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

Hyperglycemia Clinical Trial

— NiPPeR  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02509988
• Other study ID #: 13597
• Secondary ID: 341042015/00205U
• Status: Completed
• Phase: N/A
• Start date: July 2015
• Est. completion date: June 2022

Study information

• Verified date: May 2023
• Source: University of Southampton
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1729
• Est. completion date: June 2022
• Est. primary completion date: October 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 38 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperglycemia

Intervention

Dietary Supplement:
• Study nutritional drink
Study nutritional drink containing a mix of micronutrients, probiotics and myo-inositol.
• Standard nutritional drink
Standard nutritional drink containing a mix of micronutrients.

Locations

Country	Name	City	State
New Zealand	The University of Auckland	Auckland
Singapore	National University Hospital	Singapore
United Kingdom	University Hospital Southampton NHS Foundation Trust	Southampton	Hampshire

Sponsors (6)

Lead Sponsor	Collaborator
University of Southampton	Auckland UniServices Ltd., National University Hospital, Singapore, National University of Singapore, Nestec Ltd., Singapore Institute for Clinical Sciences

Countries where clinical trial is conducted

New Zealand,  Singapore,  United Kingdom, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	Offspring neurocognitive and behavioural development (behavioural and Ages & Stages questionnaires)		Up to 3.5 years, from birth to infant age 3.5 years
Other	Offspring respiratory development (absence of respiratory symptoms)		Up to 3.5 years, from birth to infant age 3.5 years
Other	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
Other	Offspring health and wellbeing (questionnaires)		Up to 3.5 years, from birth to infant age 3.5 years
Other	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
Primary	Glucose tolerance during pregnancy		Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation
Secondary	Duration of gestation		Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery
Secondary	Pregnancy weight gain and body composition		Up to 36 weeks, between date of first pregnancy visit and late gestation
Secondary	Postpartum weight retention and body composition		Up to 2 years, between date of delivery and 6,12 and 24 months postpartum
Secondary	Change in body composition before, during and after gestation		Up to 4 years, between preconception, pregnancy and 2 years postpartum
Secondary	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
Secondary	Gestational diabetes frequency		Pregnancy OGTT measurement at 24 - 32 weeks gestation
Secondary	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
Secondary	Nausea and vomiting frequency		Up to 36 weeks, between 7 weeks of gestation and delivery
Secondary	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
Secondary	Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)		Up to 2 years, between preconception and delivery
Secondary	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
Secondary	Mode of labour onset and delivery		Delivery
Secondary	Neonatal complications and admission to neonatal care facilities		Up to 4 weeks post-delivery
Secondary	Preconception maternal micronutrient status (blood analysis)		Date of second preconception visit up to 1 year before pregnancy
Secondary	Antenatal maternal micronutrient status (blood analysis)		Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Secondary	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
Secondary	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
Secondary	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
Secondary	Maternal antenatal biochemical, metabolic and molecular profiles		Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Secondary	Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles		Birth
Secondary	Maternal postnatal biochemical, metabolic and molecular profiles		6 months after delivery
Secondary	Maternal preconception epigenetic profile		Preconception to up to 1 year before pregnancy
Secondary	Maternal antenatal epigenetic profile		Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Secondary	Maternal postnatal epigenetic profile		6 months after delivery
Secondary	Breast milk macronutrient profile (subsample)		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Breast milk micronutrient profile (subsample)		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Breast milk immune factor profile (subsample)		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Breast milk epigenetic profile (subsample)		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample)		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Healthy lactogenesis		Up to 1 year, between date of delivery and 1 year postpartum
Secondary	Maternal and infant transcriptomics (including of breastmilk)		Up to 34 months, between preconception, pregnancy and 1 year postpartum
Secondary	Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans		Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation
Secondary	Offspring birthweight and size at birth		At birth
Secondary	Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age		At birth
Secondary	Offspring size for gestational age and sex at birth (percentile and standard deviation scores)		At birth
Secondary	Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass)		Up to 3.5 years, between date of delivery and 3.5 years postpartum
Secondary	Adiposity gain, body composition and linear growth during infancy and childhood		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	Cord blood C-peptide		At delivery
Secondary	Offspring cardiometabolic profile		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	Offspring allergic wellbeing		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	Offspring biochemical, metabolic and molecular profiles		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	Offspring epigenetic profile		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	Infant gut microbiota composition and activity		Up to 3.5 years, from birth to infant age 3.5 years
Secondary	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

External Links

•   Study Website