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Abstract

Vitamin D is the essential precursor of 1,25-dihydroxyvitamin D₃, the steroid hormone required for calcium absorption, bone development and growth in children. Ninety per cent of the body's vitamin D is produced in the skin from the action of sunlight (ultraviolet B light), with the remaining 10% coming from dietary sources.¹ Ultraviolet light acts on exposed skin only and does not penetrate clothing or glass. Moreover, there is an inverse relationship between the amount of skin pigmentation and vitamin D production.

Serum levels of 25-hydroxyvitamin D₃ (25OHD₃) are a measure of the body's vitamin D stores and used for diagnosing vitamin D deficiency. A serum 25OHD₃ level below 40 nmol/L is indicative of vitamin D deficiency, and a level below 25 nmol/L corresponds to osteomalacia or rickets.² The recommended daily intake (RDI), if there is inadequate sun exposure, is 400 IU in children and 200 IU in adults. Pregnancy increases the RDI for vitamin D to 500-700 IU.³ In newborn infants, vitamin D stores reflect maternal stores, and human breast milk and unfortified cow's milk are poor sources of vitamin D.

Vitamin D deficiency is being increasingly recognised in Melbourne.^4,5 Reports have focused on infants, not their mothers, and emphasised postnatal factors (unsupplemented breast feeding, reduced sun exposure, dark skin pigmentation and dietary factors) as the cause of vitamin D deficiency. Thus, although vitamin D metabolism is considered to be well understood,⁶  the importance of adequate maternal sun exposure and its relationship to perinatal vitamin D deficiency appears to be poorly appreciated in clinical practice.

We performed a retrospective audit of the medical records of infants diagnosed with rickets to determine the vitamin D status of their mothers and their mothers' country of origin.

Methods

Clinical audit

We examined medical records from the Women's and Children's Health Care Network and the Southern Health Care Network (Melbourne, VIC) for the period June 1994 - February 1999. Inpatients with nutritional vitamin D deficiency were identified by a discharge diagnosis of either hypocalcaemia or vitamin D deficiency rickets. Outpatients with vitamin D deficiency were identified from records of dispensing of cholecalciferol during the study period by the Royal Children's Hospital (RCH) pharmacy. The RCH pharmacy was the sole supplier of cholecalciferol in liquid form in Victoria, so most outpatients prescribed cholecalciferol would have received it from this source. Only patients treated privately with other forms of vitamin D would not be identified this way. Children born at less than 35 weeks' gestation or who had chronic liver or renal disease, or any other underlying systemic disorder, were excluded.

Assay

From June 1994 to September 1996, the 25OHD₃ assay was performed by an inhouse column extraction method, followed by Incstar radioimmunoassay (Incstar Corporation, Stillwater, MN, USA) (reference range, 28-165 nmol/L), and all samples were processed at the Royal Melbourne Hospital. After September 1996, samples were processed at three laboratories in Melbourne and the universal method was changed to the Incstar radioimmunoassay (reference range, 25-108 nmol/L).

Results

Children

Fifty-five children were treated for vitamin D deficiency rickets during the study period. Thirty-six were male and 19 female, with ages ranging from 11 days to 12 years, seven months (mean age, 16 months). Twenty-four of the 55 children (44%) were aged less than 12 months and, of these, 23 were exclusively breast fed at the time of diagnosis. Twenty-three of the 55 children presented in spring (September to November). To confirm the diagnosis, biochemical analyses (serum levels of calcium, phosphate, alkaline phosphatase [ALP], parathyroid hormone [PTH] and 25OHD₃ [Box 1]) and radiography of the long bones (showing widened "cupped" and frayed metaphyses and generalised osteopenia) had been performed.

Box 1 shows that hypocalcaemia was more likely in children less than 9 months of age, but ALP and/or PTH levels were elevated across all age groups. The children's symptoms at presentation are given in Box 2.

Mothers

In only 31 (56%) of the 55 children had the 25OHD₃ levels of their mothers been measured (Box 3). None of the mothers had volunteered symptoms of vitamin D deficiency at presentation of their children. Three of the children had older siblings diagnosed with rickets, but maternal vitamin D status had not been assessed when the siblings were diagnosed. Twenty-five of the 31 mothers (81%) had 25OHD₃ levels of 25 nmol/L or less, consistent with osteomalacia, and 28 (90%) had 25OHD₃ levels of 40 nmol/L or less.

In seven mothers, further biochemical evaluation had been performed, including calcium, phosphate, ALP and PTH levels. Three women had raised PTH levels indicative of osteomalacia and, after further questioning, two of these mothers described symptoms of osteomalacia. One was a 26-year-old unveiled Ethiopian woman, who complained of back pain, tiredness and occasional hand weakness. The other was a 24-year-old fully veiled Ethiopian woman, who described a seven-month history of carpopedal spasm and musculoskeletal pain. At the time of diagnosis of her 16-month-old child, she was pregnant with her second child. Treatment of this woman not only relieved her symptoms, but prevented the appearance of vitamin D deficiency in her second child.

Countries of origin

The countries of origin of the 55 mothers were Africa (25; 45%), India/Pakistan (13; 24%), the Middle East (13; 24%) and Italy (3; 5%). The remaining mother was of European descent, but suffered from agoraphobia and depression.

Discussion

Our findings show that, of the mothers of infants with rickets whose vitamin D levels were measured, most were also vitamin D deficient, but had not complained of symptoms at presentation. Presumably, these women would not otherwise have come to medical attention. Women at particular risk of vitamin D deficiency and osteomalacia are those with dark pigmented skin, reduced sun exposure for ethnocultural reasons (including veiling) and inadequate dietary intake of both calcium and vitamin D.^7-9

In children, additional risk factors include maternal vitamin D deficiency and unsupplemented breast feeding, as identified in our study and those of others.^9,10 It has been shown by Hoogenboezem et al¹¹ that total vitamin D metabolites in maternal and fetal plasma are closely correlated, indicating that vitamin D stores at birth are dependent on maternal stores. As newborn infants are generally not exposed to direct sunlight and breast milk is a poor source of vitamin D, vitamin D stores, even if normal at birth, may become depleted at eight weeks in infants exclusively breast fed.^11,12 We suggest supplementing breast fed infants with 400 IU/day of vitamin D (recommended daily requirement) as the safest option for preventing vitamin D deficiency in infants of at-risk women (in Australia, infant vitamins Penta-vite [Roche] provide 0.45 mL [405 IU] per day).

We recommend that when infants with vitamin D deficiency are diagnosed, vitamin D levels in their mothers and siblings should also be assessed, irrespective of whether they are symptomatic. We also recommend that 25OHD₃ levels are measured in all pregnant women with dark skin pigmentation and/or limited sun exposure because of veiling. During pregnancy and lactation, these women require 500-700 IU per day of vitamin D. Their infants should also be assessed for vitamin D deficiency. Vitamin D prophylaxis in infants (400 IU per day) should be commenced at birth and continued for the period of breast feeding.

References

1. Clemens TL, Adams JS, Henderson SL, et al. Increased skin pigmentation reduces the capacity of skin to synthesize vitamin D₃. Lancet 1982; 1: 74-76.
2. Salle BL, Glorieux FH, Lapillone A. Vitamin D status in breastfed term babies. Acta Paediatr 1998; 87: 726-727.
3. Briggs D, Wahlqvist M. Food facts. Chapter 13. Melbourne: Penguin Books, 1984: 119.
4. Pillow JJ, Forrest PJ, Rodda CP. Vitamin D deficiency in infants and children born to migrant parents. J Paediatr Child Health 1995; 31: 180-184.
5. Mayne V, McCredie D. Rickets in Melbourne. Med J Aust 1972; 2: 873-875.
6. DeLuca HF. The vitamin D story: a collaborative effort of basic science and clinical medicine. FASEB J 1988; 2: 224-236.
7. Nellen JF, Smulders YM, Frissen PH, et al. Hypovitaminosis D in immigrant women: slow to be diagnosed. BMJ 1996; 312: 570-572.
8. Gannage-Yared MH, Chemali R, Yaacoub N, et al. Hypovitaminosis D in a sunny country: relation to lifestyle and bone markers. J Bone Miner Res 2000; 15: 1856-1862.
9. Daaboul J, Sanderson S, Kristensen K, Kitson H. Vitamin D deficiency in pregnant and breast-feeding women and their infants. J Perinatol 1997; 17: 10-14.
10. Ahmed I, Atiq M, Iqbal J, et al. Vitamin D deficiency rickets in breast-fed infants presenting with hypocalcaemic seizures. Acta Paediatr 1995; 84: 941-942.
11. Hoogenboezem T, Degenhart HJ, de Muinck Keizer-Schrama SM, et al. Vitamin D metabolism in breast-fed infants and their mothers. Pediatr Res 1989; 25: 623-628.
12. Makin HLJ, Seamark DA, Trafford DJH. Vitamin D and its metabolites in human breast milk. Arch Dis Child 1983; 58: 750-753.

Authors' details

Reprints will not be available from the authors.
Correspondence: Dr C P Rodda, Department of Paediatrics, Monash Medical Centre, 246 Clayton Road, Clayton, VIC 3168.
c.roddaATsouthernhealth.org.au

©MJA 2001
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