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Higher Prevalence of Vitamin D Deficiency in Mothers of Rachitic Than Nonrachitic Children
HIGHER PREVALENCE OF VITAMIN D DEFICIENCY IN MOTHERS OF RACHITIC THAN NONRACHITIC CHILDREN ADEKUNLE DAWODU, FRCP, FRCPCH, MUKESH AGARWAL, MD, MATT SANKARANKUTTY, FRCS, DENIS HARDY, FRCP, FRCPCH, JOSE KOCHIYIL, MS, AND PADMANABHAN BADRINATH, PHD, MFPH
Vitamin D deficiency [serum 25-hydroxyvitamin D <25 nmol/L (<10 ng/mL)] was identified in 92% of rachitic Arab children and 97% of their mothers compared with 22% of nonrachitic children and 52% of their mothers. There was a positive correlation between maternal and child vitamin D levels. We conclude that mothers of rachitic children should be investigated and treated for vitamin D deficiency (J Pediatr 2005;147:109-11)
itamin D stores in women are low, and vitamin D deficiency rickets is common in Arab countries. The high prevalence of rickets is attributed to limited sunshine exposure and poor dietary vitamin D supplementation, especially in breastfeeding infants.1-3 In such high-risk populations, maternal vitamin D deficiency due to sunshine avoidance and low dietary vitamin D intake is also implicated in the pathogenesis of rickets.4,5 In spite of these associations, however, we are not aware of any comparative studies of vitamin D status of mothers of rachitic and nonrachitic children. We have studied the vitamin D status and relevant sociocultural risk factors of rachitic and nonrachitic children and the vitamin D status of their mothers to test the hypothesis that mothers of rachitic children would have lower serum concentrations of 25-hydroxyvitamin D (25-OHD) and higher prevalence of vitamin D deficiency compared with controls. Although the definitions of hypovitaminosis D and vitamin D deficiency are still controversial,6 we used serum 25-OHD concentrations <25 nmol/L (<10 ng/mL), clinically consistent with osteomalacia and rickets, to indicate vitamin D deficiency.6
V
METHODS Thirty-eight Arab children referred to the Pediatric Clinics of the United Arab Emirates (UAE) University’s 2 teaching hospitals in the Al Ain Medical District (AMD) and diagnosed with vitamin D deficiency rickets between January 1999 and January 2002 were included in this study. The AMD has a population of 300,000. Each child was assessed by at least one of the authors, and a questionnaire on demographic, social and dietary characteristics was completed by interviewing the mother. Usual dress mode while outdoors was used to assess the body surface area exposed to sunshine, using an appropriate chart of body surface area adapted from Lund and Browder.7 Biochemical tests performed in each child and consenting mother included serum concentrations of calcium, inorganic phosphorus, and alkaline phosphatase by autoanalyzer, 25-OHD by high performance liquid chromatography, and intact parathyroid hormone (PTH) by radioimmunoassay kits (Nichols Institute, San Juan Capistrano, Calif). Details of these methods have been reported previously.8,9 The study was approved by the Research Ethics Committee of the institutions. Fifty nonrachitic Arab children and their mothers previously studied in the same community served as controls.9 The control group was a convenience sample of children admitted to one of the Teaching Hospitals during the period February to September 2000 with conditions other than rickets. The results of relevant clinical characteristics and
AMD 25-OHD
Al Ain Medical District 25-Hydroxyvitamin D
PTH UAE
Parathyroid hormone United Arab Emirates
From the Departments of Pediatrics, Pathology, Orthopaedics, Faculty of Medicine and Health Sciences, United Arab Emirates University, and Tawam Hospital, Al-Ain, United Arab Emirates, and Southend-on-Sea, Essex, United Kingdom. Supported by a grant from the Faculty of Medicine and Health Sciences, United Arab Emirates University (NP/99/18). Submitted for publication Oct 30, 2004; last revision received Jan 19, 2005; accepted Mar 1, 2005. Reprint requests: Adekunle Dawodu, FRCPCH, International Health Program, Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 5041, Cincinnati, OH452293039. E-mail: Adekunle.Dawodu@ cchmc.org. 0022-3476/$ - see front matter Copyright ª 2005 Elsevier Inc. All rights reserved. 10.1016/j.jpeds.2005.03.001
109
Table I. Comparison of characteristics of Arab children studied
Sex (M) Age (mo.) No. still breast-feeding No. received vitamin D supplementation Sunshine exposure (min/d) % Body surface area exposed
Rachitic (n = 38)
Nonrachitic (n = 50)
P value
19 (50%) 13.5 2-30 35 (92%) 3 (8%) 0 (0-60) 32 (0-74)
30 (60%) 13.0 5-35 29 (58%) 19 (38%) 45 (0-120) 32 (0-50)
.35 .18 .004 .001 .001 .33
Results presented as number (percent) or median (range).
Table II. Biochemical tests (median and quartiles) Children’s values Rachitic (n = 38)
Tests Serum 25-OHD Concentrations (nmol/L) No. (%) 25-OHD Concentrations (,25 nmol/L) Serum Ca (mmol/L) Serum P (mmol/L) Serum alkaline phosphatase (iU/L)
8.0 (3.8, 15.3) 35 (92) 2.22 (1.88, 2.35) 0.97 (0.77, 1.13) 834 (641, 1164)
Maternal values
Nonrachitic (n = 50) 43.8 (25, 64.3) 11 (22)
P value
Rachitic (n = 38)
.001
13.3 (8.8, 17.8)
.001
2.40 (2.25, 2.50) 1.45 (1.35, 1.61) 156 (129, 219)
.001 .001 .001
37 (97) 2.28 (2.20, 2.35) 1.03 (0.90, 1.16) 89 (77, 105)
Nonrachitic (n = 50) 24.0 (15, 32.8) 26 (52) 2.28 (2.2, 2.38) 1.03 (0.84, 1.13) 75 (59, 97)
P value .001 .001 .90 .88 .011
Conversion to metric units: Serum 25-hydroxyvitamin D (25-OHD), 1 nmol/L = 0.4 ng/mL; Calcium (Ca), 1 mmol/L = 4 mg/dL; Phosphorus (P) 1 mmol/L = 3.1 mg/dL.
vitamin D status of rachitic and nonrachitic children and the vitamin D status of their mothers were compared using nonparametric statistical tests.
(r = 0.45, P < .001). Results of serum PTH levels were available only in rachitic children and their mothers and showed a trend toward negative correlation with serum 25-OHD concentrations.
RESULTS The sex distributions, median age at study, and body surface exposure while outdoors were similar among the children. However, compared with controls, rachitic children had more prolonged breast-feeding (P < .004), less exposure to sunshine (P < .001), and lower rates of vitamin D supplementation (P < .001) (Table I). Serum 25-OHD concentrations were significantly lower in rachitic children and their mothers than in controls (P < .001). Vitamin D deficiency was present in over 90% of rachitic children and their mothers compared with 22% and 52% of nonrachitic children and their mothers, respectively (P = .001). Serum concentrations of calcium and phosphorus were low in rachitic children whereas they were higher in rachitic children and their mothers (Table II).There was a positive correlation between the serum 25-OHD concentrations of mothers and children (Figure). This association persisted when the correlation was performed according to age: age < 12 months (r = 0.39, P = .012); age > 12 months 110
Dawodu et al
DISCUSSION Thirty-eight cases of rickets in almost 3 years in a population of 300,000 suggest that vitamin D deficiency rickets is common in this as in other Arab communities.1,3 We assume that the numbers are much higher because some pediatricians treated rachitic children without referral for this study. Excluding these cases, our rate remains higher than in Western countries.10 Compared with controls, rachitic children have higher risk factors for vitamin D deficiency such as less sunshine exposure and vitamin D supplementation and high rate of prolonged breast-feeding. Another study from Kuwait also found limited sunshine exposure in rachitic children. Thus rachitic children may represent the tip of the iceberg in a population at risk of vitamin D deficiency. We therefore recommend vitamin D supplementation and more sunshine exposure for all infants to eliminate vitamin D deficiency. The amount and dosing regimen of vitamin D supplementation to The Journal of Pediatrics July 2005
abundant sunshine experienced year round (unpublished observations). Recently, some authors13 have suggested that evaluation of maternal vitamin D status should be performed as a secondline investigation of rickets. However, on the basis of the results of this study, we suggest that evaluation of maternal vitamin D status and appropriate therapeutic interventions should be part of the routine management of children with rickets in populations at high risk of vitamin D deficiency. Interestingly, 3 of the mothers of rachitic children required treatment for osteomalacia. The diagnosis in these mothers would have been missed or delayed had they not participated in this study, and this suggests that maternal osteomalacia is underdiagnosed. Clearly, elimination of vitamin D deficiency in women, especially in mothers of rachitic children, requires an early recognition and a maternal vitamin D supplementation program unless more sunshine exposure can be encouraged. A comprehensive strategy that ensures adequate maternal and childhood vitamin D stores could have a significant public health impact on the health of mothers and children. Figure. Relationship between child and maternal serum 25-OHD. Child serum concentrations of 25-OHD directly correlated with maternal 25-OHD concentrations (r=0.44, P<.001).
prevent rickets in high-risk populations such as ours warrant future study. Arab women and mothers of rachitic children in other high-risk populations have very low serum 25-OHD concentrations.4,5,8,9,11 If we regard serum 25-OHD concentrations of 50 to 80 nmol/L (20 to 37 ng/mL) as the adult lower normal range on the basis of recent studies,6 none of the mothers of rachitic children and only 2 of the control mothers would be considered to have normal vitamin D status. Worse still, nearly all mothers of rachitic children and half of controls had serum 25-OHD concentrations <25 nmol/L (<10 ng/mL).6 In contrast, in a large American study, only 12% of black women and less than 1% of white women had such very low serum 25-OHD levels.12 In view of the positive correlation between maternal and child vitamin D status, this study suggests that vitamin D deficiency may be a maternal and childhood public health problem. In addition, the results support our hypothesis that mothers of rachitic children are at higher risk of vitamin D deficiency. Therefore a diagnosis of rickets should strongly suggest the possibility of maternal vitamin D deficiency. This finding could be applicable in other populations at high risk for vitamin D deficiency and warrants confirmation. A limitation of this study is that the study periods for the rachitic children and controls5 were different. The controls were studied during warmer months while rachitic children and their mothers were enrolled year round. This could theoretically result in higher 25-OHD concentrations in the controls and therefore partly explain some of the differences between the 2 groups. In support of our conclusions, however, we have not observed significant seasonal differences in serum 25-OHD concentrations in the UAE because of Higher Prevalence Of Vitamin D Deficiency In Mothers Of Rachitic Than Nonrachitic Children
We thank Dr Mohamed Hayek for collecting blood samples from some of the mothers of the children in the study and Dr Reginald Tsang for valuable comments on the manuscript.
REFERENCES 1. Majid Molla A, Badawi MH, al-Yaish S, Sharma P, el-Salam RS, Molla AM. Risk factors for nutritional rickets among children in Kuwait. Pediatr Int 2000;42:280-4. 2. Dawodu A, Khadir A, Hardy DJ, Varady E. Nutritional rickets in the United Emirates: an unresolved cause of childhood morbidity. Middle E Paediatr 2002;7:12-4. 3. Elidrissy ATH. Vitamin D deficiency rickets in Saudi Arabia. In: Glorieux FH, ed. Rickets. Nestle Nutritional workshop series, Vol 21. New York: Raven Press Ltd; 1991. p. 223-31. 4. Elidrissy ATH, Sedrani SH, Lawson DE. Vitamin D deficiency in mothers of rachitic infants. Calcif Tissue Int 1984;36:266-8. 5. Nozza JM, Rodda CP. Vitamin D deficiency in mothers of infants with rickets. Med J Aust 2001;175:253-5. 6. Zitterman A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutrition 2003;89:552-73. 7. Batchelor ADR. Burns. In: Forfar JO, Arneil GC, eds. Textbook of paediatrics. Edinburgh: Churchill Livingstone; 1984:1857. 8. Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. J Pediatr 2003;142:169-73. 9. Dawodu A, Dawson KP, Amirlak I, Kochiyil J, Agarwal M, Badrinath P. Diet, clothing, sunshine exposure and micronutrient status of Arab infants and young children. Ann Trop Paediatr 2001;21:39-44. 10. Kreiter SR, Schwartz RP, Kirkman HN Jr, Charlton PA, Calikoglu AS, Davenport ML. Nutritional rickets in African American breast-fed infants. J Pediatr 2000;137:153-7. 11. Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 2000;15:1856-62. 12. Nesby-O’Dell S, Scanlon K, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third national Health and Nutrition Survey: 1988-1994. Am J Clin Nutrition 2002;76:187-92. 13. Singh J, Moghal N, Pearce SHS, Cheetham T. The investigation of hypocalcaemia and rickets. Arch Dis Child 2003;88:403-7.
111
Vitamin D deficiency [serum 25-hydroxyvitamin D <25 nmol/L (<10 ng/mL)] was identified in 92% of rachitic Arab children and 97% of their mothers compared with 22% of nonrachitic children and 52% of their mothers. There was a positive correlation between maternal and child vitamin D levels. We conclude that mothers of rachitic children should be investigated and treated for vitamin D deficiency (J Pediatr 2005;147:109-11)
itamin D stores in women are low, and vitamin D deficiency rickets is common in Arab countries. The high prevalence of rickets is attributed to limited sunshine exposure and poor dietary vitamin D supplementation, especially in breastfeeding infants.1-3 In such high-risk populations, maternal vitamin D deficiency due to sunshine avoidance and low dietary vitamin D intake is also implicated in the pathogenesis of rickets.4,5 In spite of these associations, however, we are not aware of any comparative studies of vitamin D status of mothers of rachitic and nonrachitic children. We have studied the vitamin D status and relevant sociocultural risk factors of rachitic and nonrachitic children and the vitamin D status of their mothers to test the hypothesis that mothers of rachitic children would have lower serum concentrations of 25-hydroxyvitamin D (25-OHD) and higher prevalence of vitamin D deficiency compared with controls. Although the definitions of hypovitaminosis D and vitamin D deficiency are still controversial,6 we used serum 25-OHD concentrations <25 nmol/L (<10 ng/mL), clinically consistent with osteomalacia and rickets, to indicate vitamin D deficiency.6
V
METHODS Thirty-eight Arab children referred to the Pediatric Clinics of the United Arab Emirates (UAE) University’s 2 teaching hospitals in the Al Ain Medical District (AMD) and diagnosed with vitamin D deficiency rickets between January 1999 and January 2002 were included in this study. The AMD has a population of 300,000. Each child was assessed by at least one of the authors, and a questionnaire on demographic, social and dietary characteristics was completed by interviewing the mother. Usual dress mode while outdoors was used to assess the body surface area exposed to sunshine, using an appropriate chart of body surface area adapted from Lund and Browder.7 Biochemical tests performed in each child and consenting mother included serum concentrations of calcium, inorganic phosphorus, and alkaline phosphatase by autoanalyzer, 25-OHD by high performance liquid chromatography, and intact parathyroid hormone (PTH) by radioimmunoassay kits (Nichols Institute, San Juan Capistrano, Calif). Details of these methods have been reported previously.8,9 The study was approved by the Research Ethics Committee of the institutions. Fifty nonrachitic Arab children and their mothers previously studied in the same community served as controls.9 The control group was a convenience sample of children admitted to one of the Teaching Hospitals during the period February to September 2000 with conditions other than rickets. The results of relevant clinical characteristics and
AMD 25-OHD
Al Ain Medical District 25-Hydroxyvitamin D
PTH UAE
Parathyroid hormone United Arab Emirates
From the Departments of Pediatrics, Pathology, Orthopaedics, Faculty of Medicine and Health Sciences, United Arab Emirates University, and Tawam Hospital, Al-Ain, United Arab Emirates, and Southend-on-Sea, Essex, United Kingdom. Supported by a grant from the Faculty of Medicine and Health Sciences, United Arab Emirates University (NP/99/18). Submitted for publication Oct 30, 2004; last revision received Jan 19, 2005; accepted Mar 1, 2005. Reprint requests: Adekunle Dawodu, FRCPCH, International Health Program, Center for Epidemiology and Biostatistics, Cincinnati Children’s Hospital Medical Center, 3333 Burnet Ave, MLC 5041, Cincinnati, OH452293039. E-mail: Adekunle.Dawodu@ cchmc.org. 0022-3476/$ - see front matter Copyright ª 2005 Elsevier Inc. All rights reserved. 10.1016/j.jpeds.2005.03.001
109
Table I. Comparison of characteristics of Arab children studied
Sex (M) Age (mo.) No. still breast-feeding No. received vitamin D supplementation Sunshine exposure (min/d) % Body surface area exposed
Rachitic (n = 38)
Nonrachitic (n = 50)
P value
19 (50%) 13.5 2-30 35 (92%) 3 (8%) 0 (0-60) 32 (0-74)
30 (60%) 13.0 5-35 29 (58%) 19 (38%) 45 (0-120) 32 (0-50)
.35 .18 .004 .001 .001 .33
Results presented as number (percent) or median (range).
Table II. Biochemical tests (median and quartiles) Children’s values Rachitic (n = 38)
Tests Serum 25-OHD Concentrations (nmol/L) No. (%) 25-OHD Concentrations (,25 nmol/L) Serum Ca (mmol/L) Serum P (mmol/L) Serum alkaline phosphatase (iU/L)
8.0 (3.8, 15.3) 35 (92) 2.22 (1.88, 2.35) 0.97 (0.77, 1.13) 834 (641, 1164)
Maternal values
Nonrachitic (n = 50) 43.8 (25, 64.3) 11 (22)
P value
Rachitic (n = 38)
.001
13.3 (8.8, 17.8)
.001
2.40 (2.25, 2.50) 1.45 (1.35, 1.61) 156 (129, 219)
.001 .001 .001
37 (97) 2.28 (2.20, 2.35) 1.03 (0.90, 1.16) 89 (77, 105)
Nonrachitic (n = 50) 24.0 (15, 32.8) 26 (52) 2.28 (2.2, 2.38) 1.03 (0.84, 1.13) 75 (59, 97)
P value .001 .001 .90 .88 .011
Conversion to metric units: Serum 25-hydroxyvitamin D (25-OHD), 1 nmol/L = 0.4 ng/mL; Calcium (Ca), 1 mmol/L = 4 mg/dL; Phosphorus (P) 1 mmol/L = 3.1 mg/dL.
vitamin D status of rachitic and nonrachitic children and the vitamin D status of their mothers were compared using nonparametric statistical tests.
(r = 0.45, P < .001). Results of serum PTH levels were available only in rachitic children and their mothers and showed a trend toward negative correlation with serum 25-OHD concentrations.
RESULTS The sex distributions, median age at study, and body surface exposure while outdoors were similar among the children. However, compared with controls, rachitic children had more prolonged breast-feeding (P < .004), less exposure to sunshine (P < .001), and lower rates of vitamin D supplementation (P < .001) (Table I). Serum 25-OHD concentrations were significantly lower in rachitic children and their mothers than in controls (P < .001). Vitamin D deficiency was present in over 90% of rachitic children and their mothers compared with 22% and 52% of nonrachitic children and their mothers, respectively (P = .001). Serum concentrations of calcium and phosphorus were low in rachitic children whereas they were higher in rachitic children and their mothers (Table II).There was a positive correlation between the serum 25-OHD concentrations of mothers and children (Figure). This association persisted when the correlation was performed according to age: age < 12 months (r = 0.39, P = .012); age > 12 months 110
Dawodu et al
DISCUSSION Thirty-eight cases of rickets in almost 3 years in a population of 300,000 suggest that vitamin D deficiency rickets is common in this as in other Arab communities.1,3 We assume that the numbers are much higher because some pediatricians treated rachitic children without referral for this study. Excluding these cases, our rate remains higher than in Western countries.10 Compared with controls, rachitic children have higher risk factors for vitamin D deficiency such as less sunshine exposure and vitamin D supplementation and high rate of prolonged breast-feeding. Another study from Kuwait also found limited sunshine exposure in rachitic children. Thus rachitic children may represent the tip of the iceberg in a population at risk of vitamin D deficiency. We therefore recommend vitamin D supplementation and more sunshine exposure for all infants to eliminate vitamin D deficiency. The amount and dosing regimen of vitamin D supplementation to The Journal of Pediatrics July 2005
abundant sunshine experienced year round (unpublished observations). Recently, some authors13 have suggested that evaluation of maternal vitamin D status should be performed as a secondline investigation of rickets. However, on the basis of the results of this study, we suggest that evaluation of maternal vitamin D status and appropriate therapeutic interventions should be part of the routine management of children with rickets in populations at high risk of vitamin D deficiency. Interestingly, 3 of the mothers of rachitic children required treatment for osteomalacia. The diagnosis in these mothers would have been missed or delayed had they not participated in this study, and this suggests that maternal osteomalacia is underdiagnosed. Clearly, elimination of vitamin D deficiency in women, especially in mothers of rachitic children, requires an early recognition and a maternal vitamin D supplementation program unless more sunshine exposure can be encouraged. A comprehensive strategy that ensures adequate maternal and childhood vitamin D stores could have a significant public health impact on the health of mothers and children. Figure. Relationship between child and maternal serum 25-OHD. Child serum concentrations of 25-OHD directly correlated with maternal 25-OHD concentrations (r=0.44, P<.001).
prevent rickets in high-risk populations such as ours warrant future study. Arab women and mothers of rachitic children in other high-risk populations have very low serum 25-OHD concentrations.4,5,8,9,11 If we regard serum 25-OHD concentrations of 50 to 80 nmol/L (20 to 37 ng/mL) as the adult lower normal range on the basis of recent studies,6 none of the mothers of rachitic children and only 2 of the control mothers would be considered to have normal vitamin D status. Worse still, nearly all mothers of rachitic children and half of controls had serum 25-OHD concentrations <25 nmol/L (<10 ng/mL).6 In contrast, in a large American study, only 12% of black women and less than 1% of white women had such very low serum 25-OHD levels.12 In view of the positive correlation between maternal and child vitamin D status, this study suggests that vitamin D deficiency may be a maternal and childhood public health problem. In addition, the results support our hypothesis that mothers of rachitic children are at higher risk of vitamin D deficiency. Therefore a diagnosis of rickets should strongly suggest the possibility of maternal vitamin D deficiency. This finding could be applicable in other populations at high risk for vitamin D deficiency and warrants confirmation. A limitation of this study is that the study periods for the rachitic children and controls5 were different. The controls were studied during warmer months while rachitic children and their mothers were enrolled year round. This could theoretically result in higher 25-OHD concentrations in the controls and therefore partly explain some of the differences between the 2 groups. In support of our conclusions, however, we have not observed significant seasonal differences in serum 25-OHD concentrations in the UAE because of Higher Prevalence Of Vitamin D Deficiency In Mothers Of Rachitic Than Nonrachitic Children
We thank Dr Mohamed Hayek for collecting blood samples from some of the mothers of the children in the study and Dr Reginald Tsang for valuable comments on the manuscript.
REFERENCES 1. Majid Molla A, Badawi MH, al-Yaish S, Sharma P, el-Salam RS, Molla AM. Risk factors for nutritional rickets among children in Kuwait. Pediatr Int 2000;42:280-4. 2. Dawodu A, Khadir A, Hardy DJ, Varady E. Nutritional rickets in the United Emirates: an unresolved cause of childhood morbidity. Middle E Paediatr 2002;7:12-4. 3. Elidrissy ATH. Vitamin D deficiency rickets in Saudi Arabia. In: Glorieux FH, ed. Rickets. Nestle Nutritional workshop series, Vol 21. New York: Raven Press Ltd; 1991. p. 223-31. 4. Elidrissy ATH, Sedrani SH, Lawson DE. Vitamin D deficiency in mothers of rachitic infants. Calcif Tissue Int 1984;36:266-8. 5. Nozza JM, Rodda CP. Vitamin D deficiency in mothers of infants with rickets. Med J Aust 2001;175:253-5. 6. Zitterman A. Vitamin D in preventive medicine: are we ignoring the evidence? Br J Nutrition 2003;89:552-73. 7. Batchelor ADR. Burns. In: Forfar JO, Arneil GC, eds. Textbook of paediatrics. Edinburgh: Churchill Livingstone; 1984:1857. 8. Dawodu A, Agarwal M, Hossain M, Kochiyil J, Zayed R. Hypovitaminosis D and vitamin D deficiency in exclusively breast-feeding infants and their mothers in summer: a justification for vitamin D supplementation of breast-feeding infants. J Pediatr 2003;142:169-73. 9. Dawodu A, Dawson KP, Amirlak I, Kochiyil J, Agarwal M, Badrinath P. Diet, clothing, sunshine exposure and micronutrient status of Arab infants and young children. Ann Trop Paediatr 2001;21:39-44. 10. Kreiter SR, Schwartz RP, Kirkman HN Jr, Charlton PA, Calikoglu AS, Davenport ML. Nutritional rickets in African American breast-fed infants. J Pediatr 2000;137:153-7. 11. Gannage-Yared MH, Chemali R, Yaacoub N, Halaby G. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 2000;15:1856-62. 12. Nesby-O’Dell S, Scanlon K, Cogswell ME, Gillespie C, Hollis BW, Looker AC, et al. Hypovitaminosis D prevalence and determinants among African American and white women of reproductive age: third national Health and Nutrition Survey: 1988-1994. Am J Clin Nutrition 2002;76:187-92. 13. Singh J, Moghal N, Pearce SHS, Cheetham T. The investigation of hypocalcaemia and rickets. Arch Dis Child 2003;88:403-7.
111