Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial

Keith M Godfrey, Wayne Cutfield, Shiao-Yng Chan, Philip N Baker, Yap-Seng Chong, NiPPeR Study Group, Izzuddin Bin Mohamad Aris, Sheila J Barton, Jonathan Y Bernard, Veronica Boyle, Graham C Burdge, Christopher D Byrne, Shirong Cai, Philip C Calder, Claudia Chi, Caroline E Childs, Mary F Chong, Cathryn Conlon, Cyrus Cooper, Marilou Ebreo, Sarah El-Heis, Marielle Fortier, Lisa R Fries, Nicholas C Harvey, Joanna D Holbrook, Richard Holt, Hazel M Inskip, Neerja Karnani, Timothy Kenealy, Yung Seng Lee, Karen Lillycrop, See Ling Loy, Katherine Macé, Pamela A Mahon, Min Gong, Falk Müller-Riemenschneider, Sharon Ng, Heidi Nield, Justin M O'Sullivan, Wei Wei Pang, Charles Peebles, Anne Rifkin-Graboi, Lesley McCowan, Allan Sheppard, Nick Macklon, Tinu Mary Samuel, Shu E Soh, Lynette Pei-Chi Shek, Irma Silva-Zolezzi, Rachael Taylor, Sagar K Thakkar, Mya Thway Tint, Clare Wall, Wei Ying, Keith M Godfrey, Wayne Cutfield, Shiao-Yng Chan, Philip N Baker, Yap-Seng Chong, NiPPeR Study Group, Izzuddin Bin Mohamad Aris, Sheila J Barton, Jonathan Y Bernard, Veronica Boyle, Graham C Burdge, Christopher D Byrne, Shirong Cai, Philip C Calder, Claudia Chi, Caroline E Childs, Mary F Chong, Cathryn Conlon, Cyrus Cooper, Marilou Ebreo, Sarah El-Heis, Marielle Fortier, Lisa R Fries, Nicholas C Harvey, Joanna D Holbrook, Richard Holt, Hazel M Inskip, Neerja Karnani, Timothy Kenealy, Yung Seng Lee, Karen Lillycrop, See Ling Loy, Katherine Macé, Pamela A Mahon, Min Gong, Falk Müller-Riemenschneider, Sharon Ng, Heidi Nield, Justin M O'Sullivan, Wei Wei Pang, Charles Peebles, Anne Rifkin-Graboi, Lesley McCowan, Allan Sheppard, Nick Macklon, Tinu Mary Samuel, Shu E Soh, Lynette Pei-Chi Shek, Irma Silva-Zolezzi, Rachael Taylor, Sagar K Thakkar, Mya Thway Tint, Clare Wall, Wei Ying

Abstract

Background: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health.

Methods/design: This double-blind randomised controlled trial will recruit up to 1800 women, aged 18-38 years, who are planning a pregnancy in the United Kingdom (UK), Singapore and New Zealand, with a view to studying 600 pregnancies. The primary outcome is maternal glucose tolerance at 28 weeks' gestation following an oral glucose tolerance test. Secondary outcomes include metabolic, molecular and health-related outcomes in the mother and offspring, notably infant body composition. Participants will be randomly allocated to receive a twice-daily control nutritional drink, enriched with standard micronutrients, or a twice-daily intervention nutritional drink enriched with additional micronutrients, myo-inositol and probiotics, both demonstrated previously to assist in maintaining healthy glucose metabolism during pregnancy. Myo-inositol is a nutrient that enhances cellular glucose uptake. The additional micronutrients seek to address deficiencies of some B-group vitamins and vitamin D that are both common during pregnancy and that have been associated with maternal dysglycaemia, epigenetic changes and greater offspring adiposity. Women who conceive within a year of starting the nutritional drinks will be followed through pregnancy and studied with their infants at six time points during the first year of life. Blood, urine/stool, hair and cheek swabs will be collected from the mothers for genetic, epigenetic, hormone, nutrient and metabolite measurements, and assessments of the mother's body composition, anthropometry, health, diet and lifestyle will be made. Infants will also undergo hair, cheek swab, urine and stool sampling for similar biological measurements; infant body composition will be assessed and feeding recorded.

Discussion: There is an increasing focus on the need to optimise maternal nutrition starting prior to conception. This trial will provide evidence on the potential for nutritional interventions beginning prior to conception to promote healthy maternal and offspring outcomes.

Trial registration: ClinicalTrials.gov, identifier: NCT02509988 , Universal Trial Number U1111-1171-8056. Registered on 16 July 2015. This is an academic-led study by the EpiGen Global Research Consortium.

Keywords: Body composition; Glucose metabolism; Hyperglycemia; Metabolic diseases; Nutrition; Preconception; Pregnancy; Randomised trial.

Figures

Fig. 1
Fig. 1
Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) Figure: trial schema. Abbreviations: PCV preconception visit, PC preconception, PGV pregnancy visit, PDV post-delivery visit, BIA bioelectrical impedance analysis, BP blood pressure, DM diabetes mellitus, DXA dual-energy X-ray absorptiometry, GDM gestational diabetes, HIV, human immunodeficiency virus, IFG impaired fasting glucose, IGT impaired glucose tolerance, NGT normal glucose tolerance, OGTT oral glucose tolerance test, USS, ultrasound scan. Questionnaires: BEBQ baby eating behaviour, BM breast milk, FH family history, GH general health, IFH infant feeding and health, IIF intentions for infant feeding, L lifestyle, M mood (Edinburgh Postnatal Depression Scale, State-Trait Anxiety Inventory), MH medical history, MSH menstrual history, MTH maternal health, N nutrition/diet, OH obstetric history, PA physical activity, S sleep. Biosampling: # = blood, ♥ = breast milk, $ = buccal swabs, * = epithelial swabs, @ = hair, ^ = stool, ~ = urine

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