Food fortification and high doses of folic acid during pregnancy may be to blame for the rise in gestational diabetes.
High doses of folic acid during pregnancy and food fortification have led to excess folate levels in Australian women and may be behind the tripling of gestational diabetes rates in the past decade, researchers say.
Women who take high doses of folic acid supplements during pregnancy were at much higher risk of developing gestational diabetes, said the Australian researchers, who called for supplementation guidelines to be reviewed.
The researchers used data from 1100 women who were pregnant before food fortification was introduced and 1300 women after fortification.
They found that 15% of women in the post-fortification cohort had gestational diabetes compared with 5% in the pre-fortification group.
They also found that concentrations of serum folate, red cell folate, prolactin, human placental lactogen and placental growth hormone were all higher in the post-fortification group.
The proportion of women with red cell folate levels above the normal reference range increased from 0.5% before fortification to 57.6% after fortification, and women with red cell folate excess had 48% more gestational diabetes cases.
A combination of folic acid food fortification, high doses of supplements and taking supplements beyond the first trimester have resulted in maternal folate levels that “far exceed the established clinical reference range”, the Flinders University and University of Adelaide researchers said in Nutrients.
Lead author Dr Tanja Jankovic-Karasoulos, from the Robinson Research Institute at the University of Adelaide, said that since Australia introduced folic acid food fortification in 2009, baseline folic acid in the population was high, deficiency was rare, and excess was common.
“The challenge is to maintain protection against neural tube defects while avoiding excess exposure,” she told The Medical Republic.
“Our findings, alongside other studies, show that high folic acid intake and very high maternal folate levels increase the risk of GDM. As populations have shifted from deficiency to potential excess, we need equal focus on the consequences of maternal folate excess.”
Dr Jankovic-Karasoulos said folic acid supplements were still important to prevent neural tube defects because some women would not get enough folate from diet and fortified foods.
But patients should be reminded that it was only necessary to take 400-500µg of folic acid folic one month before conception and during the first trimester only – unless otherwise indicated – as the neural tube closes about four weeks after conception, she said.
Women should also be advised to avoid doubling up with multivitamins containing folic acid, Dr Jankovic-Karasoulos said.
“Reinforce the ‘right dose, right window’ principle,” she said.
Related
“After pregnancy is established, for many women in a FA-fortified food environment, continued supplementation may not be necessary beyond the early window unless there is a clear clinical indication. This is an area where future guidelines may need to evolve.”
Dr Jankovic-Karasoulos suggested considering folate status checks in women with high or unclear exposure and said to be vigilant with gestational diabetes screening and lifestyle counselling in women with high folic acid intake.
Higher doses – 800µg to 5mg – may be indicated for previous neural tube defect pregnancies and certain medical conditions, she said.
“Adequate folate remains essential for preventing neural tube defects and supporting pregnancy, so we are not calling for FA to be abandoned,” said Dr Jankovic-Karasoulos.
“However, in a widely fortified food environment like Australia, the message must be that more is not always better, and better regulation is needed.
“The concern is not whether to recommend FA but ensuring adherence to the correct dose and duration. GPs can support this by reviewing what women are already taking and reinforcing adherence to current guideline-based use.”
Dr Jankovic-Karasoulos said rates of gestational diabetes in Australian have more than tripled in a decade, from 5.4% in 2011 to 19.3% in 2022, but known risk factors such as maternal age, obesity, ethnicity and changes in diagnostic criteria “do not explain the magnitude nor the trajectory of this rise, suggesting additional contributors”.
While the mechanism was not clear, the researchers said animal studies had shown that high folic acid intake during pregnancy played a role in insulin resistance and impaired glucose.
Hormones secreted by the placenta “contribute to the physiological insulin resistance of pregnancy, a critical adaptation that increases maternal glucose availability for the foetus”, the authors said.
“It is plausible that increased FA/folate supply from the mother to the placenta can alter placental function (hormone secretion) placing women at increased risk of GDM,” they said.
The researchers said a recent systematic review of women taking folic acid supplements in countries with mandatory food fortification programs, including Australia, found that almost all women exceed the 1000μg daily limit.
