Pre-conceptional vitamin/folic acid supplementation 2007: the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies
ABSTRACT To provide information regarding the use of folic acid in combination with a multivitamin supplement for the prevention of neural tube defects and other congenital anomalies, so that physicians, midwives, nurses, and other health care workers can assist in the education of women in the pre-conception phase of their health care. OPTION: Supplementation with folic acid and vitamins is problematic, since 50% of pregnancies are unplanned, and women's health status may not be optimal when they conceive.
Folic acid in combination with a multivitamin supplement has been associated with a decrease in specific birth defects.
Medline, PubMed, and Cochrane Database were searched for relevant English language articles published between 1985 and 2007. The previous Society of Obstetricians and Gynaecologists of Canada (SOGC) Policy Statement of November 1993 and statements from the American College of Obstetrics and Gynecology and Canadian College of Medical Geneticists were also reviewed in developing this clinical practice guideline.
The quality of evidence was rated using the criteria described in the Report of the Canadian Task Force on Preventive Health Care.
Promoting the use of folic acid and a multivitamin supplement among women of reproductive age will reduce the incidence of birth defects. The costs are those of daily vitamin supplementation and eating a healthy diet.
1. Women in the reproductive age group should be advised about the benefits of folic acid in addition to a multivitamin supplement during wellness visits (birth control renewal, Pap testing, yearly examination) especially if pregnancy is contemplated. (III-A) 2. Women should be advised to maintain a healthy diet, as recommended in Eating Well With Canada's Food Guide (Health Canada). Foods containing excellent to good sources of folic acid are fortified grains, spinach, lentils, chick peas, asparagus, broccoli, peas, Brussels sprouts, corn, and oranges. However, it is unlikely that diet alone can provide levels similar to folate-multivitamin supplementation. (III-A) 3. Women taking a multivitamin containing folic acid should be advised not to take more than one daily dose of vitamin supplement, as indicated on the product label. (II-2-A) 4. Folic acid and multivitamin supplements should be widely available without financial or other barriers for women planning pregnancy to ensure the extra level of supplementation. (III-B) 5. Folic acid 5 mg supplementation will not mask vitamin B12 deficiency (pernicious anemia), and investigations (examination or laboratory) are not required prior to initiating supplementation. (II-2-A) 6. The recommended strategy to prevent recurrence of a congenital anomaly (anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart disease, limb defect, urinary tract anomaly, hydrocephalus) that has been reported to have a decreased incidence following preconception / first trimester folic acid +/- multivitamin oral supplementation is planned pregnancy +/- supplementation compliance. A folate-supplemented diet with additional daily supplementation of multivitamins with 5 mg folic acid should begin at least three months before conception and continue until 10 to 12 weeks post conception. From 12 weeks post-conception and continuing throughout pregnancy and the postpartum period (4-6 weeks or as long as breastfeeding continues), supplementation should consist of a multivitamin with folic acid (0.4-1.0 mg). (I-A) 7. The recommended strategy(ies) for primary prevention or to decrease the incidence of fetal congenital anomalies will include a number of options or treatment approaches depending on patient age, ethnicity, compliance, and genetic congenital anomaly risk status. OPTION A: Patients with no personal health risks, planned pregnancy, and good compliance require a good diet of folate-rich foods and daily supplementation with a multivitamin with folic acid (0.4-1.0 mg) for at least two to three months before conception and throughout pregnancy and the postpartum period (4-6 weeks and as long as breastfeeding continues). (II-2-A) OPTION B: Patients with health risks, including epilepsy, insulin dependent diabetes, obesity with BMI >35 kg/m2, family history of neural tube defect, belonging to a high-risk ethnic group (e.g., Sikh) require increased dietary intake of folate-rich foods and daily supplementation, with multivitamins with 5 mg folic acid, beginning at least three months before conception and continuing until 10 to 12 weeks post conception. From 12 weeks post-conception and continuing throughout pregnancy and the postpartum period (4-6 weeks or as long as breastfeeding continues), supplementation should consist of a multivitamin with folic acid (0.4-1.0 mg). (II-2-A) OPTION C: Patients who have a history of poor compliance with medications and additional lifestyle issues of variable diet, no consistent birth control, and possible teratogenic substance use (alcohol, tobacco, recreational non-prescription drugs) require counselling about the prevention of birth defects and health problems with folic acid and multivitamin supplementation. The higher dose folic acid strategy (5 mg) with multivitamin should be used, as it may obtain a more adequate serum red blood cell folate level with irregular vitamin / folic acid intake but with a minimal additional health risk. (III-B) 8. The Canadian Federal Government could consider an evaluation process for the benefit/risk of increasing the level of national folic acid flour fortification to 300 mg/100 g (present level 140 mg/100 g). (III-B) 9. The Canadian Federal Government could consider an evaluation process for the benefit/risk of additional flour fortification with multivitamins other than folic acid. (III-B) 10. The Society of Obstetricians and Gynaecologists of Canada will explore the possibility of a Canadian Consensus conference on the use of folic acid and multivitamins for the primary prevention of specific congenital anomalies. The conference would include Health Canada/Congenital Anomalies Surveillance, Canadian College of Medical Geneticists, Canadian Paediatric Society, Motherisk, and pharmaceutical industry representatives.
This is a revision of a previous guideline and information from other consensus reviews from medical and government publications has been used.
The Society of Obstetricians and Gynaecologists of Canada.
- SourceAvailable from: Emanuela Scolamiero
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- "In addition, the higher incidence of infertility, spontaneous abortion, preterm and low weight newborn were shown to be associated to vitamin B 12 deficiency, confirming the importance of multivitamin and, mostly, vitamin B 12 supplementation for women . Blood concentrations of propionyl carnitine (C3), arising from the excess of propionyl-CoA, homocysteine (Hcy) and methylmalonic acid (MMA) increase in cobalamin deficiency; the accumulation of these metabolites anticipates hematological and neurological signs. "
ABSTRACT: Objectives Besides the inherited form, vitamin B12 deficiency may be due to diet restrictions or abnormal absorption. The spread of newborn screening programs worldwide has pointed out that non inherited conditions are mainly secondary to a maternal deficiency. Aim of our work was to study seven cases of acquired vitamin B12 deficiency detected during our newborn screening project. Moreover, we aimed to evaluate vitamin B12 and related biochemical parameters status on delivering female to verify the consequences on newborns of eventually altered parameters. Design & Methods 35000 newborns were screened; those showing altered propionyl carnitine (C3) underwent second-tier test for methylmalonic acid (MMA) on dried blood spot (DBS). Subsequently, newborns positive to the presence of MMA on DBS and their respective mothers underwent further tests: serum vitamin B12, holo-transcobalamin (Holo-TC), folate and homocysteine; newborns were also tested for urinary MMA content. A control study was conducted on 203 female that were tested for the same parameters when admitted to hospital for delivery. Results Approximately 10 % of the examined newborns showed altered C3. Among these, seven cases of acquired vitamin B12 deficiency were identified (70 % of the MMA-positive cases). Moreover, our data show an high frequency of vitamin B12 deficiency in delivering female (approximately 48 % of examined pregnants). Conclusions We suggest to monitor vitamin B12 and Holo-TC until delivery and to reconsider the reference interval of vitamin B12 for a better identification of cases at risk. Finally, newborns from mothers with low or borderline levels of vitamin B12 should undergo second-tier test for MMA; in the presence of MMA they should be supplemented with vitamin B12 to prevent adverse effects related to vitamin B12 deficiency.Clinical Biochemistry 09/2014; 47(18). DOI:10.1016/j.clinbiochem.2014.08.020 · 2.28 Impact Factor
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- "The standard recommendation for the recurrence prevention of NTDs and to prevent their occurrence in epileptic and diabetic mothers is to take a higher dose of FA, 4–5 mg/day . Furthermore, in 2007 the Canadian Recommendations also included obesity (BMI >35) as a health risk and recommended "the higher dose FA strategy (5 mg)" in patients with a history of poor compliance with medications and additional lifestyle issues of variable diet, no consistent birth control, and alcohol, tobacco, and recreational non-prescription drugs use [120,121]. In particular, the use of FA supplements might (partially) neutralize the adverse effects of smoking on DNA methylation, since folate provides methyl groups for the synthesis of methionine and plays a critical role in homocysteine metabolism [122-124]. "
ABSTRACT: BackgroundIn 2010 a Cochrane review confirmed that folic acid (FA) supplementation prevents the first- and second-time occurrence of neural tube defects (NTDs). At present some evidence from observational studies supports the hypothesis that FA supplementation can reduce the risk of all congenital malformations (CMs) or the risk of a specific and selected group of them, namely cardiac defects and oral clefts. Furthermore, the effects on the prevention of prematurity, foetal growth retardation and pre-eclampsia are unclear.Although the most common recommendation is to take 0.4 mg/day, the problem of the most appropriate dose of FA is still open.The aim of this project is to assess the effect a higher dose of peri-conceptional FA supplementation on reducing the occurrence of all CMs. Other aims include the promotion of pre-conceptional counselling, comparing rates of selected CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age, abruptio placentae.Methods/DesignThis project is a joint effort by research groups in Italy and the Netherlands. Women of childbearing age, who intend to become pregnant within 12 months are eligible for the studies. Women are randomly assigned to receive 4 mg of FA (treatment in study) or 0.4 mg of FA (referent treatment) daily. Information on pregnancy outcomes are derived from women-and-physician information.We foresee to analyze the data considering all the adverse outcomes of pregnancy taken together in a global end point (e.g.: CMs, miscarriage, pre-eclampsia, preterm birth, small for gestational age). A total of about 1,000 pregnancies need to be evaluated to detect an absolute reduction of the frequency of 8%. Since the sample size needed for studying outcomes separately is large, this project also promotes an international prospective meta-analysis.DiscussionThe rationale of these randomized clinical trials (RCTs) is the hypothesis that a higher intake of FA is related to a higher risk reduction of NTDs, other CMs and other adverse pregnancy outcomes. Our hope is that these trials will act as catalysers, and lead to other large RCTs studying the effects of this supplementation on CMs and other infant and maternal outcomes.Trial registrationItalian trial: ClinicalTrials.gov Identifier: NCT01244347.Dutch trial: Dutch Trial Register ID: NTR3161.BMC Pregnancy and Childbirth 05/2014; 14(1):166. DOI:10.1186/1471-2393-14-166 · 2.15 Impact Factor
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- "A relevant scientific literature supports the role of FA in protecting against both the first occurrence [17, 18] and the recurrence [19, 30] of NTDs when used in the periconceptional period. For this reason expert committees worldwide have issued recommendations about supplementation with 0.4–1 mg of FA, or 4-5 mg if at higher risk of having a baby with NTD [19, 31–34], and some countries adopted a policy of food fortification with FA . "
ABSTRACT: Introduction. Folic acid (FA) supplementation is recommended worldwide in the periconceptional period for the prevention of neural tube defects. Due to its involvement in a number of cellular processes, its role in other pregnancy outcomes such as miscarriage, recurrent miscarriage, low birth weight, preterm birth (PTB), preeclampsia, abruptio placentae, and stillbirth has been investigated. PTB is a leading cause of perinatal mortality and morbidity; therefore its association with FA supplementation is of major interest. The analysis of a small number of randomized clinical trials (RCTs) has not found a beneficial role of FA in reducing the rate of PTBs. Aim of the Study. The aim of this review was to examine the results from recent observational studies about the effect of FA supplementation on PTB. Materials and Methods. We carried out a search on Medline and by manual search of the observational studies from 2009 onwards that analyzed the rate of PTB in patients who received supplementation with FA before and/or throughout pregnancy. Results. The results from recent observational studies suggest a slight reduction of PTBs that is not consistent with the results from RCTs. Further research is needed to better understand the role of FA supplementation before and during pregnancy in PTB.03/2014; 2014:481914. DOI:10.1155/2014/481914