Vitamin D Intervention in Infants - 6 Years Follow-up (VIDI2)

Study Overview
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Brief Summary
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Exposure to vitamin D intervention in early life may have permanent effects on physiology and metabolism. Bone growth and mineralization, development of immunity, body composition and brain structure and functioning may be affected. The importance of a long-term surveillance includes follow-up of both beneficial but also harmful effects of vitamin D. Vitamin D intervention in infants (VIDI) study was conducted in 2013-2016. VIDI study was a large randomized trial that aimed to evaluate effects of two vitamin D supplemental doses of daily 10 ug and 30 ug from the age 2 weeks until 2 years on bone strength, infections, immunity, allergy, atopy and asthma, neurologic and cognitive development, and genetic regulation of mineral homeostasis. Current study is a 6 Years Follow-up (VIDI2) study of the original VIDI trial. Our focuses of interest in the follow-up are: bone strength, growth pattern, body composition, and morbidity due to infections and allergic diseases, and the development of immunity. Further, in addition to more classical associates of vitamin D, our aim is to continue to follow-up children's neurocognitive development and mental health. We will also focus on the effect of vitamin D supplementation on occurrence of molar-incisor hypomineralization, dental caries, and oral immunity.

Official Title
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VITAMIN D INTERVENTION IN INFANTS: Effects of Early Vitamin D Exposure on Childhood Health at 6 Years - a Follow-up Study

Conditions
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Bone Strength, Growth, Body Composition, Infection, Allergic Diseases, Dental Health

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All who participated in the original VIDI study until last study visit at the age of 2 years. Exclusion criteria: None

Ages Eligible for Study
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Minimum Age: 6 Years
Maximum Age: 7 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Areal bone mineral quantity | Bone mineral quantity in milligrams per millimeter is measured by peripheral quantitative computed tomography (pQCT). | 6.5 years | 
| Volumetric bone mineral density | Bone mineral density in milligrams per cubic centimeter is measured by pQCT. | 6.5 years | 
| Cross-sectional area of the bone | Cross-sectional area of the bone in square millimeters is measured by pQCT. | 6.5 years | 
| Bone mineral quantity | Bone mineral quantity in grams is measured by dual-energy X-ray absorptiometry (DXA). | 6.5 years | 
| Bone mineral density | Bone mineral density in grams per centimeter squared is measured by DXA. | 6.5 years | 
| Serum intact parathyroid hormone | Serum intact parathyroid hormone concentration is measured from blood samples with the blood gas analyzer ABL 90 FLEX or ABL 835 FLEX. | 6.5 years | 
| Plasma ionized calcium | Plasma ionized calcium concentration is measured from blood samples with the blood gas analyzer ABL 90 FLEX or ABL 835 FLEX. | 6.5 years | 
| Plasma alkaline phosphatase | Plasma alkaline phosphatase concentration is measured from blood samples with photometric methods. | 6.5 years | 
| Serum C-telopeptide of type I collagen | Serum C-telopeptide of type I collagen is measured with competitive polyclonal antibody assay. | 6.5 years | 
| Plasma fibroblast growth factor 23 | Plasma intact and C-terminal fibroblast growth factor 23 is determined with enzyme-linked immunosorbent assay. | 6.5 years | 
| Morbidity due to infectious diseases | Morbidity due to infectious diseases in frequencies and type are to be collected via questionnaires filled in by parents. | 6.5 years | 
| Morbidity due to allergic diseases | Morbidity due to allergic diseases and symptoms are to be collected via questionnaires filled in by parents. | 6.5 years | 
| Weight | Weight in kilograms is measured with a Seca 285 digital measuring station. | 6.5 years | 
| Height | .Height in centimeters is measured with a Seca 285 digital measuring station | 6.5 years | 
| Fat mass | Fat mass in kilograms based on ohms is measured by InBody bioelectrical impedance analysis. | 6.5 years | 
| Fat-free mass | Fat-free mass in kilograms based on ohms is measured with InBody. | 6.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| High sensitivity C-reactive protein | High sensitivity C-reactive protein is measured with enzyme immunoassay. | 6.5 years | 
| Plasma matrix metalloproteinase 8 | Plasma matrix metalloproteinase 8 is analysed with time-resolved immunofluorometric assay. | 6.5 years | 
| Gene variants | Gene variants associated with vitamin D metabolism and primary outcomes are performed using Sanger-sequencing, Taqman and genome-wide SNP-arrays. | 6.5 years | 
| Epigenetic changes | Epigenetic changes associated with vitamin D metabolism and primary outcomes are performed using methylation assays. | 6.5 years | 
| Cognitive abilities | Cognitive abilities are measured with Wechsler Intelligence Scale for Children-IV. Scales are scored according to the manual and standardized total scores vary between 10 and 159. Higher scores present better performance. | 6.5 years | 
| Executive functioning | Executive functions are measured with performance based test called NEPSY-II. Scales are scored according to the manual. Higher scores represent better performance. | 6.5 years | 
| Psychiatric disorders and symptoms | Psychiatric disorders and symptoms are measured with parent-rated questionnaire: the Child behavioral checklist. Scales are scored according to the manual. Maximum and minimum values very between subscales scales. Higher scores represent worse outcomes, i.e. more psychiatric symptoms. | 6.5 years | 
| Attention deficient and hyperactivity symptoms | Attention deficient and hyperactivity symptoms are measured with parent rated 'ADHD Rating Scale IV'-questionnaire. Scales are scored according to the published guidelines and higher scores reflect more problems. | 6.5 years | 
| Autism spectrum disorders and symptoms | Parent-rated Autism Spectrum Screening Questionnaire is used to measure Autism spectrum disorders and symptoms. Scales are scored according to the published guidelines and higher scores reflect more problems. | 6.5 years | 
| Sleep | Sleep is measured using a parent rated Sleep Disturbance Scale for Children. Questionnaire is scored according to publishers guidelines and the minimum and maximum scores vary. Higher scores in disturbance scales present worse outcome whereas a longer time at sleep represents a better outcome. | 6.5 years | 
| Temperament | Temperament is measured using parent rated questionnaire 'The Children's Behavior Questionnaire'. Questionnaire is scored according to manual and the minimum and maximum scores vary by temperament dimension. Higher scores do not as such mean better or worse outcome. | 6.5 years | 
| Prevalence of molar-incisor hypomineralization | Clinical evaluation by dentist of tooth enamel opacities, posteruptive enamel breakdown, atypical restorations, and/or extractions of molars according to the European Academy of Paediatric Dentistry criteria | 6.5 years | 
| Prevalence of caries | Clinical evaluation by dentist as decayed or filled tooth surfaces. | 6.5 years | 
| Salivary matrix metalloproteinase 8 level | Salivary matrix metalloproteinase 8 is analysed with salivary sample test. | 6.5 years | 
| SARS-CoV-2 virus antibodies | SARS-CoV-2 virus antibodies are measured from blood samples | 6,.5 years | 
| SARS-CoV-2 virus | SARS-CoV-2 virus PCR is analyzed from saliva | 6.5 years |