MaFOS-GDM trial: Maternal fish oil supplementation in women with gestational diabetes and cord blood DNA methylation at insulin like growth factor-1 ( IGF-1) gene

Background: To evaluate the effects of maternal fish oil supplementation in women with gestational diabetes mellitus (GDM) on birthweight and DNA methylation at insulin like growth factor-1 (IGF-1) gene in their offspring. Methods: Randomized controlled trial. A total of 120 women with GDM were randomized to one of the two groups between 24 and 28 weeks of the pregnancy: Group 1 (n = 52) received fish oil liquid softgel (Ocean plus (R)) and Group 2 (Placebo) (n = 68) sunflower oil liquid softgel. The birthweight and DNA methylation at IGF-1 gene of the offsprings were assessed. Results: We observed a significant inverse association between fish oil use during pregnancy and birthweight (beta = -.18, s.e.: 125, P = .04), corresponding to a 250 g lower birthweight among infants born to fish oil users. This association didn't persist in multivariate analysis. Cord blood IGF-1 was lower in fish oil group (P = .001). Cord blood DNA methylation percentages at CpG-1044 and CpG-611 sites of IGF-1 gene promoter 1 (P1) region were higher in fish oil group compared to placebo group (P = .02 and P = .001, respectively). However, CpG-1044 and CpG-611 methylations were not associated to birthweight (beta = 0.04, s.e: 25.1, P =.66 and beta = 0.04, s.e: 22.7, P = 0.66, respectively). Conclusions: Maternal fish oil use has small effects on birthweight and DNA methylation when given to mothers with GDM at late pregnancy. Future studies are needed to show associations between maternal fish oil use and neonatal DNA methylations. Clinical Trial Registration: "Fish Oil Supplementation in Women with Gestational Diabetes". Identifier: NCT02371343. (c) 2017 Published by Elsevier Ltd on behalf of European Society for Clinical Nutrition and Metabolism.