Myo-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial

<h4>Objective</h4>Better preconception metabolic and nutritional health are hypothesized to promote gestational normoglycemia and reduce preterm birth, but evidence supporting improved outcomes with nutritional supplementation starting preconception is limited.<h4>Research design and methods</h4>This double-blind randomized controlled trial recruited from the community 1,729 U.K., Singapore, and New Zealand women aged 18-38 years planning conception. We investigated whether a nutritional formulation containing <i>myo</i>-inositol, probiotics, and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy could improve pregnancy outcomes. The primary outcome was combined fasting, 1-h, and 2-h postload glycemia (28 weeks gestation oral glucose tolerance test).<h4>Results</h4>Between 2015 and 2017, participants were randomized to control (<i>n</i> = 859) or intervention (<i>n</i> = 870); 585 conceived within 1 year and completed the primary outcome (295 intervention, 290 control). In an intention-to-treat analysis adjusting for site, ethnicity, and preconception glycemia with prespecified <i>P</i> < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] log_e mmol/L intervention vs. control -0.004 [-0.018 to 0.011], 0.025 [-0.014 to 0.064], 0.040 [0.004-0.077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes mellitus (24.8% vs. 22.6%, adjusted risk ratio [aRR] 1.22 [0.92-1.62]), birth weight (adjusted β = 0.05 kg [-0.03 to 0.13]), or gestational age at birth (mean 39.3 vs. 39.2 weeks, adjusted β = 0.20 [-0.06 to 0.46]), but there were fewer preterm births (5.8% vs. 9.2%, aRR 0.43 [0.22-0.82]), adjusting for prespecified covariates.<h4>Conclusions</h4>Supplementation with <i>myo</i>-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth.