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

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

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.

Study Overview

• Status: Completed
• Conditions: Growth; Body Composition; Infection; Dental Health; Allergic Diseases; Bone Strength

• Study Type: Observational
• Enrollment (Actual): 415

Contacts and Locations

Study Locations

• Finland
  • Helsinki, Finland
    • Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 years to 7 years (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

In the original VIDI study the eligible infants were born at term (37 weeks and 0 days' to 42 weeks and 0 days' gestation), with a birth weight within 2 SDs of the mean for gestational age. Infants excluded were those requiring intravenous glucose, antibiotics, nasal continuous positive airway pressure treatment for more than 1 day, phototherapy for more than 3 days, or nasogastric tube feeding for more than 1 day and infants with seizures.

Description

Inclusion Criteria:

All who participated in the original VIDI study until last study visit at the age of 2 years.

Exclusion criteria:

None

Study Plan

How is the study designed?

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Helsinki
• Investigators: Principal Investigator: Sture Andersson, MD, Helsinki University Central Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 1, 2019
• Primary Completion (ACTUAL): December 15, 2021
• Study Completion (ACTUAL): May 27, 2022

Study Registration Dates

• First Submitted: February 24, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (ACTUAL): March 10, 2020

Study Record Updates

• Last Update Posted (ACTUAL): November 3, 2022
• Last Update Submitted That Met QC Criteria: October 31, 2022
• Last Verified: October 1, 2022

More Information

Terms related to this study

• Other Study ID Numbers: Helsinki University

Drug and device information, study documents

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