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• Nutritional Ricketts is increasingly diagnosed in children of ethnic origin
  Dr Egware Odeka FRCP FRCPCH
  Published on: 31 May 2005
• Return of rickets points to the broader public health issue - widespread vitamin D insufficiency
  Daniel E Roth
  Published on: 23 August 2004

• Published on: 31 May 2005

  Nutritional Ricketts is increasingly diagnosed in children of ethnic origin

  • Dr Egware Odeka FRCP FRCPCH, Consultant Paediatrician
  • Other Contributors:
    • Dr Jeen Tan MRCPCH Specialist Registrar

  Dear Editor,

  We noted with interest the article published by Ladhani and colleagues [1] highlighting the problem of vitamin D deficiency. We agree that this remains a problem, especially in “at risk” ethnic minority groups.

  In Oldham, which has a population of 49992 children, 20.8% are Asians (Census 2001). Between December 2002 and March 2004, we identified 9 cases of hypocalcaemia /rickets secondary to Vi...

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  Dear Editor,

  We noted with interest the article published by Ladhani and colleagues [1] highlighting the problem of vitamin D deficiency. We agree that this remains a problem, especially in “at risk” ethnic minority groups.

  In Oldham, which has a population of 49992 children, 20.8% are Asians (Census 2001). Between December 2002 and March 2004, we identified 9 cases of hypocalcaemia /rickets secondary to Vitamin D deficiency. We excluded those with vitamin D deficiency secondary to other conditions of non-nutritional aetiologies. All of the 9 children had biochemical changes of raised alkaline phosphatase, levels of 25-OHD below 10 ng/ml and 3 had radiological evidence of rickets. 8/9 of these were of Asian extraction and 5/9 were male.

  Presentation of these children were divided into those with hypocalaemic symptoms and those with clinical rickets. 6/9 of them presented with hypocalcaemic symptoms and their ages ranged from 6 days to 13 years of age. These included 2 neonates who presented with focal seizures, 2 toddlers under two years, presented with generalized seizures and 2 thirteen year old, presented with cramps/carpopedal spasms. 3/9 presented with signs of rickets and were aged between 15 to 19 months old.

  The 2 neonates involved were born at term with their birth weights on the 25th centiles. Calcium levels were 1.39 and 1.54 mmol/l respectively. Both were on formula feeds, and tests on maternal blood, revealed levels of parathyroid and calcium suggestive of vitamin D deficiency. Four toddlers were still breast-fed, all of whom were confirmed from dietary history to have limited solid intake. Of the two teenagers, one had a diet low in calcium and the other had background problems of abdominal pain.

  All the children were treated with Vitamin D and 3 children also received oral calcium supplements. All responded to treatment with normalisation of biochemical bone profiles and vitamin D/PTH levels.

  There is no information on the prevalence of rickets in the UK, however, there are reports to say that this is growing.[2] Our experience and reports across the UK, shows that the ethnic minority population still remains at risk of vitamin D deficiency. Efforts to promote vitamin D supplementation as recommended by the Department of Health need to be implemented and targeted at the risk group.

  References

  1.Ladhani S, Srinivasan L, Buchanan C, Allgrove J. Presentation of vitamin D deficiency. Arch Dis Child 2004; 89: 781-784.

  2. Mughal MZ. Resurgence of vitamin D deficiency rickets in the UK. Osteoporosis Review 2005; 13 (1): 10-13.

  3. Department of Health, Nutrition and Bone Health: with particular reference to calcium and vitamin D. Report of the Subgroup on Bone Health, Working Group of the nutritional Status of the Population of the Committee on Medical Aspects of the Food Nutrition Policy. Rep Health Soc Subj (Lond) 1998;49: iii-ivii,1-24.

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  Conflict of Interest:
  None declared.

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• Published on: 23 August 2004

  Return of rickets points to the broader public health issue - widespread vitamin D insufficiency

  • Daniel E Roth, Resident
  • Other Contributors:
    • Adrian B. Jones

  Dear Editor,

  We thank Allgrove for drawing attention to the growing problem of vitamin D deficiency in children [1]. However, we wish to comment on several of the points raised in the commentary.

  As observed by Allgrove, a daily dose of vitamin D less than 10 mcg (400 IU) does not prevent vitamin D deficiency (serum 25(OH)D <25 nmol/L) in all newborn full-term infants [2]. This evidence conflicts...

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  Dear Editor,

  We thank Allgrove for drawing attention to the growing problem of vitamin D deficiency in children [1]. However, we wish to comment on several of the points raised in the commentary.

  As observed by Allgrove, a daily dose of vitamin D less than 10 mcg (400 IU) does not prevent vitamin D deficiency (serum 25(OH)D <25 nmol/L) in all newborn full-term infants [2]. This evidence conflicts with the conclusions of the UK Department of Health [3], as well as the US Food and Nutrition Board (FNB) [4] and the American Academy of Pediatrics [5], which suggest an ‘adequate intake’ (AI) for infants is 200 IU.

  The guidelines of the Canadian Pediatric Society are more on target [6], recommending supplementation of at least 400 IU per day for breast-fed infants (and 800 IU/day for Native infants living at northern latitudes )[7]. Safety data is scant, but Fomon et al. (1966) reported that infants receiving daily vitamin D in doses ranging from 7.5 – 54.25 mcg (300 IU – 2170 IU) did not demonstrate differences in linear growth nor serum calcium concentrations[8] , suggesting doses up to 2000 IU per day are safe. Further research would likely show that doses of at least 800 IU per day are advisable for all high-risk infants (e.g., northern latitude, dark skin, vitamin D-deficient mothers, etc).

  Allgrove mentions that single intermittent pulse doses may be useful for treatment of vitamin D deficiency when adherence is a concern. However, there is very little evidence that currently guides the selection of safe and efficacious doses or frequency of intermittent vitamin D administration in young children, particularly when used as prophylaxis in infants who do not have clinical features of rickets.

  For routine prophylaxis, the high doses suggested by Allgrove (300 000 – 600 000 IU) may be unsafe in infants. Markestad et al. (1987) advised against giving 600 000 IU vitamin D2 to German infants, after observing hypercalcemia in 34% of patients studied, and serum 25-hydroxyvitamin D concentrations above 220 nmol/L [9], which is the upper limit of the physiologic range [10]. Most of the infants in Markestad’s study had initial 25- hydroxyvitamin D concentrations in the range of overt vitamin D deficiency (<20 nmol/L); therefore, infants with rickets may be expected to experience similar effects. Alternatively, a single oral dose of 100 000 IU vitamin D3 approximately every three months may be a safe and efficacious means of delivering the equivalent of approximately 900 IU per day [11] , yet further pharmacokinetic and safety studies are needed before this regimen can be widely recommended for routine use in infants. Vieth advises the use of vitamin D3 (cholecalciferol) because it is more “physiologic”, and notes that the toxicity of vitamin D2 (ergocalciferol) is of greater concern [12] .

  We disagree with Allgrove’s statement that “there is probably no place for universal vitamin D supplementation because of the potential dangers of hypercalcaemia in a few individuals.” Although the US FNB states that the tolerable upper intake level of vitamin D is 50 mcg (2000 IU) daily (1000 IU for infants <1 year of age), concerns that intake above this threshold are harmful are largely unfounded. In the United Kingdom in the 1950s, after milk and cereals were heavily fortified with vitamin D, a small number of children who ingested more than 100 mcg (4000 IU) vitamin D per day developed vitamin D intoxication [2]. It has been suggested that most of these children had features of Williams syndrome [2]2, which is thought to be associated with abnormally increased conversion of vitamin D to 25(OH)D.

  Although the specific public health approach to improve vitamin D status in the general population is a subject of ongoing research and debate, there is good evidence to support the safety and efficacy of routine vitamin D3 supplementation in the general population with doses beyond those traditionally considered to be “toxic”. In adults, doses as high as 4000 IU/day have been shown to be very safe, and effectively raise the serum 25-hydroxyvitamin D concentration to > 75 nmol/L, widely considered to be the ideal target range[13] . Heaney et al. demonstrated that 11 000 IU/day of vitamin D3 for 20 weeks did not lead to elevations in serum calcium above the upper limits of normal [14].

  In French children aged 10 to 15 years, 100 000 IU vitamin D3 administered orally every three months during the winter maintained serum 25-hydroxyvitamin D concentrations and mitigated the wintertime rise in PTH observed in control participants, without any adverse effects (hypercalcemia, or changes in urinary serum/creatinine ratio)[15] .

  There are high rates of vitamin D insufficiency among health adolescents in Europe and North America[16,17]. In our recent study of children and adolescents aged 2 to 16 years in Edmonton (Canada)[18], we found that the prevalence of vitamin D insufficiency (25-hydroxyvitamin D <40 nmol/L) at the end of the winter was 34% overall, and 69% among boys aged 9 to 16 years. Furthermore, we found that 40 % (9/22) of the children aged 9 to 16 years who consumed at least the recommended 5 mcg (200 IU)/day had vitamin D insufficiency. Consistent with the findings described above, none of the participants with dietary vitamin D intakes greater than 0.45 mcg/kg body weight/day (which approximately corresponds to an intake of about 900 IU/day for a 50 kg adolescent), demonstrated vitamin D insufficiency. Therefore, there is now compelling evidence to suggest that supplementation of the general population, including children, with 1000 IU/day (or alternatively, 100 000 IU every 3 – 4 months) during the winter is both safe and efficacious for the prevention of vitamin D insufficiency. Given the high incidence of osteoporosis, this may prove to be a powerful public health initiative in the long-term.

  Current recommendations propose inadequate vitamin D intake, and do not recognize the growing body of literature that shows that the mere absence of rickets or osteomalacia does not imply physiologic vitamin D status[12]12. As Allgrove states, the re-appearance of rickets is likely the “tip of the iceberg” – alluding to the broader public health implications of widespread subclinical vitamin D insufficiency that begins in utero and persists into late adulthood. Illnesses found to be associated with a state of chronic vitamin D insufficiency are numerous, and include not only those chronic adult diseases cited by Allgrove, but also common childhood diseases such as lower respiratory tract infections[19] and type I diabetes[20]. Further research is clearly needed to determine the dose, methods of supplementation/fortification, and specific public health outcomes of ensuring improved vitamin D status in the general pediatric population.

  References

  (1). Allgrove J. Is nutritional rickets returning? Arch Dis Child 2004; 89: 699 - 701.

  (2). Calikoglu AS, Davenport ML. Prophylactic vitamin D supplementation. In: Hochberg Z (ed.). Vitamin D and Rickets. Endoc Dev. Basel, Karger, 2003; 6:233-58.

  (3). Subgroup on Bone Health. Department of Health Working Group on the Nutritional Status of the Population of the Committee on Medical Aspects of Food and Nutrition Policy. Nutrition and bone health: with particular reference to calcium and vitamin D. London: HMSO, 1998.

  (4). Standing Committee on the Scientific Evaluation of Dietary Reference Intakes Food and Nutrition Board, Institute of Medicine. DRI: Dietary reference intakes for calcium, phosphorus, magnesium, vitamin D, and fluoride. National Academy Press 1999; Washington D.C. (Available at http://books.nap.edu/html/dri_calcium).

  (5). Gartner LM, Greer FR; Section on Breastfeeding and Committee on Nutrition. American Academy of Pediatrics. Prevention of rickets and vitamin D deficiency: new guidelines for vitamin D intake. Pediatrics. 2003; 111(4 Pt 1):908-10.

  (6). Canadian Paediatric Society, Dietitians of Canada and Health Canada. Nutrition for Healthy Term Infants. Minister of Public Works and Government Services. Ottawa: 1998. (Available at http://www.hc- sc.gc.ca.login.ezproxy.library.ualberta.ca).

  (7). Indian and Inuit Health Committee, Canadian Pediatric Society. Vitamin D supplementation in northern Native communities. Paediatr Child Health 2002; 7(7):459-63.

  (8). Fomon SJ, Younoszai MK, Thomas LN. Influence of vitamin D on linear growth of normal full-term infants. J Nutr 1966; 88(3):345-50.

  (9). Markestad T, Hesse V, Siebenhuner M, Jahreis G, Aksnes L, Plenert W, Aarskog D. Intermittent high-dose vitamin D prophylaxis during infancy: effect on vitamin D metabolites, calcium, and phosphorus. Am J Clin Nutr 1987; 46(4):652-8.

  (10). Vieth R. Vitamin D supplementation, 25-hydroxyvitamin D concentrations, and safety. Am J Clin Nutr 1999; 69:842-56.

  (11). Zeghoud F, Ben-Mekhbi H, Djeghri N, Garabedian M. Vitamin D prophylaxis during infancy: comparison of the long-term effects of three intermittent doses (15, 5, or 2.5 mg) on 25-hydroxyvitamin D concentrations. Am J Clin Nutr 1994; 60(3):393-6.

  (12). Vieth R, Fraser D. Vitamin D insufficiency: no recommended dietary allowance exists for this nutrient. CMAJ 2002; 166:1541-1542.

  (13). Vieth R, Chan PCR, MacFarlane GD. Efficacy and safety of vitamin D3 intake exceeding the lowest observed adverse effect level. Am J Clin Nutr 2001; 73:288-94.

  (14). Heaney RP, Davies KM, Chen TC, Holick MF, Barger-Lux MJ. Human serum 25-hydroxcholecalciferol response to extended oral dosing with cholecalciferol. Am J Clin Nutr 2003; 77:204-10.

  (15). Duhamel JF, Zeghoud F, Sempe M, Boudailliez B, Odievre M, Laurans M, Garabedian M, Mallet E. Prevention of vitamin D deficiency in adolescents and pre-adolescents. An interventional multicenter study on the biological effect of repeated doses of 100,000 IU of vitamin D3 [French]. Arch Pediatr. 2000; 7(2):148-53.

  (16). Gordon CM, DePeter KC, Feldman HA, Grace E, Emans SJ. Prevalence of vitamin D deficiency among healthy adolescents. Arch Pediatr Adolesc Med 2004; 158(6):531-7.

  (17). Lehtonen-Veromaa M, Mottonen T, Irjala K, Karkkainen M, Lamberg- Allardt C, Hakola P, Viikari J. Vitamin D intake is low and hypovitaminosis D common in healthy 9- to 15-year-old Finnish girls. Eur J Clin Nutr. 1999; 53(9):746-51.

  (18). Roth DE, Martz P, Yeo R, Prosser C, Bell M, Jones AB. Vitamin D Insufficiency is Common Among Children and Adolescents in Edmonton, Alberta. [Manuscript submitted for publication].

  (19). Wayse V, Yousafzai A, Mogale K, filteau S. Association of subclinical vitamin D deficiency with severe acute lower respiratory infection in Indian children under 5 years. Eur J Clin Nutr 2004; 58:563- 567.

  (20). Hypponen E, Laara E, Reunanen A, Jarvelin M-R, Virtanen SM. Intake of vitamin D and risk of type 1 diabetes: a birth-cohort study. Lancet 2001; 358:1500-1503.

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  Conflict of Interest:
  None declared.

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