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Peripartum outcomes after combined myo-inositol, probiotics, and micronutrient supplementation from preconception: the NiPPeR randomized controlled trial

  • Shiao-Yng Chan
    Correspondence
    Corresponding author: Shiao-Yng Chan, MD, PhD;
    Affiliations
    Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore (Drs Chan and Chong)

    Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Drs Chan, Yong, and Zhang, Mr Wong, and Dr Chong)

    Department of Obstetrics and Gynaecology, National University Hospital, Singapore (Dr Chan, Ms Chang, Drs Ong, Ebreo, and Chong)
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  • Hannah E.J. Yong
    Affiliations
    Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Drs Chan, Yong, and Zhang, Mr Wong, and Dr Chong)
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  • Hsin Fang Chang
    Affiliations
    Department of Obstetrics and Gynaecology, National University Hospital, Singapore (Dr Chan, Ms Chang, Drs Ong, Ebreo, and Chong)
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  • Sheila J. Barton
    Affiliations
    Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom (Dr Barton, Ms Galani, Dr El-Heis, Ms Nield, and Dr Godfrey)
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  • Sevasti Galani
    Affiliations
    Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom (Dr Barton, Ms Galani, Dr El-Heis, Ms Nield, and Dr Godfrey)
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  • Han Zhang
    Affiliations
    Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Drs Chan, Yong, and Zhang, Mr Wong, and Dr Chong)
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  • Jui-Tsung Wong
    Affiliations
    Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Drs Chan, Yong, and Zhang, Mr Wong, and Dr Chong)
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  • Judith Ong
    Affiliations
    Department of Obstetrics and Gynaecology, National University Hospital, Singapore (Dr Chan, Ms Chang, Drs Ong, Ebreo, and Chong)
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  • Marilou Ebreo
    Affiliations
    Department of Obstetrics and Gynaecology, National University Hospital, Singapore (Dr Chan, Ms Chang, Drs Ong, Ebreo, and Chong)
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  • Sarah El-Heis
    Affiliations
    Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom (Dr Barton, Ms Galani, Dr El-Heis, Ms Nield, and Dr Godfrey)
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  • Timothy Kenealy
    Affiliations
    Liggins Institute, University of Auckland, Auckland, New Zealand (Drs Kenealy and Cutfield)
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  • Heidi Nield
    Affiliations
    Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom (Dr Barton, Ms Galani, Dr El-Heis, Ms Nield, and Dr Godfrey)
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  • Philip N. Baker
    Affiliations
    College of Life Sciences, University of Leicester, Leicester, United Kingdom (Dr Baker)
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  • Yap Seng Chong
    Affiliations
    Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore (Drs Chan and Chong)

    Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Drs Chan, Yong, and Zhang, Mr Wong, and Dr Chong)

    Department of Obstetrics and Gynaecology, National University Hospital, Singapore (Dr Chan, Ms Chang, Drs Ong, Ebreo, and Chong)
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  • Wayne S. Cutfield
    Affiliations
    Liggins Institute, University of Auckland, Auckland, New Zealand (Drs Kenealy and Cutfield)

    A Better Start, National Science Challenge, Auckland, New Zealand (Dr Cutfield)

    A Better Start, National Science Challenge, Auckland, New Zealand
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  • Keith M. Godfrey
    Affiliations
    Medical Research Council Lifecourse Epidemiology Centre, University of Southampton, Southampton General Hospital, Southampton, United Kingdom (Dr Barton, Ms Galani, Dr El-Heis, Ms Nield, and Dr Godfrey)

    National Institute for Health Research Southampton Biomedical Research Centre, University of Southampton and University Hospital Southampton, National Health Service (NHS) Foundation Trust, Southampton, United Kingdom (Dr Godfrey)
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  • On behalf of theNiPPeR Study Group

      BACKGROUND

      Evidence that nutritional supplementation before and during pregnancy improves peripartum outcomes is sparse. In the Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) trial, we previously reported that a combined myo-inositol, probiotics, and micronutrient supplement started at preconception showed no difference in the primary outcome of gestational glycemia, but did reduce the risk of preterm delivery, preterm prelabor rupture of membranes, and major postpartum hemorrhage.

      OBJECTIVE

      This study aimed to examine the hypothesis that a reduction in major postpartum hemorrhage following a combined nutritional (myo-inositol, probiotics, and micronutrients) intervention is linked with promotion of labor progress and reduced operative delivery.

      STUDY DESIGN

      This double-blind randomized controlled trial recruited 1729 women from the United Kingdom, Singapore, and New Zealand, aged 18 to 38 years, and planning conception between 2015 and 2017. The effects of the nutritional intervention compared with those of a standard micronutrient supplement (control), taken at preconception and throughout pregnancy, were examined for the secondary outcomes of peripartum events using multinomial, Poisson, and linear regression adjusting for site, ethnicity, and important covariates.

      RESULTS

      Of the women who conceived and progressed beyond 24 weeks’ gestation with a singleton pregnancy (n=589), 583 (99%) provided peripartum data. Between women in the intervention (n=293) and control (n=290) groups, there were no differences in rates of labor induction, oxytocin augmentation during labor, instrumental delivery, perineal trauma, and intrapartum cesarean delivery. Although duration of the first stage of labor was similar, the second-stage duration was 20% shorter in the intervention than in the control group (adjusted mean difference, −12.0 [95% confidence interval, −22.2 to −1.2] minutes; P=.029), accompanied by a reduction in operative delivery for delayed second-stage progress (adjusted risk ratio, 0.61 [0.48–0.95]; P=.022). Estimated blood loss was 10% lower in the intervention than in the control group (adjusted mean difference, −35.0 [−70.0 to −3.5] mL; P=.047), consistent with previous findings of reduced postpartum hemorrhage.

      CONCLUSION

      Supplementation with a specific combination of myo-inositol, probiotics, and micronutrients started at preconception and continued in pregnancy reduced the duration of the second stage of labor, the risk of operative delivery for delay in the second stage, and blood loss at delivery.

      Keywords

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