Durante mucho tiempo no había principios uniformes para la Atribución de nombres a los antibióticos https://antibioticos-wiki.es . Más a menudo se les llama por el nombre genérico o especie del producto, con menos frecuencia-de acuerdo con la estructura química. Algunos antibióticos se nombran de acuerdo con el lugar donde se asignó el producto.
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 (HealthKey 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.
DECEMBER JOGC DÉCEMBRE 2007 l 1003 JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE
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 JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE 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 JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE 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 JOINT SOGC-MOTHERISK CLINICAL PRACTICE GUIDELINE
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
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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
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1. The reduction of the causal factors of interpersonal conflict (IPC) in the Libyan cement Munira Elmagri – Built Environment, Salford One survey showed that managers spend more than 25% of their work time dealing with conflict. Therefore, conflict in organizations has received considerable attention in academia and industry. However, there is a lack of empirical studies on subject of the fac
Sarah Eckhardt’s Response to Questions on Climate Adaptation and Resilience 1) As an Austin and Travis County resident what do you see as the greatest impacts, threats, and challenges posed by extreme weather events and climate variability in our region? The biggest local impact is the likely increase in extreme drought/flood cycles. These cycles wil likely lead to continuing t