Higher Plasma Myo-Inositol in Pregnancy Associated with Reduced Postpartum Blood Loss: Secondary Analyses of the NiPPeR Trial

Abstract

We previously reported that a combined myo-inositol, probiotics, and enriched micronutrient supplement (intervention) taken preconception and in pregnancy reduced postpartum blood loss (PBL) and major postpartum hemorrhage compared with a standard micronutrient supplement (control), as secondary outcomes of the NiPPeR trial. This study aimed to identify the intervention components that may contribute to this effect. Associations of plasma concentrations of myo-inositol and vitamins B2, B6, B12, and D at preconception (before and after supplementation), early (~7-weeks), and late pregnancy (~28-weeks) with PBL were assessed by multiple linear regression, adjusting for site, ethnicity, preconception BMI, parity, and previous cesarean section. Amongst 583 women, a higher concentration of myo-inositol in early pregnancy was associated with a PBL reduction [β_adj -1.26 (95%CI -2.23, -0.29) mL per µmol/L myo-inositol increase, p = 0.011]. Applying this co-efficient to the increase in mean 7-week-myo-inositol concentration of 23.4 µmol/L with the intervention equated to a PBL reduction of 29.5 mL (~8.4% of mean PBL of 350 mL among controls), accounting for 84.3% of the previously reported intervention effect of 35 mL. None of the examined vitamins were associated with PBL. Therefore, myo-inositol may be a key intervention component mediating the PBL reduction. Further work is required to determine the mechanisms involved.

Keywords: B-vitamins; inositols; postpartum hemorrhage; prenatal nutritional supplement; vitamin D.

Figure 1

Associations of maternal plasma concentrations of vitamins and myo-inositol with postpartum blood loss. Plasma was collected at preconception post-supplementation (N = 581), 7 weeks of pregnancy (N = 579), and 28 weeks of pregnancy (N = 579). Log_e-transformed and standardized; coefficients expressed as log_e mL blood loss per SD log_e increase of measured nutrient. Regression models were adjusted for site, preconception BMI, parity, previous cesarean section, and maternal age. Model fit (represented by R²): 7-week myo-inositol (adjusted: 0.206; mutually adjusted for other nutrients: 0.213) and 28-week myo-inositol (adjusted: 0.197; mutually adjusted for other nutrients: 0.207). Statistical significance: * p < 0.05, ** p < 0.01. Abbreviations: CI, confidence interval.

Figure 2

Correlations between the maternal plasma concentration of myo-inositol at 7 weeks of gestation and postpartum blood loss. (A) All sites combined showing unadjusted raw data and (B–D) site-stratified plots using log_e-transformed plasma myo-inositol data and log_e-transformed blood loss adjusted for preconception BMI and parity generated using linear regression. Pearson’s correlation (R), R-squared (R²), and p-values are shown. The participants in the NiPPeR control group are represented by blue dots while those in the NiPPeR intervention group (taking the supplement containing myo-inositol) are represented by red dots. UK: n = 177, Singapore: n = 146, New Zealand: n = 214.

Figure 3

Sensitivity analyses examining associations between maternal plasma concentrations of vitamins and myo-inositol at 7 weeks of gestation with postpartum blood loss after excluding cases of (A) cesarean section delivery (n = 169 excluded), or (B) large-for-gestational-age neonate at birth (n = 43 excluded). Maternal plasma concentrations of vitamins and myo-inositol were log_e-transformed and standardized while postpartum blood loss was log_e-transformed. Coefficients expressed as % change in mL blood loss per standard deviation (SD) increase in log_e nutrient concentration. Regression models were adjusted for site, preconception BMI, parity, previous cesarean section, and maternal age. Statistical significance: * p < 0.05, ** p < 0.01. Abbreviations: CI, confidence interval; LGA, large-for-gestational-age.