Vitamin D and Health Outcomes in Preterm Born Population (ViDePrePop)

Vitamin D and Health Outcomes in Preterm Born Population -A Cohort and an Intervention Study of Vitamin D on Health Outcomes of Bones, Teeth, Muscles, Heart, and Lungs in Children and Adults Born Preterm in Northern Finland

Improved survival of very preterm newborn population during the last decades has challenged us neonatologists to study and improve nutritional practices including vitamin D (VitD) supplementation. However, long term outcome in this aspect has not been researched in well documented preterm populations. As VitD has receptors in almost all human cells it modulates growth of many organs. Therefore I start to assess VitD supplementation practices and later health outcome (bones, teeth, muscles, heart, lungs) in two preterm population cohorts cared in Oulu University Hospital at the age of 5 years and 24 years (born 2014-2017 and 1994-1997).

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Diseases; Bone Diseases, Metabolic; Heart Rate Variability; Prematurity; Vitamin D3 Deficiency; Stress Physiology
• Intervention / Treatment: Dietary supplement: Vitamin D

Detailed Description

Goals:

• To investigate the impact of VitD and mineral supplementation and biochemistry in infancy on health outcomes at the age of 5 years in childhood (bones, teeth, muscles, heart, lungs) after preterm birth (Preterm Child group)
• To investigate the impact of VitD and mineral supplementation and biochemistry in infancy on health outcomes at the age of 24-25 years in adulthood (bones, teeth, muscles, heart, lungs) after preterm birth (Preterm Adult group)

Subjects:

• Preterm Child group; Children, who were born prematurely before before 32 gestation weeks and before 34 gestation weeks with very low birth weight (VLBW, < 1500g) in Oulu University Hospital and/or cared in Neonatal Unit with VitD concentration measured before discharge during the years 2014 to 2017.
• Preterm Adult group; Adults, who were born prematurely before 32 gestation weeks and before 34 gestation weeks with very low birth weight (VLBW, < 1500g) in Oulu University Hospital and/or cared in Neonatal Intensive Unit during the years 1994 to 1997. For power calculation, the amount of participants for the adult group was done by estimating the inadequately low vitamin D concentration (< 50 nmol/l) to be found in 28 % of preterm born adults. (In Northern Finnish birth cohort 28 % at the age of 31 had serum 25-OH vitamin D concentration < 50 nmol/l in 1997). With the estimation of supplementation to decrease the percentage of participants with low vitamin D to 9 %, the required amount of participants would be minimum of 56 per group. Furthermore, if the level after supplementation is estimated to be low only in 2,8 %, the amount would be required as 29 cases per group.

Methods in protocol:

At the first visit and in the end of intervention; measurements of length, weight, head circumference, waist-to-hip ratio will be done; muscular power is assessed by grip test of both hands; lung function test with bronchodilatation is done at the first appointment; heart ultrasound, blood pressure measurement and bicycle stress test with a circadian electrocardiography will be done in the beginning and at the end; bone mineralisation will be measured by dual energy x-ray absorptiometry (DXA) and ultrasound methods; VitD concentration will be measured 4 months interval during the follow up. The control peers participate only the first visit. The child group will be assessed only once and without bicycle stress test.

• Study Type: Observational
• Enrollment (Actual): 87

Contacts and Locations

• Study Contact: Name: Marita Valkama, Docent; Phone Number: +35883155828; Email: arjamaritavalkama@gmail.com
• Study Contact Backup: Name: Marja Ojaniemi, Docent; Phone Number: +35883155822; Email: marja.ojaniemi@ppshp.fi

Study Locations

• Finland
  • Oulu, Finland, 90220
    • Oulu University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 25 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Healthy preterm born children and young adults. Tern born young adults as controls for the adult group.

Description

Inclusion Criteria:

• preterm and term born adults at the age of 22-25
• preterm born children at 5 years

Exclusion Criteria:

- motor disability

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Preterm Child group; Preterm children at the age of 5 years; Born before 34 gestation weeks in 2014-2017; Cared in Oulu University Hospital
Preterm Adult group; Preterm born adults at the age of 24-25 years; Born before 34 gestation weeks in 1994-1997; Cared in Oulu University Hospital	Dietary supplement: Vitamin D; To investigate the effect of one year vitamin D supplementation in preterm born adults (4000 IU = 100 micrograms a day if serum concentration is < 30 nmol/l, 2000 IU = 50 micrograms a day if 30-50 nmol/l and 1000 IU = 25 micrograms a day if > 50-80 nmol/l, and no additional supplement if > 80 nmol/l) on health outcomes (bones, teeth, muscles, heart, lungs) . The target level of vitamin D concentration by every 4 months interval is 80 - 120 nmol/l .(Preterm Adult group)
Adult Control group; Age and gender matched term born controls for comparison of the entry assessments in the Preterm Adult group

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Vitamin D of preterm adults, before = VitD 0A	S-25-OH -value; nmol/l	Baseline
Vitamin D of preterm children = VitD C	S-25-OH -value;nmol/l	Baseline
Vitamin D of preterm adults, after = VitD 1A	S-25-OH -value; nmol/l	One year
Exercise heart rate, before = HR 0A	Cycling stress test; heart rate following maximal exercise , seconds to hours	Baseline
Exercise heart rate, after = HR 1A	Cycling stress test;heart rate following maximal exercise , seconds to hours	One year
HRV of preterm adults, before = HRV 0A	Heart rate variability; autonomic function; heart rate root mean square of the successive differences (RMSSD)	Baseline
HRV of preterm adults, after = HRV 1A	Heart rate variability; autonomic function; heart rate root mean square of the successive differences (RMSSD)	One year
HRV of preterm children = HRV 0C	Heart rate variability; autonomic function; heart rate root mean square of the successive differences (RMSSD)	Baseline
Lung reversibility test in preterm adults, before = LR 0	Spirometry and bronchodilate test; reversibility: Yes or No	Baseline
Lung function capacity in preterm adults, before = LFC 0	Spirometry; z-score of FVC	Baseline
Lung function volume in preterm adults, before = LFV 0	Spirometry ; z-score of FEV1	Baseline
Lung function capacity in preterm adults, after = LFC 1	Spirometry; z-score of FVC	One year
Lung function volume in preterm adults, after = LFV 1	Spirometry; z-score of FEV1	One year
Lung function in preterm children	Auscultation and bronchodilate test; reversibility: Yes or No	Baseline
Body composition of bone mineral density in preterm adults, before = BMD 0A	DXA result; bone mineral density (BMD) g/cm2; Z-scores	Baseline
Body composition of bone mineral content in preterm adults, before = BMC 0A	DXA result; bone mineral content (BMC) g; Z-scores	Baseline
Body composition of bone mineral density in preterm children = BMD C	DXA result; bone mineral density (BMD) g/cm2; Z-scores	Baseline
Body composition of bone mineral content in preterm children = BMC C	DXA result; bone mineral content (BMC) g; Z-scores	Baseline
Body composition of bone mineral density in preterm adults, after = BMD 1A	DXA result; bone mineral density (BMD) g/cm2; Z-scores	One year
Body composition of bone mineral content in preterm adults, after = BMC 1A	DXA result; bone mineral content (BMC) g Z-scores	One year

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone mineralisation, before = BM 0	ultrasound; bone speed of sound (SOS) m/sec z-score	Baseline
Bone mineralisation, after = BM 1	ultrasound; bone speed of sound (SOS) m/sec z-score	One year

Collaborators and Investigators

• Sponsor: University of Oulu
• Investigators: Study Chair: Marita Valkama, Docent, MRC, University of Oulu; Study Director: Marja Ojaniemi, Docent, MRC, University of Oulu

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2018
• Primary Completion (Estimated): December 31, 2023
• Study Completion (Estimated): December 31, 2023

Study Registration Dates

• First Submitted: May 16, 2019
• First Submitted That Met QC Criteria: April 9, 2020
• First Posted (Actual): April 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 29, 2023
• Last Update Submitted That Met QC Criteria: November 27, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Vitamin D; Lung function; Prematurity; DXA; Heart rate; Bone mineralisation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Musculoskeletal Diseases; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Lung Diseases; Premature Birth; Bone Diseases; Bone Diseases, Metabolic; Metabolic Diseases; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Vitamin D
• Other Study ID Numbers: EETTMK 92/2017

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