To reduce risk for neural tube defects, pregnant women in Australia are advised to supplement with 400µg folic acid (FA) daily, at least one month prior to conception and during first trimester. In September 2009 the Australian government implemented mandatory fortification of bread-making flour with FA, targeting women of reproductive age who may conceive without supplementing. Soon after, manufacturers commenced voluntary fortification of numerous food products with FA, exposing the population to high levels of FA with unknown consequences for pregnancy health.
We have extensive databases and biobanks from two large prospectively recruited pregnancy cohorts from the Lyell McEwin Hospital in Adelaide, Australia prior to (SCOPE 2005-2008) and post (STOP 2015-2018) FA food fortification. Gestational diabetes mellitus (GDM) incidence has increased post (STOP, 15.2%) compared to prior to (SCOPE, 5%) FA fortification, mirroring national trends. We previously showed that in early pregnancy SCOPE women who were later diagnosed with GDM had higher serum folate than those with uncomplicated pregnancies. Here we evaluated data from uncomplicated SCOPE (n= 604) and STOP (n=711) pregnancies to identify factors that may contribute to GDM risk. We measured serum folate, vitamin B12 and homocysteine, as well as placental hormones, hPL, GH-V and prolactin, that are secreted into maternal circulation to stimulate insulin resistance and beta cell expansion.
Compared to SCOPE, STOP women with uncomplicated pregnancies were slightly older (Mean [SD]: 23.6 [5.0] vs 25.6 [4.9]) and in early pregnancy had significantly higher serum folate (Mean±SD 42.5±28.9nM vs 52.9±34.9nM), B12 (Mean±SD 263.9±101pM vs 298±121pM), homocysteine (Mean±SD 4.6±1.1µM vs 5±1.1µM) and hPL (Estimated Marginal Mean±SE 89.5±2.07 vs 100.7±1.78). Interestingly, in women <35years, all three hormones were significantly lower in obese compared to non-obese women.
Considering FA food fortification, high intake of FA during pregnancy warrants further evaluation of potential adverse effects on placental function and pregnancy health.