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

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

National University Hospital, Singapore, Auckland UniServices Ltd., Singapore Institute for Clinical Sciences, National University of Singapore, Nestec Ltd.

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 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.

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.

Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery

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

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

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)

Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)

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 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy

Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles

Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age

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

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 allergic development (clinical evaluation of atopic disorders and skin prick test reaction diameter)

Up to 4 years, between preconception visit which is up to 1 year before pregnancy and up to 2 years after delivery

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.

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.