17/11/57. Umaporn Suthutvoravut, M.D. Faculty of Medicine Ramathibodi Hospital
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1 Vitamin i D and Child Health Umaporn Suthutvoravut, M.D. Department t of Pediatrics i Faculty of Medicine Ramathibodi Hospital Mahidol luniversity, it Thailand 1
2 Outline Vitamin i D and bone health h Vitamin D and other health outcomes Approach to improve vitamin D status 2
3 Functions of Vitamin D Regulation of calcium and phosphorus homeostasis Enhancing intestinal ti absorption efficiency i of calcium and phosphorus Maintenance of normal serum calcium and phosphorus concentration Bone mineral accretion Maintenance of bone health 3
4 Peak bone mass development Strongest predictor of future fracture risk Heaney RP. Osteoporos Int 2000;11:985 4
5 Factors relating to peak bone mass Genetics Body weight Lifestyle factors Nutrition Peak Bone Mass Physical activity Hormones Medications Illness/inflammation 5
6 Essential nutrients for bone health Protein & energy Vitamins: D, K, A, C Minerals: Ca, P, Mg, Na, K I, Zn, Cu, Fe, F 6
7 Effect of nutrient deficiency on bone health Severe deficiency (Tip of the iceberg) Rickets Scurvy Mild moderate, chronic deficiency Stunting Fracture Fracture Osteoporosis 7
8 Daily vitamin D intakes reference values (IU) from recognized scientific authoritative bodies Age WHO/FAO IOM EFSA NHMRC Japan group mo (200) mo 1 18 yr yr Gradually increase
9 Tolerable upper intake levels (UL) of vitamin D (IU/day) from recognized scientific authoritative bodies Age IOM EFSA NHMRC Japan group mo 1,000 1,000 1,000 1, mo 1,500 1,000 1,000 1, yr 2, yr 3,200 Gradually 2,000 increase 1,000 2, yr 3, yr 3,200 4, yr 4,000 3,200 9
10 Nutritional rickets Original description in England in the 17 th century Global health problem among infants, children, and adolescents, particularly in developing countries Caused by vitamin D deficiency or low dietary calcium intakes or both Genetic factors and ethnics may have influences on the negative effects of calcium and vitamin D deficiency Elder CJ et al. Lancet Pettifor JM. Ann Nutr Metab
11 Rickets: Clinical manifestations Bone deformities Fractures Hypocalcemic convulsion Hypotonia Other non skeletal features 11
12 What is the impact of low serum 25(OH)D concentration on bone in healthy children? 12
13 Association between serum 25(OH)D and areal bone mineral density in children& adolescents Review of 10 cross sectional studies published during from 6 countries (in Asia, Europe, p, USA) Age 4 19 years Sample size Inconsistent findings Limitations eg. confounding factors, single measurement of 25(OH)D Moon RJ et al. Osteoporos Int
14 Meta-analysis of interventional studies 6 randomised controlled trials of vitamin D supplementation for at least 3 months Participants: healthy children and adolescents Results: No significant gain in abmd (whole body, forearm, hip, lumbar spine) Children with low baseline 25(OH)D (<35 nmol/l) had borderline significance of benefit on whole body and lumbar spine abmd Winzenberg TM et al. Cochrane Database Syst Rev 10,
15 Study Case-control study of Serum 25(OH)D status t in children with fractures Age N Serum 25(OH), mean (nmol/l) (Yr) (case,control) control) Case Control P Ceroti , 50 UL: 32 LL: NS Chan , Farr , 58 M , 50 F Mayranpaa , Olney , 57 Ryan , Moon RJ et al. Osteoporos Int
16 Case-control study of Serum 25(OH)D status t in children with fractures Study Age N Serum 25(OH)D <50 nmol/l (%) (Yr) (case,control) Case Control P Ceroti , (UL,LL) 6 NS Chan , 17 Farr , 58 M 52, 50 F Mayranpaa , Olney , NS Ryan , Moon RJ et al. Osteoporos Int
17 Outline Vitamin i D and bone health h Vitamin D and other health outcomes Approach to improve vitamin D status 17
18 Functions of Vitamin D Modulator of non skeletal systems and related diseases Muscular system Immune system Cardiovascular system Endocrine system oglucose homeostasis 18
19 Vitamin D and muscle strength in children & adolescents: Cross-sectional sectional study Study N Age (Yr) Measure Main outcome Ward Female Jumping mechano Positive association with muscle power, graphy force, velocity, jump height Foo Handgrip Positive association iti 2009 Female strength Harvey Handgrip Positive association 2014 Both strength with maternal 25(OH)D at 34 week gestation McCarthy EK et al. J Hum Nutr Diet
20 Vitamin D and muscle strength in children & adolescents: Interventional study Study N Age (Yr) El Hajj Fuleihan 2006 Ward Female 73 Female Treatment ,400 IU D3 or 14,000 IU D3 or placebo weekly for 1 yr ,000 IU D2 or placebo every 3 months for 12 months Main outcome No significant improvement in handgrip strength Improved jumping efficacy in vit D gr; No improvement in jump power, force, handgrip strength McCarthy EK et al. J Hum Nutr Diet
21 Study Wright 2009 Peroni 2011 Association between 25(OH)D and immunity : Observational studies Age N 25(OH)D Outcome Asso (Yr) (nmol/l) ciation SLE severity Yes mild mod severe Greer T1DM (newly Dx) Allen m Atopic dermatitis T1DM 928 Infantile food allergy Yes Yes Yes,with Parental 25(OH)D El Fakhri N et al. Horm ResPaediatr
22 Vitamin D supplementation for treatment of acute childhood d pneumonia Study Setting Participants Interven Outcome tion Manaseki Holland 2010 Choudhary 2012 OutpatientI nner city hospital, Afghanistan Inpatient Tertiary care hospital, India Vit D=224, Placebo=229 Age 1 36 mo Vit D=100 Placebo=100 Age 2mo 5 yr Severe pneumonia Single 100, IU oral D3 at onset Oral D3 (1000 IU for<1 yr, y, 2000 IU for>1 yr) for 5 d Number of days to recovery, P=0.17 NS, number of days to recovery, duration of hospitalization Das RR et al. ISRN Pediatrics
23 Association between 25(OH)D and immunity: Interventional studies Study Age (Yr) N (exp) 25(OH)D (nmol/l) Outcome Asso ciation Manaseki Holland Reduction of Yes, single 100,000 IU D 2010 mo pneumonia Camargo ARI attack Yes, milk in winter fortified with 300 IU D3 Manaseki ,487 Incidence of No, 100, Holland 2012 mo pneumonia IU D3 q 3 mo for 18 mo El Fakhri N et al. Horm ResPaediatr
24 Vitamin D supplement in prevention of childhood diarrhea Double blind blind RCT in 3,046 high risk month old infants in Kabul, Afghanistan 6 quarterly supplementation with 100, IU oral D 3 or placebo Follow up for 18 months Results: No reduction on time to first diarrheal illness No reduction on the risk for recurrent diarrhea Aluisio AR et al. Pediatrics
25 Vitamin D and asthma in children Systematic review of 3 prospective birth cohort studies Majormethodological limitation Results: Potential association between low serum vitamin i D and asthma in children Implication: Future high quality researches are needed Rajabbik MH et al. AACI 2014;10:31 25
26 Author Vitamin D and asthma in children Time Participants Exposure outcome Hollams 2011 Started 1989 Part of West Australian Serum 25(OH)D at Unadjusted OR 0.11 (95%CI 0.02 FU 8 yrs Pregnancy Cohort age 6 yrs 0.84) N=693 Van Oeffelen Started Part of PIAMA birth Serum Adjusted OR FU 5 yrs cohort N=372 Netherlands 25(OH)D at age 4 yrs (95%CI ) (vit D tertile 3 VS tertile 1) Tolppanen 2013 Started 1991 FU 6 yrs ys Part of ALSPAC birth cohort N=3323 for asthma outcome N= 2259 for spirometry UK Serum 25(OH)D2 and D3 at age 9.8 yrs Adjusted OR 1.02 (95%CI ) ford3 Adjusted OR 0.89 (95%CI ) for D2 26
27 Vitamin D and adipose tissue Relationship of higher BMI and lower 25(OH)D No convincing evidence for BMI lowering effectby higher 25(OH)D Active role of 1,25(OH) 2 D 3 in adipose tissue in experimental studies Modulating inflammation, adipogenesis, adipocytesecretion ti Mutt SJ et al
28 Association between 25(OH)D and glucose homeostasis Most available cross sectional sectional studies, including the NHANES, support an inverse relationship between serum 25(OH)D and glycemia and insulin resistance Results from both cross sectional and interventional ti studies are inconsistenti t Inconsistent results may be due to differences in subjectcharacteristics characteristics, studypopulation, confounders, techniques for assessing glucose homeostasis, therapeutic regimen El Fakhri N et al. Horm ResPaediatr
29 Association between 25(OH)D and cardiovascular risk factors in children Evidence from observational studies support the association of hypovitaminosis D with cardiovascular risk factors (higher BP, dyslipidemia, higher BMI, increase left ventricular mass) Interventional studies does not clearly support the use of vitamin D supplementation to prevent CVD El Fakhri N et al. Horm ResPaediatr
30 Outline Vitamin i D and bone health h Vitamin D and other health outcomes Approach to improve vitamin D status 30
31 Sources of vitamin D in infants Intrauterine Food sources: human milk provides approximately mcg/l (8 80 IU/L) Handbook of milk composition 1995 Cutaneous synthesis after exposure to sunlight: ethnic, type of skin color, sun exposure, latitude, seasoning 31
32 Maternal vitamin D status and Breast milk vitamin D 32
33 Maternal vitamin D supplementation to meet needs of breastfed infant: A systemic review Study N Maternal dose (IU) Maternal 25(OH)D,ng/ml Baseline Outcome Hollis G1: 2,000 daily G2: 4,000 daily 10 G1: 400 daily G2: 6,400 daily 27.6 (3.3) 32.9 (2.4) 36.1 (2.3)* 44.5 (3.9)* Wagner 10 G1: 400 daily * Saadi 44 G1: 2,000 daily 11.7 (4.1) 16.7 (5.6)* 2009 G2: 60,000 monthly 8.9 (4) 14.3 (4)* *P<0.05, increase from baseline Thiele DK et al. J Hum Lact
34 Maternal vitamin D supplementation to meet needs of breastfed infant: A systemic review Study N Maternal dose Breastmilk vitamin D (IU) (IU/L) Baseline Outcome Hollis 18 G1: 2,000 daily 35.5 (3.5) 69.7 (3)* 2004 G2: 4,000 daily 40.4 (3.7) (48.3) * Wagner 10 G1: 400 daily G2: 6,400 daily * Saadi 44 G1: 2,000 daily 2009 G2: 60,000 monthly Unable to detect 50.9 (0 62.5)** *P<0.05, 05 increase frombaseline; ** subset of12women Thiele DK et al. J Hum Lact
35 Maternal vitamin D supplementation to meet needs of breastfed infant: A systemic review Study N Maternal dose (IU) Infant 25(OH)D, (ng/ml) Baseline Outcome Hollis 18 G1: 2,000 daily 7.9 (1.1) 27.8 (3.9)* 2004 G2: 4,000 daily 13.4 (3.3) 30.8 (5) * Wagner 10 G1: 400 daily 13 43* 2006 G2: 6,400 daily 14 46* Saadi G1: 2,000 daily G2: 60,000 monthly *P<0.05, 05 increase from baseline 5.6 (3.4) 5.48 (4.84) 19.8 (7.4)* 17.8 (6)* Thiele DK et al. J Hum Lact
36 Vitamin D supplementation advice for prevention of rickets Pregnant and breastfeeding women UK Department of Health 2012 American Academy of Pediatrics 2008 WHO 2012 All pregnant and breastfeeding women to take a daily supplement containing 10 mcg/day (400 IU/day) Measure maternal vitamin D status and supplement if found to be insufficient Call for rigorous RCT to evaluate the benefit and safety of routine vit D supplementation in pregnancy 36
37 Vitamin D supplementation advice for prevention of rickets Pregnant and breastfeeding women Canadian Paediatric Society 50 mcg (2,000 IU)/day for 2007 pregnant and lactating women, especially during winter months Institute ofmedicine 2010 Recommended d Dietary Allowance 15 mcg/day. Upper level intake 100 mcg/day 37
38 Vitamin D supplementation advice for prevention of rickets Breastfed infants UK Department of Health 2012 Institute of Medicine 2010 If mother has not taken supplements throughout pregnancy, baby might need to receive drops from 1 month of age 10 mcg/day (400 IU/day) during first year of life 38
39 Vitamin D supplementation advice for prevention of rickets Breastfed infants Canadian Paediatric Society mcg/day (200 IU/day) for premature infants, 10 mcg/day in fullterm until 1 yr of age, but 20 mcg/day during winter and for those living at more northern latitudes than 55 th parallel or between 40 and 55 th parallel with additional risk factors 39
40 Vitamin D supplementation advice for prevention of rickets Children and adolescents American Academy of Pediatrics 2008 UK Department of Health 2012 Universal supplementation of 10 mcg/day (400 IU/day) in all children who are consuming less than 1,000 ml per day of vitamind fortified formula or milk, greater doses for at risk groups mcg/day (280 IU/day) in all children aged 6 months until the age of 5 years 40
41 Conclusion Main functions of vitamin D are regulation of calcium and phosphorus homeostasis, bone mass development, and growth Studies in children and adolescents demonstrate roles of vitamin D in other body systems but results are not consistent Vitamin D status of a child may be associated with long term health outcomes beyond bone eg. prevention of DM and CVD More high quality studies are needed to generate convincing evidence for translation into clinical practice and public health policy regarding vitamin D intakes, supplementation, and normal blood values in various age groups 41
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