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

University of Southampton1,729 enrolled

Overview

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.

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

Allocation

RANDOMIZED

Purpose

OTHER

Masking

QUADRUPLE

Enrollment

1,729

Conditions

Hyperglycemia

Interventions

Study nutritional drinkDIETARY_SUPPLEMENT

Study nutritional drink containing a mix of micronutrients, probiotics and myo-inositol.

Standard nutritional drinkDIETARY_SUPPLEMENT

Standard nutritional drink containing a mix of micronutrients.

Eligibility

Sex: FEMALEMin age: 18 YearsMax age: 38 YearsHealthy volunteers:

Medical Language ↔ Plain English

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.

Locations (3)

The University of Auckland

Auckland, New Zealand

National University Hospital

Singapore, Singapore

University Hospital Southampton NHS Foundation Trust

Southampton, Hampshire, United Kingdom

Outcomes

Primary Outcomes

Glucose tolerance during pregnancy

Time frame: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation

Secondary Outcomes

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

Pregnancy weight gain and body composition

Time frame: Up to 36 weeks, between date of first pregnancy visit and late gestation

Postpartum weight retention and body composition

Time frame: Up to 2 years, between date of delivery and 6,12 and 24 months postpartum

Change in body composition before, during and after gestation

Time frame: 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

Time frame: Between recruitment and delivery

Gestational diabetes frequency

Time frame: Pregnancy OGTT measurement at 24 - 32 weeks gestation

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

Nausea and vomiting frequency

Data from ClinicalTrials.gov

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Time frame: Up to 36 weeks, between 7 weeks of gestation and delivery

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

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

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

Mode of labour onset and delivery

Time frame: Delivery

Neonatal complications and admission to neonatal care facilities

Time frame: Up to 4 weeks post-delivery

Preconception maternal micronutrient status (blood analysis)

Time frame: Date of second preconception visit up to 1 year before pregnancy

Antenatal maternal micronutrient status (blood analysis)

Time frame: 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)

Time frame: 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)

Time frame: Up to 18 months, between 7 weeks gestation and post-delivery visits

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

Maternal antenatal biochemical, metabolic and molecular profiles

Time frame: 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

Time frame: Birth

Maternal postnatal biochemical, metabolic and molecular profiles

Time frame: 6 months after delivery

Maternal preconception epigenetic profile

Time frame: Preconception to up to 1 year before pregnancy

Maternal antenatal epigenetic profile

Time frame: Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation

Maternal postnatal epigenetic profile

Time frame: 6 months after delivery

Breast milk macronutrient profile (subsample)