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

• ClinicalTrials.gov Identifier: NCT02509988
• Recruitment Status: Active, not recruiting
• First Posted: July 28, 2015
• Last Update Posted: May 24, 2019
• Sponsor: University of Southampton
• Collaborators: National University Hospital, Singapore; Auckland UniServices Ltd.; Singapore Institute for Clinical Sciences; National University, Singapore; Nestec Ltd.
• Information provided by (Responsible Party): University of Southampton

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Hyperglycemia	Dietary Supplement: Study nutritional drink; Dietary Supplement: Standard nutritional drink	Not Applicable

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 two 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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 1729 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Other
• Official Title: Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health "(NiPPeR)"
• Actual Study Start Date: July 2015
• Actual Primary Completion Date: October 2018
• Estimated Study Completion Date: March 2021

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures :

1. Glucose tolerance during pregnancy [ Time Frame: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation ]

Secondary Outcome Measures :

1. Duration of gestation [ Time Frame: Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery ]
2. Pregnancy weight gain and body composition [ Time Frame: Up to 36 weeks, between date of first pregnancy visit and late gestation ]
3. Postpartum weight retention and body composition [ Time Frame: Up to 2 years, between date of delivery and 6,12 and 24 months postpartum ]
4. Change in body composition before, during and after gestation [ Time Frame: Up to 4 years, between preconception, pregnancy and 2 years postpartum ]
5. 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 [ Time Frame: Between recruitment and delivery ]
6. Gestational diabetes frequency [ Time Frame: Pregnancy OGTT measurement at 24 - 32 weeks gestation ]
7. Hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia/eclampsia) [ Time Frame: 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 ]
8. Nausea and vomiting frequency [ Time Frame: Up to 36 weeks, between 7 weeks of gestation and delivery ]
9. Other antenatal, perinatal and postnatal complications [ Time Frame: 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 ]
10. Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 2 years, between preconception and delivery ]
11. Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory) [ Time Frame: Up to 52 weeks, between date of delivery and infant age 1 year ]
12. Mode of labour onset and delivery [ Time Frame: Delivery ]
13. Neonatal complications and admission to neonatal care facilities [ Time Frame: Up to 4 weeks post-delivery ]
14. Preconception maternal micronutrient status (blood analysis) [ Time Frame: Date of second preconception visit up to 1 year before pregnancy ]
15. Antenatal maternal micronutrient status (blood analysis) [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
16. Preconception maternal gut microbiota composition and activity profile (analysis of sequencing and transcription data) [ Time Frame: Up to 6 weeks from the start of intervention, date of preconception visit 2 which is up to 1 year before pregnancy ]
17. Antenatal and postnatal maternal gut and epithelial microbiota composition profile (analysis of sequencing data) [ Time Frame: Up to 18 months, between 7 weeks gestation and post-delivery visits ]
18. Maternal preconception biochemical, metabolic and molecular profiles [ Time Frame: Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy ]
19. Maternal antenatal biochemical, metabolic and molecular profiles [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
20. Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles [ Time Frame: Birth ]
21. Maternal postnatal biochemical, metabolic and molecular profiles [ Time Frame: 6 months after delivery ]
22. Maternal preconception epigenetic profile [ Time Frame: Preconception to up to 1 year before pregnancy ]
23. Maternal antenatal epigenetic profile [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
24. Maternal postnatal epigenetic profile [ Time Frame: 6 months after delivery ]
25. Breast milk macronutrient profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
26. Breast milk micronutrient profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
27. Breast milk immune factor profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
28. Breast milk epigenetic profile (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
29. Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample) [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
30. Healthy lactogenesis [ Time Frame: Up to 1 year, between date of delivery and 1 year postpartum ]
31. Maternal and infant transcriptomics (including of breastmilk) [ Time Frame: Up to 34 months, between preconception, pregnancy and 1 year postpartum ]
32. Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans [ Time Frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation ]
33. Offspring birthweight and size at birth [ Time Frame: At birth ]
34. Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age [ Time Frame: At birth ]
35. Offspring size for gestational age and sex at birth (percentile and standard deviation scores) [ Time Frame: At birth ]
36. Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass) [ Time Frame: Up to 2 years, between date of delivery and 2 years postpartum ]
37. Adiposity gain, body composition and linear growth during infancy and childhood [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
38. Cord blood C-peptide [ Time Frame: At delivery ]
39. Offspring cardiometabolic profile [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
40. Offspring allergic wellbeing [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
41. Offspring biochemical, metabolic and molecular profiles [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
42. Offspring epigenetic profile [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
43. Infant gut microbiota composition and activity [ Time Frame: Up to 2 years, from birth to infant age 2 years ]
44. 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 [ Time Frame: Up to 4 years, between preconception, pregnancy and 2 years postpartum ]

Other Outcome Measures:

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

Eligibility Criteria

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

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 24 months.

Contacts and Locations

Locations

New Zealand

The University of Auckland

Auckland, New Zealand, 1142

Singapore

National University Hospital

Singapore, Singapore, 119074

United Kingdom

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom, SO16 6YD

Sponsors and Collaborators

University of Southampton

National University Hospital, Singapore

Auckland UniServices Ltd.

Singapore Institute for Clinical Sciences

National University, Singapore

Nestec 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

More Information

Additional Information:

Study Website 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: University of Southampton
• ClinicalTrials.gov Identifier: NCT02509988
• 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 )
• First Posted: July 28, 2015
• Last Update Posted: May 24, 2019
• Last Verified: May 2019

Keywords provided by University of Southampton:

Nutrition; Glucose metabolism; Body composition

Additional relevant MeSH terms:

Hyperglycemia; Glucose Metabolism Disorders; Metabolic Diseases