István Dudás

Bio: István Dudás is an academic researcher. The author has contributed to research in topics: Pregnancy & Multivitamin. The author has an hindex of 9, co-authored 16 publications receiving 4005 citations.

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Abstract: Background. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known. Methods. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. Results. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetu...

Prevention of the First Occurrence of Neural-Tube Defects by Periconceptional Vitamin Supplementation

Abstract: Background. The risk of recurrent neural-tube defects is decreased in women who take folic acid or multivitamins containing folic acid during the periconceptional period. The extent to which such supplementation can reduce the first occurrence of defects is not known. Methods. We conducted a randomized, controlled trial of periconceptional multivitamin supplementation to test the efficacy of this treatment in reducing the incidence of a first occurrence of neural-tube defects. Women planning a pregnancy (in most cases their first) were randomly assigned to receive a single tablet of a vitamin supplement (containing 12 vitamins, including 0.8 mg of folic acid; 4 minerals; and 3 trace elements) or a trace-element supplement (containing copper, manganese, zinc, and a very low dose of vitamin C) daily for at least one month before conception and until the date of the second missed menstrual period or later. Results. Pregnancy was confirmed in 4753 women. The outcome of the pregnancy (whether the fetu...

Folate Deficiency and Folic Acid Supplementation: The Prevention of Neural-Tube Defects and Congenital Heart Defects

Abstract: Diet, particularly vitamin deficiency, is associated with the risk of birth defects. The aim of this review paper is to show the characteristics of common and severe neural-tube defects together with congenital heart defects (CHD) as vitamin deficiencies play a role in their origin. The findings of the Hungarian intervention (randomized double-blind and cohort controlled) trials indicated that periconceptional folic acid (FA)-containing multivitamin supplementation prevented the major proportion (about 90%) of neural-tube defects (NTD) as well as a certain proportion (about 40%) of congenital heart defects. Finally the benefits and drawbacks of three main practical applications of folic acid/multivitamin treatment such as (i) dietary intake; (ii) periconceptional supplementation; and (iii) flour fortification are discussed. The conclusion arrived at is indeed confirmation of Benjamin Franklin’s statement: “An ounce of prevention is better than a pound of care”.

Prevention of neural-tube defects with periconceptional folic acid, methylfolate, or multivitamins?

Abstract: Background/Aims: To review the main results of intervention trials which showed the efficacy of periconceptional folic acid-containing multivitamin and folic acid supplementation in the prevention of neural-tube defects (NTD). Methods and Results: The main findings of 5 intervention trials are known: (i) the efficacy of a multivitamin containing 0.36 mg folic acid in a UK nonrandomized controlled trial resulted in an 83–91% reduction in NTD recurrence, while the results of the Hungarian (ii) randomized controlled trial and (iii) cohort-controlled trial using a multivitamin containing 0.8 mg folic acid showed 93 and 89% reductions in the first occurrence of NTD, respectively. On the other hand, (iv) another multicenter randomized controlled trial proved a 71% efficacy of 4 mg folic acid in the reduction of recurrent NTD, while (v) a public health-oriented Chinese-US trial showed a 41–79% reduction in the first occurrence of NTD depending on the incidence of NTD. Conclusions: Translational application of these findings could result in a breakthrough in the primary prevention of NTD, but so far this is not widely applied in practice. The benefits and drawbacks of 4 main possible uses of periconceptional folic acid/multivitamin supplementation, i.e. (i) dietary intake, (ii) periconceptional supplementation, (iii) flour fortification, and (iv) the recent attempt for the use of combination of oral contraceptives with 6S-5-methytetrahydrofolate (methylfolate), are discussed. Obviously, prevention of NTD is much better than the frequent elective termination of pregnancies after prenatal diagnosis of NTD fetuses.

Higher Rate of Multiple Births after Periconceptional Vitamin Supplementation

Abstract: To the Editor: Periconceptional supplementation with multivitamins including folic acid or with folic acid alone can reduce both the first occurrence and the recurrence of neural-tube defects1–3. We examined the effect of such supplementation on multiple births. The Hungarian trial of periconceptional multivitamin supplementation was stopped in 1992, and the outcomes of the pregnancies were evaluated one year later1. The multivitamin supplement contained 12 vitamins, including 0.8 mg of folic acid, four minerals, and three trace elements; a control supplement contained three trace elements. Pregnancy was confirmed in 5502 women, and outcome could be evaluated in 5453. . . .

‘Mendelian randomization’: can genetic epidemiology contribute to understanding environmental determinants of disease?

Abstract: Associations between modifiable exposures and disease seen in observational epidemiology are sometimes confounded and thus misleading, despite our best efforts to improve the design and analysis of studies. Mendelian randomization-the random assortment of genes from parents to offspring that occurs during gamete formation and conception-provides one method for assessing the causal nature of some environmental exposures. The association between a disease and a polymorphism that mimics the biological link between a proposed exposure and disease is not generally susceptible to the reverse causation or confounding that may distort interpretations of conventional observational studies. Several examples where the phenotypic effects of polymorphisms are well documented provide encouraging evidence of the explanatory power of Mendelian randomization and are described. The limitations of the approach include confounding by polymorphisms in linkage disequilibrium with the polymorphism under study, that polymorphisms may have several phenotypic effects associated with disease, the lack of suitable polymorphisms for studying modifiable exposures of interest, and canalization-the buffering of the effects of genetic variation during development. Nevertheless, Mendelian randomization provides new opportunities to test causality and demonstrates how investment in the human genome project may contribute to understanding and preventing the adverse effects on human health of modifiable exposures.

A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects?

Abstract: Summary Recently, we showed that homozygosity for the common 677(C→T) mutation in the methylenetetrahydrofolate reductase (MTHFR) gene, causing thermolability of the enzyme, is a risk factor for neural-tube defects (NTDs). We now report on another mutation in the same gene, the 1298(A→C) mutation, which changes a glutamate into an alanine residue. This mutation destroys an Mbo II recognition site and has an allele frequency of .33. This 1298(A→C) mutation results in decreased MTHFR activity (one-way analysis of variance [ANOVA] P P P n = 86) of the NTD patients compared with 20% ( n = 403) among controls, resulting in an odds ratio of 2.04 (95% confidence interval: .9–4.7). These data suggest that the combined heterozygosity for the two MTHFR common mutations accounts for a proportion of folate-related NTDs, which is not explained by homozygosity for the 677(C→T) mutation, and can be an additional genetic risk factor for NTDs.

Prevention of Neural-Tube Defects with Folic Acid in China

Abstract: Background Periconceptional use of multivitamins containing folic acid can reduce a woman's risk of having a baby with a neural-tube defect. Methods As part of a public health campaign conducted from 1993 to 1995 in an area of China with high rates of neural-tube defects (the northern region) and one with low rates (the southern region), we evaluated the outcomes of pregnancy in women who were asked to take a pill containing 400 μg of folic acid alone daily from the time of their premarital examination until the end of their first trimester of pregnancy. Results Among the fetuses or infants of 130,142 women who took folic acid at any time before or during pregnancy and 117,689 women who had not taken folic acid, we identified 102 and 173, respectively, with neural-tube defects. Among the fetuses or infants of women who registered before their last menstrual period and who did not take any folic acid, the rates of neural-tube defects were 4.8 per 1000 pregnancies of at least 20 weeks' gestation in the nort...

5, 10-Methylenetetrahydrofolate Reductase Gene Variants and Congenital Anomalies: A HuGE Review

Abstract: The enzyme 5,10-methylenetetrahydrofolate reductase (MTHFR) is involved in folate metabolism. The MTHFR gene is located on chromosome 1 (1p36.3), and two common alleles, the C677T (thermolabile) allele and the A1298C allele, have been described. The population frequency of C677T homozygosity ranges from 1% or less among Blacks from Africa and the United States to 20% or more among Italians and US Hispanics. C677T homozygosity in infants is associated with a moderately increased risk for spina bifida (pooled odds ratio = 1.8; 95% confidence interval: 1.4, 2.2). Maternal C677T homozygosity also appears to be a moderate risk factor (pooled odds ratio = 2.0; 95% confidence interval: 1.5, 2.8). The A 1298C allele combined with the C677T allele also could be associated with an increased risk for spina bifida. Some data suggest that the risk for spina bifida associated with C677T homozygosity may depend on nutritional status (e.g., blood folate levels, intake of vitamins) or on the genotype of other folate-related genes (e.g., cystathionine-beta-synthase and methionine synthase reductase). Studies of the C677T allele in relation to oral clefts, Down syndrome, and fetal anticonvulsant syndrome either have yielded conflicting results or have not been yet replicated.

Impact of Folic Acid Fortification of the US Food Supply on the Occurrence of Neural Tube Defects

Abstract: ContextDaily consumption of 400 µg of folic acid before conception and during early pregnancy dramatically reduces the occurrence of neural tube defects (NTDs). Before food fortification, however, only an estimated 29% of US reproductive-aged women were taking a supplement containing 400 µg of folic acid daily. The US Food and Drug Administration authorized addition of folic acid to enriched grain products in March 1996, with compliance mandatory by January 1998.ObjectiveTo evaluate the impact of food fortification with folic acid on NTD birth prevalence.Design, Setting, and PopulationNational study of birth certificate data for live births to women in 45 US states and Washington, DC, between January 1990 and December 1999.Main Outcome MeasureBirth certificate reports of spina bifida and anencephaly before fortification (October 1995 through December 1996) compared with after mandatory fortification (October 1998 through December 1999).ResultsThe birth prevalence of NTDs reported on birth certificates decreased from 37.8 per 100 000 live births before fortification to 30.5 per 100 000 live births conceived after mandatory folic acid fortification, representing a 19% decline (prevalence ratio [PR], 0.81; 95% confidence interval [CI], 0.75-0.87). During the same period, NTD birth prevalence declined from 53.4 per 100 000 to 46.5 per 100 000 (PR, 0.87; 95% CI, 0.64-1.18) for women who received only third-trimester or no prenatal care.ConclusionsA 19% reduction in NTD birth prevalence occurred following folic acid fortification of the US food supply. However, factors other than fortification may have contributed to this decline.