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A decreasing rate of neural tube defects following the recommendations for periconceptional folic acid supplementation.

BACKGROUND/AIM: Neural tube defects (NTDs) are the most common birth defects, resulting in severe mortality and morbidity. In 1995, the supplementation of folic acid periconceptionally was officially recommended in Germany. The impact of the recommendations on the rate of NTDs was assessed. METHODS: An active surveillance system was established in the northern Rhine area. From 1996, all departments of obstetrics were asked to report cases of NTDs in all abortions, live births and stillbirths. Compliance with the recommendations was evaluated in a sample of mothers who delivered at the Department of Obstetrics of Düsseldorf University in 2001. RESULTS: From 1996-2003, 520 NTDs were reported. Compared to the rate of NTDs in 1996 (10.5/10,000), the average incidence in the years 1997 to 2003 dropped (6.8/10,000). The intake of folic acid, as recommended, was low among the general population (21.1%). CONCLUSION: Active surveillance data on the rate of NTDs are compatible with the maximum decrease of about 20% to be expected from data on the implementation of the recommendations. A much greater decrease in NTDs should be the challenge for the future.

Anencephaly↗

Effect of folic acid fortification of food on homocysteine-related mortality.

PURPOSE: In 1998, the Food and Drug Administration mandated the fortification of food products with folic acid. The effect of this rule on mortality associated with homocysteine levels in patients with coronary artery disease is unknown. METHODS: We studied 2481 consecutive patients with coronary artery disease who underwent coronary angiography between 1994 and 1999, and who had baseline homocysteine measurements and at least 2 years of follow-up. Patients were divided into prefortification (1994 to 1997, n = 1595) and postfortification (1998 to 1999, n = 886) groups, as well as classified based on baseline homocysteine levels (normal to low, intermediate, and high). Homocysteine levels were measured by fluorescence polarization immunoassay. Mortality was determined by telephone survey or from a national Social Security database or hospital records. RESULTS: After implementation of the fortification rule, median homocysteine levels declined from 13.8 to 12.3 micromol/L (P <0.001), and the proportion of patients with high homocysteine levels (>15 micromol/L) decreased from 41% (n = 650) to 28% (n = 249) (P <0.001). Overall, homocysteine was a modest risk factor for mortality (adjusted relative risk [RR] = 1.03 per micromol/L; 95% confidence interval [CI]: 1.01 to 1.05; P = 0.006). There was no significant interaction between fortification status and homocysteine category with mortality (P for interaction = 0.85). Two-year mortality was reduced minimally (7.8% [n = 124] to 7.2% [n = 64]; RR = 0.93; 95% CI: 0.68 to 1.27; P = 0.63; adjusted RR = 0.97; 95% CI: 0.68 to 1.40), but was consistent with the expectation of a modest reduction in homocysteine levels. CONCLUSION: Homocysteine is an independent, graded risk factor for mortality. Homocysteine levels decreased modestly after the fortification of food with folic acid, but the effects on mortality were minor and likely attributable to other factors, indicating the need for more aggressive measures to reduce homocysteine-associated cardiovascular risk.

Aged↗

Histochemical demonstration of folic acid metabolism, some lysosomal activities and NADH2-cytochrome-C-reductase in corpora mammillaria in the ageing process.

In bovine corpora mammillaria of young animals, a folic acid positive reaction was found in the neurons and in the neuroglia, in parallel with high dihydrofolate-reductase activity in the nerve cells. In old animals, folate and lysosome enzymes were different in the lateral and in medial nucleus, the highest amount being observed in the lateral nucleus; in the glial cells the lysosomal enzymes increased and in the nerve cells the concentration of folic acid increased. In the medial nucleus only relatively few enzyme modifications in the process of senescence were noticed.

Aging↗

Possible basis for primary prevention of birth defects with folic acid.

Prepregnancy counselling is efficient in cases of chronic maternal disease, selection of medication and avoiding bad life habits. A new policy is the use of folic acid in the periconceptional period for the purpose of reducing the chance of having a baby with neural tube defects (NTD). Research in progress at the Department of Obstetrics and Gynaecology in Nijmegen, the Netherlands, is presented demonstrating that a derangement of methionine-homocysteine metabolism could be the underlying mechanism of pathogenesis and prevention with folic acid. Such derangement was found in +/- 20% of cases with NTD, recurrent miscarriage and placental infarcts (abruption) and offers new possibilities for primary prevention in three major areas.

Abortion, Habitual↗

ACUTE FOLIC ACID DEFICIENCY OF UNKNOWN AETIOLOGY: TEMPERATE SPRUE.

The 20 patients described could be included in the group of patients diagnosed as ;idiopathic steatorrhoea'. However, their histories were short and diarrhoea was not a major feature. Since megaloblastic anaemia due to folic acid deficiency was a common feature it is suggested that these patients may form a homogeneous group and the diagnostic label of temperate sprue is suggested.

Adolescent↗

Psychological disturbances and folic acid in chronic epileptic outpatients.

The relationship between serum folate level and psychological disturbances was studied in a series of 95 chronic epileptic outpatients. All were nondrinkers. Serum folic acid in all cases and vitamin B12 in 83 cases were determined by radioimmunoassay. Only three factors were significantly related with psychological disturbances: serum levels of folic acid were significantly lower and the mean corpuscular volume of the erythrocytes was significantly higher in disturbed patients, particularly in those with the most severe psychiatric syndromes, and the incidence of disturbances was significantly higher in patients treated with three or more drugs. Conversely, variables such as number or type of seizures, duration of epilepsy, duration of treatment, presence of structural neurological lesions, previous mental retardation, or focal temporal lobe disturbances in the EEG did not show any statistical relationship to the presence of psychological disturbances. No relevant relationship was found between serum vitamin B12 and psychological disturbances.

Adolescent↗

Folic acid enhances lithium prophylaxis.

A double-blind trial was carried out to investigate the effect on affective morbidity of a daily supplement of 200 micrograms folic acid or a matched placebo in a group of 75 patients on lithium therapy. During the trial the patients with the highest plasma folate concentrations showed a significant reduction in their affective morbidity. Patients who had their plasma folate increased to 13 ng/ml or above had a 40% reduction in their affective morbidity. It is suggested that a daily supplement of 300-400 micrograms folic acid would be useful in long-term lithium prophylaxis.

Adult↗

The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA glycosylase-deficient Aag null mice.

Folic acid deficiency (FA-) augments DNA damage caused by alkylating agents. The role of DNA repair in modulating this damage was investigated in mice. Weanling wild-type or 3-methyladenine glycosylase (Aag) null mice were maintained on a FA- diet or the same diet supplemented with folic acid (FA+) for 4 weeks. They were then treated with methyl methanesulfonate (MMS), 100mg/kg i.p. Six weeks later, spleen cells were collected for assays of non-selected and 6-thioguanine (TG) selected cloning efficiency to measure the mutant frequency at the Hprt locus. In wild-type mice, there was no significant effect of either MMS treatment or folate dietary content on splenocyte non-selected cloning efficiency. In contrast, non-selected cloning efficiency was significantly higher in MMS-treated Aag null mice than in saline treated controls (diet-gene interaction variable, p=0.04). The non-selected cloning efficiency was significantly higher in the FA+ diet than in the FA- diet group after MMS treatment of Aag null mice. Mutant frequency after MMS treatment was significantly higher in FA- wild-type and Aag null mice and in FA+ Aag null mice, but not in FA+ wild-type mice. For the Aag null mice, mutant frequency was higher in the FA+ mice than in the FA- mice after either saline or MMS treatment. These studies indicate that in wild-type mice treated with MMS, dietary folate content (FA+ or FA-) had no effect on cytotoxicity, but FA- diet increased DNA mutation frequency compared to FA+ diet. In Aag null mice, FA- diet increased the cytotoxic effects of alkylating agents but decreased the risk of DNA mutation.

Animals↗

Folic acid and vitamin B12 deficiency in pregnancy and in the neonatal period.

The fetus, the neonate, and the pregnant woman have a greater requirement for folic acid and vitamin B12 and are more likely to suffer from a deficiency of these vitamins. This article reviews the source, requirement, absorption, and metabolism of these vitamins and discusses the problems attributed to their deficiency in pregnancy and in the neonatal period.

Abortion, Spontaneous↗

Folic acid fortification of grain: an economic analysis.

OBJECTIVES: The purpose of this study was to compare the economic costs and benefits of fortifying grain with folic acid to prevent neural tube defects. METHODS: A cost-benefit analysis based on the US population, using the human capital approach to estimate the costs associated with preventable neural tube defects, was conducted. RESULTS: Under a range of assumptions about discount rates, baseline folate intake, the effectiveness of folate in preventing neural tube defects, the threshold dose that minimizes risk, and the cost of surveillance, fortification would likely yield a net economic benefit. The best estimate of this benefit is $94 million with low-level (140 micrograms [mcg] per 100 g grain) fortification and $252 million with high-level (350 mcg/100 g) fortification. The benefit-to-cost ratio is estimated at 4.3:1 for low-level and 6.1:1 for high-level fortification. CONCLUSIONS: By averting costly birth defects, folic acid fortification of grain in the United States may yield a substantial economic benefit. We may have underestimated net benefits because of unmeasured costs of neural tube defects and unmeasured benefits of higher folate intake. We may have overestimated net benefits if the cost of neurologic sequelae related to delayed diagnosis of vitamin B12 deficiency exceeds our projection.

Cost-Benefit Analysis↗

College women's reported behaviors and beliefs regarding fish and folic acid and their roles in birth defects.

The purpose of the current study was to examine college women's beliefs and behaviors regarding birth defect prevention via folic acid intake and avoidance of fish with high mercury levels. We surveyed 313 college women and found that the majority of them reported eating fish despite their awareness that certain types of fish contained levels of mercury that are dangerous for women of childbearing age. We also found that the majority of the women did not comply with dietary guidelines for vegetable and legume consumption, and more than half of them did not take vitamin supplements that provide folic acid.

Adolescent↗