Evaluation of Preconception Dietary Patterns in Women Enrolled in a Multisite Study

(c) The Author(s) 2022.BACKGROUND: Diet indices are widely used in nutritional research across communities but do not "capture" the full extent of diet variability across multiple countries. Empirically derived dietary patterns can provide additional information because they reflect combinations of foods potentially associated with health outcomes. Limited studies have evaluated preconception dietary patterns in heterogeneous populations. OBJECTIVES: In the multisite Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR) study, the secondary aims included: 1) derive pooled and site-specific preconception dietary patterns, and 2) evaluate these patterns using anthropometric measures and metabolic biomarkers. METHODS: Women planning pregnancy (n = 1720) in the United Kingdom, Singapore, and New Zealand completed interviewer-administered harmonized FFQs and lifestyle questionnaires at recruitment. Across-cohort ("pooled") and site-specific dietary patterns were derived, and associations between dietary pattern scores and BMI, waist-to-hip ratio, plasma lipids, and glycemia assessed using multivariable linear regression, expressing results as SD change in outcome per SD change in dietary pattern score. RESULTS: The pooled analysis identified 3 dietary patterns: "Vegetables/Fruits/Nuts" ("Healthy"), "Fried potatoes/Processed meat/Sweetened beverages" ("Less Healthy"), and "Fish/Poultry/Noodles/Rice" ("Mixed"). The "Healthy" and "Less Healthy" pooled pattern scores were highly correlated with their corresponding site-specific dietary pattern scores ("Healthy": ρ = 0.87-0.93; "Less Healthy": ρ = 0.65-0.88). Women with higher scores for the "Healthy" pooled pattern had a lower waist-to-hip ratio (standardized β: -0.10; 95% CI: -0.18, -0.01); those with higher scores for the "Less Healthy" pooled pattern had a higher BMI (standardized β: 0.17; 95% CI: 0.09, 0.24), higher LDL cholesterol (standardized β: 0.10; 95% CI: 0.01, 0.19), and less optimal glucose profiles. However, we noted higher adherence to the "Healthy" pooled pattern with higher BMI. CONCLUSIONS: The "Healthy" and "Less Healthy" pooled patterns were comparable to the corresponding site-specific patterns. Although the associations between these patterns and objective anthropometric/metabolic measures were largely in the expected directions, future studies are required to confirm these findings. This trial is registered at clinicaltrials.gov (NCT02509988).fals

A nutritional supplement during preconception and pregnancy increases human milk vitamin D but not B-vitamin concentrations.

BACKGROUND & AIMS: Optimal maternal vitamin status during pregnancy and lactation is essential to support maternal and infant health. For instance, vitamin D3 is involved in infant bone development, and B-vitamins are involved in various metabolic processes, including energy production. Through a double-blind randomised controlled trial, we investigated the effects of maternal supplementation from preconception throughout pregnancy until birth on human milk (HM) concentrations of vitamin D3 and B-vitamins. In addition, we aimed to characterise longitudinal changes in milk concentrations of these vitamins. METHODS: Both control and intervention supplements contained calcium, iodine, iron, β-carotene, and folic acid, while the intervention also contained zinc, vitamins B2, B6, B12, and D3, probiotics, and myo-inositol. HM samples were collected across 4 time points from 1 week to 3 months post-delivery from 158 mothers in Singapore, and 7 time points from 1 week to 12 months from 180 mothers in New Zealand. HM vitamin D was quantified using supercritical fluid chromatography and B-vitamins with mass spectrometry. Potential intervention effects on HM vitamins D3, B2, B6, and B9, as well as other B-vitamin (B1 and B3) concentrations were assessed using linear mixed models with a repeated measures design. RESULTS: Over the first 3 months of lactation, HM 25-hydroxyvitamin D3 concentrations were 20% (95% CI 8%, 33%, P = 0.001) higher in the intervention group, with more marked effects in New Zealand. There were no observed intervention effects on HM concentrations of vitamins B1, B2, B3, B6, and B9. In New Zealand mothers, longitudinally, vitamin D3 concentrations gradually increased from early lactation up to 12 months, while vitamins B1 and B2 peaked at 6 weeks, B3 at 3 weeks, and B6 and B9 at 3 months. CONCLUSIONS: Maternal supplementation during preconception and pregnancy increased HM vitamin D, but not B-vitamin concentrations in lactation. Further studies are required to examine the discrete benefits of vitamin D supplementation starting preconception vs during pregnancy, and to further characterise the effects of supplementation on later offspring health outcomes. CLINICAL TRIAL REGISTRATION: Registered at ClinicalTrials.gov on the 16 July 2015 (identifier NCT02509988); Universal Trial Number U1111-1171-8056. This study was academic-led by the EpiGen Global Research Consortium.fals

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.gov (NCT02509988)fals

An offpspring's health starts before conception and results of the NiPPeR randomized trial

Improved maternal nutritional status is hypothesized to promote good pregnancy and infant health outcomes but trial evidence supporting the commencement of nutritional supplementation before conception is sparse. The NiPPeR (Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health) multinational double-blind randomized controlled trial conducted in United Kingdom, Singapore and New Zealand tested a nutritional formulation containing myo-inositol, probiotics and multiple micronutrients (intervention), compared with a standard micronutrient supplement (control), taken preconception and throughout pregnancy. The primary outcome of gestational glycemia at 28 weeks’ gestation showed no difference. However, differences in several pre-specified secondary outcomes were notable. The intervention reduced the incidence of preterm delivery particularly those associated with preterm pre-labor rupture of membranes, operative delivery for delayed second stage and major postpartum hemorrhage. It may also shorten time-to-conception in overweight women, to that similar to non-overweight/obese women. Importantly, the intervention associated with a reduction in the incidence of rapid infant weight gain and high body mass index at 2 years among offspring. Such evidence indicate the potential for preconception maternal nutritional interventions to have appreciable impact in shaping the long-term health of an individual and building resilience against non-communicable chronic diseases in the future

Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial.

BackgroundImproved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health.Methods/designThis double-blind randomised controlled trial will recruit up to 1800 women, aged 18–38 years, who are planning a pregnancy in the United Kingdom (UK), Singapore and New Zealand, with a view to studying 600 pregnancies. The primary outcome is maternal glucose tolerance at 28 weeks’ gestation following an oral glucose tolerance test. Secondary outcomes include metabolic, molecular and health-related outcomes in the mother and offspring, notably infant body composition. Participants will be randomly allocated to receive a twice-daily control nutritional drink, enriched with standard micronutrients, or a twice-daily intervention nutritional drink enriched with additional micronutrients, myo-inositol and probiotics, both demonstrated previously to assist in maintaining healthy glucose metabolism during pregnancy. Myo-inositol is a nutrient that enhances cellular glucose uptake. The additional micronutrients seek to address deficiencies of some B-group vitamins and vitamin D that are both common during pregnancy and that have been associated with maternal dysglycaemia, epigenetic changes and greater offspring adiposity. Women who conceive within a year of starting the nutritional drinks will be followed through pregnancy and studied with their infants at six time points during the first year of life. Blood, urine/stool, hair and cheek swabs will be collected from the mothers for genetic, epigenetic, hormone, nutrient and metabolite measurements, and assessments of the mother’s body composition, anthropometry, health, diet and lifestyle will be made. Infants will also undergo hair, cheek swab, urine and stool sampling for similar biological measurements; infant body composition will be assessed and feeding recorded.DiscussionThere is an increasing focus on the need to optimise maternal nutrition starting prior to conception. This trial will provide evidence on the potential for nutritional interventions beginning prior to conception to promote healthy maternal and offspring outcomes

Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial.

BACKGROUND: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health. METHODS/DESIGN: This double-blind randomised controlled trial will recruit up to 1800 women, aged 18-38 years, who are planning a pregnancy in the United Kingdom (UK), Singapore and New Zealand, with a view to studying 600 pregnancies. The primary outcome is maternal glucose tolerance at 28 weeks' gestation following an oral glucose tolerance test. Secondary outcomes include metabolic, molecular and health-related outcomes in the mother and offspring, notably infant body composition. Participants will be randomly allocated to receive a twice-daily control nutritional drink, enriched with standard micronutrients, or a twice-daily intervention nutritional drink enriched with additional micronutrients, myo-inositol and probiotics, both demonstrated previously to assist in maintaining healthy glucose metabolism during pregnancy. Myo-inositol is a nutrient that enhances cellular glucose uptake. The additional micronutrients seek to address deficiencies of some B-group vitamins and vitamin D that are both common during pregnancy and that have been associated with maternal dysglycaemia, epigenetic changes and greater offspring adiposity. Women who conceive within a year of starting the nutritional drinks will be followed through pregnancy and studied with their infants at six time points during the first year of life. Blood, urine/stool, hair and cheek swabs will be collected from the mothers for genetic, epigenetic, hormone, nutrient and metabolite measurements, and assessments of the mother's body composition, anthropometry, health, diet and lifestyle will be made. Infants will also undergo hair, cheek swab, urine and stool sampling for similar biological measurements; infant body composition will be assessed and feeding recorded. DISCUSSION: There is an increasing focus on the need to optimise maternal nutrition starting prior to conception. This trial will provide evidence on the potential for nutritional interventions beginning prior to conception to promote healthy maternal and offspring outcomes. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02509988 , Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium

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