The government has costed the benefit of fortification but ignored the harm
Dr Clare Craig
| Key points ● The UK government model gives an expected benefit of fortification of 624 quality adjusted life years (QALYs) per year of fortification. ● Half of the harm from one problem – gestational diabetes – is enough to wipe out this benefit in terms of QALYs. ● Adding the complications and consequences of gestational diabetes would make the balance even worse. |
An Australian group measured gestational diabetes recruited before and after mandatory folic acid fortification. It tripled. From 5% to 15%. Furthermore, there was a clear dose response relationship where risk increased stepwise for each increase in a marker of the mother’s folic acid intake. The evidence is set out in a companion article. The study’s own authors call for urgent assessment of the safety of folic acid in pregnancy.
If Britain sees anything like what Australia saw, how much of the rise would have to be caused by folic acid before the harm from gestational diabetes alone outweighs the claim made for benefit based on government modelling?
The answer is only a half.
What is the claimed benefit?
The most optimistic claim is that adding folic acid to our food will prevent around 200 neural tube defects a year.
The government assessment carried out at the time the regulations were put through covers England only and is more specific. It takes an average of 165 babies born alive with a neural tube defect each year (2.75 per 10,000 births, which implies about 600,000 births a year in England) and applies a 19 percent reduction in risk. That estimate of 19 percent is the average of predictions from two other models — 15.4 percent and 22.4 percent. The claimed potential benefit is 31 fewer affected live births a year: 24 spina bifida, 4 encephalocele and 3 anencephaly, which is fatal within hours of birth. The remaining benefit is in reduced terminations.
The assessment assumed a baseline of about 800 affected pregnancies a year in England. The English registry recorded only 621. The number has been falling for years. The reasons the assessment’s figure is too high are set out elsewhere. For the sums here the registry figure is used, which reduces every case count by a fifth (621 ÷ 800 = 0.78).
On the corrected figures, England alone would have 118 fewer affected pregnancies (19% of 621) which equates to a fall of 2.0 per 10,000. Australian surveillance recorded a fall of 1.5 per 10,000 (44 fewer across 290,000 births). There are numerous reasons to think the British claim is optimistic, but, to be conservative, the full benefit is taken here for the purposes of comparing with the harm.
Balancing benefit and harm
To compare benefit against harm, healthcare economists use quality adjusted life years, or QALYs. One QALY is a full year of totally healthy life. A year lived with illness or disability counts as a fraction of a QALY.
The government’s assessment puts the whole life of a healthy newborn at 41.9 QALYs, which works out at being 81 years of life discounted at the Treasury’s 1.5 percent rate for health effects. It then works out what each neural tube defect costs against that.
| Condition | Life expectancy | Quality of life | QALYs lived | QALYs lost |
| Healthy newborn | 81 years | 1.00 | 41.9 | 0 |
| Spina bifida | 43 years | 0.55 | 17.6 | 24.2 |
| Encephalocele | assumed as spina bifida | 0.55 | 17.6 | 24.2 |
| Anencephaly | under one day | 0 | 0 | 41.9 |
Table 14 of the assessment: QALYs lost by each affected child that could be prevented if benefit claim were true
The earlier 2019 consultation assessment valued prevented terminations as equivalent to stillbirths i.e. the whole full life for a fatal case. However, in the final assessment terminations were not included in the health costs and counted as part of the economic analysis based on the cost of the procedure avoided i.e. £500 to £1,600 each.
Applying these valuations to the claimed reduction in cases gives an annual benefit of 803 QALYs (28 surviving cases × 24.2, plus 3 fatal cases × 41.9). Correcting the case count to the registry baseline gives 624 QALYs (28 × 0.78 = 21.7 surviving cases × 24.2, plus 3 × 0.78 = 2.3 fatal cases × 41.9).
Any harm in the whole population that exceeds 624 QALY per year will wipe out the optimistic gain from putting folic acid into the flour.
Quantifying the harm
For the mother, a diagnosis of gestational diabetes at 26 to 28 weeks gestation will result in about thirteen weeks of diabetes management with four finger-prick tests a day. Of women diagnosed, 43 percent receive insulin while 8.1 percent receive oral medication.
The thirteen weeks of testing, restricted eating and the insulin injections (for those who need them), lived at about 92 percent of full health, comes to 0.02 QALYs per case, or about one week of healthy life lost.
Based only on this one harm, if England saw the same rise in incidence of gestational diabetes that Australia saw, a rise of 10.2 percentage points (5.0 percent to 15.2), that would be 61,200 additional diagnoses a year (600,000 births × 10.2 percentage points).
The comparison
It would take 31,200 cases of gestational diabetes at 0.02 reduction in QALYs to equal the 624 claim of benefit. That could be expressed as 51 percent of the 61,200 more cases that Australia saw.
If folic acid accounted for half of an Australian-sized rise in gestational diabetes the burden of the disease and its treatment would cancel the whole claimed benefit in terms of neural tube defects.
It is impossible to know what fraction of the rise in Australia was directly due to folic acid. When the researches took a conservative view of the impact of folic acid and compared the rate among women with folate levels in the normal range and the rate for the whole cohort, they estimated 26 percent could be due to folic acid. However, they had no actual control group. The “normal” women were also exposed to folic acid. It would take a randomised controlled trial to measure it properly. But taken at face value, if 51 percent cancels the benefit then 26 percent takes us half way there without a single complication from gestational diabetes being counted.
What about the complications?
The 0.02 QALY estimate only includes the mother’s management of the diagnosis. The complications, for mother and child, are excluded. For the baby the sum excludes the induced labours, the caesarean sections, the large babies and the shoulder injuries and birth trauma that come with them, the newborns with low blood sugar, the jaundice, the admissions to special care and the future risk of impaired glucose tolerance. For the mother it excludes her cardiovascular risk and the raised risk of type 2 diabetes in the decades afterwards, which is the best documented long-term consequence of the condition.
For each of those complications the QALYs lost mount up. The later maternal diabetes alone would change the balance dramatically such that only a few percent of the increase would have to be due to folic acid.
There are plenty of other harms
Evidence of other types of harm swing the pendulum further still away from justifying the intervention. The 41 percent excess of multiple births in the Hungarian trial is a serious complication which leads to a variety of pregnancy and neonatal complications. The same study found statistically significant increases in illness in the children and these also haven’t been costed. The mothers in that trial were never followed up. The excess fetal losses in that trial, nine for every claimed prevention are not costed either. The cancer risk and risk to those with heart stents and with vitamin B12 deficiency are not included either despite these groups representing millions of people.
The burden of proof
The decision on folic acid is to add a licensed drug to a staple food eaten by an entire population. It was once widely accepted that the standard that applies to a measure like this is that its proposer must demonstrate that it is safe. Its critics are not required to demonstrate that it is harmful. On this single measure of one harm, the sums do not survive. A risk benefit analysis of the health impact was never done. A debate in the House of Commons was never had. The regulations that were passed make no legal requirement that any of these harms should be measured and monitored.
