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Evaluation of Food Fortification with Folic Acid for the Primary Prevention of Neural Tube Defects

Table 1: Framework for a two-phase, multi-site study to examine the effects of food fortification with folic acid

Content Study objective Sample** Location
I. Knowledge and intake of folic acid supplements Determine knowledge and consumption of folic acid supplements, pre- and post-fortification Non-pregnant women of childbearing age (19-44 years) St. John's
Rural Newfoundland
Kingston, Ontario
II. Dietary assessment* Determine dietary intake of folate, pre- and post- fortification

A) Non-pregnant women of childbearing age (19-44 years), not taking supplements containing folic acid;

B) Seniors (65 years or older) not taking supplements containing folic acid or B12 supplements and not diagnosed with anaemia

St. John's
Rural Newfoundland
Kingston, Ontario

 

III. Blood analysis* Determine blood folate and vitamin B12 status, pre- and post-fortification St. John's only
IV Rates of NTDs Determine incidence of NTD-affected pregnancies, pre- and post-fortification Provincial population Province of Newfoundland and Labrador
*
  
For each phase, the same sample of women and seniors were analyzed in Components II and III.
**  Sampling was done separately for Phases I and II.

Table 2: Knowledge and use of supplements containing folic acid

 
Newfoundland
Ontario
Phase I
Phase II
Phase I
Phase II
Participants (n)
469
443
481
451
Knowledge (%)
32.8
45.6*
35.6
51.2*
Use of supplements (%)
17.1
28.0*
33.0
38.8
*   Increase from Phase I to Phase II is statistically significant.

Table 3: Use of supplements containing folic acid by likelihood of pregnancy

Likelihood of pregnancy
Newfoundland
Ontario
Phase I
Phase II
Phase I
Phase II
Number
% users
Number
% users
Number
% users
Number
% users
Not using birth control
50
18.0
33
54.5*
53
41.5
38
50.0
Using birth control
202
19.8
200
27.0
224
29.4
172
40.6
No chance
198
11.1
193
20.7
199
34.2
236
35.6
Information not available
19
47.4
17
70.6
5
60.0
5
40.0
Total
469
17.1
443
28.0
481
33.0
451
38.8
*   Increase from Phase I to Phase II is statistically significant.

Table 4: Laboratory data (geometric mean and 95% confidence interval) for young women participants (age 19-44 years) for Phase I and Phase II

Characteristics
Phase I
Phase II
p value*
Total participants (n)
322
305
-
Serum folate (nmol/L)
14.4
(13.9-15.0)
19.0
(18.4-19.7)
<0.001
RBC Folate (nmol/L)
647
(627-669)
796
(769-824)
<0.001
Plasma HCY (µmol/L)
10.0
(9.6-10.4)
8.9
(8.6-9.2)
<0.001
Serum vitamin B12 (pmol/L)
188
(180-197)
199
(191-207)**
0.02
Plasma MMA (µmol/L)
0.18
(0.17-0.19)
0.20
(0.18-0.21)**
0.169
*   Significance test of difference between Phase I and Phase II is based on non-parametric Mann-Whitney U test.
** The distribution of log-transformed data failed when tested for normality by the Komogorov-Smirnov test for p <0.05.

Table 5: Laboratory data (geometric mean and 95% confidence interval) for senior participants (age 65 or over) for Phase I and Phase II

Characteristics
Phase I
Phase II
p value*
Total participants (n)
202
186
-
Serum folate (nmol/L)
14.8
(14.0-15.6)
23.0
(22.0-24.1)
<0.001
RBC Folate (nmol/L)
745
(713-779)
916
(873-961)**
<0.001
Plasma HCY (µmol/L)
13.6
(13.0-14.2)**
12.3
(11.7-12.9)**
0.001
Serum vitamin B12 (pmol/L)
183
(173-194)
216
(202-231)
<0.001
Plasma MMA (µmol/L)
0.24
(0.22-0.27)**
0.26
(0.24-0.28)
0.229
*   Significance test of difference between Phase I and Phase II is based on non-parametric Mann-Whitney U test.
** The distribution of log-transformed data failed when tested for normality by the Komogorov-Smirnov test for p <0.05.

Table 6: Incidence of neural tube defects (NTDs) in Newfoundland before folic acid supplementation (1991-1993), prior to folic acid fortification (1994-1997) and after fortification (1998-2001)

Year
Number of cases of NTDs
Total number of births*
Average incidence per 1,000 births per year
In live births and stillbirths
In terminated pregnancies
Total
Pre-supplementation
1991-1993
50
40
90
20,711
4.35
Pre-fortification
1994-1997
53
50
103
23,592
4.37
Post-fortification
1998-2001
8
11
19
19,816
0.96
*   The total number of births includes live births, stillbirths and terminations for NTD.

Figure 1: Incidence of NTDs in Newfoundland, 1976 to 2001 (3-year moving average rates)*

*   The rate for 1976 is a 2-year average based on data for 1976 and 1977 and the rate for 2001 is a 2-year average based on data for 2000 and 2001.
** Live births, stillbirths and terminations for NTDs.