Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: A randomized trial. Sina Gallo¹, Kathryn Comeau¹, Catherine Vanstone¹, Sherry Agellon¹, Atul Sharma², Glenville Jones 3 , Mary L’Abbé 4 , Ali Khamessan 5 , Celia Rodd¹²*, Hope Weiler¹* - PowerPoint PPT Presentation
Sina Gallo¹, Kathryn Comeau¹, Catherine Vanstone¹, Sherry Agellon¹, Atul Sharma², Glenville Jones 3 , Mary L’Abbé 4 , Ali Khamessan 5 , Celia Rodd¹²*, Hope Weiler¹* 1 School of Dietetics and Human Nutrition, McGill University, Montréal, Québec 2 Montreal Children’s Hospital, McGill University Health Centre, Montréal, Québec 3 Departments of Biomedical & Molecular Sciences & Medicine, Queen’s University, Kingston, Ontario 4 Department of Nutritional Sciences, University of Toronto, *Senior authors Effect of different dosages of oral vitamin D supplementation on vitamin D status in healthy, breastfed infants: A randomized trial
Transcript
Sina Gallo¹, Kathryn Comeau¹, Catherine Vanstone¹, Sherry Agellon¹, Atul Sharma², Glenville Jones3, Mary L’Abbé4, Ali Khamessan5, Celia Rodd¹²*, Hope Weiler¹*1School of Dietetics and Human Nutrition, McGill University, Montréal, Québec
2Montreal Children’s Hospital, McGill University Health Centre, Montréal, Québec3Departments of Biomedical & Molecular Sciences & Medicine, Queen’s University,
Kingston, Ontario4Department of Nutritional Sciences, University of Toronto, Toronto, Ontario
5Euro-pharm International Canada Inc., Montréal, Québec
*Senior authors
Effect of different dosages of oral vitamin D supplementation on
vitamin D status in healthy, breastfed infants: A randomized trial
• Role of the Sponsor: The funding organizations had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; and preparation, review, or approval of the manuscript. – Canadian Institutes of Health Research, Nutricia Research
Foundation and the Canadian Foundation for Innovation– Fonds de la Recherche en Santé du Québec doctoral scholarship – The Canada Research Chairs professor salary award
• Conflict of Interest Disclosures: All authors have completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. AK is an employee of Europharm International Canada Inc. All other authors have no conflicts of interest.
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Role of the Sponsor andConflict of Interest DisclosuresConflict of Interest Disclosures
25(OH)D
http://www.freedigitalphotos.net
Mother’s Skin
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Maternal Sources: Sun, food and supplements
Vitamin D Sources and Use:Infant Nutrition and Growth
Infant Vitamin D Sources
25(OH)D
CYP27A1(liver)
http://www.freedigitalphotos.net
Mother’s Skin
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Maternal Sources: Sun, food and supplements
Infant Sources: Maternal-fetal transfer, breast milk, supplements
Vitamin D Sources and Use:Infant Nutrition and Growth
DBP
Infant Vitamin D
Stores
Infant Vitamin D Sources
25(OH)D
CYP27A1(liver)
1,25(OH)2D
CYP27B1(kidneys)
“Biologically Active”
http://www.freedigitalphotos.net
Mother’s Skin
DBP
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Maternal Sources: Sun, food and supplements
Infant Sources: Maternal-fetal transfer, breast milk, supplements
Vitamin D Sources and Use:Infant Nutrition and Growth
DBP
Healthy bone growth
Infant Vitamin D
Stores
(International Units)
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Prevention of Rickets and for Healthy Infant Growth
Adequate Intake,
Institute of Medicine USA;
American Academy of Pediatrics
Health Canada; Canadian Paediatric
Society
Canadian Paediatric
Society
Tolerable Upper Intake
Level,Institute of
Medicine USA
No observed adverse effect level,Institute of Medicine
USA
Vitamin D Recommendations and Safety Levels: year 2006
http://www.freedigitalphotos.net
Recommendations Safety Levels
25(OH)D concentrations (nmol/L)
Oginni 1996 Graff 2004(Nigeria)
Dawodu 2005(UAE)
Garabedian 1983(Belgium/France)
Rickets
Molla 2000(Kuwait)
Cesur 2003(Turkey)
Arnaud 1976“Severe”(Canada/US)
Arnaud 1976“Mild” (Canada/US)
Balasubraman 2003 (India)
Canadian Paediatric Society
Recommendation----------------------------Based on adults and older children; but unclear in infants.
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Vitamin D Status based on Body Stores and Bone Health: year 2006
1. establish a vitamin D dosage which would support 25(OH)D concentrations ≥ 75 nmol/L in 97.5% of breast fed infants• ≥ 50 nmol/L
2. further define the appropriate dosage using:• weight, length and head circumference growth; • the addition of mineral to growing bone.
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Ethics: McGill University Institutional Review Board; Health Canada Clinical Trials; Trial Registration clinicaltrials.gov Identifier: NCT00381914.
The study was conducted with the objectives to:
75 nmol/L = 30 ng/mL50 nmol/L = 20 ng/mL
Randomized (n=132)
800 IU/d (n=39)
1600 IU/d (n=16)
400 IU/d (n=39)
n=29
1200 IU/d (n=38)
n=34
Follow-up 3 mo
Follow-up 12 mo
n=28
n=35 n=32
n=29
n=15
n=12
Discontinued July 2008 - 81% of group pl. 25(OH)D >125 nmol/L after 2 mo
Analyzed as intent-to-treat
Did not meet criteria (n= 275)
Contact declined or unavailable (n=185)
Other reason (n=345)
74% retention 9
Study Groups: Healthy InfantsStudy Groups: Healthy Infants
Assessed for eligibility (n=937)
Visit 2
87% on vitamin D Birth
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Age (months)
Visit 4 Visit 5 Visit 6
6 9 12
RecruitmentVisit 3
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BaselineVisit 1
Infants were randomized to receive 400, 800, 1200 or 1600 IU of vitamin D3 daily
Baseline Characteristics Mothers on average 33 y of age, 85% were white High income (60% > Canadian average $75,000) University educated mothers (89%) Infants (58% males) Born April-October (60%)
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Trial Time CourseTrial Time Course
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*p<0.01 vs. 400 IU/d at same time; logistic regression at each time point 11
How many infants met the vitamin D How many infants met the vitamin D status target of 75 nmol/L of 25(OH)D?status target of 75 nmol/L of 25(OH)D?
3 months800 vs 400 IU OR 3.5 95% CI, 1.1-11
1200 vs 400 IU OR 9.7 95% CI, 1.9-49.7
*p<0.01 vs. 400 IU/d at same time; logistic regression at each time point 12
How many infants met the vitamin D How many infants met the vitamin D status target of 75 nmol/L of 25(OH)D?status target of 75 nmol/L of 25(OH)D?
3 months800 vs 400 IU OR 3.5 95% CI, 1.1-11
1200 vs 400 IU OR 9.7 95% CI, 1.9-49.7
*p<0.01 vs. 400 IU/d at same time; logistic regression at each time point 13
How many infants met the vitamin D How many infants met the vitamin D status target of 75 nmol/L of 25(OH)D?status target of 75 nmol/L of 25(OH)D?
3 months800 vs 400 IU OR 3.5 95% CI, 1.1-11
1200 vs 400 IU OR 9.7 95% CI, 1.9-49.7
No differences among treatments over time by logistic regression at each time point 14
How many infants met the vitamin D How many infants met the vitamin D status target of 50 nmol/L of 25(OH)D?status target of 50 nmol/L of 25(OH)D?
Recommended Status Target
IOM, AAP
Assessment of GrowthAssessment of Growth
0123456789
10111213
Age (months)
Wei
ght (
kg)
1 2 3 6 9 12
+ 2SD
- 2SD
0123456789
10111213
Age (months)
Wei
ght (
kg)
1 2 3 6 9 12
+ 2SD
- 2SD
400 IU/d800 IU/d1200 IU/d1600 IU/d
+/-2 Weight-for-ageZ-score (WHO)
Girls Boys
Mean ± 95% CI; No differences among treatments over time by repeated measures ANOVA 15
0
50
100
150
200
250
300
1200 IU/d 800 IU/d 400 IU/d
Age (months)
Who
le B
ody
BM
C (g
)
1 3 6 9 12
Whole Body
1600 IU/d
Assessment of Bone HealthAssessment of Bone Health
Mean ± SEM; No differences among treatments over time by repeated measures ANOVA accounting for race after adjustment for multiple comparisons
400 IU dosage: sufficient to achieve 50 nmol/L of 25(OH)D; Higher dosages needed if target is 75 nmol/L of 25(OH)D; No further benefits to growth or bone health of infants.
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Healthy Infant Nutrition: Public Policy & Position Statements for daily vitamin D supplementation
dosages (International Units)
Vitamin D Recommendations and Safety Levels: year 2013
400 IU dosage: sufficient to achieve 50 nmol/L of 25(OH)D; Higher dosages needed if target is 75 nmol/L of 25(OH)D; No further benefits to growth or bone health of infants.
6 to12 monthsTolerable Upper
Intake LevelInstitute of Medicine
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Institute of Medicine Health Canada
Canadian Paediatric Society
American Academy of Pediatrics
Canadian Paediatric
Society
Birth to 6 monthsTolerable Upper
Intake LevelInstitute of Medicine
Healthy Infant Nutrition: Public Policy & Position Statements for daily vitamin D supplementation
dosages (International Units)
Vitamin D Recommendations and Safety Levels: year 2013
• Identify status targets– Benefits to bone health
• Underpowered to detect early and longer-term benefits– Other health benefits
• Needs of other population groups– Underrepresented darker skin pigmentation– Higher risk for deficiency
• Remote geographic location• Infant born with low vitamin D stores
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Unanswered Questions:During and beyond infancy
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Leading Institutions Funding Agencies
Recruitment and Monitoring Families and Infants
RecruitmentFive Pediatric Clinics West Island & Greater Montreal AreaLakeshore General HospitalSafety OfficerDr. J. Mitchell, M.D., F.R.C.P.C.
