Voluntary Fortification Research Articles

Persistent circulating unmetabolised folic acid in a setting of liberal voluntary folic acid fortification. Implications for further mandatory fortification?

BackgroundIreland is an example of a country that has extensive voluntary fortification with folic acid. After a public consultation process, in 2006, the Food Safety Authority in Ireland FSAI [1] recommended mandatory fortification. However due to safety considerations this decision is now on hold. Before mandatory fortification goes ahead, existing levels of unmetabolised folic acid and their anticipated increase after fortification needs investigation because of the potential of folic acid to mask pernicious anaemia and possibly accelerate the growth of existing cancers. The aim of this study was to examine the levels of circulatory unmetabolised folic acid in Irish adults (both fasted and un-fasted) and new-born infants (fasted) before the proposed implementation of mandatory folic acid fortification. A secondary aim was to predict the increase in circulatory unmetabolised folic acid levels after fortification.MethodsStudy 1. Setting: Irish Blood Transfusion Service (IBTS). Whole blood samples were collected from blood donors (n = 50) attending for routine blood donation sessions (representing the general population). Subjects were not fasted prior to sampling. Study 2. Setting: Coombe Women's and Infant's University Hospital, Dublin. Whole blood samples were collected by venipuncture from mothers (n = 20), and from their infant's umbilical-cords (n = 20) immediately after caesarean section. All women had been fasted for at least 8 hours prior to the surgery. A questionnaire on habitual and recent dietary intakes of folic acid was administered by an interviewer to all subjects. The data collection period was February to April 2006. Serum samples were analysed for plasma folate, plasma folic acid and red cell folate.ResultsBlood Donor Group: Circulatory unmetabolised folic acid was present in 18 out of 20 mothers (fasted) (CI: 68.3%–99.8%) comprising 1.31% of total plasma folate, 17 out of 20 babies (fasted) (CI: 62.1%–96.8%), and 49 out of 50 blood donors (unfasted) (CI: 88.0%–99.9%), comprising 2.25% of total plasma folate,ConclusionWhile the levels of circulatory unmetabolised folic acid reported are low, it is persistently present in women immediately after caesarean section who were fasting indicating that there would be a constant/habitual exposure of existing tumours to folic acid, with the potential for accelerated growth. Mandatory fortification might exacerbate this. This has implications for those with responsibility for drafting legislating in this area.

Toward an optimal use of folic acid: an advisory report of the Health Council of the Netherlands

In this report, benefits (preventing neural tube defects and folate deficiency), risks (masking vitamin B(12) deficiency), and uncertain effects (risk of colon cancer) of folic acid supplementation and fortification have been weighted. On the basis of the available evidence, the Health Council of the Netherlands advises the Dutch government to improve the use of folic acid approximately at the time of conception by increased education and the implementation of preconception care. It further recommends considering fortifying staple foods, provided that voluntary fortification of specific foods is banned, as otherwise children are at risk of having an excessively high intake of folic acid. Policy making in relation to fortification should take into account all possible health effects, even if the evidence is not strong.

Neural tube defects in Australia: Trends in encephaloceles and other neural tube defects before and after promotion of folic acid supplementation and voluntary food fortification

Use of periconceptional folic acid supplementation has been promoted in Western Australia since late 1992, and voluntary fortification of some foods with folic acid has been permitted in Australia since 1996. Reduced rates of neural tube defects (NTDs) have been observed since 1995. Aboriginal infants have a higher rate of NTDs, but no fall in rates has been documented. Encephaloceles have not been examined separately. Data on anencephaly, spina bifida, and encephalocele were obtained from the Western Australian Birth Defects Registry. The prevalence ratio for each type of NTD was calculated, comparing 1993 to 1995 (promotion of supplements, no fortification) and 1996 to 2006 (promotion of supplements and voluntary fortification) with 1980 to 1992 (no promotion or fortification). From 1996 to 2006, there was a 32% reduction in anencephaly, 23% in spina bifida, and 34% in encephalocele compared with 1980 to 1992. There were no differences seen from 1993 to 1995 compared with 1980 to 1992. For Aboriginal infants, the rates were higher than for non-Aboriginal infants, for each type of NTD. The prevalence ratios, comparing 1996 to 2006 with 1980 to 1995, were 0.70 (CI, 0.61-0.79) for non-Aboriginal infants and 0.90 (CI, 0.61-1.32) for Aboriginal infants. Overall, the rates of encephalocele, anencephaly, and spina bifida have fallen to a similar extent in association with promotion of folic acid supplements and voluntary fortification. No such falls were seen for Aboriginal infants. These data will provide a useful baseline against which to monitor the effects of mandatory fortification on NTDs when it is introduced in Australia in September 2009.

Intake of selected nutrients from foods, from fortification and from supplements in various European countries

Background: Recent European Union regulation requires setting of maximum amount of micronutrients in dietary supplements or foods taking into account the tolerable upper intake level (ULs) established by scientific risk assessment and population reference intakes.Objective: To collect and evaluate recently available data on intakes of selected vitamins and minerals from conventional foods, food supplements and fortified foods in adults and children. Intake of calcium, copper, iodine, iron, magnesium, phosphorus, selenium, zinc, folic acid, niacin and total vitamin A/retinol, B6, D and E was derived from nationally representative surveys in Denmark, Germany, Finland, Ireland, Italy, the Netherlands, Poland, Spain and the United Kingdom. Intake of high consumers, defined as the 95th percentile of each nutrient, was compared to the UL.Results: For most nutrients, adults and children generally consume considerably less than the UL with exceptions being retinol, zinc, iodine, copper and magnesium. The major contributor to intakes for all nutrients and in all countries is from foods in the base diet. The patterns of food supplements and voluntary fortification vary widely among countries with food supplements being responsible for the largest differences in total intakes. In the present study, for those countries with data on fortified foods, fortified foods do not significantly contribute to higher intakes for any nutrient. Total nutrient intake expressed as percentage of the UL is generally higher in children than in adults.Conclusion: The risk of excessive intakes is relatively low for the majority of nutrients with a few exceptions. Children are the most vulnerable group as they are more likely to exhibit high intakes relative to the UL. There is a need to develop improved methods for estimating intakes of micronutrients from fortified foods and food supplements in future dietary surveys.

Folate awareness and the prevalence of neural tube defects in South Australia, 1966–2007

To ascertain changes in: women's knowledge of the role of folic acid in the prevention of neural tube defects (NTDs); intake of folic acid among pregnant women; and prevalence of NTDs in South Australia. Computer-assisted telephone interviews of South Australian households from 1994 to 2007 over a period encompassing a statewide folate promotion campaign (1994-1995), continuing folate promotion, as well as the introduction of voluntary folate fortification of foods (1996); ascertainment of the total prevalence of NTDs from births and terminations of pregnancy from 1966 to 2007. Changes in women's knowledge of the role of folic acid in the prevention of NTDs; changes in the prevalence of NTDs. From 1994 to 2006 and 2007, knowledge about the role of folic acid increased from 25% to 77% (P < 0.001) and knowledge that folic acid needs to be taken in the periconceptional period increased from 12% to 39% (P < 0.001). The proportion of pregnant women who increased their periconceptional intake of folate rose from 61% in 1998 to 81% in 2006 and 2007 (P < 0.001), with significant increases in the consumption of fortified cereals (from 15% to 29%) and folic acid tablets (from 37% to 64%). The total prevalence of NTDs fell from 2.06 per 1000 births in 1986-1990 to 1.23 per 1000 births in 2002-2007 (relative risk, 0.60; 95% CI, 0.48-0.74; P < 0.001). Folate promotion and voluntary fortification of certain foods with folic acid were associated with increased awareness of the role of periconceptional folic acid, increased folate consumption and a reduction in the prevalence of NTDs in South Australia by 40% (95% CI, 26%-52%).

Folate and vitamin B12status in relation to cognitive impairment and anaemia in the setting of voluntary fortification in the UK

Concerns about risks for older people with vitamin B12 deficiency have delayed the introduction of mandatory folic acid fortification in the UK. We examined the risks of anaemia and cognitive impairment in older people with low B12 and high folate status in the setting of voluntary fortification in the UK. Data were obtained from two cross-sectional studies (n 2403) conducted in Oxford city and Banbury in 1995 and 2003, respectively. Associations (OR and 95 % CI) of cognitive impairment and of anaemia with low B12 status (holotranscobalamin < 45 pmol/l) with or without high folate status (defined either as serum folate >30 nmol/l or >60 nmol/l) were estimated after adjustment for age, sex, smoking and study. Mean serum folate levels increased from 15.8 (sd 14.7) nmol/l in 1995 to 31.1 (sd 26.2) nmol/l in 2003. Serum folate levels were greater than 30 nmol/l in 9 % and greater than 60 nmol/l in 5 %. The association of cognitive impairment with low B12 status was unaffected by high v. low folate status (>30 nmol/l) (OR 1.50 (95 % CI 0.91, 2.46) v. 1.45 (95 % CI 1.19, 1.76)), respectively. The associations of cognitive impairment with low B12 status were also similar using the higher cut-off point of 60 nmol/l for folate status ((OR 2.46; 95 % CI 0.90, 6.71) v. (1.56; 95 % CI 1.30, 1.88)). There was no evidence of modification by high folate status of the associations of low B12 with anaemia or cognitive impairment in the setting of voluntary fortification, but periodic surveys are needed to monitor fortification.

Session 1: Public health nutrition Folic acid food fortification: the Irish experience

Adequate intake of folic acid by women during very early pregnancy can markedly reduce risk of the development of neural-tube defects (NTD). The effectiveness of advice to women to take folic acid supplements is limited, mainly because 50% of pregnancies are unplanned. However, mandatory folic acid food fortification programmes in North America have been very successful in reducing NTD rates. In Ireland higher rates of pregnancies are affected by NTD and the option of termination is illegal. Consequently, the much higher burden of disease makes primary prevention of NTD an important public health issue in Ireland. During 2006 a decision was taken in Ireland to initiate mandatory folic acid fortification of most bread to prevent NTD. Priority work was immediately undertaken to establish reliable and comprehensive baseline information on factors that will be affected by fortification. This information included data on: the national prevalence of pregnancies affected by NTD; the current extent of voluntary folic acid fortification of food on the Irish market and how it affects folic acid intakes; blood folate status indicators assessed for various subgroups of the Irish population. In addition, scientific developments that have arisen since 2006 relating to the risks and benefits of folic acid intake are under ongoing review. The present paper summarises the rationale for mandatory folic acid food fortification in Ireland and recent scientific developments relating to risks and benefits of folic acid intake. In this context, preliminary findings of baseline monitoring investigations in Ireland are considered.

Framework for intake simulation of functional ingredients

To create a general framework for the simulation of intakes from mandatory or voluntary fortification, which will make outcomes of simulation studies more comparable and give insight on uncertainties. A general framework was developed based on methods used in already published case studies of mandatory fortification. The framework was extended to be suitable for the simulation of voluntary fortification. Case studies of folic acid fortification were used to illustrate the general framework. The developed framework consists of six steps. First, the definition of the fortification strategy (step 1), followed by the identification of potential carrier products (step 2), and the definition of fortification levels or ranges (step 3). Thereafter, virtual food/supplement composition data are created (step 4) and food/supplement consumption data are required (step 5). Finally, the intake of the functional ingredient from functional foods, other foods and dietary supplements is calculated during the simulation resulting in total habitual intake distributions (step 6). Simulation of both mandatory and voluntary folic acid fortification in The Netherlands showed that the general framework is applicable. Also with incomplete data or data from different sources, the (habitual) intake distributions can be estimated using assumptions, statistical procedures or probabilistic modelling approaches. It is important that the simulation procedure is described well, so that an insight on uncertainties and knowledge gaps to be filled is given.

Effect of a voluntary food fortification policy on folate, related B vitamin status, and homocysteine in healthy adults

Background: Mandatory folic acid fortification of food is effective in reducing neural tube defects and may even reduce stroke-related mortality, but it remains controversial because of concerns about potential adverse effects. Thus, it is virtually nonexistent in Europe, albeit many countries allow food fortification on a voluntary basis.Objective: The objective of the study was to examine the effect of a voluntary but liberal food fortification policy on dietary intake and biomarker status of folate and other homocysteine-related B vitamins in a healthy population.Design: The study was a cross-sectional study. From a convenience sample of 662 adults in Northern Ireland, those who provided a fasting blood sample and dietary intake data were examined (n = 441, aged 18–92 y). Intakes of both natural food folate and folic acid from fortified foods were estimated; we used the latter to categorize participants by fortified food intake.Results: Fortified foods were associated with significantly higher dietary intakes and biomarker status of folate, vitamin B-12, vitamin B-6, and riboflavin than were unfortified foods. There was no difference in natural food folate intake (range: 179–197 μg/d) between the fortified food categories. Red blood cell folate concentrations were 387 nmol/L higher and plasma total homocysteine concentrations were 2 μmol/L lower in the group with the highest fortified food intake (median intake: 208 μg/d folic acid) than in the nonconsumers of fortified foods (0 μg/d folic acid).Conclusions: These results show that voluntary food fortification is associated with a substantial increase in dietary intake and biomarker status of folate and metabolically related B vitamins with potential beneficial effects on health. However, those who do not consume fortified foods regularly may have insufficient B vitamin status to achieve the known and potential health benefits.

Homocysteine, vitamins, and vascular disease prevention

In mid-20th century United States, deaths from vascular disease reached a peak incidence in 1955, but little was known about the underlying causes of this epidemic of disease. The significance of homocysteine in human disease was unknown until 1962, when cases of homocystinuria were first associated with vascular disease. Analysis of an archival case of homocystinuria from 1933 and a case of cobalamin C disease from 1968 led to the conclusion that homocysteine causes vascular disease by a direct effect of the amino acid on arterial cells and tissues. The homocysteine theory of arteriosclerosis attributes one of the underlying causes of vascular disease to elevation of blood homocysteine concentrations as the result of dietary, genetic, metabolic, hormonal, or toxic factors. Dietary deficiency of vitamin B-6 and folic acid and absorptive deficiency of vitamin B-12, which result from traditional food processing or abnormal absorption of B vitamins, are important factors in causing elevations in blood homocysteine. Numerous clinical and epidemiologic studies have established elevated blood homocysteine as a potent independent risk factor for vascular disease in the general population. Dietary improvement, providing abundant vitamin B-6, folic acid, and cobalamin, may prevent vascular disease by lowering blood homocysteine. The dramatic decline in cardiovascular mortality in the United States since 1950 may possibly be attributable in part to voluntary fortification of the food supply with vitamin B-6 and folic acid. Fortification of the US food supply with folic acid in 1998, as mandated by the US Food and Drug Administration, was associated with a further decline in mortality from vascular disease, presumably because of increased blood folate and decreased blood homocysteine in the population.

Awareness and consumption of folate-fortified foods by women of childbearing age in Western Australia

The introduction of voluntary fortification of some foods with folic acid in Australia has been implemented since evidence of the prevention of neural tube defects with periconceptional folic acid was published. Our objectives were to determine how many women were aware of folate and when they became aware, what was the awareness of labels on foods that mentioned folate, and how much folate-fortified food women ate. To address these objectives we collected data by self-administered questionnaire from a random sample of 578 recently pregnant women in Western Australia between September 1997 and March 2000. Overall, 89% of women had heard, seen or read anything about the link between folate and birth defects such as spina bifida, 62% first became aware of the folate message before their recent pregnancy and 42% of women noticed any labels on foods that mention folate before or during their recent pregnancy. Overall, 53% of women were aware of foods that have folate added to them and 33% usually or always read the labels on food packaging. The folate-fortified foods most often consumed by women were cereals (69%), breads (34%) and milk (15%). Of the women who consumed folate-fortified foods (78%), the earlier they became aware of the folate message and noticed labels on food, the more fortified foods they consumed. These results indicate that staple foods fortified with folate are consumed by almost 80% of women in the population. Therefore, mandatory fortification of staple foods may reach most women, providing improved opportunity for the prevention of neural tube defects in Australia.

The impact of voluntary fortification of foods on micronutrient intakes in Irish adults

The objective of this work was to quantify the impact of the voluntary fortification of foods on dietary intakes of vitamins and minerals of Irish adults. Foods that were voluntarily fortified were identified and pre- and post-fortification levels of micronutrients were determined from data supplied by manufacturers and food composition tables. Using food consumption data in 1379 adults aged 18-64 years, estimated using a 7-d food diary during the North/South Ireland Food Consumption Survey, intakes of micronutrients were determined, both including and excluding the fortification component in foods. Of approximately 3000 foods recorded as consumed, 1.9 % were fortified, mainly breakfast cereals and beverages. Median micronutrient content of fortified foods (FF) ranged from 18-33 % EC RDA per typical serving. Among consumers (65 % of men, 68 % of women), FF contributed, on average, 3.9 % (men) and 5.0 % (women) to mean daily intake (MDI) of energy. Relative to their contribution to MDI of energy, FF contribute a greater % MDI for Fe (men 16, women 19), folate (men 18, women 21), vitamins B1 (men 14, women 16), B2 (men 16, women 18), B6 (men 12, women 15), D (men 5, women 11), B12 (men 5, women 7) and niacin (men 10, women 12). Fortification significantly improved the adequacy of intake of some micronutrients, particularly of riboflavin, folate, vitamin D and Fe in women and did not contribute to an increased risk of adverse effects from excessive intake of any micronutrient.

Iodine status of Tasmanians following voluntary fortification of bread with iodine

To describe changes in the iodine status of Tasmanians following voluntary fortification of bread with iodine in October 2001. Post-intervention, cross-sectional urinary iodine surveys of Tasmanian schoolchildren aged 8-11 years were used to assess population iodine status. Participants were selected using a one-stage cluster sampling method. The sampling frame comprised classes containing fourth-grade children from all Tasmanian government, Catholic and independent schools. Results were compared with pre-intervention survey results. Median urinary iodine concentration (UIC) and percentage of UIC < 50 microg/L ascertained from spot urine samples. Median UIC was 75 microg/L in 1998, 72 microg/L in 2000, 105 microg/L in 2003, 109 microg/L in 2004 and 105 microg/L in 2005. Median UIC in post-intervention years (2003-2005) was significantly higher than in pre-intervention years. The percentage of UIC results < 50 microg/L was 16.9% in 1998, 18.7% in 2000, 10.1% in 2003, 10.0% in 2004 and 10.5% in 2005. Despite methodological differences between the pre- and post-intervention surveys, switching to iodised salt in bread appears to have resulted in a significant improvement in iodine status in Tasmania. Given iodine deficiency has been identified in other parts of Australia and in New Zealand, mandatory iodine fortification of the food supply in both countries is worthy of consideration. As voluntary fortification relies on industry goodwill, mandating fortification could be expected to enhance population reach and give a greater guarantee of sustainability in Tasmania.

Successful Food‐Based Programmes, Supplementation and Fortification

This review highlights interventions and delivery mechanisms to alleviate macro- and micronutrient deficiencies in preschool children. These deficiencies can be addressed through an integrated combination of improved dietary intake, supplementation, commercial and home-based fortification of complementary foods. Several developed and developing countries have implemented successful approaches to eliminate protein-energy malnutrition and micronutrient deficiencies with sustained impact. These include provision of oral supplements in capsule, tablet or syrup form. Certain micronutrients (eg, vitamin A) can be provided as high-dose supplements twice per year. Most other vitamins and minerals (eg, iron, zinc, iodine) need to be provided in daily doses. Fortified complementary foods provided through public feeding programmes and commercially marketed foods have also made a positive impact. There is growing evidence of the impact of home-based fortification of complementary foods using premixes in single-serving sachets. The fortification of commercially marketed staple foods such as cereal flours, cooking oils and dairy products could have a small but significant impact on preschool children. Cereal flours with iron, folic acid and other nutrients have expanded rapidly, with evidence of impact. A key need is to deliver micronutrients to remote and impoverished populations in an affordable and sustainable manner. Government commitment, clear policy and programme direction, advocacy and communication combined with a strong public-private partnership is essential for successful programmes. Often a period of voluntary fortification needs to be followed by mandatory requirement to ensure full compliance and sustained impact. The review concludes that proven technologies, communications and infrastructure can be harnessed to ensure that the nutrient needs of preschool children are met. When administered systematically with the commitment of and participation by the public and private sectors, most of the major deficiencies can be bridged on a sustained basis, contributing to improved health and well-being of millions of children around the world.

Vitamin D deficiency in Australia and New Zealand: What are the dietary options?

AbstractMeasurement of serum vitamin D levels in population samples has revealed unexpectedly high prevalence of vitamin D deficiency among children, adults, the elderly and other vulnerable groups in Australia and New Zealand. The new Nutrient Reference Values report has established dietary recommendations for vitamin D of between 5 and 15 µg/day, depending on age. Dietary intakes of vitamin D in Australia typically fall in the range of 2–3 µg/day, below intakes in comparable countries. Dietary intake of vitamin D is currently dependent on consumption of a few key foods, notably margarine and oily fish. Current models of healthy eating do not deliver the recommended amounts of vitamin D and need review. Consideration should be given to the range of foods fortified with vitamin D, which is currently limited. Higher dietary intakes of vitamin D in overseas countries have been achieved through the fortification of margarine, milk and breakfast cereals. Increased voluntary fortification of dairy products with vitamin D would be a safe and simple means of increasing vitamin D intakes in Australasia in the short term. The relatively high dietary recommendation for vitamin D for elderly people cannot be met through the existing food supply and supplementation appears to be a desirable option for many.

Primary prevention of neural tube defects with folate in Western Australia: the value of the Western Australian Birth Defects Registry

This paper reviews the role of the Western Australian Birth Defects Registry in the primary prevention of neural tube defects. The Registry provides complete and up-to-date information on all neural tube defects (NTD), including terminations of pregnancy. These data have been used to determine a baseline rate of NTD and to monitor trends in NTD over time, when health promotion of folic acid supplement use and voluntary fortification of food with folate were introduced. The register has also been used to investigate NTD in special populations (Indigenous infants in Australia) and as a sampling frame for case control studies. The data derived from these studies have been used to assist in assessing whether mandatory food fortification in Australia is indicated to prevent NTD.

Maximum levels of vitamins and minerals for safe addition to foods in the current diets of Koreans

Significant subgroups of Koreans were at risk of suboptimal intake of vitamins and minerals. Voluntary fortification was suggested to be an important means of alleviating micronutrient deficiencies. This study was conducted to estimate the levels of vitamins and minerals that can be safely added to foods by voluntary fortification. One day diet record data of 2,201 adult males aged 20–50 years drawn from the 2001 national nutrition survey were analyzed while considering the guidelines of the Institute of Medicine and the experiences by European Union (EU) and Canada. Selected food vehicles for voluntary fortification included all foods except for fresh non processed foods, alcoholic beverages, and widely used standardized staple foods and seasonings. The mean proportion of dietary energy from all potentially fortifiable foods was about 30%. The fractions of foods in the market available for fortification were assumed to be 5, 10, 25, 50, and 100%. With all of the fractions assumed, maximum levels of the addition of micronutrients to foods were greater than 100% Korean Recommended Dietary allowances (KRDAs) for vitamins B12, B1, niacin, B2, B6, E and C. With fortification of 50% of all potentially fortifiable foods, the maximum levels of the addition ranged 40–60% of the KRDAs for calcium, folic acid, iron and zinc. Results of this study suggest a wide range of micronutrients added safely to foods in the current diets of Koreans. (Supported by a grant from the Korean Food and Drug Administration, 2005)

Promotion of folate for the prevention of neural tube defects: who benefits?

Since the publication of randomised trials showing firm evidence of prevention of neural tube defects with periconceptional folic acid, there have been population health promotion programmes to encourage women to take folic acid supplements, and the introduction of voluntary fortification of some foods with folic acid in Australia. In order to evaluate these two strategies, we collected data by self-administered questionnaire from a random sample of recently pregnant women in Western Australia between September 1997 and March 2000. Response to health promotion was measured in three ways: (1) knowledge of the association between periconceptional folate and prevention of spina bifida (the 'correct message'); (2) use of periconceptional vitamin supplements of folic acid daily in the periconceptional period; and (3) daily folate intake from fortified foods in the 6 months before pregnancy. We examined the relationship of maternal demographic and behavioural characteristics with these three measures. Overall, 62.3% of women were aware of the correct message before pregnancy, 28.5% reported taking 200 microg or more of folic acid from supplements daily in the periconceptional period and 56.6% of women obtained 100 microg or more of folic acid from fortified foods. Women who first became aware of the correct message during pregnancy or who were unaware of the correct message before or during pregnancy were more likely than women aware before pregnancy to be younger, having their first pregnancy, be single or in a de facto relationship, have no tertiary education, and be a public patient. Similar associations were seen for women taking either no folic acid or < 200 microg of folic acid in supplements daily in the periconceptional period. There were no significant associations between these demographic variables and amount of folate obtained from fortified foods. Women who were unaware of the correct message and did not take folic acid supplements were more likely to have smoked, not to have engaged in exercise, and not to have planned their pregnancy, whereas there was no association with these behavioural characteristics and intake of folate from fortified foods. These results indicate that health promotion strategies have not reached all segments of the target population equally, but there is no such disparity with folate-fortified foods, and they suggest that mandatory fortification of a staple food is likely to reach all women regardless of demographic and behavioural characteristics, and hence provide improved opportunity for prevention of neural tube defects in Australia.

Sustained Homocysteine-Lowering Effect over Time of Folic Acid-Based Multivitamin Therapy in Stroke Patients despite Increasing Folate Status in the Population

Background and Aims: It is uncertain what impact increasing voluntary folate fortification may be having on the statistical power of randomized trials testing the homocysteine hypothesis of atherothrombosis. The objective of this study was to determine whether there has been a change in folate status between 1998 and 2002 in stroke patients randomized into the VITAmins TO Prevent Stroke (VITATOPS) Study at a single center in Perth, Australia, and what impact this may have had on the magnitude of the homocysteine-lowering effect achieved over time with folic acid-based multivitamin therapy. Methods: We conducted a randomized, double-blind, placebo-controlled study involving 285 patients with stroke or transient ischemic attack who were recruited between 1998 and 2002 and randomized to long-term folic acid 2.0 mg/day, pyridoxine 25 mg/day and cobalamin 0.5 mg/day (active VITATOPS medication) or placebo. Fasting plasma total homocysteine, red cell folate, serum cobalamin and serum pyridoxine levels were measured at baseline and 6 months, and the change in blood levels over 4 time quartiles and differences in levels between the two randomized treatments were examined. Results: Between 1998 and 2002, there was a significant rise in baseline mean red cell folate levels over 4 time quartiles among the entire stroke cohort (723.3, 780.1, 922.6 and 1,023.7 nmol/l in the first, second, third and fourth quartiles, respectively; p < 0.0001), but this was not associated with a spontaneous reduction in mean baseline total homocysteine levels during the same time period (12.7, 14.3, 12.1 and 12.8 µmol/l in the first, second, third and fourth quartiles, respectively; p = 0.55). The homocysteine-lowering effect of the active VITATOPS trial medication at 6 months after randomization also did not change significantly between 1998 and 2002 (difference between randomized groups: –4.1, –4.1, –3.1 and –3.6 µmol/l in the first, second, third and fourth quartiles, respectively; p = 0.56). Conclusions: The homocysteine-lowering effect of the active VITATOPS trial medication has not attenuated significantly in the past 5 years despite increasing voluntary fortification of foods with folic acid as reflected by a progressive rise in baseline folate status. These data suggest that in the continuing absence of a program of mandatory folate fortification of food in populations served by centers participating in the VITATOPS trial, the study will remain adequately powered to test the homocysteine-lowering hypothesis for which it was designed.

Descriptive epidemiology of lipomyelomeningocele, Hawaii, 1986–2001

The epidemiology of neural tube defects (NTDs) may depend on the type of the defect and its location. There is little epidemiologic information on lipomyelomeningocele, a type of NTD. The objective of this investigation was to describe the epidemiology of lipomyelomeningocele. Cases were obtained from a Hawaii birth defect registry and consisted of all infants delivered during 1986-2001 with lipomyelomeningocele. Lipomyelomeningocele rates per 10,000 births were calculated for various factors. A total of 17 cases of lipomyelomeningocele were identified, for a total rate of 0.57. When the lipomyelomeningocele rate was examined with respect to the time period of folic acid fortification of cereal grains in the United States, the rate was 0.57 during 1986-1996 (prefortification), 0.57 during 1997-1998 (voluntary fortification), and 0.58 during 1999-2001 (mandatory fortification). A total of 11 (64.7%) of the cases were female. Lipomyelomeningocele rates were higher among infants born to mothers in younger and older age groups. The rate was highest among Pacific Islanders, followed by Filipinos and Far East Asians, and lowest among whites. Rates were greater with lower birth weight and gestational age and among multiple births. Lipomyelomeningocele rates were not found to be affected by folic acid fortification. The majority of cases were female. Other demographic and clinical factors appear to be associated with lipomyelomeningocele risk. None of the differences in rates between the various subgroups were statistically significant, and due to the small number of cases, the 95% confidence interval (CI) ranges were wide. However, the findings suggest possible patterns of occurrence. Additional studies involving larger numbers of cases are recommended.