EFSA NDA Panel (EFSA Panel on Dietetic Products, Nutrition and Allergies), 2013. Scientific Opinion on the substantiation of a health claim related to increasing maternal folate status by supplemental folate intake and reduced risk of neural tube defects pursuant to Article 14 of Regulation (EC) No 1924/2006

Following an application from Rank Nutrition Ltd, submitted for authorisation of a health claim pursuant to Article 14 of Regulation (EC) No 1924/2006 via the Competent Authority of the United Kingdom, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver an opinion on the scientific substantiation of a health claim related to increasing maternal folate status by supplemental folate intake and reduced risk of neural tube defects. The Panel considers that the food constituent, supplemental folate, which is the subject of the claim, is sufficiently characterised. Increasing maternal folate status by supplemental folate intake is a beneficial physiological effect in the context of reducing the risk of neural tube defects. In weighing the evidence, the Panel took into account that the association between low maternal folate intakes and an increased risk of neural tube defects is well established, and that a recent systematic review showed an effect of maternal folic acid intakes on the risk of neural tube defects. The Panel concludes that a cause and effect relationship has been established between increasing maternal folate status by supplemental folate intake and a reduced risk of neural tube defects

Public health failure in the prevention of neural tube defects: time to abandon the tolerable upper intake level of folate.

The neural tube defects anencephaly and spina bifida are two of the most common serious congenital malformations. Most cases can be prevented by consuming sufficient folic acid immediately before pregnancy and in early pregnancy. Fortification of flour with folic acid to prevent these defects has been implemented in 81 countries without public objection or indication of harm. An obstacle to the wider adoption of fortification arises from the creation of a "tolerable upper intake level" for folate (which includes natural food folate as well as synthetic folic acid), and which has been set at 1 mg/day, thereby proscribing higher folate intakes. Increasing the intake of folic acid in a population will necessarily increase the number of people with a folate intake greater than 1 mg per day, and this concern is obstructing folic acid fortification. This paper shows that the scientific basis for setting any upper limit, let alone one at 1 mg/day, is flawed. An upper intake level is therefore unnecessary and should be removed, thus allaying unjustified concerns about folic acid fortification. As a result, the full global opportunity to prevent two serious fatal or disabling disorders can and should be realized

Periconceptional bread intakes indicate New Zealand's proposed mandatory folic acid fortification program may be outdated: results from a postpartum survey

Abstract Background In September 2009, a folic acid fortification mandate (135 μg/100 g bread) was to be implemented in New Zealand. However, due to political and manufacturer objection, fortification was deferred until May 2012. Based on estimates of bread consumption derived from a 1997 nationally representative survey, this program was intended to deliver a mean additional intake of 140 μg folic acid/d to women of childbearing age. Little is known about current bread consumption patterns in this target group. The aim of this study was to assess bread consumption among women prior to and during pregnancy with the intent to estimate periconceptional folic acid intakes that would be derived from bread if mandatory fortification were implemented as currently proposed. Methods A retrospective survey of 723 postpartum women in hospitals and birthing centres across New Zealand was conducted using a self-administered questionnaire on bread intake prior to and during pregnancy and maternal socio-demographic and obstetric characteristics. Results Median bread intake before conception (2 slices/d) was below that of previous data upon which the current fortification proposal was modeled (3-4 slices/d). If mandatory fortification is implemented as proposed, only 31% (95% CI = 24%-37%) of childbearing-age women would attain an additional folic acid intake of ≥ 140 μg/d, with a mean of 119 μg/d (95% CI = 107 μg/d-130 μg/d). Based on these data, a fortification level of 160 μg/100 g bread is required to achieve the targeted mean of 140 μg folic acid/d. Nonetheless, under the current proposal additional folic acid intakes would be greatest among the least advantaged segments of the target population: Pacific and indigenous Māori ethnic groups; those with increased parity, lower income and education; younger and single mothers; and women with unplanned pregnancies. Subgroups predicted to derive less than adequate folic acid intakes from the proposed policy were women of Asian descent and those with a postgraduate education. Conclusions This study provides insight on the ability of a fortification policy to benefit the groups at highest risk of poor folate intakes in a population. However, bread consumption among the target group of childbearing women appears to have declined since the data used in previous dietary modeling were collected. Thus, it seems prudent to re-model dietary folic acid intakes based on more recent national survey data prior to the implementation of a mandatory folic acid fortification policy.</p

Health Care Provider Knowledge and Practices Regarding Folic Acid, United States, 2002–2003

Objective: To assess health care providers (HCP) knowledge and practices regarding folic acid (FA) use for neural tube defect (NTD) prevention. Methods: Two identical surveys were conducted among 611 obstetricians/gynecologists (OB/GYNs) and family/general physicians (FAM/GENs) (2002), and 500 physician assistants (PAs), nurse practitioners (NPs), certified nurse midwives (CNMs), and registered nurses (2003) to ascertain knowledge and practices regarding FA. For analysis, T-tests, univariate and multivariate logistic regression modeling were used. Results: Universally, providers knew that FA prevents birth defects. Over 88% knew when a woman should start taking folic acid for the prevention of NTDs; and over 85% knew FA supplementation beyond what is available in the diet is necessary. However, only half knew that 50% of all pregnancies in the United States are unplanned. Women heard information about multivitamins or FA most often during well woman visits in obstetrical/gynecology (ob/gyn) practice settings (65%), and about 50% of the time during well woman visits in family/general (fam/gen) practice settings and 50% of the time at gynecology visits (both settings). Among all providers, 42% did not know the correct FA dosage (400 μg daily). HCPs taking multivitamins were more than twice as likely to recommend multivitamins to their patients (Odds Ratio [OR] 2.27 95%, Confidence Interval [CI] 1.75–2.94). HCPs with lower income clients (OR 1.49, CI 1.22–1.81) and HCPs with practices having more than 10% minorities (OR 1.46, CI 1.11–1.92) were more likely to recommend supplements. NPs in ob/gyn settings were most likely and FAM/GENs were least likely to recommend supplements (OR 3.06, CL 1.36–6.90 and OR 0.64, CL 0.45–0.90 respectively). Conclusions: Knowledge about birth defects and the necessity of supplemental FA was high. Increasing knowledge about unintended pregnancy rates and correct dosages of FA is needed. The strongest predictor for recommending the use of FA supplements was whether the provider took a multivitamin

CHKA and PCYT1A gene polymorphisms, choline intake and spina bifida risk in a California population

BACKGROUND: Neural tube defects (NTDs) are among the most common of all human congenital defects. Over the last two decades, accumulating evidence has made it clear that periconceptional intake of folic acid can significantly reduce the risk of NTD affected pregnancies. This beneficial effect may be related to the ability of folates to donate methyl groups for critical physiological reactions. Choline is an essential nutrient and it is also a methyl donor critical for the maintenance of cell membrane integrity and methyl metabolism. Perturbations in choline metabolism in vitro have been shown to induce NTDs in mouse embryos. METHODS: This study investigated whether single nucleotide polymorphisms (SNPs) in human choline kinase A (CHKA) gene and CTP:phosphocholine cytidylytransferase (PCYT1A) gene were risk factors for spina bifida. Fluorescence-based allelic discrimination analysis was performed for the two CHKA intronic SNPs hCV1562388 (rs7928739) and hCV1562393, and PCYT1A SNP rs939883 and rs3772109. The study population consisted of 103 infants with spina bifida and 338 non-malformed control infants who were born in selected California counties in the period 1989–1991. RESULTS: The CHKA SNP hCV1562388 genotypes with at least one C allele were associated with a reduced risk of spina bifida (odds ratio = 0.60, 95%CI = 0.38–0.94). The PCYT1A SNP rs939883 genotype AA was associated with a twofold increased risk of spina bifida (odds ratio = 1.89, 95% CI = 0.97–3.67). These gene-only effects were not substantially modified by analytic consideration to maternal periconceptional choline intake. CONCLUSION: Our analyses showed genotype effects of CHKA and PCYT1A genes on spina bifida risk, but did not show evidence of gene-nutrient interactions. The underlying mechanisms are yet to be resolved

How well do blood folate concentrations predict dietary folate intakes in a sample of Canadian lactating women exposed to high levels of folate? An observational study

<p>Abstract</p> <p>Background</p> <p>In 1998, mandatory folic acid fortification of white flour and select cereal grain products was implemented in Canada with the intention to increase dietary folate intakes of reproducing women. Folic acid fortification has produced a dramatic increase in blood folate concentrations among reproductive age women, and a reduction in neural tube defect (NTD)-affected pregnancies. In response to improved blood folate concentrations, many health care professionals are asking whether a folic acid supplement is necessary for NTD prevention among women with high blood folate values, and how reliably high RBC folate concentrations predict folate intakes shown in randomized controlled trials to be protective against NTDs. The objective of this study was to determine how predictive blood folate concentrations and folate intakes are of each other in a sample of well-educated lactating Canadian women exposed to high levels of synthetic folate.</p> <p>Methods</p> <p>The relationship between blood folate concentrations and dietary folate intakes, determined by weighed food records, were assessed in a sample of predominantly university-educated lactating women (32 ± 4 yr) at 4-(n = 53) and 16-wk postpartum (n = 55).</p> <p>Results</p> <p>Median blood folate concentrations of all participants were well above plasma and RBC folate cut-off levels indicative of deficiency (6.7 and 317 nmol/L, respectively) and all, except for 2 subjects, were above the cut-off for NTD-risk reduction (>906 nmol/L). Only modest associations existed between total folate intakes and plasma (r = 0.46, <it>P </it>< 0.001) and RBC (r = 0.36, <it>P </it>< 0.01) folate concentrations at 16-wk postpartum. Plasma and RBC folate values at 16-wk postpartum correctly identified the quartile of folate intake of only 26 of 55 (47%) and 18 of 55 (33%) of subjects, respectively. The mean RBC folate concentration of women consuming 151–410 μg/d of synthetic folate (2^ndquartile of intake) did not differ from that of women consuming >410 μg/d (3^rdand 4^thquartile).</p> <p>Conclusion</p> <p>Folate intakes, estimated by food composition tables, and blood folate concentrations are not predictive of each other in Canadian lactating women exposed to high levels of folate. Synthetic intakes > 151–410 μg/d in these women produced little additional benefit in terms of maximizing RBC content. More studies are needed to examine the relationship between blood folate concentration and NTD risk. Until data from such studies are available, women planning a pregnancy should continue to consume a daily folic acid supplement of 400 μg.</p

Predicted contribution of folic acid fortification of corn masa flour to the usual folic acid intake for the US population: National Health and Nutrition Examination Survey 2001–2004

Background: Folic acid can prevent up to 70% of neural tube defects (NTDs) if taken before pregnancy. Compared with other race-ethnicities, Hispanic women have higher rates of NTDs, lower rates of folic acid supplement use, and lower total folic acid intakes. Objective: The objective was to assess potential effects of fortifying corn masa flour with folic acid on Mexican American women and other segments of the US population. Design: A model was developed by using data from the National Health and Nutrition Examination Survey 2001-2004 to estimate the folic acid content in foods containing corn masa flour if fortified at a level of 140 ug folic acid/100 g corn masa flour. Results: Had corn masa flour fortification occurred, we estimated that Mexican American women aged 15-44 y could have increased their total usual daily folic acid intake by 19.9% and non-Hispanic white women by 4.2%. Among the US population, estimated relative percentage increases in total usual daily folic acid intake with corn masa flour fortification were greatest among Mexican Americans (16.8%) and lowest among children aged 1-3 y (2%) and adults aged \u3e51 y (0-0.5%). Conclusion: Analyses suggest that corn masa flour fortification would have effectively targeted Mexican Americans, specifically, Mexican American women, without substantially increasing folic acid intake among other segments of the population. Such increases could reduce the disparity in total folic acid intake between Mexican American and non-Hispanic white women of childbearing age and implies that an additional NTD preventive benefit would be observed for Mexican American women

Fortification of wheat and maize flour with folic acid for population health outcomes

ABSTRACT: This is the protocol for a review and there is no abstract. The objectives are as follows: To evaluate the health benefits and safety of folic acid fortification of wheat and maize flour (alone or in combination with other micronutrients) on folate status and health outcomes in the overall population, with emphasis on populations at risk. For the purposes of this review, a fortified wheat product includes any food prepared from fortified wheat flour; a fortified maize flour product includes any food prepared from fortified corn meal or maize flour. We will include composite flours that contain more than 50% wheat or maize within the definition of flour in this review

Trends in Folic Acid Awareness and Behavior in the United States: The Gallup Organization for the March of Dimes Foundation Surveys, 1995–2005

Objective: To summarize changes in folic acid awareness, knowledge, and behavior among women of childbearing age in the United States since the U.S. Public Health Service (USPHS) 1992 folic acid recommendation and later fortification. Methods: Random-digit dialed telephone surveys were conducted of approximately 2000 women (per survey year) aged 18–45 years from 1995–2005 in the United States. Results: The percentage of women reporting having heard or read about folic acid steadily increased from 52% in 1995 to 84% in 2005. Of all women surveyed in 2005, 19% knew folic acid prevented birth defects, an increase from 4% in 1995. The proportion of women who reported learning about folic acid from health care providers increased from 13% in 1995 to 26% in 2005. The proportion of all women who reported taking a vitamin supplement containing folic acid increased slightly from 28% in 1995 to 33% in 2005. Among women who were not pregnant at the time of the survey in 2005, 31% reported taking a vitamin containing folic acid daily compared with 25% in 1995. Conclusions: The percentage of women taking folic acid daily has increased modestly since 1995. Despite this increase, the data show that the majority of women of childbearing age still do not take a vitamin containing folic acid daily. Health care providers and maternal child health professionals must continue to promote preconceptional health among all women of childbearing age, and encourage them to take a vitamin containing folic acid daily

Nutrient intakes and nutritional biomarkers in pregnant adolescents: a systematic review of studies in developed countries

Background: Babies born to adolescent mothers have been shown to have poorer outcomes compared to those born to adults. Nutritional status may have an important role to play in improving the health of pregnant adolescents; however there is a lack of evidence regarding the adequacy of adolescent diets during pregnancy. This systematic review aims to examine what is known about the nutritional status of adolescent pregnant women. Methods: A systematic search of the literature identified 21 studies which met the inclusion criteria for the review. Primary research papers using any methods were included where they were published in English between January 1995 and May 2015 and included measurements of nutrient intakes or biological markers of nutritional status in pregnant women aged 11-19 years. Individual study data was first summarised narratively before study means were pooled to give an estimate of nutritional status in the population. Results: The results show that individual studies reported intakes of energy, fibre and a number of key micronutrients which were below recommended levels. Biological markers of iron and selenium status also showed cause for concern. Pooled analysis of individual means as a percentage of UK Dietary Reference Intakes showed intakes of vitamin D (34.8 % CI 0-83.1) to be significantly below recommendations (p=0.05). Serum selenium levels were also found to be low (61.8 μg/L, CI 39-84). Conclusions: This review has identified a number of areas where the nutritional status of pregnant adolescents is sub-optimal, which may have implications for the health of adolescent mothers and their babies. It was not however possible to examine the impact of supplement use or socio-demographic characteristics which limits the interpretation these results. Further work is needed to establish the characteristics of those most at risk within this population, how this differs from adult pregnant women and the role of supplementation in achieving adequate nutrition