3 sources of folic acid: fortified enriched cereal grain products (ECGPs), fortified ready-to-eat (RTE) cereals, and dietary supplements. Our objectives were as follows: 1) to estimate the usual daily folic acid intake and distributions of red blood cell (RBC) folate concentrations among women consuming folic acid from different sources; 2) to assess the usual daily total folic acid intake associated with optimal RBC folate concentrations for NTD prevention; 3) to predict NTD prevalence; and 4) to estimate the number of preventable folate-sensitive NTDs. NHANES data (2007-2012) for nonpregnant women of reproductive age (12-49 y) were used to estimate usual daily intakes of synthetic folic acid and natural food folate. We applied existing models of the relation between RBC folate concentrations and NTD risk to predict NTD prevalence. Based on the distribution of overall RBC folate concentrations (4783 women), the predicted NTD prevalence was 7.3/10,000 live births [95% uncertainty interval (UI): 5.5-9.4/10,000 live births]. Women consuming folic acid from ECGPs as their only source had lower usual daily total folic acid intakes (median: 115 µg/d; IQR: 79-156 µg/d), lower RBC folate concentrations (median: 881 nmol/L; IQR: 704-1108 nmol/L), and higher predicted NTD prevalence (8.5/10,000 live births; 95% UI: 6.4-10.8/10,000 live births) compared with women consuming additional folic acid from diet or supplements. If women who currently consume folic acid from ECGPs only (48% of women) consumed additional folic acid sources, 345 (95% UI: 0-821) to 701 (95% UI: 242-1189) additional NTDs/y could be prevented. This analysis supports current recommendations and does not indicate any need for higher intakes of folic acid to achieve optimal NTD prevention. Ensuring 400 µg/d intake of folic acid prior to pregnancy has the potential to increase the number of babies born without an NTD.

Descriptive study on neural tube defects in Argentina.

Neural tube defects (NTDs) are the most common congenital anomalies of the central nervous system. Prevalence of NTDs varies depending on geographic region and folic acid fortification. The main objectives of this study are to analyze the prevalences of NTDs reported to the National Registry of Congenital Anomalies of Argentina (RENAC) during the period 2009 to 2013, to compare them with data from other selected surveillance systems of the Americas, and to evaluate the impact of folic acid fortification on the prevalence of NTDs in Argentina. We analyzed changes in prevalence between 2009 and 2013 for the RENAC, and differences in prevalence between RENAC and other surveillance systems. We evaluated changes for the pre and postfortification time periods in Argentina. In Argentina, anencephaly and spina bifida showed no statistically significant variation between 2009 and 2013, and encephalocele showed a statistically significant decline. The RENAC showed a statistically significant higher prevalence for all three defects when compared with surveillance systems from Chile, Colombia, and Costa Rica, and a statistically significant lower birth prevalence than Cuba for anencephaly. No differences were observed when comparing it to the Atlanta-USA and Mexico systems. A significant decrease in prevalence was observed for all three anomalies for the postfortification period in Argentina. The characteristics of cases reported to the RENAC are similar to those already reported in the literature. The differences in prevalence between the RENAC and other surveillance systems could be artifactual or real. We confirmed the decrease of prevalence of NTDs after folic acid fortification.

Predicting the Impact of Folic Acid Fortification, Ready to Eat Cereals and Supplement Use on the Risk of Neural Tube Defects in the United States

It has been reported that as RBC folate concentrations in women increase, the risk of having a neural tube defect (NTD)-affected pregnancy decreases and that this relationship is consistent between Chinese and Irish populations. We applied the Bayesian prediction model developed using data from the Chinese population to predict the risk of NTD affected pregnancies among U.S. women of childbearing age (12-49 years) using RBC folate concentration distributions from the 2007-2010 National Health and Nutrition Examination Survey. The overall predicted NTD risk was 6.9 per 10,000 births (95% uncertainty interval [UI] 5.0-9.0) based on a median RBC folate concentration of 1222nmol/L (σ =0.40). There was a moderate reduction in the predicted NTD prevalence between individuals who reported consumption of supplements containing folic acid compared to those who did not (3 NTDs per 10,000 births; 95% UI 0.8-5.2 NTDs; RBC folate concentration of 1557nmol [σ = 0.42] vs. 1134nmol/L [σ = 0.39]). Women reporting enriched cereal grain products (e.g. bread) as their only source of folic acid intake had a predicted elevated risk of NTD affected pregnancy (8.2 NTD per 10,000 births [95%UL 6.2-10.5]; median RBC folate concentration 1073nmol/L, σ = 0.36). Adding sources of folic acid (i.e. ready-to-eat cereals, supplements) was associated with increased RBC folate concentrations and predicted reduced NTD risk. Non-Hispanic white and Hispanic women had predicted NTD risks similar to that expected from published surveillance data (6.2 per 10,000 [95%UI 4.5- 8.2] and 7.2 per 10,000 [95%UI 5.3-9.3]);non-Hispanic black women had a predicted NTD risk (9.2 per 10,000; 95% UI 7.1-11.7) higher than expected. Further analyses are underway.

Stability of orofacial clefting rate in alberta, 1980-2011.

Objective : To determine the prevalence and trends of orofacial clefts in Alberta (Canada) over a 33-year period (1980 through 2011) and to determine whether the trends differ for subcategories of orofacial clefts for the period from 1997 through 2011. Design : A prevalence study based on the Alberta Congenital Anomalies Surveillance System, which has multiple sources of ascertainment, capability of verification, and an upper age limit of 1 year. Inclusion : All live born and stillborn babies and fetal deaths less than 20 weeks' gestation (including terminations of pregnancy) born in Alberta of mothers who reside in Alberta. Results and Conclusions : Rates for cleft lip with or without cleft palate and cleft palate only have been very stable over the 33-year period (1980 through 2011). These rates include all clefts (isolated, syndromes, recognizable conditions, chromosomal and multiple congenital anomalies). Ascertainment of fetal deaths less than 20 weeks' gestation began in 1997. There are trends for the 1997 through 2011 cohort with a marginally significant increase for cleft lip with or without cleft palate in the isolated category and a significant decrease for cleft palate, mainly in the associated groups. The impact of folic acid fortification and/or multivitamins/folic acid supplementation reports in the literature have shown no consensus with respect to a change in the prevalence of orofacial clefts. It is unclear whether folic acid fortification has had any impact in Alberta.

Impact of folic acid fortification on global DNA methylation and one-carbon biomarkers in the Women's Health Initiative Observational Study cohort

DNA methylation is an epigenetic mechanism that regulates gene expression and can be modified by one-carbon nutrients. The objective of this study was to investigate the impact of folic acid (FA) fortification of the US food supply on leukocyte global DNA methylation and the relationship between DNA methylation, red blood cell (RBC) folate, and other one-carbon biomarkers among postmenopausal women enrolled in the Women's Health Initiative Observational Study. We selected 408 women from the highest and lowest tertiles of RBC folate distribution matching on age and timing of the baseline blood draw, which spanned the pre- (1994–1995), peri- (1996–1997), or post-fortification (1998) periods. Global DNA methylation was assessed by liquid chromatography-tandem mass spectrometry and expressed as a percentage of total cytosine. We observed an interaction (P = 0.02) between fortification period and RBC folate in relation to DNA methylation. Women with higher (vs. lower) RBC folate had higher mean DNA methylation (5.12 vs. 4.99%; P = 0.05) in the pre-fortification period, but lower (4.95 vs. 5.16%; P = 0.03) DNA methylation in the post-fortification period. We also observed significant correlations between one-carbon biomarkers and DNA methylation in the pre-fortification period, but not in the peri- or post-fortification period. The correlation between plasma homocysteine and DNA methylation was reversed from an inverse relationship during the pre-fortification period to a positive relationship during the post-fortification period. Our data suggest that (1) during FA fortification, higher RBC folate status is associated with a reduction in leukocyte global DNA methylation among postmenopausal women and; (2) the relationship between one-carbon biomarkers and global DNA methylation is dependent on folate availability.

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

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. 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. 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. 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.

Health needs assessment for congenital anomalies in middle-income countries: Examining the case for neural tube defects in Brazil.

Recent economic improvement in Brazil has been reflected in better maternal-child health indicators, with decreases in infant and perinatal mortality. However, under-five mortality due to congenital disorders remained unchanged, and congenital disorders have become the second leading cause of infant mortality. In the present study, we used the PHG Foundation Health Needs Assessment (HNA) Toolkit with the objective of first assessing the burden of disease caused by neural tube defects (NTDs) in Brazil and the impact of interventions already put in place to address the burden, and second to evaluate and prioritize further interventions and policies required for its prevention and treatment. The results from these two components of the HNA process are described in this paper. The published literature was reviewed to identify studies of NTDs (prevalence; morbidity; prenatal, perinatal, and postnatal mortality; treatment or prevention). Data on indicators of maternal and child health were obtained directly from the Brazilian Ministry of Health, through the online Live Births Information System (SINASC) and from the Mortality Information System (SIM). Descriptive analyses included reports of the rates of NTD in liveborns, fetal, and infant deaths. Differences between folic acid flour pre-fortification (2001-2004) and post-fortification (2006-2010) periods were expressed as prevalence rate ratios. Around 20% of fetal deaths were related to congenital disorders with approximately 5% of those being NTDs. For infant mortality, congenital disorders were notified in approximately 15% of cases, with NTDs present in 10% of the malformed children. Although statistically significant, the prevalence rate ratio (PRR) for spina bifida in live births was only 0.937 (95% confidence interval (CI) 0.884-0.994), a decrease of 6.3% when comparing the pre and post-fortification periods. The impact of fortification seemed to be more visible in fetal deaths due to anencephaly (PRR = 0.727, 95% CI 0.681-0.777) and for spina bifida (PRR = 0.700, 95% CI 0.507-0.967) with associated decreases of 27.3 and 30%. The lower impact of folic acid fortification in Brazil, compared to other Latin-American countries, can be due to differences in dietary habits, concentration of folic acid in flour, as well as characteristic population ethnic composition. The HNA led to the identification of the needs to be addressed in Brazil, including the improvement of reporting congenital disorders within the nationwide birth certification system, and revision of the policy of flour folic acid fortification.

Neural tube defects in Latin America and the impact of fortification: a literature review.

Data on the prevalence of birth defects and neural tube defects (NTD) in Latin America are limited. The present review summarizes NTD prevalence and time trends in Latin American countries and compares pre- and post-fortification periods to assess the impact of folic acid fortification in these countries. We carried out a literature review of studies and institutional reports published between 1990 and 2010 that contained information on NTD prevalence in Latin America. NTD prevalence in Latin American countries varied from 0·2 to 9·6 per 1000 live births and was influenced by methods of ascertainment. Time trends from Bogota, Costa Rica, Dominican Republic, Guatemala City, Mexico and Puerto Rico showed average annual declines of 2·5 % to 21·8 %. Pre- and post-fortification comparisons were available for Argentina, Brazil, Chile, Costa Rica, Puerto Rico and Mexico. The aggregate percentage decline in NTD prevalence ranged from 33 % to 59 %. The present publication is the first to review data on time trends and the impact of folic acid fortification on NTD prevalence in Latin America. Reported NTD prevalence varied markedly by geographic region and in some areas of Latin America was among the lowest in the world, while in other areas it was among the highest. For countries with available information, time trends showed significant declines in NTD prevalence and these declines were greater in countries where folic acid fortification of staples reached the majority of the population at risk, such as Chile and Costa Rica.

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

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

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

To review the impact of folic acid fortification of flour on the prevalence of neural tube defects (NTD). 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 (1999-2009) 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 (2005-2009). We explored the potential association between median folic acid in flour (mg/kg) and the prevalence of NTD. Chile, Argentina, Brazil, Canada, Costa Rica, Iran, Jordan, South Africa and the USA. Live births and stillbirths. 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. 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.

Impacto de la Fortificación con Ácido Fólico Sobre el Estado Nutricional en Mujeres y la Prevalencia de Defectos del Tubo Neural

ABSTRACT Impact of folic acid fortification on women nutritional status and on the prevalence of neural tube defects Introduction: In 2003 iron and folic acid fortification of wheat flour became mandatory in Argentina. Folate nutritional status was assessed in a national probabilistic sample of women 10-49 years old and pregnant women. Changes in the prevalence of neural tube defects (NTDs) were evaluated before and after fortification. Population and Methods: Data from the National Nutritional and Health Survey done in 2005 were used for folate intakes (24 h dietary recall) and serum levels. Fetal and infant mortality rates for NTDs were assessed in the period 2000-2006 from Vital Statistics Series, based on birth and death certificates. Prevalence of NTDs in hospital discharge statistics were analyzed in the pre and post fortification period. Results: Median folate in-takes were 532 and 821 µg/ day in women 10-49 years-old and pregnant women, respectively. In both groups, folic acid from wheat flour represented 245 and 331 µg/day. Serum folate was assessed in 5,322 women 10-49 years old and in 1,321 pregnant women. Prevalence of serum folate concentration < 3 ng/mL was 0.8% in women of child-bearing age and 2.7% in pregnant women. Mortality rate due to anencephaly in 2000-2003 was 53.1 per 100.000 births and decreased to 23.3 per 100.000 births in 2005-2006. Spina bifida mortality rate decreased 67% in the same period. In a similar way, hospital discharge statistics showed a decrease of 54% for anencephaly, 33% for encephalocele, and 45% for spina bifida between 2000 and 2005. Conclusions: Food fortification with folic acid was associated with adequate intakes and serum folate levels in women. Concur-rently, NTDs prevalence and mortality showed a significant reduction. (Key words: Folic acid, neural tube defects, intake, serum folate, Vitamin B12). Arch Argent Pediatr 2008; 106 (6): 492-498/492RESUMENIntroduccion: Se evaluo el efecto de la fortificacion de la harina de trigo con acido folico (iniciada en 2003) sobre la ingesta de folatos en la poblacion de mujeres en edad reproductiva y en embarazadas y los niveles sericos de folato y vitamina B12 en los mismos grupos. Asimismo, se analizaron los cambios ocurridos en CONO SURRev Chil Pediatr 2010; 81 (1): 78-79SOUTH CONE OF AMERICA

Folic acid fortification: a double-edged sword

To examine the impact of folic acid fortification, including its use as a functional food component, on human health. There is a consensus view that folic acid supplementation has numerous health benefits, many of which are significant in their impact. However, emerging evidence suggests that increased population exposure to folic acid may also have a negative impact with respect to certain developmental and degenerative disorders. As examples, presently much attention is focused on the role of folic acid fortification augmenting colon cancer risk, whereas earlier in the life cycle, the vitamin may additionally influence insulin resistance. Without question, conditions that are influenced by folic acid are both diverse and many - from concerns relating to cognitive decline, breast cancer and vascular disease through to preconceptional issues where maternal folate levels might conceivably alter the phenotype of offspring via epimutations. The highly complex and critical biological importance of folic acid-related molecular nutrition makes it a difficult micronutrient to deploy as a simple intervention at a population level - it has far too many biochemical spheres of influence to predict effects in a generalized way. Additionally, several gene variants and other nutrients are interactive factors. It is, therefore, hardly surprising that the scientific community does not have a true consensus view on whether mandatory fortification is appropriate as a population measure. This latter point not withstanding, any ultimate decisions on fortification should be well rooted in scientific fact rather than political expediency.

Impact of folic acid fortification on women's nutritional status and on the prevalence of neural tube defects

In 2003 iron and folic acid fortification of wheat flour became mandatory in Argentina. Folate nutritional status was assessed in a national probabilistic sample of women 10-49 years old and pregnant women. Changes in the prevalence of neural tube defects (NTDs) were evaluated before and after fortification. Data from the National Nutritional and Health Survey done in 2005 were used for folate intakes (24 hs dietary recall) and serum levels. Fetal and infant mortality rates for NTDs were assessed in the period 2000-2006 from Vital Statistics Series, based on birth and death certificates. Prevalence of NTDs in hospital discharge statistics were analyzed in the pre and post fortification period. Median folate intakes were 532 and 821 microg/ day in women 10-49 years-old and pregnant women, respectively. In both groups, folic acid from wheat flour represented 245 and 331 microg/day. Serum folate was assessed in 5.322 women 10-49 years old and in 1.321 pregnant women. Prevalence of serum folate concentration <3 ng/mL was 0.8% in women of child-bearing age and 2.7% in pregnant women. Mortality rate due to anencephaly in 2000-2003 was 53.1 per 100.000 births and decreased to 23.3 per 100.000 births in 2005-2006. Spina bifida mortality rate decreased 67% in the same period. In a similar way, hospital discharge statistics showed a decrease of 54% for anencephaly, 33% for encephalocele, and 45% for spina bifida between 2000 and 2005. Food fortification with folic acid was associated with adequate intakes and serum folate levels in women. Concurrently, NTDs prevalence and mortality showed a significant reduction.

Folate during reproduction: the Canadian experience with folic acid fortification

Folate has received international attention regarding its role in the risk-reduction of birth defects, specifically neural tube defects (NTDs). In 1998, health officials in Canada, like the United States, mandated the addition of folic acid to white flour and select grain products to increase the folate intake of reproductive-aged women. Subsequent to this initiative there has been an increase in blood folate concentrations in Canada and a 50% reduction in NTDs. Many countries, including Korea, have not mandated folic acid fortification of their food supply. Reasons vary but often include concern over the masking of vitamin B12 deficiency, a belief that folate intakes among womenare adequate, low priority relative to other domestic issues, and the philosophy that individuals have the right not to consume supplemental folic acid if they so choose. Prior to folic acid fortification of the food supply in Canada, the folate intakes of women were low, and their blood folate concentrations while not sufficiently low to produce overt signs of folate deficiency (eg. anemia) were inconsistent with a level known to reduce the risk of an NTD-affected pregnancy. The purpose of this article is to describe the role of folate during the periconceptional period, pregnancy, and during lactation. The rationale for, and history of recommending folic acid-containing supplements during the periconceptional period and pregnancy is described as is folic acid fortification of the food supply. The impact of folic acid fortification in Canada is discussed, and unresolved issues associated with this policy described. While the incidence of NTDs in Canada pre-folic acid fortification were seemingly higherthan that of Korea today, blood folate levels of Korean women are strikingly similar. We will briefly explore these parallels in an attempt to understand whether folic acid fortification of the food supply in Korea might be worth consideration

Reduction in orofacial clefts following folic acid fortification of the U.S. grain supply

Folic acid fortification in the United States became mandatory January 1, 1998, to reduce the occurrence of neural tube defects (NTDs). We evaluated the impact of folic acid fortification on orofacial clefts using United States birth certificate data for 45 states and the District of Columbia. Prevalence ratios (PRs) were calculated comparing orofacial cleft prevalence among births prefortification (1/1990-12/1996) and postfortification (10/1998-12/2002), based on fortification status at conception. The JoinPoint Regression Program and exponentially weighted moving average charts (EWMA) were used to assess the timing of any statistically significant changes in prevalence. Data were stratified by maternal race/ethnicity, age, smoking, and timing of prenatal care. Orofacial clefts declined following folic acid fortification (PR=0.94; 95% CI: 0.92-0.96). The EWMA chart flagged a significant decrease in the fourth quarter of 1998. The JoinPoint graph had one change in slope, with a significant quarterly percent change (-0.34) between 1996 and 2002. The decline in orofacial clefts occurred in non-Hispanic Whites but not other racial/ethnic groups, nonsmokers but not women who reported smoking during pregnancy, and women who received prenatal care in the first trimester but not women who began receiving care later in pregnancy. Folic acid fortification in the United States was associated with a small decrease in orofacial cleft prevalence, with the timing of the decline consistent with the introduction of fortification. The decline is much smaller than that observed for NTDs, but nonetheless suggests an additional benefit of this public health intervention.

Impact of Folic Acid Fortification on Orofacial Clefts

Impact of Folic Acid Fortification on Orofacial Clefts