Prenatal Nutrition Guidelines for Health Professionals - Folate Contributes to a Healthy Pregnancy

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Folate^{Footnote 1}, a B vitamin, plays an important role in cell division and in the synthesis of amino acids and nucleic acids like DNA (Antony, 2007). It is essential to the normal development of the spine, brain and skull of the fetus, especially during the first four weeks of pregnancy. This is a time when many women are not yet aware that they are pregnant. Folate also supports the pregnant woman's expanding blood volume and growing maternal and fetal tissues (IOM, 1998).

Recommended Folate Intakes For Women Of Childbearing Age

Folate requirements have been set mainly based on the amount of dietary folate equivalents (DFEs)^{Footnote 2} needed to maintain normal red blood cell concentrations (IOM, 1998). The Recommended Dietary Allowance (RDA)^{Footnote 3} for women of childbearing age is 400 mcg DFEs (IOM, 1998). In addition to dietary folate intake from a varied diet, all women who can become pregnant should take a multivitamin^{Footnote 4} containing 400 mcg (0.4 mg) of folic acid every day. This reduces the risk of neural tube defects (Van Allen et al., 2002).

Recommended Folate Intake During Pregnancy

Folate requirements increase during pregnancy. There is a dramatic acceleration in cell division and red blood cell development as the uterus enlarges, the placenta develops, maternal blood volume expands, and the fetus grows (IOM, 1998). The mother also transfers folate to the fetus (Antony, 2007). Evidence supports a RDA of 600 mcg DFEs per day to maintain normal folate status during pregnancy (IOM, 1998).

Not Getting Enough Folate

Because the body has a high demand for folate, women may not get enough of this nutrient during their childbearing years (Power, 2005; Ortega et al, 2006; Sherwood et al, 2006; Kirkpatrick and Tarsuk, 2008). Women who are at higher risk include those who:

• are not taking the recommended folic acid supplement,
• are on restricted diets (such as chronic dieters),
• have a lower socio-economic status, and
• are experiencing food insecurity^{Footnote 5}.

How Folate Helps Prevent Neural Tube Defects

Neural tube defects (NTDs)^{Footnote 6} include spina bifida and anencephaly. They occur when the neural tube fails to close properly during the third and fourth week of pregnancy. Often a woman doesn't yet know that she is pregnant during this critical time. A decreased risk of NTD is associated with both increased folate intake and higher red blood cell folate concentrations (greater than 906 nmol/L); though the experimental evidence is stronger for increased folate intake and NTD risk reduction (IOM, 1998).

The risk is reduced when women start taking a daily multivitamin containing folic acid three months before the beginning of pregnancy and continuing in early pregnancy while the neural tube is closing (from 21 to 28 days after conception, or the 6^th week after the beginning of the last menstrual period)^{Footnote 7} (Van Allen et al, 2002). The reduced risk has been observed in women who took a supplement containing 360 to 800 mcg of folic acid per day, in addition to an intake of 200 to 300 mcg per day of natural folate (IOM, 1998).

Many studies also show that multivitamins containing folic acid taken in the early weeks of pregnancy are associated with a decreased risk of oral cleft and cardiovascular anomalies (IOM, 1998; Cziezel et al, 1999; Cziezel, 2004; Eichholzer et al, 2006; Goh et al, 2006). Some evidence also suggests an association with reduced risk of preeclampsia (Bodnar et al, 2006; Wen et al, 2008). This is an area of active and on-going research.

In light of this evidence, and recognizing that pregnancies are not always planned, the Government of Canada has taken steps to help women of childbearing age increase the amount of folate they consume through mandatory food fortification and the promotion of vitamin supplementation for all women who could become pregnant.

Reducing The Risk Of Neural Tube Defects

Mandatory Food Fortification

Adding folic acid to white flour, enriched pasta, and enriched corn meal has been mandatory in Canada since November 1998. Studies show that this measure has increased folate intake and improved folate status in Canadian women of childbearing age (Ray et al, 2002; Liu et al, 2004). This population health approach has also been associated with a significant reduction in the rate of NTDs. For example, a 7-province study (from 1993 to 2002) showed a reduction of 46% in the overall rate of NTDs^{Footnote 8} post-fortification (De Wals et al, 2007).

Vitamin Supplementation For All Women Who Could Become Pregnant

Considering that the level of intake of folic acid from fortified foods is estimated to be no more than 100 to 200 mcg per day^{Footnote 9}, and recognizing that many pregnancies are unplanned, all women who could become pregnant should take a multivitamin containing 400 mcg (0.4 mg) of folic acid daily. This is in addition to the dietary folate provided by a varied diet. Having women supplement their diets with folic acid between pregnancies can help reduce the risk of NTDs in subsequent births.

Some women, such as those who have had a previous NTD affected pregnancy and those with a near relative who has a NTD, are at higher risk of having a NTD-affected pregnancy. They may need more than 400 mcg (0.4 mg) of folic acid daily (Van Allen and McCourt, 2002). These women should be assessed early and advised on the steps to take to prepare for a healthy pregnancy.

Promoting The Use Of Folic Acid Supplementation

According to Canadian survey data, 58% of women said they took a multivitamin containing folic acid or a folic acid supplement in the three months before becoming pregnant (Public Health Agency of Canada, 2009). It has been shown that the use of supplements is influenced by economic status and educational background (Botto et al, 2005). For instance, the use of folic acid supplements before pregnancy in Canada was lowest among women in lower-income households, among women with less than high school graduation, and among immigrant mothers (Millar, 2004). Women with unplanned pregnancies, mothers under the age of 25 and single mothers are also less likely to supplement with folic acid (Ray et al, 2004).

Although the majority of Canadian women take folic acid supplements in the three months before pregnancy, continued public health efforts are needed to promote awareness of the importance of folic acid supplementation for all women of childbearing age. To avoid increasing socio-economic inequalities in folic acid use, interventions should provide practical support to vulnerable groups (Stockley and Lund, 2008).

Continued Supplementation Throughout Pregnancy

Canadian survey data show that it is difficult for most women of childbearing age to consume enough folate from diet alone to meet their pregnancy needs. Over 75% of non-pregnant/non-breastfeeding women aged 19 - 50 have intakes less than the Estimated Average Requirement (EAR)^{Footnote 10} for pregnancy, 520 mcg of DFEs (Health Canada, 2008). To meet folate needs during pregnancy, women should consume a varied diet that provides dietary folate (see Table I), and continue taking a multivitamin containing 400 mcg (0.4 mg) of folic acid throughout their pregnancy.

Table I This table charts the sources of dietary folate from different food.

Food	1 Food Guide Serving	MicrogramsTable 1 footnote a of folate as dietary folate equivalents (µg DFEs)
Table 1 footnotes Table 1 footnote 1 Amounts are approximate based on Canadian Nutrient File, 2007b. Return to table 1 footnote a referrer
Lentils and romano beans	175 mL	265-270
Black beans	175 mL	190
Okra	125 mL	140
White beans	175 mL	125
Asparagus and spinach, cooked	125 mL	120
Salad greens, such as Romaine lettuce, mustard greens and endive	250 mL	80-110
Pinto beans, kidney beans and chickpeas	175 mL	70-100
Pasta made with enriched wheat flour	125 mL	90
Avocado	½ fruit	80
Sunflower seeds, shelled	60 mL	80
Bagel made with enriched wheat flour	½ bagel (45 g)	60-75
Brussels sprouts, beets and broccoli, cooked	125 mL	70
Bread made with enriched wheat flour or enriched corn meal	1 slice or ½ pita or ½ tortilla (35 g)	45-65
Spinach, raw	250 mL	60
Orange juice from concentrate	125 mL	60
Parsley	125 mL	50
Parsnips	125 mL	50
Peanuts, shelled	60 mL	45
Eggs	2 large	45
Corn	125 mL	40
Seaweed	125 mL	40
Orange	1 medium	40
Green peas	125 mL	40
Raspberries, strawberries, blackberries	125 mL	15-35
Enriched ready to eat cereal	30 g	10-35
Broccoli and cauliflower, raw	125 mL	30
Snow peas	125 mL	30
Pineapple juice	125 mL	30
Walnuts, almonds and hazelnuts, shelled	60 mL	20-30
Baby carrots	125 mL	25
Kiwifruit	1 large	20
Clementine	1 fruit	20

Implications for practice

Optimizing dietary folate intake

Following a healthy eating pattern and choosing foods that are rich in nutrients helps women meet their requirement for folate and other nutrients. To promote adequate dietary folate intake:

• Encourage women to use Canada's Food Guide . It describes a healthy eating pattern that is rich in dietary folate. Following Canada's Food Guide will also help women meet their needs for other nutrients and can help them achieve overall health.
• Promote use of tools such as My Food Guide Servings Tracker . This can help women keep track of the amount and type of food they eat each day and compare their intake to Canada's Food Guide.
• Encourage women to include grain products fortified with folic acid each day, such as enriched bread or enriched pasta^{Footnote 11}. They can make informed choices, by looking for the term 'folic acid' in the ingredient list.
• Encourage women to have legumes, such as beans or lentils, often and eat at least one dark green vegetable, such as peas or romaine lettuce, each day. (See Table I for more dietary choices.)
• Refer women to a Registered Dietitian if they have a significantly restricted food intake. This can happen when women exclude an entire food group or have severe nausea or vomiting. These women can benefit from comprehensive nutritional assessment and counselling.
• Refer nutritionally at-risk women to services or programs that can help. The Canada Prenatal Nutrition Program ^{Footnote 12} Website provides contact information for programs and services for vulnerable pregnant women.

Selecting a multivitamin containing folic acid

For women who can become pregnant, health care professionals play an important role in motivating them to use supplements (Eichholzer et al, 2006). To ensure proper use of multivitamin supplements:

• Use the 'Key messages on folate for women of childbearing age' to write or talk about folic acid supplementation during the childbearing years.
• Encourage women to look for a multivitamin^{Footnote 13} that provides 400 mcg (0.4 mg) of folic acid per daily dose. The product should also include vitamin B₁₂.
• Advise women that prenatal supplements contain higher amounts of nutrients than are usually needed by women who are not pregnant. A non-prenatal multivitamin supplement is often enough. Following this advice can help women avoid taking excessive amounts of nutrients over time.
• Ensure that women look for a Drug Identification Number (DIN) or Natural Product Number (NPN) on the product label showing that the product is government-approved for safety, efficacy, and quality.
• Emphasize the importance of reading product labels. Some supplements may include cautionary notes about their use during pregnancy and breastfeeding.
• Caution women not to take more than one daily dose. This will help women not go over the Tolerable Upper Intake Level (UL) for vitamin A^{Footnote 14}, which is 3,000 mcg retinol activity equivalent (RAE) or 10,000 IU.
• Remind women to keep all supplements stored out of reach of young children.

Advising on the upper limits of folic acid supplementation

High doses of folic acid can hide signs of vitamin B₁₂ deficiency. They can also bring on or accelerate neurological complications associated with B₁₂ deficiency (IOM, 1998). As well, women who have low vitamin B₁₂ status are at higher risk for NTD (Van Allen and McCourt, 2002; Ray et al, 2007; Molloy et al, 2009). The prevalence of vitamin B₁₂ deficiency in women of childbearing age is considered very low (IOM, 1998). However, some studies suggest that more women in this life stage group may have low vitamin B₁₂ status than expected (Ray et al, 2008). Women who do not or infrequently consume foods of animal origin and do not take a vitamin B₁₂ containing supplement are most likely to have deficient or marginal vitamin B₁₂ status (Allen, 2009).

Emerging data also suggest there may be additional health risks associated with taking folic acid, including the development of colon cancer when preneoplastic cells are present (Kim, 2006; Ashokkumar et al, 2007; Smith et al, 2008). It is important that health care professionals do not advise higher doses of folic acid than is recommended in this document, unless duly warranted.

References

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• Antony AC. 2007. In utero physiology: role of folic acid in nutrient delivery and fetal development. Am J Clin Nutr 85(suppl):598S-603S.
• Ashokkumar B, Mohammed ZM, Vaziri ND, Said HM. 2007. Effect of folate oversupplementation on folate uptake by human intestinal and renal epithelial cells. Am J Clin Nutr 86(1):159-166.
• Bodnar LM, Tang G,  Ness RB, Harger G, Roberts JM. 2006. Periconceptional multivitamin use reduces the risk of preeclampsia. Am J Epidemiol 164(5):470-7.
• Botto LD, Lisi A, Robert-Gnansia E, Erickson JD, Vollset SE, Mastroiacovo P, Botting B, Cocchi G, de Vigan C, de Walle H, Feijoo M, Irgens LM, McDonnell B, Merlob P, Ritvanen A, Scarano G, Siffel C, Metneki J, Stoll C, Smithells R, Goujard J. 2005. International retrospective cohort study of neural tube defects in relation to folic acid recommendations: are the recommendations working? Br Med J 330(7491):571. Epub 2005 Feb 18.
• Canada Gazette part II. 1998. Regulatory impact analysis statement, SOR/98-550. 132(24):3029-33.
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• Cziezel AE. 2004. The primary prevention of birth defects: multivitamins or folic acid? Int J Med Sci 1(1):50-61.
• De Wals P, Tairou F, Van Allen MI, Uh SH, Lowry RB, Sibbald B, Evans JA, Van den Hof MC, Zimmer P, Crowley M, Fernandez B, Lee NS, Niyonsenga T. 2007. Reduction of neural-tube defects after folic acid fortification in Canada. N Engl J Med 357(2):135-42.
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• Kirkpatrick SI, Tarasuk V. 2008. Food insecurity is associated with nutrient inadequacies among Canadian adults and adolescents. J. Nutr. 138(3):604-12.
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• Ortega RM, López-Sobaler AM, Andrés P, Rodríguez-Rodríguez E, Aparicio A, Bermejo LM, López-Plaza B. 2006. Changes in folate status in overweight/obese women following two different weight control programmes based on increased consumption of vegetables or fortified breakfast cereals. Br J Nutr 96(4):712-8.
• Power EM. 2005. Determinants of healthy eating among low-income Canadians. Can J Public Health 96 (Suppl. 3):S37-S42.
• Public Health Agency of Canada. 2009. What Mothers Say: The Canadian Maternity Experiences Survey. (Accessed March 31, 2009).
• Ray JG, Goodman J, O'Mahoney PRA, Mamdani JM, Jiang D. 2008. High rate of maternal vitamin B12 deficiency nearly a decade after Canadian folic acid flour fortification. QJM 101(6):475-7. Epub 2008 Mar 12.
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• Ray JG, Vermeulen MJ, Boss SC, Cole DE. 2002. Increased red cell folate concentrations in women of reproductive age after Canadian folic acid fortification. Epidemiology 13(2):238-40.
• Ray JG, Wyatt PR, Thompson MD, Vermeulen MJ, Meier C, Wong P-Y, Farrell SA, Cole DEC. 2007. Vitamin B12 and the risk of neural tube defects in a folic-acid-fortified population. Epidemiology 18(3):362-6.
• Sherwood KL, Houghton LA, Tarasuk V, O'Connor DL. 2006. One-third of pregnant and lactating women may not be meeting their folate requirements from diet alone based on mandated levels of folic acid fortification. J Nutr 136(11):2820-6.
• Smith AD, Young-In K, Refsum H. 2008. Is folic acid good for everyone? Am J Clin Nutr 87(3): 517-33.
• Stockley L., Lund V. 2008. Use of folic acid supplements, particularly by low-income and young women: a series of systematic reviews to inform public health policy in the UK. Public Health Nutr 11(8):807-21. Epub 2008 May 6.
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Acknowledgement

Health Canada sincerely thanks the members of the Expert Advisory Group on National Nutrition Pregnancy Guidelines who generously gave their time and expertise over the course of preparing these guidelines:

• Aline Allain-Doiron, RD, Public Health Nutritionist-Dietitian, Regional Health Authority B, Zone 7
• Andrée Gruslin, MD, FRCS, Director of the Post-graduate Residency Training Program in Obstetrics and Gynaecology, University of Ottawa
• Sheila M. Innis, RD, PhD, Director of Nutrition Research Program, Child and Family Research Institute, University of British Columbia
• Kristine G. Koski, RD, PhD, Director School of Dietetics and Human Nutrition, McGill University
• Michel Lucas, PhD, MPH, RD, Epidemiologist/Nutritionist, Axe Santé des populations et environnement, Centre Hospitalier de l'Université Laval (CHUL-CHUQ)
• Ann Montgomery, RM, associate midwife and preceptor, Midwifery Collective of Ottawa
• Deborah L. O'Connor, RD, PhD, Director of Clinical Dietetics, The Hospital for Sick Children, and Associate Professor, Department of Nutritional Sciences, University of Toronto
• Kay Yee, RD, Public Health Nutritionist, Regina Qu'Appelle Health Region

Health Canada would also like to thank the many stakeholders who took part in the online consultation process and provided feedback on draft content of the guidelines.