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

Diabetes Care

Mar 2021

DOI: 10.2337/dc20-2515

Citations:51

Influential Citations:4

Interventional (Human) Studies

Enhanced Details

Methods

International, multicenter, double-blind randomized controlled trial enrolling 1,729 women aged 18–38 planning conception from the U.K., Singapore, and New Zealand. Community-based recruitment; excluded pregnancy or lactation at enrollment and preexisting type 1 or type 2 diabetes. Randomized 859 to control and 870 to intervention. Primary outcome: glycemia after a 75-g OGTT at 28 weeks; 585 pregnancies reached 28 weeks and provided primary outcome (295 intervention, 290 control).

Intervention

Preconception- and pregnancy-started supplementation with myo-inositol (4 g/day), probiotics (Lactobacillus rhamnosus NCC 4007; Bifidobacterium animalis subsp. lactis NCC 2818), and micronutrients (vitamin D 10 μg/day; riboflavin 1.8 mg/day; vitamin B6 2.6 mg/day; vitamin B12 5.2 μg/day; zinc 10 mg/day; folic acid 400 μg/day; iron 12 mg/day; calcium 150 mg/day; iodine 150 μg/day; beta-carotene 720 μg/day). Taken as a powder in sachets twice daily, mixed in water; stored at 2–6°C; started before conception and continued through pregnancy.

Results

Primary outcome: no difference in gestational glycemia at 28 weeks between groups after adjustment for site, ethnicity, and preconception glycemia. GDM incidence: 24.8% intervention vs 22.6% control (aRR 1.22 [0.92–1.62]); not statistically significant. Birth weight and gestational age at birth were similar. Preterm birth reduced with intervention (5.8% vs 9.2%; aRR 0.43 [0.22–0.82]); late preterm births and PPROM also reduced; PPROM incidence lower (2.9% vs 6.8%; aRR 0.39 [0.16–0.97]). Major postpartum hemorrhage lower in intervention (3.1% vs 8.2%; aRR 0.44 [0.20–0.94]). No differences in hypertensive disorders or most neonatal outcomes. Adherence was high; 25-hydroxyvitamin D higher at 28 weeks in the intervention group. Conclusion: Starting this preconception- and pregnancy-based nutritional formulation did not improve maternal glycemia or GDM risk but reduced preterm birth; potential benefit for preterm birth warrants further study.

Limitations

Generalizability limited by underrepresentation of Latina and Native American populations and only a few Black and Polynesian participants; study population largely not overweight/obese, limiting applicability to higher-risk groups; conducted in high-resource settings; microbiome data not collected to confirm probiotic viability; adherence measured by sachet counts (imperfect); intervention combined multiple components, so individual contributions cannot be disentangled; secondary outcomes were not adjusted for multiple comparisons; not powered for all subgroup analyses.

Abstract

OBJECTIVE 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. RESEARCH DESIGN AND METHODS 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 myo-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). RESULTS Between 2015 and 2017, participants were randomized to control (n = 859) or intervention (n = 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 P < 0.017 for multiplicity, there were no differences in gestational fasting, 1-h, and 2-h glycemia between groups (β [95% CI] loge 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. CONCLUSIONS Supplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth. show less