Oral Presentation Australasian Diabetes in Pregnancy Society Annual Scientific Meeting 2024

Maternal Folate Status and the Prevalence of Gestational Diabetes Mellitus: Insights from Australian Pregnancy Cohorts (107640)

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

Background: The WHO recommends women supplement with 400μg folic acid (FA; synthetic folate) daily when trying to conceive until 12 weeks of gestation, to reduce the risk of fetal neural tube defects1. Given the neural tube closes ~4 weeks post-conception2 (before most women know they are pregnant) and that many pregnancies are unplanned, the Australian government mandated FA food fortification in 20093. Concurrent with this has been an increase in the use of prenatal multivitamins that contain double the recommended FA dose, and women who continue to supplement throughout pregnancy4 despite no established benefit of FA supplementation beyond the first trimester. Observational studies provide evidence that high FA intake and supplementation beyond the first trimester are associated with an increased risk of gestational diabetes mellitus (GDM)5,6. Animal studies provide evidence that high FA causes insulin resistance and metabolic dysfunction7-10, but mechanisms remain unknown. Given that the placenta is a key regulator of maternal glucose homeostasis during pregnancy11, it is likely that FA acts via the placenta to increase GDM risk.

Aims: 1. Measure GDM incidence, maternal folate status and concentrations of hormones that regulate glucose homeostasis during pregnancy in women prior to and post FA fortification; 2. Perform in vitro experiments to establish direct effects of FA on placental hormone secretion.

Methods: 1: Maternal folate, prolactin (PRL), human placental lactogen (hPL) and placental growth hormone (GH2) were measured in early pregnancy maternal blood taken from women prior to (SCOPE; 2005-2008; Total N=1164) and post (STOP; 2015-2018; Total N=1300) FA food fortification. GDM incidence was established using the 2014 WHO diagnostic criteria. 2: First and second trimester human placentas (N=66) were treated with increasing doses of FA to determine direct effects on PRL, hPL and GH2 secretion.

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<0.0001), red cell folate (RCF; 259%; p<0.0001), hPL (29%; p<0.0001) and GH2 (12%; p=0.01) concentrations in early gestation. Increasing RCF placed STOP women at 34% increased risk of developing GDM (RR [95% CI]: 1.34 [1.01, 1.78], p=0.04). In vitro, high FA increased placental secretion of GH2 and hPL by 31% and 34% (p<0.05), respectively.

Interpretation: Elevated maternal folate in early gestation is a significant GDM risk factor. We propose the role for FA in increasing the GDM incidence in Australia, potentially via altering placental endocrine function.