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



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.



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.



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.
NIHR Southampton Biomedical Research Centre, University Hospital Southampton, NHS Foundation Trust, Southampton, UK. kmg@mrc.soton.ac.uk.|MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton General Hospital, Mailpoint 95, Southampton, SO16 6YD, UK. kmg@mrc.soton.ac.uk.
Keith M
KM
Godfrey
Liggins Institute, University of Auckland, Auckland, New Zealand.|A Better Start, New Zealand National Science Challenge, Auckland, New Zealand.
Wayne
W
Cutfield
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.|Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.
Shiao-Yng
SY
Chan
Liggins Institute, University of Auckland, Auckland, New Zealand.|College of Medicine, Biological Sciences and Psychology, University of Leicester, Leicester, UK.
Philip N
PN
Baker
Department of Obstetrics and Gynaecology, Yong Loo Lin School of Medicine, National University of Singapore and National University Health System, Singapore, Singapore.|Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore, Singapore.
Yap-Seng
YS
Chong
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D001628:Beverages; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D002985:Clinical Protocols; D019587:Dietary Supplements / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005865:Gestational Age; D005951:Glucose Tolerance Test; D006801:Humans; D000068104:Infant Health; D007227:Infant Nutritional Physiological Phenomena; D007231:Infant, Newborn; D007294:Inositol / Q000008:administration & dosage; D039382:Maternal Nutritional Physiological Phenomena; D009520:New Zealand; D009752:Nutritional Status; D016742:Preconception Care / Q000379:methods*; D011247:Pregnancy; D011295:Prenatal Care / Q000379:methods*; D019936:Probiotics / Q000008:administration & dosage; D012107:Research Design; D012846:Singapore; D006113:United Kingdom; D014815:Vitamins / Q000008:administration & dosage; D055815:Young Adult
D015415:Biomarkers; D001786:Blood Glucose; D014815:Vitamins; D007294:Inositol
Body composition; Glucose metabolism; Hyperglycemia; Metabolic diseases; Nutrition; Preconception; Pregnancy; Randomised trial