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

Keith M Godfrey, Sheila J Barton, Sarah El-Heis, Timothy Kenealy, Heidi Nield, Philip N Baker, Yap Seng Chong, Wayne Cutfield, Shiao-Yng Chan, NiPPeR Study Group, Veronica Boyle, Shirong Cai, Ryan Carvalho, Julie Ann Guiao Castro, Mary Cavanagh, Hsin Fang Chang, Claudia Chi, Caroline E Childs, Mary F Chong, Cathryn Conlon, Cyrus Cooper, Paula Costello, Vanessa Cox, Marilou Ebreo, Judith Hammond, Nicholas C Harvey, Richard Holt, Hazel M Inskip, Mrunalini Jagtap, Neerja Karnani, Gene Jeon, Yung Seng Lee, Karen Lillycrop, See Ling Loy, Pamela A Mahon, Chiara Nembrini, Sharon Ng, Justin M O'Sullivan, Judith Ong, Gernalia Satianegara, Lynette Pei-Chi Shek, Shu E Soh, Irma Silva-Zolezzi, Karen Tan, Vicky Tay, Rachael Taylor, Elizabeth Tham, Mya Thway Tint, Mark Vickers, Clare Wall, Gladys Woon, Wong Jui-Tsung Ray, Wei Ying, Mei Ling Chang, Hannah Yong, Keith M Godfrey, Sheila J Barton, Sarah El-Heis, Timothy Kenealy, Heidi Nield, Philip N Baker, Yap Seng Chong, Wayne Cutfield, Shiao-Yng Chan, NiPPeR Study Group, Veronica Boyle, Shirong Cai, Ryan Carvalho, Julie Ann Guiao Castro, Mary Cavanagh, Hsin Fang Chang, Claudia Chi, Caroline E Childs, Mary F Chong, Cathryn Conlon, Cyrus Cooper, Paula Costello, Vanessa Cox, Marilou Ebreo, Judith Hammond, Nicholas C Harvey, Richard Holt, Hazel M Inskip, Mrunalini Jagtap, Neerja Karnani, Gene Jeon, Yung Seng Lee, Karen Lillycrop, See Ling Loy, Pamela A Mahon, Chiara Nembrini, Sharon Ng, Justin M O'Sullivan, Judith Ong, Gernalia Satianegara, Lynette Pei-Chi Shek, Shu E Soh, Irma Silva-Zolezzi, Karen Tan, Vicky Tay, Rachael Taylor, Elizabeth Tham, Mya Thway Tint, Mark Vickers, Clare Wall, Gladys Woon, Wong Jui-Tsung Ray, Wei Ying, Mei Ling Chang, Hannah Yong

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.

Trial registration: ClinicalTrials.gov NCT02509988.

© 2021 by the American Diabetes Association.

Figures

Figure 1
Figure 1
Consolidated Standards of Reporting Trials (CONSORT) diagram outlining participant flow. *Premature ovarian failure. †New-onset Graves’ disease, hemoglobinopathy with iron overload, prolactinoma, endometrial polyp, endometrial atypia, breast cancer. ‡Withdrew because product may contain animal remnants, no storage space in refrigerator, participant suspicion of product-related symptoms. §Includes two cases of trisomy 21, Klinefelter syndrome. ¶Includes hypoplastic left heart syndrome, unknown reason in private clinic. #Includes one stillbirth and one neonatal death. T2D, type 2 diabetes.

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Source: PubMed

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