Folic acid and neural tube defects: Discovery, debate and the need for policy change.

Neural tube defects (NTDs) are a group of relatively common fatal or severely disabling birth defects that result in about 300,000 cases a year world-wide. The search for a cause was elusive, but in 1991 it was shown that about 8 out of 10 cases are due to a lack of vitamin B9 (folate) and are therefore preventable. This article (i) describes the challenge in finding the cause; (ii) examines the reasons for the failure of many countries to introduce folic acid fortification of staple foods such as flour and rice; (iii) shows that countries that have introduced fortification failed to do so in a fully effective way; (iv) shows how current preventive polices are confusing, inconsistent and sub-optimal; (v) shows that the proposed UK folic acid fortification policy is expected to prevent about 1 out of 10 NTD cases only; and (vi) proposes a simple, fully effective fortification policy that would prevent about 8 out of 10 NTDs and avoid the need for women to start taking folic acid supplements before pregnancy, a policy that has been shown to fail because only a small percentage of women adopt this practice.

Randomized Crossover Trial of Phosphate-binding Medication on Serum Phosphate Levels in Patients With Aortic Stenosis.

PURPOSE: Aortic stenosis is a common cause of valvular heart disease with no means of prevention. The recognized association between aortic stenosis and serum phosphate raises the possibility of preventing progression of the disorder by using phosphate-binding drugs, but there is uncertainty whether such treatment lowers serum phosphate levels in patients without diagnosed renal failure. This pilot study was conducted to answer this question in patients with aortic stenosis. METHODS: A randomized, double-blind, crossover trial of the phosphate-binding drug sevelamer was conducted in 72 patients. Patients were prescribed sevelamer 0.8 g (low-dose), sevelamer 2.4 g (high-dose), and matching placebo, 3 times daily with food; each regimen lasted 6 weeks and was allocated at random. Serum phosphate levels were measured at the end of each treatment period, and within-person levels were compared. FINDINGS: Sixty-one patients completed the 3 treatment periods. There was no significant difference in the mean end-treatment phosphate levels across all patients (3.38, 3.36, and 3.31 mg/dL with placebo, low-dose sevelamer, and high-dose sevelamer, respectively). Post hoc analysis showed a reduction in phosphate levels with increasing sevelamer dose in the highest baseline phosphate quartile group; a 0.3 mg/dL reduction (mean, 4.09 mg/dL with placebo, 3.95 mg/dL with low-dose sevelamer, and 3.79 mg/dL with high-dose sevelamer; Ptrend = 0.027). IMPLICATIONS: Sevelamer had no overall statistically significant effect in lowering serum phosphate levels, but a reduction was observed in patients with phosphate levels in the highest quartile group of the population distribution. This hypothesis-generating result requires confirmation in an independent study. If confirmed, a trial of sevelamer in preventing the progression of aortic stenosis may be justified in patients with high phosphate levels. ISRCTN Registry identifier: ISRCTN17365679.

Quantifying the health benefits of chronic disease prevention: a fresh approach using cardiovascular disease as an example.

Current methods of determining the proportion of people who benefit from a preventive intervention and the years of life gained can underestimate the former and overestimate the latter. We describe how to overcome these errors, using two examples relating to the prevention of myocardial infarction (MI) and stroke, one using a specified polypill daily from age 50 and another reducing salt intake in the population. Standard life table analysis was used to calculate the person-years of life gained without an MI or stroke, based on estimates of the incidence of these disorders in England and Wales. The proportion of individuals who benefit was taken as everyone who would, without treatment, have an MI or stroke (holistic model), rather than limiting the benefit to the proportion calculated from the relative risk reduction (reductionist model), as is current practice. Under the holistic model, 33% of people who take the polypill from age 50 benefit, gaining, on average, 8 years of life without an MI or stroke (19% and 14 years under the reductionist model). Estimates for reducing salt intake by 6 g/day are 33% and 2.8 years respectively under the holistic model (6% and 16 years under the reductionist model). In the prevention of disorders such as stroke by reducing exposure to causal factors such as blood pressure, the use of a holistic model corrects the underestimation of the proportion of people who benefit and the overestimation of their years of life gained associated with current methods.

Prevention of neural tube defects: a cross-sectional study of the uptake of folic acid supplementation in nearly half a million women.

BACKGROUND: Taking folic acid supplements before pregnancy to reduce the risk of a neural tube defect (NTD) is especially important in countries without universal folic acid fortification. The extent of folic acid supplementation among women who had antenatal screening for Down's syndrome and NTDs at the Wolfson Institute of Preventive Medicine, London between 1999 and 2012 was assessed. METHODS AND FINDINGS: 466,860 women screened provided details on folic acid supplementation. The proportion of women who took folic acid supplements before pregnancy was determined according to year and characteristics of the women. The proportion of women taking folic acid supplements before pregnancy declined from 35% (95% CI 34%-35%) in 1999-2001 to 31% (30%-31%) in 2011-2012. 6% (5%-6%) of women aged under 20 took folic acid supplements before pregnancy compared with 40% of women aged between 35 and 39. Non-Caucasian women were less likely to take folic acid supplements before pregnancy than Caucasian women; Afro-Caribbean 17% (16%-17%), Oriental 25% (24%-25%) and South Asian 20% (20%-21%) compared with 35% (35%-35%) for Caucasian women. 51% (48%-55%) of women who previously had an NTD pregnancy took folic acid supplements before the current pregnancy. CONCLUSIONS: The policy of folic acid supplementation is failing and has led to health inequalities. This study demonstrates the need to fortify flour and other cereal grain with folic acid in all countries of the world.