New findings spark a call to revisit folic acid guidelines for pregnancy
An Australian study is drawing attention to a potential unintended consequence of long-standing folic acid (FA) fortification and high-dose supplementation during pregnancy. Researchers report that excessive folate exposure may be linked to a marked rise in gestational diabetes mellitus (GDM) over the past decade. As policy-makers weigh the balance between preventing neural tube defects (NTDs) and avoiding excess folate, the study adds urgency to re-examine how folic acid is used in pregnancy care.
What the study found
The team analyzed data from two cohorts of pregnant women: 1,100 who conceived before food fortification of folic acid was introduced in Australia and 1,300 who conceived after fortification began in 2009. They observed a striking difference in GDM rates: 5% in the pre-fortification group versus 15% in the post-fortification group. In addition, biomarkers of folate status—serum folate and red cell folate—were markedly higher after fortification, along with hormones such as prolactin, human placental lactogen, and placental growth hormone. The researchers reported that red cell folate levels above the normal range rose from 0.5% to 57.6% post-fortification, and women with red cell folate excess had 48% more GDM cases.
Interpreting the link between folate and GDM
While causality cannot be concluded from observational data alone, the study’s authors argue that a combination of fortified foods, high-dose supplements, and continued supplementation beyond the first trimester may push maternal folate levels well above clinical norms. They suggest a plausible mechanism: high maternal folate could alter placental hormone secretion or function in a way that promotes insulin resistance, a hallmark of GDM. The placenta produces hormones that naturally contribute to insulin resistance in pregnancy to optimize fetal glucose supply; excess FA/folate might influence this balance.
Guideline implications and a call for balance
Dr. Tanja Jankovic-Karasoulos, lead author from the Robinson Research Institute at the University of Adelaide, emphasizes a nuanced approach: folic acid remains essential to prevent neural tube defects, particularly for women who may not obtain enough folate from diet alone. The key is the right dose, right window strategy. The study suggests limiting folic acid supplements to 400–500 µg before conception and during the first trimester unless a clinical indication justifies higher doses. Clinicians are urged to avoid duplicating folic acid from multivitamins and fortified foods, and to tailor guidance to individual exposure levels.
What this means for pregnant patients
For many women in a fortified environment like Australia, ongoing supplementation beyond the early pregnancy window may not be necessary unless there is a clear medical reason. Physicians could consider assessing folate status, especially in women with high or unclear exposure to boosters and fortified foods, and strengthen gestational diabetes screening and lifestyle counseling for those with elevated folate intake. In some cases, higher doses (800 µg to 5 mg) may be warranted—for a prior neural tube defect pregnancy or certain medical conditions—though these are exceptional scenarios requiring specialist oversight.
Moving forward
The researchers emphasize that folate remains a critical element of prenatal care. The challenge is to reduce the risk of excess exposure while maintaining protection against neural tube defects. They advocate for clearer guidelines that promote adherence to the dose and duration principle, with clinicians reviewing what patients are taking and whether supplementation is still indicated after early pregnancy. Ongoing research and systematic reviews—particularly in countries with mandatory fortification—will help refine recommendations and protect both maternal and fetal health.
Conclusion
As Australia and other fortifying nations reassess their strategies, the message is evolving: more folate is not always better when it comes to pregnancy. Balanced, individualized guidance could help sustain neural tube defect prevention while curbing unintended metabolic risks, including gestational diabetes.
