Oral Presentation ESA-SRB 2023 in conjunction with ENSA

Is maternal folate excess following Australian folic acid food fortification doing harm in pregnancy? (#187)

Tanja Jankovic-Karasoulos 1 , Melanie D Smith 1 , Shalem Leemaqz 1 , Jessica Williamson 1 , Dylan McCullough 1 , Anya L Arthurs 1 , Gustaaf A Dekker 2 3 , Claire T Roberts 1
  1. Flinders University, Bedford Park, ACT, Australia
  2. Lyell McEwin Hospital, Elizabeth Vale, Adelaide, South Australia, Australia
  3. The University of Adelaide, Adelaide, SA, Australia

Gestational diabetes mellitus (GDM) incidence in Australia increased from 5.6 to 19.3% over a decade1, coinciding with the 2009 folic acid (FA) food fortification mandate. FA has been associated with increased insulin resistance and GDM2. Given that most pregnant women in countries with FA food fortification are exceeding the recommended daily FA intake3, we aimed to establish how maternal folate status, placental endocrine function, maternal insulin resistance and GDM incidence have changed post-FA food fortification.

We analysed data from pregnancy cohorts recruited prior to (SCOPE; 2005-2008; N=1164) and post (STOP; 2015-2018; N=1300) FA food fortification. Circulating folate, red cell folate (RCF), insulin, glucose, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in SCOPE and STOP early pregnancy maternal blood.

GDM incidence increased from 5% (SCOPE) to 15.2% (STOP), in line with the national GDM rise, and was associated with increased maternal folate status and altered levels of placental hormones that regulate maternal glucose homeostasis. Compared to women pre-FA food fortification, women post-FA food fortification had higher serum folate (↑18%, p<0.0001), RCF (↑259%, p<0.0001), hPL (↑29%, p<0.0001) and GH2 (↑12%, p=0.01), but lower insulin resistance (↓24%, p=0.003). Although women post-FA food fortification had overall lower insulin resistance, those with maternal folate excess (concentrations exceeding the RCPA reference range) were 23% more likely to be insulin resistant (p=0.002) and had 11% higher PRL (hormone that promotes insulin secretion, p=0.03). Furthermore, obese women post-FA food fortification had 20% higher GH2 (hormone that promotes maternal insulin resistance; p=0.0006) compared to obese women pre-FA food fortification.

Whilst adequate maternal folate may protect against insulin resistance, excess maternal folate may perturb secretion of placental hormones which regulate maternal insulin resistance and glucose homeostasis during pregnancy, to increase insulin resistance and risk of GDM, particularly in the setting of maternal obesity.

  1. 1. AIHW. https://www.aihw.gov.au/reports/diabetes/diabetes/contents/ total-diabetes/gestational-diabetes; Accessed August 2023. 2022
  2. 2. Williamson JM, Arthurs AL, Smith MD, Roberts CT and Jankovic-Karasoulos T. High Folate, Perturbed One-Carbon Metabolism and Gestational Diabetes Mellitus. Nutrients. 2022;14(19): 3930.
  3. 3. Ledowsky C, Mahimbo A, Scarf V and Steel A. Women Taking a Folic Acid Supplement in Countries with Mandatory Food Fortification Programs May Be Exceeding the Upper Tolerable Limit of Folic Acid: A Systematic Review. Nutrients. 2022;14(13): 2715.