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Maternal knowledge, attitude and practice on folic acid intake among Arabian Qatari women.

BACKGROUND: Periconceptional folic acid supplementation is effective in preventing primary and secondary neural tube defects (NTDs) and other congenital defects. It is important to estimate folate intake and knowledge in women of child-bearing age, in relation to risk of congenital anomalies. AIM: The aim of this study was to determine the level of knowledge about the usefulness of periconceptional folic acid supplementation in a sample of women in the child-bearing age. DESIGN: This is a cross-sectional survey. SETTING: Eleven primary health care centers and women's hospital in Qatar. SUBJECTS: A multistage sampling design was used and a representative sample of 1,800 Qatari women aged between 18 and 45 years were surveyed during the period June to November 2004. One thousand four hundred and eighty women (82.2%) expressed their consent to participate in this study. METHODS: A confidential, anonymous questionnaire was completed by the selected subjects assessing folic acid awareness. Questionnaires were administered to women who were seeking routine antenatal care at health centers and Women's Hospital. Questions covered knowledge and use of folic acid supplements, pregnancy intention, and demographic and socioeconomic characteristics. Factors affecting study outcomes were examined individually by computing crude odd ratios and adjusted for other covariates using unconditional logistic regression. RESULTS: Out of 1480 women surveyed, 53.7% of them reported that they heard of folate. Of these, only half of the subjects knew that folate was something important. Overall, 20.3% of the respondents took folic acid. The most common information sources on folate were physicians (63.4%), and newspapers/magazine/books (21.7%). From those who heard of folate, only 14% knew that it can prevent birth defects. 40.6% of the subjects who heard folate were aware that green leafy vegetables were fortified with folic acid. In univariate analysis, awareness of folic acid was significantly associated with education of mother. Again, higher educated women (41.3%) knew more about folic acid and used it more often in the periconceptional and first trimester period. CONCLUSION: Awareness and use of folic acid was less prevalent among Qatari women. Educated women were aware of the importance of the intake of folic acid. The study findings suggested possible avenue for intervention to increase awareness and intake of folic acid.

Adult↗

[Safety aspects of folic acid for the general population].

Periconceptional use of folic acid reduces the risk of neural tube defects considerably. In Switzerland, implementation of these findings could be improved through fortification of a staple food with folic acid. The present paper reviews possible hazards associated with high intake of folic acid in the general population. Among the potential safety issues are interaction between folic acid and zinc, interaction between folic acid and drugs (phenytoin, methotrexate etc.) and hypersensitivity to folic acid. Of main concern are adverse effects of folic acid in cobalamin deficiency. Solutions are discussed.

Adult↗

The effect of aminopterin-induced folic acid deficiency on spermatogenesis.

Folic acid deficiency was produced by injecting aminopterin into adult male albino rats, resulting in inhibition of spermatogenesis. Bone marrow smears were studied to serve as an index of folic acid deficiency; however, changes in spermatogenesis were noticed earlier than the bone marrow changes. Meiotic division was affected more than mitotic division. The nuclei of spermatogenic cells showed degenerative changes. Chromosomal abnormalities, chiefly sticky chromosomes, were noticed in squashed preparations of seminiferous tubules.

Aminopterin↗

Effectiveness of a free folic acid supplement program in family planning clinics.

BACKGROUND: Adequate periconceptional folic acid consumption lowers the risk for neural tube defects. We report the results of an evaluation of a folic acid intervention in Georgia family planning clinics that provided free folic acid supplements or fortified breakfast cereal. METHODS: Six family planning clinics participated in the evaluation. Three clinics provided folic acid pills and educational materials to clients, two provided super-fortified cereal and educational materials, and one clinic provided educational materials only. Participants between the ages of 18 and 45 who visited the clinics in 2000 completed a brief survey and provided a blood sample. Of the 1093 women who participated, we evaluated the 165 women who had returned to the clinic at least once during the study period. We compared participants' survey and serum folate data from their first and subsequent visits. RESULTS: Participation in the intervention was associated with increased knowledge about folic acid, (odds ratio, 1.94; 95% confidence interval, 1.37-2.76), but was not directly associated with increased self-reported folic acid consumption or increased serum folate levels. Reported use of folic acid supplements or cereal within two days of a visit was associated with higher serum folate levels. Knowledge about folic acid was one of the best predictors of self-reported folic acid consumption. CONCLUSIONS: Participation in the intervention increased clients' knowledge about folic acid but did not directly increase reported folic acid consumption. Because knowledge predicted folic acid consumption, the intervention may be indirectly associated with increased consumption of folic acid.

Adolescent↗

Pancytopenia--a rare manifestation of folic acid deficiency.

In the western world folic acid deficiency is a relatively rare cause of anaemia in the elderly population. A 79-year-old woman presented with pancytopenia (haemoglobin 3.4 mmol l-1, leucocytes 1.2.10(9)l-1, thrombocytes 22.10(9)l-1) due to folic acid deficiency. The deficiency was caused by an extremely low dietary intake. The case was complicated with infection and haemorrhagic manifestations. Administration of folic acid increased the number of erythrocytes, leucocytes and thrombocytes markedly. Beside vitamin B12 deficiency folic acid deficiency must be borne in mind in megaloblastic anaemias complicated with leucopenia and/or thrombocytopenia. Since the body stores of folic acid are low, rapid diagnosis and treatment are important.

Aged↗

Stability of folic acid in 25% dextrose, 3.5% amino acids, and multivitamin solution.

The chemical stability of folic acid in 25% dextrose, 3.5% amino acids, and multivitamin solution was investigated. Solutions of 0.25, 0.5, 0.75, and 1.0 mg/liter of folic acid admixed in the study solution were prepared. Solutions were stored in light-room temperature, light-refrigeration, dark-room temperature, or dark-refrigeration. Samples were drawn to determine folic acid concentration and again at 4, 8, 12, 18, 24, 36, and 48 hr after admixture. Folic acid concentration was determined by competitive binding radioassay, and results are expressed as percent of initial folic acid concentration. Folic acid was stable for 48 hr with each tested concentration and stability was found to be independent of temperature or light storage effects. Folic acid admixed in the study solution is chemically stable for up to 48 hr after initial admixture under normal total parenteral nutrition storage conditions.

Amino Acids↗

[Inhibitors of folic acid metabolism (author's transl)].

In contrast to antibiotic research, the study of folic acid metabolism and folic acid antagonists is conducted in the classical tradition of chemotherapy established by Paul Ehrlich. The elucidation of the mechanism of action of sulphonamides created an important prerequisite for the understanding of the biosynthesis of folic acid. The synthesis of inhibitors of dihydrofolate-reductase was guided on the one hand by the structure of dihydrofolate itself, and on the other hand by the fact that this substnce is essential for the growth of certain bacteria. Both approaches led to the synthesis of compounds which were effective and could be used therapeutically. The mechanism of selectivity of folic acid antagonists is described. A short account of the biochemical and genetic basis of resistance to folic acid antagonists is also given. The study of folic acid metabolism and folic acid antagonists provides a good example of the successful interaction of mechanistically inspired biochemical and chemical methods on the one hand, and an empirical approach characterised by the study of more complex biological phenomena on the other hand.

Folic Acid↗

Experimental folic acid nephropathy.

In rats, single intravenous doses of folic acid induce damage to renal tubular epithelium, deposition of folic acid in tubular lumens, increase in wet kidney weight, oliguria and interstitial connective tissue proliferation. Separation of the nephrotoxic and obstructive effects of folic acid was attempted by pretreatment with NH4Cl or NaHCO3. These effects of folic acid were unaltered by pretreatment with NH4Cl and there was, in addition, accumulation of eosinophilic droplets in papillary collecting duct epithelium. After pretreatment with NaHCO3, folic acid deposition is decreased or absent; there is a smaller increase in wet kidney weight; the rats are polyuric rather than oliguric; interstitial connective tissue proliferation is reduced; and no droplets form in papillary collecting ducts, but lesions are still present in proximal convoluted tubule epithelial cells. These findings indicate that folic acid has direct nephrotoxic effects independent of intraluminal folic acid deposition, and that damage to renal epithelium, unlike that induced by many nephrotoxins, occurs at several levels of the nephron.

Ammonium Chloride↗

Blood-brain barrier transport of reduced folic acid.

PURPOSE: The brain is relatively resistant to folic acid deficiency, indicating specialized transport systems may exist for this vitamin localized within the brain capillary endothelial wall, which makes up the blood-brain barrier (BBB) in vivo. The present studies quantify the BBB transport of [3H]-methyltetrahydrofolic acid (MTFA) in vivo and in isolated human brain capillaries in vitro. METHODS: BBB transport of [3H]-MTFA was compared to that of 14C]-sucrose, a plasma volume marker, following either intravenous injection or intracarotid perfusion in anesthetized rats. Competition by 10 microM MTFA or 10 microM folic acid was examined to determine whether folic acid is also transported by the MTFA uptake system. RESULTS: The BBB permeability-surface area (PS) product of [3H]-MTFA, 1.1 +/- 0.3 microL/min/g, was 6-fold greater than that of [14C]-sucrose following intravenous injection. The BBB PS product determined by intracarotid arterial perfusion was not significantly different from the BBB PS product calculated following intravenous injection. A time- and temperature- dependent uptake of [3H]-MTFA in human brain capillaries was observed. The uptake of [3H]-MTFA by either rat brain in vivo or by human brain capillaries in vitro was equally inhibited by 10 microM concentrations of either unlabeled MTFA or unlabeled folic acid. CONCLUSIONS: (1) A saturable transport system exists at the BBB for folic acid derivatives and since this transport is equally inhibited by either folic acid or MTFA, it is inferred that this transport system is the folic acid receptor, and not the reduced folic acid carrier. (2) The presence of a folate transport system at the BBB may offer an endogenous transport system for brain drug delivery of conjugates of folates and drugs that do not normally cross the BBB in vivo.

Animals↗

Folic acid and psychopathology.

1. The incidence of folic acid deficiency is high in patients with various psychiatric disorders including depression, dementia and schizophrenia. 2. In epileptics on anticonvulsants, folate deficiency often occurs because anticonvulsants inhibit folate absorption. In these patients folate deficiency is often associated with psychiatric symptoms. 3. In medical patients psychiatric symptoms occur more frequently, and in psychiatric patients symptoms are more severe, in those with folate deficiency than in those with normal levels. 4. Many open studies have demonstrated therapeutic effects of folate administration on psychiatric symptoms in folate deficient patients. 5. Several placebo-controlled studies have not demonstrated therapeutic effects, possibly because the doses they used (15-20 mg/day) are known to be toxic and to cause mental symptoms. 6. Two placebo-controlled studies have demonstrated beneficial effects of folic acid administration, one in patients with a syndrome of psychiatric and neuropsychological changes associated with folate deficiency and the other in patients on long-term lithium therapy. In the latter study the dose was only 0.2 mg/day. 7. Folic acid deficiency is known to lower brain S-adenosylmethionine and 5-hydroxytryptamine. S-Adenosylmethionine, which has antidepressant properties, raises brain 5-hydroxytryptamine. Thus, depression associated with folate deficiency is probably related to low brain 5HT. 8. S-Adenosylmethionine is involved in many methylation reactions, including methylation of membrane phospholipids, which influences membrane properties. This may explain the wide variety of symptoms associated with folate deficiency. 9. Because the costs and risks associated with low doses of folic acid (up to 0.5 mg/day) are small, folic acid should be given as an adjunct in the treatment of patients with unipolar or bipolar affective disorders and anorexia, epileptics on anticonvulsants, geriatric patients with mental symptoms and patients with gastrointestinal disorders who exhibit psychiatric symptoms. 10. Although the majority of the patients listed above will probably not be helped by folic acid therapy, a significant minority are likely to have folate-responsive symptoms.

Folic Acid↗

DNA instability (strand breakage, uracil misincorporation, and defective repair) is increased by folic acid depletion in human lymphocytes in vitro.

Folic acid is essential for the synthesis and repair of DNA. We report the effects of folate depletion on DNA stability in normal human lymphocytes in vitro. DNA strand breakage, uracil misincorporation, oxidative DNA base damage, and DNA repair capability were determined using variants of the comet assay (single cell gel electrophoresis). Lymphocyte proliferation was measured as an indicator of normal replication. Lymphocytes isolated from human venous blood were stimulated to grow in either complete medium containing folic acid (1 ng/ml-2 microgram/ml) or medium deficient in folic acid for up to 10 days. Cells prepared for comet analysis were treated either with the bacterial DNA repair enzyme endonuclease III to determine the level of oxidized pyrimidines in lymphocyte DNA or with uracil DNA glycosylase, which detects misincorporated uracil. Cell number and viability were measured. Normal human lymphocyte DNA contained detectable amounts of misincorporated uracil (estimated as approximately 1000 per cell). DNA strand breakage and uracil misincorporation increased in a time- and concentration-dependent manner after lymphocytes were cultured with decreasing amounts of folic acid. DNA damage was induced at folic acid concentrations routinely observed in plasma from the human population (1-10 ng/ml). Lymphocytes cultured under folate-deficient conditions failed to grow normally compared with control cells. However, all lymphocytes remained viable as measured by Trypan blue exclusion. Cells deprived of folate were unable to efficiently repair oxidative DNA damage induced by hydrogen peroxide. Inhibition of repair was maximal after 8 days in culture. Folate supply had no effect on the level of oxidized pyrimidines in lymphocyte DNA, even after 10 days in culture, suggesting that folate deficiency increases uracil misincorporation relatively specifically. These in vitro results help to determine the mechanism(s) through which folic acid maintains DNA stability.

Adult↗

Kinetic analysis of the effect of luminal pH on transport of folic acid in the small intestine.

Transport of folic acid in the small intestine is markedly affected by luminal pH and is optimal at pH 5.5-6.5. To clarify the nature of this pH sensitivity, we measured transport of [3H] folic acid into rat jejunum at pH 5.5 and 7.4, at folic acid concentrations of 1 to 30 microM, using the influx chamber method. At this range of concentrations, uptake of folic acid exhibited Michaelis-Menten kinetics. In order to determine the kinetic parameter which is pH sensitive, we have fitted a modified Michaelis-Menten equation to the pooled data at the two pH conditions such as they share a common Vmax but distinct Km values. This model fitted closely the experimental data (F = 0.693), yielding Km values (+/- SE) of 24.22 (+/- 5.96) and 36.32 (+/- 8.73) microM for pH 5.5 and 7.4 respectively. The difference in the Km at the two pH conditions was statistically significant (p less than 0.01). The change in affinity for folic acid transport at the two pH conditions may reflect different membrane carriers, or may be due to protonation of a membrane carrier and/or the folic acid molecule, favored at low pH.

Acid-Base Equilibrium↗

Neural tube defects in relation to use of folic acid antagonists during pregnancy.

Periconceptional folic acid supplementation reduces the risk of neural tube defects (NTDs). To determine whether periconceptional exposure to folic acid antagonists (FAAs) might therefore increase the risk of NTDs, the authors examined data from an ongoing case-control study of birth defects (1979-1998) in the United States and Canada. They compared data on 1,242 infants with NTDs (spina bifida, anencephaly, and encephalocele) with data from a control group of 6,660 infants with malformations not related to vitamin supplementation. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors and about medication use. The adjusted odds ratios of NTDs related to exposure to FAAs (including carbamazepine, phenobarbital, phenytoin, primidone, sulfasalazine, triamterene, and trimethoprim) during the first or second months after the last menstrual period, compared with no use in either month, were 2.8 (95% confidence interval: 1.7, 4.6) for FAAs as a group, 4.8 (95% confidence interval: 1.5, 16.1) for trimethoprim (based on five exposed cases), and 6.9 (95% confidence interval: 1.9, 25.7) for carbamazepine (six exposed cases). These results are adjusted for region, interview year, periconceptional folic acid supplementation, maternal age, weight, education, and infections early in pregnancy. These findings suggest that a number of FAAs may increase NTD risk, and they provide estimates of risk for selected drugs.

Adult↗

Occurrence of low birthweight and preterm delivery among California infants before and after compulsory food fortification with folic acid.

OBJECTIVES: Studies suggest that folic acid intake influences the occurrence of low birthweight and preterm delivery. Since 1998, there has been compulsory fortification of flour and other grains with folic acid in the U.S. The objective of this study was to investigate the frequencies of low birthweight and preterm delivery after mandatory folic acid fortification among approximately six million California births. METHODS: The authors investigated prevalences of low birthweight and preterm delivery before and after compulsory fortification among 5,916,630 singleton California live births that occurred from January 1990 through December 2000. RESULTS: The unadjusted prevalences of very low birthweight, low birthweight, and preterm delivery did not substantially vary across birth years. That is, substantial decreased prevalences during the fortification period relative to the period preceding it were not observed. However, analyses that simultaneously adjusted for maternal age, parity, race/ethnicity, education, year of birth, and fortification period revealed the following relative risk ratios (RR) and 95% confidence intervals (CI): RR = 0.91, CI 0.88, 0.94 for very low birthweight, RR = 0.94; 95% CI 0.93, 0.96 for low birthweight, and RR = 0.96; 95% CI 0.94, 0.97 for preterm delivery. CONCLUSION: Findings indicate small reductions in prevalences of these outcomes associated with the timing of fortification of the U.S. food supply.

Adult↗

Early detection of folic acid deficiency in elderly patients.

Folic acid deficiency is very common in elderly patients who have a mean red cell volume greater than 94 fl. Eighteen out of 40 elderly patients with red cell macrocytosis who initially had normal red cell folate and serum B12 levels subsequently developed folic acid deficiency.

Aged↗

Knowledge and use of peri-conceptional folic acid among antenatal patients.

Peri-conceptional folic acid can prevent more than half of all neural tube defects (NTDs). A cross-sectional interviewer administered study was undertaken among 300 women attending their first antenatal appointment in the three major Dublin maternity hospitals. The aim of the study was to monitor knowledge and behaviour with respect to peri-conceptional folic acid among antenatal patients. There was a 98% (295/300) response rate. 53.6% (158/295) had heard of folic acid. Such knowledge was significantly associated with age over 30 years (p < 0.001), a planned pregnancy (p < 0.001) and being married (p < 0.001). The majority (58.2%) found out about folic acid from lay sources such as friends or the media. One eighth (12.9%, 38/295) had been advised to take folic acid before pregnancy, the majority (58.3%, 21/38) having been advised by doctors. 21% (62/295) knew that it prevented spina bifida. 5.8% (17/295) had taken it before becoming pregnant. Taking folic acid before pregnancy was significantly associated with having a planned pregnancy (p < 0.005) and being married (p < 0.005). This study highlights the poor impact of health promotion campaigns to date and provides a challenge to health professionals.

Adolescent↗