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Nutrient Requirements and Optimal Nutrition

One-Third of Pregnant and Lactating Women May Not Be Meeting Their Folate Requirements from Diet Alone Based on Mandated Levels of Folic Acid Fortification¹

² Department of Nutritional Sciences, University of Toronto, Toronto, Canada, and ³ The Research Institute, The Hospital For Sick Children, Toronto, Canada

^* To whom correspondence should be addressed. E-mail: deborah_l.o'connor{at}sickkids.ca.

	ABSTRACT

TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

 
Many women are advised to consume a folic acid–containing prenatal supplement for the duration of pregnancy and lactation. Whether this remains necessary after folic acid fortification of the food supply in North America has yet to be determined. Our objective was to assess the dietary folate intake of a sample of pregnant and lactating women at mandated and predicted folic acid–fortification levels and determine the prevalence of inadequate and excessive intakes. Weighed food records (for 3 d) were collected from predominantly university-educated women (32 ± 4 y of age) at 36 wk of pregnancy (n = 61) and at 4 and 16 wk of lactation (n = 60). Dietary folate intakes during pregnancy and lactation, assuming fortification at mandated levels (140–150 µg/100g), were 562 ± 106 and 498 ± 99 µg/d dietary folate equivalents (DFE), respectively. The prevalence of inadequacy for folate, or the proportion of individuals with usual folate intakes less than their nutrient requirement, was 36% for women during pregnancy (estimated average requirement of 520 µg/d DFE), and 32% during lactation (estimated average requirement of 450 µg/d DFE). Assuming fortification at twice the mandated level, mean dietary intakes during pregnancy and lactation were 786 ± 132 and 716 ± 150 µg/d DFE, respectively, producing only a 3% prevalence of folate inadequacy. Grains contributed 41% of total folate intake followed by fruits and vegetables (21%). To conclude, at mandated levels of fortification many pregnant and lactating women are unlikely to meet their folate requirements from dietary sources alone; however, the actual level of inadequacy cannot be determined until the level of folic acid in the food supply is known with greater precision.

	Introduction

TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

Although these data suggest a significant shift in blood folate indices of women after folic acid fortification, information on the folate status of pregnant (following closure of the neural tube) and lactating women, except for a couple of reports, are notably absent (11,12). The estimated average requirement (EAR)⁴ of folate during pregnancy (520 µg/d) and lactation (450 µg/d) exceeds that in the nonreproductive state (320 µg/d) (1). Prior to folic acid fortification of the food supply, pregnant and lactating women in North America had dietary intakes of folate well below recommended levels, and blood folate concentrations declined during pregnancy and with the increased duration of breastfeeding (2,13–16). Health experts advised many women to consume a folic acid supplement, usually in the form of a prenatal supplement, for the duration of pregnancy (17) and to continue taking and/or finish their supply during lactation. Whether women need to continue taking a folic-acid containing supplement after closure of the neural tube has not been addressed since the introduction of folic acid fortification to the food supply. Historically, for generally well-nourished women in Canada, the purpose of recommending a prenatal supplement was to address the predicted dietary shortfall in dietary folate and iron (not necessary if prepregnancy stores are adequate) necessary to support expanded blood volume and the growth of maternal and fetal tissues (17,18). Hence, if the incremental increase in folate intakes subsequent to fortification is sufficient, a prenatal or multivitamin/mineral supplement for the duration of pregnancy and lactation may no longer be necessary for many women. The purpose, then, of the present study was to 1) assess the dietary and folate intakes of a sample of pregnant and lactating women at mandated and predicted folic acid–fortification levels of the food supply, and 2) to determine the prevalence of inadequate and excessive intakes.

	Subjects and Methods

TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

 
    Subjects. The dietary data presented herein were collected as part of a prospective randomized control trial (April 2002–December 2003) designed to assess the folate status of lactating women and the efficacy of [6S]-5-methyltetrahydrofolate (L-MTHF) vs. folic acid as a dietary supplement during lactation (12). The study protocol was approved by the Human Ethics Committee at The Hospital for Sick Children, Toronto, and participants gave written, informed consent. Women were eligible to participate in the original study if they were healthy, <36 wk of gestation at recruitment, nonsmokers, 16–40 y of age, and planned to exclusively breastfeed for >4 mo postpartum. There were no restrictions at enrollment based on whether women consumed a prenatal vitamin and/or mineral supplement. Subjects were identified through the Motherisk Program at The Hospital for Sick Children and by word-of-mouth. Motherisk is a telephone counseling program that provides evidence-based information to 150–200 women each day on the safety or risk to a developing fetus of maternal exposure to drugs, chemicals, or disease. Of the 71 women enrolled, 62 completed a minimum of 3 d of food records and were included in the present analyses. One subject was unable to complete records during pregnancy but completed the records during lactation (n = 61 pregnancy) and 2 subjects dropped out in the early weeks of lactation and therefore completed only the pregnancy records (n = 60 lactation).

    Study design. Subjects were given a self-administered demographic questionnaire at the first study visit to collect information on their household income and education level. Women were asked to complete 3-d weighed food records at 36 wk of gestation and at 4 and 16 wk postpartum (± 1 wk).

In the overall study, women at delivery were assigned to 1 of 3 postpartum supplementation groups: placebo (control), L-MTHF (416 µg/d), or folic acid (400 µg/d). In addition, all subjects received a daily multivitamin and mineral supplement containing 1 mg vitamin B-6, 3 µg vitamin B-12, and 4 mg ferrous fumurate (Exact; Pharmetics). The latter supplement contained no folate. Mothers were instructed to consume supplements up to 16-wk postpartum and to avoid additional folic acid supplementation during the postpartum study period. All mothers had access to a qualified lactation consultant to ensure that each woman could meet her breastfeeding goals.

    Dietary assessment. Dietary intakes of energy, carbohydrate, protein, fat, folate, and vitamin B-12 were estimated using 3-d weighed food records. Food records were completed over 2 nonconsecutive days and 1 weekend day by study participants who were trained by 1 of 2 registered dietitians on how to complete food records using an electronic digital scale accurate to 1 g (CS2000; Ohaus Corporation). Nutrient intakes were then tabulated using Health Canada's Canadian Nutrient File (CNF), version 2001b (19), which was updated to reflect current Canadian fortification regulations and is based on the USDA Nutrient Database for Standard Reference (20). Folate values in the CNF were not determined after a trienzyme extraction procedure. No adjustment was made to the database to reflect possible overages in folic acid–fortification levels. Folate intake was expressed as the mean of 3 d of recorded intake. In the event that an ingested food was not found in the CNF, we either estimated the folate content from the package label claim or made an appropriate food substitution.

For the purpose of estimating energy and nutrient intakes during lactation, data from 4 and 16 wk postpartum were combined, providing up to 6 d of food records per subject. The rationale for combining these visits is that the accuracy of data are improved as the number of collection days increases (21). Further preliminary statistical analysis did not yield differences in nutrient intake between these 2 time-points.

Major sources of dietary folate during pregnancy and lactation were identified by determining the contribution to total folate intake made by various food combinations. In this analysis both naturally occurring folates and folic acid as a fortificant were included.

    Correction for the bioavailability of folic acid from food. The CNF reports 1) total values for dietary folate intake (µg/d) or the sum of naturally occurring folate and folic acid added as a fortificant and 2) folic acid as a fortificant separately. In this study, dietary folate intakes are expressed as µg/d dietary folate equivalents (DFEs). This unit was developed by the U.S. Institute of Medicine to help account for differences in the bioavailability of naturally occurring food folates and synthetic folic acid (1,22,23). Because folic acid ingested with food is estimated to be 85% bioavailable and food folates are thought to be 50% bioavailable, folic acid taken with food is believed to be 85/50 (i.e., 1.7 times or 70% more) more available than naturally occurring food folates (1). To convert all forms of dietary folate into DFEs, the following calculation was developed: µg of DFEs provided = µg food folate + (µg folic acid x 1.7) (1).

    Assessment of folate intake from dietary supplements. At 36 wk of gestation, each subject was asked to recall any vitamins or minerals consumed during pregnancy. Frequency, dose, and duration of use and name brand were recorded. During lactation, compliance with the prescribed supplement regimen was calculated by determining the difference between the number of capsules provided by the study investigators at randomization (immediately postpartum) and those remaining at the end of the study period (16 wk postpartum).

    Data analysis. Energy and select nutrient intakes were analyzed using Software for Intake Distribution Estimation (SIDE), version 1.0 (Department of Statistics and Center for Agricultural and Rural Development, Iowa State University). The SIDE program operates within SAS for WINDOWS (version 9.1; SAS Institute) (24). With SIDE, a mean estimate of subjects' usual (long-term) intake was generated using the distribution of their observed intakes and partially removing the day-to-day variation in individuals' intakes. In addition, SIDE was used to estimate the prevalence of inadequacy or the proportion of subjects with usual folate and vitamin B-12 intakes below their requirements, using a technique called the EAR cut-point method (25–27). The EAR is defined as the average intake level that is estimated to meet the requirement of half of the healthy individuals (by gender and life stage) in the population as opposed to the RDA representing an intake level that meets the nutrient requirements of most healthy individuals (25). As recommended by the Institute of Medicine, we have used the EAR to estimate the prevalence of nutrient inadequacy insofar as the use of RDA generally overestimates the true prevalence of inadequacy (25).

The proportion of women with usual intakes above the tolerable upper level (UL) of 1000 µg for folate was also calculated, giving consideration to the intake from supplemental and fortificant sources of folic acid only. The UL applies to folic acid only because this form of folate, and not naturally occurring folates, is capable of masking a vitamin B-12 deficiency (1).

Energy intakes of women in our study were compared with the Institute of Medicine's estimated energy requirement (EER) for a nonpregnant, nonlactating reference woman, who is 160 cm tall, has a BMI of 24.9, and a low activity level plus additional kJ to meet the energy requirements for pregnancy and lactation (28). This estimate was used due to the fact that we did not collect information on subjects' anthropometrics or activity levels. Values in the text are expressed as means ± SD.

	Results

TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

 
    Participant characteristics. Sixty-two women, 32 ± 4 y of age, were included in the present analyses (Table 1). Women were well-educated (57 of 62 had completed college or university) and were predominantly from households with incomes >75,000 Canadian dollars (46 of 61) (Table 1). In Ontario, the mean household income in 2001 was estimated to be 66,836 Canadian dollars (29). Mothers had a gravity and parity of 1.7 ± 0.9 and 0.6+0.7, respectively. Thirty-three of 62 women were first-time mothers.

View larger version (10K): [in this window] [in a new window]   Figure 1  Folate intakes of a sample of Canadian pregnant women with and without folic acid supplementation after fortification of the food supply (n = 61). The vertical line represents the EAR (520 µg/d DFE). The y-axis, labeled density values, shows the likelihood for each level of intake in the population.

View larger version (11K): [in this window] [in a new window]   Figure 2  Folate intakes of a sample of Canadian lactating women with and without folate supplementation after fortification of the food supply (n = 60). The vertical line represents the EAR (450 µg/d DFE). The y-axis, labeled density values, shows the likelihood for each level of intake in the population.

During pregnancy, women had a daily mean supplemental folic acid intake of 925 ± 238 µg primarily from prenatal supplements containing 1000 µg folic acid (Table 3). Supplement compliance was not evaluated prospectively in pregnancy; however, when asked, mothers reported taking the prenatal supplement daily. During lactation the mean compliance rate was 84 ± 14% for the subjects consuming folic acid (400 µg/d) or L-MTHF (416 µg/d) resulting in a mean supplemental intake of 337 ± 55 µg/d. Table 4 presents data on the major dietary contributors of folate in the diets of pregnant and lactating women in our study. Orange juice was found to be the largest source of folate, contributing 11.1% to total dietary folate intake. Pasta products were the second largest contributor, providing 8.8% of dietary folate intake. The grains food group, based on the USDA Food Guide Pyramid and Canada's Food Guide, contributed 41.0% of total dietary folate (30,31). Fruits and vegetables excluding orange juice and french fries provided 21.2% of total dietary folate intake.

	Discussion

TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

Interestingly, pregnant and lactating women in the present study consumed the greatest proportion of total dietary folate (µg folate) from the grains food group (41%). Fruits and vegetables (excluding orange juice and french fries) contributed the next largest fraction of dietary folate (21%). Dietrich et al. (8), in their comparison of NHANES data before and after folic acid fortification of the food supply, suggest that the bread, rolls and crackers food category is now the single largest contributor of folate in the American diet (15.6%), surpassing vegetables, which was the number one food source of folate before fortification.

It has been suggested that the regulatory allowance for overages is resulting in higher amounts of folic acid in the food supply than the intended level. Indeed, shortly after the initiation of the folic acid fortification program, Rader et al. (35) measured the folic acid content in a number of enriched products in the U.S. and reported that food folate concentrations were much higher than expected. Using changes in serum folate concentration before and soon after folic acid fortification of the U.S. food supply from 2 published reports, Quinlivan and Gregory predicted that typical intakes in the U.S. from fortified foods were twice than anticipated (5). In a letter to the editor, this same group estimated that the Canadian fortification program had increased folic acid consumption by 150 µg/d vs. the projected 100 µg/d (6). Blood folate values from a single Canadian study, before and soon after folic acid fortification, were used in their analyses. Rerunning our dietary analysis, with folic acid fortification double the amount of targeted values, the prevalence of folate inadequacy, from diet alone, would be reduced to virtually zero during pregnancy and lactation. In this case, there would be little benefit of including folic acid in supplements designed for use during pregnancy (postclosure of the neural tube) and lactation. It is important to note, however, that fortifying at double the currently mandated level may put nontarget groups in danger of over consumption. In actual fact, no one has directly measured the amount of folate added to the food supply in Canada. Furthermore, there is some evidence to suggest that, in the U.S., the amount of over-fortification may be changing with time (36). As others have suggested, our data underscore the necessity to determine and to continually monitor just how much folic acid is being added to enriched and fortified foods (5,37,38).

Although concerns about suboptimal folate status during reproduction are well founded, overzealous use of folic acid is not risk-free (1,39–41). Many countries have not adopted a national folic acid fortification program because of the potential adverse effects of folic acid, in particular, that high intakes can delay the diagnosis of vitamin B-12 deficiency by correcting its characteristic symptom, megaloblastic anemia (42). Undetected vitamin B-12 deficiency can result in neurologic damage that could be irreversible (1). None of the women in our study had dietary intakes of folic acid above the UL from dietary sources alone. As anticipated, given the dose of folic acid in prenatal supplements (1000 µg folic acid), a majority (67%) of pregnant women in our study had folic acid intakes above the UL when their supplemental sources of folate were also considered. To assess the impact of lowering the dose of folic acid in prenatal supplements (1000 µg to 400 µg) on the prevalence of dietary intakes below the EAR and above the UL for folate during pregnancy, we adjusted our database so that prenatal supplements contained 400 µg folic acid. Interestingly, not only was the prevalence of inadequacy 0%, so was the percentage of intakes above the UL, suggesting, that for well nourished women, a 400 µg folic acid supplement might approach the correct balance of reducing the risks of under and over folic acid supplementation.

Although women in our study had adequate intakes of vitamin B-12, we were uncertain this would be true of pregnant or lactating women who followed vegetarian diets or who were young and/or of low SES. Available evidence suggests that the prevalence of low serum vitamin B-12 levels may be higher among reproductive-aged females than previously appreciated. House et al. (43) reported that 44% of a large sample of pregnant women in Newfoundland (n = 1424) had serum vitamin B-12 concentrations during the first trimester of pregnancy below a commonly used cut-off value indicative of below-normal or deficient vitamin B-12 status (<130 pmol/L). Koebnick et al. (44) reported a 22% prevalence of low serum vitamin B-12 and elevated plasma homocysteine concentrations among pregnant ovo-lactovegetarians in Germany.

Our data are among the first, that we are aware of, that specifically examine the folate intake of pregnant and lactating women after folic acid fortification of the food supply; however, there are a number of limitations inherent to the study. First, the actual folate content of the food supply is unknown. As described above, it is likely there is a certain amount of over-fortification of the food supply, but the extent is uncertain. In addition, the endogenous folate content of foods as listed in the CNF and the USDA Nutrient Database for Standard Reference was, for the most part, not determined after the state-of-the-art trienzyme folate extraction procedure. Hence, the quality of folate values in the best of the North American nutrient databases remains uncertain and is likely to underestimate their true content (1,35). Second, as described elsewhere, study subjects may underreport dietary intake in dietary records (45–48). Underreporting could lead to an overestimation of the proportion of women not meeting their requirements and an underestimation of women who had folic acid intakes above the UL. Energy and endogenous folate intakes during pregnancy and lactation, reported herein, are quite similar to those reported by others suggesting that while we cannot discount underreporting as an issue in the present study, there is no reason to believe that it is a significant issue relative to other studies (13,15,16).

In conclusion, at mandated levels of folic acid fortification of the food supply, many pregnant and lactating Canadians are not likely to meet their dietary requirements for folate. For this reason, prenatal supplements should continue to contain folate, although investigation of a lower dose may be fruitful in striking the right balance between meeting requirements and minimizing the risk of high intakes of supplemental folic acid. Given the role of folate in the prevention of neural tube defect, health care professionals need to continue to use recommended tools of improving the folate intakes of lactating women capable of becoming pregnant, including educating them about foods rich in folate and encouraging the use of a folic acid-containing supplement (17,49).

	ACKNOWLEDGMENTS

 
We thank Anja Martina Bohlmann of Merck KGaA, Darmstadt, Germany and Rudolf Moser of Merck Eprova AG, Schaffhausen, Switzerland for ongoing support and enthusiasm for the project and for ensuring that both implementation of study protocol and data collection efforts complied with applicable regulatory requirements. We also thank Glynnis Dubois for lactation support and the research nurses from the Clinical Investigation Unit.

	FOOTNOTES

 
¹ Funding for this research was provided by Merck Eprova AG, an affiliate of Merck KGaA, Darmstadt, Germany and the Natural Sciences and Research Council of Canada. K.L.S. and L.A.H. were funded by the Ontario Student Opportunity Trust Fund—The Hospital for Sick Children Foundation Scholarship Program and the Canadian Institute of Health Research Training Program in Clinical Nutrition.

⁴ Abbreviations used: CNF, Canadian nutrient file; DFE, dietary folate equivalent; EAR, estimated average requirement; EER, estimated energy requirement; L-MTHF, [6S]-5-methyltetrahydrofolate; RDA, recommended dietary allowance; SIDE, software for intake distribution estimation; UL, tolerable upper level.

Manuscript received 12 May 2006. Initial review completed 30 June 2006. Revision accepted 2 August 2006.

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TOP ABSTRACT Introduction Subjects and Methods Results Discussion LITERATURE CITED

 

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