mia. (For a more complete review of nutritional ricketsand its management, please refer to the recent publica-tion in
Endocrinology and Metabolism Clinics of North Amer-ica
on the topic.
23
)There are 2 forms of vitamin D: D
2
(ergocalciferol,synthesized by plants) and D
3
(cholecalciferol, synthe-sized by mammals). The main source of vitamin D forhumans is vitamin D
3
through its synthesis in the skinwhen UV-B in the range of 290 to 315 nm converts7-dehydrocholesterol into previtamin D
3
. Through theheat of the skin, previtamin D
3
is further transformedinto vitamin D
3
, which then binds to the vitaminD–binding protein and is transported to the liver andconverted to 25-hydroxyvitamin D (25-OH-D) by the ac-tion of 25-hydroxylase. 25-OH-D, the nutritional indicatorof vitamin D, undergoes a second hydroxylation in thekidneyandothertissuestobecome1,25-dihydroxyvitaminD (1,25-OH
2
-D). Vitamin D is an important prehormonewith active metabolites (25-OH-D and 1,25-OH
2
-D) thatare involved in many metabolic processes beyond boneintegrityandcalciumhomeostasis.
24
More-detailedreviewsofvitaminDphysiologyandmetabolismareavailablefromHathcock et al,
25
Holick,
26
Webb,
27
and Misra et al.
23
It is important to note that measuring the concentra-tion of 1,25-OH
2
-D instead of 25-OH-D for assessment ofvitamin D status can lead to erroneous conclusions, be-cause 1,25-OH
2
-D concentrations will be normal or evenelevated in the face of vitamin D deficiency as a result ofsecondary hyperparathyroidism (see Table 1). Preven-tion of vitamin D deficiency and achieving adequateintake of vitamin D and calcium throughout childhoodmay reduce the risk of osteoporosis as well as otherlong-latency disease processes that have been associatedwith vitamin D–deficiency states in adults.
28–31
The presence of vitamin D as a natural ingredient infood in most diets is limited, occurring in relatively sig-nificant amounts only in fatty fish and certain fish oils,liver and fat from aquatic mammals, and egg yolks ofchickens fed vitamin D.
32
In adults, new evidence sug-gests that vitamin D plays a vital role in maintaininginnate immunity
33
and has been implicated in the pre-vention of certain disease states including infection,
34,35
autoimmune diseases (multiple sclerosis,
28,33,36,37
rheu-matoid arthritis
38
), some forms of cancer (breast, ovar-ian, colorectal, prostate),
24,30,39–42
and type 2 diabetesmellitus.
43–45
Results from prospective observationalstudies also suggest that vitamin D supplements in in-fancy and early childhood may decrease the incidence oftype 1 diabetes mellitus.
46–50
RECOMMENDEDDAILYINTAKEOFVITAMINDFORINFANTSANDCHILDREN
In partnership with the Institute of Medicine, the Na-tional Academy of Sciences Panel for Vitamin D recom-mended in 1997 a daily intake of 200 IU vitamin D toprevent vitamin D deficiency in normal infants, childrenand adolescents.
51
This recommendation was endorsed by the AAP in a previous clinical report.
1
The NationalAcademy of Sciences guidelines for infants were basedon data primarily from the United States, Norway, andChina, which showed that an intake of at least 200IU/day of vitamin D prevented physical signs of vitaminD deficiency and maintained the concentration of 25-OH-D at or above 27.5 nmol/L (11 ng/mL).† Theserecommendations were made despite 50 years of clinicalexperience demonstrating that 400 IU of vitamin D (theconcentration measured in a teaspoon of cod liver oil)not only prevented rickets but also treated it.
52–55
Primar-ily on the basis of new information in adults linking
†
Universal units of measure for 25-OH-D and 1,25-OH
2
-D are nmol/L. Conversion to ng/mL ismadebydividingthevalueexpressedinnmol/Lby2.496.Thus,80nmol/Lbecomes32ng/mL.
TABLE 1
VitaminDDeficiency:StagesandClinicalSigns
1. Stages of vitamin D deficiency
Stage I25-OH-D level decreases, resulting in hypocalcemia and euphosphatemia; 1,25-OH
2
-D may increase or remain unchangedStage II25-OH-D level continues to decrease; PTH acts to maintain calcium through demineralization of bone; the patient remains eucalcemic and hypophosphatemic andhas a slight increase in the skeletal alkaline phosphatase levelStage IIISevere 25-OH-D deficiency with hypocalcemia, hypophosphatemia, and increased alkaline phosphatase; bones have overt signs of demineralization
2. Clinical signs of vitamin D deficiency
●
Dietary calcium absorption from the gut decreases from 30%–40% to 10%–15% when there is vitamin D deficiency
●
Low concentrations of 25-OH-D trigger the release of PTH in older infants, children, and adolescents in an inverse relationship not typically seen with young infants;the increase in PTH mediates the mobilization of calcium from bone, resulting in a reduction of bone mass; as bone mass decreases, the risk of fracturesincreases
RicketsEnlargement of the skull, joints of long bones, and rib cage; curvature of spine and femurs; generalized muscle weakness
Osteomalacia and osteopenia
Abnormal immune function with greater susceptibility to acute infections and other long-latency disease states (see below)
3. Potential latent disease processes associated with vitamin D deficiency
●
Dysfunction of the innate immune system is noted with vitamin D deficiency
Immunomodulatory actions may include•Potent stimulator of innate immune system acting through Toll-like receptors on monocytes and macrophages•Decrease threshold for long-latency diseases such as cancers (including leukemia and colon, prostate, and breast cancers), psoriasis, diabetes mellitus, andautoimmune diseases (eg, multiple sclerosis, rheumatoid arthritis, systemic lupus erythematosis)PEDIATRICS Volume 122, Number 5, November 2008
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