Time-to-conception and clinical pregnancy rate with a myo-inositol, probiotics, and micronutrient supplement: Secondary outcomes of the NiPPeR randomized trial

Objective: To determine whether a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rates. Design: Secondary outcomes of a double-blind randomized controlled trial. Setting: Community recruitment. Patients: Women aged 18 to 38 years planning to conceive in the United Kingdom, Singapore, and New Zealand, excluding those with diabetes mellitus or receiving fertility treatment. Intervention: A standard (control) supplement (folic acid, iron, calcium, iodine, β-carotene), compared with an intervention additionally containing myo-inositol, probiotics, and other micronutrients (vitamins B2, B6, B12, D, zinc). Main Outcome Measures: Number of days between randomization and estimated date of natural conception of a clinical pregnancy, as well as cumulative pregnancy rates at 3, 6, and 12 months. Results: Of 1729 women randomized, 1437 (83%; intervention, n=736; control, n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% confidence interval: 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HRs) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, body mass index, and gravidity) were similar at 3, 6, and 12 months. Among both study groups combined, overall time-to-conception lengthened with higher preconception body mass index, and was longer in non-White than in White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12-month HR=1.47 [1.07, 2.02], P=.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to nonoverweight/nonobese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12-month HR=0.69 [0.47, 1.00]; P=.053; 20% conceived by 132.7 vs. 108.5 days); an effect predominantly observed in non-White women with obesity. Conclusions: Time-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the nonoverweight/nonobese women. Further studies are required to confirm this. Clinical Trial Registration Number: clinicaltrials.go

Time-to-conception and clinical pregnancy rate with myo-inositol, probiotics and micronutrient supplement: secondary outcomes of the NiPPeR Randomized Trial.

ObjectiveTo determine if a combined myo-inositol, probiotics and micronutrient nutritional supplement impacts time-to-natural-conception and clinical pregnancy rate.DesignSecondary outcomes of a double-blind randomized controlled trial.SettingCommunity recruitment of women planning to conceive in UK, Singapore and New Zealand.PatientsWomen aged 18-38 years, excluding those with diabetes mellitus or on fertility treatment.InterventionsA standard (control) supplement (folic acid, iron, calcium, iodine, ß-carotene), compared with an intervention additionally containing myo-inositol, probiotics and other micronutrients (Vitamins B2, B6, B12, D, zinc).Main Outcome MeasuresNumber of days between randomization and estimated date of natural conception of a clinical pregnancy, and cumulative pregnancy rates at 3, 6 and 12 months (m).ResultsOf 1729 women randomized, 1437 (83%; intervention n=736, control n=701) provided data. Kaplan-Meier curves of conception were similar between intervention and control groups; the time at which 20% achieved natural conception was 90.5 days (95% CI 80.7, 103.5) in the intervention group compared with 92.0 days (76.0, 105.1) in the control group. Cox's proportional hazard ratios (HR) comparing intervention against control for cumulative achievement of pregnancy (adjusted for site, ethnicity, age, BMI and gravidity) were similar at 3m, 6m and 12m. Among both study groups combined, overall time-to-conception lengthened with higher preconception BMI, and was longer in non-White compared with White women. Among women who were overweight the intervention shortened time-to-conception compared with control regardless of ethnicity (12 months HR=1.47 [1.07, 2.02], p=0.016; 20% conceived by 84.5 vs. 117.0 days) and improved it to that comparable to non-overweight/non-obese women (20% conceived by 82.1 days). In contrast, among women with obesity, time-to-conception was lengthened with intervention compared with control (12 months HR=0.69 [0.47, 1.00] p=0.053; 20% conceived by 132.7 vs 108.5 days); an effect predominantly observed in non-White women with obesity.ConclusionTime-to-natural-conception and clinical pregnancy rates within a year were overall similar in women receiving the intervention supplement compared with control. Overweight women had a longer time-to-conception but there was suggestion that the supplement may shorten their time-to-conception to that comparable to the non-overweight/non-obese women. Further studies are required to confirm this.<br/

Maternal mood, anxiety and mental health functioning after combined myo-inositol, probiotics, micronutrient supplementation from preconception: findings from the NiPPeR RCT

Observational studies have reported associations between nutrition during pregnancy and mental wellbeing. As secondary outcomes, the NiPPeR double-blind randomized trial in women planning conception investigated whether a myo-inositol, probiotics and enriched micronutrients formulation (intervention) taken preconception and throughout pregnancy could improve mental wellbeing during pregnancy and post-delivery, compared with a standard micronutrient supplement (control). Mood and anxiety symptoms were ascertained (Edinburgh Postnatal Depression Scale (EPDS), State-Trait Anxiety Inventory (STAI-state)) at preconception (baseline), 7, 28 and 34 weeks gestation, 3-weeks and 6-months post-delivery. EPDS&gt;=13 was categorised as low mood; STAI-state&gt;=45 as high anxiety. Change in mental health functioning was assessed as difference between preconception baseline and 6-month post-delivery 12-item Short-Form Health Survey (SF-12v2) mental component scores. Adjusting for site, ethnicity and baseline scores, there were no robust differences in EPDS and STAI-state scores between intervention and control groups across pregnancy (n = 630) and post-delivery (n = 532). Compared to controls, intervention group women averaged a 1.21 (95 %CI 0.04,2.39) higher change in SF-12v2 mental component score from preconception to 6-months post-delivery. Taking a myo-inositol, micronutrient and probiotic supplement during preconception/pregnancy had no effect on mood and anxiety, but there was evidence of a modest improvement in mental health functioning from preconception to 6-months post-delivery.</p

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

&lt;b&gt;Objective:&lt;/b&gt; 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. &lt;p&gt;&lt;b&gt;Research Design and Methods:&lt;/b&gt; Double-blind randomized controlled trial recruited from the community 1729 UK, Singapore and New Zealand women aged 18-38 years planning conception. We investigated if 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-hour and 2-hour post-load glycemia (28 weeks’ gestation oral glucose tolerance test).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt;: Between 2015-2017, 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 pre-specified p&lt;0.017 for multiplicity, there were no differences in gestational fasting, 1-hour and 2-hour glycemia between groups (β [95%CI] log&lt;sub&gt;e&lt;/sub&gt; mmol/L intervention versus control: -0·004 [-0·018, 0·011], 0·025 [-0·014, 0·064], 0·040 [0·004, 0·077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes (24·8% versus 22·6%, adjusted risk ratio aRR=1·22 [0·92, 1·62]), birthweight (adjusted β=0·05kg [-0·03, 0·13]), or gestational age at birth (mean 39.3 versus 39.2 weeks, adjusted β=0·20 [-0·06, 0·46]), but there were fewer preterm births (5·8% versus 9·2%, aRR=0·43 [0·22, 0·82]) adjusting for pre-specified covariates.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions: &lt;/b&gt;Supplementation with myo-inositol, probiotics and micronutrients preconception and in pregnancy did not lower gestational glycemia, but did reduce preterm birth. &lt;/p&gt; &lt;br&gt;</jats:p

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

&lt;b&gt;Objective:&lt;/b&gt; 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. &lt;p&gt;&lt;b&gt;Research Design and Methods:&lt;/b&gt; Double-blind randomized controlled trial recruited from the community 1729 UK, Singapore and New Zealand women aged 18-38 years planning conception. We investigated if 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-hour and 2-hour post-load glycemia (28 weeks’ gestation oral glucose tolerance test).&lt;/p&gt; &lt;p&gt;&lt;b&gt;Results&lt;/b&gt;: Between 2015-2017, 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 pre-specified p&lt;0.017 for multiplicity, there were no differences in gestational fasting, 1-hour and 2-hour glycemia between groups (β [95%CI] log&lt;sub&gt;e&lt;/sub&gt; mmol/L intervention versus control: -0·004 [-0·018, 0·011], 0·025 [-0·014, 0·064], 0·040 [0·004, 0·077], respectively). Between the intervention and control groups there were no significant differences in gestational diabetes (24·8% versus 22·6%, adjusted risk ratio aRR=1·22 [0·92, 1·62]), birthweight (adjusted β=0·05kg [-0·03, 0·13]), or gestational age at birth (mean 39.3 versus 39.2 weeks, adjusted β=0·20 [-0·06, 0·46]), but there were fewer preterm births (5·8% versus 9·2%, aRR=0·43 [0·22, 0·82]) adjusting for pre-specified covariates.&lt;/p&gt; &lt;p&gt;&lt;b&gt;Conclusions: &lt;/b&gt;Supplementation with myo-inositol, probiotics and micronutrients preconception and in pregnancy did not lower gestational glycemia, but did reduce preterm birth. &lt;/p&gt; &lt;br&gt;</jats:p

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

ObjectiveBetter 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 methodsThis 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).ResultsBetween 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 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.ConclusionsSupplementation with myo-inositol, probiotics, and micronutrients preconception and in pregnancy did not lower gestational glycemia but did reduce preterm birth

Myo-inositol, probiotics and micronutrient supplementation from preconception for glycemia in pregnancy: NiPPeR international multi-center double-blind randomized controlled trial

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 &lt; 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