IRON DEFICIENCY AND ITS RELATION TO FOLIC-ACID STATUS IN PREGNANCY: RESULTS OF A CLINICAL TRIAL.
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BACKGROUND: Nuevo León is a state in northeastern Mexico, near the border of Texas. Mean mortality rate from 1996-98 due to anencephaly cases was 0.6/1,000. In 1999 a surveillance program for the registry and prevention of neural tube defects (NTD) cases was initiated. METHODS: Cases were obtained from hospitals and OB-GYN clinics by immediate notification, death certificates, or fetal death registries. Only isolated cases of NTD were included. In August 1999 a folic acid campaign was initiated with the free distribution of the vitamin to low-income women with a recommendation to take a 5.0-mg pill once a week. Number of cases and rates from 1999 to 2001 were compared (chi(2) test). RESULTS: After 2 years there has been a significant reduction in the number of cases and rates. In 1999 there were 95 NTD cases and in the years 2000 and 2001 there were only 59 and 55 respectively (P < 0.001). NTD rate decreased from 1.04/1,000 in 1999 to 0.58/1,000 in 2001. Anencephaly and spina bifida rates decreased from 0.55/1,000 to 0.29/1,000 and from 0.47/1,000 to 0.22/1,000 respectively, from 1999-2001. Decrease of female cases was higher than male cases for both phenotypes. CONCLUSION: After 2 years there was a 50% decrease in the incidence of anencephaly and spina bifida cases with a significant reduction of infant mortality and disability. These results encourage us to propose the use of a single tablet of 5.0-mg of folic acid per week as an alternative to supplementation on a daily basis.
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The growth of 73 erythroblastotic infants (18 mild, 19 moderate, and 36 severe) was followed. In all three grups the average centiles for weight rose during the first half of the year. There was a fall in centiles during the second half of the year in 35 of 55 infants, 17 of them dropping below their birth centiles. Throughout the first year of life there was a strong correlation between serum folate of 8 mug/1 or more and rising weight centiles, and 5 mug/1 or less and falling centiles. None of the infants had macrocytic anaemia and their haemoglobin level rose even when their weight gain fell below the expected rate. It is suggested that in some erythroblastotic infants a shortage of folic acid may be a limiting factor for a normal growth rate.
Liver microsomal suspensions from pregnant and nonpregnant Sprague-Dawley rats were assayed for NADPH-dependent metabolism of phenytoin to the hydroxylated products, 5-(rho-hydroxyphenyl)-5-phenylhydantoin (rhoHPPH) and 5-(3,4-dihydroxy-1,5-cyclohexadien-1-yl)5-phenylhydantoin (H2DIOL). UDP-glucuronic acid-dependent glucuronyltransferase activity for conjugating rhoHPPH was also measured. The specific activity for formation of rhoHPPH decreased by 35% in 21-day pregnant rats compared with nonpregnant rats, whereas specific activity for production of H2DIOL was increased approximately 2-fold on the 7th and 14th but not the 21st day of pregnancy. Because of a 25% increase in liver weight during pregnancy, the total hepatic phenytoin hydroxylase activity in pregnant rats (day 21) was not significantly different from that of nonpregnant controls. Folic acid treatment during pregnancy prevented the decrease in phenytoin hydroxylase specific activity. The KM for production of either rhoHPPH or H2DIOL was similar (90 micrometer) in pregnant (day 21) and nonpregnant animals. Thus, overall hepatic microsomal enzyme activity for metabolizing phenytoin was not significantly reduced during pregnancy in rats, although the ratio of H2DIOL to rhoHPPH was increased during the first two weeks. Folic acid may play a role in pregnancy-associated changes in phenytoin hydroxylase activity.
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Neural tube defects (NTDs) are common and serious malformations that originate early in pregnancy. In the United States, approximately 4000 pregnancies each year are affected by the two most common NTDs (spina bifida and anencephaly). In 1992, the Texas Department of Health (TDH), with support from a CDC cooperative agreement, implemented the Texas Neural Tube Defect Project (TNTDP), a program of NTD surveillance and risk-reduction activities in the 14 counties that border Mexico. The project was initiated in response to an anencephaly cluster identified during 1990-1991 in Brownsville (Cameron County), Texas (1). Whether the high anencephaly rate (19.7 per 10,000 live births) was unique to Cameron County or was characteristic of the entire border was unknown. This report summarizes NTD surveillance rates for the 14 Texas-Mexico border counties for 1993-1998 and presents preliminary results of TNTDP efforts to prevent the recurrence of NTDs by providing folic acid to high-risk women. Findings indicate that the baseline rate along the border is high (13.4 per 10,000 live births) and largely reflects the rate among Hispanics (13.8). Although a longer period is needed to obtain definitive results, folic acid appears to be effective for reducing the risk for NTD recurrence in Hispanics.
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The folic acid content of vegetables (including potatoes) and fruits was determined by means of high-performance liquid chromatography (HPLC). Free folate (monoglutamate forms) and total folate (monoglutamate+polyglutamate forms) are differentiated. Vegetables contained 27-187 micrograms/100 g and fruits 10-80 micrograms/100 g total folate. The free folate portion ranged from 6.3% to 96.8% (mean 35%) in vegetables and from 11.6% to 89.0% (mean 56%) in fruits. In addition, the results of the quantification of the main folate derivatives tetrahydrofolic acid (THF), 5-methyltetrahydrofolic acid (5-CH3-THF) and 5-formyltetrahydrofolic acid (5-CHO-THF) are presented. The mean values were 70% 5-CH3-THF, 20% 5-CHO-THF and 10% THF. Their total, resulting from the addition of pteroylglutamate equivalences, is comparable with the results of microbiological methods reported in the tables of nutritive values.
OBJECTIVE: Our purpose was to assess the incidence of hyperhomocysteinemia in patients with a history of preeclampsia or fetal growth restriction, to evaluate the effects of vitamin supplementation on the methionine loading test, and to study the course of subsequent pregnancies in women with hyperhomocysteinemia and a history of preeclampsia or fetal growth restriction. STUDY DESIGN: A total of 207 consecutive patients with a history of preeclampsia or fetal growth restriction was tested for hyperhomocysteinemia. Thirty-seven were found to be positive and were treated with folic acid and vitamin B6, and 27 had a second methionine loading test after vitamin supplementation. Fourteen patients became pregnant again while receiving vitamins and aspirin. RESULTS: All patients who underwent a methionine loading test after vitamin supplementation had a completely normalized methionine loading test. Of the 14 pregnancies in women receiving vitamins and aspirin, 7 were complicated by preeclampsia. Birth weights were 2867 +/- 648 g compared with 1088 +/- 570 g in the previous pregnancies. CONCLUSIONS: Vitamin B6 and folic acid correct the methionine loading test in patients with hyperhomocysteinemia. Perinatal outcome in patients with a history of preeclampsia or fetal growth restriction and hyperhomocysteinemia appears to be favorable.
The effect of homocysteine-lowering treatment on thrombin generation was investigated in 17 subjects with hyperhomocysteinemia (aged 22-60 years), 11 of whom had symptomatic atherosclerotic vascular disease. All subjects had fasting total homocysteine levels above 16 micromol/L. The formation of thrombin was assessed by measuring thrombin-antithrombin III complexes and prothrombin fragment 1+2 in peripheral venous blood and in the bleeding time blood collected at 30-second intervals from skin incisions on a forearm. All the tests were performed before and after an 8-week treatment with folic acid p.o. 5 mg/day, vitamin B6 p.o. 300 mg/day, and vitamin B12 i.m. 1000 microg given on a weekly basis. Following the 8-week therapy, the median plasma homocysteine concentration became significantly reduced from 20 to 10 micromol/L, while plasma levels of fibrinogen, prothrombin, and antithrombin III as well as activity of protein C, S, and factor VII showed no changes. Vitamin treatment was associated with a significant fall in thrombin-antithrombin III complexes and prothrombin fragment 1+2 concentrations in peripheral venous blood. Bleeding time became prolonged by about 60 seconds. At sites of hemostatic plug formation, plasma concentrations of both thrombin markers significantly decreased. Compared with pretreatment values, significantly less thrombin was produced during the first 3 minutes of bleeding after homocysteine-lowering therapy. In subjects with hyperhomocysteinemia a reduction of plasma fasting homocysteine concentration by folic acid and vitamins B12 and B6 administration is associated with attenuation of thrombin generation both in peripheral blood and at sites of hemostatic plug formation.
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