孕前补充小剂量叶酸预防胎儿NTD临床探讨

目的:探讨孕前补充小剂量叶酸(斯利安或福施福)在预防胎儿NTD的临床意义。方法:濮阳市计划生育指导中心及濮阳市妇幼保健院2007年12月31日～2009年12月31日收集全市各区领取生育证的60000例待孕妇女中成功受孕者中随机抽取50000例,并于孕前3个月至孕后前3个月每日增补400ug叶酸,与50000例孕妇未服用叶酸者组成对照组,进行孕期彩超产前筛查及尸解结果进行分析。结果:待孕妇女妊娠前后单纯服用400ug叶酸片,可以降低NTD的发生,预防率达到86%以上。结论:待孕妇女孕前3个月至孕后3个月末每日增补400ug叶酸(北大药业提供),可有效降低胎儿NTD的发生,达到优生优育的目的,进一步提高我市出生人口素质。     

Preconceptional and prenatal predictors of folic acid intake in Hungarian pregnant women

Objective

The purpose of the study was to determine demographic, obstetric and pregnancy care related factors of folic acid intake during preconceptional and prenatal period of pregnancy.

Study design

A questionnaire-based retrospective study was delivered at the Department of Obstetrics and Gynecology and Pregnancy Care Centre. The frequency of folic acid intake was measured before and during pregnancy in 349 pregnant women.

Results

Factors influencing preconceptional folic acid consumption were planning of pregnancy, previous infertility therapy, multivitamin intake before pregnancy, and folic acid intake during pregnancy. Probability of taking folic acid during pregnancy increased with age, and decreased with gestational age. Earlier detection of pregnancy corresponded to a higher chance of folic acid intake. Prenatal folic acid intake significantly related to the earlier intake of folic acid, and prenatal multivitamin medication.

Conclusion

It is important to target women who are less likely to take periconceptional folic acid as well as to increase awareness of women of childbearing age in general through an intensive campaign and improved education.     

Periconceptional intake of folic acid and food folate and risks of preterm delivery

We investigated multiple sources of folate and folic acid to determine whether their periconceptional intakes were associated with preterm delivery. Studied were controls from the National Birth Defects Prevention Study delivered September 1998 to December 2005. Telephone interviews were conducted with 5952 (68% of eligible) mothers. Women were queried about intake of vitamin supplements in the 12 weeks before conception through delivery. A version of the Nurse's Health Study food frequency questionnaire was used to assess food sources. Eight percent of infants ( N?=?487) were preterm (<37 weeks). Compared with women who began intake of supplements with folic acid before pregnancy, those who began any time during pregnancy had an ~20% lowered risk of preterm delivery. Lower dietary intakes showed a modest increased risk of preterm delivery: odds ratios were 1.44 (1.01 to 2.04) for lowest quartile intake of folate and 1.27 (0.95 to 1.69) for lowest quartile intake of folic acid compared with the highest. Findings suggest some evidence that folates influenced risks; however, an interpretation of results was also consistent with no association between intake of folates and preterm delivery.     

Fatty acid synthase is a marker of increased risk of recurrence in endometrial carcinoma

PURPOSE: To explore the expression of fatty acid synthase (FAS) and human erythrocyte glucose transporter 1 (GLUT1) in endometrial carcinomas and to detect associations with clinicopathological features and prognosis. FAS and GLUT1 are two molecules involved in energy supply of normal cells. These markers are overexpressed in neoplastic tissues because of their increased necessity of energy. METHODS: Ninety-five patients with endometrial carcinoma were followed-up for an average period of 5 years. FAS and GLUT1 expressions were evaluated by immunohistochemistry on formalin-fixed paraffin-embedded tissues. Staining was determined with a semiquantitative method. Negative controls were obtained from patients submitted to hysterectomy for uterine prolapse. RESULTS: Eighty-five cases were endometrioid, 7 were serous, and 1 was a mucinous carcinoma. Seventy-two cases (75%) were stage I, 12 (13%) were stage II, and 11 (12%) were stage III carcinomas. Sixteen (15%) carcinomas recurred. Nine patients (8%) died for cancer during the follow-up period. FAS expression was observed in 53 cases (56%). GLUT1 expression was observed in 32 (43%) cases. Statistical analysis revealed that FAS (P = 0.04) and stage (P = 0.001) of the disease were the only two independent predictors of recurrence. GLUT1 and other clinicopathologic parameters had no prognostic association. CONCLUSIONS: FAS is a reliable marker of clinically aggressive endometrial carcinomas. The knowledge of FAS expression in endometrial carcinomas is an important finding that may stratify patients into selected groups and determine therapeutic approaches for patient care.     

Supplementation of folic acid in pregnancy and the risk of preeclampsia and gestational hypertension: a meta-analysis

Objectives

We aimed to systematically assess the relationship between folic acid supplementation in pregnancy and risk of preeclampsia and gestational hypertension.

Methods

The relevant studies were included by retrieving the Embase, PubMed and Cochrane library databases. Data extraction was conducted by two investigators independently. The risk ratio (RR) and 95% confidence interval (CI) were used as effect indexes to evaluate the relationship between folic acid supplementation and risk of gestational hypertension or preeclampsia. A subgroup analysis was performed according to the supplementation patterns of folic acid. The homogeneity of the effect size was tested across the studies, and publication biases were examined.

Results

In total, 13 cohort studies and 1 randomized controlled trial study was included, containing 160,562 and 149,320 women with and without folic acid supplementation during pregnancy. Pooled results showed that risk of gestational hypertension was not associated with the supplementation of folic acid. However, folic acid supplementation during pregnancy could significantly reduce the risk of preeclampsia. Moreover, the results of subgroup analysis showed that the decreased preeclampsia risk was associated with supplementation of multivitamins containing folic acid rather than folic acid alone.

Conclusions

Our findings indicate that the supplementation of multivitamins containing folic acid during pregnancy could significantly lower preeclampsia risk.

     

The importance of folic acid

Folic acid is necessary for cell development; for the metabolism of specific biochemical reactions in the body, such as the conversion of homocysteine to methionine; and for the metabolism of specific anticonvulsant drugs. Folic acid has an interrelationship with vitamin B12. A deficiency of folate increases the risk of NTDs, as well as contributing to hyperhomocystinemia, a condition associated with increased cardiovascular disease and NTDs. For the prevention of NTDs, it is recommended that a woman of childbearing age consume a daily folate intake of 400 micrograms; however, the average dietary folate intake is half that amount, and the FDA folate fortification of cereal grains adds only 100 micrograms daily. The woman in her childbearing years does not meet the recommendation with dietary and food fortification. Periconceptional folic acid supplementation is essential, because the neural tube closes 23 to 27 days after conception. Therefore, a multiple vitamin containing folic acid is the practical solution at present if the food fortification is not increased. The bioavailability of folate in the vitamin preparation is approximately double that of dietary folate. Most preparations contain 400 micrograms of folic acid, and if the woman took a multiple vitamin (400 micrograms of folate) in addition to her diet (230 micrograms of folate), she would not exceed 1000 micrograms (1 mg) daily, which is considered the upper limit of daily folate ingestion by dietary fortification and supplementation before the masking of vitamin B12 becomes a concern. However, in this group of patients, pernicious anemia is rare. Regarding cardiovascular disease in men and women, there are no long-term studies showing the benefit of folic acid in reducing the homocysteine level. At present, there are only estimations. However, they should not be ignored. Although it is not the current standard of practice, adding a multiple vitamin containing folic acid to the regimen of men and women starting anticonvulsant medication should be considered in order to prevent the folate lowering observed with such commonly used drugs as PHT and carbamazepine. Women in childbearing years should be on a folic acid supplement when taking an anticonvulsant drug. In general, it appears that all men and women would benefit from increased folate intake. This can be accomplished through vitamin supplementation when there is compliance. However, if the food fortification for folate is increased in the future, then the issue of vitamin supplementation will have to be readdressed.     

Awareness of the role of folic acid, dietary folate intake and plasma folate concentration in Japan

AIM: To investigate awareness of the role of folic acid in the prevention of neural tube defects, dietary intake of folate, and plasma folate concentration. METHODS: Postal questionnaires were collected from 1190 lay female subjects in three different groups and from seven groups of 3067 health-care providers. Dietary folate was investigated by assessing food frequency charts that were kept for 3 days by 245 women, and plasma folate was assessed by analyzing the blood serum of 194 women. RESULTS: Less than 15% of citizens and mothers who had live births knew that there was a link between folic acid and neural tube defects. The exception was with myelodysplastic families, in which awareness was 92%. Awareness among health-care professionals was generally low. The highest level was found in obstetricians-gynecologists (76%) and the lowest in nurses (12%). Dietary folate intake and plasma concentration were highest in pregnant women (356 microg/day and 11.9 ng/mL) and the lowest in student nurses (217 microg/day and 6.8 ng/mL). When the recommended dietary allowance of folate in Japan is taken into consideration, 22% of the non-pregnant women and 71% of the pregnant women did not fulfill the recommended dietary allowance. CONCLUSIONS: Information on the role of periconceptional intake of folic acid is not sufficiently disseminated to young women and health-care professionals alike. Pregnant women should be repeatedly recommended to take folic acid supplements of 400 microg/day.     

Low-dose folic acid supplementation reduces plasma levels of the cardiovascular risk factor homocysteine in postmenopausal women

OBJECTIVE: The aim of our randomized, controlled trial was to verify the effect of folic acid supplementation on homocysteine levels in postmenopausal women. STUDY DESIGN: Thirty-six women were divided randomly into 2 groups as follows: a placebo group (n = 18) and a group receiving 500 microg folic acid per day for 4 weeks (n = 18). To assess concentrations of plasma homocysteine, venous blood samples were taken on enrollment and after 4 weeks of treatment. RESULTS: Mean plasma homocysteine levels were 10.9 +/- 2.7 micromol/L in the placebo group and 7.8 +/- 2.35 micromol/L (P <.01) in the group receiving 500 microg folic acid per day for 4 weeks. The thirds (referred to as tertiles) of women with the highest baseline homocysteine plasma levels showed the greatest reduction in homocysteine, with a mean decrease of 4.35 micromol/L (32%; P <.01), in comparison with a decrease of 3.35 micromol/L (29%; P <.01) in the middle tertile and 1.3 micromol/L (22.4%; P =.09) in the lower tertile. CONCLUSIONS: The results show that low doses of folic acid are associated with a significant reduction in plasma concentrations of homocysteine. The highest initial levels of homocysteine showed the most important reduction after therapy.     

Greater maternal weight and the ongoing risk of neural tube defects after folic acid flour fortification

OBJECTIVE: Maternal obesity is likely a risk factor for neural tube defects (NTDs). By late 1997, it became mandatory in Canada that all refined wheat flour be fortified with folic acid. Because overweight women may consume greater quantities of refined wheat flour, we questioned whether their risk of NTD changed after flour fortification. METHODS: A retrospective population-based study was conducted between 1994 and late 2000. We included all Ontarian women who underwent antenatal maternal screening at 15 to 20 weeks of gestation. Self-declared maternal date of birth, ethnicity, current weight, and the presence of pregestational diabetes mellitus were recorded in a standardized fashion on the maternal screening requisition sheet. The presence of NTDs was systematically detected both antenatally and postnatally. The risk of open NTD was evaluated across maternal weight quartiles and deciles, and an interaction between greater maternal weight and the presence of flour fortification was tested using multiple logistic regression analysis. RESULTS: A total of 292 open NTDs were detected among 420,362 women. The adjusted odds ratio (OR) for NTD was 1.2 (95% confidence interval [CI] 1.1-1.3) per 10-kg incremental rise in maternal weight. Comparing the highest with the lowest quartile of maternal weight, the adjusted OR for NTD was 2.6 (95% CI 1.8-4.0). A similar finding was observed for the highest compared with lowest weight deciles (adjusted OR 3.3, 95% CI 1.7-6.2). The interaction between elevated maternal weight and the presence of folic acid flour fortification was of borderline significance (P = .09). Before fortification, greater maternal weight was associated with a modestly increased risk of NTD (adjusted OR 1.4, 95% CI 1.0-1.8); after flour fortification, this effect was more pronounced (adjusted OR 2.8, 95% CI 1.2-6.6). CONCLUSION: These data emphasize the higher risk of NTD associated with increased maternal weight, even after universal folic acid flour fortification. Beyond periconceptional folic acid use, consideration should be given to testing whether prepregnancy weight reduction is an independent means of preventing NTD. LEVEL OF EVIDENCE: II-2.     

Periconceptional use of folic acid supplements in Oslo

BACKGROUND: Periconceptional supplementation with folic acid has been shown to decrease the occurrence of neural tube defects (NTD). A daily supplement of 400 micro g folic acid from the month before pregnancy and the first 2 to 3 months of pregnancy is recommended in Norway. We wanted to evaluate the use of folic acid supplements among pregnant women in Oslo, and to explore demographic factors that were associated with periconceptional intake. METHODS: All women attending antenatal ultrasound screening at the two main obstetric departments in Oslo during 3 months in 2001 were invited to answer questions regarding folic acid supplementation before and during their present pregnancy. RESULTS: A total of 1541 women (91, 5%) participated in the study, of which 26% were nonwestern immigrants. Only 17% of all women had started the folic acid supplementation preconceptionally (22% of the nonimmigrant vs. 2% of the immigrant population). Folic acid had been used by 58% at some time during the present pregnancy (73% of the nonimmigrant vs. 19% of the immigrant population). Regression analysis demonstrated that the difference in periconceptional use of folic acid between the two population groups could not be explained by registered demographic factors other than immigrant status. CONCLUSIONS: Most pregnant women in Oslo do not use folic acid as recommended and a dramatically low usage is seen among the immigrant population, indicating that more widespread information is necessary. Furthermore, fortification of cereals with folic acid should be considered to secure a sufficient intake of folic acid in all fertile women.     

Prevention of neural tube defects with folic acid

Neural Tube Defects (NTD's) include a large number of congenital malformations produced when the open neural tube presents a very early stages in the development of the human embryo fails to close on or before the first month post conception. NTD's are considered to be one of the most common forms of malformations with varying degrees depending of genetic and environmental conditions. The studies prove that the additional taken of folic acid plays an important role against the NTD's. Numerous studies prove this "B" vitamin has an important protective effect not only for the recurrence of NTD's, but for new cases too. In light of these, in 1992 the US Public Health Services issued the recommendation that all women in child-bearing age should consume at least 0.4 mg (400 micrograms) of folic acid daily.     

Cervical cytology in folic acid deficiency of pregnancy

Abnormal cervical cytology was discovered among pregnant women demonstrating deficient levels of serum folate, neutrophil hypersegmentation, and megaloblastic bone marrow maturation. In a double blind evaluation, the abnormal cells were not seen on smears acquired from a control group of normal pregnant patients. Cytologic preparations obtained later in the developing deficiency state had a greater chance of showing abnormal cytology. Therefore, this cellular change precedes overt folate depletion in pregnancy by many weeks and represents another subclinical manifestation of the disease. With folic acid therapy, the observed cytologic alterations may revert to normal in a period of days. It is apparent that squamous cell alterations in vaginal smears of pregnant patients do not necessarily reflect precancerous lesions. The finding of abnormal cytology in pregnancy, while demanding conventional investigation, should suggest the possibility of associated folic acid deficiency.     

Periconceptional folic acid use among women giving birth at Queen Mary Maternity Hospital in Dunedin

BACKGROUND: The New Zealand Ministry of Health advises that all women planning a pregnancy take a folic acid supplement to reduce the risk of having a neural tube defect (NTD)-affected pregnancy. There is little information available to determine if women are following this advice. OBJECTIVE: The purpose of this study was to determine periconceptional folic acid use among women in the postnatal ward of Queen Mary Maternity Hospital in Dunedin. METHODS: A questionnaire was administered to women in the postnatal ward between 14 November and 22 December 2004. RESULTS: One hundred and six women were interviewed during the study period. Forty women (39%) used folic acid supplements before conception. Sixty-seven women (64%) planned their pregnancy. The proportion of women (P<0.001) who planned their pregnancy (53%) and used folic acid before conception was higher than those who did not (11%). The proportion of women 30 years of age (55%) who took folic acid supplements before conception was higher than women aged 17 to <25 years (10%). CONCLUSION: Despite a lack of a public health campaign in New Zealand, a high proportion of participants, especially those who planned their pregnancy, took folic acid during the periconceptional period. A comprehensive public health campaign is needed to increase folic acid use. Fortification may be required to reach those women who do not plan their pregnancies.