Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health (NiPPeR)

Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health "(NiPPeR)"

The study aims to assess whether a nutritional drink taken before conception and continuing through pregnancy, assists in the maintenance of healthy glucose metabolism in the mother and promotes offspring health.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia
• Intervention / Treatment: Dietary supplement: Study nutritional drink; Dietary supplement: Standard nutritional drink

Detailed Description

It is known that maternal insulin resistance and high blood glucose levels in early pregnancy alter the functioning of the placenta in ways that persistently affect the supply of nutrients and fat in the unborn baby. There is an increasing focus on the need to optimise preconception nutrition but as yet, limited preconception interventions that are recognized as promoting health for the mother and her child.

The Investigators will recruit up to 1800 women, aged 18-38 years, who are planning a pregnancy in the United Kingdom, Singapore and New Zealand with the aim of securing 600 or more pregnancies. The participants will be randomly allocated to receive the standard nutritional drink or the study nutritional drink. Women who conceive between one and twelve months after starting the nutritional drink will be followed through pregnancy and studied with their babies for three years after delivery. Various testing will be carried out at relevant time points. Mothers will undergo blood, urine, hair and cheek swab sampling, dual-energy X-ray absorptiometry (DXA) scans along with body measurements and health and lifestyle questionnaires. Infants will undergo hair, cheek swab, urine and stool sampling along with body measurements, measurements of body composition and a DXA scan. Placental, cord and other perinatal tissues/samples will be collected.

The data collected will allow identification of the contributions of nutritional and lifestyle factors, social and economic status, ethnicity, genetics and metabolomics and gut microbes to maintaining healthy glucose metabolism in pregnancy, enhancing fertility, mood and reproductive outcomes in the mother, and promoting healthy growth, body composition and wellbeing in the children.

The effect of the intervention on the primary outcome will be examined in two special interest groups; i) women who are overweight or obese prior to conception & ii) women with documented evidence of dysglycemia prior to conception.

• Study Type: Interventional
• Enrollment (Actual): 1729
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1142
    • The University of Auckland
• Singapore
  • Singapore, Singapore, 119074
    • National University Hospital
• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Women aged 18-38 years
• Planning to conceive within 6 months
• Able to provide written, informed consent
• In Singapore: Chinese, Malay and Indian ethnicity or mixed Chinese/Malay/Indian ethnicity

Exclusion Criteria:

• Pregnant or lactating at recruitment
• Assisted fertility, apart from those taking clomiphene or letrozole alone
• Pre-existing diabetes (type 1 or type 2)
• Oral or implanted contraception currently or in the last month, or with an Intrauterine Contraceptive Device (IUCD) in situ
• On metformin or systemic steroids currently or in the last month
• Known serious food allergy
• Not able to give informed consent
• Women on anticonvulsants (who are treated with high dose B vitamins in pregnancy) currently or in the last month
• On treatment for Human Immunodeficiency Virus (HIV), Hepatitis B or C currently or in the last month

The partners of the women (over 16 years of age) will also be invited to participate in the study. After having gained written informed consent, fathers will have blood, urine, hair sampling, cheek swabs and body measurements taken and will complete a health and a lifestyle questionnaire at one of the visits during pregnancy.

The mother will consent for their babies to have body measurements, buccal, hair, stool samples and allergy testing from birth to 3.5 years.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention (study nutritional drink); Study nutritional drink comes in the form of a sachet to mix with water & take twice a day (once in the morning and once in the evening). The drink will be taken before the participant becomes pregnant (for up to 1 year) and throughout pregnancy.	Dietary supplement: Study nutritional drink; Study nutritional drink containing a mix of micronutrients, probiotics and myo-inositol.
Active Comparator: Control (standard nutritional drink); Standard nutritional drink comes in the form of a sachet to mix with water & take twice a day (once in the morning and once in the evening). The drink will be taken before the participant becomes pregnant (for up to 1 year) and throughout pregnancy.	Dietary supplement: Standard nutritional drink; Standard nutritional drink containing a mix of micronutrients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Glucose tolerance during pregnancy	Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation

Secondary Outcome Measures

Outcome Measure	Time Frame
Duration of gestation	Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery
Pregnancy weight gain and body composition	Up to 36 weeks, between date of first pregnancy visit and late gestation
Postpartum weight retention and body composition	Up to 2 years, between date of delivery and 6,12 and 24 months postpartum
Change in body composition before, during and after gestation	Up to 4 years, between preconception, pregnancy and 2 years postpartum
Clinical pregnancy, pregnancy loss and live birth rates, including median time to conception of those who conceive during the treatment period and proportions conceiving within 3 months, 6 months and a year of commencing the NiPPeR drink	Between recruitment and delivery
Gestational diabetes frequency	Pregnancy OGTT measurement at 24 - 32 weeks gestation
Hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia/eclampsia)	Up to 49 weeks, between conception derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery, and up to 6 weeks after delivery
Nausea and vomiting frequency	Up to 36 weeks, between 7 weeks of gestation and delivery
Other antenatal, perinatal and postnatal complications	Up to 49 weeks, between conception from estimated date of conception derived from menstrual and ultrasound scan data, and up to 6 weeks after delivery
Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)	Up to 2 years, between preconception and delivery
Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)	Up to 52 weeks, between date of delivery and infant age 1 year
Mode of labour onset and delivery	Delivery
Neonatal complications and admission to neonatal care facilities	Up to 4 weeks post-delivery
Preconception maternal micronutrient status (blood analysis)	Date of second preconception visit up to 1 year before pregnancy
Antenatal maternal micronutrient status (blood analysis)	Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Preconception maternal gut microbiota composition and activity profile (analysis of sequencing and transcription data)	Up to 6 weeks from the start of intervention, date of preconception visit 2 which is up to 1 year before pregnancy
Antenatal and postnatal maternal gut and epithelial microbiota composition profile (analysis of sequencing data)	Up to 18 months, between 7 weeks gestation and post-delivery visits
Maternal preconception biochemical, metabolic and molecular profiles	Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy
Maternal antenatal biochemical, metabolic and molecular profiles	Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles	Birth
Maternal postnatal biochemical, metabolic and molecular profiles	6 months after delivery
Maternal preconception epigenetic profile	Preconception to up to 1 year before pregnancy
Maternal antenatal epigenetic profile	Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Maternal postnatal epigenetic profile	6 months after delivery
Breast milk macronutrient profile (subsample)	Up to 1 year, between date of delivery and 1 year postpartum
Breast milk micronutrient profile (subsample)	Up to 1 year, between date of delivery and 1 year postpartum
Breast milk immune factor profile (subsample)	Up to 1 year, between date of delivery and 1 year postpartum
Breast milk epigenetic profile (subsample)	Up to 1 year, between date of delivery and 1 year postpartum
Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample)	Up to 1 year, between date of delivery and 1 year postpartum
Healthy lactogenesis	Up to 1 year, between date of delivery and 1 year postpartum
Maternal and infant transcriptomics (including of breastmilk)	Up to 34 months, between preconception, pregnancy and 1 year postpartum
Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans	Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Offspring birthweight and size at birth	At birth
Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age	At birth
Offspring size for gestational age and sex at birth (percentile and standard deviation scores)	At birth
Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass)	Up to 3.5 years, between date of delivery and 3.5 years postpartum
Adiposity gain, body composition and linear growth during infancy and childhood	Up to 3.5 years, from birth to infant age 3.5 years
Cord blood C-peptide	At delivery
Offspring cardiometabolic profile	Up to 3.5 years, from birth to infant age 3.5 years
Offspring allergic wellbeing	Up to 3.5 years, from birth to infant age 3.5 years
Offspring biochemical, metabolic and molecular profiles	Up to 3.5 years, from birth to infant age 3.5 years
Offspring epigenetic profile	Up to 3.5 years, from birth to infant age 3.5 years
Infant gut microbiota composition and activity	Up to 3.5 years, from birth to infant age 3.5 years
Influence of parental and offspring genotype, sociodemography, body composition, metabolism, lifestyle and diet on the above primary and secondary outcomes at baseline and with the intervention	Up to 5.5 years, between preconception, pregnancy and 3.5 years postpartum

Other Outcome Measures

Outcome Measure	Time Frame
Health economics analysis (cost benefit analysis)	Composite analysis between preconception visit which is up to 1 year before pregnancy and infant age 3.5 years, assessed up to 5.5 years
Offspring neurocognitive and behavioural development (behavioural and Ages & Stages questionnaires)	Up to 3.5 years, from birth to infant age 3.5 years
Offspring respiratory development (absence of respiratory symptoms)	Up to 3.5 years, from birth to infant age 3.5 years
Offspring allergic development (clinical evaluation of atopic disorders and skin prick test reaction diameter)	Up to 3.5 years, from birth to infant age 3.5 years
Offspring health and wellbeing (questionnaires)	Up to 3.5 years, from birth to infant age 3.5 years
Maternal health and wellbeing	Up to 4 years, between preconception visit which is up to 1 year before pregnancy and up to 2 years after delivery

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: National University Hospital, Singapore; Singapore Institute for Clinical Sciences; Nestec Ltd.; National University of Singapore; Auckland UniServices Ltd.
• Investigators: Principal Investigator: Wayne Cutfield, BHB MB ChB DCH MD FRACP, The University of Auckland; Principal Investigator: Shiao-Yng Chan, MBBChir (UK), FRCOG (UK), PhD, National University Hospital, Singapore; Principal Investigator: Keith Godfrey, BM PhD FRCP, MRC Lifecourse Epidemiology Unit, University of Southampton

Publications and helpful links

General Publications

• Godfrey KM, Cutfield W, Chan SY, Baker PN, Chong YS; NiPPeR Study Group. Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial. Trials. 2017 Mar 20;18(1):131. doi: 10.1186/s13063-017-1875-x.
• Godfrey KM, Barton SJ, El-Heis S, Kenealy T, Nield H, Baker PN, Chong YS, Cutfield W, Chan SY; NiPPeR Study Group. Myo-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial. Diabetes Care. 2021 May;44(5):1091-1099. doi: 10.2337/dc20-2515. Epub 2021 Mar 29.

Helpful Links

• Study Website

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2015
• Primary Completion (Actual): October 1, 2018
• Study Completion (Actual): June 1, 2022

Study Registration Dates

• First Submitted: July 16, 2015
• First Submitted That Met QC Criteria: July 27, 2015
• First Posted (Estimate): July 28, 2015

Study Record Updates

• Last Update Posted (Actual): May 15, 2023
• Last Update Submitted That Met QC Criteria: May 12, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Nutrition; Body composition; Glucose metabolism
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia
• Other Study ID Numbers: 13597; 34104 (Other Identifier: Auckland UniServices Ltd.); 2015/00205 (Other Identifier: National University Hospital Singapore); U1111-1171-8056 (Other Identifier: Universal Trial Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No