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

Abstract

BackgroundImproved 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/designThis 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.DiscussionThere 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 registrationClinicalTrials.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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13063-017-1875-x) contains supplementary material, which is available to authorized users.

The developing world of DOHaD

“…24 NiPPeR trial (Nutritional intervention Preconception and during Pregnancy to maintain healthy glucosE levels and offspRing health) is another largescale interventional study looking at effects of nutrients and probiotics before and during pregnancy. 25 In Japan, the Hokkaido Study on Environment and Children's Health is underway recruiting~20,000 mother-child pairs. 26 The Tohoku Medical Megabank project is designed for reconstruction of regional healthcare in areas affected by the Great East Japan Earthquake of 2011, aiming for the provision of research infrastructure for the development of personalized genomic medicine.…”

Risks Assessment Before Pregnancy: A Healthy Mother and Baby After Delivery

“…All patients that are diagnosed with diabetes need glycaemic control through self-assessment skills, physician directed assessment, care of disease and complications, counselling about diet, exercise, and reproductive advice before conception (Lassi et al 2014). Godfrey (2017) conclude that there are consequent benefits for the infant and the mother if maternal nutrition and glycaemic control is instituted before and during pregnancy. Optimising preconception nutrition is significant to avoid major risks like macrosomia (Godfrey et al 2017).…”

Diet, nutrient status and gestational diabetes

“…The largest RCT in 400 Finnish women with at least one risk factor for GDM receiving intensive individual counselling on diet and physical activity showed a 39% reduction in GDM prevalence compared to standard care [97]. However, others, including a large European multicentre trial in overweight and obese pregnant women, did not find a reduction in GDM prevalence after lifestyle or dietary counselling [98][99][100][101]. Differences in dietary intervention (e.g.…”

“…Therefore, new trials aim to start already in the preconception period. One of these trials is the recently started large multicentre, multi-ethnic randomized "Nutritional intervention Preconception and during Pregnancy to maintain healthy glucose metabolism and offspring health (NiPPeR)" trial investigating the effect of an optimized nutritional drink with myo-inositol, micronutrients and probiotics on glucose tolerance that starts with the intervention in the preconception phase [98]. A major challenge of this study, however, is the large number of women needed, n=1800, to be able to study the aimed 600 pregnancies, as not all women will conceive and anticipating dropout.…”

“…Recruitment of women in the preconception period was the biggest challenge in our small-scale GLIMP2 study. The currently ongoing NiPPeR trial [98] will not only provide information on the effect of a nutritional drink on GDM development, but also provide vital information on feasibility and practicality of research in the preconception period on a large scale.…”