Clinical trial NCT02509988: Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health
Official title: Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health "(NiPPeR)"
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Hyperglycemia
Keywords: Nutrition
Glucose metabolism
Body composition
Lead sponsor: University of Southampton
Sponsor class: OTHER
Collaborators: name: National University Hospital, Singapore
name: Auckland UniServices Ltd.
name: Institute for Human Development and Potential (IHDP), Singapore
name: National University of Singapore
name: Nestec Ltd.
First posted: 2015-07-28
Enrollment: 1729
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 38
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Glucose tolerance during pregnancy
timeFrame: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation
Secondary outcomes:
measure: Duration of gestation
timeFrame: Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery
measure: Pregnancy weight gain and body composition
timeFrame: Up to 36 weeks, between date of first pregnancy visit and late gestation
measure: Postpartum weight retention and body composition
timeFrame: Up to 2 years, between date of delivery and 6,12 and 24 months postpartum
measure: Change in body composition before, during and after gestation
timeFrame: Up to 4 years, between preconception, pregnancy and 2 years postpartum
measure: 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
timeFrame: Between recruitment and delivery
measure: Gestational diabetes frequency
timeFrame: Pregnancy OGTT measurement at 24 - 32 weeks gestation
measure: Hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia/eclampsia)
timeFrame: 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
measure: Nausea and vomiting frequency
timeFrame: Up to 36 weeks, between 7 weeks of gestation and delivery
measure: Other antenatal, perinatal and postnatal complications
timeFrame: 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
measure: Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)
timeFrame: Up to 2 years, between preconception and delivery
measure: Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)
timeFrame: Up to 52 weeks, between date of delivery and infant age 1 year
measure: Mode of labour onset and delivery
timeFrame: Delivery
measure: Neonatal complications and admission to neonatal care facilities
timeFrame: Up to 4 weeks post-delivery
measure: Preconception maternal micronutrient status (blood analysis)
timeFrame: Date of second preconception visit up to 1 year before pregnancy
measure: Antenatal maternal micronutrient status (blood analysis)
timeFrame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
measure: Preconception maternal gut microbiota composition and activity profile (analysis of sequencing and transcription data)
timeFrame: Up to 6 weeks from the start of intervention, date of preconception visit 2 which is up to 1 year before pregnancy
measure: Antenatal and postnatal maternal gut and epithelial microbiota composition profile (analysis of sequencing data)
timeFrame: Up to 18 months, between 7 weeks gestation and post-delivery visits
measure: Maternal preconception biochemical, metabolic and molecular profiles
timeFrame: Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy
measure: Maternal antenatal biochemical, metabolic and molecular profiles
timeFrame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
measure: Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles
timeFrame: Birth
measure: Maternal postnatal biochemical, metabolic and molecular profiles
timeFrame: 6 months after delivery
measure: Maternal preconception epigenetic profile
timeFrame: Preconception to up to 1 year before pregnancy
measure: Maternal antenatal epigenetic profile
timeFrame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
measure: Maternal postnatal epigenetic profile
timeFrame: 6 months after delivery
measure: Breast milk macronutrient profile (subsample)
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Breast milk micronutrient profile (subsample)
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Breast milk immune factor profile (subsample)
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Breast milk epigenetic profile (subsample)
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample)
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Healthy lactogenesis
timeFrame: Up to 1 year, between date of delivery and 1 year postpartum
measure: Maternal and infant transcriptomics (including of breastmilk)
timeFrame: Up to 34 months, between preconception, pregnancy and 1 year postpartum
measure: Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans
timeFrame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
measure: Offspring birthweight and size at birth
timeFrame: At birth
measure: Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age
timeFrame: At birth
measure: Offspring size for gestational age and sex at birth (percentile and standard deviation scores)
timeFrame: At birth
measure: Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass)
timeFrame: Up to 3.5 years, between date of delivery and 3.5 years postpartum
measure: Adiposity gain, body composition and linear growth during infancy and childhood
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Cord blood C-peptide
timeFrame: At delivery
measure: Offspring cardiometabolic profile
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring allergic wellbeing
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring biochemical, metabolic and molecular profiles
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring epigenetic profile
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Infant gut microbiota composition and activity
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: 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
timeFrame: Up to 5.5 years, between preconception, pregnancy and 3.5 years postpartum
Other outcomes:
measure: Health economics analysis (cost benefit analysis)
timeFrame: 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
measure: Offspring neurocognitive and behavioural development (behavioural and Ages & Stages questionnaires)
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring respiratory development (absence of respiratory symptoms)
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring allergic development (clinical evaluation of atopic disorders and skin prick test reaction diameter)
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Offspring health and wellbeing (questionnaires)
timeFrame: Up to 3.5 years, from birth to infant age 3.5 years
measure: Maternal health and wellbeing
timeFrame: Up to 4 years, between preconception visit which is up to 1 year before pregnancy and up to 2 years after delivery
Locations:
city: Auckland
country: New Zealand
facility: The University of Auckland
city: Singapore
country: Singapore
facility: National University Hospital
city: Southampton
country: United Kingdom
facility: University Hospital Southampton NHS Foundation Trust
state: Hampshire
Study officials:
affiliation: The University of Auckland
name: Wayne Cutfield, BHB MB ChB DCH MD FRACP
role: PRINCIPAL_INVESTIGATOR
affiliation: National University Hospital, Singapore
name: Shiao-Yng Chan, MBBChir (UK), FRCOG (UK), PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: MRC Lifecourse Epidemiology Unit, University of Southampton
name: Keith Godfrey, BM PhD FRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.