Gestational Diabetes Mellitus prevalence and folic acid food fortification: Insights from Australian pregnancy cohorts

<b>Objectives:</b> Gestational diabetes mellitus (GDM) incidence in Australia increased from 5.6% in 2010 to 19.3% in 2022, coinciding with national folic acid (FA) food fortification. High FA intake has been associated with increased insulin resistance and GDM. We examined the association between Australian FA food fortification and maternal folate, placental endocrine function, maternal insulin resistance and GDM incidence.<b>Design and setting:</b> Case control study of two pregnancy cohorts recruited at the same hospital prior to (SCOPE; 2005-2008; Total N=1164) and post (STOP; 2015-2018; Total N=1300) FA food fortification.<b>Outcomes:</b> Circulating folate, red cell folate (RCF), insulin, glucose, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood. Results: GDM incidence increased from 5% (SCOPE) to 15.2% (STOP) and was associated with increased maternal folate. Compared to pre-FA fortification, women post-fortification had higher serum folate (18%; p&lt;0.0001), RCF (259%; p&lt;0.0001), hPL (29%; p&lt;0.0001) and GH2 (12%; p=0.01) concentrations. Despite overall lower insulin resistance in STOP (24%; p=0.003), women with maternal folate excess (levels above the normal RCF 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, STOP women with obesity had 20% (p=0.0006) higher GH2 (hormone that promotes maternal insulin resistance) compared to SCOPE.<b>Conclusions:</b> GDM is associated with higher maternal folate in early gestation. Excess maternal folate due to FA fortification may alter placental endocrine function to increase insulin resistance and risk of GDM, particularly in women with obesity.Note: Data is in long format with repeated measures for Prolactin, HPL, GH2 and HOMA-IR. Folate, demographics and outcome data only measured at one timepoint.