Please refer to anzfa’s guide to applications and proposals for a more detailed explanation of the process on how to undertake

7. Based on the expected increase in folic acid intake from mandatory fortification what are the likely health benefits and risks?

7.1 Expected reduction in neural tube defects

The number of NTDs that could be prevented for Scenario 1 described in Section 6.7.1.2 has been estimated using an approach recommended by (Wald et al., 2001). The Wald model is underpinned by a dose-response relationship between folic acid intake and risk of NTDs according to serum folate concentrations (Attachment 9).
Fortifying bread with folic acid at a concentration of 135 µg /100 g of bread will result in an estimated 14-49 NTD-affected pregnancies being prevented in Australia and 4-14 NTD-affected pregnancies prevented in New Zealand. This represents a reduction of between
4-14% in Australia and 5-20% in New Zealand (Table 5).
Table 5: Estimated number of NTD pregnancies prevented based on adding 135 µg of folic acid per 100 g of bread in Australia and New Zealand

	Mean increase in folic acid intake^* µg/day	Estimated number of NTD pregnancies prevented/year (95% CI)^**		Estimated number of NTD live births/year	Estimated number of NTD stillbirths/year	Estimated number of NTD terminations /year
Australia	101	26 (14-49)		5	3	18
New Zealand	140	8 (4-14)		1	1	5

* Estimates of the mean increase in folic acid intake are based on dietary modelling using DIAMOND.

** Estimates of the number of NTDs prevented are based on the approach by Wald et al. (2001) (see Attachment 9).

As some Indigenous populations in Australia have double the NTD rate (2.56/1,000 total births) compared with the non-Indigenous population (1.32/1,000 total births) (Bower et al., 2006), the fall in NTD incidence among some Australian Indigenous populations may be greater.
It is estimated that up to 70% of NTDs could be prevented through universal use of folic acid supplements (Berry et al., 1999) although the extent of the potential fall is dependent on the folate status of the target population.
The numbers of NTDs have been falling for some years and so the proportion potentially preventable will diminish with time. Where Australia and New Zealand are currently lying in relation to the potential fall of up to 70% of NTD-affected pregnancies from increased folic acid intake remains unknown. The available Australian data on the fall in the number of NTDs since the introduction of voluntary fortification is shown in Figure 1. Lancaster and Hurst (2001) reported the numbers and rates of NTDs in Australia between 1991-95 (pre-fortification) and 1996-97 but concluded that they were likely to be a substantial underestimate; hence the number of pregnancies affected with an NTD pre-fortification remains unknown for this period. The NHMRC (1995) reported 400-500 NTDs per year nationally based on extrapolation of State-based data. This period equates to the time voluntary fortification was introduced. More recently, Bower and de Klerk (2005) reported approximately 340 NTDs per year based on extrapolation of State-based data with good ascertainment rates. Thus, although a similar increase in mean folic acid intake is expected from mandatory fortification as has been achieved with voluntary fortification to date (about 100 µg), the number of NTDs potentially prevented declines because of the increase in the folate status of the population.
Figure 1: Decline in numbers of NTD-affected pregnancies since voluntary folic acid fortification was introduced in Australia in 1996

S
ources:

1 NHMRC (1995)

2 Bower & de Klerk (2005)

3 Predicted by FSANZ at Final Assessment.

7.2 Health risks to the whole population

To assess health risks that might arise from mandatorily fortifying bread with folic acid, the folic acid intakes of population sub-groups were compared to the appropriate UL. The health risks to the whole population are discussed in greater detail in Attachment 8.

7.2.1 Comparison of estimated dietary folic acid intakes with the UL

The proportion of each population group exceeding the UL²⁶ is shown in Table 6.

Table 6: Per cent of Australian and New Zealand respondents with folic acid intakes above the UL at Baseline and Scenario 1

Population Group	Baseline	Scenario 1: All bread 135 g folic acid /100 g
Australia
2-3 years	1	7
4-8 years	<1	3
9-13 years	<1	2
14-18 years	<1	1
19+ years	<1	<1
Women aged 16-44 years	<1	<1
New Zealand*
15-18 years	0	<1
19+ years	<1	<1
Women aged 16-44 years	<1	<1

* Data from the New Zealand national nutrition survey is only available for ages 15 years and over.

7.2.2 Masking of the diagnosis of vitamin B₁₂ deficiency

7.2.2.1 Young children

Vitamin B₁₂ deficiency is rare in children and so the relevance of the UL and hence the risk to children is not clear.

At all fortification levels, including the Baseline level, Australian children aged 2-3 years were the most likely population sub-group to exceed the UL, due to their relatively higher food consumption on a body weight basis. However, for Baseline and the mandatory fortification scenario, the percentage of respondents with intakes greater than the UL declined with increasing age.
Fortifying bread at 135 µg /100 g results in a small percentage of children aged 2-3 and 4-8 years exceeding the UL (7% and 3%, respectively; previously 6% of 2-3 year exceeded the UL based on the Draft Assessment proposal). Of the small proportion of children that are estimated to exceed the UL following the introduction of fortification at this level all are predicted to have intakes below those which would be expected to cause adverse effects. That is, these intakes still remain within the margin of safety. This, combined with the low probability of vitamin B₁₂ deficiency within this age group, suggests that fortification up to 135 µg/100 g bread is very unlikely to put children at risk.

Based on assessments conducted for New Zealand children external to FSANZ using different methodologies²⁷ the results indicate that a similar proportion of New Zealand children 5-14 years would exceed the UL compared to Australian children of the same age.

7.2.2.2 Target group (women 16-44 years)

Only a very small percentage (<1%) of women aged 16-44 years exceed the UL at a fortification level of 135 µg/100 g of bread. This percentage is unchanged from the percentage of women exceeding the UL at Baseline and unchanged from the percentages exceeding the UL at Draft Assessment. Thus, there is no additional risk to health among women of child-bearing age from the level of folic acid intakes likely to arise from mandatory fortification.

The percentage of the target group exceeding the UL increases significantly when folic acid intake from supplements is considered, in addition to folic acid from fortified food. The
800 µg supplement recommended in New Zealand in conjunction with fortified foods could lead to 44% of New Zealand women in the target group exceeding the UL. However, due to the low prevalence of vitamin B₁₂ deficiency in women of child-bearing age, intakes of folic acid at or above the UL are unlikely to have adverse effects.

7.2.2.3 Older people

The sub-group most at risk of adverse effects if the UL is exceeded are older people as vitamin B₁₂ deficiency is most prevalent in this group (see Section 5.2.1). Dietary intake assessment showed none of the individuals aged 70 years and over exceeded the UL at a fortification level of 135 µg/100 g of bread. Only a very small proportion (<1%) of individuals aged 50-69 years exceed the UL at these fortification levels. This is unchanged from the percentage exceeding the UL at Baseline and unchanged from the percentages exceeding the UL at Draft Assessment. Therefore, it is unlikely that at a fortification level of 135 µg/100 g of bread will increase the risk of adverse effects in this population sub-group because of the increased incidence of masking the diagnosis of vitamin B₁₂ deficiency.