Mandatory Folic Acid Fortification Research Articles

Folate Deficiency in an Urban Safety Net Population

PurposeSince mandatory fortification of grain products with folic acid in the United States in 1998, folate deficiency has become rare. Some have suggested that serum folate levels should be tested rarely in countries with mandatory folic acid fortification, given low rates of deficiency, high cost per deficiency diagnosis, and low rates of supplementation for those diagnosed as deficient. Given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these suggestions may not apply to all populations. We examine the rate at which serum testing detected folate deficiency in an urban safety net hospital and the characteristics of folate-deficient patients. MethodsWe reviewed the charts of all inpatients and emergency department patients with low serum folate results at a safety net hospital in Boston in 2018. We collected data concerning demographics, social determinants of health, clinical factors, and whether folate supplementation was prescribed. Finally, we performed a cost analysis. ResultsOf 1368 patients tested, 76 (5.5%) met criteria for folate deficiency. Overall, 86.8% of these patients were anemic, and 17.1% had macrocytic anemia; 42% were diagnosed with malnutrition. Common social determinants in folate-deficient patients included birth outside of the United States, homelessness, and alcohol use disorder. Of folate-deficient patients, 88% were newly prescribed folic acid supplementation at discharge. The estimated charge per deficient test was $1278. ConclusionCompared with a nearby institution, serum folate testing at our safety net hospital detected deficiency at a higher rate, incurred a lower charge per deficient test, and was more likely to impact management.

Folate fortification and supplementation in prevention of folate-sensitive neural tube defects: a systematic review of policy.

Neural tube defects (NTDs) are common congenital neurological defects, resulting in mortality, morbidity, and impaired quality of life for patients and caregivers. While public health interventions that increase folate consumption among women who are or plan to become pregnant are shown to reduce folate-sensitive NTDs, public health policy reflecting the scientific evidence lags behind. The authors aimed to identify the types of policies applied, associated outcomes, and impact of folate fortification and supplementation on NTDs worldwide. By identifying effective legislation, the authors aim to focus advocacy efforts to more broadly effect change, reducing the burden of NTDs in neurosurgery. A systematic review was conducted exploring folate fortification and supplementation policies using the PubMed and Scopus databases. Titles and abstracts from articles identified were read and selected for full-text review. Studies meeting inclusion criteria were reviewed in full and analyzed for study design, aim, population, interventions, and outcomes. Of 1637 resultant articles, 54 were included. Mandatory folate fortification was effective at reducing folate-sensitive NTDs. Mandatory fortification also decreased hospitalization rates and deaths after discharge and increased 1st-year survival for infants with NTDs. Recommended folate supplementation also resulted in decreased NTDs; however, issues with compliance and adherence were a concern and impacted effectiveness. Folate fortification and/or supplementation resulted in decreased NTD prevalence, although more change was attributed to fortification. Dual policies may hold the most promise. Furthermore, reductions in NTDs were associated with significant cost savings over time. Both mandatory folate fortification and recommended supplementation policies were found to effectively decrease folate-sensitive NTD rates when applied. A comprehensive approach incorporating mandatory folate fortification, appropriate folate supplementation, and improved infrastructure and access to prenatal care may lead to decreased NTDs worldwide. This approach should be context-specific, emphasize education, and account for regional access to healthcare and social determinants of health. With wide implications for NTDs, associated health outcomes, quality of life of patients and caregivers, and economic impacts, policy changes can drastically improve global NTD outcomes. As caretakers of children with NTDs, the authors as neurosurgeons advocate for a comprehensive policy, the engagement of stakeholders, and a broader global impact.

Colorectal cancer incidence in Australia before and after mandatory fortification of bread flour with folic acid.

Mandatory fortification of bread flour with folic acid has helped to reduce the incidence of neural tube defects in several countries. However, it has been suggested that folic acid may have potential adenoma-promoting effects, and reports from some countries have suggested that mandatory folic acid food fortification programmes have increased the incidence of colorectal cancer. The objective of this study was to evaluate colorectal cancer incidence patterns before and after introduction of mandatory folic acid fortification of bread flour in Australia in 2009. Data from the Australian Cancer Database were used to plot age-standardised incidence of colorectal cancer. We calculated age-adjusted rate ratios with 95 % CIs. Australia. We used population-level aggregate data obtained from cancer registries. Age-standardised colorectal cancer incidence generally decreased between 1999 and 2016. Although there was a slight increase in rates in 2010 compared with 2009 (62·8 v. 61·6 cases per 100 000, age-adjusted rate ratio 1·02 (95 % CI 0·99, 1·04), joinpoint regression indicated decreases of -0·4 % (95 % CI -0·7, 0·0) per year from 1999 to 2010 and -2·2 % (95 % CI -3·1, -1·3) per year from 2010 to 2016. While causation cannot be assessed from these population-level data, our observations indicate that there is no evidence that introduction of mandatory folic acid fortification of bread flour has influenced colorectal cancer incidence in Australia.

Projected impact of mandatory food fortification with folic acid on neurosurgical capacity needed for treating spina bifida in Ethiopia.

Spina bifida, also known as meningomyelocele, is a major birth defect mostly associated with folate deficiency in the mother early in pregnancy. The prevalence of spina bifida is disproportionately high in Ethiopia compared to the global average; about 10,500 liveborn are affected annually. Many affected infants do not receive timely repair surgery. There are a high number of stillbirths, and neonatal, infant, and under‐five deaths. Mandatory fortification of staple foods such as wheat and maize flour with folic acid, a B vitamin, is an effective primary prevention strategy for spina bifida. Survival in those with spina bifida increases if neurosurgical intervention is available soon after birth, along with continuous surgical and clinical aftercare throughout the lifespan. Currently, Ethiopia does not have mandatory food fortification for primary prevention or adequate neurosurgical capacity to meet the need to prevent adverse outcomes associated with spina bifida. We present in this paper two concurrent and complementary policy and practice solutions occurring in Ethiopia through global partnerships: (1) capacity‐building of neurosurgery care through training programs; and (2) promoting national mandatory folic acid fortification of staples for primary prevention of spina bifida. These two policy and practice interventions ensure all affected infants can receive timely pediatric neurosurgery and sustained surgical aftercare through required neurosurgeon availability, and ensure primary prevention of spina bifida. Primary prevention of spina bifida frees up significant neurosurgical capacity in resource‐poor settings that can then be directed to other critical neurosurgical needs thus lowering child mortality and morbidity.

Folate Deficiency in an Urban Safety Net Population

Introduction: Folate deficiency is a known cause of megaloblastic anemia. Serum folate level is therefore a common component of the workup for megaloblastic and other anemias. Following mandatory fortification of grain products with folic acid in the US in 1998, folate deficiency has become relatively rare in both the general population and in hospitalized patients. Some authors have suggested that serum folate levels should be tested rarely if at all in countries with mandatory folic acid fortification given low rates of deficiency, high cost per diagnosis of deficiency, and low rates of supplementation for those found to be deficient. However, given persistent racial, ethnic, and socioeconomic disparities in folate deficiency, these conclusions may not apply to all populations. In this study, we examine the rate at which serum folate testing detected folate deficiency in an urban safety net hospital and the characteristics of patients found to be folate deficient. Methods: All serum folate tests performed on inpatients and emergency department patients in 2018 at a large safety net hospital in Boston were reviewed. Serum folate levels under 4 ng/mL were considered deficient per WHO criteria. We reviewed the charts of all patients found to be folate deficient, collecting demographic data; data concerning social determinants of health; and clinical data such as hematologic lab data, stated reason for testing, and pertinent disease states such as malnutrition and substance use. We also noted whether the medical team acted upon the folate deficiency. Finally, we performed a cost analysis. Results: Out of 1368 patients whose serum folate was tested, 76 patients (5.5%) met criteria for folate deficiency. Of those patients, chart review found that hematologic abnormality was a documented cause of testing for 63%. Overall, 79% of folate deficient patients were anemic, but only 20% had a macrocytic anemia. 42% had a documented diagnosis of malnutrition. Common social determinants in patients found to be folate deficient include birth outside of the US (25%), homelessness (12%), and alcohol use disorder (29%). Of those found to be folate deficient, 93% were either started on folic acid supplementation or had already been prescribed supplementation prior to testing (5%). Given that our institution charges $71 per folate test, the expected charges per deficient test would total $1278. Discussion: While the decreased incidence of folate deficiency after fortification has led many to conclude that serum folate tests have limited utility, our data show that this conclusion may not apply to all populations. The 5.5% rate with which testing detects folate deficiency at our institution, with 46% of 2018 income from Medicaid, was markedly higher than the 0.4% rate reported in a similar study done at nearby hospital that derived 14% of 2018 income from Medicaid (Theisen-Toupal et al. J Hosp. Med. 2013). Comparisons to other studies are limited, as the cutoff for folate deficiency varies significantly between institutions. However, the markedly higher frequency with which folate deficiency was detected at our institution as compared to others suggests that folate testing may still have a role within safety net and many public hospital systems. In addition, serum folate testing may be more cost effective at such hospitals. At our hospital, the charge per deficient folate test was $1278, while previously published data from the nearby hospital described above showed a charge of over $35,000 per result under 4 ng/mL (Theisen-Toupal et al. J Hosp Med 2013). In addition, our results showed that deficient folate results usually prompted change in management. At our hospital, over 90% of folate deficient patients were prescribed a folic acid supplement at discharge, while prior studies reported rates of supplementation in the range of 0-65% (e.g. Ashraf et al. J Gen Intern Med 2008). This may reflect greater cognizance among our providers of nutritional deficiencies associated with social determinants of health common to our patient population. As our results indicated high rates of anemia, malnutrition, immigrant status, and substance use disorders among folate deficient patients, future research may include comparisons between patients found to have normal vs low folate levels. Identifying correlations between folate deficiency and other patient characteristics may help to target testing towards those most likely to benefit. Disclosures No relevant conflicts of interest to declare.

A 2019 global update on folic acid-preventable spina bifida and anencephaly.

Mandatory folic acid fortification of staples is a proven intervention to prevent spina bifida and anencephaly, two life-threatening and disabling neural tube defects. We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) prevented through mandatory folic acid fortification of wheat and/or maize flour in 2019. Using data from the Global Fortification Data Exchange, we identified countries with mandatory fortification policies that required at least 1.0 ppm folic acid be added to wheat and/or maize flour and had information on percentage of industrially milled flour that is fortified. We built FAP SBA prevention models assuming mandatory folic acid fortification at 200 μg/day of folic acid fully protects against FAP SBA and would lower the prevalence neural tube defects to 0.5 per 1,000 live births. In 2019, 56 countries met our criteria for mandatory folic acid fortification of wheat (n = 56 countries) and/or maize (n = 15 countries) flour and with complete data for our modeling. Overall, our prevention model estimated that 65,380 FAP SBA cases were prevented in 2019 through folic acid fortification of wheat and/or maize flour. We estimated the current global prevention proportion of all preventable FAP SBA cases worldwide to be at 23% of total possible prevention. Global prevention efforts for FAP SBA are slow and have stalled. Mandatory fortification should be urgently implemented in all countries to prevent epidemics of FAP SBA, and to achieve health-related Sustainable Development Goals for year 2030 by reducing child mortality due to preventable FAP SBA.

Folate status in women of childbearing age in the Urban Metropolitan Region of Chile: results from the National Health Survey 2016-2017.

To analyse serum folate levels in women of childbearing age in the Metropolitan Region (MR) of Chile. Cross-sectional design as part of the 2016-2017 National Health Survey (Encuesta Nacional de Salud, ENS 2016-2017), using a household-based multistage stratified random sample. Serum folate levels measured by electrochemiluminescence immunoassay in fasting venous blood samples were classified as deficient (<4·4 ng/ml), normal (4·4-20 ng/ml) or supraphysiological (>20 ng/ml). The MR of Chile. Women of reproductive age (15-49 years, n 222) from the MR participated in the ENS 2016-2017. The mean, median and range of serum folate were 14·2 (se 0·4), 13·9 and 2·1-32·2 ng/ml, respectively. Folate deficiency was detected in 0·9 % of women, while 7·0 % had supraphysiological levels of the vitamin. No significant effects of age, educational level, marital status, parity, smoking status or nutritional status on serum folate levels were detected by univariate or multivariate analyses. Intake of folic acid supplements showed a significant association with serum folate levels, but only 1·2 % of women used supplements. Folate deficiency in women of reproductive age living in the MR of Chile is almost inexistent according to the ENS 2016-2017, suggesting that the current population-wide mandatory folic acid fortification of flour is an effective and equitable measure to prevent folate deficiency. These results support the option of maintaining current folic acid fortification in Chile, particularly based on the low adherence to supplementation regimes evidenced in other populations.

Abstract 1104: Folate intake and colorectal cancer risk during 36 years of follow-up in US women: A prospective cohort study

Abstract Background: Folate intake has been reported to be associated with a lower colorectal cancer (CRC) risk in several epidemiological studies. However, there are concerns about the potential for cancer promotion with an overly-abundant folate intake, especially after the mandatory folate fortification in the United States in 1998. Method: We investigated the association between folate intake and CRC risk among 83,165 women in the Nurses' Health Study, including 18 years of post-fortification follow-up; 2268 incident CRC cases were ascertained from 1980 to 2016. Folate intake from foods and supplements was assessed at baseline and updated every 4 years using a validated food-frequency questionnaire. Multivariate hazards ratios (HR) and 95% confidence intervals (CI) were calculated by Cox proportional hazards regression. Results: Over the entire follow-up period (1980-2016), higher total folate intake was associated with a decreased risk of CRC (HRQ5vsQ1=0.80; 95% CI: 0.64-0.99). This association was stronger when total folate was assessed 12-24 years before CRC diagnosis. Multivitamin use for &amp;gt;15 years, but not a shorter duration of use, was associated with lower CRC risk. In the post-fortification period (1998-2016, n= 1169 CRC cases), high total folate intake (HRQ5vsQ1=0.80; 95% CI: 0.64-1.00) and current multivitamin uses, regardless of duration, were each associated with lower CRC risk. Conclusions: There was no evidence that high folate intake in the post-fortification period was related to increased CRC risk. Rather, high total folate intake was inversely associated with risk of CRC. Citation Format: Fenglei Wang, Kana Wu, Yanping Li, Stephanie Smith-Warner, Edward Giovannucci, Walter Willett. Folate intake and colorectal cancer risk during 36 years of follow-up in US women: A prospective cohort study [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1104.

Modeling shows high potential of folic acid-fortified salt to accelerate global prevention of major neural tube defects.

We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) potentially prevented through mandatory double fortification of iodized salt with folic acid. Using United Nations Children's Fund (UNICEF) and Global Fortification Data Exchange (GFDx) data sets, we modeled country-specific number of FAP SBA cases prevented annually using (a) current coverage of the salt in households worldwide and (b) expected daily amount of folic acid intake from folic acid-fortified iodized salt. Our evidence-based modeling strategy assumed mandatory folic acid fortification of salt at 20 ppm, and that at 200 μg/day intake of folic acid through fortified salt, should achieve 100% prevention of all FAP SBA in countries. One hundred countries that have data on percent of households consuming iodized salt globally were examined; 55 of them have ≥80% households consuming iodized salt. Our model estimated approximately 180,000 cases of FAP SBA could be prevented in these 100 countries through folic acid-fortified iodized salt, and 150,000 of them would be in countries where ≥80% households consuming iodized salt that can be potentially fortified with folic acid. Salt fortification with folic acid could contribute to the prevention of about 65% global FAP SBA cases annually. Our evidence-based model shows that there is high potential to prevent FAP SBA using folic acid-fortified iodized salt. Prevention will reach countries where there is a limited reach of centrally processed folic acid-fortified wheat or maize flour. If this intervention is made feasible by the salt industry, it can accelerate the prevention of FAP SBA significantly.

Folate Nutritional Status among Psoriasis Patients not Exposed to Antifolate Drug

Background:Folic acid fortification program has been established to prevent tube defects. However, concern has been raised among patients using anti-folate drug, i.e. psoriatic patients, a common, chronic, autoimmune inflammatory skin disease associated with obesity and smoking.Objective:To investigate dietary and circulating folate, vitamin B12 (B12) and homocysteine (hcy) in psoriatic subjects exposed to the national mandatory folic acid fortification program.Methods:Cross-sectional study using the Food Frequency Questionnaire, plasma folate, B12, hcy and psoriasis severity using the Psoriasis Area and Severity Index score. Median, interquartile ranges (IQRs) and linear regression models were conducted to investigate factors associated with plasma folate, B12 and hcy.Results:82 (73%) mild psoriasis, 18 (16%) moderate and 12 (11%) severe psoriasis. 58% female, 61% non-white, 31% former smokers, and 20% current smokers. Median (IQRs) were 51 (40, 60) years. Only 32% reached the Estimated Average Requirement of folate intake. Folate and B12 deficiencies were observed in 9% and 6% of the blood sample respectively, but hyperhomocysteinaemia in 21%. Severity of psoriasis was negatively correlated with folate and B12 concentrations. In a multiple linear regression model, folate intake contributed positively to 14% of serum folate, and negative predictors were psoriasis severity, smoking habits and saturated fatty acid explaining 29% of circulating folate.Conclusion:Only one third reached dietary intake of folate, but deficiencies of folate and B12 were low. Psoriasis severity was negatively correlated with circulating folate and B12. Stopping smoking and a folate rich diet may be important targets for managing psoriasis.

Folic acid supplementation in children with sickle cell disease: study protocol for a double-blind randomized cross-over trial

BackgroundSickle cell disease (SCD) is a genetic disorder which causes dysfunctional red blood cells (RBC) and is thought to increase requirements for folate, an essential B vitamin, due to increased RBC production and turnover in the disease. High-dose supplementation with 1–5 mg/d folic acid, synthetic folate, has been the standard recommendation for children with SCD. There is concern about whether children with SCD need such high doses of folic acid, following mandatory folic acid fortification of enriched grains in Canada, and advancements in medical therapies which extend the average lifespan of RBCs. In animal and human studies, high folic acid intakes (1 mg/d) have been associated with accelerated growth of some cancers, and the biological effects of circulating unmetabolized folic acid (UMFA), which can occur with doses of folic acid ≥ 0.2 mg/d, are not fully understood. The objective of this study is to determine efficacy of, and alterations in folate metabolism from high-dose folic acid in children with SCD during periods of folic acid supplementation versus no supplementation.MethodsIn this double-blind randomized controlled cross-over trial, children with SCD (n = 36, aged 2–19 years) will be randomized to either receive 1 mg/d folic acid, the current standard of care, or a placebo for 12 weeks. After a 12-week washout period, treatments will be reversed. Total folate concentrations (serum and RBC), different folate forms (including UMFA), folate-related metabolites, and clinical outcomes will be measured at baseline and after treatment periods. The sum of the values measured in the two periods will be calculated for each subject and compared across the two sequence groups by means of a test for independent samples for the primary (RBC folate concentrations) and secondary (UMFA) outcomes. Dietary intake will be measured at the beginning of each study period.DiscussionAs the first rigorously designed clinical trial in children with SCD, this trial will inform and assess current clinical practice, with the ultimate goal of improving nutritional status of children with SCD.Trial registrationClinicalTrials.govNCT04011345. Registered on July 8, 2019

Distribution of 5-Methyltetrahydrofolate and Folic Acid Levels in Maternal and Cord Blood Serum: Longitudinal Evaluation of Japanese Pregnant Women.

“Total” folate in blood has usually been measured to evaluate the folate status of pregnant women. However, folate is composed of many metabolites. The main substrate is 5-methyltetrahydrofolate (5-MTHF), with folic acid (FA) representing a very small component as an unmetabolized species in blood. We longitudinally evaluated 5-MTHF, FA and total homocysteine in maternal and cord blood from Japanese pregnant women. Subjects were 146 pregnant women who participated in the Chiba study of Mother and Child Health (C-MACH) prospective cohort study. Sera were obtained in early and late pregnancy, at delivery, and from cord blood. Species levels were measured by isotope-dilution mass spectrometry. Both 5-MTHF and FA levels were lower than reported levels from pregnant women in populations from countries with mandatory FA fortification. As gestational age progressed, serum 5-MTHF levels decreased, whereas serum FA levels were slightly reduced only at delivery compared to early pregnancy. A significant negative association between serum 5-MTHF and total homocysteine was shown at all examined times, but no associations with FA were evident. At delivery, cord 5-MTHF was significantly higher than maternal levels, while FA again showed no significant correlation. These results suggest that 5-MTHF is actively transported to the fetus through placental transporters and may reflect folate status during pregnancy as a physiologically important species.

Periconceptional folic acid supplement use among women of reproductive age and its determinants in central rural Germany: Results from a cross sectional study

Prevalence of neural tube defects (NTD) has not decreased in Germany despite longstanding recommendations for folic acid supplementation. To examine the prevalence of periconceptional folic acid supplement use and associated factors among German women of reproductive age. Cross-sectional survey was conducted in hospital-based maternity units in rural Germany. A sample of 1,004 women of reproductive age, either pregnant or in their early postpartum period, took interviewer/self-administered paper-based survey questionnaire. Prevalence of periconceptional folic acid supplement use was assessed, where periconception was defined as 1 month prior to and 3 months post-conception. Prevalence odds ratios (POR) and 95% confidence intervals (CI) using crude and adjusted logistic regression analysis were estimated to examine determinants of folic acid supplement use. Prevalence of folic acid supplement use was 41.5% (95% CI: 37.7%, 45.7%). Multivariable analysis showed lack of educational qualifications, unplanned pregnancy, later diagnosis of pregnancy, increased parity, and not having an awareness of importance of folic acid for optimal pregnancy outcomes were associated with not taking periconceptional folic acid supplements. Books, doctors, friends, media, were sources of information. Periconceptional folic acid is sub-optimal in rural Germany and thus failing to prevent NTDs. Targeted promotion of folic acid supplement use should be conducted periodically by gynecologists and primary care physicians during annual medical screenings. Mandatory folic acid fortification of staple foods is a complementary approach to overcome limitations of individual behaviors of folic acid supplement intake, and should be considered as it has been proven effective in multiple countries.

Male-to-female ratios among NTDs and women's periconceptional intake of folic acid.

About a decade ago, a hypothesis was put forward to explain the preponderance of females among neural tube defect (NTD) fetuses. That hypothesis predicts that a woman's higher levels of early gestational intake of methyl groups, such as folic acid, will be associated with lesser male-to-female ratio differences in NTD-affected births, specifically less preponderance of females. We explored this hypothesis in four distinct studies that investigated human NTDs, obtained information on folic acid, and capitalized on timing of folic acid fortification by investigating data that were collected both prior to and after the 1998 initiation of U.S. mandatory folic acid fortification of grains. We analyzed data from four population-based case control studies conducted in California for birth years spanning 1987-2011. Two studies were conducted before folic acid fortification of the U.S. food supply. Each of the four studies included interviews of women who either had NTD-affected pregnancies (cases) or who did not have a pregnancy affected by a birth defect (controls). In each study, information on periconceptional supplement use was elicited. We explored male-to-female ratios and 95% binomial confidence limits in each data set. Our analyses of two case-control studies performed prior to and two performed post mandatory folate fortification in the United States showed that more NTD-affected fetuses were female in the first two studies. In the studies done before fortification, the frequency of females was even greater among those pregnancies without folic acid supplementation. Our findings suggest folic acid may differentially reduce risk of NTDs among female fetuses.

Prevention of birth defects in East Africa: A review of national policies

Close to 8 million children are born annually with a serious birth defect, accounting for 5% of all newborn deaths globally. Many birth defects are associated with folic acid insufficiency, non-communicable diseases (NCDs), teenage or advanced age pregnancies, short birth intervals, and exposure to harmful substances. The majority of countries with the highest birth defects prevalence are in Africa, and the East African Community has made important commitments to improving reproductive, child, and adolescent health and nutrition. The aim of this review was to identify the advances and gaps in national policies addressing birth defect risk factors in the East African Community (Burundi, Kenya, Rwanda, Tanzania, and Uganda) in order to inform additional actions. National laws, regulations and policies were reviewed from the East African Community countries related to grain fortification and supplementation with folic acid; reducing too-early, unwanted and rapid successive pregnancies; and addressing NCDs and exposure to tobacco. All five countries have adopted a policy of mandatory folic acid fortification of wheat and maize flour. However, only in Kenya and Tanzania, are the folic acid levels in line with international recommendations. And, only Uganda has a policy requiring folic acid supplementation administration in the preconceptional period. The East African Community countries have made efforts to reduce too-early, unwanted and rapid successive pregnancies. All countries have banned child marriage and three of five countries have introduced laws to allow unrestricted access to contraception for adolescents. With regards to promoting prevention and control of NCDs and reducing populations’ exposure, compliance with World Health Organization (WHO) guidelines is limited. Only two countries have developed multi-sectoral policies for NCDs and no countries comply fully with the recommendations of the Framework Convention on Tobacco Control. Much work remains in ensuring that opportunities for prevention of birth defects are fully realized in the East African Community countries. This review revealed that all countries in the East African Community have, to some extent, adopted policies that are conducive to reducing the risk of birth defects in the region, but significant gaps remain in some key areas of either policy development or implementation. Key words: Congenital abnormalities, Folic acid, Family planning services, Child marriage, Non-communicable Diseases

The Fallacy of Using Administrative Data in Assessing the Effectiveness of Food Fortification. Comment on: "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset. Nutrients 2020, 12, 247".

Our objective in this comment is to highlight several limitations in an ecological research study that was published in Nutrients by Murphy and Westmark (2020) in January 2020. The study used data from the Food Fortification Initiative (FFI) website, and applying an ecological study design, made an error of “ecologic fallacy” in concluding that “national fortification with folic acid is not associated with a significant decrease in the prevalence of neural tube defects (NTDs) at the population level”. We list study limitations that led to their erroneous conclusions, stemming from incorrect considerations regarding NTD prevalence, the average grain availability for a country, the fortification coverage in a country, the population reach of fortified foods within a country, and the absence of the consideration of fortification type (voluntary vs. mandatory), country-specific policies on elective terminations for NTD-affected pregnancies, stillbirth proportions among those with NTDs, and fortification implementation. FFI data are derived from many sources and intended for fortification advocacy, not for hypothesis testing. The flawed study by Murphy & Westmark (2020) in Nutrients promotes a confusing and incorrect message to stakeholders, misguides policy makers, and hinders progress in global NTD prevention through a cost-effective, safe, and effective intervention: the mandatory large-scale folic acid fortification of staple foods.

Plasma concentrations of vitamin B12 and folate and global cognitive function in an older population: cross-sectional findings from The Irish Longitudinal Study on Ageing (TILDA).

The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.

Circulating unmetabolized folic acid and 5-methyltetrahydrofolate and risk of breast cancer: a nested case-control study.

Folates found in natural foods are thought to protect against cancer. However, folic acid (FA), a synthetic form of folate used in supplements and fortified foods, may increase breast cancer risk if present in unmetabolized form (UMFA) in the circulation. This study examined the associations of serum UMFA and 5-methyltetrahydrofolate (5-mTHF), the predominant form of circulating folate, with breast cancer risk. We conducted a nested case-control study in a prospective cohort. In total, 553 cases of invasive breast cancer, diagnosed before mandatory FA fortification of grain in the US in 1998, were individually-matched to 1059 controls. Serum UMFA and 5-mTHF were measured using liquid chromatography-tandem mass spectrometry in stored serum samples, and 5-mTHF was corrected for storage degradation. Serum UMFA was not associated with breast cancer risk: the percentage of women with detectable levels of UMFA was similar in cases and controls (18% and 20%, respectively; p = 0.46). Two tag-SNPs in the promoter region of the FA-metabolizing gene were also not associated with risk. There was a marginally significant inverse association of 5-mTHFcorrected with breast cancer risk (odds ratio for the highest vs. lowest quintile = 0.69, 95% CI = 0.49 to 0.97; ptrend = 0.08). Circulating UMFA was not associated with breast cancer risk. These results apply to countries without mandatory FA food fortification. Studies are needed in countries with mandatory fortification, where levels of UMFA are much higher than in our study.

Modeling Shows High Potential of Folic Acid Fortified Salt to Accelerate Global Prevention of Major Neural Tube Defects

Background: We estimated the global proportion of folic acid-preventable spina bifida and anencephaly (FAP SBA) potentially prevented through mandatory double fortification of iodized salt with folic acid. Methods: Using UNICEF and Global Fortification Data Exchange (GFDx) datasets, we modelled country-specific number of FAP SBA cases prevented annually using: 1) current coverage of the salt in households worldwide; and 2) expected daily amount of folic acid intake from folic acid fortified-iodized salt. Our evidence-based modeling strategy assumed mandatory folic acid fortification of salt at 20 ppm, and that at 200 μg/day intake of folic acid through fortified salt, should achieve 100% prevention of all FAP SBA in countries. Findings: One hundred countries that have data on percent of households consuming iodized salt globally were examined; 65 of them have ≥80% households consuming iodized salt. Our model estimated approximately 180,000 cases of FAP SBA could be prevented in these 100 countries through folic acid fortified-iodized salt, and 150,000 of them would be in countries where ≥80% households consuming iodized salt that can be potentially fortified with folic acid. Salt fortification with folic acid could contribute to the prevention of about 65% global FAP SBA cases annually. Interpretation: Our evidence-based model shows that there is high potential to prevent FAP SBA using folic acid-fortified iodized salt. Prevention will reach countries where there is a limited reach of centrally-processed folic acid-fortified wheat or maize flour. If this intervention is made feasible by the salt industry, it can accelerate the prevention of FAP SBA significantly. Funding Statement: No funding was received to conduct any aspect of this study Declaration of Interests: The authors have no financial relationships relevant to this article to disclose. Dr. Godfrey P. Oakley Jr. is a co-inventor (while at CDC, compensation is under the regulations of CDC) of a patent that covers adding folic acid to contraceptive pills, and he has been a consultant to Ortho McNeil on this issue.

Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset.

The United States implemented mandatory fortification of cereal grains with folic acid in 1998 to prevent neural tube defects (NTDs) during pregnancy. The health benefits of folate (vitamin B9) are well documented; however, there are potential risks of exceeding the upper tolerable limit, particularly in vulnerable populations. We conducted a population-based analysis of the Food Fortification Initiative dataset to determine the strength of the evidence regarding reports of decreased NTDs at the national level in response to mandatory folic acid fortification of cereal grains. We found a very weak correlation between NTD prevalence and the level of folic acid fortification, irrespective of the cereal grain fortified (wheat, maize or rice). Stratification of the data based on socioeconomic status (SES) indicated a strong linear relationship between reduced NTDs and better SES. We conclude that national fortification with folic acid is not associated with a significant decrease in the prevalence of NTDs at the population level.