A randomized controlled double-blinded trial to assess the risk of gestational diabetes mellitus in non-anemic pregnant women who receive oral iron supplementation

Pregnant women in India are routinely prescribed oral iron supplements as part of the national Anemia Mukt Bharat (AMB) program for anemia control. In women with iron-deficiency anemia, the benefits of iron supplementation during pregnancy, both for the mother and child, are very clear. In non-anemic pregnant women, however, the benefits of iron supplementation vis-à-vis associated risks that have been reported have not been studied adequately. Studies have suggested that iron may impair insulin secretion, thus increasing the risk of gestational diabetes mellitus (GDM). Primary objective: To determine the incidence of GDM among non-anemic pregnant women receiving 60 mg/day of elemental iron as oral supplementation, compared with those receiving 30 mg/day. Secondary objectives: To assess beta-cell functional capacity and quantify unmethylated insulin promoter DNA (a sensitive and specific marker of beta-cell damage) in blood samples from the two study groups. This study is a randomized, parallel-group, double-blinded clinical trial, with 800 non-anemic primigravidae in each arm. One arm will receive oral supplementation at a dose of 60 mg per day (as per current national guidelines), while the other arm will receive 30 mg per day, for a duration of 12 weeks in the second trimester. The incidence of GDM in the two arms will be compared. Insulin secretion kinetics will be assessed using an oral glucose tolerance test (OGTT) done at the end of the intervention. Additionally, the unmethylated insulin promoter DNA in circulating free DNA (a marker of beta-cell damage) will be quantified in both arms. The study’s findings will provide important evidence relevant to the current national guidelines in India on universal oral iron supplementation during pregnancy. The results are expected to inform future policy decisions on whether universal supplementation for all pregnant women is appropriate or whether it should be targeted to those with low iron status. CTRI/2024/04/065301 [registered on 05/04/2024]—trial registered prospectively.