1,25-dihydroxycholecalciferol in renal osteodystrophy. Epiphysiolysis--anticonvulsant therapy.

Three children with azotaemic renal osteodystrophy were treated with 1,25-dihydroxycholecalciferol (1,25(OH)2D3). All showed clinical, biochemical, and radiological improvement within 6 months of starting treatment. There were no complications. The dose of 1,25(OH)2D3 required was 0-5 microgram per day for 2 children aged 22 and 30 months, and 2 microgram per day for a 15-year-old boy. 2 of the patients were receiving phenobarbitone and phenytoin and in one of them prior treatment with dihydrotachysterol 0-5 mg daily and 6 microgram 1alpha-hydroxycholecalciferol (1alphaOHD3) daily had failed to induce improvement. In one patient, in whom serial iliac bone samples were available, 2 microgram 1,25(OH)2D3 resulted in histological improvement in previously severe osteomalacia. 1,25(OH)2D3 appears to be an effective and safe drug in the treatment of uraemic osteodystrophy.     

Effects of 1,25-dihydroxyvitamin-D3 treatment on mineral balance in children with end stage renal disease undergoing chronic hemofiltration

Ten children with end stage renal disease on chronic hemofiltration (HF) were studied for a 1-yr period to evaluate the efficacy of 1,25-dihydroxyvitamin-D3 (1,25(OH)2D3) therapy on biohumoral parameters of renal osteodystrophy and bone mineral content. In six of these children an acute study was done of the direct effect of the HF procedure on calcium and phosphate balance during 12 HF sessions. During the first 6 months of the study all children were treated with 1,25(OH)2D3 (0.25-0.50 microgram/day) to maintain plasma calcium at 9.5-11.0 mg/dl. There was a significant increase in plasma calcium (p less than 0.05) and a significant decrease in plasma phosphate (p less than 0.01) and alkaline phosphatase concentrations (p less than 0.05). The circulating levels of NH2 immunoreactive parathyroid hormone did not change, remaining at the upper limits of reference values. Immunoreactive parathyroid hormone-COOH terminal fragment levels decreased significantly (p less than 0.05). Bone mineral content rose significantly (p less than 0.01). During the last 6 months of the study, to evaluate the possibility that HF alone might control secondary hyperparathyroidism, 1,25(OH)2D3 treatment was discontinued in five children; plasma calcium and phosphate were well controlled whereas hyperparathyroidism worsened in all five, and one also developed intense pruritus and hypertension. The other five children remained on 1,25(OH)2D3 treatment; two of these were transplanted, and the other three continued to show an improvement of mineral balance. The results of the acute study showed that calcium balance was positive with a mean Ca++ gain of 140 mg/HF session. The mean total phosphate removed per HF run was 574 mg.(ABSTRACT TRUNCATED AT 250 WORDS)     

1,25-Dihydroxyvitamin D3 in childhood hepatic osteodystrophy.

Osteodystrophy frequently accompanies severe childhood hepatobiliary disease. Proposed causes include malabsorption of vitamin D and calcium, and diminished 25-hydroxylation of vitamin D. Two children, ages 23 and 35 months, with radiographic and biochemical evidence of rickets with extrahepatic biliary atresia, were treated with 1,25-dihydroxyvitamin D3. The minimal effective therapeutic dose and efficacy of 1,25-(OH)2D3 in the treatment of rickets associated with severe childhood hepatic disease were determined. Oral 1,25-(OH)2D3 was ineffective at doses of 0.10 microgram/kg/day. Parenteral doses of 0.20 microgram/kg/day effectively produced radiographic, bone mineral (photon absorptiometric), and biochemical evidence of healing. The need for four times the physiologic dose of 1,25-(OH)2D3 by the parenteral route suggested enhanced catabolism of, or end-organ resistance to, 1,25-(OH)2D3 in our patients with severe cholestatic liver disease treated with phenobarbital.     

Vitamin D metabolism in biliary atresia: intestinal absorptions of 25-hydroxyvitamin D3 and 1,25-dihydroxyvitamin D3

In children with biliary atresia, defective intestinal absorption of vitamin D and impaired hepatic uptake and 25-hydroxylation of vitamin D lead to a deficiency of vitamin D and rickets. We recently observed severe rickets in a 3-year-old boy with corrected biliary atresia resulting in jaundice, despite oral treatment with 1 alpha-hydroxyvitamin D3 (1 alpha-OHD3) or 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3]. He had low 25-hydroxyvitamin D (25-OHD) and high 1,25-(OH)2D serum levels. Intramuscular vitamin D2 administration produced radiological and biochemical evidence of recovery. Oral 1,25-(OH)2D3 (0.1 microgram/kg) and 25-OHD3 (10 micrograms/kg) tolerance tests were done to assess the ability to absorb vitamin D and the effectiveness of using these drugs orally. Eleven children with corrected biliary atresia, aged 9 months to 7 years, were studied. In oral 1,25-(OH)2D3 tolerance tests, the increments above the baseline serum levels of 1,25-(OH)2D were 140.7 +/- 27.4 pg/ml in nonjaundiced patients (n = 5). In jaundiced patients (n = 3), 1,25-(OH)2D3 absorption in two patients with high basal 1,25-(OH)2D values was lower than that of nonjaundiced patients; however, the absorption in the third patient with a low basal value was similar to that of nonjaundiced patients. In oral 25-OHD3 tolerance tests, the mean increase of serum 25-OHD was 48.9 +/- 30.6 ng/ml in nonjaundiced patients (n = 5) and 23.7 +/- 9.5 ng/ml in jaundiced patients (n = 4), the peak serum 25-OHD levels being reached 6-12 h after 25-OHD3 loading.(ABSTRACT TRUNCATED AT 250 WORDS)     

Renal Osteodystrophy in Children Treated with 1,25-Dihydroxy-Cholecalciferol [1,25-(OH)2D3]: Histologic Bone Studies

ABSTRACT. Eleven uremic children with osteodystrophy aged 3 to 17 years were studied during administration of l, 25-(OH)₂D, for periods up to 21 months. Nine children presented with pure hyperparathyroidism, one with osteomalacia and one with mixed bone disease. Bone biopsies were performed before initiation of therapy and after 6 to 21 months of treatment following double tetracycline labeling. Skeletal lesions were improved but not cured in 5 of 9 children with hyperparathyroidism. In three instances lesions remained unchanged and worsened in one. No significant change was observed in the child with osteomalacia. Moderate improvement was noted in the patient with mixed bone disease. The propensity to develop hypercalcemia was the major factor associated with treatment failure since it precluded administration of adequate amounts of medication. Therapy with l, 25-(OH)₂D₃ was associated with a spectacular improvement in growth velocity in two of six children under age twelve.     

Early response to vitamin D2 in children with calcium deficiency rickets

OBJECTIVE: To assess the effect of vitamin D(2) administration on serum vitamin D metabolite concentrations in calcium deficiency rickets. STUDY DESIGN: We administered vitamin D(2), 50,000 IU orally to 16 Nigerian children 15 to 48 months of age with radiographically active rickets. We measured calcium and vitamin D metabolites at baseline and at 1, 3, 7, and 14 days. RESULTS: At baseline, ranges of serum 25-hydroxyvitamin D (25(OH)D) concentrations were 18 to 40 nmol/L (7-16 ng/mL), and 1,25-dihydroxyvitamin D (1,25-(OH)(2)D) concentrations were 290 to 790 pmol/L (120-330 pg/mL). After vitamin D administration, serum 25(OH)D and 1,25(OH)(2)D concentrations rapidly rose and peaked at 2.8 and 1.9 times the baseline values (P < .001), respectively, at 3 days. Positive correlations between 1,25(OH)(2)D and 25(OH)D were strongest at day 3 (r = 0.84, P < .001) and weakest at day 14 (r = 0.41, P = .11). The relationship of 1,25(OH)(2)D with 25(OH)D at baseline and the increase in 1,25(OH)(2)D in response to vitamin D were similar to those described in children with vitamin D deficiency. However, unlike the pattern in vitamin D deficiency, 1,25(OH)(2)D remained positively correlated with 25(OH)D after administration of vitamin D. CONCLUSION: Dietary calcium deficiency increases the demand for 25(OH)D above that required in vitamin D deficiency to optimize 1,25(OH)(2)D concentrations. Assessment of vitamin D sufficiency in persons or communities may need to be adjusted for habitual dietary calcium intake.     

Effect of the treatment with oxydevit on calcium metabolism, immune status and 1,25(OH)2D3 receptors in the lymphocytes of children with glomerulonephritis]

In all the examined children with chronic glomerulonephritis (GN), peripheral blood lymphocytes had a high concentration of receptors of 1,25 (OH)2D3, a hormonal form of vitamin D. At the same time as to the healthy children, 1,25 (OH)2D3 receptors were identified only in 27%, with the concentration being lower. A large amount of 1,25 (OH)2D3 receptors may be related to the expression of the hormone in activated lymphocytes. In addition to the normalization of calcium metabolism, the treatment with oxydevit favoured the normalization of the content of IgG and T lymphocytes as well as a reduction (to normal) of the content of 0 lymphocytes regardless of the previous treatment. Partial remission was attained in 14 out of 20 GN patients. In 10 of these children, the remission lasting 1-2 years was attained for the first time. In 17 children treated with oxydevit, the incidence of acute respiratory viral infection decreased from 6-8 times to 1-2 times a year. The data obtained allowed one to ascertain the immunomodulatory capacities of oxydevit in children with chronic glomerulonephritis.     

Renal Osteodystrophy in Children Treated with 1,25-Dihydroxy-Cholecalciferol [1,25-(OH)2D3]: Histologic Bone Studies

ABSTRACT. Eleven uremic children with osteodystrophy aged 3 to 17 years were studied during administration of l, 25-(OH)₂D, for periods up to 21 months. Nine children presented with pure hyperparathyroidism, one with osteomalacia and one with mixed bone disease. Bone biopsies were performed before initiation of therapy and after 6 to 21 months of treatment following double tetracycline labeling. Skeletal lesions were improved but not cured in 5 of 9 children with hyperparathyroidism. In three instances lesions remained unchanged and worsened in one. No significant change was observed in the child with osteomalacia. Moderate improvement was noted in the patient with mixed bone disease. The propensity to develop hypercalcemia was the major factor associated with treatment failure since it precluded administration of adequate amounts of medication. Therapy with l, 25-(OH)₂D₃ was associated with a spectacular improvement in growth velocity in two of six children under age twelve.     

Serum vitamin D metabolites in very low birth weight infants with and without rickets and fractures

Seventy-one very low birth weight (less than or equal to 1500 gm) infants were studied to determine the sequential changes in serum vitamin D metabolite concentrations between infants with and without radiographically documented rickets, fractures, or both (R/F). Usual intake of vitamin D included 20 IU/kg/day from parenteral nutrition or 400 IU/day supplementation with enteral feeding. Radiographs of both forearms and serum samples were obtained at 3, 6, 9, and 12 months. Twenty-two infants had R/F. At 3 months, significantly lower mean (+/- SEM) serum phosphorus levels (4.5 +/- 0.4 vs 6.1 +/- 0.2 mg/dl), higher 1,25-dihydroxyvitamin D (1,25-[OH]2D) concentrations (96 +/- 5 vs 77 +/- 4 pg/ml), and higher free 1,25-(OH)2D index (1,25-[OH]2D:vitamin D binding protein ratio; 5.2 +/- 0.3 x 10(5) vs 4.0 +/- 0.2 x 10(5] were found in the R/F group. These values returned to normal and were similar between groups on subsequent measurements. Serum calcium, magnesium, and 25-hydroxyvitamin D (25-OHD) concentrations were normal and similar between groups. In both groups, serum vitamin D binding concentrations increased initially but remained stable and normal beyond 6 months. We conclude that in very low birth weight infants with R/F, the vitamin D status (as indicated by serum 25-OHD concentrations) is normal, and that lowered serum phosphorus levels, higher serum 1,25-(OH)2D levels, and a higher free 1,25-(OH)2D index support the thesis that mineral deficiency (especially of phosphorus) may be important in the pathogenesis of R/F in small preterm infants.     

Mineral metabolism and calcitriol therapy in idiopathic juvenile osteoporosis

Idiopathic juvenile osteoporosis is a rare cause of osteoporosis during childhood. We examined four children (three boys and one girl, ranging in age from 2.3 to 12.6 years) with idiopathic juvenile osteoporosis. All of these patients had normal serum calcium, ionized calcium, phosphate, magnesium, 25-hydroxyvitamin D, intact parathyroid hormone, and total and extractable calcitonin levels. 1,25-Dihydroxyvitamin D values were low in three patients and slightly decreased in one. Three children were treated with calcitriol (1,25-dihydroxycholecalciferol) (0.50 micrograms/d in two and 0.25 microgram/d in the other). The fourth patient was not treated because of parental refusal. Therapy reduced the fracture rate. Follow-up at 6 and 12 months showed a significant increase in bone mineralization, which reached normal values in two children after 12 months of treatment. No side effects of calcitriol therapy were observed. The untreated patient did not show an improvement of bone mineralization in the same time.     

Treatment of hypophosphataemic vitamin D-resistant rickets with massive doses of 1 alpha-hydroxy-vitamin D3 during childhood.

Plasma levels of 1,25 dihydroxy-vitamin D (1,25-(OH)2-D) were low in 3 children with hypophosphataemic vitamin D-resistant rickets (HVDRR) during childhood, but increased after very large doses (0.5 to 2 micrograms/kg per day) of 1 alpha-hydroxy-vitamin D (1 alpha-OH-D3). This treatment has two advantages. Firstly, hypercalcaemia is easily controlled by reducing the dose of 1 alpha-OH-D3 because of its short half-life. Secondly, the administration of 1 alpha-OH-D3 to patients with HVDRR can enhance the tubular reabsorption of phosphate, and this seems desirable in treating HVDRR.     

Increased serum concentrations of 1,25(OH)2 vitamin D in children with fasting hypercalciuria

Inappropriately elevated concentrations of 1,25(OH)2 vitamin D in serum appear to be responsible for excessive gastrointestinal absorption of dietary calcium in patients with absorptive hypercalciuria. We have examined serum 1,25(OH)2 vitamin D concentrations in another group of children with hypercalciuria in whom urinary calcium excretion was excessive after an overnight fast. Eleven children with idiopathic fasting hypercalciuria (IH) (urinary calcium excretion greater than 4 mg/kg/24 hr and fasting urinary calcium/urinary creatinine ratio greater than 0.21) and seven healthy children were observed while they were eating a diet containing 1 gm calcium per day. Fasting serum 1,25(OH)2 vitamin D concentrations were elevated in children with IH compared with control values (35.3 +/- 3.2 vs 21 +/- 2 pg/ml, P = 0.003), whereas fasting serum parathyroid hormone, 25-OH vitamin D, phosphorus, and ionized calcium concentrations were similar in the two groups. These data suggest that disordered 1,25(OH)2 vitamin D metabolism occurs in children with fasting IH. Absorptive and fasting IH may represent a spectrum of a single disorder characterized by excessive urinary calcium excretion and inappropriately elevated serum concentrations of 1,25(OH)2 vitamin D.     

Vitamin D and parathyroid hormone status in children with the nephrotic syndrome and chronic mild glomerulonephritis

The serum concentrations of 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D (1,25(OH)2D), calcium, creatinine, albumin and immunoreactive parathyroid hormone (iPTH) were measured in eight children with chronic glomerulonephritis not treated with prednisone (group I), in nine non-edematous children with the nephrotic syndrome treated with prednisone for more than 18 months (group II) and in five children with overt edema also treated with prednisone (group III). Serum creatinine was under 1.2 mg/dl in all 22 patients. Reductions in serum calcium, albumin and 25(OH)D were found in group III patients only, whereas both group II and group III patients showed reduced values of 1,25(OH)2D (p less than 0.001 vs. group I or controls). Chronic glucocorticoid administration in children with glomerulonephritis and minimally impaired renal function (group II) is associated with a reduction in the circulating level of 1,25(OH)2D, since children with comparable type and degree of renal disease but non glucocorticoid treatment (group I) have normal 1,25 (OH)2D values. Children with nephrotic edema (group III) have greater reduction of 1,25(OH)2D values, as well as lower 25(OH)D values and serum calcium values, presumably related to a urinary loss of vitamin D-binding protein. No changes in iPTH were evident in either glucocorticoid-treated or edematous patients, suggesting that the acute elevation in iPTH seen after prednisone treatment is an acute phenomenon. Additional short-term studies are needed to more clearly define the effect of glucocorticoids on vitamin D metabolism.     

Congenital adrenal hyperplasia associated with hyperphosphatemic rickets

The authors describe a boy with precocious puberty due to adrenal hyperplasia associated with rickets, hypocalcemia, hyperphosphatemia, elevated PTH and alkaline phosphatase levels, and concentrations of 25-OH-D and 1,25-(OH)2D at the upper limit or above normal range. Treatment with hydrocortisone for 9 months did not normalize hypocalcemia and hyperphosphatemia. The addition of 1,25-(OH)2D3 (0.5-2 micrograms/day) to the corticoid treatment for 1 year was followed by a progressive normalization of plasma calcium, phosphorus, PTH and alkaline phosphatase concentrations with improvement of the osteomalacia on bone biopsy.     

Acute effects of calcitriol and phosphate salts on mineral metabolism in children with hypophosphatemic rickets.

We investigated the acute effects of oral administration of 1,25-dihydroxyvitamin D (1,25-(OH)2D) and phosphate on the major mineral metabolism indexes in six children with vitamin D-resistant rickets treated with a long-term regimen of phosphate and calcitriol. Two acute tests were performed in which plasma calcium, phosphate, immunoreactive parathyroid hormone (iPTH) (intact molecule), 25-hydroxyvitamin D (25-OHD), and 1,25-(OH)2D levels were measured: the first after an oral phosphate load (20 mg/kg) was administered after calcitriol had been discontinued for 10 days, and the second after a calcitriol load (0.03 microgram/kg) plus the same phosphate load but with the children receiving the usual combination treatment. There were no significant differences in basal levels of calcium, phosphate, iPTH, 25-OHD, or 1,25-(OH)2D between the two tests, nor were delta percent calcium and 25-OHD values significantly different. The delta percent plasma phosphate concentration at 60 minutes was significantly higher during test 2 than during test 1 (p less than 0.01) and delta percent iPTH concentration at 60 minutes was significantly higher during test 1 than during test 2 (p less than 0.01). In test 2 the iPTH level returned to baseline at 180 minutes. Higher delta percent 1,25-(OH)2D values at 60 minutes were observed in test 2 than in test 1 (p less than 0.01). Furthermore, the delta percent 1,25-(OH)2D levels were still higher at 180 minutes in test 2 than during test 1 (p less than 0.01). Our study indicates that oral calcitriol has an inhibitory effect on iPTH secretion in the hours immediately after oral phosphate administration in children with vitamin D-resistant rickets.     

Rickets with alopecia: an inborn error of vitamin D metabolism.

Rickets with alopecia, an inborn error of vitamin D metabolism, is described in two sisters. The rachitic disorder began during the first year of life and was refractory to 50,000 IU of vitamin D2/day. Surprisingly, both children had marked elevations in serum concentrations of 1,25-(OH)2D. Although the molecular basis for this disorder is not evident to date, intestinal end-organ unresponsiveness to exceedingly high levels of 1,25-(OH)2D was present, in addition to hyporesponsiveness of bone to these high levels of the hormone, since normocalcemia was maintained despite elevated serum levels of PTH. Therapy with oral 1,25-(OH)2D3 failed to reverse the disorder, but oral phosphorus supplements resulted in significant radiographic and clinical improvement.     

Evaluation of 25-hydroxyvitamin D and vitamin D binding protein losses in thirteen children on continuous ambulatory peritoneal dialysis

Thirteen children, 6 females, 7 males, aged 2 to 13 years were studied. At the time of study they were on continuous ambulatory peritoneal dialysis (CAPD) for 1 to 22 months. 25-(OH)D loss in daily dialysate fluids represented 2 to 22 micrograms/day. A significant correlation was found between 25-(OH)D plasma concentration and 25-(OH)D dialysate concentration. 25-(OH)D clearance was correlated to 25-(OH)D binding protein clearance (p less than 0.001). These findings of important 25-(OH)D losses in the dialysate fluid of children on CAPD demonstrate the necessity of carefully adapted vitamin D intakes with such a treatment.     

Calcium metabolism and growth during early treatment of children with X-linked hypophosphataemic rickets

To evaluate the effect of early treatment on calcium metabolism and growth of infants with X-linked hypophosphataemic rickets (XLH), we enrolled eight infants (one boy) with XLH in a prospective study before and during combined treatment with 40–60 mg/kg per day phosphate and 20–40 ng/kg per day 1,25(OH)₂D₃ (calcitriol). The duration of treatment ranged from 12 to 68 months (median 27 months). We measured the height and several indices of calcium and bone metabolism before and at intervals of 6 weeks to 3 months thereafter during treatment. The diagnosis XLH was established between the age of 3 to 12 weeks by the detection of elevated alkaline phosphatase activities (n=8) and urinary hydroxyproline (n=7), whereas only five patients had also hypophosphataemia. Six of seven untreated patients had decreased 1,25(OH)₂ vitamin D levels in serum. During treatment alkaline phosphatase and hydroxyproline decreased to normal or slightly elevated levels, whereas serum phosphate remained below the normal range. Several patients treated with more than 40–50 mg/kg per day phosphate developed secondary hyperparathyroidism. One patient receiving a low dose of 20 ng/kg per day calcitriol had prolonged radiological and biochemical signs of rickets and growth delay. The other patients presented with no or only slightly transient signs of rickets. Three patients developed moderate nephrocalcinosis. The statural growth rate decreased slightly below 2 SDs without a further decrease in two patients and remained within the normal range in the other patients. Only four patients developed moderate leg deformities. Conclusions Early treatment with calcitriol at a daily dose of at least 30–40 ng/kg and phosphate at a daily dose of maximal 40–50 mg/kg improves mineral metabolism and seems to obviate severe growth delay and leg deformities. Received: 11 February 1998 / Accepted in revised form: 31 May 1998     

Vitamin D-dependent rickets type II: extreme end organ resistance to 1,25-dihydroxy vitamin D3 in a patient without alopecia

Vitamin D-dependent rickets type II (VDDR II) is a rare syndrome resulting in severe rickets and is resistant to treatment with vitamin D and its derivatives. Patient with this disease, who are frequently the children of consanguinous marriages, present with elevated circulating concentrations of 1,25-dihydroxy vitamin D, the active metabolite of vitamin D, and in vitro studies have indicated a failure of intracellular binding of the hormone. Alopecia has been noted in many of these patients and it has been suggested that this feature may indicate a more marked resistance to treatment. However we describe a 3-year-old boy with this disease who, although having normal hair growth, displayed extreme resistance to treatment with active vitamin D metabolites. In vitro studies of skin fibroblasts disclosed not only an absence of hormone binding or 1,25(OH)₂D₃-induced 24-hydroxylase activity but reduced metabolism of 1,25(OH)₂D₃ itself. In this child, treatment with exogenous 1,25-dihydroxy vitamin D₃ at doses of up to 24g/day, which increased the circulating concentration of the metabolite to greater than 100 times the normal adult mean, failed to alleviate his condition and he died at the age of 39 months. This would therefore suggest that absence of alopecia, in this condition, cannot be regarded as a constant predictive sign of a lesser resistance and of responsivenes to Vitamin D treatment.Abbreviations VDDRII vitamin D-dependent rickets type II - AIK Phos alkaline phosphatase     

Vitamin D and mineral metabolism in the very low birth weight infant receiving 400 IU of vitamin D

STUDY OBJECTIVE: To examine (1) the effect of vitamin D intake (380 to 480 IU daily) on plasma 25-hydroxyvitamin D (25-OHD) and 1,25-dihydroxyvitamin D (1,25-(OH)2D) concentrations and (2) the relationship of 1,25-(OH)2D to calcium and phosphorus absorption and retention in the very low birth weight infant receiving a preterm infant formula. SUBJECTS: Eleven "well" infants with a birth weight and gestational age (mean +/- SD) of 1078 +/- 128 gm and 29 +/- 1.9 weeks, respectively, were studied for a 3-week period. Weight and postnatal age (mean +/- SD) at the beginning of the study were 1132 +/- 56 gm and 16 +/- 6 days, respectively. All infants were fed a preterm infant formula and tolerated a full enteral intake (120 kcal/kg/day) for the duration of the study. INTERVENTIONS: Plasma 25-OHD and 1,25-(OH)2D concentrations were measured at the beginning of the study and at the beginning of each 48-hour balance period. Calcium and phosphorus balance studies (n = 33) were performed weekly. MAIN RESULTS: Plasma 25-OHD (30 +/- 10 ng/ml) and 1,25-(OH)2D (54 +/- 14 pg/ml) concentrations were normal at the beginning of the study. Plasma 25-OHD values did not change, but 1,25-(OH)2D values increased (p less than 0.001) throughout the study. Plasma 1,25-(OH)2D concentrations were not related to calcium or phosphorus absorption and retention, but were a linear function of postconceptional age. CONCLUSIONS: Normal vitamin D status and activity are maintained in the very low birth weight infant fed a high calcium formula (380 to 480 IU of vitamin D daily). Plasma 1,25-(OH)2D concentrations are not related to calcium absorption but are linearly related to maturity.