Jogc-dec-07.vp

JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE
No. 201 (Replaces guideline No. 138), December 2007 JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE
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
Objective: To provide information regarding the use of folic acid in
This guideline was prepared by the Genetics Committee of the combination with a multivitamin supplement for the prevention of Society of Obstetricians and Gynaecologists of Canada and The neural tube defects and other congenital anomalies, so that Motherisk Program, The Hospital for Sick Children Toronto, and physicians, midwives, nurses, and other health care workers can approved by the Executive and Council of the Society of assist in the education of women in the pre-conception phase of Obstetricians and Gynaecologists of Canada.
PRINCIPAL AUTHOR
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.
GENETICS COMMITTEE
Outcomes: Folic acid in combination with a multivitamin supplement
R. Douglas Wilson, MD, MSC (Chair), Philadelphia PA has been associated with a decrease in specific birth defects.
Valerie Désilets, MD, Montreal QC Evidence: 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 andGynecology and Canadian College of Medical Geneticists were also reviewed in developing this clinical practice guideline.
Values: The quality of evidence was rated using the criteria
described in the Report of the Canadian Task Force on PreventiveHealth Care.
Benefits, Harms, and Costs: Promoting the use of folic acid and a
multivitamin supplement among women of reproductive age will MOTHERISK
reduce the incidence of birth defects. The costs are those of daily vitamin supplementation and eating a healthy diet.
Recommendations
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, yearlyexamination) 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 Key Words: Folic acid, neural tube defect, prevention, spina bifida,
Canada). Foods containing excellent to good sources of folic acid risk reduction, multivitamin, preconception, birth defects are fortified grains, spinach, lentils, chick peas, asparagus, This guideline reflects emerging clinical and scientific advances as of the date issued and is subject to change. The information
should not be construed as dictating an exclusive course of treatment or procedure to be followed. Local institutions can dictate
amendments to these opinions. They should be well documented if modified at the local level. None of these contents may be
reproduced in any form without prior written permission of the SOGC.
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broccoli, peas, Brussels sprouts, corn, and oranges. However, it is • Option C: Patients who have a history of poor compliance with
unlikely that diet alone can provide levels similar to medications and additional lifestyle issues of variable diet, no folate-multivitamin supplementation. (III-A) consistent birth control, and possible teratogenic substance 3. Women taking a multivitamin containing folic acid should be use (alcohol, tobacco, recreational non-prescription drugs) advised not to take more than one daily dose of vitamin require counselling about the prevention of birth defects and supplement, as indicated on the product label. (II-2-A) health problems with folic acid and multivitaminsupplementation. The higher dose folic acid strategy (5 mg) 4. Folic acid and multivitamin supplements should be widely available with multivitamin should be used, as it may obtain a more without financial or other barriers for women planning pregnancy adequate serum red blood cell folate level with irregular to ensure the extra level of supplementation. (III-B) vitamin / folic acid intake but with a minimal additional health 5. Folic acid 5 mg supplementation will not mask vitamin B12 deficiency (pernicious anemia), and investigations (examination or 8.The Canadian Federal Government could consider an evaluation laboratory) are not required prior to initiating supplementation. (II-2-A) process for the benefit/risk of increasing the level of national 6. The recommended strategy to prevent recurrence of a congenital folic acid flour fortification to 300 mg/100 g (present level anomaly (anencephaly, myelomeningocele, meningocele, oral facial cleft, structural heart disease, limb defect, urinary tract 9.The Canadian Federal Government could consider an evaluation anomaly, hydrocephalus) that has been reported to have a process for the benefit/risk of additional flour fortification with decreased incidence following preconception / first trimester folic multivitamins other than folic acid. (III-B) acid +/- multivitamin oral supplementation is planned pregnancy+/- supplementation compliance. A folate-supplemented diet with 10.The Society of Obstetricians and Gynaecologists of Canada will additional daily supplementation of multivitamins with 5 mg folic explore the possibility of a Canadian Consensus conference on acid should begin at least three months before conception and the use of folic acid and multivitamins for the primary prevention of continue until 10 to 12 weeks post conception. From 12 weeks specific congenital anomalies. The conference would include post-conception and continuing throughout pregnancy and the Health Canada/Congenital Anomalies Surveillance, Canadian postpartum period (4–6 weeks or as long as breastfeeding College of Medical Geneticists, Canadian Paediatric Society, continues), supplementation should consist of a multivitamin with Motherisk, and pharmaceutical industry representatives.
Validation: This is a revision of a previous guideline and information
7. The recommended strategy(ies) for primary prevention or to from other consensus reviews from medical and government decrease the incidence of fetal congenital anomalies will include a number of options or treatment approaches depending on patient Sponsor: The Society of Obstetricians and Gynaecologists of
age, ethnicity, compliance, and genetic congenital anomaly risk • Option A: Patients with no personal health risks, planned
J Obstet Gynaecol Can 2007;29(12):1003–1013 pregnancy, and good compliance require a good diet offolate-rich foods and daily supplementation with a multivitamin INTRODUCTION
with folic acid (0.4–1.0 mg) for at least two to three monthsbefore conception and throughout pregnancy and thepostpartum period (4–6 weeks and as long as breastfeeding It is estimated that at least 5% of babies are born with some serious congenital anomaly1; 2% to 3% will have • Option B: Patients with health risks, including epilepsy, insulin
anomalies that can be recognized prenatally by non-invasive dependent diabetes, obesity with BMI >35 kg/m2, family history screening test, through invasive diagnostic testing, or at of neural tube defect, belonging to a high-risk ethnic group(e.g., Sikh) require increased dietary intake of folate-rich foods birth, and 2% will have developmental or functional anom- and daily supplementation, with multivitamins with 5 mg folic alies recognized during the first year of life.1 Folic acid acid, beginning at least three months before conception andcontinuing until 10 to 12 weeks post conception. From ingested prior to conception and during the early stages of 12 weeks post-conception and continuing throughout pregnancy plays a role in preventing neural tube defects and pregnancy and the postpartum period (4–6 weeks or as longas breastfeeding continues), supplementation should consist of has been associated with preventing other congenital anom- a multivitamin with folic acid (0.4–1.0 mg). (II-2-A) alies.2 Folic acid helps produce and maintain new cells; it isimportant during times of rapid cell division and growth(i.e., embryonic and fetal periods). Public health initiativesto increase the awareness and prevention of birth defectshave focused on folic acid intake for the prevention of ABBREVIATIONS
NTDs, but several studies have indicated that taking multi-vitamins containing folic acid during the periconception period can reduce the risk of other conditions such as heart defects,2–5 urinary tract anomalies,5,6 oral facial clefts,2,7–9 limb defects,2 and pyloric stenosis.3 It has been estimated that as many as half of all birth defects can be prevented if MTHFR 5.10-methylenetetrahydrofolate reductase women of childbearing age consume an adequate amount of folic acid, either by eating sufficient quantities of food that are fortified with folic acid or by taking vitaminsupplements.10–12 The objective of this clinical practice 1004 l DECEMBER JOGC DÉCEMBRE 2007
Pre-conceptional Vitamin/Folic Acid Supplementation 2007 Table 1. Key to evidence statements and grading of recommendations, using the ranking of the Canadian Task
Force on Preventive Health Care
Evidence obtained from at least one properly randomized A. There is good evidence to recommend the clinical preventive II-1: Evidence from well-designed controlled trials without B. There is fair evidence to recommend the clinical preventive II-2: Evidence from well-designed cohort (prospective or C. The existing evidence is conflicting and does not allow to retrospective) or case-control studies, preferably from more make a recommendation for or against use of the clinical preventive action; however, other factors may influencedecision-making II-3: Evidence obtained from comparisons between times or places with or without the intervention. Dramatic results in D. There is fair evidence to recommend against the clinical uncontrolled experiments (such as the results of treatment with penicillin in the 1940s) could also be included in this E. There is good evidence to recommend against the clinical III: Opinions of respected authorities, based on clinical There is insufficient evidence (in quantity or quality) to make experience, descriptive studies, or reports of expert a recommendation; however, other factors may influence *The quality of evidence reported in these guidelines has been adapted from The Evaluation of Evidence criteria described in the Canadian Task Forceon Preventive Health Care.13†Recommendations included in these guidelines have been adapted from the Classification of Recommendations criteria described in the The CanadianTask Force on Preventive Health Care.13 guideline update is to give women’s health care providers contribution in different regions, but an estimated 1% new data/information about the use of folic acid with a recurrence with folic acid prophylaxis is given.1,10,17,20–29 multivitamin supplement for the prevention of neural tube In Canada, the birth prevalence of NTDs has declined from defects and other congenital anomalies. The quality of evi- a rate of 10.0 per 10 000 live births in 1991 to 5.8 per 10 000 dence reported in this guideline has been described using total births (live births and stillbirths) in 1999.28 Reasons the evaluation of evidence criteria of the Canadian Task given for this decrease in the rate of NTDs include an Force on Preventive Health Care (Table 1).13 increased use of tests (ultrasound, maternal serum screen-ing) and subsequent pregnancy termination, the fortifica- Peer-reviewed articles, government publications (Health tion of food with folic acid, and increased vitamin Canada, Preconception Health 200214; NIH Clinical Cen- supplementation.28 The rate of NTDs tends to be higher in ter, Office of Dietary Supplements 2005),15 the 2003 Soci- Eastern Canada than in Western Canada.30,31 Women of ety of Obstetricians and Gynaecologists of Canada (SOGC) certain ethnic groups, including Celtic32 and Sikh,33 as well Policy Statement, The Use of Folic Acid for Prevention of as women from Northern China,34 are at a higher risk of Neural Tube Defects,16 and statements from The American having children with NTDs.30–34 It remains unclear whether College of Obstetrics and Gynecology17 and Canadian Col- these risks vary because of genetic predisposition, cultural lege of Medical Geneticists,18 were reviewed in developing dietary preferences, or a combination of these factors.
Multifactorial inheritance30,35,36 is the most common cause NEURAL TUBE DEFECTS: INCIDENCE AND INHERITANCE
of NTDs, but monogenic, chromosomal, and teratogeniccauses have specific effects that have not been studied in Neural tube defects are severe birth anomalies that occurs association with folic acid deprivation or supplementation because of a lack of neural tube closure at either the upper (Table 2).19 The prevalence of aneuploidy and additional or lower end in the third to fourth week after conception anatomical abnormalities in fetuses with open spina bifida (day 26 to day 28 post conception).19 The incidence was reviewed using Utah Birth Defect Network data.37 (0.5–4.0/1000 births) of NTDs varies across North Ameri- Chromosome results were known in 45 of 51 cases of open can regions and a decreasing incidence (1.58 per 1000 births spina bifida, with six cases (13%) of aneuploidy. Additional to 0.86 per 1000 births) is shown with folic acid major anatomic abnormalities were present in four of the supplementation.20 Recurrence risks reflect the genetic six cases and included cardiac, renal, omphalocele, brain, DECEMBER JOGC DÉCEMBRE 2007 l 1005
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Table 2. Recognized conditions associated with neural tube defects19
Miller-Dieker syndrome (deletion 17p13.3) CHILD syndrome (mutation NSDHL gene X q 28) Fetal valproate/carbamazepine/maternal epilepsy syndrome Maternal pre-existing diabetes (pre-conception) and bilateral oral clefting. There was a 4% risk of aneuploidy • use of folic acid antagonists (amniopterin, in sonographically isolated spina bifida cases within this Non-invasive prenatal diagnostic testing by ultrasound andmaternal serum screening,44 which should be offered at 16 PRENATAL DIAGNOSIS
to 20 weeks’ gestation and 15 to 20 weeks’ gestation, respec-tively, will identify 95% to 100% of NTDs (anencephaly, All pregnant women should be offered routine screening 100%; spina bifida, 95%). Ultrasound imaging47,48 of the for NTDs with specific and appropriate timing.38–44 Folic cranium and the identification of cranial scalloping (lemon acid supplementation will not eliminate but will reduce the sign) and cerebellar crowding (banana sign) in association risk of NTDs.45 Women with an increased risk for a preg-nancy complicated by NTDs often have a history of with mild ventriculomegaly is diagnostic of an openmyelomeningocele if, even with improved ultrasound tech- • a previous fetus or child with an NTD16,17,43,46 nique and resolution, a defect is not easily identifiable in the • a first-, second-, or third-degree relation with an spine because of the level of the spinal defect, fetal position, or maternal habitus. After 15 weeks of pregnancy, invasive • pre-existing maternal diabetes as well as prenatal diagnostic testing with ultrasound-guided amnio- insulin-dependent (type 1) diabetes16,43,46 centesis can evaluate the fetal karyotype and measure • epilepsy and the ingestion of valproic acid or amniotic fluid alpha fetoprotein and acetylcholinesterase to carbamazepine for seizure control16,43,46 assist in differentiating between open or closed lesions.44 1006 l DECEMBER JOGC DÉCEMBRE 2007
Pre-conceptional Vitamin/Folic Acid Supplementation 2007 FOLIC ACID AND PREVENTION
5 ng/mL, about 0.2 mg/day (the US level of folic acidfortification) would be expected to reduce NTDs by A Health Canada document,14 Preconception Health: Folic Acid about 20%; a similar effect can be expected from the for Primary Prevention of Neural Tube Defects–a Resource Document current British recommendation (0.24 mg/day). An for Health Professionals 2002, states that, from the human data, increase of 0.4 mg/day would reduce risk by about it is clear that periconceptional use of supplements contain- 36%, of 1 mg/day by 57%, and taking a 5-mg tablet ing folic acid substantially reduces the risks of occurrence (first affected pregnancy) and recurrence (additionalaffected pregnancies) of neural tube defects. Similar sum- Wald et al.56 concluded that folic acid fortification levels mary information is available from the National Institutes should be increased accordingly and that women planning a of Health Clinical Center document, Dietary Supplement Fact pregnancy should take 5 mg folic acid tablets daily instead of the 0.4 mg dose currently recommended. Some of thesubsequent letters to the editor showed support 57,58 for the Women should be advised to maintain a healthy diet, as rec- concept, although others recommended caution.59 This ommended in Eating Well With Canada’s Food Guide (Health increased dosage of folic acid has not yet been widely imple- Canada).49 Good or excellent sources of folic acid include mented for preconception populations.
broccoli, spinach, peas, Brussels sprouts, corn, lentils, andoranges.
Folic acid supplementation reduces NTDs,60–66 but newdata (2006) for Ontario analyzed by Motherisk indicated A randomized trial50 for the prevention of primary occur- that 40% of females in the reproductive age had RBC folate rence found periconceptional vitamin supplementation (12 below 900 nmol/L and half of these (20%) were below vitamins including 0.8 mg of folic acid, 4 minerals, 3 trace 700 nmol/L, with 900 nmol/L or greater being necessary elements) decreased the incidence of a first occurrence of for maximum protection against NTDs. On the basis of NTD. Previous case–control studies had provided support- this information, it can be estimated that 200 000 pregnant ive or equivocal evidence that pregnant women using multi- Canadian women are suboptimally protected against NTD vitamins containing folic acid or dietary folic acid had a each year.67 Other investigators have indicated that women lower risk of occurrence NTDs than women not taking attempting pregnancy will achieve a level of 900 nmol/L with a supplementation dosage of 0.4 mg folic acid.68 Addi- With respect to prevention of recurrence of NTDs, a ran- tional information indicates that only 28% of Canadian domized double-blind clinical trial45 involving 1195 com- women took folic acid or a multivitamin containing folic pleted high-risk pregnancies women from 33 centres acid and that supplementation was not used the same reported 72% fewer cases of NTDs among the offspring of way/to the same extent in all ethnic groups.69 Other strate- the folic acid supplementation group than among the off- gies have been proposed to influence and improve folic acid spring of controls who did not take folic acid supplementation.45 The recurrence rate decreased from3.5% to 1% for women randomized to receive 4 mg folic FOLIC ACID AND VITAMIN SUPPLEMENTATION AND
acid supplementation prior to pregnancy and throughout BIRTH DEFECTS OTHER THAN NEURAL TUBE DEFECTS
the first six weeks of pregnancy. The results in the group Folic acid in combination with multivitamin supplements taking vitamins without folic acid were similar to the results has been shown to reduce other congenital anomalies, such in the group not taking vitamin supplementation, with as heart defects,2–5 urinary tract anomalies,5–6 oral facial clefts,33–35, 73,74 limb defects,2 and pyloric stenosis.3 Wald et al.56 evaluated the dose of folic acid required to A recent review has analyzed the published literature maximize the already known benefit of folic acid in prevent- regarding the prevention of congenital anomalies with ing NTDs. The study analyzed published data from 13 stud- periconceptional folic acid supplementation.75 Meta- ies of folic acid supplementation on serum folate analysis of prenatal multivitamin supplementation contain- concentrations, as well as results from a large cohort study ing folic acid and the rates of congenital anomalies has on the risk of NTDs according to serum folate.
Such results predict that the preventive effect is • NTD (OR case-control 0.67; [0.58–0.77] cohort/RCT greater in women with low serum folate than in those with higher concentrations. The results have also • Cardiovascular defects (OR case-control 0.78; [0.67– been used to predict direct observations from large randomised trials and the effect of food fortification.
• Limb defects (OR case-control 0.48; [0.30–0.76] From a typical western background serum folate of DECEMBER JOGC DÉCEMBRE 2007 l 1007
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Table 3. Interactions: Drugs and folic acid14–17,46,63,84
• Cleft palate (OR case-control 0.76; [0.62–0.93] states that further investigation of the potential cancer pro- moting effects of exposure to folic acid in susceptible peo- • Oral clefts with or without cleft palate (OR ple is desirable before mandatory fortification starts. Folic case-control 0.63; [0.54–0.73] cohort/RCT 0.58 [0.28– acid has not been shown to promote breast cancer81 or to prevent82 it. Ovarian cancer studies83 suggest (but not with • Urinary tract anomalies (OR case-control 0.48; [0.30– statistical significance) that relatively high dietary folate intake may be associated with a reduction in ovarian cancer risk among woman with high alcohol and methionine Congenital hydrocephalus (OR case-control 0.37; [0.24–0.56] cohort/RCT 1.54[0.53–4.50] ) No effects were shown in preventing Down syndrome, FOLIC ACID METABOLISM
pyloric stenosis, undescended testis, or hypospadias.75 Thismeta-analysis is limited to studies with the combined multi- The risk of toxicity from folic acid intake from supplements vitamin-folic acid treatment and excludes studies that did and/or fortified foods is low. It is a water soluble vitamin, not report malformation rates, focused on folic acid alone, so any excess intake is usually excreted in urine.
and did not contain a control group. Additional studies sup-port these associations. 76,77 Medical conditions that increase the need for folic acid orresult in increased excretion of folic acid include Other pediatric benefits have been identified following pre- pregnancy/lactation, alcohol abuse, malabsorption (gastric natal multivitamin supplementation before and in early bypass patients may be at risk), renal dialysis, liver disease, pregnancy.78,79 Maternal use of prenatal multivitamins is associated with a decreased risk for pediatric brain tumours(OR 0.73, [0.60–0.88]), neuroblastoma (0.53, [0.42–0.68]), Serum folate acid levels may be affected by the metabolism of and leukemia (ALL) (OR 0.61, [0.50–0.74]).78 It was stated other medications, including antineoplastic agents, epileptic that it is not known which constituent(s) among the multivi- medications, and other medications (Table 3).14–17,46,84 tamins confers this protective effect.
OTHER VITAMIN ISSUES
MATERNAL ISSUE WITH FOLIC ACID FORTIFICATION
Multivitamins should have vitamin A as beta-carotene A debate entitled Should Folic Acid Be Mandatory80 was rather than as retinol. Excess retinol (10 000 IU; 3300 RE) recently published. The “yes” opinion states a clear benefit on a daily basis may cause birth defects.85 For this reason, in preventing neural tube defects, with substantial evidence women should not take more than one daily dose, as indi- on safety and no valid indication of harm. The “no” opinion 1008 l DECEMBER JOGC DÉCEMBRE 2007
Pre-conceptional Vitamin/Folic Acid Supplementation 2007 FOLIC ACID FOOD FORTIFICATION
folate levels with a selected diet, supplemented foods, andcompliant daily oral folic acid supplementation (0.4–1.0 In Canada since 1998, in an effort to try and reduce the rate mg), but this situation may represent less than 15% to 20% of NTDs, there has been mandatory folic acid fortification of white flour, enriched pasta, and cornmeal. The overallbenefit of fortification in reducing NTDs has been deter- The combination of multivitamin and folic acid can be mined.14,15,45,74–77,86 The most recent Canadian data have taken as oral supplementation or single combined pill (mul- shown that the prevalence of neural tube defects decreased tivitamin with 0.4–1.0 mg or 5 mg) or as a multiple tablet from 1.58 per 1000 births before fortification to 0.86 per option (multivitamin with 0.4–1.0 mg; for higher folic acid 1000 births during the full fortification period (1998–2002), doses, add single 1 mg folic acid tablets as necessary). Oral a 46% reduction (95% CI, 40–51). The decrease was greater supplementation may be variable because of compliance for spina bifida than for anencephaly and encephalocele.20 issues with daily oral tablet use (nausea, “forgot,” “don’t liketo take pills”).98,99 POTENTIAL HARM OF FOLIC ACID INTAKE
Folic acid, in a 0.4 to 1.0 mg daily dose12–15,46, 87 is not known Conception data indicate that 50% of pregnancies are to cause demonstrable harm to the developing fetus or the unplanned with no additional oral supplement (multi- pregnant woman. Folic acid is water soluble and excess is vitamin with folic acid) being used. The options described excreted through the urinary tract. Patients aged 50 years or over are at greater risk for vitamin B12 deficiency than youn-ger women, but this is not the age group in which pregnancy TREATMENT OPTIONS
usually occurs. A recent Australian study88 found that highserum folate did not mask the macrocytosis of cobalamin Option A: Patients with no personal health risks, planned
deficiency of pernicious anemia. Macrocytosis appears to pregnancy, and good compliance require a good diet of retain its value as a marker of cobalamin deficiency in peo- folate-rich foods and daily supplementation with a multi- ple with serum folate concentrations above the population vitamin with folic acid (0.4–1.0 mg) for at least two to three average. The folic acid dose of 5 mg has not been reported months before conception and throughout pregnancy and to have maternal or fetal risks.55–63,89 the postpartum period (4–6 weeks and as long as breast-feeding continues). (II-2-A) Folic acid and multivitamin supplementation is possiblyassociated with an increased incidence of twins.12,90–92 Option B: Patients with health risks, including epilepsy,
There are some concerns about folic acid supplementation insulin dependent diabetes, obesity with BMI > 35 kg/m2, being associated with an increased risk of neoplasia or pos- family history of neural tube defect, belonging to a high-risk sible exacerbation of pre-existing colorectal cancer.
ethnic group (e.g., Sikh) require increased dietary intake of Increased rates for colorectal cancer have been observed folate-rich foods and daily supplementation, with multi- since food fortification was introduced in Canada and vitamins with 5 mg folic acid, beginning at least three United States. This effect has not been proven but needs to months before conception and continuing until 10 to 12 weeks post conception. From 12 weeks post-conceptionand continuing throughout pregnancy and the postpartum This guideline recommends the use of folic acid in the period (4–6 weeks or as long as breastfeeding continues), perinatal period; the use of folic acid is therefore limited to supplementation should consist of a multivitamin with folic usually recurrent 6- to 12-month time periods. Other long-term uses for folic acid in the clinical context (alcohol-ics, anemia, liver disease, kidney disease, malabsorption, Option C: Patients who have a history of poor compliance
cardiac disease, cancer treatment) are not discussed. Aller- with medications and additional lifestyle issues of variable gic responses to folic acid are rare, but may include ery- diet, no consistent birth control, and possible teratogenic thema, rash, itching, general malaise, and bronchospasm.94 substance use (alcohol, tobacco, recreational non-prescription drugs) require counselling about the preven- CURRENT SITUATION IN CANADA
tion of birth defects and health problems with folic acid and In Canada, flour is fortified with folic acid. Its introduction multivitamin supplementation. The higher dose folic acid coincided with an observed decrease in NTDs in strategy (5 mg) with multivitamin should be used, as it may liveborns,20,95 but this may be related to prenatal diagno- obtain a more adequate serum red blood cell folate level sis/termination rather than fortification alone.96,97 Women with irregular vitamin / folic acid intake but with a minimal who are motivated may be able to reach appropriate RBC DECEMBER JOGC DÉCEMBRE 2007 l 1009
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diet with additional daily supplementation of multivita- Folic acid (in the diet and/or in a supplement)with a multi- mins with 5 mg folic acid should begin at least three vitamin has been proven to decrease or minimize specific months before conception and continue until 10 to 12 birth defects including neural tube defects, congenital heart weeks post conception. From 12 weeks post conception disease, urinary tract anomalies, oral facial clefts with or without cleft palate, limb defects, and hydrocephalus, as postpartum period (4–6 weeks or as long as breastfeed- well as some pediatric cancers. The public health flour forti- ing continues), supplementation should consist of a mul- fication initiative has been very beneficial with respect to tivitamin with folic acid (0.4–1.0 mg). (I-A) primary prevention of birth defects. The recent compre- 7. The recommended strategy (ies) for primary prevention hensive Canadian analysis of neural tube reduction after or to decrease the incidence of fetal congenital anomalies folic acid flour fortification has reported a 46% reduction.
will include a number of options or treatment The observed reduction was greater for spina bifida (53%) approaches depending on patient age, ethnicity, compli- than for anencephaly (38%) and encephalocele (31%). Fur- ance, and genetic congenital anomaly risk status.
ther reductions in the incidence of congenital anomalies • Option A: Patients with no personal health risks,
sensitive to folic acid and multivitamins should be possible planned pregnancy, and good compliance require a with the participation of key stakeholders.
Recommendations
supplementation with a multivitamin with folic acid 1. Women in the reproductive age group should be advised (0.4–1.0 mg) for at least two to three months before about the benefits of folic acid in addition to a multivita- conception and throughout pregnancy and the min supplement during wellness visits (birth control postpartum period (4–6 weeks and as long as renewal, Pap testing, yearly examination) especially if • Option B: Patients with health risks, including
2. Women should be advised to maintain a healthy diet, as epilepsy, insulin dependent diabetes, obesity with recommended in Eating Well With Canada’s Food Guide BMI >35 kg/m2, family history of neural tube (Health Canada). Foods containing excellent to good defect, belonging to a high-risk ethnic group sources of folic acid are fortified grains, spinach, lentils, (e.g., Sikh) require increased dietary intake of chick peas, asparagus, broccoli, peas, Brussels sprouts, folate-rich foods and daily supplementation, with corn, and oranges. However, it is unlikely that diet alone multivitamins with 5 mg folic acid, beginning at least can provide levels similar to folate-multivitamin three months before conception and continuing until 10 to 12 weeks post conception. From 12 weekspost-conception and continuing throughout 3. Women taking a multivitamin containing folic acid pregnancy and the postpartum period (4–6 weeks or should be advised not to take more than one daily dose of as long as breastfeeding continues), supplementation vitamin supplement, as indicated on the product label.
should consist of a multivitamin with folic acid 4. Folic acid and multivitamin supplements should be • Option C: Patients who have a history of poor
widely available without financial or other barriers for compliance with medications and additional lifestyle women planning pregnancy to ensure the extra level of issues of variable diet, no consistent birth control, and possible teratogenic substance use (alcohol, 5. Folic acid 5 mg supplementation will not mask vitamin tobacco, recreational non-prescription drugs) require B12 deficiency (pernicious anemia), and investigations counselling about the prevention of birth defects (examination or laboratory) are not required prior to ini- and health problems with folic acid and multivitamin supplementation. The higher dose folic acid strategy 6. The recommended strategy to prevent recurrence of a (5 mg) with multivitamin should be used, as it may congenital anomaly (anencephaly, myelomeningocele, obtain a more adequate serum red blood cell folate meningocele, oral facial cleft, structural heart disease, level with irregular vitamin / folic acid intake but limb defect, urinary tract anomaly, hydrocephalus) that with a minimal additional health risk. (III-B) has been reported to have a decreased incidence follow- 8. The Canadian Federal Government could consider an ing preconception / first trimester folic acid +/- multi- evaluation process for the benefit/risk of increasing the vitamin oral supplementation is planned pregnancy +/- level of national folic acid flour fortification to supplementation compliance. A folate-supplemented 300 mg/100 g (present level 140 mg/100 g). (III-B) 1010 l DECEMBER JOGC DÉCEMBRE 2007
Pre-conceptional Vitamin/Folic Acid Supplementation 2007 9. The Canadian Federal Government could consider an 16. SOGC Genetics Committee: The use of folic acid for the prevention of neural tube defects and other congenital anomalies. SOGC Clinical Practice evaluation process for the benefit/risk of additional Guidelines, No. 138, November 2003. J Obstet Gynaecol Can 2003; flour fortification with multivitamins other than folic 17. Neural Tube Defects. American College of Obstetrics and Gynecology 10. The Society of Obstetricians and Gynaecologists of Educational Bulletin 2003:44;754–64.
Canada will explore the possibility of a Canadian 18. Van Allen MI, Fraser FC, Dallaire L, Allanson J, McLeod DR, Andermann E, et al. Recommendations on the use of folic acid supplementation to Consensus conference on the use of folic acid and prevent the recurrence of neural tube defects. Clinical Teratology multivitamins for the primary prevention of specific Committee, Canadian College of Medical Geneticists. CMAJ congenital anomalies. The conference would include Health Canada/Congenital Anomalies Surveillance, 19. Jones KL. Smith’s recognizable patterns of human malformation. 6th ed.
Canadian College of Medical Geneticists, Canadian Philadelphia WB Saunders; 2006:704–05.
Paediatric Society, Motherisk, and pharmaceutical 20. De Wals P, Tairou F, Van Allen M, Uh SH, Lowry RB, Sibbald B, et al.
Reduction in neural-tube defects after folic acid fortification in Canada.
N Engl J Med 2007;357:135–42.
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