Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health "(NiPPeR)"
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,729
- 试验地点
- 6
- 主要终点
- Glucose tolerance during pregnancy
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Other
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 38 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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.
结局指标
主要结局
Glucose tolerance during pregnancy
时间窗: Pregnancy Oral Glucose Tolerance Test (OGTT) measurement at 24 - 32 weeks gestation
次要结局
- Postpartum weight retention and body composition(Up to 2 years, between date of delivery and 6,12 and 24 months postpartum)
- Hypertensive disorders of pregnancy (pregnancy-induced hypertension and pre-eclampsia/eclampsia)(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)
- Duration of gestation(Up to 43 weeks, derived from estimated date of conception from menstrual and ultrasound scan data and date of delivery)
- Maternal postnatal biochemical, metabolic and molecular profiles(6 months after delivery)
- Gestational diabetes frequency(Pregnancy OGTT measurement at 24 - 32 weeks gestation)
- Other antenatal, perinatal and postnatal complications(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)
- Postnatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)(Up to 52 weeks, between date of delivery and infant age 1 year)
- Preconception maternal micronutrient status (blood analysis)(Date of second preconception visit up to 1 year before pregnancy)
- Maternal antenatal biochemical, metabolic and molecular profiles(Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation)
- Breast milk micronutrient profile (subsample)(Up to 1 year, between date of delivery and 1 year postpartum)
- Breast milk immune factor profile (subsample)(Up to 1 year, between date of delivery and 1 year postpartum)
- Maternal and infant transcriptomics (including of breastmilk)(Up to 34 months, between preconception, pregnancy and 1 year postpartum)
- Placental and cord tissue, and their cellular derivatives: biochemical, metabolic and molecular profiles(Birth)
- Pregnancy weight gain and body composition(Up to 36 weeks, between date of first pregnancy visit and late gestation)
- Change in body composition before, during and after gestation(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(Between recruitment and delivery)
- Nausea and vomiting frequency(Up to 36 weeks, between 7 weeks of gestation and delivery)
- Mode of labour onset and delivery(Delivery)
- Antenatal and postnatal maternal gut and epithelial microbiota composition profile (analysis of sequencing data)(Up to 18 months, between 7 weeks gestation and post-delivery visits)
- Maternal postnatal epigenetic profile(6 months after delivery)
- Intrauterine growth and wellbeing as assessed by antenatal serial ultrasound scans(Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation)
- Offspring epigenetic profile(Up to 3.5 years, from birth to infant age 3.5 years)
- Infant gut microbiota composition and activity(Up to 3.5 years, from birth to infant age 3.5 years)
- Preconception and antenatal maternal wellbeing/mood (Edinburgh Post-natal Depression Scale and State-Trait Anxiety Inventory)(Up to 2 years, between preconception and delivery)
- Antenatal maternal micronutrient status (blood analysis)(Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation)
- Breast milk biochemical, metabolic, microbiome and molecular profiles (subsample)(Up to 1 year, between date of delivery and 1 year postpartum)
- Offspring size for gestational age and sex at birth (percentile and standard deviation scores)(At birth)
- Offspring adiposity (skinfold thicknesses, regional, total and percentage fat mass)(Up to 3.5 years, between date of delivery and 3.5 years postpartum)
- Adiposity gain, body composition and linear growth during infancy and childhood(Up to 3.5 years, from birth to infant age 3.5 years)
- Offspring biochemical, metabolic and molecular profiles(Up to 3.5 years, from birth to infant age 3.5 years)
- Neonatal complications and admission to neonatal care facilities(Up to 4 weeks post-delivery)
- 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)
- Maternal preconception biochemical, metabolic and molecular profiles(Up to 6 weeks from the start of intervention, date of second preconception visit which is up to 1 year before pregnancy)
- Maternal preconception epigenetic profile(Preconception to up to 1 year before pregnancy)
- Breast milk macronutrient profile (subsample)(Up to 1 year, between date of delivery and 1 year postpartum)
- Breast milk epigenetic profile (subsample)(Up to 1 year, between date of delivery and 1 year postpartum)
- Healthy lactogenesis(Up to 1 year, between date of delivery and 1 year postpartum)
- 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(Up to 5.5 years, between preconception, pregnancy and 3.5 years postpartum)
- Maternal antenatal epigenetic profile(Up to 30 weeks, between 7 weeks gestation and 37 weeks of gestation)
- Offspring birthweight and size at birth(At birth)
- Offspring size for gestational age at birth, less than the 10th, 10th - 90th, and above the 90th percentiles for gestational age(At birth)
- Cord blood C-peptide(At delivery)
- Offspring cardiometabolic profile(Up to 3.5 years, from birth to infant age 3.5 years)
- Offspring allergic wellbeing(Up to 3.5 years, from birth to infant age 3.5 years)