NiPPeR Randomised Trial - Child Follow Up Study

Study Overview
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Brief Summary
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There is an increasing focus on the need to optimise nutrition, lifestyle and metabolism of parents before and during pregnancy and of the infant after birth, but as yet there is limited understanding of the specific influences and of the underlying mechanisms. This study is a follow up of children from the NiPPeR trial of a nutritional drink enriched with micronutrients, myo-inositol and probiotics taken preconception and during pregnancy. In this setting we will examine the influence of parental nutrition, lifestyle and metabolism before and during pregnancy on child growth, development and well-being; ascertaining growth, adiposity, metabolism, neurobehavioural and health outcomes in the children, and characterising the underlying mechanisms. The data collected will allow identification of the contributions of parental and offspring characteristics, nutritional, lifestyle and medical factors, social and economic status, ethnicity, genetics, metabolism and microbes to promoting healthy growth, body composition and wellbeing in the children.

Official Title
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Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health - Child Health and Well-being Follow Up Study

Conditions
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Cognition, Obesity, Childhood, Neurobehavioral Manifestations, Metabolic Disturbance, Growth Disorders, Allergy, Atopic Dermatitis, Atopy, Nutrition, Healthy, Lifestyle, Microbial Colonization, Breastfeeding

Intervention / Treatment
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* Other: Intervention (Study Nutritional Drink)
* Other: Control (Standard Nutritional Drink)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All children still participating in the NiPPeR study at 6-8 years. Exclusion Criteria: Known significant congenital anomaly or genetic condition that influences child growth or neurodevelopment.

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 8 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prior Intervention - enhanced micronutrients, probiotics, myo-inositol in preconception & pregnancy<br>NiPPeR Study intervention drink containing a mix of micronutrients, probiotics and myo-inositol given to the mother during preconception & pregnancy | Other: Intervention (Study Nutritional Drink)<br>* Study nutritional drink containing a mix of enriched micronutrients, probiotics and myo-inositol.<br>|
| Active Comparator: Prior Control - standard micronutrients in preconception & pregnancy<br>NiPPeR Study control nutritional drink containing a mix of micronutrients given to the mother during preconception & pregnancy | Other: Control (Standard Nutritional Drink)<br>* Control nutritional drink containing a standard mix of micronutrients<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child Body Mass Index (kg/m2), derived from weight and height | Child size and body composition | Up to age 8 years, from periconception to age 8 years | 
| Intellectual function (WASI-II IQ [4 sub-test scores], higher score is a higher IQ) | Child cognition | Up to age 8 years, from periconception to age 8 years | 
| Child insulin resistance (HOMA2-IR [no units], higher value is greater insulin resistance) | Child insulin resistance | Up to age 8 years, from periconception to age 8 years | 
| Dimensional Change Card Sort Test (raw & T-scores) | Child executive functioning - NIH Toolbox Cognition Battery component | Up to age 8 years, from periconception to age 8 years | 
| Flanker Inhibitory Control & Attention Test (raw & T-scores) | Child executive functioning - NIH Toolbox Cognition Battery Component | Up to age 8 years, from periconception to age 8 years | 
| Strengths & Difficulties Questionnaire score (no units) | Child neurobehavioural functioning | Up to age 8 years, from periconception to age 8 years | 
| Child Behaviour Check List score (no units) | Child neurobehavioural functioning | Up to age 8 years, from periconception to age 8 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Body fat mass (kg, % and indices) | Obesity and body composition | Up to age 8 years, from periconception to age 8 years | 
| Change in body fat mass (kg) | Adiposity gain | Up to age 8 years, from periconception to age 8 years | 
| Body lean mass (kg, % and indices) | Child body composition - lean mass | Up to age 8 years, from periconception to age 8 years | 
| Change in lean mass (kg) | Lean mass gain | Up to age 8 years, from periconception to age 8 years | 
| Body bone mass (kg, % and indices) | Child body composition - bone mass | Up to age 8 years, from periconception to age 8 years | 
| Change in bone mass (kg) | Bone mass gain | Up to age 8 years, from periconception to age 8 years | 
| Child height (cm) | Child height | Up to age 8 years, from periconception to age 8 years | 
| Height growth (cm) | Linear growth | Up to age 8 years, from periconception to age 8 years | 
| Change in body mass index (z-score & percentile) | Change in BMI | Up to age 8 years, from periconception to age 8 years | 
| Change in weight (kg) | Weight gain | Up to age 8 years, from periconception to age 8 years | 
| Child mid-upper arm circumference (cm) | Child arm circumference | Up to age 8 years, from periconception to age 8 years | 
| Change in mid-upper circumference (z-score) | Change in soft tissue mass | Up to age 8 years, from periconception to age 8 years | 
| Child waist circumference (cm) | Child waist circumference | Up to age 8 years, from periconception to age 8 years | 
| Change in waist circumference (z-score) | Adiposity gain | Up to age 8 years, from periconception to age 8 years | 
| Heart rate response to step test (beats per minute) | Cardiovascular fitness and function | Up to age 8 years, from periconception to age 8 years | 
| Child blood pressure (mm Hg) | Cardiovascular fitness and function | Up to age 8 years, from periconception to age 8 years | 
| Child resting heart rate (beats per minute) | Cardiovascular fitness and function | Up to age 8 years, from periconception to age 8 years | 
| Child minutes to return to resting heart rate (minutes) | Cardiovascular fitness and function | Up to age 8 years, from periconception to age 8 years | 
| Diagnosed medical conditions or disorders ascertained by questionnaire, including child medical conditions, infections, gastrointestinal, cardiovascular, respiratory, dermatological, neuropsychological, mental and musculoskeletal health and wellbeing | Child health and wellbeing | Up to age 8 years, from periconception to age 8 years | 
| Dietary patterns ascertained by frequency questionnaires | Child diet | Up to age 8 years, from periconception to age 8 years | 
| Child Eating Behaviour Questionnaire | Child eating behaviours | Up to age 8 years, from periconception to age 8 years | 
| Parental Feeding Practices Questionnaire | Parental feeding practices | Up to age 8 years, from periconception to age 8 years | 
| Children's Sleep Habits Questionnaire | Child sleep patterns | Up to age 8 years, from periconception to age 8 years | 
| Children's actigraphy measurements of activity behaviours [minutes/day] | Child physical activity, sleep and sedentary behaviours | Up to age 8 years, from periconception to age 8 years | 
| Child Movement Behaviour Questionnaire | Child activity behaviours | Up to age 8 years, from periconception to age 8 years | 
| Skin pricks test results to allergens [mm] | Child atopic sensitisation | Up to age 8 years, from periconception to age 8 years | 
| Child asthma, wheezing illnesses, eczema, rhinitis and food allergy by clinical examination & questionnaires | Child atopic and allergic wellbeing and disorders | Up to age 8 years, from periconception to age 8 years | 
| Hair metabolome panel concentrations (pmol/L) | Biomarkers of health and wellbeing measured in hair samples | Up to age 8 years, from periconception to age 8 years | 
| Urine micronutrient concentrations (nmol/L) | Child micronutrient status | Up to age 8 years, from periconception to age 8 years | 
| Blood micronutrient concentrations (nmol/L) | Child circulating micronutrient profile | Up to age 8 years, from periconception to age 8 years | 
| Blood trace element concentrations (pmol/L) | Child circulating trace element profile | Up to age 8 years, from periconception to age 8 years | 
| Urine trace element concentrations (pmol/L) | Child trace element status | Up to age 8 years, from periconception to age 8 years | 
| Stool metagenomic profile (abundance) | Child gut microbiota composition | Up to age 8 years, from periconception to age 8 years | 
| Skin metagenomic profile (abundance) | Child skin microbiota composition | Up to age 8 years, from periconception to age 8 years | 
| Stool metatranscriptomic profile (relative activity) | Child gut microbiota activity profile | Up to age 8 years, from periconception to age 8 years | 
| Skin metatranscriptomic profile (relative activity) | Child skin microbiota activity profile | Up to age 8 years, from periconception to age 8 years | 
| Stool metabolomic profile (pmol/L) | Child gut microbiota metabolite profile | Up to age 8 years, from periconception to age 8 years | 
| Skin metabolomic profile (pmol/L) | Child skin microbiota metabolite profile | Up to age 8 years, from periconception to age 8 years | 
| Blood molecular profile (% methylation) | Child blood epigenetic profile | Up to age 8 years, from periconception to age 8 years | 
| Buccal molecular profile (% methylation) | Child buccal cell epigenetic profile | Up to age 8 years, from periconception to age 8 years | 
| Blood transcriptomic profile (relative expression) | Child blood transcriptomic profile | Up to age 8 years, from periconception to age 8 years | 
| Buccal transcriptomic profile (relative expression) | Child buccal cell transcriptomic profile | Up to age 8 years, from periconception to age 8 years | 
| Genetic variation (DNA sequence analysis) | Genetic variant analysis | Up to age 8 years, from periconception to age 8 years | 
| Circulating chemocytokine measurements (nmol/L) | Child chemocytokine profile | Up to age 8 years, from periconception to age 8 years | 
| Circulating adipokine measurements (nmol/L) | Child adipokine profile | Up to age 8 years, from periconception to age 8 years | 
| Circulating inflammatory marker measurement (nmol/L) | Child inflammatory factor profile | Up to age 8 years, from periconception to age 8 years | 
| Plasma glucose concentration (mmol/L) | Child's plasma glycemia | Up to age 8 years, from periconception to age 8 years | 
| Plasma lipid concentrations (mmol/L) | Child's metabolic profile - lipid concentrations | Up to age 8 years, from periconception to age 8 years | 
| Plasma high-sensitivity C-reactive protein concentrations (mmol/L) | Child's inflammatory marker status | Up to age 8 years, from periconception to age 8 years | 
| Blood metabolome panel concentrations (pmol/L) | Child's blood metabolomic status | Up to age 8 years, from periconception to age 8 years | 
| Urine metabolome panel concentrations (pmol/L) | Child's urine metabolomic status | Up to age 8 years, from periconception to age 8 years | 
| Urine measurement of environmental pollutant exposure (pmol/L) | Urine exposome pollutant profile | Up to age 8 years, from periconception to age 8 years | 
| Blood measurement of environmental pollutant exposure (ng/gm lipid) | Blood exposome pollutant profile | Up to age 8 years, from periconception to age 8 years | 
| Hair measurement of environmental pollutant exposure (pmol/L) | Hair exposome pollutant profile | Up to age 8 years, from periconception to age 8 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nutrition, Body composition, Neurodevelopment, Lifestyle, Endocrinology and metabolism, Preconception, Supplementation, Pregnancy, Infancy, Breast milk