NiPPeR Randomised Trial - Child Follow Up Study (NiPPeR Child)

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

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.

Study Overview

• Status: Enrolling by invitation
• Conditions: Neurobehavioral Manifestations; Allergy; Microbial Colonization; Growth Disorders; Atopic Dermatitis; Obesity, Childhood; Metabolic Disturbance; Cognition; Lifestyle; Breastfeeding; Nutrition, Healthy; Atopy
• Intervention / Treatment: Other: Intervention (Study Nutritional Drink); Other: Control (Standard Nutritional Drink)

• Study Type: Interventional
• Enrollment (Estimated): 510
• Phase: Not Applicable

Contacts and Locations

Study Locations

• New Zealand
  • Auckland, New Zealand, 1142
    • The University of Auckland
• Singapore
  • Singapore, Singapore, 119228
    • National University Hospital
• United Kingdom
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child
• Accepts Healthy Volunteers: Yes

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Healthcare utilisation (US$)	Health economics analysis of child outcomes	Up to age 8 years, from periconception to age 8 years

Collaborators and Investigators

• Sponsor: University of Southampton
• Collaborators: National University Hospital, Singapore; Singapore Institute for Clinical Sciences; National University Health System, Singapore; University of Auckland, New Zealand; National University of Singapore; Auckland UniServices Ltd.
• Investigators: Principal Investigator: Wayne S Cutfield, MB MD FRACP, The University of Auckland; Principal Investigator: Shiao-Yng Chan, MD PhD FRCOG, National University of Singapore; Principal Investigator: Keith M Godfrey, BM PhD FRCP, MRC Lifecourse Epidemiology Centre, University of Southampton

Publications and helpful links

General Publications

• Godfrey KM, Cutfield W, Chan SY, Baker PN, Chong YS; NiPPeR Study Group. Nutritional Intervention Preconception and During Pregnancy to Maintain Healthy Glucose Metabolism and Offspring Health ("NiPPeR"): study protocol for a randomised controlled trial. Trials. 2017 Mar 20;18(1):131. doi: 10.1186/s13063-017-1875-x.
• Godfrey KM, Barton SJ, El-Heis S, Kenealy T, Nield H, Baker PN, Chong YS, Cutfield W, Chan SY; NiPPeR Study Group. Myo-Inositol, Probiotics, and Micronutrient Supplementation From Preconception for Glycemia in Pregnancy: NiPPeR International Multicenter Double-Blind Randomized Controlled Trial. Diabetes Care. 2021 May;44(5):1091-1099. doi: 10.2337/dc20-2515. Epub 2021 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): June 16, 2023
• Primary Completion (Estimated): August 30, 2026
• Study Completion (Estimated): August 30, 2026

Study Registration Dates

• First Submitted: May 4, 2023
• First Submitted That Met QC Criteria: June 27, 2023
• First Posted (Actual): July 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 7, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: June 1, 2023

More Information

Terms related to this study

• Keywords: Supplementation; Pregnancy; Nutrition; Body composition; Neurodevelopment; Preconception; Lifestyle; Breast milk; Infancy; Endocrinology and metabolism
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Skin Diseases; Neurologic Manifestations; Disease Attributes; Overnutrition; Nutrition Disorders; Overweight; Body Weight; Obesity; Infections; Communicable Diseases; Pediatric Obesity; Dermatitis; Neurobehavioral Manifestations; Growth Disorders
• Other Study ID Numbers: 79093

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No