New research led by Flinders University highlights the urgent need to establish a safe upper limit for folic acid intake during pregnancy and to improve guidelines on folic acid supplementation during pregnancy.
A new study by published in the journal Nutrients links the rise in gestational diabetes in part to excess maternal folate levels, due to the dual impact of folic acid (FA, or synthetic folate) in food fortification and higher-than-recommended supplementation doses during pregnancy.
National surveillance shows the incidence of gestational diabetes mellitus (GDM) in Australia has more than tripled, rising from 5.6% in 2010 to 19.3% in 2022.
The research - led by Dr Tanja Jankovic-Karasoulos, now at The University of Adelaide, and Professor Claire Roberts, at Flinders University - highlights both the need to establish a safe upper limit for FA intake during pregnancy, and to re-evaluate supplementation guidelines in the context of widespread food fortification and increased dose and duration of real-world supplementation practice.
"Our study shows that excess maternal folate significantly increases GDM risk in our post-fortification pregnancy cohort," says Dr Jankovic-Karasoulos, from the Robinson Research Institute at University of Adelaide.
"We suspect that increased FA intake over the past 10-15 years is contributing to the steady rise in GDM prevalence in Australia."
Adequate folate is essential for DNA formation and proper cell growth and development. Current guidelines recommend supplementation with 400-500 µg of FA daily, starting at least one month prior to conception and continuing through the first trimester to reduce the risk of neural tube defects such as spina bifida.
"Our study suggests that higher-than-recommended FA intake may have unintended consequences for pregnancy," says Dr Jankovic-Karasoulos, who last year was awarded an NHMRC Ideas Grant, Flinders Foundation Health Seed Grant and Diabetes Australia Project Grant to further investigate the effects of high FA intake during pregnancy on placental function, maternal insulin resistance and glucose handling.
"The placenta is central to regulating maternal glucose tolerance in pregnancy, so we need to understand how high FA intake affects placental function and, in turn, insulin resistance and gestational diabetes risk."
NHMRC Investigator Research Fellow Professor Claire Roberts, from the Pregnancy Health and Beyond Laboratory at Flinders University, says understanding the potential harms of excess FA intake is of major public health importance.
"The use of FA is widely recommended worldwide, but we need to keep investigating unexpected implications, plus how to identify women at risk of gestational diabetes early in pregnancy to protect the baby from adverse effects of high maternal blood glucose for the best start in life," says Professor Roberts, from the Flinders Health and Medical Research Institute.
Researchers emphasise the importance of adequate folate in pregnancy but highlight the need to establish a safe upper limit of FA intake. They would also like to see improved guidelines on FA supplementation during pregnancy which would protect the fetus right at the beginning of gestation against neural tube defects but also protect the mother and fetus from adverse effects of high blood glucose.
Findings from this study are based on more than 2000 women recruited to the pre-FA fortification SCOPE (Screening for Pregnancy Endpoints), Adelaide and post-fortification STOP (Screening Tests to identify poor Outcomes of Pregnancy) pregnancy cohorts.
The article, Maternal folate excess, placental hormones, and gestational diabetes mellitus: Findings from prospective cohorts before and after mandatory folic acid food fortification (2025) by Tanja Jankovic-Karasoulos, Melanie D Smith, Shalem Leemaqz, Murthy Mittinty, Jessica Williamson, Dylan McCullough, Anya L Arthurs, Gustaff A Dekker (Robinson Research Institute & Lyell McEwin Hospital) and Claire T Roberts has been published in Nutrients DOI: 10.3390/nu17172863.
Acknowledgement: This project is funded by the National Health and Medical Research Council Investigator grant program (GNT1174971 and GNT1161079) and Flinders Foundation Health Seed grants.
