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A Strategy That Can Help to Prevent Neural Tube Defects Is for Women to Take:

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A comprehensive evaluation of food fortification with folic acid for the primary prevention of neural tube defects

  • Roy Due west2,
  • Edward Randelliii,
  • Linda Longerichii,
  • Kathleen Steel O'Connor4,
  • Helen Scott5,
  • Marian Crowley6,
  • Angeline Lamiii,7,
  • Victor Prabhakaranviii &
  • Catherine McCourt1

BMC Pregnancy and Childbirth volume 4, Article number:20 (2004) Cite this article

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Abstract

Groundwork

Periconceptional use of vitamin supplements containing folic acid reduces the risk of a neural tube defect (NTD). In Nov 1998, nutrient fortification with folic acrid was mandated in Canada, as a public health strategy to increase the folic acid intake of all women of childbearing age. We undertook a comprehensive population based study in Newfoundland to appraise the benefits and possible adverse effects of this intervention.

Methods

This study was carried out in women aged 19–44 years and in seniors from November 1997 to March 1998, and from November 2000 to March 2001. The evaluation was comprised of four components: I) Determination of rates of NTDs; Ii) Dietary assessment; Three) Blood assay; IV) Assessment of cognition and use of folic acid supplements.

Results

The annual rates of NTDs in Newfoundland varied profoundly between 1976 and 1997, with a hateful rate of 3.40 per ane,000 births. There was no meaning change in the average rates between 1991–93 and 1994–97 (relative take a chance [RR] 1.01, 95% confidence interval [CI] 0.76–1.34). The rates of NTDs fell by 78% (95% CI 65%–86%) afterward the implementation of folic acid fortification, from an boilerplate of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35). The average dietary intake of folic acid due to fortification was 70 μg/day in women aged xix–44 years and 74 μg/day in seniors. There were significant increases in serum and RBC folate levels for women and seniors after mandatory fortification. Among seniors, at that place were no pregnant changes in indices typical of vitamin B12 deficiencies, and no evidence of improved folate condition masking haematological manifestations of vitamin B12 deficiency. The proportion of women anile xix–44 years taking a vitamin supplement containing folic acid increased from 17% to 28%.

Conclusions

Based on these findings, mandatory food fortification in Canada should continue at the electric current levels. Public education regarding folic acid supplement apply past women of childbearing historic period should also continue.

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Background

Neural tube defects (NTDs) are nascency defects resulting from the failure of neural tube closure during early development of the man embryo. The 1997 Canadian national NTD birth prevalence was 0.75 per 1,000 births (live births and stillbirths), downwards from i.xvi per ane,000 in 1989 [1]. The rates tend to be higher in the eastern provinces than in the westward [2–4]. Historically, Newfoundland has had i of the highest rates in North America with a reported boilerplate yearly rate for 1976–1997 of 3.4 per ane,000 births (including live births, stillbirths and fetuses from pregnancies terminated later on a prenatal diagnosis of an NTD) [4].

Evidence from a number of studies has demonstrated that periconceptional utilize of vitamin supplements containing folic acid reduces the risk of NTDs [5–8]. Although the mechanism of action of this nutrient in influencing the hazard of NTDs is poorly understood, the evidence of the benefit of folic acid has led many health organizations since late 1992 to recommend periconceptional folic acid supplementation, at a level of 400 μg /day for low risk women [nine–xi].

Considering of concern that public education campaigns alone would not exist constructive in achieving optimal periconceptional folic acrid intake for the majority of women, food fortification with folic acid was proposed as a strategy to ensure that all women of childbearing age increase their dietary intake of this vitamin. In November 1998, Health Canada mandated fortification of white flour and enriched pasta and cornmeal with folic acrid [12]. Since diets vary, information technology was known that it would be virtually impossible to fortify food with folic acid at a level that ensures that the target population receives an additional 400 μg /solar day, while protecting the not-targeted population from an undesirably loftier amount. As a result, conservative levels of fortification were introduced. White flour is fortified with folic acid at a level of 0.15 mg per 100 g of flour. This intervention was expected to increase the average daily folic acid intake of women of childbearing age by about 100 μg [13].

The question of whether folic acid fortification of grain products poses any serious wellness hazard has been controversial. The master concern has been the potential masking of vitamin B12 deficiency, a condition that affects x–15% of the population over historic period sixty years [14, 15]. Increased folic acid intake may correct the haematologic signs of vitamin B12 deficiency, thus delaying diagnosis and handling of the condition while its bellboy neurologic manifestations progress. Seniors may exist at item risk since the incidence of vitamin B12 deficiency increases with age.

We therefore undertook a comprehensive population based study to evaluate the effectiveness of the public health strategy of food fortification with folic acid and to decide possible adverse effects resulting from fortification.

Methods

Study design

This evaluative study was designed as a population based study and included four components as follows: I) Decision of rates of NTDs; Two) Dietary assessment; III) Blood assay; IV) Cess of knowledge and use of folic acid supplements. The latter three components of the written report were carried out in two phases; the first stage took identify prior to the introduction of mandatory fortification, from November 1997 to March 1998 and the second phase occurred from November 2000 to March 2001, after two years of implementation of mandatory fortification.

This study was undertaken in Newfoundland because of the historically high rates of NTDs in the province, and because of strong interest in the wellness community in this initiative. Newfoundland and Labrador, with a population of approximately 500,000, has about five,000 births annually. An urban (St. John's) and rural (Clarenville, Port Blandford, Random Island area) location in the province were chosen as the sites for this study. Data nerveless from these sites were compared betwixt Phase I (November 1997 to March 1998) and Phase II (November 2000 to March 2001). Tabular array 1 shows schematically the framework including objectives and sampling of subjects for this report. As role of this projection, dietary assessment, blood analysis and assessment of cognition and use of supplements were also carried out in a 2-stage population based study of women of reproductive age in Kingston, Ontario and environs. The results of this written report will be reported elsewhere.

Tabular array one Framework for a two phase, multi site study to examine the effects of food fortification with folic acid

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Data collection

In order to examine temporal changes in the rates of NTDs in Newfoundland, information were compiled from the Newfoundland and Labrador Medical Genetics Programme from 1976 to 2001. This Program ascertains cases of NTDs annually and maintains an NTD database. The database has recorded cases of NTD since 1976. Cases are identified in the following ways: provincial live nascence and stillbirth notification forms, maternal-fetal medicine referrals (only one tertiary care unit in the province), and messages sent to all medical records departments of all provincial hospitals requesting data on cases assigned ICD-nine/ten codes associated with NTDs or terminations for NTDs. These multiple sources are utilized to ensure complete ascertainment. NTD cases include anencephaly, spina bifida and encephalocele diagnosed in live births, stillbirths (a gestational historic period of 20 weeks and above or birthweight of 500 thou and above) and fetuses from pregnancies terminated (at whatever gestational historic period) after a prenatal diagnosis of an NTD.

For the knowledge cess component of the study, women between the ages of nineteen and 44 years were recruited through a random telephone survey. In the initial telephone survey, women were asked nigh their use of vitamin supplements and knowledge of the importance of folic acid for reducing the risk of NTDs or for fetal development. Women who completed the initial telephone survey were afterwards screened for their eligibility for dietary and blood assessments. Women who were not taking supplements containing folic acid and non pregnant were eligible to participate. This sampling process for Stage I and Phase II resulted in a response charge per unit of 59.7% and 65.iv%, respectively, with no difference between urban and rural response rates. A total of 233 women were recruited into Phase I and 204 women were recruited in Phase Ii, who completed components II, 3 and Four of the report.

Seniors were recruited in the same manner as the samples of women, but were drawn simply from St. John'south, Newfoundland. Seniors anile 65 years or over, not diagnosed with vitamin B12 deficiency or anaemia and non taking vitamin B12 or supplements containing folic acid, were eligible for dietary and claret sample assessments. A full of 202 seniors were recruited in Stage I and 186 were recruited in Stage II (response rate 45.one% and 44.9%, respectively).

In order to determine intakes of naturally occurring folate (the course of the vitamin constitute naturally in foods) pre and mail service fortification, and dietary intakes of folic acid (the synthetic course of the vitamin) post fortification, a Willett food frequency dietary questionnaire [16] was administered to subjects during an in-person interview. At that place were some modifications to the questionnaire to include common Newfoundland foods and to ensure that all foods high in folate were included. The dietary questionnaire was used to estimate an boilerplate frequency of consumption of 124 nutrient items over the previous period of 1 year.

The women and senior participants were also asked to provide a sample of blood in order to make up one's mind blood folate and vitamin B12 status in Phase I and Phase Two. Laboratory tests for complete claret count (CBC), carmine blood cell (RBC) folate, serum folate, creatinine, vitamin B12, plasma homocysteine (HCY) and methylmalonic acid (MMA) were conducted at the laboratories of the Health Intendance Corporation of St. John's.

Data assay

Rate of NTDs was defined equally the number of in a higher place described NTD cases, divided by the full number of alive births, stillbirths, and pregnancy terminations for an NTD (termed as "births" time to come). First nosotros examined the temporal trend in annual rates of NTDs from 1976 to 2001 using 3-twelvemonth moving boilerplate rates, then we focused on comparison of the NTD information for the most recent xi years, identified every bit pre-supplementation (1991–1993), pre-fortification (1994–1997) and mail-fortification (1998–2001). We regard the year 1997 as a transition menses, or partial fortification period, since fortification of white flour and enriched pasta and cornmeal was permitted in Canada as of December 1996 [17]. Thus we as well analysed the NTD data using 1994–1996 every bit a pre-fortification period.

Mean daily intakes of naturally occurring folate were calculated for women aged 19–44 years and for seniors in Stage I and Stage II. As well, for Phase Ii, average daily intakes of folic acrid from fortified foods were calculated.

Data from the claret analyses were tested for normality with the Komogorov-Smirnov test, and differences between groups were tested using the non-parametric Mann-Whitney U test. The distributions of plasma MMA, plasma HCY, serum folate, RBC folate and serum vitamin B12were skewed. Values were therefore log transformed to give an gauge normal distribution for estimation of geometric hateful and conviction intervals. Unless otherwise stated, all laboratory values presented in this paper are geometric ways and 95% confidence intervals (CI). Differences in the frequency of high or low results based on reference values were tested by Pearson chi-square statistics.

All data for this report were entered into SPSS (the Statistical Package for Social Sciences) Rel. x.0 afterwards the finish of each stage. Data from the dietary interviews were analyzed using Epi-Info (Version 6.04d), while the laboratory data and the data most knowledge and use of supplements were analyzed using SPSS.

Results

1. Rate of NTDs

At that place were 617 ascertained cases of NTD among live births, stillbirths and pregnancies terminated for an NTD in Newfoundland over the 26 year period. The annual rates of NTDs in the province varied greatly over time, with the lowest rate of ii.18 per 1,000 births in 1989, and the highest charge per unit of v.92 per ane,000 births in 1995. The boilerplate rate of NTDs between 1976 and 1997 was 3.40 per i,000 births. A dramatic drop is seen in 1997, in which the rate of NTDs was two.twenty per ane,000 births, down from 5.49 per 1,000 births in the previous year. The decreasing trend connected after 1998 (Figure ane shows 3-year moving average rates).

Figure 1
figure 1

Rates of NTDs in Newfoundland and Labrador, 1976 to 2001 (3-twelvemonth moving average rates) *The rate for 1976 is a 2-yr average based on data for 1976 and 1977 and the charge per unit for 2001 is a 2-yr average based on data for 2000 and 2001.

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The NTD information for the years 1991–2001 are presented in three periods in Table 2. The mean annual rates were 4.35 per 1,000 births during 1991–1993 and 5.02 per 1,000 births during 1994–1996 (1994–96 vs 1991–93, relative risk [RR] ane.fifteen, 95% CI 0.86–1.54, p = 0.95), and 4.37 per 1,000 births during 1994–1997 (1994–97 vs 1991–93, RR 1.01, 95% CI 0.76–1.34, p = 0.54).

Table 2 Annual rates of neural tube defects (NTDs) in Newfoundland and Labrador before folic acid supplementation (1991–1993), prior to folic acid fortification (1994–1997) and after fortification (1998–2001)

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The total annual rate of NTDs brutal by 78% after the implementation of folic acid fortification, from an average of 4.36 per 1,000 births during 1991–1997 to 0.96 per 1,000 births during 1998–2001 (RR 0.22, 95% CI 0.14–0.35, p < 0.0001). It is worthwhile to annotation that at that place has been no significant increase in the proportion of NTDs from terminated pregnancies since 1994.

2. Dietary Assessment

At that place was no statistically significant alter in the boilerplate daily intake of naturally occurring folate amongst either women aged 19–44 years or seniors between Phase I and Phase 2 (p = 0.19 and p = 0.18, respectively). Seniors generally had dietary folate intake slightly college than women of childbearing age. In Phase I, the average daily intake of naturally occurring folate was 306 μg/day for seniors and 262 μg/24-hour interval for women anile 19–44 years, while in Phase Ii, the average daily intake of naturally occurring folate was 290 μg/solar day for seniors and 248 μg/day for women aged xix–44 years.

The implementation of mandatory fortification resulted in an average additional dietary intake of 70 μg/twenty-four hours of folic acid in women aged nineteen–44, and 74 μg/twenty-four hour period of folic acid among seniors. It is noteworthy that for the women the average daily folic acrid intake due to food fortification was less than the approximately 100 μg that was previously predicted for women of childbearing age. The maximum dietary intake of folic acid due to fortification for an private woman was 235 μg/twenty-four hour period, and for an private senior was 219 μg/solar day.

Iii. Blood Analysis

Serum folate and RBC folate increased significantly from Phase I to Phase II in both women aged nineteen–44 years and seniors (p < 0.001). For both age groups, in that location was a corresponding decrease in mean plasma HCY levels (Tables 3 and four). The prevalence of low serum folate (≤vi.eight nmol/L) was eliminated from the sample of seniors and the proportion of elderly participants with depression stores every bit indicated by RBC folate levels (< 373 nmol/L) was reduced from two.v% to one.6%. The proportion of women aged 19–44 years with high HCY(>13.2 μmol/L) also decreased from xv.9% to 7.6% (p = 0.002) (data non shown).

Tabular array 3 Laboratory information (geometric hateful and 95% confidence interval) for immature women participants (historic period 19–44 years) in Stage I and Stage Ii

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Table 4 Laboratory information (geometric mean and 95% confidence interval) for senior participants (historic period 65 years or over) between Phase I and Phase Ii

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There was a significant increment in mean vitamin B12 levels in women anile nineteen–44 and seniors (p = 0.020 and p < 0.001, respectively, Tables 3 and iv). The proportion of seniors with low vitamin B12 (<133 pmol/50) was xviii.8% prior to fortification and following fortification this proportion declined to 11.viii% (p = 0.032) (data not shown). A statistically significant increase in mean plasma MMA levels was observed in women subjects (p = 0.008) but not in seniors (p = 0.229) (Tables 3 and 4). There was also an increase in the proportion of women anile 19–44 years with MMA values above the upper reference value of 0.37 μmol/Fifty from iii.half-dozen% in Phase I to 14.9% in Phase II (p < 0.001). There was no pregnant alter in the proportion of abnormal MMA values in seniors. Moreover, amidst seniors, blood assay showed no pregnant difference in mean haemoglobin concentrations, mean corpuscular book (MCV), or proportion with abnormally loftier MCV (>99 fL) or low haemoglobin (<120 g/L) concentrations.

4. Knowledge and use of folic acid supplements

There was a significant increment from Phase I to Phase 2 in the proportion of women aged nineteen–44 years who knew the importance of folic acid (from 33% to 46%, p < 0.001). The proportion of women taking a vitamin supplement containing folic acid increased essentially between the 2 time periods (from 17% to 28%, p < 0.003). Data about folic acid dosage was not collected.

Discussion

The results of a number of studies take led to the conclusion that periconceptional folic acrid supplementation reduces the chance of NTDs [five–viii]. Among the responses to this research evidence were calls in the early 1990s for mandatory fortification of food with folic acid. Information technology was argued that this public health intervention would address concerns about achieving population level compliance with recommendations to women to take vitamin supplements containing folic acid before becoming pregnant and in the first weeks of pregnancy. These concerns were borne out in several Canadian studies suggesting that many caregivers [18, xix] and women [20, 21] remained unaware of the relationship betwixt folic acid and NTDs. More than contempo studies have shown an increase in noesis most folic acrid, but supplementation rates remain low [22–25].

In March 1996 the The states Food and Drug Assistants (FDA) appear that it would allow improver of folic acid to enriched flour and other enriched cereal grain products, and that this add-on would exist mandatory as of January 1998. The level of fortification was set at 0.xiv mg folic acrid per 100 thou of cereal grain production. It was adamant that at this level of fortification, the intake of folate (from all sources) for the target and the full general population would exist kept below 1,000 μg/day, which was deemed to be the safety upper limit. This level of fortification was estimated to increase the boilerplate daily intake of folic acid in women of childbearing age by about 100 μg [26]. Subsequent to the The states determination, Canada followed suit, permitting folic acid fortification at an equivalent level in December 1996 (addition of folic acid to white flour and enriched pasta and cornmeal at 0.15 mg folic acid per 100 thou of flour and 0.20 mg folic acrid per 100 g of pasta). In Canada, fortification became mandatory in November 1998.

Rate of NTDs

Our results show a highly significant drop in the charge per unit of NTDs in Newfoundland, taking into account all identified affected pregnancies (live births, stillbirths and pregnancies terminated later a prenatal diagnosis of an NTD). The 78% (95% CI 65%–86%) reduction in the NTD charge per unit afterwards implementation of fortification is greater than the 18%–22% reduction predicted at current levels of fortification [27, 28], and greater than the 19% reduction in nascency prevalence of NTDs reported in the US after mandatory fortification [29]. The results in Newfoundland are closer to the 54% reduction (95% CI 34%–68%) in rate of NTDs reported in Nova Scotia after fortification [two]. De Wals et al. observed a 32% reduction (95% CI 23%–41%) in NTDs in Quebec betwixt 1992–97 and 1998–2000 [30]. Ray et al. [31] analyzed maternal serum screening information for Ontario and observed a decline in NTD prevalence from 1.thirteen per 1,000 pregnancies before fortification to 0.58 per 1,000 pregnancies thereafter (prevalence ratio 0.52, 95% CI 0.40–0.67).

The big reduction in the rate of NTDs in Newfoundland may be due, at least in function, to the fact that Newfoundland had higher groundwork rates of NTDs. This population may exist more sensitive to the influence of folic acid. In a large-scale public health campaign in northern and southern Red china, periconceptional employ of 400 μg/day folic acid supplements was associated with a reduction in NTD adventure of 79% for women in northern China, where the baseline NTD rate was high and similar to that observed in Newfoundland. A lower chance reduction of 41% was observed in the southern region where the pre-campaign NTD charge per unit was much lower [32].

The 65% increase in the proportion of women taking vitamin supplements containing folic acid, from 17% in Phase I to 28% in Phase II, suggests that an increasing trend in folic acid supplementation may take played a office in the declining NTD rate in Newfoundland. In this study it was not possible to determine the private contribution of supplementation and fortification to the tendency in NTDs.

The annual rate of NTDs in the pre-fortification period (1994–97) did non differ significantly from that of the pre-supplementation menstruum (1991–93); this is truthful whether 1997 is excluded or included in the pre-fortification period. The increase in the rates of NTDs in 1995 and 1996 appears random and largely unexplainable. The changes in the NTD rates between 1994–1996 and 1991–1993 and between 1995–1997 and 1991–1993 were non statistically significant. In addition, our data do non bear witness an obvious increment in the proportion of NTDs in terminated pregnancies during 1994 and 1996 (data available upon asking).

Dietary intakes and blood folate levels

The questionnaire used in this dietary assessment was a modified Willett questionnaire [16], administered in a face up-to-confront interview with trained personnel. The Willett food frequency dietary questionnaire has been well validated [33] and proved easy to administer for this sample population.

The daily intake of naturally occurring folate amid women aged 19–44 years in this written report (average 248 μg/twenty-four hour period in the Stage II sample) was like to values found in other studies of women'southward diet [34, 35]. For seniors in Stage II, naturally occurring folate in the diet averaged 290 μg/day which was comparable to values found for persons historic period 49 and older in an Australian written report [36]. The dietary folic acid intake due to fortification did non exceed the Tolerable Upper Intake Level (UL) of one,000 μg folic acid/day [fourteen] for any of the participants (this UL for folic acrid does not include naturally occurring folate). It is important to note that this office of the study excluded persons taking vitamin supplements containing folic acid. While it was not possible to estimate the proportion of people in the full general Newfoundland population who may be consuming more than 1,000 μg/24-hour interval of folic acid from fortification and supplementation combined, it is likely that this proportion is small. The average dietary intake and maximum intake of folic acid due to fortification were 70 μg/solar day and 235 μg/day, respectively, for women aged 19–44 years, and 74 μg/day and 219 μg/twenty-four hours, respectively, for seniors. The average folic acid dose in folic acid containing over-the-counter supplements marketed in Canada is about 350 μg/24-hour interval (Health Canada unpublished information).

The results of this study provide potent prove of improved blood folate status in women anile 19–44 years following mandatory fortification with folic acid. Women showed evidence of increased levels of serum and RBC folate and decreased levels of plasma HCY. These results are consequent with an earlier study examining the effect of fortification in the Framingham offspring study cohort [37].

Mandatory food fortification with folic acid has resulted in improvements in folate indices in seniors. Both hateful serum folate and mean RBC folate increased following folic acid fortification (55% and 23%, respectively, Table 4). Consequent with this was a moderate decrease in mean plasma HCY levels amidst seniors by ane.3 μmol/L. Fortification of food with folic acrid and an upwards shift in claret folate levels is of benefit to the elderly population especially with regard to chance of cardiovascular affliction. High levels of homocysteine are associated with both cerebrovascular and coronary middle illness [38–xl].

Vitamin B12status

There was a turn down in the proportion of seniors with depression vitamin B12 levels, and there was actually a slight increase in hateful vitamin B12 levels. In vitamin B12 deficiency, plasma MMA is usually elevated. Plasma MMA is believed to be a better indicator of vitamin B12 status at the tissue level than serum vitamin B12 levels are. Our report showed no alter in mean MMA levels nor increased proportion of elderly with loftier levels. In add-on, there was no change in the indicators of anaemia (i.e., haemoglobin and MCV) in seniors postal service fortification in our report. Thus, these results show no evidence of a deterioration in vitamin B12 status among seniors. Furthermore, there is no show of improved folate status resulting in masking of the haematological manifestations of vitamin B12 deficiency amid seniors as a group. There was no show of deteriorating vitamin B12 condition among young women participants based on vitamin B12 measurements. The upward trend in plasma MMA levels and higher proportion of abnormal values amid immature women is being further evaluated. It is unlikely that this is a direct effect of folic acid fortification and this ascertainment is non consistent with any known furnishings of folic acrid on vitamin B12 condition.

Limitations

We have documented the charge per unit of NTDs amid live births, stillbirths and terminated pregnancies known to have an NTD. It was not possible to include NTDs that may take occurred in pregnancies that resulted in a spontaneous ballgame or a termination that occurred for reasons other than a congenital bibelot.

This study, and other studies of fortification in Canada, are limited by the fact that there was no precise appointment when exposure to food fortified with folic acid began. The addition of folic acid to white flour and enriched pasta and cornmeal was permitted every bit of December 1996. Industry was switching to folic acrid-containing enrichment premixes, peculiarly towards the cease of 1997, in anticipation of both U.s. requirements for fortification equally of January 1, 1998, and Canadian plans to implement mandatory fortification. Although this requirement did not come into force in Canada until tardily 1998, the Phase I (November 1997 to March 1998) subjects of our study may have consumed at least some food fortified with folic acrid. This would event in an underestimate of improvements in blood folate status due to fortification, and might pb us to miss adverse effects on vitamin B12 condition. On the other mitt, the fact that we observed such marked improvements in blood folate status leads u.s.a. to conclude that there was a real increase in exposure to folic acid through fortification, over the study catamenia.

Some other limitation of this written report is the possible underestimation of folic acrid intake due to fortification. Our calculations were based on the supposition that manufacturers are fortifying flour at the required level. It has been suggested that allowance for "overages" is resulting in college amounts in the afflicted products [41]. Too, for enriched pasta, the required level of fortification is from a minimum of 0.20 mg/100 g pasta to a maximum of 0.27 mg/100 g. In our calculations we assumed the minimum level of fortification.

We initially selected a random sample of subjects through random digit dialling, and asked eligible respondents for voluntary participation in the study. The reasonable level of response for the dietary questionnaire and blood sampling amid rural and urban women aged xix–44 years suggests that with caution, we can generalize the results to all Newfoundland women of childbearing historic period. Notwithstanding, these findings may not be representative of the remainder of Canada because of population differences in factors such equally genetic background and dietary behaviour. These differences may also affect the generalizability of the NTD tendency.

The sample response rate for the dietary questionnaire and blood sampling in seniors was approximately 45% both in Stage I and in Phase II. Many of the refusals to participate were due to illness of the eligible person. Furthermore, seniors residing in long term care settings were not included. Thus our sample population of seniors may be healthier than the general population age 65 and over in the province.

Conclusions

The implementation of nutrient fortification with folic acrid has been accompanied by a marked decrease (78%) in the rate of NTDs in Newfoundland. The blood folate status of women aged 19–44 years improved following mandatory fortification. In that location is no evidence of agin furnishings of the current levels of fortification on individuals aged 65 years and older. Specifically, at that place is no prove to suggest an adverse result of folic acrid fortification on detection of abnormalities in vitamin B12 status based on biochemical and haematological indices.

Based on these findings, mandatory food fortification with folic acid should continue in Canada at the electric current levels. Over the time period of this study, the proportion of women anile 19–44 years taking a vitamin supplement containing folic acid increased. Information technology was not possible to determine the magnitude of the separate contributions of fortification and supplementation to the refuse in NTDs. Therefore, we recommend that public health efforts to promote awareness of the importance of folic acid supplementation amidst women of childbearing age keep. Ongoing surveillance of NTDs in Newfoundland and other parts of Canada is necessary to determine if the decline in NTD rate is maintained, and to enable farther evaluation of prevention strategies. National surveillance of congenital anomalies including NTDs is a critical public health function that should be strengthened where necessary.

We expect forrard to the results of a electric current epidemiologic written report, funded by the Canadian Institutes of Health Inquiry (CIHR), of NTDs in 7 Canadian provinces between 1993 and 2002. There is also research into the human relationship between increased folic acid consumption and reduced risk of other congenital anomalies, cardiovascular disease and cancer [42–45]. Equally this body of noesis grows, public wellness practitioners and regulators in Canada and internationally volition have more than prove with which to refine existing disease prevention policies and develop new ones.

Abbreviations

CBC:

complete blood count

CI:

confidence interval

CIHR:

Canadian Institutes of Wellness Research

FDA:

Food and Drug Administration

HCY:

homocysteine

MCV:

mean corpuscular volume

MMA:

methylmalonic acrid

NTD:

neural tube defect

RBC:

reddish claret jail cell

SPSS:

Statistical Package for Social Sciences

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Acknowledgements

This study was funded by Health Canada's Wellness Surveillance and Epidemiology Division. This written report was granted full ethics approving by Research Ethics Boards at Memorial University of Newfoundland and at Queen's Academy. All study subjects gave written informed consent prior to participation in this study.

Nosotros especially thank Linda Turner for her earlier work on this written report. We gratefully admit the back up and assistance of many individuals for their participation in this written report, including the interviewers, laboratory and clinical back up staff, and information entry and analysis staff. Item thanks to Vicki Gill, project coordinator in Newfoundland, Millie Trask, for aid with data entry and word processing in the laboratory component of the report, and Ernesto Delgado, for his logistical back up inside Wellness Canada.

Author information

Affiliations

  1. Health Surveillance and Epidemiology Sectionalization, Middle for Healthy Human Development, PPHB, Health Canada, Ottawa, Ontario, Canada

    Shiliang Liu & Catherine McCourt

  2. Division of Community Wellness, Faculty of Medicine, Memorial University, St. John'south, Newfoundland and Labrador, Canada

    Roy West & Linda Longerich

  3. Health Sciences Center and Division of Laboratory Medicine; Kinesthesia of Medicine, Memorial University, St. John's, Newfoundland and Labrador, Canada

    Edward Randell & Angeline Lam

  4. Public Health Research, Education and Evolution Program, Kingston, Frontenac and Lennox & Addington Health Unit, Kingston, Ontario, Canada

    Kathleen Steel O'Connor

  5. Department of Public Health Sciences, University of Toronto, Toronto, Ontario, Canada

    Helen Scott

  6. Provincial Medical Genetics Program, Wellness Care Corporation of St. John's, St. John's, Newfoundland and Labrador, Canada

    Marian Crowley

  7. Department of World Sciences, University of Waterloo, Waterloo, Ontario, Canada

    Angeline Lam

  8. London Wellness Sciences Centre & Section of Clinical Biochemistry, University of Western Ontario, London, Ontario, Canada

    Victor Prabhakaran

Corresponding author

Correspondence to Catherine McCourt.

Additional information

Competing interests

The authors declare that they accept no competing interests.

Authors' contributions

SL and CM oversaw the whole report and drafted the manuscript. SL carried out the analysis of NTD charge per unit and statistical analysis. RW, LL, KSO and HS designed the study and carried out the data drove and the dietary assessment. ER, AL and VP participated in the blueprint and carried out the blood analysis. MC carried out the collection of NTD data. All authors read, revised and approved the final manuscript.

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Liu, S., West, R., Randell, E. et al. A comprehensive evaluation of nutrient fortification with folic acrid for the main prevention of neural tube defects. BMC Pregnancy Childbirth 4, twenty (2004). https://doi.org/10.1186/1471-2393-four-20

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  • DOI : https://doi.org/10.1186/1471-2393-4-20

Keywords

  • Folic Acrid
  • Neural Tube Defect
  • Folic Acid Intake
  • Food Fortification
  • Folic Acid Fortification

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