Researchers asked for an urgent safety assessment
Dr Clare Craig
For close to seventeen years, folic acid has been added to almost all bread-making flour in Australia and eaten across the population. Britain has begun to do the same with a mandate from 13 December 2026.
There has been only one randomised trial of a modest dose in low-risk women, which tested a multivitamin containing 0.8 mg of folic acid. It recorded about nine excess fetal losses for every neural tube defect prevented. It also found a 41 percent increase in multiple births and, years afterwards, more illness in the children. The mothers were never followed up at all.
Australia now supplies an additional warning of risks to pregnant women.
What was found
Researchers in Adelaide compared two large pregnancy cohorts recruited at the same hospital under near identical entry criteria. The first was recruited in the years before the 2009 fortification mandate and the second six to nine years after. Both excluded women who already had diabetes. Both were scored for gestational diabetes against the same diagnostic threshold. Gestational diabetes, meaning diabetes first recognised in pregnancy, tripled between the two cohorts, from 5.0 percent of women to 15.2 percent. Other pregnancy complications were stable or falling and none of the other differences were statistically significant.
| Outcome | Before | After | p |
|---|---|---|---|
| Gestational diabetes | 5.0% | 15.2% | <0.0001 |
| Gestational hypertension | 8.1% | 6.4% | 0.14 |
| Pre-eclampsia | 10.1% | 9.2% | 0.37 |
| Spontaneous preterm birth | 5.9% | 4.7% | 0.14 |
| Small for gestational age | 12.1% | 11.9% | 0.65 |
Pregnancy complications in the two Adelaide cohorts, before and after fortification, with the p value for each difference.
Across the whole of Australia, gestational diabetes rose from 5.6 percent of pregnancies in 2010 to 19.3 percent in 2022. That is 13.7 more women diagnosed in every hundred and the national rise matched the trajectory seen in the study.
What else might explain the rise?
Diagnosis. Australia adopted new diagnostic criteria for gestational diabetes in 2015. The new thresholds require lower blood sugar levels for a diagnosis, so inevitably there have been more diagnoses. Both the study’s cohorts were scored against the same threshold and when the earlier cohort was rescored on the new criteria its rate only moved from 4.4 percent to 5.0. The authors accept that the criteria change explains part of the national rise but not its magnitude or its trajectory.
Demographics. The later cohort was older and heavier. The researchers adjusted for maternal age, weight, ethnicity, socioeconomic status and metabolic syndrome together, and the tripling remained significant after all of them. Metabolic syndrome, the cluster of raised blood pressure, blood sugar, blood fats and waist measurement that most strongly predicts gestational diabetes, was in fact half as common in the later cohort, 8.6 percent against 17.2. The women in the later cohort had a lower predicted risk yet developed three times the disease.
General metabolic decline. If Australians generally were becoming more diabetic, diagnosed type 2 diabetes in the wider population would be expected to climb a comparable curve. It has not. Age-standardised type 2 prevalence has been broadly stable for the past decade and the incidence rate has been falling steadily since 2000, while gestational diabetes tripled. Whatever is driving this change from 2009, it acts on pregnancy rather than on glucose metabolism generally.
What changed
2009 is the year Australia mandated folic acid in flour. It takes many hours for the body to remove folic acid but when it does it turns it into folate the body can use. The measure of blood stores of folate, red cell folate, therefore reflects intake over the preceding months. It was measured in 1,191 women in the post-fortification cohort and, because the earlier cohort was not tested, in a separate group of 410 women recruited at the same hospital in the same pre-fortification years. Across those two measurements the median rose from 561 nmol/L to 1,490, against a clinical reference range of 360 to 1,400. Those with the lowest stores fell from 22.7 percent of women to 0.6. Levels above the normal reference range rose from 0.5 percent to 57.6. A large share of post-fortification samples were recorded as 1,790 nmol/L, which is the highest figure the laboratory assay can register, so the true rise is larger than the measured one. The authors rightly called this “maternal folate excess”.
Supplement exposure was also high. Reported use of supplements containing 800 micrograms of folic acid or more, twice the recommended dose, rose from 25.9 percent of women to at least 60 percent.
There was a clear dose response relationship. The post-fortification cohort showed a correlation with those with higher folate being more likely to have gestational diabetes. After the same adjustment for age, weight, ethnicity, socioeconomic status and metabolic syndrome, every 500 nmol/L increase in red cell folate raised the risk of gestational diabetes by 34 percent. The risk was 12.5 percent for those with folate within the normal range, 16.2 for those above it and 18.5 for those at or beyond the assay ceiling. Women whose folate was too high to measure had 48 percent more gestational diabetes than women in the normal range, a difference too large to be put down to chance. A dose response relationship is a core piece of evidence of causation in epidemiology.
The study’s own authors conclude that maternal folate status is an independent risk factor for gestational diabetes which has likely contributed to the national rise. They called for urgent assessment of the safety of folate excess in pregnancy. That call comes seventeen years after the exposure began.
How much of the rise did folic acid cause?
Since 2009 there has been no unexposed Australian population left to compare against, so no attributable fraction can be estimated from these data.
Start with the lower end. In the two cohorts, gestational diabetes went from 5.0 percent of women to 15.2, a increase of 10.2. The women who remained within the reference range of folate levels still saw an increase in risk. Instead of a risk of 5.0, these women were affected at a rate of 12.5 percent. In theory it could be argued that other factors were causative for these women. Taking that conservative view we can assume that all women in the cohort would have been affected at a rate of 12.5 percent in a folic acid free environment. Based on that assumption only the difference between 12.5 and the actual average of 15.2 would be attributed to folic acid i.e. 2.7 percent. It is worth remembering that the women within the reference range were still exposed to folic acid but may have handled it differently and the 12.5 figure is an observed category rate rather than a true control baseline. Nevertheless, this is a reasonable lower end scenario.
At the other extreme, if we attribute to folic acid the whole residual increase in risk once the diagnostic criteria change and demographic drift are removed, then the causal share of the increase that can be attributed to folic acid rises to about 80 percent (10.9 of the 13.7 percentage point rise). This would assume every other unmeasured change across the period that could impact on prevalence remained static. Nevertheless, it gives a useful upper estimate.
The honest position is that the causal share sits somewhere between zero and four-fifths, and that the evidence for it being well above zero is the clear dose-response relationship.
What a diagnosis means for a woman
Australia has about 290,000 births a year, so a rise of 13.7 percentage points represents roughly 39,700 women a year being diagnosed who would not have been diagnosed at the old rate. On the lower scenario about 10,300 of those diagnoses would be attributable to folic acid. On the upper scenario it would be about 31,800.
A diagnosis at 26 to 28 weeks means about thirteen weeks of diabetes management with four finger-prick tests a day. Of women diagnosed, 43 percent receive insulin and 8.1 percent oral medication. On the lower scenario that is about 4,400 additional insulin-treated pregnancies a year, 3.8 million finger-prick tests (10,300 × 13 weeks × 7 days × 4 tests) and 2,600 woman-years of restricted diet, every year the policy runs. On the upper scenario it is 13,700 insulin-treated pregnancies, 11.6 million tests and 7,900 woman-years.
Gestational diabetes also results in more induced labours, more caesarean sections, more large babies with the shoulder injuries and birth trauma that follow, and more newborns with low blood sugar, jaundice or an admission to special care. Afterwards it carries a substantially raised risk of type 2 diabetes in the mother, a raised cardiovascular risk and impaired glucose tolerance in the child.
Nobody is looking
Britain begins fortifying in December 2026, at 250 micrograms per 100 grams of flour, above the 200 microgram minimum Australia set. Nothing in the regulations monitors for gestational diabetes. If Britain sees what Australia saw, nothing is in place to notice.
